Search results for “molecular

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88 articles
Zoological Research Open Access

Molecular Approaches for Assessing Some Iranian Freshwater Fish Species

Dec 2025 DOI 10.14302/issn.2694-2275.jzr-25-5455
Saeed Heydaranjad MohammadCorresponding author

Monitoring fish biodiversity and its changes over time and their ecological research is one of the important sources of information in their protection. They can be used to find fish biodiversity at different times, such as the capture and maintenance of whole fish, genetic samples, or the use of scales. In this regard, to check the prepared sample, 10-15 scales were prepared from the area of the lid, dorsal fin, and tail stem. Then, they were treated in 5% potassium solution and settled on a slide using a loop microscope equipped with a camera. Among the examined species, Luciobarbusbraczcephalus, Luciobarbuscapito and Capoetasaadispecies could be distinguished from other species with the highest accuracy. In the genetic studies conducted using the cytochrome oxidase subunit 1 gene, the patterns observed in the neighbor joining genealogical tree were consistent with the differences in the genera and species studied. The results of this investigation show that the origin of species can be determined with more than 50% accuracy using genetic data.

Embryology Open Access

Molecular Control of Human Embryonic Development: A Comprehensive Study

Nov 2025 DOI 10.14302/issn.3070-5657.je-24-5327
Khanday ShifanCorresponding author

Human embryonic development is a highly coordinated and complex process that transforms a single fertilized cell into a fully formed human organism. This process is governed by intricate molecular mechanisms involving genetic regulation, signal transduction pathways, and intercellular communication. This study explores key molecular pathways controlling human embryonic development, focusing on the roles of morphogens, transcription factors, signaling molecules, and epigenetic modifications. By reviewing the most recent literature and experimental studies, we aim to highlight the molecular orchestration that directs cell fate decisions, tissue patterning, and organogenesis in humans.

Thyroid Cancer Open Access

Molecular Diagnosis in Clinical Management and Diagnosis of Thyroid Cancer

Jan 2024 DOI 10.14302/issn.2574-4496.jtc-23-4835
Hussein Saleh Hussein AbbasCorresponding author

The prevalence of thyroid cancer is rapidly increasing worldwide, majorly due to overdiagnosis and overtreatment methods of differentiated thyroid cancer. The emergent and potent preclinical models, high-throughput molecular techniques, and genetic expression microarrays have delivered deeper insights into understanding the molecular features in oncogenesis. Thus, molecular markers have become a promising tool in managing thyroid cancer for differentiating benign and malignant tumors, prognosis, recurrence, and determination of novel therapeutic targets. In differentiated thyroid cancer, molecular markers are majorly utilized for guiding the development of indeterminate thyroid nodules on fine needle aspiration (FNA) histologies. Dissimilar to this, in advanced thyroid cancer, molecular markers permit targeted treatment of a modified signaling cascade. Determining causal mutation of targeted kinase receptors in advanced thyroid cancer can depict a promising treatment strategy with mutation-targeted tyrosine kinase inhibitors to reduce progression and eradicate mutation effects when conventional methods fail to manage. This review will focus on the molecular landscape and discuss the impact of molecular markers on the prognosis, treatment, and surveillance of differentiated and anaplastic thyroid cancer.

CERN Large Hadron Collider (LHC) Radiation Source for Magnetic Resonance Biospectroscopy in Metabolic and Molecular Imaging and Diagnosis of Cancer

Dec 2022 DOI 10.14302/issn.2377-2549.jndc-22-4351
Heidari AlirezaCorresponding author Faculty of Chemistry, California South University, 14731 Comet St. Irvine, CA 92604, USA. 

Molecular imaging is a new method in examining physiological studies in molecular dimensions. Among the various methods that have been introduced for this purpose, the magnetic resonance spectroscopy (MRS) method has made it possible to more accurately study the activities of the brain region as well as tumors in different parts of the body. MRS imaging is a type of non– invasive imaging technique that is used to study metabolic changes in the brain, stroke, seizure disorders, Alzheimer's disease, depression and also metabolic changes in other parts of the body such as muscles. In fact, since metabolic changes in the human body appear faster than anatomical and physiological changes, the use of this method can play an important role in the early detection and diagnosis of cancers, infections, metabolic changes and many other diseases. (Graphical Abstract) Graphical Abstract. CERN Large Hadron Collider (LHC) radiation source for magnetic resonance biospectroscopy in metabolic and molecular imaging and diagnosis of cancer.

Molecular Confirmation of Staphylococci Strain’s Identification Isolated in the Hospital and University Center of Brazzaville, Republic of Congo

Nov 2022 DOI 10.14302/issn.2690-4721.ijcm-22-4341
Gwladys Gangoue LéaCorresponding author Laboratoire de Biologie Cellulaire et Moléculaire (BCM), Faculté des Sciences et Techniques, Université Marien NGOUABI, BP 69 Brazzaville, Congo

Bacteria of the genus Staphylococcus are pathogenic Gram-positive bacteria responsible for various infections, including skin suppuration, which can be severe or chronic. The objective of this study was to confirm Staphylococci strain’s identification isolated by bacteriological methods from biological products of CHU-B patients, by molecular methods based on the analysis of the gene coding for 16S rRNA. In total, 30 strains of Staphylococci were isolated including 8 (26.66%) community strains, 22 (73.33%) hospital strains. The products of the amplification of gene fragments encoding 16S rRNA from 10 strains of Staphylococci including 6 strains of Staphylococcus aureus (S. aureus) and 4 Coagulase Negative Staphylococci (CNS) were sequenced. The sequences obtained were subjected to bioinformatics analysis to confirm the results of conventional bacteriological methods. Six (6) S. aureus strains, 2 Staphylococcus haemolyticus strains, 1 uncultured bacterium clone nbw618g09c1, and one Staphylococcus sp. have been identified. These results made it possible to confirm the effectiveness of the molecular method and to show the limits of traditional bacteriological methods in the complete identification of bacteria.

Molecular Detection of Mycoplasma Gallisepticum and Mycoplasma Synoviae Infection in Poultry

Aug 2022 DOI 10.14302/issn.2835-2165.jfsh-22-4263
Mazhar WaqarCorresponding author Pakistan 

In Pakistan, production of poultry has been evolved as a good alternate of beef and mutton. In this study multiplex PCR approaches were adopted to differentiate and detect avian mycoplasma in a single PCR reaction as a step forward in the economization of PCR detection. From the total of 25 samples, 25 (100%) had a positive Mycoplasma isolation result. The biochemical test yielded the highest number of isolations, with MG accounting for 10/25. Commercial DNA-based PCR kits have been developed as a result of recent advancements in diagnostic techniques for Mycoplasma infections. Tetracyclines, fluoroquinolones, tilmicosin, tylosin, spiramycin Infections should be reduced as much as possible.

Tay-Sachs Disease: From Molecular Characterization to Ethical Quandaries and the Possibility of Genetic Medicine

Jun 2022 DOI 10.14302/issn.2470-5020.jnrt-22-4217
O. Henderson JeffreyCorresponding author Department of Science and Mathematics, Judson University, Elgin, IL 60123, USA

Tay-Sachs disease (TSD) is a rare neurodegenerative disorder caused by mutations in the HEXA gene, which encodes the ɑ subunit of the enzyme β-hexosaminidase A. Lacking this key enzyme in GM2 ganglioside catabolism, individuals who are homozygous for HEXA mutations suffer from abnormal accumulation of GM2 ganglioside in brain and nerve cells, ultimately resulting in the progressive deterioration of the central nervous system. TSD is one of three disorders characterized by β-hexosaminidase deficiency; Sandhoff disease (SD) and the AB variant arise by mutations in the HEXB and GM2A genes respectively, which disrupt other points of GM2 ganglioside degradation. Characterized by developmental delay and stagnation, muscular weakness, coordination deficits, seizures, and eventual hearing and vision loss, these three disorders are clinically indistinguishable and occur in three forms defined by age of onset. While there is a much higher incidence of TSD in the Ashkenazi Jewish population, community carrier screening and counseling initiatives have reduced disease prevalence to about the equivalent of non-Jewish populations; however, such efforts have raised ethical concerns in the Jewish community that are increasingly relevant in light of scientific and medical advancements. Currently, treatments for TSD and its related disorders focus on symptom management, with gene therapies and the application of modified CRISPR-Cas-9 technology being explored.

Use of the Remaining Sample from the Panbio COVID-19 Antigen Rapid Test Device for the Molecular Screening of the SARS-CoV-2 Variant of Concern B.1.1.7

May 2021 DOI 10.14302/issn.2690-4721.ijcm-21-3835
Montes MilagrosaCorresponding author Biodonostia Health Research Institute, Vaccine Preventable Diseases Group; Osakidetza Basque Health Service, Donostia University Hospital, Microbiology Department, 20014 San Sebastian, Spain.

Objective Real-time surveillance of SARS-CoV-2 variants of concern (VOC) is of essential public health importance. Rapid Antigen Detection Tests (RAgDT) have become first-line COVID-19 diagnostic methods in many regions, but this strategy can hamper the surveillance of the virus variants due to their decentralized performance. The aim of this study was to assess the usefulness of the remaining sample of a widely used RAgDT (Panbio) for the surveillance of the B.1.1.7 VOC using molecular methods. Methods Symptomatic individuals and asymptomatic close contacts of confirmed cases were routinely screened for SARS-CoV-2 infection using the RAgDT in Primary Health Care Centers. After performing the test, the extraction tubes containing the remaining biological material of RAgDT-positive cases were sent to the clinical microbiology laboratory where RT-PCRs detecting key mutations of the VOC were conducted. Results A valid result was obtained in 1770/1812 (97.7%) RAgDT-positive cases. Variant B.1.1.7 was detected in 34.7% of the patients, increasing from 0% to 87.7% between the weeks beginning January 4 and March 15, 2021. Conclusion The sample remaining after performing the Panbio RAgDT allowed to monitor the emergence and circulation of the B.1.1.7, greatly improving the population screened for the molecular study of SARS-CoV-2 variants.  

Evolutionary Science Open Access

Molecular Evolution of the Novel Coronavirus SARS-CoV-2

May 2021 DOI 10.14302/issn.2689-4602.jes-21-3837
O. Henderson JeffreyCorresponding author Department of Science and Mathematics, Judson University, Elgin, IL 60123, USA

The coronavirus infectious disease (20)19 (COVID-19) pandemic is caused by a newly identified virus (2019) SARS-CoV-2, a beta coronavirus that shares similarities with other human-infecting coronaviruses. Genomic analysis suggests that SARS-CoV-2 is closely related to SARS-CoV, a bat-related coronavirus, RaTG13, and to other pangolin-associated coronaviruses. The spike protein of coronaviruses are glycoproteins and are responsible for attaching the virus to the host cell and entering. Amino acid changes within the spike protein-encoding gene from SARS-CoV to SARS-CoV-2 enable SARS-CoV-2 to form a stable spike protein, to form a stable complex between the S protein and the receptor ACE2, to increase binding points between the S protein and ACE2, and to survive at higher temperatures. SARS-CoV-2 is zoonotic, with genomic analysis implicating bats as the original host and pangolins as the most likely intermediate host to infect humans. As SARS-CoV-2 infects humans, viral point mutations will continually occur and cause the emergence of new competitive SARS-CoV-2 strains. Two major strains include D614G and N501Y and have increased infectivity and transmission, further complicating the scope of the current COVID-19 pandemic. Vigilant monitoring of viral development and evolution is necessary for developing proper treatment methods and vaccine targets.

Molecular Evolutionary Characteristics of the 2019 Novel Coronavirus (SARS-CoV-2) Contracted by Tunisian Citizens : Comparison and Relationship to Other Human and Animal Coronaviruses Based on Spike Glycoprotein-Coding Gene Sequences Analysis

Mar 2021 DOI 10.14302/issn.2692-1537.ijcv-21-3756
Boulila MoncefCorresponding author Professor, Université de Sfax- Institut de l’Olivier- B.P. 14, 4061 Sousse Ibn Khaldoun, Tunisia.

In contributing to the initiative to address the COVID-19 pandemic and in order to enhance the knowledge on driving forces shaping the evolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (isolated from Tunisian patients), a comparison in relation to other coronaviruses infecting humans (SARS-CoV-1, MERS-CoV, HCoV/229E, HCoV/NL63, HCoV/OC43, and HCoV/HKU1) as well as animals (SARS-CoVs in tiger, bats, civet, pangolin, bovine, and MERS-CoV in dromedary/camel), was conducted. In-depth analysis was carried out involving 115 sequences of spike glycoprotein-coding gene extracted from the international databases. Phylogeny inference allowed the reconstruction of a bifurcating tree where four distinct groups were delineated and at the same time, three animal accessions (SARS-CoV-2/tiger, MERS-CoV/camel, and SARS-CoV/bovine) shifted from the animal group and integrated the human coronaviruses clades. Nonetheless, in the presence of reticulate events such as recombination, networks described better the phylogenetic relationships rather than the classic dendrogram. Thus, networks were produced and identified four clusters containing sharply demarcated subgroups (eight subdivisions). Except networked phylogenies of SARS-CoV-1, SARS-CoV-2, and HCoV/HKU1, all the others showed edges and boxes illustrating the occurrence of incompatibilities related to the sequences of spike glycoprotein-coding gene. Thereby and consolidating this result, three methods (RDP package, GARD, and RECCO) were used to detect breakpoints in aligned sequences. Except the clades SARS-CoV-1 and SARS-CoV-2, all the remaining phylogenetic subdivisions were subject to recombination. Furthermore, the screening of selection pressure in all studied sequences by various statistics-based models of the HyPhy package, showed that, similarly, the lineages belonging to the clades SARS-CoV-1 and SARS-CoV-2 were not under selection. In contrast, all members of the remaining clades underwent, to different extents, adaptive selection as well as purifying selection.

Veterinary Healthcare Open Access

Aerobic Plate Count of Contaminants and Molecular Characterization of Eschereichia Coli in Raw Chicken Meat in Ismailia, Egypt

Sep 2020 DOI 10.14302/issn.2575-1212.jvhc-20-3477
A Shaltout FahimCorresponding author Department of Food Control, Faculty of Veterinary Medicine, Benha University. Animal Health Research Institute, Dokki, Giza.

A total number of 100 samples from ten random broiler chicken carcasses (breast and thigh) were collected from an automatic poultry slaughtering plant in Ismailia city, Egypt. The mean values of Enterobacteriacae count were 5.9x104±9.7x103 cfu/g and 7.1x 104 ± 1.1x104 cfu/g for chicken breast and thigh samples respectively. The prevalence of E.coli were 12% and 9% breast and thigh samples examined, respectively. They are serologically identified as 33.35 and 22.2% O157:H7 (EHEC) , 16.6% and 11.1% O114:H21(EPEC), 16.6% and 33.3 %O127:H6 (ETEC) , 0% and 0% O126 (ETEC) and 33.3% and 0% O26 (EHEC) for breast and thigh samples, respectively. The incidence of E.coli O157:H7 was 100% in both serological and PCR methods from biochemical positive E.coli samples. Culture is specific and cheap whereas PCR is sensitive and expensive, hence, we recommend both culture and molecular methods, which improve sensitivity and specificity, to enhance detection of foodborne pathogens including E.coli.

Molecular Analysis of 6-pyruvoyltetrahydropterin Synthase Gene in Atypical Phenylketonuric Egyptian Patients

Jul 2020 DOI 10.14302/issn.2576-6694.jbbs-20-3450
M. Mahmoud MagdyCorresponding author Faculty of Science, Ain Shams University, Cairo Egypt.

Background Hyperphenylalaninemia (HPA) combined with neurological signs due to impaired catecholamine, dopamine and serotonin synthesis. Symptoms may appears in first week of life but most seen in age of 4 months. Atypical PKU disease caused mainly by deficiency in 6-pyruvoyltetrahydropterin synthase (PTPS) involved in synthesis of BH4. Clinical symptoms may include poor sucking, impaired tone, ataxia, and seizures. The purpose of this study was to analyze the genotype-phenotype relation among BH4 deficient patients because of PTPS mutations in different state of Egypt. Methods Suspected PKU patients loaded with phenylalanine/Kuvan, and the level of phe and phe/tyrosine ratio determined using tandem mass spectrometry by dried blood spots. Blood samples of 13 unrelated Egyptian patients were collected for total RNA extraction, amplification of PTPS gene by PCR followed with sequencing by Sanger method and finally mutations were recorded for genetic analysis. Results The mean value of phe in 13 patients decreased after loaded of phenylalanine from 482.5μmol/L to 270.63 μmol/L as well as phe/tyrosine ratio was decreased from 13.4 to 6.36 after 24hour of treatment with Kuvan. Sanger sequencing of PTPS gene of those patient showed 21 SNPs and Indels mutations. The most repeated mutation is a novel 23 base pair homozygous deletion in 12/13; c.200C>T in four patients, a novel c.86A>T in two patients and three different mutations located once in three different patients (novel c.22C>T; novel c.273G>A and 405T>C) among patients. On amino acid predicted sequences 4 different types of mutations on protein level were presented, 1 deletion mutation in seven amino acid and 3 different missense mutations in addition to 2 silent mutations among 13 patients. Conclusion Patients were the first case of clinical diagnosis as hyperphenylalaninemia (HPA) undergoing genetic diagnosis for PTPS deficiency in Egypt. The sever HPA patients with severe nervous system damage mainly accompanied with deletion mutations and should pay more attention to the BH4 deficiency. While mild HPA is associated with base substitution mutations with mainly transition mutations (7/9; 78%). Next-generation sequencing technique can increase the mutation detection rate when the hereditary diseases are highly suspected in clinic.

DNA And RNA Research Open Access

Molecular Study of Hepcidin HAMP (-582A/G) Gene Polymorphisms and Measurement of Serum Hepcidin Level among Sudanese Patients with Anemia of Chronic Kidney Disease

May 2020 DOI 10.14302/issn.2575-7881.jdrr-20-3343
Hussen Abdelrhman AmgedCorresponding author Assis Professor, Department of Hematology and Immunohematology, Omdurman Islamic university / Sudan

Background Anemia of chronic disease is anemia found in certain chronic disease states, is typically marked by the disturbance of iron homeostasis or hypoferremia. Chronic renal failure is currently known as Chronic Kidney Disease (CKD) or Chronic Renal Insufficiency (CRI) implies long-standing, progressive and irreversible renal parenchyma disease resulting in diminished renal function up to 40 to 60%. Often, chronic kidney disease is diagnosed as a result of screening of people known to be at risk of kidney problems, such as those with high blood pressure or diabetes and those with a blood relative with chronic kidney disease. This disease may also be identified when it leads to one of its recognized complications such as cardiovascular disease, anemia, or pericarditis.                             Methods Sysmex kx21 used to CBC and the Cobase411 used to iron profile. Enzyme-Linked immunoassay (ELISA) was used to determine the level of serum hepcidin.  Sample preparation and PCR detection of HAMP DNA Polymorphisms: Restriction digestion of PCR products was done using Fast Digest. (Figure 1).                                                                                         Results Serum hepcidin levels higher in patients with anemia of chronic kidney disease compared with healthy controls mean. The polymorphisms of the hepcidin gene promoter in Sudanese patients with ACKD showed that the hepcidin HAMP AA genotype 70, AG 23, and GG 7 in 100 patients dialysis-dependent and AA 83, AG 17 and GG 0, and the allele A are more frequent in patients affected by ACKD. Significant statistical association observed between the hepcidin level and end-stage kidney disease. Conclusion This study evaluates for the first time the association between anemia of chronic kidney disease and hepcidin genes promoter polymorphisms and show that the hepcidin HAMP AA genotype and the allele A are more frequent in patients affected by ACKD, further investigation is needed, our data support the hypothesis and hepcidin HAMP are important in the pathophysiology of ACKD.

Molecular and Metabolic Pathogenesis of Familial Combined Hyperlipidemia and Association with Metabolic Syndrome

Sep 2019 DOI 10.14302/issn.2572-5424.jgm-19-3024
Hayat Khan  SikandarCorresponding author PNS HAFEEZ Hospital

Background The objective of this review is to unify the various genetic defects along with elaborating metabolic pathways in Familial Combined Hyperlipidemia(FCHL) and also to differentiate the phenotype of FCHL from metabolic syndrome. Methods PubMed and Cochrane’s library was searched for keyword “Familial combined hyperlipidemia” and latter with “Familial combined hyperlipidemia genes” to finally shortlist 23 articles. Further search with key words “molecular pathogenesis of familial combined hyperlipidemia” and “metabolic syndrome and familial combined hyperlipidemia” was carried out for finding molecular defects in FCHL, non-molecular findings distinguishing FCHL from metabolic syndrome and overlapping features between FCHL and metabolic syndrome. Results Major culprit regions identified included Chromosome-1q21-q24(USF1 and FOXA2) , Ch-11q (APOA5), Ch-16q24, Ch-20q12-q13.1, Ch.4q32.3 (rs6829588), and Ch-19q13.32 containing PVRL-2 gene (Also known as Nectin-2). The genetic and metabolic pathways linked to FCHL may involve: 1-Defective clearance of Apo-B containing lipoproteins, 2-Overproduction of Apo-B containing lipoprotein i.e., VLDL and 3-Adipose tissue dysfunction. FCHL phenotype showed close resemblance with metabolic syndrome clinical and biochemical features with slight differences. Conclusion The reviewed data suggested that FCHL phenotype is the resultant end outcome from multiple molecular defects and thus underlying genetic defect identification in the index case is important for personalized medicine and incoming gene therapy. Further research is warranted to explore specific genetic defects.

Model Based Research Open Access

Construction of Virtual Neuron and Consolidation of Sleep and Memory Process– A Molecular Docking and Biomathematical Approach

Mar 2019 DOI 10.14302/issn.2643-2811.jmbr-19-2652
Zhao BinCorresponding author School of Science, Hubei University of Technology, Wuhan, Hubei, China.

This methods paper combines molecular docking and biomathematical modeling to construct a virtual neuron framework for studying sleep‑related memory consolidation. It outlines model components and validation approach.

Molecular Composition of and Potential Health Benefits Offered by Natural East African Virgin Sunflower Oil Products: A 400 MHz 1H NMR Analysis Study

Mar 2019 DOI 10.14302/issn.2379-7835.ijn-19-2677
Grootveld MartinCorresponding author Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, United Kingdom

Objectives: Sunflower oil (SFO) is regularly employed for cosmetic, emollient and food frying purposes, the latter representing its foremost use globally. Therefore, full investigations of the molecular composition and quality of SFO products are a major requirement. In this study high-field 1H NMR analysis was employed to explore the molecular composition and authenticities of East African virgin (EAV) SFO products, particularly their acylglycerol fatty acid contents, together with those of selected minor constituents. Results acquired were statistically compared to those obtained on commercially-available, EU-approved refined SFO products via NMR-linked multivariate chemometrics strategies. Methodology: High-field 1H NMR spectra of EAV and refined SFOs (n = 55 and 4 respectively) were acquired at an operating frequency of 400 MHz. Their triacylglycerol fatty acid, triacylglycerol hydrolysis product, and sterol and stanol contents were determined via intelligent frequency bucketing and electronic integration of selected resonances. Univariate analysis-of-variance, and multivariate ROC curve evaluations were conducted to determine the magnitude and statistical significance of analyte concentration differences between these two sample classifications. Further multivariate NMR-linked chemometrics analyses such as principal component, random forest and support vector machine classification analyses were also utilised for this purpose. Key Results: Multicomponent 1H NMR analysis demonstrated that EAV SFOs had significantly higher and lower contents of monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), respectively, than those of refined SFOs. Furthermore, significantly higher concentrations of ‘health-friendly’, cholesterol-blocking sterols and stanols were also found in these virgin SFO products. Major Conclusions: 1H NMR analysis provides much valuable molecular information regarding the composition and virginal status of SFOs.The high [MUFA]:[PUFA] content ratio of unrefined EAV SFO products renders them more suitable and safer for commercial or domestic deep-frying episodes than refined SFOs (MUFAs are much more resistant to thermally-induced peroxidation than PUFAs). These products also potentially offer valuable health benefits in view of their high natural sterol and stanol contents.

Developing Cellular & Molecular Biomarkers for Anti-Inflammatory Activities of Probiotic Bacteria in Fermented Foods

Mar 2019 DOI 10.14302/issn.2379-7835.ijn-19-2578
E. Ahmed FaridCorresponding author GEM Tox Labs, Institute for Research in Biotechnology, 2905 South Memorial Drive, Greenville, NC 27834, USA.

We present below a mechanistic cellular and molecular approaches for the development of Anti-Inflammatory biomarkersof Probiotic Bacteria in Fermented Foods. Probiotics are live microorganisms that promote human health by counteracting the noxious toxic gut microflora in human intestine, by modulating of the tight junctions, and by increasing mucin production, enforcing intestinal epithelial cell barrier function, modifying microbial community within the gut intestinal disorders, and improving immune responses associated with chronic inflammation in experimental animal models, collectively enhancing human health. Cytokine secretion by intestinal epithelial cells and macrophages are regulated by probiotics through key signaling pathways such as nuclear factor-κB and mitogen-activated kinases, resulting in alleviation of several disorders such as allergies, diabetes, obesity, heart diseases and cancer. MicroRNAs are small non-coding RNA molecules involved in transcriptional and post-translational regulation of gene expression by inhibiting gene translation. Using in vitro and in vivo approaches in cell lines and mice models to study effects of probiotic conditional media and heat-killed bacterial strains with anti-inflammatory effect to elucidate the mechanisms by which probiotics affect signaling pathways, and by using global cytokine and microRNA gene expression analyses approaches to develop biomarkers for studying different pro- and anti-inflammatory activities, and using statistical approaches to analyse the data, we show that cytokines and miRNAs have an essential role in regulation of cancerous and inflammatory pathways. This mechanistic approach will result in developing specific disease biomarkers for the early diagnosis of certain pathogenic states, as well as evaluating the effect of different dietary components on developed biomarkers in health states that will promote and enhance human health. Comparing the concordance of the in vitro to the in vivo research findings will confirm the correspondence of both approaches to each other. Moreover, this study will have a major public health relevance in elucidating the role of miRNAs and their targets in inflammation, paving the way to diagnosing and treating of pathogenic human disease stages.

Molecular Survey on Symbiodinium of Some Scleractinean Coral Spp. and a Fire Coral sp. along the Red Sea of Egypt

Feb 2019 DOI 10.14302/issn.2643-0282.imsj-18-2508
F. Madkour FedekarCorresponding author Department of Marine Science, Faculty of Science, Port Said University, Port Said- 42526, Egypt

The present study introduce an overview on the cladal structure of Symbiodinium population associated with some species of scleractinean corals and fire coral in the Egyptian Red Sea coast and discuss the possible consequences of recent climate changes on coral reefs. Cladal structure of Symbiodinium populations associated with eight keystone species of scleractinean corals and one species of fire coral that collected along Egyptian Red Sea coast, during 2012-2013, had been resolved based on 18S nrDNA and ITS2 genetic markers. Only Symbiodinium subclades C1 and A1 were identified from all examined species. Symbiodinium C1 was the dominant subclade that associated with 61% of coral samples. Results revealed that the studied pocilloporid corals were associated with Symbiodinium C1 and/or A1 while acroporids were only associated with Symbiodinium C1. The present data also indicated that Symbiodinium C1 occurred at high densities than A1 or A1+C1 combination. Because of the relative thermal susceptibility of clades C and A, the current study addresses that the recent climate changes may derive dramatic changes on community structure of coral reefs at the Red Sea.

Perioperative Period is a Critical Gap for Minimal Residual Cancer Cells Progression and Therapy: Biological and Molecular Based Evidences

Oct 2018 DOI 10.14302/issn.2372-6601.jhor-18-2396
Tawfik Amin AnwarCorresponding author Surgical Oncology Department, South Egypt Cancer Institute Assiut University, Egypt.

Although surgery is the main treatment for solid tumors, it could enhance the growth and metastasis of minimal residual cancer. In this review article we have discussed the perioperative changes in cancer cells and surrounding environment as well as the alterations in the immune system. Several trials are ongoing to develop new diagnostic and therapeutic options for minimal residual cancer after surgery.

Molecular and Cell Biological Considerations in the Initiation and Development of Sporadic Non-Hereditary Solid Cancers  

Aug 2018 DOI 10.14302/issn.2572-3030.jcgb-18-2183
F. Niculescu VladimirCorresponding author Cell Biologist, Germany, Kirschenweg 1, 86420 Diedorf

This paper reviews the state of cancer research in the post-mutation era. It presents cancer as a highly complex disease viewed differently by scientists from various research fields. Histopathologists considered cancer as a disease of cell differentiation, cancer cell biologists overestimated the causal role of accumulated DNA mutations. More recently molecular biologists have focused on driver genes and driver mutations, regulatory gene networks and deregulation of the genomic balance between unicellular and multicellular gene sets (UG/MG balance). From a developmental biological standpoint, there is a clear analogy between the reproductive life cycles of cancer and protists. The key player of both analogous life cycles is the polyploid cyst, the atavistic cyst-like structure aCLS (PGCC). In the analogy to protists, we assume that the first aCLS initiating cancer originates from a mitoticly blocked cell (cell of origin of cancer, protoprecursor) that escapes death entering an atavistic reproductive process of polyploidisation and depolyploidisation; it forms the atavistic cyst-like structure aCLS and numerous daughter cells (microcells). The microcell progeny develops a multi-lined cell lineage containing stem cells as well as somatic and reproductive cells and clones. Subsequent aCLSs are formed sequentially by committed daughter cells or occasionally by stressed somatic cells. Accordingly, cancer initiation occurs by genomic changes leading to the amitotic cell state and reactivation of an atavistic life cycle. In humans, atavistic life cycles and hyperpolyploidisation (n >16) are mostly repressed by stable gene regulatory networks – but not in cancer. The permanent UG/MG gene conflict and robust ancient surveillance mechanisms trigger a cascade of molecular lesions leading to genomic heterogeneity and aberrant cancer cell states.

Molecular Spectroscopy and Molecular Docking Studies on (E)-1-(4-Bromobenzylidene) Thiourea

Feb 2018 DOI 10.14302/issn.2377-2549.jndc-18-1933
Bharanidharan S.Corresponding author Department of Physics, Bharath Institute of Higher Education and Research, Bharath University, Chennai-600 073, India

The organic molecule (E)-1-(4-bromobenzylidene)thiourea (BBTU) have been synthesized and characterized using FT-IR and FT-Raman spectral studies. The quantum chemical calculations of BBTU have been studied using DFT/B3LYP/6-31G(d,p) level of theory. The stable conformer is identified by the potential energy surface scan. The complete vibrational assignments were performed on the basis of PED analysis with the help of SQM method. NBO analysis was carried out to explore the various conjucative/hyperconjucative interactions within the molecule and their second order stabilization energy. The NLO activity of BBTU is calculated and compared with the standard Urea molecule. The energies of the FMOs are used for the determination of global reactivity descriptors. The electrophilic and nucleophilic charge sites were identified by the molecular electrostatic potential mapped surface. The molecular docking of BBTU is carried out with the receptors of 3U2D and 1JIJ to screen the bacterial activity.

A Review of the Histologic, Genetic and Molecular Characteristics of Meningioma Pathogenesis and Progression

Aug 2017 DOI 10.14302/issn.2572-3030.jcgb-14-383
Maurer AdrianCorresponding author Department of Neurosurgery, University of Oklahoma, Oklahoma City, Oklahoma, USA

Meningiomas are the most common intracranial tumor in humans. The heterogeneity of these tumors lends difficulty to the genetic, epigenetic, and molecular changes that occur in meningioma pathogenesis, progression, and recurrence. Current de facto classification schemes are based on histologic evaluation of tumor specimens and do not consider molecular markers or other newer modalities. In this paper, we review the major genetic, epigenetic, and molecular changes that have been associated with the oncogenesis and progression of meningiomas. We pay special attention to those changes associated with recurrence and higher grade tumors. Finally, we comment on the challenges and potential for future therapies of these tumors.

Molecular Structure and Vibrational Analysis of 2-(4-methoxyphenyl)-2, 3-Dihydro-1H-Perimidine using Density Functional Theory

Apr 2017 DOI 10.14302/issn.2377-2549.jndc-17-1488
H.SaleemCorresponding author Department of Physics, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India

The compound 2-(4-methoxyphenyl)-2, 3-dihydro-1H-perimidine (MPDP) was synthesized. The molecular structure and its functional groups were characterized with the help of Fourier Transform Infrared: FTIR/ Fourier Transform FT-Raman spectra in the regions of 400-4000/50-4000cm-1, respectively. The geometrical parameters, harmonic vibrational wavenumbers, Infrared (IR) & Raman scattering intensities, Nuclear Magnetic Resonance (NMR) chemical shift and Ultraviolet-Visible (UV-Vis) spectra were computed using B3LYP/6-311++G(d,p) level of theory. The complete vibrational analysis were made on the basis of Potential energy distribution (PED) calculation with the help of VEDA4 programme. The Highest occupied molecular orbital (HOMO) – Lowest unoccupied molecular orbital (LUMO) energy gap and intra-molecular charge transfer (ICT) were studied using NBO analysis. The first order hyperpolarizability (β0) and other related properties (β, α0, Δα) of MPDP were computed. The molecular electrostatic potential (MEP), Mulliken atomic charges were calculated using the same level of theory. In addition, the various thermodynamic parameters were also calculated.

DNA And RNA Research Open Access

Investigations of Molecular Evolutionary Mechanisms in Partially Sequenced Heat Shock Protein70 Homologue-Coding Gene of Olive Leaf Yellowing-Associated Virus Isolates from Tunisia

Feb 2016 DOI 10.14302/issn.2575-7881.jdrr-15-849
BOULILA MoncefCorresponding author Professor, Université de Sfax- Institut de l’Olivier- B.P. 14, 4061 Sousse Ibn Khaldoun, Tunisia.

Reverse Transcription Polymerase Chain Reaction (RT-PCR) using new designed primers pair for Heat Shock Protein70 homologue (HSP70h) of Olive leaf yellowing-associated virus revealed 667 amplified product of 10 olive accessions collected from various olive-growing regions in Tunisia. Amplicons were cloned and sequenced. The sequences were deposited in the international databases. Pairwise sequence comparisons among 10 Tunisian isolates along with a reference sequence (AJ440010) extracted from GenBank revealed a nucleotide identity of 86.06-99.40 and an amino acid similarity of 91.89-99.55. Sequence multiple alignments were searched for evidence of recombination using three methods, ie. Differences of Sums of Squares (DSS) implemented in TOPALi v2.5 software and Single Breakpoint (SBP) along with GARD, a genetic algorithm, both incorporated in HyPhy package. All used methods pointed out the presence of putative breaking points in partially sequenced HSP70h-coding gene. Since failing to account for recombination can mislead the phylogeny inference and can elevate the false positive error rate in positive selection assessment, the use of GARD resulted in the reconstruction of different phylogenies on the left as well as on the right sides of putative recombination breaking points, and the 11 accessions were distributed into at least three clusters compared to MEGA6 software which delineated only two clades. Nonetheless, by dividing the aligned sequences at breakpoints into separate sequence sets, MEGA6 delineated a clustering pattern different from the former two. As a result, recombination reshuffled the affiliation of the different accessions to the clusters. Analysis of selection pressures exerted on HSP70h encoded protein using different models (SLAC, IFEL, FEL, REL, PARRIS, FUBAR, MEME, GA Branch, and PRIME) taking into account recombination, and implemented in HyPhy package, revealed that it underwent predominantly purifying selection as confirmed by Tajima’s D, Fu and Li’s D and F tests, and SNAP algorithm. However, a few sites were also under positive selection as assessed by various models such as FEL, IFEL, REL, MEME, and PRIME.

Understanding Ubl-Rpn1 Intermolecular Interaction

Jun 2014 DOI 10.14302/issn.2328-0182.japst-13-288
Pradhan N.Corresponding author Sr. Professor and Head, Department of Psychopharmacology, NIMHANS, Bangalore, INDIA, 560001

ALS is the neurodegenerative disease which is caused due to breakdown in interaction between UBL and rpn1. In this study, we explore the interaction of UBL and rpn1 which is involved in protein degradation. Protein recycling system plays a crucial role in degradation of deformed or damaged proteins. Task of degradation of damaged ubiquitinated proteins is completed by proteasome with the help of ubiquilin2 protein which links 19s proteasome and poly-Ub chain attached to damaged protein. More specifically, N-terminal UBL domain interacts with rpn1 subunit of base complex of 19s proteasome and C-terminal UBA domain interacts with tetra poly-Ub chain attached to damaged protein. In present study, UBL domains are docked against homology modeled rpn1 with the help of Patch dock server. Further the docked structures are refined using fire dock server and best docked structure is chosen having global energy -16.71. Best docked structures are analyzed using swiss-pdb viewer software to show hydrogen bonds between interacting proteins. Here we explore a mutation E6A and P11A in UBL structure with the help of YASARA which is significantly increasing the interaction between interacting proteins in terms of hydrogen bonds.

Molecular Cytogenetic Investigations in a Novel Chromosomal Abnormality of t(10;15)(q22;q22) in a Pediatric Precursor-B-Acute Lymphoblastic Leukemia Patient

Feb 2014 DOI 10.14302/issn.2372-6601.jhor-13-358
Mandava SwarnaCorresponding author Cytogenetic division, SRL Ltd., Mumbai, India.

Acute lymphoblastic leukemia (ALL) is a rapid form of leukemia characterized by clonal proliferation and accumulation of immature hematopoietic stem cells of the lymphoid lineage in the bone marrow as well as peripheral blood. Chromosomal aberrations identified in childhood ALL have an important role in disease diagnosis, prognosis and management. We present the results of hematologic, immunophenotypic, cytogenetic, FISH and Multiplex RT-PCR analysis of a 6-year-old boy diagnosed with B-cell precursor Acute Lymphoblastic Leukemia (BCP- ALL). In this study, we identified a novel chromosomal translocation t(10;15)(q22;q22) by cytogenetic and FISH analysis. To the best of our knowledge, this is the first report of this novel chromosomal translocation in this subset of ALL and has not yet been reported elsewhere. This rearrangement may include certain cancer associated tumor suppressor gene(s) or genes involved in apoptosis and transcription regulation, which on loss of normal function may lead to leukaemogenesis.

High-Throughput Complex Disease Modeling for Ethical Drug Discovery: Clinical Relevance of a NAM Platform for Cancer Biomarker Development

May 2026 DOI 10.14302/issn.2572-3030.jcgb-26-6307
Faisst Arne-C.Corresponding author

The development of tumor biomarkers derived from blood, or its components, has become pivotal in advancing early cancer diagnosis. Malignant transformations induce cancer-specific alterations in the transcriptome, proteome, and secretome of tumor cells. Recent studies highlighted similar alterations in peripheral blood mononuclear cells (PBMCs) in cancer patients, which appear to mirror the state of transformation in tumor cells. These findings suggest an intercellular communication–driven mechanism rather than a systemic inflammatory response and, in addition to current ctDNA-based liquid biopsy biomarkers, point to a novel, simple, and highly robust approach for the early detection of cancer. Using this phenomenon to advance PBMC-based biomarker development, it will be essential to achieve 3D in vitro tumor models that reproduce a highly physiological tumor microenvironment (TME). Likewise, more enhanced 3D ex vivo models are required to enable the replication of cell-to-cell and organ-to-organ communication. These systems will guide the self-organization of mixed microenvironments derived from different tissues and enable them to accurately reproduce the molecular connections underlying these alterations. In this study, an innovative new modular 3D co-culturing approach was used to expose PBMCs to lung tumoroids, under physiologically relevant conditions. Changes in DNA fragmentation of PBMCs in the presence of lung cancer were quantified and used as a biomarker. To validate the predictiveness of this biomarker, our results were compared with clinical data from a clinical evaluation study. Similar to the clinical trial observations, PBMCs, when exposed to lung tumoroids, showed a significantly lower level of DNA fragmentation (37%). This modular 3D co-culturing model showed a predictiveness of the clinical data of > 90%, demonstrating its power to monitoring cell-to-cell communication effects and support the development of blood-based biomarkers.

Farming Open Access

Modulation of Summer Squash Growth and Productivity Via Spiritual Blessings (Biofield) Energy Treatment (SBET)

May 2026 DOI 10.14302/issn.3070-2232.jf-26-6197
Jana SnehasisCorresponding author

Background The increasing demand for sustainable and eco-friendly agricultural practices has led to the exploration of non-traditional methods to enhance crop yield and resilience. Spiritual Blessings (Biofield) Energy Treatment (SBET), a form of consciousness-driven energy healing, is increasingly being investigated for its potential to modulate biological systems at the cellular and molecular levels without use of chemical additives Objective This study aimed to evaluate the impact of SBET on the growth characteristics and overall productivity of summer squash (Cucurbita pepo L.). Methods The study was conducted using a controlled experimental design, where seeds and plots were divided into two groups: control and treated. The treated group received a remote SBET by a recognized practitioner, while the control group remained untreated. Both groups were maintained under identical environmental conditions (soil, water). Parameters such as germination rate, plant height, leaf area index, and total fruit yield were monitored over a full growth cycle. Results Results showed that plant height, number of branches, and total number of leaves per plant were significantly improved by 35.14% (p ≤ 0.001), 41.64% (p = 0.011), and 49.01% (p = 0.029), respectively, in the treatment group compared to the control group. Additionally, fruit length and total fruit yield (tons per hectare) were significantly increased by 39.68% (p = 0.002) and 15.92%, respectively, in the treatment group compared to the control group. Conclusion Exposure of SBET significantly improved both vegetative and reproductive development, yielding substantial increases in plant height, branching, and leaf production.

Lineage-Specific Disruption of Hematopoiesis by Oxaliplatin: Mechanisms of Erythropoietin Resistance and Immune Suppression

Feb 2026 DOI 10.14302/issn.2372-6601.jhor-25-5944
Y. Berezin MikhailCorresponding author

Background Oxaliplatin, a widely used chemotherapeutic agent, is associated with hematologic toxicities such as anemia, leukopenia, and thrombocytopenia. Despite their clinical relevance, the molecular mechanisms underlying lineage-specific bone marrow suppression remain poorly understood. Methods We administered oxaliplatin to mice over eight weeks and performed RNA-sequencing (RNA integrity >8) on bone marrow alongside peripheral blood analysis and cytokine profiling. Transcriptomic data were analyzed to identify differentially expressed genes (DEGs) and enriched pathways. For that, we applied a thematic Gene Ontology (thematicGO) enrichment method that groups GO terms into biologically meaningful categories, such as hematopoietic lineage disruption, cell cycle arrest, and cytokine signaling. Results Oxaliplatin induced broad transcriptional suppression of erythropoiesis and lymphopoiesis, with 3,691 DEGs identified (FDR<0.05, |FC|>1.5). Upregulation of Cdkn1a and downregulation of E2f2 suggest G1/S cell cycle arrest, correlating with repression of key erythroid maturation genes (e.g., Spta1, Slc4a1, Alas2) and hemoglobin subunits (Hba-a1/2, Hbb-bs/t). Despite a ~3000-fold increase in renal Epo expression, bone marrow Epor was reduced, indicating erythropoietin resistance. B and T cell markers were also significantly downregulated, signifying a collapse in adaptive immunity. Notably, neutrophil populations were largely spared. Cytokine analysis in plasma revealed a pro-inflammatory shift with elevated TNF-α and reduced TGF-β, potentially exacerbating hematopoietic dysfunction. Conclusions Oxaliplatin induces a lineage-dependent suppression of hematopoiesis, driven by coordinated cell cycle arrest, metabolic stress, and disrupted cytokine signaling. RNA-seq analysis enabled integration of transcriptomic findings into coherent biological themes. These findings provide mechanistic insights into oxaliplatin’s hematologic toxicity linking bone marrow failure (potentially reversible) via interconnected inflammatory and metabolic pathways and may inform therapeutic strategies to minimize or restore myelosuppression in cancer patients.

Cervical Cancer Open Access

Review: The Role of Human Papillomavirus in Virus-Induced Carcinogenesis

Dec 2025 DOI 10.14302/issn.2997-2108.jcc-25-5657
M Essam ZahraaCorresponding author

Viral infections contribute to a significant proportion of human cancers, with human papillomavirus (HPV) being one of the most well-established oncogenic viruses. This review summarizes HPV biology, transmission, classification, molecular mechanisms of carcinogenesis, epidemiology of HPV-associated cancers, and current and emerging preventive and therapeutic approaches. particularly HPV-16 and HPV-18, drives malignant transformation through the E6 and E7 oncoproteins, which disrupt tumor suppressor pathways p53 and Rb. Prophylactic vaccination programs have demonstrated remarkable success in reducing HPV-related disease burden, but disparities in coverage remain. Cutting-edge strategies such as CRISPR/Cas9 and RNA-based therapeutics offer promising avenues for treating established infections. Integrating these biomedical advances with robust public health initiatives is essential to ultimately eliminate HPV-associated cancers worldwide (Figure1).

Diagnostic Performance of Smear Microscopy and Xpert MTB/RIF Versus MGIT Culture in Republic of Congo

Nov 2025 DOI 10.14302/issn.2690-4721.ijcm-25-5786
Ornelle Elion Assiana DarrelCorresponding author

In the Republic of the Congo, tuberculosis (TB) remains a major public health concern. Although the GeneXpert MTB/RIF assay is the WHO-recommended first-line diagnostic test, smear microscopy is still used for treatment monitoring and in facilities where molecular testing is limited. Evaluating the diagnostic accuracy of smear microscopy compared to GeneXpert and MGIT culture is essential to guide diagnostic strategies and strengthen TB control in the country. A cross-sectional study was conducted among 92 presumptive pulmonary TB patients at Makelekele Hospital. Sputum samples were analyzed by smear microscopy, GeneXpert MTB/RIF, and MGIT culture. Sensitivity, specificity, positive and negative predictive value were calculated for smear microscopy and GeneXpert, using culture as the reference standard. Culture detected more Mycobacterium tuberculosis than microscopy (49% vs. 32%, P<0.001). Smear microscopy showed a sensitivity of 58% (95% CI: 43–71%) and specificity of 92% (95% CI: 80–97%). GeneXpert detected more MTB (62% vs. 49%, P<0.001) with a sensitivity of 98% (95% CI: 89–100%) and specificity of 72% (95% CI: 58–83%). GeneXpert showed superior sensitivity for TB detection, while microscopy remained specific. Expanding GeneXpert testing across the Republic of the Congo will improve TB management.

Proteomic and Genomic Techniques in Medical Research: Applications in Cancer, Diagnostics, and Personalized Medicine

Nov 2025 DOI 10.14302/issn.2326-0793.jpgr-25-5573
E. Imiruaye OghenetegaCorresponding author

Advancements in proteomic and genomic technologies have transformed molecular biology by enabling comprehensive analysis of biological systems at the molecular level. This literature review explores the evolution, methodologies, and practical applications of key proteomic and genomic techniques. In proteomics, tools such as two-dimensional electrophoresis, mass spectrometry, Western blotting, Edman degradation, and functional protein microarrays have facilitated high-throughput protein identification, post-translational modification analysis, and biomarker discovery. Similarly, genomic methodologies like PCR, recombinant DNA technology, gel electrophoresis, and Southern blotting have revolutionized gene detection, manipulation, and expression profiling. The review also highlights the interdisciplinary impact of these technologies across clinical diagnostics, oncology, autoimmune disorders, infectious disease surveillance, cardiovascular research, and personalized nutrition. Integrative approaches combining proteomics and genomics are enabling the discovery of novel therapeutic targets, improving disease classification, and advancing precision medicine. Despite current limitations, such as the absence of amplification techniques for proteins and challenges in data interpretation, ongoing innovations promise to bridge these gaps. This synthesis underscores the pivotal role of molecular techniques in deepening our understanding of human biology and accelerating biomedical advancements for improved healthcare outcomes.

Human Psychology Open Access

The Human Soul as a Manifestation of Quantum-Like Fields

Oct 2025 DOI 10.14302/issn.2644-1101.jhp-25-5737
W. Kamen EdwardCorresponding author

It is proposed that the human soul is a manifestation of a soul field consisting of a collection of quantum-like fields. The soul field interacts with the electromagnetic field, manifested by photons interacting with the quanta of the soul field. Evidence for this comes from near-death experiences where reported events that could not have been seen through the eyes of the individual are verified. Since bioelectric fields are a type of electromagnetic field, bioelectric fields may also interact with the soul field. This could result in the transfer of information on working memory content to the soul via interactions with bioelectric fields produced by neural ensembles in the human brain. The soul field may also affect neurons on the molecular level in the brain through interactions with bioelectric fields and the recently proposed mechanism of cytoelectric coupling. The human soul is coupled to the body through its interactions with bioelectric fields in the body. Manifestations of the quantum-like fields comprising the soul field may carry out different functions such as encoding memories and experiences, representing emotion states, and defining personal identity. Interactions of these fields and their quanta could produce emergent properties such as self-awareness and consciousness.

Stereoselective Synthesis of N-Glycosyl Oxazolines and Evaluation of Their Antiproliferative Activity

Dec 2023 DOI 10.14302/issn.2377-2549.jndc-23-4740
G. Sivets GrigoriiCorresponding author

A stereoselective synthesis of protected N-glycosyl oxazolines has been developed from available acylated sugar 1,2-O-acetonides using intramolecular Ritter-like reactions. New N-α- and β-D-pentofuranosyl, α-D-hexofuranosyl oxazolines as valuable intermediates for preparation of diverse N-glycosides were obtained by BF3.OEt2-KHF2 or BF3.OEt2-promoted reactions of pentofuranose and hexafuranose acetonide derivatives with nitriles. When selectively acylated D-xylo- or ribofuranoses were employed in the reactions, N-α-pentofuranosyl oxazolines were prepared in good yields. A mechanism for the formation of glycosyl oxazolines was proposed. A series of oxazoline derivatives were evaluated for their antiproliferative activity on three human cancer cell lines (MCF-7, Hela and K562).

Comparative Analysis of Five Commercial RT-PCR Diagnostic Assay for Detection of Covid-19

Sep 2023 DOI 10.14302/issn.2692-1537.ijcv-23-4660
Amel Jamehdar SaeidCorresponding author

SARS-CoV-2 real-time reverse-transcription PCR (rRT-PCR) is the most effective testing system available to combat COVID-19, given the absence of any specific treatment or vaccine. Moreover, numerous SARS-CoV-2 rRT-PCR kits have been approved under emergency-use-authorization (EUA) worldwide. In this article, we present a comparison of important performance features among five commercial RT-PCR assays. A total of consecutive nasopharyngeal (NPS) samples and oropharyngeal (OP) swabs were collected from 50 COVID-19 patients to analyze sensitivity and specificity. The results showed variations in sensitivity among all the RT-PCR kits examined. The Pishtaz teb assays demonstrated the highest positive percent agreement (PPA) of 95.2% (40/42), followed by Covitech (90.5% - 38/42), DaAn Gene (83.3% - 35/42), Sansure (66.66% - 28/42), and Power check of SARS- CoV-2 panel (64.3% - 27/42). Conversely, all five molecular assays demonstrated a negative percent agreement (NPA) of 100% (8/8). These findings provide a technical baseline for assessing the performance of five distinct commercial PCR assays for detecting SARS-CoV-2. They could prove practical and useful for laboratories seeking to purchase any of these assays for further clinical validation. Highlights ·Compared five COVID-19 RT-PCR kits approved and available by Iran Ministry of Health. ·Pishtaz teb's kit identified the highest number of positive clinical samples.

Veterinary Healthcare Open Access

Detection of carbapenem resistance mechanisms among Avian Pathogenic Escherichia coli (APEC) isolated from broiler chickens

May 2023 DOI 10.14302/issn.2575-1212.jvhc-23-4521
El- shaer AyaCorresponding author

Background The emergence and spread of carbapenem-resistant gram-negative bacteria pose a serious threat to human health. Currently, little is known about the molecular mechanisms underlying carbapenem -resistance and their prevalence among APEC in Egypt. The aim of this study was to detect APEC in clinically diseased broiler chickens collected from broilers farms located at Dakahalia governorates, asses their virulence –associated genes, detect the antimicrobial susceptibility of recovered isolates and to detect genes encoding carbapenemase resistant. Methods A total of 100 organ tissue samples subjected to conventional culture technique for isolation of E. coli. The confirmed E. coli were subjected to disc diffusion method for detection their susceptibility to antimicrobials. Polymerase chain reaction (PCR) was used for detection of APEC virulence genes (hlyA, iutA, ompT, iss, iroN) and six carbapenem- resistant genes namely, blaIMP, blaVIM, blaKPC, blaOXA-48 blaGES and blaNDM,. Results Forty isolates were confirmed to be E. coli  among them, three or more APEC virulence- genes were detected from all isolates. The hlyA gene was detected in 90% (36/40), iroN in 95% (38/40), ompT in 97.5% (39/40), iutA in 92.5% (35/40) and iss was detected in 95% (38/40) of APEC isolates The tested isolates exhibited a remarkable resistance to ampicillin (97.5%), cefuroxime (92.5%), clindamycin (90%), chloramphenicol (62.5%), doxycycline (45%), amikacin (25%) and ciprofloxacin (12.5%). While, the retrieved isolates displayed 100 % sensitivity against imipenem, meropenem, ertapenem, ceftazidime and colistin. Concerning carbapenemase-encoding genes, blaIMP, blaVIM, blaKPC, blaOXA-48, blaGES  couldn’t be detected among the E. coli isolates, while, blaNDM was confirmed in three isolates . Conclusion The detection of NDM as one of the carbapenem resistant genes reveals that the resistant strains are not only capable of infecting humans, but that carbapenams- resistant E. coli (CREC)  has also started to pose a threat to poultry farm and other livestock animals. This may give rise to worries that these food-carrying creatures could infect humans or colonize them.

Prolonged survival of Diamond-Blackfan anemia and RPS19 mutation: an observation in Togo

Apr 2023 DOI 10.14302/issn.2372-6601.jhor-23-4530
Padaro EssohanaCorresponding author

Objective Drawing up a balance sheet of 16 years follow-up of the sole case of Diamond-Blackfan anemia diagnosed in Togo with arguments of molecular biology. Observation T.S a boy, born on 5th september 2006 has been followed up since he was three months, for Diamond-Blackfan anemia (DBA) in whom there has been found the mutation of ribosomial protein RPS19 in july 2010. It was the first observation in Subsaharian Africa. The treatment by transfusions from december 2006 to december 2022 has been associated with iron chelation through deferoxamin and promptly with corticotherapy at the dosage of 2mg/kg/day. The corticotherapy has been reduced as a consequence of corticoresistance from the fourth week, then definitely interrupted after four months. The evolution is marked by a clinical improvement with a staturo-balanced curve, and during the last control of 28th december 2022, the child was 53 kg heavy and 160 cm tall. The monthly physical tests did not reveal any signs of eventual overloading and the echocardiography of 26th december 2022 was normal. On the biological plan, the rate of the haemoglobin had been stable around 50g/l as a resultant of a transfusion each 4 to 6 weeks of red blood cell pellet. The chelation of iron had been done through deferoxamin with a monthly control of serum ferritin. That serum ferritin was 738,39ng/mg at diagnosis before the beginning of transfusions and during the follow-up, we noticed an average of 2977,3ng/ml (range 1817,1ng/ml and 4448,5ng/ml) Conclusion Thanks to the regular transfusions derived from the survey of the parameters of iron and the use of deferoxamin, we have succeded in keeping alive during sixteen years a patient who caught a disease whose evolution is unpredictable.

The trajectory of immunoglobulins immune response against the different amounts of xenobiotics matches the trajectory of biological changes associated with ageing: A systematic review

Mar 2023 DOI 10.14302/issn.2474-7785.jarh-22-4381
Tariku Belay YilkalCorresponding author

Background Ageing is a life process in which progressive molecular, cellular, physiological and anatomical changes manifesting in humans and animals including other organisms lead to the decline of biological functions. Immunoglobulins (Igs) are glycoprotein molecules produced by white blood cells mainly B lymphocytes following signal transduction as a result of their interaction with pathogenic microbes or poisonous substances introduced into the body systems. They elicit responses against the side effects of pathogens and poisons in which their response efficiency usually declines as we are ageing. Objective Thus, the similarities between Igs’ immune response against the different amounts of xenobiotics and the biological changes associated with ageing have been systematically assessed using the reports of different study results on humans and animals. Methods First, a literature search was carried out in google, PubMed and google scholar using planned search terms related to the title of this study. Review and original articles were retrieved, downloaded and saved on a computer. And then the effects of different factors i.e. xenobiotics, age, sex and lifestyle-based practices on the levels of serum Igs (IgG, IgA and IgM) in animals and humans have been studied using a systematic review of different literature sources. Finally, the relationship between the findings of various studies has been assessed and judgment on the possible cause of ageing has been made. Results The findings of different research have demonstrated that the signaling efficiency of immunoglobulin M (IgM) has been limited by the amount of test compounds administered to study Balb c mice in the oral route. The response efficiency of IgM immune response against the lower doses of test compounds were high compared to the higher doses of test compounds which was low. The results of different other studies also demonstrated that the decline of serum IgM levels was associated with ageing. The relationship between alcohol consumption and the concentration of serum Igs was also described in the report of different studies. These studies have shown that there was lower level of IgG in the blood serum of alcohol consumers compared to non-consumers. The study has also demonstrated a lower level of serum IgM with higher alcohol consumption and higher serum concentration with moderate beer consumption. Conclusion The trajectory of Igs’ immune response against different amounts of xenobiotics was highly associated with the trajectory of biological changes during ageing. These research findings might be the possible evidence to conclude that ageing is caused by the foodstuffs and non-foodstuffs we usually consume, the lifestyles we usually experience and the way of life we usually live in the environment which gradually defiling the natural processes of the body.

A Review on Drug Design by the Application of Computer

Dec 2022 DOI 10.14302/issn.2328-0182.japst-22-4363
S. Patil NikitaCorresponding author Department of Pharmaceutics P.S.G.V.P.M’s College of Pharmacy, Shahada.

The process of creating new pharmaceuticals is incredibly costly and time-consuming, and it dates back millions of years to the time when only herbal remedies were used. Furthermore, the solvation energies of the ligand and receptor site are crucial to this process because partial to complete dedication must take place before binding. The full form of CADD is computer-added drug design. To enhance the design and discovery of, CADD stands for computational methodologies and resources. Smaller numbers of chemicals are chosen from extensive compound libraries for experimental testing. There is less screening. Pharmacogenomics’ main benefit is the ability to develop medication based on the genomiy organization of each individual. The immense potential of enzymes as therapeutic targets is exemplified by under R's leadership, Merck's strategy. Both the two exemplary PP'S were the (APS, a class of proteins, are making progress it will blossoms in computational thermodynamics.3D-QSAR mode was developed last year for the follow-up forecast of action of chemicals in a molecular database or newly created target's spatial organization is known.

A Patient with Monoclonal Gammopathy of Undetermined Significance and Detected Philadelphia Chromosome

Apr 2022 DOI 10.14302/issn.2372-6601.jhor-22-4133
Qing XinCorresponding author Department of Pathology, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA.

Background Monoclonal gammopathy of undetermined significance (MGUS) and chronic myeloid leukemia (CML) are diseases of different lineages. The diagnosis of both MGUS and CML in the same patient is a rare occurrence and has not been reported in much literature. Case Presentation We describe a 56-year-old man with a history of rheumatoid arthritis incidentally found to have an increase in IgA paraprotein. With less than 10% monoclonal plasma cells on the bone marrow biopsy and absence of hypercalcemia, renal failure, anemia and bone lesions, MGUS was diagnosed. The conventional cytogenetics at the time showed the presence of the Philadelphia chromosome in 30% of metaphases. However, there was no morphologic evidence of CML in the peripheral blood or bone marrow. Patient received no treatment and lost follow-up until 3 years later when a routine CBC showed leukocytosis and thrombocytosis. CML, chronic phase was diagnosed following a bone marrow aspiration and biopsy with Philadelphia chromosome observed in 100% of metaphases. Patient was treated with imatinib and later switched to dasatinib and complete molecular remission was continued to be achieved. Discussion and Conclusion Here we report a case of pre-leukemic CML as an incidental finding during the diagnosis of MGUS. The possible underlying mechanisms of the association are discussed although the exact cause of the coexistence is unclear.

Skeletal Muscle Open Access

BaMtox, a Myotoxic Enzyme Isolated from the Venom of the Bothrops Alternatus

Mar 2022 DOI 10.14302/issn.2832-4048.jsm-21-3986
Fernando Moreira Izidoro LuizCorresponding author Faculdade de Medicina, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.

Snake envenomations are responsible for a high percentage of deaths, as these toxic proteins induce severe local and systemic effects. In Brazil, the Bothrops genus is responsible for a satisfactory fraction of accidents, including Bothropsalternatus, recognized as urutu, whose venom is capable of inducing severe myotoxicity. In this work, the BaMtox toxin was purified through a combination of three chromatographic steps, ion exchange in DEAE-Sepharose, affinity in Benzamidine Sepharose 6B columns and reversed-phase HPLC chromatography on a C18 column. The BaMtox toxin has a molecular mass of approximately 14kDa and did not show phospholipase activity or hemorrhage. On the other hand, it induced edema and a significant increase in plasma levels of the creatine kinase enzyme. Thus, the protein called BaMtox is able to induce myotoxicity.

Challenger and Propose Novel Methods and Techniques for Prevention, Prognosis, Diagnosis, Imaging, Screening, Treatment and Management of Lung Cancer

Feb 2022
Gobato RicardoCorresponding author Green Land Landscaping and Gardening, Seedling Growth Laboratory, 86130-000, Parana, Brazil.

Using samples of small cell lung tumors, a research team led by biologist Dr. Raymond discovered two new ways to induce tumor cell death. By activating ferroptosis, one of two subtypes of tumor cells can be targeted: first, iron-dependent cell death due to oxidative stress, and second, oxidative stress. Therefore, cell death can also be induced in a different way. Both types of cell death must be caused by drugs at the same time to eliminate the majority of the tumor mass. It is currently in clinical trials for cancer treatment. Auranofin, which inhibits the production of protective antioxidants in cancer cells, has been used to treat rheumatoid arthritis for decades. Future clinical trials using this combination therapy will determine the extent to which this targeted treatment option improves the prognosis of small cell lung cancer patients. It is currently in clinical trials for cancer treatment. Lung cancer is the leading cause of cancer death in the United States. Despite evidence of molecular abnormalities in biological specimens, progress in this disease is hampered by the lack of diagnostic markers useful for clinical practice. The majority of patients with lung cancer are still diagnosed at an advanced stage, when prognosis is poor. This article reviews new strategies being studied for the early detection of lung cancer. These strategies involve new methods of imaging (including low-dose computed tomography CT scanning), DNA analysis, and proteomic-based techniques. These strategies have not only improved our understanding of lung cancer but show promise in offering better survival to patients with this deadly disease. Of paramount importance in the search for methods of early detection is the need for the identification of the ideal population to screen, a multidisciplinary approach, and validation of promising techniques.

Photobiomodulation, Depression, Anxiety, and Cognition

Aug 2021 DOI 10.14302/issn.2474-7785.jarh-21-3935
Marks RayCorresponding author Department of Health and Behavior Studies, Teachers College, Columbia University, New York, NY 10027, USA.

Background Anxiety and depression are key barriers to healthy aging and greatly heighten the risk for many negative health issues that seriously impact life quality. Aim This mini review examines the potential of low level laser treatments or photobiomodulation therapy for ameliorating severe anxiety and depression in older adults. Methods and Procedures Articles that adressed the current topic of interest extracted from PUBMED and Google Scholar were carefully and presented in narrative form. Results Photobiomodulation therapy appears to be a safe efficacious modality for ameliorating various degrees of anxiety and depression and for improving cognition, and is supported by several well established mechanisms of action at the molecular, cellular, and tissue levels. Conclusion More research to examine who might benefit most from this form of therapy, and in what respect in this area of growing global concern and few intervention options is strongly warranted.

Lennert Lymphoma (lymphoepithelioid lymphoma) with Extensive Necrosis: A Case Report

Apr 2021 DOI 10.14302/issn.2372-6601.jhor-21-3801
Qing XinCorresponding author Department of Pathology, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA.

Lennert lymphoma (lymphoepitheloid lymphoma) is an extremely rare variant of peripheral T-cell lymphoma, not otherwise specified. Here we report a case of Lennert lymphoma diagnosed in a 57-year-old woman. She had a three-year history of waxing and waning lymphadenopathy with a rapid increase in size in the past four months before presentation. A needle biopsy and a fine needle aspiration were non-diagnostic due to extensive necrosis. The patient underwent a right neck lymph node excisional biopsy which showed the lymph node architecture was effaced by numerous and sometimes confluent clusters of epithelioid histiocytes and infiltration of small lymphocytes. Extensive necrosis was present. Immunohistochemical stains revealed a mixed population of B- and T-cells with the T-cells showing diminished T-cell markers CD3, CD5, and CD7. Flow cytometric analysis detected a small population (7% of total lymphocytes) of CD4-positive T-lymphocytes with loss of CD3, CD5, and CD7 expressions. PCR-based T-cell receptor gene rearrangement studies showed positive results (clonal peaks) in both gamma and beta genes. Stains for microorganisms were negative. The overall findings indicate Lennert lymphoma. To our knowledge, this is the first reported case of Lennert lymphoma with extensive necrosis. The patient is undergoing chemotherapy. The diagnosis of Lennert lymphoma can be challenging, particularly in cases with extensive necrosis. Our case highlights that adequate sampling is important in the investigation of patients with suspected Lennert lymphoma. A careful pathologic examination with ancillary studies including flow cytometry, immunohistochmistry, and cytogenetic and molecular studies leads to the accurate diagnosis.  

Structural Characterization and Isotopic Abundance Ratio Analysis of the Consciousness Energy Healing Treated Ofloxacin

Apr 2021 DOI 10.14302/issn.2766-8681.jcsr-21-3770
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd., Thane (W), Maharashtra, India.

Ofloxacin is an antibiotic, useful against the number of bacterial infections. This scientific investigation was performed to identify the impact of the Trivedi Effect®-Consciousness Energy Healing Treatment on the structural properties and the isotopic abundance ratio of ofloxacin using sophisticated analytical techniques. Ofloxacin sample was divided into control and treated parts. Only the treated ofloxacin received the Consciousness Energy Healing Treatment remotely by a well-known Biofield Energy Healer, Mr. Mahendra Kumar Trivedi. The LC-MS spectra of both the samples of ofloxacin at retention time 3 minutes exhibited the mass of the protonated molecular ion peak at m/z 362.17 (M+H)+. The chromatographic peak area% of the treated ofloxacin (52.4%) was increased by 2.03% compared to the control sample (51.36%). The LC-MS based isotopic abundance ratio of PM+1/PM in the Biofield Treated ofloxacin was significantly increased by 22.43% compared with the control sample. Similarly, the GC-MS based isotopic abundance ratio of PM+1/PM in the Biofield Treated ofloxacin was significantly increased by 19.24% compared with the control sample. The LC-MS and GC-MS based isotopic abundance ratio of PM+1/PM (2H/1H or 15N/14N or 13C/12C or 17O/16O) was significantly increased in the Biofield Treated ofloxacin as compared to the control sample. Thus,2H, 15N, 13C, and17O contributions from (C18H21FN3O4)+ to m/z 363.17 in the treated ofloxacin were significantly increased compared with the control sample. The increased isotopic abundance ratio of the Trivedi Effect®-Consciousness Energy Healing Treated ofloxacin may increase the intra-atomic bond strength and increase its physical stability. The new form of treated ofloxacin would be more stable, better soluble, and bioavailable compared to the control sample. It would be more useful to design efficacious pharmaceutical formulations that might offer better therapeutic response against infections in the urethra, urinary tract, gonorrhoea, pneumonia, infectious diarrhoea, bronchitis, cellulitis, bacterial infection of the eye and ear, multidrug-resistant tuberculosis, prostatitis, otitis media, plague, etc.  

Study of the Consciousness Energy Healing Treatment and It’s Effect on the Isotopic Abundance Ratio of Ascorbic Acid (Vitamin C)

Apr 2021 DOI 10.14302/issn.2689-2855.jan-21-3771
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd., Thane (W), Maharashtra, India.

Ascorbic acid is a water-soluble vitamin (Vitamin C) essential for both the plants and animals for the metabolic process. In this study, the liquid chromatography-mass spectrometry (LC-MS) analytical technique was used to characterize the structural properties and isotopic abundance ratio to evaluate the effect of the Trivedi Effect®-Consciousness Energy Healing Treatment on L-ascorbic acid compared to the control sample. The ascorbic acid sample was divided into control and treated parts. Only the treated part received the Trivedi Effect®-Consciousness Energy Healing Treatment remotely by a well-known Biofield Energy Healer, Mahendra Kumar Trivedi. The control and treated samples showed a chromatographic peak at retention time (Rt) 1.8 minutes exhibited the deprotonated molecular ion peak at m/z 175 (M-H)- (calculated for C6H7O6-, 175.02) in the mass spectra. The peak area of the treated sample (12817614.01) was significantly increased by 8.81% compared to the control sample (11779918.9). The LC-MS based isotopic abundance ratio of PM+1/PM (2H/1H or 13C/12C or 17O/16O) in the treated ascorbic acid was significantly increased by 23.22% compared with the control sample. Thus,13C, 2H, and17O contributions from (C6H7O6)- to m/z 176 in the treated ascorbic acid were significantly increased compared with the control sample. The increased isotopic composition of the treated ascorbic acid might have altered the neutron to proton ratio in the nucleus. The changes in isotopic abundance could be due to changes in nuclei possibly through the interference of neutrino particles via the Trivedi Effect®-Consciousness Energy Healing Treatment. The increased isotopic abundance ratio and peak area of the treated ascorbic acid may increase the intra-atomic bond strength and its stability. This novel ascorbic acid after the Trivedi Effect®-Consciousness Energy Healing Treatment would be very useful to design more efficacious pharmaceutical formulations against scurvy, obesity, cardiovascular diseases, hypertension, rheumatoid arthritis, Alzheimer's disease, cancer, etc.

Characterization of the Consciousness Energy Healing Treated Cholecalciferol Using LC-MS and GC-MS Spectrometry

Apr 2021 DOI 10.14302/issn.2328-0182.japst-21-3772
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd., Thane (W), Maharashtra, India.

Vitamin D3 (cholecalciferol) is a fat-soluble vitamin, which widely used for the prevention and treatment rickets, osteoporosis, arthritis, Parkinson’s and Alzheimer’s diseases, autoimmune disease, dementia, glucose intolerance, etc. The impact of the Trivedi Effect®-Consciousness Energy Healing Treatment on the structural properties and the isotopic abundance ratio of cholecalciferol were evaluated using LC-MS and GC-MS spectroscopy. The test sample cholecalciferol was divided into control and treated parts. Only, the treated cholecalciferol was received the Trivedi Effect®-Consciousness Energy Healing Treatment remotely by a renowned Biofield Energy Healer, Dahryn Trivedi. The LC-MS spectra of both the samples at retention time (Rt) ~22 minutes exhibited the mass of the molecular ion peak at m/z 385.25 (calcd for C27H45O+, 385.35). The LC-MS based isotopic abundance ratio of PM+1/PM in the treated cholecalciferol was increased by 0.74% compared with the control sample. But, the GC-MS based isotopic abundance ratio of PM+1/PM and PM+2/PM in the treated cholecalciferol was significantly increased by 66.39% and 62.69%, respectively compared with the control sample. Hence,13C, 2H, 17O, and 18O contributions from C27H44O+ to m/z 386 and 387 in the treated cholecalciferol were significantly increased compared with the control sample. The isotopic abundance ratios of PM+1/PM (2H/1H or 13C/12C or 17O/16O) and PM+2/PM (18O/16O) in the treated cholecalciferol were significantly increased as compared to the control sample. The increased isotopic composition of the Trivedi Effect®-Consciousness Energy Healing Treated cholecalciferol might have altered the neutron to proton ratio in the nucleus via the possible mediation of neutrino. The increased isotopic abundance ratio of the treated cholecalciferol may increase the intra-atomic bond strength, increase its stability. The new form of cholecalciferol would be better designing novel pharmaceutical formulations that might be more stable and more efficacious for the prevention and treatment of various diseases such as vitamin D deficiency, rickets, osteoporosis, arthritis, multiple sclerosis, cancer, diabetes mellitus, mental disorders, cardiovascular diseases, hypertension, infections, influenza, cognitive impairment in older adults, Parkinson’s and Alzheimer’s diseases, autoimmune disease, dementia, glucose intolerance, multiple sclerosis, etc.

Evaluation of the Isotopic Abundance Ratio of Consciousness Energy Healing Treated L-Tryptophan Using LC-MS Spectrometry

Apr 2021 DOI 10.14302/issn.2576-6694.jbbs-21-3773
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd., Thane (W), Maharashtra, India.

L-tryptophan is an essential α-amino acid, necessary for the normal growth in newborns, nitrogen balance in adults, protein synthesis, precursor of serotonin, melatonin, niacin, and albeit inefficiently in human, also the precursor of indole alkaloids and auxins in plants. This current study was designed to investigate the impact of the Trivedi Effect®-Biofield Energy Healing Treatment (Blessing) on the structural properties and the isotopic abundance ratio of L-tryptophan using LC-MS analytical technique. L-tryptophan sample was divided into two parts, one part of L-tryptophan was considered as the control sample (no Biofield Energy Treatment was provided), while the second part was treated with the Trivedi Effect®-Consciousness Energy Healing Treatment/Blessing remotely by a renowned Biofield Energy Healer, Dahryn Trivedi and termed as the treated sample. The mass spectra of both the control and treated samples with respect to the chromatographic peak at retention time (Rt) 2.1 minutes exhibited the mass of the molecular ion peak adduct with hydrogen ion at m/z 205.08 (calcd for C11H13N2O2+, 205.1), along with low molecular fragmented mass peaks at m/z 188, 159, and 102 for C11H12N2O2+, C10H11N2+, and C8H6+, respectively were also observed. The isotopic abundance ratio of PM+1/PM (2H/1H or 13C/12C or 15N/14Nor17O/16O) in the treated L-tryptophan was significantly increased by 35.93% compared with the control sample. Hence,the 13C, 2H, 15N, and 17O contributions from C11H13N2O2+ to m/z 206.08 in the treated L-tryptophan was significantly increased compared to the control sample. It could be hypothesized that the changes in the isotopic abundance and mass peak intensities due to the modification in nuclei possibly through the interference of neutrino particles using the Trivedi Effect®-Consciousness Energy Healing Treatment. The Biofield Energy Treated/Blessed L-tryptophan with increased stable isotopic abundance ratio might have changed the physicochemical properties with higher force constant in the molecule. The new form of treated L-tryptophan would be a better and more stable in the supplements, nutraceutical, and pharmaceutical formulations, which would be advantageous for the prevention and treatment of pellagra, depression, kynurenine. It could also maintain the normal label of tryptophan and avoid increase of its metabolite, lower the neurotoxin and a metabotoxin behavior, glutaric aciduria type I (glutaric acidemia type I) disorder, eosinophilia-myalgia syndrome (EMS), incurable and sometimes fatal flu-like neurological condition, etc. As tryptophan is the precursor for the plant hormones like indole alkaloids and auxins, hence, this treated L-tryptophan would be advantageous for the improvement of yield, productivity, and quality of crops and other plants.

Analysis of Isotopic Abundance Ratio of Consciousness Energy Healing Treated Metronidazole Using LC-MS and GC-MS Spectrometry

Nov 2020 DOI 10.14302/issn.2328-0182.japst-20-3618
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd., Thane (W), Maharashtra, India.

Metronidazole is an antibiotic and useful for the antibacterial and antiprotozoal medication. This study was performed to investigate the impact of the Trivedi Effect®-Biofield Energy Healing Treatment on the structural properties and the isotopic abundance ratio of metronidazole using LC-MS and GC-MS spectroscopy. Metronidazole sample was divided into two parts, one part of metronidazole was considered as control (no Biofield Energy Treatment was provided), while the second part was treated with the Trivedi Effect®-Consciousness Energy Healing Treatment remotely by a renowned Biofield Energy Healer, Alice Branton and termed as a treated sample. The LC-MS spectra of both the samples of metronidazole at the retention time (Rt) 2.61 minutes exhibited the mass of the protonated molecular ion peak at m/z 172 M+H+ (calculated for C6H10N3O3+, 172.07). The LC-MS based isotopic abundance ratio of PM+1/PM (2H/1H or 13C/12C or 15N/214N or 17O/16O) in the treated metronidazole was significantly increased by 8.24% compared with the control sample. Thus,13C, 2H, 15N,and17O contributions from (C6H10N3O3)+ to m/z 173 in the treated sample were significantly increased compared with the control sample. The GC-MS based isotopic abundance ratio of PM+1/PM in the treated metronidazole was significantly increased by 5.92% compared with the control sample. Hence,13C, 2H, 15N, and217O contributions from (C6H9N3O3)+ to m/z 172 in the Biofield Energy Treated sample were significantly increased compared with the control sample. However, the isotopic abundance ratio of PM+2/PM in the treated metronidazole was significantly decreased by 18.2% compared with the control sample. Hence,18O contributions from (C6H9N3O3)+ to m/z 173 in the treated sample were significantly decreased compared with the control sample. The isotopic abundance ratio of PM+1/PM (2H/1H or 13C/12C or 15N/14N or 17O/16O) and PM+2/PM (18O/16O) in the treated metronidazole was significantly altered compared to the control sample. From the results, it can be hypothesized that the changes in isotopic abundance and mass peak intensities could be due to changes in nuclei possibly through the interference of neutrino particles via the Trivedi Effect® - Consciousness Energy Healing Treatment. The new form of treated metronidazole would be better designing novel pharmaceutical formulations that might offer better therapeutic response against bacterial and protozoal infection in the vagina (bacterial vaginosis), stomach (giardiasis, trichomoniasis, pseudomembranous colitis), joints (pelvic inflammatory disease), liver, skin, brain, and respiratory tract, aspiration pneumonia, rosacea, intra-abdominal infections, lung abscess, fungating wounds, periodontitis, amoebiasis, oral infections, etc.

Understanding the Stealth Properties of PEGylated lipids: A Mini-Review

Aug 2020 DOI 10.14302/issn.2835-513X.ijl-20-3457
Gupta AnjuCorresponding author Department of Mechanical, Industrial and Manufacturing Engineering, University of Toledo, Toledo, OH 43614, USA

PEGylation is a well-established strategy for improving the target specificity, circulation time and stability of liposomes, thereby improving their stealth properties. This brief review provides an insight on the composition of PEGylated liposomes and the characteristics that dictate the functionality of PEGylated liposomes such as surface density, molecular weight, presence of linkers and acyl groups. Physicochemical techniques used to characterize the PEG liposomes and test their stability are also discussed along with their clinical implications. This review provides the readers with a broad range of understanding of various PEGylated lipids, techniques to access their stability in liposomal formulations and state-of -the-art development of PEGylated liposomal formulations.

Enzymes Open Access

Cloning, Expression and Characterization of the α-glucuronidase from the Hyperthermophile DictyoglomusturgidumDSM 6724Ô

Jul 2020 DOI 10.14302/issn.2690-4829.jen-20-3480
Brumm PhillipCorresponding author C5-6 Technologies LLC, 5627 Old Oak Drive, Fitchburg, WI 53711, USA

Conversion of biomass into fermentable sugars is a major requirement for successful and cost-effective biofuels production. The conversion of xylan to sugars requires multiple enzymes including α-glucuronidase. Here we report the cloning, expression, purification and characterization of the α-glucuronidase from Dictyoglomusturgidum(DtuAgu). DtuAgu is an intracellular protein of 685 amino acids and a predicted molecular weight of 79.4 kD. Enzymatic activity was optimum between pH 7.0 and 8.0 and at 85°C. The specific activity of the enzyme was 10 u/mg when measured using mixed aldouronic acids. The specific activity on isolated glucuronoxylan was approximately 20% of the value obtained with xylooligosaccharides. DtuAgu significantly improved xylan conversion to xylose when evaluated using two mixtures of thermostable bacterial enzymes and two sources of xylan. DtuAgu has the potential to be a key player in thermostable enzyme cocktails for the conversion to biomass to biofuels.α

Peroxidase from Coleus Forskohlii: Purification and Biochemical Characterization

Jan 2020 DOI 10.14302/issn.2379-7835.ijn-19-3139
Q. Almulaiky YaaserCorresponding author Chemistry Department, Faculty of Sciences and Arts, University of Jeddah, Khulais, P.O. Box 355, Khulais, 21921, Saudi Arabia

In this study, a peroxidase from new source was purified using ion exchange and gel filtration techniques. The recovery for peroxidase activity was 19% with 11-fold purification and specific activity of 749 unit/mg protein. Purified peroxidase demonstrated a molecular mass of 39 kDa using gel filtration and was confirmed as a single band on SDS-PAGE. The purified peroxidase revealed a broad optimum pH activity at 6.0-6.5 and 50°C temperature. The kinetic parameters for purified peroxidase toward H2O2 and guaiacol as substrates were found to be Km = 3.355, 5.395 mM, Kcat = 99.52, 79.56 s-1 and Vmax =1.531, 1.242 µmole ml-1 min-1, respectively. The catalytic efficiency (kcat/Km) of the purified peroxidase was 14.75 and 29.66 s−1 mM−1 for guaiacol and H2O2, respectively. Peroxidase activity was observed to be enhanced by Cu2+, Co2+, Ni2+ and inhibited in the presence of Sn2+, Al3+, Hg2+, NaN3, EDTA and urea. Characterization showed that peroxidase purified from C. forskohlii has the ability to be used for food industrial applications.

Evaluation of the Impact of Consciousness Energy Healing Treatment on the Isotopic Abundance Ratios (PM+1/PM and PM+2/PM) of Ofloxacin

Nov 2019 DOI 10.14302/issn.2377-2549.jndc-19-3080
Jana SnehasisCorresponding author Trivedi Science Research Laboratory Pvt. Ltd., Thane (W), India

Ofloxacin is a class of fluorinated quinolone antibiotics, useful against most of the Gram-positive and Gram-negative bacterial infections. This study was designed to investigate the impact of the Trivedi Effect®-Consciousness Energy Healing Treatment on the structural properties and the isotopic abundance ratio of ofloxacin using LC-MS and GC-MS spectroscopy. Ofloxacin sample was divided into control and treated parts. The control ofloxacin did not receive the Consciousness Energy Healing Treatment, while the treated ofloxacin receives the Consciousness Energy Healing Treatment remotely by a renowned Biofield Energy Healer, Dahryn Trivedi. The LC-ESI-MS spectra of both the samples of ofloxacin at the retention time 3.05 minutes exhibited the mass of the protonated molecular ion peak at m/z 362.17 (M+H)+ (calculated for C18H21FN3O4+, 362.15). The LC-MS based isotopic abundance ratio of PM+1/PM in the treated ofloxacin was significantly increased by 56.57% compared with the control sample. Thus, 2H, 15N, 13C, and 17O contributions from (C18H21FN3O4)+ to m/z 363.17 in the treated ofloxacin were considerably increased compared with the control sample. The GC-MS based isotopic abundance ratios of PM+1/PM and PM+2/PM in the treated ofloxacin was significantly increased by 9.53% and 12.94%, respectively compared with the control sample. Hence, 2H, 15N, 13C, 17O, and 18O contributions from (C18H21FN3O4)+ to m/z 318 and 319 in the treated ofloxacin were significantly increased compared with the control sample. The LC-MS and GC-MS based isotopic abundance ratios of PM+1/PM (2H/1H or 15N/14N or 13C/12C or 17O/16O), and PM+2/PM (18O/16O) in the treated ofloxacin were considerably improved compared to the control sample. The increased isotopic abundance ratio of the treated ofloxacin would increase the chemical bond strength and increase the stability in the body. The new form of treated ofloxacin would be more stable compared to the control sample and would be very useful to design improved pharmaceutical formulations that might offer better therapeutic response against infections of the urethra and cervix, infectious diarrhoea, urinary tract infections, cellulitis, chronic bronchitis, pneumonia, prostatitis, multidrug-resistant tuberculosis, plague, otitis media, etc.

Tetrodotoxin (TTX) Time–Resolved Absorption and Resonance FT–IR and Raman Biospectroscopy and Density Functional Theory (DFT) Investigation of Vibronic–Mode Coupling Structure in Vibrational Spectra Analysis

Jun 2019 DOI 10.14302/issn.2377-2549.jndc-19-2765
Heidari AlirezaCorresponding author Faculty of Chemistry, California South University, 14731 Comet St. Irvine, CA 92604, USA

Tetrodotoxin (TTX) is a potent neurotoxin. Its name derives from Tetraodontiformes, an order that includes pufferfish, porcupinefish, ocean sunfish, and triggerfish; several of these species carry the toxin. Although tetrodotoxin was discovered in these fish and found in several other aquatic animals (e.g., in blue–ringed octopuses, rough–skinned newts, and moon snails), it is actually produced by certain infecting or symbiotic bacteria like Pseudoalteromonas, Pseudomonas, and Vibrio as well as other species found in animals. Parameters such as FT–IR and Raman vibrational wavelengths and intensities for single crystal Tetrodotoxin (TTX)are calculated using density functional theory and were compared with empirical results. The investigation about vibrational spectrum of cycle dimers in crystal with carboxyl groups from each molecule of acid was shown that it leads to create Hydrogen bounds for adjacent molecules. The current study aimed to investigate the possibility of simulating the empirical values. Analysis of vibrational spectrum of Tetrodotoxin (TTX) is performed based on theoretical simulation and FT–IR empirical spectrum and Raman empirical spectrum using density functional theory in levels of F/6–31G*, HF/6–31++G**, MP2/6–31G, MP2/6–31++G**, BLYP/6–31G, BLYP/6–31++G**, B3LYP/6–31G and B3LYP6–31–HEG**. Vibration modes of methylene, carboxyl acid and phenyl cycle are separately investigated. The obtained values confirm high accuracy and validity of results obtained from calculations. Molecular structure of Tetrodotoxin (TTX) 1–42.

Antioxidant Activity Open Access

Purification and Characterization of Xanthine Oxidase from Liver of the Sheep (Ovis Aries)

Mar 2019 DOI 10.14302/issn.2471-2140.jaa-19-2699
M.M. Masoud HassanCorresponding author Molecular Biology Department, National Research Centre, El-Tahrir st., Dokki, Giza, Egypt.

Xanthine oxidase is a commercially important enzyme with wide area of medical applications to develop diagnostic kits. Xanthine oxidase was extracted, purified and characterized from sheep liver (SLXO). The purification procedure involved acetone precipitation and chromatography on DEAE-cellulose and Sephacryl S-300 columns. The sheep liver xanthine oxidase was homogeneously purified 31.8 folds with 3.5 U/mg specific activity and 24.1% recovery. SLXO native molecular weight was 150 kDa and on SDS-PAGE appeared as single major band of 75 kDa representing a homodimer protein. Isoelectric focusing of the purified SLXO resolved into two closely related isoforms with pI values of 5.6 and 5.8. The apparent Km for xanthine oxidase at optimum pH 7.6 was found to be 0.9 mM xanthine. FeCl2 and NiCl2 increased the activity of SLXO, while CuCl2 and ZnCl2 were found to be potent inhibitors of the purified enzyme. Allopurinol inhibits SLXO competitively with one binding site on the purified molecule and Ki value of 0.06 mM.

In Silico Inhibition of Essential Candida albicans Proteins by Arenicin, a Marine Antifungal Peptide

Jan 2019 DOI 10.14302/issn.2643-0282.imsj-18-2448
Santiago Freitas e Silva KleberCorresponding author Biological Sciences Institute, Federal University of Goiás, Brazil

Fungal infections increased substantially in the last years, becoming a relevant public health problem. Many of these infections account for high rates of morbidity and mortality. The emergence of resistant fungal clinical isolates have also motivate studies to find new antifungal therapies. Candida albicans is an oportunistic pathogen and affects a great number of immunocompromised patients worldwide. The marine ecosystem has been considered a rich source of bioactive metabolites due to the complexity and originality of its structures. Proteins and peptides from marine organisms have been shown to have antiviral, anti-inflammatory, antimalarial, anticancer, antimicrobial and antifungal properties. Arenicins are antimicrobial peptides isolated from the marine lugworm Arenicola marina with 21 amino acid residues in a β-hairpin structure. Dihydrofolate reductase, exo-b-(1,3)-glucanase and sterol 14α-demethylase are essential C. albincas enzymes that take part in DNA, cell wall and membrane metabolism, respectively. The present study evaluates the interaction of arenicin with important enzymes of C. albicans related to cell wall, ergosterol and DNA metabolism in order to elucidate possible molecular targets. We showed through an in silico approach, that a single compound from a marine worm (A. marina), can bind to three C. albicans essential proteins. The interaction occurs in regions inside the active site or at least near, with amino acid residues evaluated as hot spots. Arenicin is a new promising antifugal drug. The next step is to investigate protein-protein interactions performed by DHFR, EBG and CYP51 and assess whether arenicin is able to disrupt essential interaction or not.

The Current Immunoassays and Emerging Immunogenomic Approaches for Immunomonitoring Cancer and Infectious Diseases

Jan 2019 DOI 10.14302/issn.2572-3030.jcgb-18-2527
Zhang XiCorresponding author Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, United States

As remarkable advances have been made in immunotherapies, the overall goal of immunotherapy has become the selection of patients and evaluating the benefits of treatment. One of the major obstacles to develop immunotherapies is the lack of effective immune monitoring. Monitoring of key changes in the immune system during immunotherapy (immunomonitoring) provides important insights into efficacy as well as the immune mechanisms of response at the molecular and cellular levels. Immunomonitoring techniques include traditional immunoassays that use specific antibodies to recognize the analytes of interest, new high-throughput immunoassays that target immune cells and nucleic acids, and less classical immunogenomic approaches that rely on genome-wide profiling and computational analysis on various types of clinical samples. Substantial progress has been made in the application of immunomonitoring strategies to pre-clinical and clinical studies, especially for patients with cancer and infectious diseases. Current and emerging immunoassays performed in clinical practice will be examined herein, and immunogenomic approaches that complement these techniques will be highlighted and compared with traditional methods. Finally, we will discuss several new computational methods for analyzing gene signatures for immunomonitoring, including gene expression data profiling by microarray, the nCounter technique, regular RNA-seq, and single-cell RNA-seq. Novel immunomonitoring techniques, especially immunogenomic approaches, will continue to be developed to facilitate assessment of immunotherapeutic response and predict patient outcomes in cancer and infectious disease.  

Epigenetic Biomarkers in Head and Neck Cancer 

Nov 2018 DOI 10.14302/issn.2572-3030.jcgb-18-2428
Gupta ShilpiCorresponding author Stem Cell and Cancer Research Lab, Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Sector-125, Noida-201313, India.

Head and neck cancers (HNCs) are the most prevalent and aggressive type of cancers. Genetic, epigenetic, environmental and viral risk-factors are associated with HNC carcinogenesis. Persistent infection of oncogenic human papillomaviruses (HR-HPVs) represent distinct biological, molecular and epigenetic entities in HNCs. There are three main epigenetic mechanisms that regulate transcription, these are DNA methylation, histone modifications and alteration in non-coding RNA networks, which can dissected to identify innovative and accurate epigenetic biomarkers for diagnosis and prognosis of HNC patients. Due to the lacunae of accurate distinctive biomarkers for the definite diagnosis of HNC, the identification of predictive epigenetic markers is necessary that might modify or increase HNC patient’s survival. In this mini review, we briefly summarize the current knowledge of different epigenetic biomarkers in HNC.

Nephrology Advances Open Access

Action Mechanisms and Therapeutic Targets of Renal Fibrosis

Nov 2018 DOI 10.14302/issn.2574-4488.jna-18-2443
Su WeiCorresponding author Department of Nephrology, Baoji Central Hospital, No. 8 Jiangtan Road, Baoji, Shaanxi 721008, China

Renal fibrosis was a chronic and progressive process affecting kidneys in chronic kidney disease (CKD), regardless of cause. Although no effective targeted therapy yet existed to retard renal fibrosis, a number of important recent advances have highlighted the cellular and molecular mechanisms underlying the renal fibrosis. The advances including TGF-β/Smad pathway, oxidative stress and inflammation, hypoxia and gut microbiota-derived from uremic solutes were highlighted that could provide therapeutic targets. New therapeutic targets and strategies that are particularly promising for development of new treatments for patients with CKD were also highlighted.

Biosemiotic Research Open Access

Space of Cross-Disciplinary Researches of Life, Nature and Society

Aug 2018
Paranina AlinaCorresponding author Department of physical geography and environmental management, Herzen State Pedagogical University of Russia, Russia

Journal of Biosemiotic Research is a new periodical devoted to a young, actively developing science. A review of recent scientific publications shows that in the broad scientific space of biosemiotics contemporary questions and "eternal themes" interact, not finding an answer in the private sciences - anthropology, semiotics of culture and philosophy1,2. To solve them, the fundamental foundations of science and new achievements, the opportunities of the latest technologies and scientific communications are attracted. Like all young sciences, biosemiotics has many definitions. We give here the most famous ones. "Biosemiotics: (bios, life + semion = sign) is an interdisciplinary field of theoretical and empirical research, analyzing communication and signification in living systems. Signed processes, ranging from molecular to ecological and evolutionary, have been studied throughout the history of biology; however, very often descriptions of information and communication aspects of living systems were considered only metaphorical, believing that the essence of them can be understood with the help of physical and chemical descriptions. In biosemiotics, on the other hand, information sign processes are considered as the primordial, basic system of phenomena of life, requiring a new understanding..."3. "Biosemiotics explores sign systems of various levels: molecular biological (genetic code), intracellular (signal peptides), intercellular (mediators, immune interactions), intraorganism (hormones, conditioned reflex reactions) and interorganism (telergons, pheromones, attractants) ... In addition, biosemiotics covers all the problems associated with the problem of the existence of language and thinking in animals." However, today we can go further and add to the analysis the next stage of evolution, standing between animals and modern human (Homo sapiens sapiens).

Drug Design Progress of In silico, In vitro and In vivo Researches

Aug 2018
Bai QifengCorresponding author Key Lab of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P. R. China

Drug design, referred to the fields of pharmacology, biotechnology and medicine, is in silico, in vitro and in vivo assay processes of finding new candidate medications based on the biological targets. The in silicoexperiments of drug discovery are involved in the macromolecular structure databases, small molecule databases, molecular docking, de novo drug design and molecular dynamics simulations. The in vitro experiments of drug discovery need evaluate the direct interaction information between ligands and targets as well as the function of ligands on signaling pathway in the cell. The in vivo experiments of drug discovery give the convincing evidence for preclinical trial at the physiological level. In this review, we outline the drug design components of databases, virtual screening tools, biochemical assays, cell-based system and animal models.

Evolutionary Science Open Access

Is Natural Selection still have to be Regarded A Foundation Stone of Evolutionary Process?

Jun 2018 DOI 10.14302/issn.2689-4602.jes-18-2128
I. Granovitch AndreyCorresponding author Department of Invertebrate Zoology, Faculty of Biology, St. Petersburg State University

Natural selection is a buzzword used to describe the main driving force of evolution. Its creative role is believed to be based on: a) an unlimited variety of organisms caused by hereditary variation and b) a direct connection between hereditary changes and their phenotypic expression. These are the two requirements that can lead to the genetically based changing modalities of characters through “iterations” of natural selection in the series of successive generations. Are these two requirements fulfilled in the nature, however? The present study focuses on the analysis of these two “foundation stones” of natural selection. Firstly, hereditary variation is shown to be essentially non-homogenous. New hereditary characteristics of individuals fall onto a narrow “strip of land” in the sea of potential possibilities. Secondly, the consequences of changes in the genotype of an organism are involved into a system of hierarchical multiple compensation, from the molecular to the biocenotic level. In a way, the signal of hereditary change passes through a series of “system filters” at epigenetic, ontogenetic, physiological, behavioural, populational and biocenotic level. Each filter is represented by multiple feedbacks maintaining the integrity of systems at each level and at all the hierarchical levels taken together. It is in these “system filters” the adaptive nature of characters is formed representing the every individual as a subject to the Law of Multilevel Self-Organization. The emerging understanding of this provides a strong reason to change the evolutionary paradigm from the mainly selectogenetic to the mainly orthogenetic one.  

Lipid Components in the Dynamin Fraction Prepared from Rat Brain

May 2018 DOI 10.14302/issn.2835-513X.ijl-18-2122
Maekawa ShoheiCorresponding author Department of Biology, Graduate School of Science, Kobe-University, Japan.

Membrane dynamics in the presynaptic region of the neuron is a key process of neuronal signal transduction. Dynamin plays a central part during endocytosis participating in the deformation of membrane structure and constriction. During the study of molecular interaction of presynaptic proteins, we found that dynamin fraction prepared from brain extract contains several lipid components. Fractionation of lipids with thin layer chromatography and mass-analysis showed the presence of phosphatidylcholine, phosphatidylethanolamine, cerebroside, cholesterol and its-derivatives, and triacylglycerol. Since the GTPase activity of bacterially expressed dynamin was activated by the extracted lipid fraction, lipid components that affect the GTPase activity of dynamin was screened and cerebroside, hydroxycholesterols, cholesterol, and triacylglycerol were found to activate the GTPase activity. This result not only suggests the possibility that several neutral lipids participate in the membrane dynamics, but also revealed the possibility that a protein fraction contains lipid components even if its purity was confirmed with SDS-PAGE.

Endocrine Disrupting Chemicals: Epigenetic Relevance and Mechanisms

May 2018
Alatsathianos IoannisCorresponding author Laboratory of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Genetics alone cannot thoroughly expound the environmental impact on the molecular complexity of the endocrine system. Epigenetic-induced alteration in gene expression has emerged as a way in which environmental compounds may exert endocrine effects. The environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to, on a daily basis. Epigenetic mechanisms, mainly the methylation of DNA and the modification of histones, lead to differentiated activation and deactivation of genome domains creating phenotype plasticity and divergent endocrine function among populations and individuals, as well. The issues examined in the present review are related to environmental epigenetics, and more precisely, the epigenetic-mediated modulation and relevance of endocrine disrupting chemicals, focusing on three broad aspects: 1) persistence of EDs, 2) their major hormonal effects and 3) the potential of compounds previously considered as endocrine disruptors to induce epigenetic effects. Evidence suggests that environmental exposures notably impact expression of endocrine-related genes and, thus, affect clinical endocrine outcomes.

Emerging Roles of Plant Circular RNAs

Feb 2018 DOI 10.14302/issn.2832-5311.jpcd-18-1955
Zhu Qian-HaoCorresponding author CSIRO Agriculture and Food, GPO Box 1700, Canberra, ACT 2601, Australia

Circular RNAs (circRNAs) are covalently closed single-stranded loop RNA molecules with or without protein coding capability. CircRNAs were previously considered to be splicing intermediates or artifacts but are now found to be pervasively expressed in all eukaryotes studied with some demonstrated to have important molecular functions in various biological processes. CircRNA is now a hot study topic of molecular biology. In this review, we summarize the progress achieved so far on plant circRNAs, including identification and functional characterization, compare the similarities and differences of circRNAs between plants and animals, and discuss the challenges for confident detection and functional investigation of plant circRNAs. Similar to what have been found in animals, plant genomes contain a large number of circRNAs that potentially regulate a wide range of biological progresses related to plant development and biotic/abiotic responses. Despite only a few plant circRNAs have been functionally characterized, novel function/mechanism that has not been reported in animals was revealed, implying more exciting findings about plant circRNAs are expected in future studies.

Towards Precision Rheumatology?

Feb 2018
Paganelli RobertoCorresponding author Department of Medicine & Sciences of Aging University "G. 'Annunzio", Chair of Clinical Immunology and Rheumatology, Chieti – Pescara, Italy

The possibility of tailoring treatment on specific characteristics of patients – i.e. personalized medicine – has received attention in the field of rheumatic diseases since biological DMARDs targeting a unique pathway have become available. However the idea of personalized rheumatology has advanced slowly, at different paces in different disease groups, and it is only now surfacing in the recommendations for assessment and treatment of rheumatoid arthritis (RA). Many of the difficulties encountered stem from the recognition that many rheumatic diseases are not a single entity but encompass different subsets identified on the basis of genetic traits, cellular and molecular characterization both in blood and in tissues, laboratory markers and clinical manifestations (most notably in SLE). These differences suggest a multiplicity of pathogenetic triggers, whose various combination results in slightly or very diverse presentations. Developments in companion diagnostics and the identification of distinct subsets within complex syndromes are going to allow the definition of predictive biomarkers able to reduce poor treatment outcome, thus ensuring that we are treating “the right patient with the right drug”.

Fertility Biomarkers Open Access

Signal Transduction of hCG Induces Decidualization and Uterine Receptivity

Aug 2017 DOI 10.14302/issn.2576-2818.jfb-14-553
Bernardini LCorresponding author Lunicare Medical Center-SISMER Satellite, Sarzana, Italy

All independent experimental data on epithelial and glandular cells lines of human endometrium support the evidence for a rapid production of eicosanoids from the LH/hCG receptors when exposed to the hCG hormone. Prostaglandins rapidly act on the surrounding endometrial stromal cells throughout the adenylyl cyclase enzyme leading to very large amounts of cAMP and angiogenic factors (VEGF) production. The cAMP is the most important intracellular second messenger and along with progesterone accomplishes the full process of decidualization and acquisition of receptivity after estrogenic priming of the endometrium. The status of uterine receptivity lasts few days only and timing for successful embryo-signal transduction system activation by the endometrium is probably short. In absence of in vivo embryonic signals it is impossible to predict, on individual bases, how the intensity of all the complex interlinked molecular changes of decidualization might ever be in case of exposure to native hCG. In other terms, amount of prostaglandins and cAMP produced in response to variably glycosylated hCG are all, in vivo, not measurable variables and should be viewed as a “wave” of biochemical chain reactions. Embryonic hCG is secreted in form of multiple isomers having an unpredictable variable level of glycosylation and control of this variable remains elusive. During cycles of ovarian stimulation many drugs (FSH, LH, HCG) interact with different G-protein coupled receptors (GPCRs) making it possible to alter the prostaglandins-mediated decidualization process ready to be elicited only by hCG of pregnancy. Since the molecules (cAMP and progesterone) controlling endometrial stromal cells differentiation into decidual cells are critical for successful implantation and placenta formation, the evidence of fast eicosanoids production associated with endometrial LH/hCG receptors exposure to hCG and the potential by human endometrium to produce, in response, very large amounts of cAMP has biological and clinical relevance.

Ketamine-Based Treatment of MDD: A Biologist’s Perspective

Aug 2017 DOI 10.14302/issn.2476-1710.jdt-17-1673
Li ShupengCorresponding author School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China

Ketamine’s potential as a fast-acting reagent to treat MDD, especially treatment-resistant depression has caught much attention recently. Although much has been learned about the biological mechanisms underlying ketamine’s effect, there are a few critical issues remained to be resolved. This mini review will briefly discuss several controversial issues that warrant further studies, regarding the molecular, physiological, psychopharmacological, and behavioral effects of ketamine. Understand how ketamine works as an anti-depressant will open the door to better understanding of MDD and its treatment.

Dimerization of the BASIC PENTACYSTEINE Domain in Plant GAGA-Factors is Mediated by Disulfide Bonds and Required for DNA-Binding.

Aug 2017 DOI 10.14302/issn.2638-4469.japb-17-1563
Wanke DierkCorresponding author Universität des Saarlandes, Molekulare Pflanzenbiologie, Campus A2.4, 66123 Saarbrücken, Germany

GAGA-binding proteins in plants are encoded by the BARLEY B-RECOMBINANT / BASIC PENTACYSTEINE (BBR/BPC) family, which can be spilt into several groups on the basis of sequence divergence. The proteins of the different groups share an evolutionary conserved BASIC PENTACYSTEINE (BPC) domain at their very C-terminus that is important for DNA binding. Hallmark of this domain are five Cysteines at defined positions and spacing, which are considered to form a zinc-finger like structure that is involved in GAGA-motif recognition. Here, we report the formation of stabile homodimers between Arabidopsis thaliana group I member BPC1 or between group II member BPC6 in SDS-PAGE. Serial mutations of the highly conserved five Cysteines in the BPC domain of Arabidopsis thaliana BPC1 were tested for their capacity to bind to GAGA-motifs by DPI-ELISA. Our results do not support the idea of a direct involvement of these residues in making physical contact with the DNA, e.g. by formation of a zinc-finger structure. Instead, the data implies an indispensable function for the five Cysteines in homodimerization and stabilization of the protein structure by disulfide bonds. Accordingly, protein folding and structure prediction suggests the formation of a scaffold for dimerization that is supported by three intermolecular and one intramolecular S-S bond. The high degree of conservation between the BPC domains from the different groups and from different species denotes that this role for the five Cysteines might be evolutionary retained.

AB Initio (DFT) and Vibrational Studies of the Synthesized Heterocyclic Compound 2-6-oxo-2-Thioxotetrahydropyrimidin-41H-Ylidene Hydrazine Carbothioamide

Aug 2017 DOI 10.14302/issn.2377-2549.jndc-17-1645
Manivarman S.Corresponding author Assistant Professor, Post Graduate and Research Department of Chemistry, Government Arts College, C-Mutlur, Chidambaram, Tamil Nadu, India.

The structure of the newly synthesized hydrazone derivative 2 - 6 – oxo - 2-thioxotetrahydropyrimidin – 4 1H - ylidene hydrazine carbothioamide (OTTHPYHCT)compound is determined by using spectral information and elemental study. Density functional theory (DFT) studies were performed using the B3LYP/6-31G (d, p) basis set to expand imminent into their structural properties. Frontier molecular orbital (FMO’s) analysis of title compoundwas computed at the same level of theory to get knowledge about their kinetic stability of the molecule by the energy gap value obtained. Global reactivity descriptors are determined to explain the biological activity of the molecule. NBO analysis provides information about charge transfer, delocalization effect, hyperconjugative interactions and the energy responsible for the stabilization of the compound. First hyperpolarizability analysis nonlinear optical response was simulated at the B3LYP/6-31G d, p level of theory as well. Thermodynamic parameters explain vibrational intensity of the molecule.

Neoplasms Open Access

The Role of Heparin in Lung Cancer

Jul 2017 DOI 10.14302/issn.2639-1716.jn-17-1499
Abu Arab WalidCorresponding author Service de Chirurgie thoracique, Université de Sherbrooke, Québec, Canada

Non-small cell lung cancer is a major health problem worldwide. Surgery is still the mainstay of treatment especially in early stages of the disease. Despite the fact that surgery is the potentially curative treatment, the recurrence and mortality rates are still high specifically with more advanced stages of cancer. Heparin has been suggested to have a positive impact on the outcome of various cancers through its anticoagulants properties and; in some instances; due to their antitumor activity. Recently, the molecular mechanisms of tumor cell spreading have been recognised. Metastasis is a complex process that could be therapeutically affected wherever certain extra-cellular matrix proteins could play an important role in prevention of tumor cell migration and invasion. Experimental studies have shown decreased metastases development after heparin use in rat models. We have reviewed the literature to study the role of anticoagulants in cancer patients in general and in patients with Non Small Cell Lung Cancer (NSCLC) specifically.

Colorectal Carcinogenic Pathways and Chemotherapeutic Responsiveness : A Review

Jun 2017 DOI 10.14302/issn.2574-4526.jddd-16-1321
Harrison SanjayCorresponding author Queen Elizabeth Hospital, Queen Elizabeth Avenue, Gateshead

This review synthesizes key molecular pathways in colorectal carcinogenesis and relates them to differential chemotherapeutic responsiveness. It discusses mismatch repair, chromosomal instability, and serrated pathways, linking biomarkers to therapeutic decision‑making.

FT-IR, FT-Raman, Homo-Lumo and UV-Visible Spectral Analysis of E-(N′-(1H-INDOL-3YL) Methylene Isonicotinohydrazide)

May 2017 DOI 10.14302/issn.2377-2549.jndc-17-1459
Saleem H.Corresponding author Department of Physics, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India

A combined experimental and theoretical study on molecular and vibrational structure of E-N¢ (ICINH) had been carried out. The FTIR, FT-Raman and UV-Vis spectra of ICINH were recorded in the solid phase. The optimized geometry was calculated by B3LYP method with 6-311++G(d,p) level of basis set. The harmonic vibrational frequencies, IR intensities and Raman scattering activities of the title compound were calculated at same level of theory. The scaled theoretical wavenumber showed very good agreement with the experimental values. The mulliken charges and thermodynamic functions of the ICINH were also performed at same level of theory. NLO and a study on the electronic properties such as excitation energies and wavelength, were performed by TD-DFT approach. HOMO–LUMO energy gap was also calculated and interpreted.

Sub-Types and Treatment Outcomes of adolescent and Adult Non-Hodgkin Lymphomas in a Resource Poor Setting

Feb 2017 DOI 10.14302/issn.2372-6601.jhor-17-1423
YA Dei-AdomakohCorresponding author Departments of Haematology

Background: The diagnosis and treatment outcomes of Non- Hodgkin Lymphoma’s (NHL) in resource poor countries in the absence of routine molecular studies and immunohistochemistry is challenging. Methods: A retrospective review of case folders of NHL patients aged13 years and above. Information obtained from the case folders included age, sex, histological subtype, subtypes using the Working Formulation and WHO classifications. Treatment given and follow up information were also evaluated. Results: A total of 279 cases of NHL were identified within the study period. The mean age of the patients was 48.8 ± 17.0 years. The male to female ratio was approximately 1.5:1. The majority of cases seen (53%) were diffuse large B- cell lymphoma. Chronic lymphocytic leukaemia/ small lymphocytic lymphoma (22.2%) was the next most common subtype. Other sub types seen, in order of frequency, included diffuse mixed cell lymphoma (6.4%), gastric lymphomas (3.9%), mediastinal B- cell lymphoma (2.9%), Burkitt’s lymphoma (1.8%), splenic marginal zone B-cell lymphoma (1.1%), lymphoblastic lymphoma (1.1%), mucosa- associated lymphoid tissue (MALT) type B- cell lymphoma (0.7%) and follicular lymphoma (0.7%). Conclusion: This study provides an overview of the distribution of NHL subtypes and their outcomes in a resource constrained setting. Immunohistochemistry, cytogenetics and specific molecular studies which are important in characterization of NHLs, should be made affordable and accessible in low income countries.

Functional, Structural and Contextual Analysis of a Variant of Uncertain Clinical Significance in BRCA1: c.5434C->G (p. Pro1812Ala)

Jan 2017 DOI 10.14302/issn.2572-3030.jcgb-16-1307
Morales RafaelCorresponding author Genetic Counselling Unit, Medical Oncology Department, Hospital La Mancha Centro, Av La Constitución, Nº 3, 13600, Alcázar de San Juan, Ciudad Real (Spain)

Interpreting variants of uncertain significance (VUS) for their effect on protein function, and therefore for the risk of developing cancer, has become a challenge in clinical practice for genetic counselling services. The present work combines structural bioinformatics and systems biology based mathematical modelling approaches with the aim of determining the pathogenicity of the mutation c.5434C->G (p.Pro1812Ala) in the BRCA1 gene (detected in a patient from a high risk family) and also to mechanistically understand the effect of this mutation in DNA damage response, a key process in cancer development. The results obtained showed that this mutation prevents the interaction of BRCA1 with key proteins of the cell cycle, subsequently impairing BRCA1-dependent induction of cell cycle arrest. The comparison of the molecular mechanisms associated with the native BRCA1 protein and the mutated variant function in DNA damage response showed that the latter undergoes a reduction in its ability to modulate pathways that are critical for DNA repair and cell cycle control. Therefore, this variant will not be able to exert its tumor suppressive action. Interestingly, these conclusions can be extrapolated to all mutations that, like c.5434C>G (p.Pro1812Ala) BRCA1, cause loss of BRCT domain activity.

The Identification of Somatic Mutations in Interferon-G Signal Molecules in Human Uterine Leiomyosarcoma

Oct 2016 DOI 10.14302/issn.2572-3030.jcgb-16-1276
Hayashi TakumaCorresponding author Dept. of Obstetrics and Gynecology, Shinshu University School of Medicine, Japan,

Human uterine leiomyosarcoma (LMS) is neoplastic malignancy that typically arises in tissues of mesenchymal origin. The identification of novel molecular mechanism leading to human uterine LMS formation and the establishment of new therapies has been hampered by several critical points. We earlier reported that mice with a homozygous deficiency for proteasome beta subunit 9 (PSMB9)/b1i, an interferon (IFN)-g inducible factor, spontaneously develop uterine LMS. The use of research findings of the experiment with mouse model has been successful in increasing our knowledge and understanding of how alterations, in relevant oncogenic, tumour suppressive, and signaling pathways directly impact sarcomagenesis. The IFN-g pathway is important for control of tumour growth and invasion and, has been implicated in several malignant tumours. In this study, experiments with human tissues revealed a defective PSMB9/b1i expression in human uterine LMS that was traced to the IFN-g pathway and the specific effect of somatic mutations of Janus kinase (JAK1) molecule or promoter region on the transcriptional activation of PSMB9/b1i gene. Understanding the molecular mechanisms of human uterine LMS may lead to identification of new diagnostic candidates or therapeutic targets in human uterine LMS.

Vibrational, Ultra Violet, Natural Bond Orbital Analysis of E-1 using Quantum Mechanical Computations and Experimental Spectra.

Sep 2016 DOI 10.14302/issn.2377-2549.jndc-16-1119
Saleem H.Corresponding author Department of Physics, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India

The FT-IR, FT-Raman and UV-Vis spectra of E-[1-(3'-methylthienyl)-5-Phenyl-2,4-Pentadiene-3-one (MPPO) were recorded. The optimized molecular bond parameters, harmonic frequencies were calculated using B3LYP method with 6-311++G (d,p) basis set.The various normal modes were precisely assigned with thehelp ofTED calculation. The theoretical spectrograms for FT-IR, FT-Raman and Ultra Violet visible. Spectra of the title molecule had been constructed. The ICT was calculated by means of Natural Bond Orbital analysis. The Non Linear Optical properties related to polarizability and hyperpolarizability based on the finite-field approach were calculated.The band gap energy was calculated using HOMO-LUMO analysis. Furthermore, the Molecular Electrostatic Potential, Mulliken atomic charges and thermodynamic properties of MPPO were also calculated.

Mucosa-Muscular Signaling for Bile-Induced Esophageal Dysmotility. An Experimental Study in Ex-Vivoguinea-Pig Isolated Esophagi

Jun 2016 DOI 10.14302/issn.2574-4526.jddd-16-1101
A. M. Herbella FernandoCorresponding author Department of Surgery, Escola Paulista de Medicina, Federal University of Sao Paulo, São Paulo, Brazil

Background/Aims: Esophageal motor abnormalities are frequently found in patients with gastroesophageal reflux disease. The effect of bile in esophageal dysmotility is probably secondary to mucosal signaling to the muscular layer and not a transmural process. This study aims to identify the mucosa-muscular signaling path by receptors blockage in an experimental study. Methods: Fifteenguinea pig esophagi were isolated and ex-vivo esophageal contractility was assessed with force transducers. The esophagi were incubated in 100 µM ursodeoxycholic acid for 1 hour and 5 sequential contractions induced by 40 mM KCl spaced by 5 minutes were measured. After 30 minutes, esophagi specimens were incubated in 3 different smooth-muscle contraction antagonists: atropine (1µM) in 5, suramin (1µM) in 5 and genistein (1µM) in 5. The same protocol for contractions was repeated. Values are expressed as mean ± standard deviation and encompass the mean of five stimuli. Experimental procedures were approved by the University Institutional Review Board. Results: Contraction amplitudes after bile incubation but before antagonist incubation were 1.6±0.6 g, 1.2±0.8 g, and 1.2±0.4 g for atropine, suramin and genistein, respectively. Mean contraction amplitudes after antagonists instillation were 1.2±0.6 g, 1.4±0.5 g, 0.9±0.2 g, respectively. There was no different in contraction amplitude before and after instillation of atropine (p=0.188), suramin (p=0.488) or genistein (p=0.079). Conclusion: Our results show that blockage of cholinergic (atropine), purinergic (suramin) or tyrosine kinase (genistein) paths do not change esophageal dysmotility induced by bile. Other molecular path may play the role in this scenario.

Vibrational Spectral Analysis and First Order Hyperpolarizability Calculations on (E)-N′-(furan-2-yl methylene) Nicotinohydrazide

Apr 2016 DOI 10.14302/issn.2377-2549.jndc-16-949
Saleem H.Corresponding author Department of Physics, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India

Vibrational spectral analysis and first order hyperpolarizability calculations on (E)-N′-(furan-2- ylmethylene) nicotinohydrazide (F2CNH), a novel, organic, hydrozone Schiff base compound was synthesized and its structure was characterized by FT-IR, FT-Raman and UV-visible spectrum. The optimized molecular structure, vibrational frequencies and corresponding vibrational assignments of F2CNH were performed on the basis of TED analysis using SQM method. Natural boding orbital (NBO) assessment has been carried out to clarify the charge transfer or conjugative interaction and delocalization of electron density within the molecule. Electronic transitions were studied employing UV-visible spectrum and the observed values were compared with theoretical values. The first order hyperpolarizability and related properties of F2NH were calculated. Besides FMO’s MEP, mulliken atomic charge and various thermodynamic paramefress such as Zero-point energy, rotational constant and enthalpy were also calculated and analyzed.

Ophthalmic Science Open Access

Ciliary Neurotrophic Factor Activated Signaling Pathways in Retinal Müller Cells

Mar 2016 DOI 10.14302/issn.2470-0436.jos-15-739
P. Sarthy VijayCorresponding author Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL 606111.

Ciliary neurotrophic factor (CNTF) is a well-tested, neuroprotective agent that has been shown to retard photoreceptor degeneration in several animal models of retinitis pigmentosa. The molecular mechanisms underlying CNTF-mediated neuroprotection are currently not understood. CNTF could act directly on photoreceptors or it could act indirectly by stimulating Müller glial cells to produce photoreceptor neuroprotective agents. To better characterize CNTF action on Müller cells, we have studied signaling pathways activated by CNTF using an established retinal Müller cell line, rMC-1. RNA was isolated from CNTF-treated cultures, and suppressor of signal transducer and activator of transcription (SOCS3) and Glial fibrillary acidic protein (GFAP) transcript levels were assessed by quantitative real-time PCR. Immunoblotting was used to examine activation ofmitogen activated protein kinase (ERK1/2/MAPK) and phosphoinositide 3-kinase (PI3-K)/Aktpathways in response to CNTF. Additionally, the level of5' AMP-activated protein kinase (AMPK), an enzyme that plays a key role in cellular energy homeostasis levels, was determined by immunoblotting. CNTF treatment resulted strong upregulation of SOCS3 and GFAP transcripts that were blocked by expression of a dominant-negative STAT3 mutant. CNTF treatment also resulted in transient activation of ERK1/2/MAPK but not PI3K/Akt signaling pathway. There was no change in activation of AMPK. We conclude that CNTF treatment leads to stimulation of JAK-STAT and MAPK signaling pathways but not the PI3K/AKT pathway, associated with cell death, in Müller cells.

Newly-Detected Solitary Bony Lytic/Sclerotic Lesion with Soft Tissue Mass in a Previously Treated Case of High-Risk Medulloblastoma: Importance of Contemporary Pathology Techniques to Differentiate Second Malignant Neoplasm from Extra-Neuraxial Metastasis 

Jun 2015 DOI 10.14302/issn.2576-182X.jbsc-14-576
Gupta TejpalCorresponding author Department of Radiation Oncology, Tata Memorial Hospital (TMH) and Advanced Centre for Treatment Research & Education in Cancer (ACTREC), Tata Memorial Centre, Parel, Mumbai: 400 012, INDIA

Multi-modality therapy has led to significant improvement in outcomes for childhood medulloblastoma; however, long-term survivors have become more susceptible to late effects of therapy including induction of second malignant neoplasms and even remain at an increased risk of late relapses including extra-neuraxial metastases. A newly detected solitary lytic/sclerotic osseous lesion in a medulloblastoma survivor away from the radiation field poses considerable diagnostic challenge as it could represent either a second malignant neoplasm or extra-neuraxial metastasis. We report one such case highlighting the importance of contemporary pathology techniques as useful adjuncts to differentiate a second primary osseous Ewing’s sarcoma (ES)/primitive neuro-ectodermal tumor (PNET) from bony metastasis and review the pertinent literature on second malignant neoplasms and extra-neuraxial metastases in medulloblastoma. To the best of our knowledge, this is the first report of a molecularly confirmed second primary osseous ES/PNET in a survivor of childhood medulloblastoma.

Evaluating Circadian Oscillators in Cancer Stem Cells

Jun 2015 DOI 10.14302/issn.2574-4372.jesr-14-607
E. Geusz MichaelCorresponding author Bowling Green State University, Dept. of Biological Sciences, Bowling Green, OH 43403

Cancer is influenced by the ability of cells to maintain circadian rhythms in molecular and metabolic processes. Disturbance of the underlying circadian timing mechanism in circadian clock cells leads to a higher frequency and more rapid progression of cancer. Cancer stem cells with properties of embryonic and somatic stem cells have been implicated as tumor initiators in several types of cancers. Although tumors are reported to have disorganized circadian rhythms, evidence of in vitro circadian rhythms in cancer stem cells of gliomas was recently presented. The possibility and consequences of circadian clocks functioning in cancer stem cells within tumors is examined, and the possible benefits to these cells from circadian timing is discussed in relation to cancer treatments.

Identification of Novel Biomarker for Human Uterine Leiomyosarcoma

Jun 2014 DOI 10.14302/issn.2372-6601.jhor-13-379
Hayashi TakumaCorresponding author Dept. of Immunology and Infectious Disease, Shinshu University, School of Medicine, Matsumoto, Nagano 390-8621, Japan

Sarcomas are neoplastic malignancies that typically arise in tissues of mesenchymal origin. The identification of novel molecular mechanisms leading to sarcoma formation and the establishment of new therapies has been hampered by several critical factors. Human uterine leiomyosarcoma (Ut-LMS) develops more frequently in the muscle tissue layer of the uterine body than in the uterine cervix. Although the development of gynecologic tumors is often correlated with the secretion of female hormones; that of human Ut-LMS does not and its risk factors remain unknown. Importantly, a diagnostic biomarker that can distinguish malignant Ut-LMS from benign tumor uterine leiomyoma (LMA) has yet to be established. Therefore the risk factor(s) associated with human Ut-LMS to establish a diagnosis and novel therapeutic method. Proteasome b-ring subunit LMP2/b1i-deficient mice spontaneously develop Ut-LMS, with a disease prevalence of ~40% by 14 months of age. We shown that LMP2/b1i expression was absent in human Ut-LMS, but present in other human uterine mesenchymal tumors including uterine LMA. Therefore, defective-LMP2/b1i expression may be one of the risk factors for human Ut-LMS. LMP2/b1i is a potential diagnostic biomarker for human Ut-LMS, and may be a targeted-molecule for a new therapeutic approach.

Fine Needle Aspiration (FNA) Cytology of Lymphoid Lesions; Definition and the Outcome of the Atypical/suspicious Diagnostic Category: Study of 34 Cases.

Feb 2014 DOI 10.14302/ISSN.2372-6601.JHOR-13-344
Raddaoui EmadCorresponding author Department of Pathology, King Khalid University Hospital; College of Medicine, King Saud University.

Context: Fine needle aspiration cytology (FNA) is increasingly replacing excisional lymph node biopsy in the assessment of various lymphoid lesions. Recent changes in the classification of non-Hodgkin’s lymphoma, namely the WHO (World Health Organization) Classification of Tumors of Haematopoietic and Lymphoid Tissues has considerably expanded its classification of lymphomas based on the molecular and cytogenetic profiling and immunophenotyping. FNA diagnosis includes varied cytomorphologic diagnostic categories; one of them is the atypical/suspicious. Objective: The atypical/suspicious category constitutes about 20 % of all cases studied by FNA cytology. The objective of this study is to determine the definition and the outcome of this unique category. Design: A retrospective analysis of 34 fine needle aspirations with the diagnosis of atypical/suspicious cases were obtained during the period between 1995 –2000, and the histological and/or clinical follow-up was performed. Results: Flow cytometry was performed on all of the atypical/suspicious lesions. It was positive/diagnostic in 16 (47%) and negative in 18(53%) cases. Excisional follow-up biopsy was obtained in 30 cases. Of these 7(21%) confirmed to be negative, 17(50%) Non-Hodgkin’s lymphoma and 6 (18%) Hodgkin’s Lymphoma. Conclusion: The atypical/suspicious category by fine needle aspiration is a crucial diagnosis as it has proved to represent some type of lymphoma in about two third (68%) of cases.

Kynurenines and Vitamin B6: Link Between Diabetes and Depression.

Sep 2013 DOI 10.14302/issn.2374-9431.jbd-13-218
Oxenkrug GregoryCorresponding author Psychiatry and Inflammation Program, Department of Psychiatry, Tufts University School of Medicine and Tufts Medical Center, Boston MA, USA.

The increased association between depression and diabetes mellitus is generally acknowledged. Recent studies suggest that depression leads to diabetes.However, the underlying molecular mechanisms for this association remain unclear.Literature and our data indicate that inflammatory and/or stress factors in depression up-regulate tryptophan (TRP) conversion into kynurenine (KYN), a substrate for nicotinamide adenine dinucleotide (NAD) biosynthesis. Deficiency of vitamin B6, a co-factor of the key enzymes of KYN – NAD pathway, shunts KYN metabolism from formation of NAD towards production of xanthurenic (XA) and kynurenic (KYNA) acids. Human and experimental studies reveal that XA, KYNA and their metabolites interfere with production, release and biological activity of insulin. We propose that inflammation- and/or stress-induced up-regulation of TRP – KYN metabolism in combination with vitamin B6 deficiency is one of the mechanisms mediating increased risk of diabetes in depression. Consequently, monitoring formation of diabetogenic KYN derivatives might help to identify subjects-at-risk for the development of diabetes. Pharmacological down-regulation of the TRP – KYN – NAD pathway and maintenance of adequate vitamin B6 status might help to prevent the development of diabetes in depression and other conditions associated with inflammation/stress–induced excessive production of KYN and vitamin B6 deficiency, e.g., obesity, cardiovascular diseases, aging, menopause, pregnancy, and hepatitis C virus infection.

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