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The work emphasizes the need for additional research to create novel biomarkers based on the use of microRNAs as a less invasive and precise diagnostic technique for identifying diseases in newborns.
The purpose of this work is to emphasize the possible benefits of a microRNA-based diet in reducing the negative effects of a number of diseases, such as cancer, diabetes mellitus, obesity, hypertension, chronic respiratory conditions, and others.
Melanoma treatment has improved significantly with the development of immune checkpoint inhibition (ICI), which has greatly enhanced the survival rates of patients with metastatic melanoma. However, a significant number of patients do not respond well to ICI treatment and experience progression. This highlights the critical need for practical means to track melanoma patients' response to ICI. To address this issue, the patterns of circulating miRNAs were studied in liquid biopsies of melanoma patients. These miRNAs have the potential to provide essential information regarding the cancer stage, progression, and the presence of PD-L1 in tumor tissue. A sophisticated flow cytometric test was used to measure up to 63 different miRNAs at once. The study identified a combination of nine miRNAs that are capable of distinguishing between different stages of melanoma, particularly stage IV. Additionally, five miRNAs were pinpointed which are downregulated in patients who do not respond to ICI treatment. Furthermore, two miRNAs were found that correlate to the level of PD-L1 in tumor tissue, and low levels of miR-150-5p were linked to poorer overall survival. These findings suggest that circulating miRNAs could serve as valuable markers to predict the effectiveness of ICI, provide insights into the cancer's stage and PD-L1 status, and ultimately help physicians make better treatment decisions in the future. However, further research is needed to confirm these findings and establish their clinical usefulness.
Isolation methods that employ readily-available inexpensive supplies on the open market, which are reliable, as well as economical, such as nucleic acid amplification techniques (NAAT) based on microfluidic technology in low-resource research settings (LRRS) that meets the ASSURED guidelines are essential to develop a noninvasive diagnostic colon cancer screen in stool using micro(mi)RNA molecules. A combination of a microfluidic-based MiRNA stool test with a reliable rolling circle amplification/detection method applied to the quantification of miRNA molecules, result in an affordable sensitive and specific isothermal method for the noninvasive quantitative detection of miRNAs in LRRS. Scientists and engineers have become interested in miRNAs, and they have intensified their efforts to apply emerging simple detection tools to the important bioanalytical challenge of quantifying these small 18-26 nt long molecules. Some of the proposed approaches incorporate novel material, such as simple centrifuges and methods based on microfluidic technology, while others utilize the interesting biological properties of these molecules, such as forming branched RCA structures, allowing for the detection of these biomarker molecules at an attomolar "aM" concentration level, using low cost extraction and isothermal amplification methods in LRRS. We have been interested in studying colorectal cancer (CRC) because it is the 3rd most common malignancy worldwide, and stool can be obtained noninvasively from the patients. We have focused in this research on colon cancer (CC) because it is more common in the USA than rectal cancer (RC). The innovation of our approach lies in the exploratory use of an affordable, quantitative miRNA profiling in noninvasive stool samples in LRRS, whose extracted fragile total RNA is stabilized shortly after excretion from stool by commercially available kits, so it does not ever fragment, followed by quantitative standardized analytical tests that are neither labor intensive, nor require expensive instrumentation, in order to develop apanel of novel miRNA genes for the noninvasive diagnostic screening of early left and right sporadic colon cancers, more economically, and with higher sensitivity and specificity than any other colon cancer screening test currently available on the market. To show the clinical sensitivity and specificity of the proposed quantitative miRNA test using simple methodologies in LRRS,the miRNA results are to be correlated with FOBT, colonoscopy, and pathology data. Standardization establishes test’s performance criteria (sample selection, optimal sample running conditions, preservation and storage), in order to ensure that the assay will perform the same way in any laboratory, by any trained personnel, anywhere in low-resource laboratory settings worldwide.
Isolation methods that employ readily-available inexpensive supplies on the open market, which are reliable, as well as economical, such as nucleic acid amplification techniques (NAAT) based on microfluidic technology in low-resource research settings (LRRS) that meets the ASSURED guidelines are essential to develop a noninvasive diagnostic colon cancer screen in stool using micro(mi)RNA molecules. A combination of a microfluidic-based MiRNA stool test with a reliable rolling circle amplification/detection method applied to the quantification of miRNA molecules, result in an affordable sensitive and specific isothermal method for the noninvasive quantitative detection of miRNAs in LRRS. Scientists and engineers have become interested in miRNAs, and they have intensified their efforts to apply emerging simple detection tools to the important bioanalytical challenge of quantifying these small 18-26 nt long molecules. Some of the proposed approaches incorporate novel material, such as simple centrifuges and methods based on microfluidic technology, while others utilize the interesting biological properties of these molecules, such as forming branched RCA structures, allowing for the detection of these biomarker molecules at an attomolar "aM" concentration level, using low cost extraction and isothermal amplification methods in LRRS. We have been interested in studying colorectal cancer (CRC) because it is the 3rd most common malignancy worldwide, and stool can be obtained noninvasively from the patients. We have focused in this research on colon cancer (CC) because it is more common in the USA than rectal cancer (RC). The innovation of our approach lies in the exploratory use of an affordable, quantitative miRNA profiling in noninvasive stool samples in LRRS, whose extracted fragile total RNA is stabilized shortly after excretion from stool by commercially available kits, so it does not ever fragment, followed by quantitative standardized analytical tests that are neither labor intensive, nor require expensive instrumentation, in order to develop apanel of novel miRNA genes for the noninvasive diagnostic screening of early left and right sporadic colon cancers, more economically, and with higher sensitivity and specificity than any other colon cancer screening test currently available on the market. To show the clinical sensitivity and specificity of the proposed quantitative miRNA test using simple methodologies in LRRS,the miRNA results are to be correlated with FOBT, colonoscopy, and pathology data. Standardization establishes test’s performance criteria (sample selection, optimal sample running conditions, preservation and storage), in order to ensure that the assay will perform the same way in any laboratory, by any trained personnel, anywhere in low-resource laboratory settings worldwide.
There is currently no validated micro(mi)RNA diagnostic stool test to screen for colon cancer (CC) on the market because of the complexity of fecal density, vulnerability of stool to daily changes, and the presence of three sources of miRNAs in stool (cell-free from fecal homogenates, exsosomal miRNAs from fecal exosomes, and fecal colonocytes). To address these complexities, we have first carried out a microarray miRNA experiment, using Affymetrix GeneChip miRNA 2.0 Arrays, on immunocaptured and enriched stool colonocytes of 15 subjects (three healthy controls and twelve colon cancer patients [three TNM stage 0-1 (e.g., polyps◻ ³ 1 cm, villous or tubvillous, or with high grade dysplasia), three stage 2, three stage 3, and three stage 4 in triplicates to select a smaller panel of 14 preferentially expressed mature miRNAs associated with colon cancer (12 Up-Regulated, miR-19a, miR-20a, miR-21, miR-31, miR-34a, miR-96, miR-106a, miR-133a, miR-135b, miR-206, miR-224 and miR-302; and 2 Down-Regulated, miR-143 and miR-145). In a subsequent validation study carried out on total small RNA extracted by immunocapture, followed by RT that employed TaqMan® miRNA Reverse Transcription (RT) Kit and a Custom TaqMan RT Primer Pool, absolute quantification of miRNAs, in copies/µl, was measured using a chip-based Absolute QuantStudio 3D Digital PCR analysis. To ensure that we have chosen human and not bacterial small total RNA, we have carried out coextraction protocols with E. coli K1 strain RS18, compare Agilent electrophoretic patterns, and also sequenced random samples throughout this research using mRNA/miRNA sequencing. Our initial quantitative dPCR miRNA data presented herein showe that the quantitative changes in the expression of a few mature miRNA genes in stool, which are associated with right and left colon cancer, would provide for a more convenient, sensitive and specific diagnostic screening markers thatare more useful than those test markers currently available on the market, such as the low-sensitivity (<15%) fecal occult blood test (FOBT); result in better compliance; and is more economical than the invasive and expensive colonoscopy exam in colon cancer, which can be cured if that cancer is detected at the early TNM stages, and that becomes incurable and deadly if not diagnosed before metastasis. Initial test performance characteristics of the miRNA approach showed that the test has a high numerical predictive value in colon cancer. Moreover, underpinning of the miRNA markers as a function of total RNA showed that the test can numerically differentiate between control subjects and colon cancer patients, particularly at the early stages of that curable cancer. We propose to extend our initial research results to a larger prospective and randomized five-years nested case-control study, to validate the expression of the above 14 miRNAs, in stool of 180 individuals in an epidemiologically designed study, using (30 controls and 150 colon cancer patients (thirty precancerous polyps (stage 0-1), forty five stage 2, and seventy-five colon cancer stages 3 or 4). chosen randomly by an epidemiological method from 900 control and CC subjects to allow for an adequate time to collect the required 900 stool samples, as well as allowing for statistically valid analysis, standardized test conditions, and to provide a mean for determining the true sensitivity and specificity of a miRNA-screening approach in noninvasive human stool. Power-analysis has indicated that a total of 180 individuals, which will take us 5 years to enroll in testing, is an appropriate number of subjects to standardize and validate our proposed miRNA screening test. We may find out at the end of the proposed validation study in stool that fewer miRNAs, or even one miRNA, may suffice to serve as an efficient and a quantitative marker for the non-invasive diagnostic screening of colon cancer in human stool. The above approach when combined with bioinformatics analysis, to correlate miRNA seed data with our previously published messenger (m)RNA target data in stool, allows for a thorough mechanistic understanding of how miRNA genes regulate mRNA expression, and would offer a better comprehensive diagnostic screening test for the non-invasive early detection stage (0-1) of colon cancer. In order to show the clinical sensitivity and specificity of the proposed miRNA test, the absolute miRNA PCR values, in copies/µl, will be correlated with FOBT, colonoscopy, and pathology data. Standardization will establish test’s performance characteristics (sample selection, optimal sample running conditions, preservation and storage) to ensure that the assay will perform the same way in any laboratory, by any trained personnel, anywhere in the World. Ultimately, a smaller number of selected validated miRNAs (<10) showing increased and reduced expression could suffice to give quantitative miRNAs colon cancer expression values, useful for the early diagnostic screening of that curable cancer.
Rooting of cuttings is very important for production of economically important plants. We produced thousands of plantlets in Taxus chinensisvar. mairei using the technology of rooting of cuttings and identified two types of rooted cuttings, one with low rate of root formation and another with high rate of root formation. To determine the physiological role of antioxidative enzymes and microRNAs during the process of rooting, we measured the levels of these antioxidative enzymes and microRNAs in the stem portion, needles, roots, and basal portion of cuttings. Compared to the cuttings with low rate of root formation, cuttings with high rate of root formation had higher expression of polyphenoloxidase (PPO), catalase (CAT), peroxidase (POD), ascorbate peroxidase (APOX), glutathione reductase (GR), and superoxide dismutase (SOD) in the adventitious roots and basal portion of the rooted cuttings 77 days after planting. In the basal portion of cuttings, the content of thiobarbituric acid reactive substances (TBARS) and total phenols were decreased and the content of antioxidants was increased, but they did not changed in the needles of cuttings during planting. Analysis of microRNAs by quantitative realtime PCR demonstrated that expression of miR162, miR408, and miR857 increases in the basal portion of cuttings, but not in the stem portion of cuttings, 77 days after planting. Expression of miR408 and miR857 were also increased in the needles of cuttings 77 days after planting. Changes of these antioxidative enzymes and microRNAs associated with the rooting features of T. chinensisvar. maireicuttings and their functions have been discussed.
Over the last few decades, many research works highlighted the role of miRNAs on cardiac diseases. Ischaemic heart disease (IHD) or coronary heart disease is a condition that is mainly caused by atherosclerosis. It has been established that microribonucleic acids regulate many factors that are involved in the development and pathophysiology of IHD. As a result, there are great potential opportunities for miRNAs to be used as a biomarker for disease differentiation, as well as novel drug targets or therapeutics for the treatment and also as a diagnostic approach. As it is now evident that miRNAs play critical roles in the disease mechanisms, this review article tried to focus on the pathway, in which; the miRNAs stimulate the IHD to develop. By understanding the mechanisms, it will be possible to present a complete strategy of IHD treatment and also solving all the impediments that are highlighted in this article. Still, there are a number of limitations and obstacles on the way of developing a proper therapeutic approach that can be approved and well accepted. This review is mainly dependent on the potential of miRNAs as a promising arena on the field of cardiac treatment and the possible obstacles that are needed to be explored and overcome.
The human OCT4 gene encodes a transcription factor that maintains pluripotency and self-renewal in Embryonic Stem (ES) cells. This gene generates several known transcripts by alternative promoter and alternative splicing (OCT4A, OCT4B and OCT4B1). Even though OCT4A is the main isoform responsible for stemness properties, several recent controversial studies claimed that this isoform is expressed in cancer cell lines and differentiated cells, in addition to the ES cells. Our in silico studies revealed that OCT4A promoter has a completely match binding site for hsa-miR-1285. This microRNA was detected in the human embryonic stem cells for the first time and further studies showed that miR-1285 can target some tumor suppressor genes,(TSGs), such as p53, and oncogenic genes, such as TGM2. Additional bioinformatics analysis of short RNA sequencing data from ENCODE cell lines showed that miR-1285 is expressed in different cancer cell lines and differentiated cells. In this study, we supposed that miR-1285 potentially can bind to the OCT4 promoter and might regulate transcription of the OCT4 in the human cancer cell lines and differentiated cells.
The aim of this review is to compile our understanding of microRNA (miRNA) and its significance in Hypertension (HTN) pathophysiology. The wide spectrum of health disparity is one of the reasons for the dominance of HTN in humans for decades. We are striving hard to understand these variations, and we know to some extent that genetic susceptibilities do exist in HTN. Understanding miRNA will add to the current understanding of the disease process. In later parts, we discussed possible clinical implications of miRNAs in HTN as a biomarker of disease expression and its potential in prognostic and therapeutic applications in HTN.
Thyroid carcinomas encompass a wide spectrum ranging from differentiated thyroid carcinoma (DTC) to poorly differentiated (PDC) and anaplastic thyroid carcinoma (ATC). DTC of both follicular (FTC) and papillary (PTC) types can progress to PDC and AC. The aim of our study was to evaluate if there is differential microRNA (miRNA) expression in various tumor subtypes during this progression. The miRNA profile of differentiated carcinomas (Follicular and Papillary) and ATC were compared with that of PDCs either by itself or in a background of differentiated carcinomas and anaplastic carcinomas. Unsupervised hierarchical clustering analysis revealed that FTC and PDC tend to cluster together in the absence of ATC. Interestingly, in cases with presence of all components i.e. FTC, PDC and ATC, the miRNA profile of poorly differentiated component clusters with that of the Anaplastic carcinoma component. miR-494 and miR-125a-5p were found to be differentially regulated in tumors with an anaplastic component and even the well-differentiated component (FTC) of these tumors were found to be aligned with the anaplastic profile. In addition, we also discovered some differentially regulated miRNAs in follicular variant of papillary thyroid carcinoma as compared to follicular thyroid carcinoma (miR-486-5p and miR-31).
Dengue is a global arbovirus disease primarily carried by Aedes aegypti and Aedes albopictus mosquitoes. It has four serotypes (DENV1, DENV2, DENV3, and DENV4) and is classified into distinct genotypes. The epidemic is complicated by immunological interactions and viral lineage turnover. Neurological problems are commonly associated with DENV2 and DENV3, with DENV2 displaying the most severe symptoms. Direct viral invasion, host-mediated immune system reactions, or host-mediated metabolic alterations can all result in dengue-related neurological issues. The three dengue vaccinations and the significance of meta-analyses for genetic data will also be covered. Finally, establish a connection with the microRNAs associated with dengue fever, creating new opportunities for the creation of dengue treatment regimens involving microRNAs.
Cardiovascular disease is actually a major cause of mortality, illness and hospitalization worldwide. Several risk factors have been identified that are strongly associated with the development of cardiovascular disease. Public prevention strategies have relied predominately on managing environmental factors that contribute to cardiovascular disease, such as obesity, smoking and lack of exercise. The understanding of the role of genetics in cardiovascular disease development has become much more important to link genetics with the onset of disease and response to therapy. This seeks to examine how genes can predispose individuals to cardiovascular disease and how this knowledge might be applied to more comprehensive preventive strategies in the future. In addition, the review explores possibilities for genetics in cardiovascular disease treatment, particularly through the use of identified driver genes and gene therapy. To fully understand the biological implications of these associations, there is a need to relate them to the exquisite, multilayered regulation of protein expression and regulatory elements, mutation, microRNAs and epigenetics. Understanding how the information contained in the DNA relates to the operation of these regulatory layers will allow us not only to better predict the development of cardiovascular disease but also to develop more effective therapies.
Circular RNAs (circRNAs) are recently rediscovered eukaryotic molecules that form a covalently closed-loop structure through a special type of alternative splicing known as backsplicing. These closed-loop structures are highly stable and resistant to RNase degradation, and are thereby expressed in a tissue-specific and evolutionarily conserved manner, which regulates the expression of proteins and mRNAs that are involved in the metabolic pathways associated with specific diseases. Recent evidence of the ubiquitous expression of circRNAs in cancer under physiological and pathophysiological conditions indicates that dysregulation of gene and protein expression might promote tumorigenesis and carcinogenesis, and that circRNAs have important clinical significance in the diagnosis, treatment, and prognosis of cancer and other diseases. This review provides a brief introduction to the characteristics, formation, and function of circRNAs. Some of circRNAs act as microRNA (miRNA) sponges to regulate the level of transcriptional splicing and the expression of parental genes through the circRNA-miRNA-mRNA regulation axis. We summarize recent progress in above-mentioned circRNAs associated with Alzheimer's disease (AD).
Gene therapy has entered a new era with the dawn of CRISPR/Cas9 technology which though were always available in nature but rediscovered to tame into a real-tlife genome editing tool. With the modernization upsurge and changes in ways the “homo sapiens” survived on this planet from hunger to current era of exuberance has led to multiple metabolic issues like type-2 diabetes. Notwithstanding the rapid emergence of medication to suppress the hyperglycemia and insulin resistance associated with this menace, need has definitely emerge to find more personalized and curative dimensions to therapeutics of type-2 diabetes mellitus. Gene therapy is one more addition to Type-2 Diabetes Mellitus (T2DM) therapy, where multiple options have emerged in the shape of microRNA, direct knocking out of cellular structures like proteins and enzymes and very recently the precision nucleases associated with CRISPR technologies. This mini-review attempt to summarize some of the recent examples of gene therapy with major focus on CRISPR/Cas technologies.
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.
MicroRNAs are short sequences of non-coding RNAs crucial in regulation of cell development, proliferation and differentiation. Some of them showed to be related with the expression of osteogenic genes. Aim of the present review was to evaluate the biological effects of titanium implant surfaces activated with miRNAs or antimiRNAs. A bibliographical electronic research was carried out on PubMed/Medline. Articles investigating the influences of miRNA functionalized surfaces on human or animal cells were included. Reports were excluded if investigating surfaces modified with molecules different from miRNAs, if miRNAs were not loaded to titanium surfaces. Five articles met the inclusion criteria. Surfaces functionalized with miRNAs showed to up-regulate the expression of osteogenic genes like RUNX2, OPN, OCN, BMP, OSX, ALP, COL1 and COL3. Investigated surfaces additionally showed more bone-like mineralized tissues, bone lacunae, osteocytes and new blood vessels. MiRNAs loaded to titanium implant surfaces stimulate the expression of genes related to osteoblasts differentiation, osteogenesis, osseointegration and reparation of mineralized tissues. Vectors used to link titanium surfaces and miRNAs did not show cytotoxicity or interference with cells’ viability.
Objective: MicroRNAs are involved in the onset, progression and dissemination of esophageal cancer, and they may be useful as prognostic biomarkers. This study aims to evaluate the relation of miR-21 expression and the prognosis of esophageal cancer patients. Methods: In this study, a meta-analysis is performed by searching PubMed, Science Direct databases, and Cochrane Library. Data are extracted from studies evaluating survival of esophageal cancer patients with either high or low miR-21 expression. Pooled hazard ratios (HRs) and 95% confidence intervals (CI) are calculated. Results: A total of 579 cases of esophageal cancer from five studies are involved for this global meta-analysis. The HR of survival of patients with high miR-21 expression is 1.47 (95% CI: 1.12–1.91; p<0.01) as compared with those with low expression. Conclusions: miR-21 may be a predictor for survival of esophageal cancer patients.