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Objective: This study aimed to analyse the diagnostic performance of miR200b in epithelial ovarian cancer (EOC) in a group of Egyptian patients and to evaluate the combined use of miR200b with other biomarkers as a reliable diagnostic and prognostic indicator of EOC. Methods: We tested the expression of cell-free miR200b in 30 EOC patients before undergoing optimum cytoreductive surgery, 19 females with benign ovarian disease and 14 normal healthy females using quantitative real time PCR. All cases were tested for CA125, HE4 and CRP. The results were compared between the three groups. The double combination of miR200b with each biomarker was tested for a possible improvement of the diagnostic power of the test. Results: MiR200b was significantly overexpressed in EOC patients compared to the other groups, we determined 1.88 folds as the best cutoff for miR200b expression to discriminate between EOC and non-malignant cases with a sensitivity of 63.3% and a specificity of 71%. CA125, HE4 and CRP were evaluated and showed a sensitivity of 96.7%, 45.5%, 81.8% respectively and a specificity of 75.9%, 66.7% and 90% respectively. We evaluated the combined use of miR200b with each biomarker, the best results were seen with the combined use of miR200b and CA125. Conclusion: We concluded that the combined use of miR200b and CA125 could serve as a reliable tool in the initial diagnosis of EOC, and a predictor of event free survival of the disease. [ABSTRACT FROM AUTHOR]

Ionizing radiation is still one of the most effective treatment options for various cancers. It is possible to reduce the side effects of this effective treatment method and increase the chance of success by elucidating the responses it creates at the molecular level in the cell. This study aims to investigate of the molecular effects of therapeutic ionizing radiation on breast cancer, which is the most prevalent cancer type.

Depression accounts for a high proportion of neuropsychiatric disorders and is associated with abnormal states of neurons in specific brain regions. Microglia play a pivotal role in the inflammatory state during depression development; however, the exact mechanism underlying chronic mood states remains unknown. Thus, the present study aimed to determine whether microRNAs (miRNAs) alleviate stress-induced depression-like behavior in mice by regulating the expression levels of their target genes, explore the role of neuroinflammation induced by microglial activation in the pathogenesis and progression of depression, and determine whether the role of the miR-29a-5p/transmembrane protein 33 (TMEM33) axis. In this study, chronic unpredictable mild stress (CUMS) mouse depression model, various behavioral tests, western blotting, dual-luciferase reporter assay, enzyme-linked immunosorbent assay, real-time quantitative reverse transcription PCR, immunofluorescence and lentivirus-mediated gene transfer were used. After exposure to the CUMS paradigm, miR-29a-5p was significantly down-regulated. This downregulation subsequently promoted the polarization of microglia M1 by upregulating the expression of TMEM33, resulting in enhanced inflammatory chemokines affecting neurons. Conversely, the upregulation of miR-29a-5p within the prefrontal cortex (PFC) suppressed TMEM33 expression, facilitated microglia M2-polarization, and ameliorated depressive-like behavior. Only rodent models of depression were used, and human samples were not included. The results of this study suggest that miR-29a-5p deficits within the PFC mediate microglial anomalies and contribute to depressive-like behaviors. miR-29a-5p and TMEM33 may, therefore, serve as potential therapeutic targets for the treatment of depression. • miR-29a-5p is downregulated by chronic stress. • Upregulation of miR-29a-5p improved depression-like behavior. • miR-29a-5p deficits in prefrontal cortex mediate microglial anomalies. • miR-29a-5p and TMEM33 are potential therapeutic targets for depression treatment. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates reaching 60%, mainly due to its excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules exhibiting expressional dysregulation in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting seed-matching and the reverse interplay between miRNA levels and their target genes' expression. Incorporating gene-expression data from our group's experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia, and early invasion, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is under-expressed in dysplasia and early invasion. The malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p, and miR-34a-5p. The identification of stage-specific miRNAs may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis. [ABSTRACT FROM AUTHOR]

A previous study using miRNA sequencing revealed that exposure to a mixture of phthalates during pregnancy and lactation dysregulated rno‐miR‐184 and rno‐miR‐141‐3p in the ventral prostate (VP) of offspring. Here, rno‐miR‐184 and rno‐miR‐141‐3 expressions were obtained by RT‐qPCR in the VP of F1 males as well as in F2 offspring, aiming to establish a relationship with possible oncogenic targets through in silico analyses with multigenerational approach. Additionally, some targets were measured by western blots to highlight a possible relationship between the deregulated miRNAs and some of their targets. VP samples from rats exposed to a mixture of phthalates maternally during pregnancy and lactation (GD10 to PND21‐F1) and VP from offspring (F2) were examined. The phthalate mixture at both concentrations (20 μg and 200 mg/kg/day) increased the expression of both miRNAs in the F1 (PND22 and 120) and F2 (descendants of F1‐treated males) prostate. Target prediction analysis revealed that both microRNAs are responsible for modulating the expression and synthesis of 40 common targets. A phthalate target association analysis and the HPA database showed an interesting relationship among these possible miRNAs modulated targets with prostate adenocarcinoma and other oncogenic processes. Western blots showed alteration in P63, P53, WNT5, and STAT3 expression, which are targeted by the miRNAs, in the VP of F1/F2 males. The data draw attention to the epigenetic modulation in the prostate of descendants exposed to phthalates and adds to one of the few currently found in the literature to point to microRNAs signature as biomarkers of exposure to plasticizers. [ABSTRACT FROM AUTHOR]

This study examined the acute effects of 7-d energy restriction normal-protein (NP; ∼15% of daily intake as protein) compared with higher-protein (HP; ∼38% of daily intake as protein) diets varying in quantities of fresh, lean beef on circulating miRNA expression associated with cardiometabolic disease in 16 women with overweight (mean ± SD; age: 35 ± 8.7 y; body mass index: 28.5 ± 1.9 kg/m2). Fasting blood samples were collected at the end of each diet for miRNA expression, glucose, insulin, adiponectin, C-reactive protein (CRP), and IL-6. Of the 12 surveyed, 10 miRNAs (miR-320a-3p, miR-146a-5p, miR-150-5p, miR-423-5p, miR-122-5p, miR-223-3p, miR-199a-5p, miR-214-3p, miR-24-3p, and miR-126-3p) were detected. Several miRNAs were associated with fasting CRP (i.e., miR-150-5p, miR-24-3p, miR-423-5p; all P < 0.05). miR-423-5p was also associated with fasting glucose, IL-6, and homeostasis model assessment 2 %β cell function (all, P < 0.05). No differences in miRNA expression were identified between diets. These data suggest that fresh, lean beef in a short-term HP, energy restriction diet does not negatively influence circulating miRNAs associated with cardiometabolic disease in women.This trial was registered at clinicaltrials.gov as NCT02614729.

Human and viral microRNAs (miRNAs) are involved in the regulation of gene transcription, and the establishment of their profiles in acute (AHI) and chronic (CHI) HIV infections may shed light on the pathogenetic events related to different phases of HIV disease. Next-generation sequencing (NGS) of miRNA libraries was performed, and the reads were used to analyze miRNA differential expression in the plasma with AHI and CHI. Functional analysis was then undertaken to investigate the biological processes characterizing the two phases of HIV infection. Except for hsa-miR-122-5p, which was found in 3.39% AHI vs. 0.18% CHI, the most represented human miRNAs were similarly represented in AHI and CHI. However, when considering the overall detected miRNAs in AHI and CHI, 15 displayed differential expression (FDR p < 0.05). Functional analysis identified 163 target mRNAs involved in promoting angiogenesis activation in AHI versus CHI through the action of hsa-miR10b-5p, hsa-miR1290, hsa-miR1-3p, and hsa-miR296-5p. The viral miRNAs detected, all belonging to herpesviruses, accounted for only 0.014% of total reads. The present data suggest that AHI patients exhibit strong innate immune activation through the upregulation of hsa-miR-122-5p and early activation of angiogenesis. More specific investigations are needed to study the role of viral miRNAs in HIV pathogenesis. [ABSTRACT FROM AUTHOR]

The aim of this work is to study the effect of platelet factors on the differentiation of mesenchymal stem cells (MSCs) to hyaline cartilage chondrocytes in a three-dimensional environment. MSCs were cultured in a microgel environment with a chondrogenic medium. The microgel consisted of microspheres that combine gelatin and platelet-rich plasma (PRP). The gelatin/PRP microdroplets were produced by emulsion. The gelatin containing the microdroplets was enzymatically gelled, retaining PRP and, just before seeding the cells, platelets were activated by adding calcium chloride so that platelet growth factors were released into the culture media but not before. Platelet activation was analyzed before activation to rule out the possibility that the gelatin cross-linking process itself activated the platelets. The gene expression of characteristic chondrogenic markers and miRNA expression were analyzed in cells cultured in a differentiation medium and significant differences were found between gelation/PRP microgels and those containing only pure gelatin. In summary, the gelatin microspheres effectively encapsulated platelets that secreted and released factors that significantly contributed to cellular chondrogenic differentiation. At the same time, the microgel constituted a 3D medium that provided the cells with adherent surfaces and the possibility of three-dimensional cell–cell contact. [ABSTRACT FROM AUTHOR]

Allergic diseases are one of the most common chronic conditions and their prevalence is on the rise. Environmental exposure, primarily prenatal and early life influences, affect the risk for the development and specific phenotypes of allergic diseases via epigenetic mechanisms. Exposure to pollutants, microorganisms and parasites, tobacco smoke and certain aspects of diet are known to drive epigenetic changes that are essential for immune regulation (e.g., the shift toward T helper 2-Th2 cell polarization and decrease in regulatory T-cell (Treg) differentiation). DNA methylation and histone modifications can modify immune programming related to either pro-allergic interleukin 4 (IL-4), interleukin 13 (IL-13) or counter-regulatory interferon γ (IFN-γ) production. Differential expression of small non-coding RNAs has also been linked to the risk for allergic diseases and associated with air pollution. Certain exposures and associated epigenetic mechanisms play a role in the susceptibility to allergic conditions and specific clinical manifestations of the disease, while others are thought to have a protective role against the development of allergic diseases, such as maternal and early postnatal microbial diversity, maternal helminth infections and dietary supplementation with polyunsaturated fatty acids and vitamin D. Epigenetic mechanisms are also known to be involved in mediating the response to common treatment in allergic diseases, for example, changes in histone acetylation of proinflammatory genes and in the expression of certain microRNAs are associated with the response to inhaled corticosteroids in asthma. Gaining better insight into the epigenetic regulation of allergic diseases may ultimately lead to significant improvements in the management of these conditions, earlier and more precise diagnostics, optimization of current treatment regimes, and the implementation of novel therapeutic options and prevention strategies in the near future. [ABSTRACT FROM AUTHOR]

Suicide is an important public‐health concern, with more than 700,000 people dying by suicide yearly. It is a multifactorial phenomenon, shaped by the effects of sociodemographic, environmental and biological factors. The latter two factors can be linked through epigenetic studies, which examine differences in gene expression that are not due to changes in the DNA sequence itself. Epigenetic mechanisms include micro RNAs (miRNAs), which have a direct effect on already translated mRNA, leading to either decay or translational repression of the target mRNA. MiRNA molecules have been identified as cargo of extracellular vesicles (EVs) used by cells for long‐distance communication, and pathophysiological changes in miRNA in brain cells may be reflected in cerebrospinal fluid (CSF) vesicles. In this study we investigated the presence and differential expression of selected miRNAs in EVs from the CSF of male suicide completers and controls. Western blot and nanoparticle tracking analyses confirmed the presence of small and medium sized EVs. Of the miRNA analyzed (miR‐16‐5p, miR‐19a‐3p, miR‐34c‐5p, miR‐17‐5p, miR‐4286, miR‐26b‐5p, miR‐381‐3p, and miR‐4516) miR‐19a‐3p and miR‐4516 reached statistical significance with p‐values of 0.0408 and 0.0168, respectively. Mir‐4516 and miRNA‐19a‐3p have been previously studied in suicide, and target SLC6A4 and TNF‐α expression, correspondingly. Approximately 70% of known miRNAs are expressed in the central nervous system, and therefore represent an important biomarker potential. Investigating the cargo of CFS and blood EVs would further support the identification of miRNAs with clinical use potential. [ABSTRACT FROM AUTHOR]

Cardiac hypertrophy (CH) is an adaptational enlargement of the myocardium, in exposure to altered stress conditions or in case of injury which can lead to heart failure and death. MicroRNAs (miRNAs) are non-coding RNAs that play a significant role in modulating gene expression. Here, we aimed to identify new miRNAs effective in an experimental CH model and to find an epigenetic biomarker that could demonstrate therapeutic targets responsible for the pathology of heart tissue and serum. In this study, Sprague–Dawley male rats were divided into the training group (TG, n=9) and the control group (CG, n=6). Systolic and diastolic dimensions of the left ventricle and myocardial wall thickness were measured by echocardiography to assess CH. After the exercise program of the rats, miRNA expression measurements and histological analyses were performed. The 25,000 genes in the rat genome were searched using microarray analysis. A total of 128 miRNAs were selected according to the fold change rates, and nine miRNAs were validated for expression analysis. The terminal deoxynucleotidyl transferase dUTP nick (TUNEL) method was used to detect apoptotic cells. Cell proliferation was evaluated by the proliferative cell nuclear antigen (PCNA) method. Necrosis, bleeding, and intercellular edema were detected in TG. The mean histopathological score was higher in TG (p=0.03). There were rarely positive cells for apoptosis of both groups in cardiomyocytes. In the receiver characteristic curve analysis (ROC), the heart tissue rno-miR-290 had an area under the curve (AUC) of 0.920 with 100% sensitivity and 89.90% specificity (p=0.045), rno-miR-194-5p had AUC of 0.940 with 83.33% sensitivity and 100% specificity (p=0.003), and the serum rno-miR-132-3p AUC was 0.880 with 66.67% sensitivity and 100% specificity (p=0.004) in TG. miR-194-5p was used as a therapeutic target for remodeling the cardiac process. While miR-290 contributes to CH as a negative regulator, miR-132 in serum is effective in the pathological and physiological cardiac remodeling process and is a candidate biomarker. [ABSTRACT FROM AUTHOR]

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Atherosclerosis is one of the most fatal diseases in the world. The associated thickening of the arterial wall and its background and consequences make it a very composite disease entity with many mechanisms that lead to its creation. It is an active process, and scientists from various branches are engaged in research, including molecular biologists, cardiologists, and immunologists. This review summarizes the available information on the pathophysiological implications of atherosclerosis, focusing on endothelium dysfunction, inflammatory factors, aging, and uric acid, vitamin D, and miRNA expression as recent evidence of interactions of the molecular and cellular elements. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the mechanism of antitumor effect of (E)-6-morpholino-9-(styrylsulfonyl)-9H-purine (6-Morpholino-SPD) and (E)-6-amino-9-(styrylsulfonyl)-9H-purine (6-Amino-SPD). The effects on apoptosis induction, mitochondrial potential, and accumulation of ROS in treated K562 cells were determined by flow cytometry. The RT-PCR method was used to measure the expression of Akt, CA IX, caspase 3, and cytochrome c genes, as well as selected miRNAs. Western blot analysis was used to determine the expression of Akt, cytochrome c, and caspase 3. The results demonstrate the potential of the tested derivatives as effective antitumor agents with apoptotic-inducing properties. In leukemic cells treated with 6-Amino-SPD, increased expression of caspase 3 and cytochrome c genes was observed, indicating involvement of the intrinsic mitochondrial pathway in the induction of apoptosis. Conversely, leukemic cells treated with 6-Morpholino-SPD showed reduced expression of these genes. The observed downregulation of miR-21 by 6-Morpholino-SPD may contribute to the induction of apoptosis and disruption of mitochondrial function. In addition, both derivatives exhibited increased expression of Akt and CA IX genes, suggesting activation of the Akt/HIF pathway. However, the exact mechanism and its relations to the observed overexpression of miR-210 need further investigation. The acceptable absorption and distribution properties predicted by ADMET analysis suggest favorable pharmacokinetic properties for these derivatives. [ABSTRACT FROM AUTHOR]

Abstract Background The microRNAs (miRs) secreted by the trophectoderm (TE) cells have recently been implicated in the conceptus‐endometrial cross talk during implantation and placentation. These miRs modulate various cellular processes during conception and throughout the pregnancy by regulating the gene expression in the foetal and maternal tissues. Objectives This study was undertaken to elucidate the function of TE secreted miRNAs in the maternal‐foetal cross‐talk during implantation/placentation in buffalo. Methods The in vitro produced blastocysts were cultured on a cumulus feeder layer for 21 days. The relative expression profiles of a selected panel of miRs was generated using the spent media collected on Days 0, 7, 12, 16, and 21. A custom‐designed mirVana™ miRNA mimic was used to transfect the endometrial epithelial cells (EECs) in order to determine the role of miRNA exhibiting highest expression on Days 21 and 21. Results The expression of miR‐1246 (p < 0.001) and let‐7b (p < 0.01) was found to be significantly higher on Day 21 of TE culture in comparison to the control (Day 0). This elevated expression indicated the involvement of these miRs in the maternal‐foetal cross‐talk. Interestingly, after the transfection of EECs with miRNA mimic for miR‐1246 (a novel molecule vis‐à‐vis implantation), the expression of beta‐catenin and mucin1 in these cells was found to be significantly (p < 0.05) downregulated vis‐à‐vis the control, that is, the IFN‐τ primed EECs (before transfection). Conclusions The TE secreted miR‐1246 appeared to lower the expression of the endometrial receptivity genes (mucin1 and beta‐catenin) which apparently assists the endometrium in preparing for placentation.

miRNA expression profiles are heterogeneously expressed among cancer types, with miRNAs serving as highly tissue specific tumor suppressors and oncogenes. Machine learning methodologies have been used to develop high performance pan-cancer classification models and identify potentially novel miRNA biomarkers for clinical investigation. However, it is important to understand how such data science techniques correlate to established biological processes to advance integration into clinical environments. This research aims to assess how the top miRNA features selected by machine learning models relate to clinically and biologically verified miRNA biomarkers. We developed Support Vector Machine and Random Forest machine learning models for cancer classification, iteratively adding cancer classes to the multiclass models. The relationship between the selected top features (miRNAs) and clinically verified miRNA biomarkers was assessed through percent relevance, i.e., the number of verified miRNAs vs the number of selected features. We found that as the number of cancer classes increased, the performance metrics decreased, yet the percentage relevance of the miRNA feature selection signature slightly increased before stabilizing. Additionally, after conducting principal component analysis, the non-cancer tissues from all samples had very similar expression visualizations, while all cancerous tissues had unique profiles. The results indicated that models with a greater number of cancer classes shift towards focusing on cancer-diverse miRNAs of greater relevance with characterized functionality. This work suggests that miRNAs may be highly unique to specific cancerous tissues and can be strong biomarkers for detection and classification, but current verified biomarkers fall toward more cancer-wide miRNAs when detecting cancer.

Subfertility in beef heifers leads to a substantial economic loss for producers and beef industry. To overcome this problem, producers require an efficient system to discriminate beef heifers with varying reproductive potential as early as possible. MicroRNAs are short non-coding RNAs that post-transcriptionally regulate gene expression. Herein, we profiled the miRNAs in peripheral white blood cells (PWBC) of beef heifers at weaning to investigate the differences in the beef heifers with varying reproductive outcomes. Blood samples from Angus-Simmental crossbred heifers were collected at weaning. The blood was processed to extract the PWBC pellet and was stored at -80 °C until further processing. After the synchronization of estrus and breeding protocol (artificial insemination (AI) followed by natural bull service) and pregnancy diagnosis, the heifers were categorized as fertile (pregnant to AI) or subfertile (not pregnant to AI or bull exposure). Total RNA was extracted from PWBC collected at the time of weaning from the fertile and subfertile heifers. After quality assessment, the total RNA was used to prepare libraries. The quality-checked libraries (n = 14; 7 samples per fertile and subfertile group) were pooled and sequenced (single-end 50 bp) using a NextSeq 500 platform. The raw sequence reads were analyzed using a bioinformatics workflow utilizing FastQC and MultiQC for quality control, Cutadapt for adapter trimming, miRDeep2 for alignment, and DESeq2 for differential expression analysis. The raw and normalized miRNA counts were deposited and made publicly available on the gene expression omnibus database (GEO; GSE225854). This is the first dataset investigating the miRNA expression level in PWBC at weaning in beef heifers to predict the future reproductive outcome. The results from the data presented here are reported in the research article titled “miRNA expression profiles of peripheral white blood cells from beef heifers with varying reproductive potential” [1].

Exercise-released extracellular vesicles (EVs) are emerging as a novel class of exerkines that promotes systemic beneficial effects. However, slight differences in the applied exercise protocols in terms of mode, intensity and duration, as well as the need for standardized protocols for EV isolation, make the comparison of the studies in the literature extremely difficult. This work aims to investigate the EV amount and EV-associated miRNAs released in circulation in response to different physical exercise regimens. Healthy individuals were subjected to different exercise protocols: acute aerobic exercise (AAE) and training (AT), acute maximal aerobic exercise (AMAE) and altitude aerobic training (AAT). We found a tendency for total EVs to increase in the sedentary condition compared to trained participants following AAE. Moreover, the cytofluorimetric analysis showed an increase in CD81+/SGCA+/CD45− EVs in response to AAE. Although a single bout of moderate/maximal exercise did not impact the total EV number, EV-miRNA levels were affected as a result. In detail, EV-associated miR-206, miR-133b and miR-146a were upregulated following AAE, and this trend appeared intensity-dependent. Finally, THP-1 macrophage treatment with exercise-derived EVs induced an increase of the mRNAs encoding for IL-1β, IL-6 and CD163 using baseline and immediately post-exercise EVs. Still, 1 h post-exercise EVs failed to stimulate a pro-inflammatory program. In conclusion, the reported data provide a better understanding of the release of circulating EVs and their role as mediators of the inflammatory processes associated with exercise. [ABSTRACT FROM AUTHOR]

Chronic venous disease (CVD) is a common disease caused by hemodynamic disorders of the venous circulation in the lower extremities. The clinical image of this disease is complex and includes such signs as telangiectases, varicose veins, leg edema and skin changes, usually accompanied with ache, pain, tightness, heaviness, swelling and muscle cramps of legs. Venous ulcers develop in the advanced stages of the disease and lead to significant impairment of patient abilities and reduction of the quality of life. CVD is diagnosed based on physical and image examinations, and main treatment options include compression therapy, invasive treatments like endovenous ablation and foam sclerotherapy, as well as pharmacotherapy. Currently, there is no biochemical and molecular biomarkers utilized in diagnosis or treatment of CVD. With regard to this situation, one of the most investigated fields for identification of disease biomarkers is microRNA (miRNA). These constitute a pool of small, non-coding RNAs that play crucial roles in maintaining cellular homeostasis through posttranscriptional regulation of genes expression. Dysregulations of miRNA expression profiles have been found in patients with various diseases, and this situation provides information about potential miRNA signatures involved in pathophysiology. In this review, the studies focused on investigations of miRNA expression patterns in patients with CVD were collected. The performed literature analysis provides contemporary knowledge in the field of miRNA-dependent mechanisms involved in the etiopathogenesis of CVD and shows gaps that need to be filled in further studies.

Allergic diseases are one of the most common chronic conditions and their prevalence is on the rise. Environmental exposure, primarily prenatal and early life influences, affect the risk for the development and specific phenotypes of allergic diseases via epigenetic mechanisms. Exposure to pollutants, microorganisms and parasites, tobacco smoke and certain aspects of diet are known to drive epigenetic changes that are essential for immune regulation (e.g., the shift toward T helper 2-Th2 cell polarization and decrease in regulatory T-cell (Treg) differentiation). DNA methylation and histone modifications can modify immune programming related to either pro-allergic interleukin 4 (IL-4), interleukin 13 (IL-13) or counter-regulatory interferon γ (IFN-γ) production. Differential expression of small non-coding RNAs has also been linked to the risk for allergic diseases and associated with air pollution. Certain exposures and associated epigenetic mechanisms play a role in the susceptibility to allergic conditions and specific clinical manifestations of the disease, while others are thought to have a protective role against the development of allergic diseases, such as maternal and early postnatal microbial diversity, maternal helminth infections and dietary supplementation with polyunsaturated fatty acids and vitamin D. Epigenetic mechanisms are also known to be involved in mediating the response to common treatment in allergic diseases, for example, changes in histone acetylation of proinflammatory genes and in the expression of certain microRNAs are associated with the response to inhaled corticosteroids in asthma. Gaining better insight into the epigenetic regulation of allergic diseases may ultimately lead to significant improvements in the management of these conditions, earlier and more precise diagnostics, optimization of current treatment regimes, and the implementation of novel therapeutic options and prevention strategies in the near future.

Background: The microRNAs (miRs) secreted by the trophectoderm (TE) cells have recently been implicated in the conceptus‐endometrial cross talk during implantation and placentation. These miRs modulate various cellular processes during conception and throughout the pregnancy by regulating the gene expression in the foetal and maternal tissues. Objectives: This study was undertaken to elucidate the function of TE secreted miRNAs in the maternal‐foetal cross‐talk during implantation/placentation in buffalo. Methods: The in vitro produced blastocysts were cultured on a cumulus feeder layer for 21 days. The relative expression profiles of a selected panel of miRs was generated using the spent media collected on Days 0, 7, 12, 16, and 21. A custom‐designed mirVana™ miRNA mimic was used to transfect the endometrial epithelial cells (EECs) in order to determine the role of miRNA exhibiting highest expression on Days 21 and 21. Results: The expression of miR‐1246 (p < 0.001) and let‐7b (p < 0.01) was found to be significantly higher on Day 21 of TE culture in comparison to the control (Day 0). This elevated expression indicated the involvement of these miRs in the maternal‐foetal cross‐talk. Interestingly, after the transfection of EECs with miRNA mimic for miR‐1246 (a novel molecule vis‐à‐vis implantation), the expression of beta‐catenin and mucin1 in these cells was found to be significantly (p < 0.05) downregulated vis‐à‐vis the control, that is, the IFN‐τ primed EECs (before transfection). Conclusions: The TE secreted miR‐1246 appeared to lower the expression of the endometrial receptivity genes (mucin1 and beta‐catenin) which apparently assists the endometrium in preparing for placentation. [ABSTRACT FROM AUTHOR]

Spermatogenesis is tightly controlled at transcriptional, post-transcriptional, and epigenetic levels by various regulators, including miRNAs. This study deals with the identification of miRNAs critical to the three important stages of germ cell development (spermatocytes, round spermatids, and mature sperm) during spermatogenesis. We used high-throughput transcriptome sequencing to identify the differentially expressed miRNAs in the pachytene spermatocytes, round spermatids, and mature sperm of rat. We identified 1843 miRNAs that were differentially expressed across the three stages of germ cell development. These miRNAs were further categorized into three classes according to their pattern of expression during spermatogenesis: class 1 — miRNAs found exclusively in one stage and absent in the other two stages; class 2 — miRNAs found in any two stages but absent in the third stage; class 3 — miRNAs expressed in all the three stages. Six hundred forty-six miRNAs were found to be specific to one developmental stage, 443 miRNAs were found to be common across any two stages, and 754 miRNAs were common to all the three stages. Target prediction for ten most abundant miRNAs specific to each category identified miRNA regulators of mitosis, meiosis, and cell differentiation. The expression of each miRNA is specific to a particular developmental stage, which is required to maintain a significant repertoire of target mRNAs in the respective stage. Thus, this study provided valuable data that can be used in the future to identify the miRNAs involved in spermatogenic arrest at a particular stage of the germ cell development. [ABSTRACT FROM AUTHOR]

Purpose: Radiation therapy (RT) is one of the main treatments for cancer. The response to radiotherapy varies widely between individuals and some patients have poor response to RT treatment due to tumor radioresistance. Stratifying patients according to molecular signatures of individual tumor characteristics can improve clinical treatment. In here, we aimed to use clinical and genomic databases to develop miRNA signatures that can predict response to radiotherapy in various cancer types. Methods: We analyzed the miRNAs profiles using tumor samples treated with RT across eight types of human cancers from TCGA database. These samples were divided into response group (S, n = 224) and progressive disease group (R, n = 134) based on RT response of tumors. To enhance the discrimination for S and R samples, the predictive models based on binary logistic regression were developed to identify the best combinations of multiple miRNAs. Results: The miRNAs differentially expressed between the groups S and R in each canertype were identified. Total 47 miRNAs were identified in eight cancer types (p values <0.05, t-test), including several miRNAs previously reported to be associated with radiotherapy sensitivity. Functional enrichment analysis revealed that epithelial-to-mesenchymal transition (EMT), stem cell, NF-KB signal, immune response, cell death, cell cycle, and DNA damage response and DNA damage repair processes were significantly enriched. The cancer- type-specific miRNA signatures were identified, which consist of 2-13 of miRNAs in each caner type. Receiver operating characteristic (ROC) analyses showed that the most of individual miRNAs were effective in distinguishing responsive and non-responsive patients (the area under the curve (AUC) ranging from 0.606 to 0.889). The patient stratification was further improved by applying the combinatorial model of miRNA expression (AUC ranging from 0.711 to 0.992). Also, five miRNAs that were significantly associated with overall survival were identified as prognostic miRNAs. Conclusion: These mRNA signatures could be used as potential biomarkers selecting patients who will benefit from radiotherapy. Our study identified a series of miRNA that were differentially expressed between RT good responders and poor responders, providing useful clues for further functional assays to demonstrate a possible regulatory role in radioresistance. [ABSTRACT FROM AUTHOR]

Background: Increased dietary protein at breakfast promotes cardiometabolic health; however, whether these improvements occur at the molecular level is unknown., Objectives: The objective was to examine whether long-term consumption of breakfast, varying in protein quantity, alters the expression of circulating microRNAs (miRNAs) associated with cardiometabolic health in "breakfast-skipping" adolescents., Methods: Thirty adolescents (age: 19 ± 1 y; body mass index: 25.4 ± 3 kg/m 2 ) completed a 6-mo tightly controlled breakfast trial in which participants consumed 350 kcal normal-protein (NP, 10 g protein) or higher-protein (HP, 30 g protein) breakfasts or continued to BS for 6 mo. Fasting blood samples were collected at baseline (PRE) and 6 mo (POST) for assessment of 12 a priori circulating plasma miRNA expression levels (real-time quantitative polymerase chain reaction), glucose, insulin, IL-6, and C-reactive protein., Results: No main effects of group were observed for any miRNAs; however, a time-by-group interaction was detected for the expression of miR-126-3p (P = 0.05). HP breakfast tended to increase miR-126-3p expression throughout the study (POST-PRE, P = 0.09) leading to greater expression at POST compared with BS (P = 0.03), whereas NP breakfast did not. Additionally, several miRNAs predicted fasting concentrations of IL-6: miR-320a-3p, -146a-5p, -150-5p, -423-5p, -122-5p, glucose: miR-24-3p, -126-3p; insulin: miR-24-3p, -126-3p, -15b-5p; insulin sensitivity: miR-24-3p, -126-3p, -199a-5p, -15b-5p; and β-cell function: miR-15b-5p (R 2 between 0.2 and 0.39; P < 0.05) from PRE and POST samples across groups., Conclusions: These data support the daily consumption of a HP breakfast to promote cardiometabolic health, potentially through changes in miRNA expression, in a sensitive life-stage where early intervention strategies are critical to reduce the risk of adult-onset chronic disease., Trial Registration Number: NCT03146442., Competing Interests: Conflict of interest KAP, LMM, and JAG have no conflicts of interest to report. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Army or the Department of Defense. Any citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement or approval of the products or services of these organizations. HJL is an Editor for The Journal of Nutrition and played no role in the Journal's evaluation of the manuscript., (Copyright © 2024 American Society for Nutrition. All rights reserved.)

Since the non-coding control region (NCCR) and microRNA (miRNA) could represent two different and independent modalities of regulating JC polyomavirus (JCPyV) replication at the transcriptional and post-transcriptional levels, the interplay between JC viral load based on NCCR architecture and miRNA levels, following JCPyV infection with archetypal and rearranged (rr)-NCCR JCPyV variants, was explored in COS-7 and SVGp12 cells infected by different JCPyV strains. Specifically, the involvement of JCPyV miRNA in regulating viral replication was investigated for the archetypal CY strain—which is the transmissible form—and for the rearranged MAD-1 strain, which is the first isolated variant from patients with progressive multifocal leukoencephalopathy. The JCPyV DNA viral load was low in cells infected with CY compared with that in MAD-1-infected cells. Productive viral replication was observed in both cell lines. The expression of JCPyV miRNAs was observed from 3 days after viral infection in both cell types, and miR-J1-5p expression was inversely correlated with the JCPyV replication trend. The JCPyV miRNAs in the exosomes present in the supernatants produced by the infected cells could be carried into uninfected cells. Additional investigations of the expression of JCPyV miRNAs and their presence in exosomes are necessary to shed light on their regulatory role during viral reactivation. [ABSTRACT FROM AUTHOR]

Lower extremity artery disease (LEAD) is an underestimated chronic vascular disease caused by the formation of atherosclerotic plaques in the lower limb arteries. The pathological processes underlying this disease are regulated by many various factors, including microRNAs (miRNAs). miRNAs constitute a pool of small, non-coding RNAs with a gene expression modulatory function. In the presented study, differentially expressed miRNAs were identified in peripheral blood mononuclear cells from 18 patients with LEAD compared to 10 healthy volunteers using OpenArray RT-qPCR. Sixteen miRNAs were significantly differentially expressed in the LEAD group. Four out of them, hsa-miR-138-5p, -34a-3p, -34a-5p, and -766-3p, were consistent with a previous next-generation sequencing study. The in silico analysis performed for these four miRNAs showed associations with vascular smooth muscle cells differentiation, inflammation, and apoptosis, potentially resulting from modulation of genes involved in cell cycle, cellular adhesion, and Notch signaling. The presented study expands our knowledge on the role of miRNA in the pathology of LEAD, providing potential candidates for biomarkers of this disease. [ABSTRACT FROM AUTHOR]

Abstract The most common gynecologic cancers detected in women in Turkey are uterine cancer, ovarian cancer, and cervical cancer. These data reported that a mean of 3800 individuals were diagnosed with uterine cancer, 2790 were diagnosed with ovarian cancer, and 1950 were diagnosed with cervical cancer, and 400 individuals were diagnosed with other gynecologic cancers each year in Turkey. A mean of 14.270 individuals were detected to have been diagnosed with gynecologic cancers each year in the United States of America (USA). Ovarian cancer treatment is generally composed of chemotherapy, and surgery. In general, chemotherapy is administered after surgery. The identification of the molecular pathogenesis of ovarian cancer, and discovery of new moleculer biomarkers which facilitate the ovarian cancer treatment are required for an effective ovarian cancer treatment in clinics. miRNAs are reported to be the possible biologic indicators for various cancer types. We aimed to investigate 2 miRNAs which were suggested to have effect in ovarian cancer in our (previous) monozygotic twin study from miR-1260 microRNA family whose association with ovarian cancer yet has not been reported in the literature. We investigated the expression levels of miR-1260a, and miR-1260b miRNAs, in the peripheral blood lymphocytes of 150 familial and sporadic ovarian cancer patients, and of 100 healthy individuals of the control group who were matched for age, sex, and ethnicity with the patient group, and investigated their possible property of being a biologic indicator for ovarian cancer. The expression results of ovarian cancer patients were evaluated by comparison of the results of the control group in the study. The expression levels of miR-1260a, and miR-1260b in ovarian cancer patients were found highly increased compared with the levels in the control group. miR-1260a expression level in ovarian cancer patients was detected to have increased approximately 17 fold compared with the control group, and miR-1260b expression level in ovarian cancer patients was detected to have increased approximately 33 fold compared with the levels in the control group. The String Analyses showed that the miR-1260a was associated with the ribosomal protein family which was known to be effective in the translation stage of cell and that miR-1260b was associated with CHEK2 protein which was a member of the serine/threonine-protein kinase family. It should be investigated for larger cohorts in benign ovarian diseases and in different stages of patients receiving ovarian cancer treatment whether these two molecules are a noninvasive biomarker and therapeutic target to be used especially in the early diagnosis and prognosis of ovarian cancer in future.

Abstract Background Morphological features are the most common criteria used to select human embryos for transfer to a receptive uterine cavity. However, such characteristics are not valid for embryos in cellular arrest. Even aneuploid embryos can have normal morphology, and some euploid embryos have aberrant morphology. The aim of this study was to quantify the expression profile of hsa-miR-21-3p, -24-1-5p, -191-5p, and -372-5p in culture media on day 5 of in vitro embryo development, and compare the profiles of two groups of media classified by outcome: successful (n = 25) or unsuccessful (n = 25) implantation pregnancy. Methods Fifty patients were accepted in the Department of Reproductive Biology of a Hospital in México City, based on the Institutional inclusion criteria for in vitro fertilization. Embryos were transferred to the women on day 5 of cultivation, and the culture media were collected. RNA was isolated from each culture medium with TRIzol reagent, and microRNA (miRNA) expression was detected through RT-PCR with specific primers. Expression bands were quantified by reading optical density. Results There was a 5.2-fold greater expression of hsa-miR-191-5p in the pregnancy-related culture media (p ≤ 0.001) and a 1.6-fold greater level of hsa-miR-24-1-5p (p = 0.043) in the media corresponding to non-pregnant women. No significant difference existed between the two groups hsa-miR-21-3p (p = 0.38) or hsa-miR-372-5p (p = 0.41). Conclusions Regarding adequate in vitro embryo development, hsa-miR-191-5p could possibly represent a positive biomarker, while has-miR-24-1-5p may indicate poor prognosis. This former miRNA modulates IGF2BP-1 and IGF2R, associated with the implantation window. On the other hand, hsa-miR-24-1-5p may be related to a poor prognosis of human embryo development.

Abstract Background MicroRNAs (miRNAs) are small RNA molecules that modulate post-transcriptional gene regulation. They are often used as promising non-invasive biomarkers for the early diagnosis of cancer. However, their roles in assisted reproduction are still unknown. Methods This prospective study was designed to evaluate the expression profiles of seven extracellular miRNAs (miR-7-5p, miR-202-5p, miR-378-3p, miR-224, miR-320a, miR-212-3p, and miR-21-5p) in human follicular fluid (FF) to explore the outcomes of in vitro fertilization (IVF). Of 255 women, 145 were without polycystic ovary syndrome (PCOS), and their ovarian assets were normal (NOR), while 110 were with normo-androgenic PCOS. Results The combination of six FF miRNAs expression profile discriminated between PCOS and NOR women with a sensitivity of 79.2% and a specificity of 87.32% (AUC = 0.881 [0.61; 0.92], p = 0.001). MiR-202-5p significantly had a lower abundance level, and miR-378-3p had a high abundance level in pooled FF samples from patients treated with human menopausal gonadotropin (hMG) than those treated with recombinant follicle-stimulating hormone (rFSH) (p

A growing body of evidence indicates a crucial role of miRNA regulatory function in a variety of mechanisms that contribute to the development of diseases. In our previous work, alterations in miRNA expression levels and targeted genes were shown in peripheral blood mononuclear cells (PBMCs) from patients with lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA), and chronic venous disease (CVD) in comparison with healthy controls. In this paper, previously obtained miRNA expression profiles were compared between the LEAD, AAA, and CVD groups to find either similarities or differences within the studied diseases. Differentially expressed miRNAs were identified using the DESeq2 method implemented in the R programming software. Pairwise comparisons (LEAD vs. AAA, LEAD vs. CVD, and AAA vs. CVD) were performed and revealed 10, 8, and 17 differentially expressed miRNA transcripts, respectively. The functional analysis of the obtained miRNAs was conducted using the miRNet 2.0 online tool and disclosed associations with inflammation and cellular differentiation, motility, and death. The miRNet 2.0 tool was also used to identify regulatory interactions between dysregulated miRNAs and target genes in patients with LEAD, AAA, and CVD. The presented research provides new information about similarities and differences in the miRNA-dependent regulatory mechanisms involved in the pathogenesis of LEAD, AAA, and CVD. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of most common cancers worldwide, with high rates of mortality. Epidemiological findings demonstrate that coffee consumption reduces the risk of developing CRC by ~13%. In general, in vivo and in vitro findings demonstrate the antiproliferative, antioxidant and proapoptotic effects of brewed coffee or major bioavailable coffee compounds. Thus, it was assessed whether caffeine (CAF) and/or chlorogenic acid (CGA) attenuates the early-stage of chemically induced mouse colon carcinogenesis. Male Swiss mice were submitted to a 1,2-dimethylhydrazine/deoxycholic acid (DMH/DCA)-induced colon carcinogenesis model. These animals received CAF (50 mg/kg), CGA (25 mg/kg) or CAF+CGA (50 + 25 mg/kg) intragastrically for five times/week for ten weeks. CAF+CGA had the most pronounced effects on decreasing epithelial cell proliferation (Ki-67) and increasing apoptosis (cleaved caspase-3) in colonic crypts. This treatment also decreased the levels of proinflammatory cytokines IL-6, IL-17 and TNF-α, and downregulated the oncomiR miR-21a-5p in the colon. Accordingly, the analysis of miR-21a-5p targets demonstrated the genes involved in the negative regulation of proliferation and inflammation, and the positive regulation of apoptosis. Ultimately, CAF+CGA attenuated preneoplastic aberrant crypt foci (ACF) development. Our findings suggest that a combination of coffee compounds reduces early-stage colon carcinogenesis by the modulation of miR-21a-5p expression, highlighting the importance of coffee intake to prevent CRC. [ABSTRACT FROM AUTHOR]

In response to environmental and cellular cues, the spatiotemporal expression of differentially expressed miRNAs (DEmiRs) during in vitro regeneration of plants is prominent. Nevertheless, the influence of stress conditions on the functional imprints of DEmiRs during plant organogenesis is inadequately understood. Target-mimicry based constitutive diminution of miR167 genes in transgenic tobacco revealed their functional contributions in salt-stress tolerance during organogenesis. Up to 61.6% relative increment in the shoot emergence on leaf explants of miR167 mimic lines (cultured on 12.5 and 25 mM NaCl concentrations) exhibited greater magnitude of organogenesis under stress, most probably through upregulated auxin signalling. Relative expression analysis of auxin transporter genes AUX1, PIN1 and PIN2 revealed synergistic effect of percent miR167 diminution and salt-stress (up to 12.5 mM) resulting into enhanced callogenesis and reduced organogenesis. Biochemical assessment of in vitro grown miR167 mimic shoot initials revealed an increase in the relative water content, chlorophyll and antioxidant activity, which suggested a shift in the molecular equilibrium in response to miR167 diminution-associated signalling pathways. Remarkably, independent miR167 diminution lines exhibited expression variations among associated miR156, miR159, and miR394 and validated by the expression analysis of selected target genes SPL9, ARF6 and ARF8. The expression ratios of these miRNAs revealed their coordinated regulatory network in response to salt-stress during organogenesis. These results demonstrate a link between miR167 diminution and salt-stress tolerance in mimic lines, and suggest that a regulatory shift in the cellular metabolism may contribute to salt-stress tolerance in plants. These observations may create new avenues for strategic utilization of such genic resources for future crop research. [ABSTRACT FROM AUTHOR]

Background/aim: In tuberculsosis (TB), miRNA has been used as a biomarker to distinguish between healthy individuals and TB patients. The aim of this study was to investigate (i) the association of the miRNA and cytokine expression levels, the course of tuberculosis infection, clinical forms and response to treatment, and (ii) the effects of genotypic features of bacteria on the course of tuberculosis and the relationship between miRNA and cytokine expressions and bacterial genotypes. Materials and methods: A total of 200 cases (100: culture positive active tuberculosis, 50: quantiferon positive latent tuberculosis infection and 50: quantiferon negative healthy controls) were included in the study. For the tuberculosis group at the time of admission and after treatment, for the latent tuberculosis infection and healthy control groups at the time of admission, miRNA and cytokine expressions were determined. Genotyping of M. tuberculosis isolates was performed by spoligotyping method. Results: While, in the comparison of miRNA expressions between the pretreatment patient group and the healthy control group, there was a statistically significant decrease in the expression of miR-454-3p, miR-15a-5p, miR-590-5p, miR-381, and miR-449a in the Pulmonary TB group, there was no significant change in miRNA expression in extrapulmonary TB patients. When the cytokine expressions of the patient group and the healthy control group were compared before treatment, the expressions of all cytokines in the patient group decreased. However, the only cytokine that showed a significantly lower expression was IL12A in PTB patients. Conclusion: There is no significant relationship between the clinical course of the disease, cytokine and miRNA expression, and the genotype of the bacteria. [ABSTRACT FROM AUTHOR]

Radiation therapy is an important component of cancer treatment scheduled for cancer patients, although it can cause numerous deleterious effects. The use of adjuvant molecules aims to limit the damage in normal surrounding tissues and enhance the effects of radiation therapy, either killing tumor cells or slowing down their growth. Melatonin, an indoleamine released by the pineal gland, behaves as a radiosensitizer in breast cancer, since it enhances the therapeutic effects of ionizing radiation and mitigates side effects on normal cells. However, the molecular mechanisms through which melatonin modulates the molecular changes triggered by radiotherapy remain mostly unknown. Here, we report that melatonin potentiated the anti-proliferative effect of radiation in MCF-7 cells. Treatment with ionizing radiation induced changes in the expression of many genes. Out of a total of 25 genes altered by radiation, melatonin potentiated changes in 13 of them, whereas the effect was reverted in another 10 cases. Among them, melatonin elevated the levels of PTEN and NME1, and decreased the levels of SNAI2, ERBB2, AKT, SERPINE1, SFN, PLAU, ATM and N3RC1. We also analyzed the expression of several microRNAs and found that melatonin enhanced the effect of radiation on the levels of miR-20a, miR-19a, miR-93, miR-20b and miR-29a. Rather surprisingly, radiation induced miR-17, miR-141 and miR-15a but melatonin treatment prior to radiation counteracted this stimulatory effect. Radiation alone enhanced the expression of the cancer suppressor miR-34a, and melatonin strongly stimulated this effect. Melatonin further enhanced the radiation-mediated inhibition of Akt. Finally, in an in vivo assay, melatonin restrained new vascularization in combination with ionizing radiation. Our results confirm that melatonin blocks many of the undesirable effects of ionizing radiation in MCF-7 cells and enhances changes that lead to optimized treatment results. This article highlights the effectiveness of melatonin as both a radiosensitizer and a radioprotector in breast cancer. Melatonin is an effective adjuvant molecule to radiotherapy, promoting anti-cancer therapeutic effects in cancer treatment. Melatonin modulates molecular pathways altered by radiation, and its use in clinic might lead to improved therapeutic outcomes by enhancing the sensitivity of cancerous cells to radiation and, in general, reversing their resistance toward currently applied therapeutic modalities. [ABSTRACT FROM AUTHOR]

Background: The miRNAs have been shown to be involved in breast cancer. The aim of the present research was to evaluate the impacts of extract from Euphorbia szovitsii Fisch & C.A. Mey on the expression level of microRNAs in triple-negative breast cancer (MDA-MB-231) cell line. Methods and Result: The alterations in the expression level of miRNAs in MDA-MB-231 cell line exposed to the extract of E. szovitsii were determined exploiting qRT-PCR technique. The expression of MDA-MB-231 cell microRNAs including miR-15, miR-16, miR-21, miR-29, miR-34a, miR-146b, miR-151, miR-155, miR-181b, miR-221, miR-222, and Let-7 was evaluated at 24 and 48 h after treatment with the E. szovitsii extract. The treatment of MDA-MB-231 cells with E. szovitsii caused a significant elevation in the expression of miR-155, miR-146b (P < 0.05), miR-16, miR-21, miR-151 (P < 0.01), and miR-34a (P < 0.001) after 24 h, and also miR-155, Let-7 (P < 0.05), miR-15, miR-29, miR-151 (P < 0. 01), miR-146b and miR-34a (P<0.001) after 48 h. Conclusions: The qRT-PCR findings at 24 and 48 h after treatment revealed that the MDA-MB-231 cell line in the presence of E. szovitsii extract showed an alteration in the expression profile of miRNAs implicated in the induction of cell proliferation, apoptosis and migration. These results may be helpful in determining the anticancer activity of E. szovitsii in MDA-MB-231 cell line. [ABSTRACT FROM AUTHOR]

BackgroundUp to one-third of concussed children develop persistent post-concussive symptoms (PPCS). The identification of biomarkers such as salivary miRNAs that detect concussed children at increased risk of PPCS has received growing attention in recent years. However, whether and how salivary miRNA expression levels differ over time between concussed children with and without PPCS is unknown.AimTo identify salivary MicroRNAs (miRNAs) whose expression levels differ over time post-concussion in children with vs. without PPCS.MethodsWe conducted a prospective cohort study with saliva collection at up to three timepoints: (1) within one week of injury; (2) one to two weeks post-injury; and (3) 4-weeks post-injury. Participants were children (ages 11 to 17 years) with a physician-diagnosed concussion from a single hospital center. We collected participants' daily post-concussion symptom ratings throughout their enrollment using the Post-concussion Symptom Scale, and defined PPCS as a total symptom score of ≥ 5 at 28 days post-concussion. We extracted salivary RNA from the saliva samples and measured expression levels of 827 salivary miRNAs. We then compared the longitudinal expression levels of salivary miRNAs in children with vs. without PPCS using linear models with repeated measures.ResultsA total of 135 saliva samples were collected from 60 children. Of the 827 miRNAs analyzed, 91 had expression levels above the calculated background threshold and were included in the differential gene expression analyses. Of these 91 miRNAs, 13 had expression levels that differed significantly across the three timepoints post-concussion between children with and without PPCS (i.e., hsa-miR-95-3p, hsa-miR-301a-5p, hsa-miR-626, hsa-miR-548y, hsa-miR-203a-5p, hsa-miR-548e-5p, hsa-miR-585-3p, hsa-miR-378h, hsa-miR-1323, hsa-miR-183-5p, hsa-miR-200a-3p, hsa-miR-888-5p, hsa-miR-199a-3p+hsa-miR-199b-3p). Among these 13 miRNAs, one (i.e., hsa-miR-203a-5p) was also identified in a prior study, with significantly different expression levels between children with and without PPCS.ConclusionOur results from the longitudinal assessment of miRNAs indicate that the expression levels of 13 salivary miRNAs differ over time post-injury in concussed children with vs. without PPCS. Salivary miRNAs may be a promising biomarker for PPCS in children, although replication studies are needed.

Long-term physical restriction may lead to affective and physiological disorders in sows; pupillary light reflex (PLR) characteristics might be a good indicator to diagnose these symptoms. Accordingly, the physiological and psychological states of sows with different PLR characteristics were investigated in this study. Gestating sows of three parities (parity 0, 2, and 5) were divided into strong reflex (SR) and weak reflex (WR) groups, according to a PLR test. In each group, miRNA expression and serum physiological indices were detected. Compared with the SR group, WR group showed lower 5-hydroxytryptamine levels and higher cortisol, interleukin-6, and beta-endorphin levels (p

The use of easily accessible peripheral samples, such as blood or saliva, to investigate neurological and neuropsychiatric disorders is well-established in genetic and epigenetic research, but the pathological implications of such biomarkers are not easily discerned. To better understand the relationship between peripheral blood- and brain-based epigenetic activity, we conducted a pilot study on captive baboons (Papio hamadryas) to investigate correlations between miRNA expression in peripheral blood mononuclear cells (PBMCs) and 14 different cortical and subcortical brain regions, represented by two study groups comprised of 4 and 6 animals. Using next-generation sequencing, we identified 362 miRNAs expressed at ≥ 10 read counts in 80% or more of the brain samples analyzed. Nominally significant pairwise correlations (one-sided P < 0.05) between peripheral blood and mean brain expression levels of individual miRNAs were observed for 39 and 44 miRNAs in each group. When miRNA expression levels were averaged for tissue type across animals within the groups, Spearman's rank correlations between PBMCs and the brain regions are all highly significant (r s = 0.47–0.57; P < 2.2 × 10–16), although pairwise correlations among the brain regions are markedly stronger (r s = 0.86–0.99). Principal component analysis revealed differentiation in miRNA expression between peripheral blood and the brain regions for the first component (accounting for ∼75% of variance). Linear mixed effects modeling attributed most of the variance in expression to differences between miRNAs (>70%), with non-significant 7.5% and 13.1% assigned to differences between blood and brain-based samples in the two study groups. Hierarchical UPGMA clustering revealed a major co-expression branch in both study groups, comprised of miRNAs globally upregulated in blood relative to the brain samples, exhibiting an enrichment of miRNAs expressed in immune cells (CD14+, CD15+, CD19+, CD3+, and CD56 + leukocytes) among the top blood-brain correlates, with the gene MYC , encoding a master transcription factor that regulates angiogenesis and neural stem cell activation, representing the most prevalent miRNA target. Although some differentiation was observed between tissue types, these preliminary findings reveal wider correlated patterns between blood- and brain-expressed miRNAs, suggesting the potential utility of blood-based miRNA profiling for investigating by proxy certain miRNA activity in the brain, with implications for neuroinflammatory and c-Myc-mediated processes. [ABSTRACT FROM AUTHOR]

Lower extremity artery disease (LEAD) is an underdiagnosed and globally underestimated vascular disease caused by the progressive and chronic formation of atherosclerotic plaques in the arteries of the lower limbs. Much evidence indicates that the abnormal course of pathophysiological processes underlying LEAD development is associated with altered miRNA modulatory function. In the presented study, relationships between miRNA expression and clinical indicators of this disease (ABI, claudication distance, length of arterial occlusion, Rutherford category, and plaque localization) were identified. MiRNA expression profiles were obtained using next-generation sequencing in peripheral blood mononuclear cells (PBMCs) of 40 LEAD patients. Correlation analysis performed using the Spearman rank correlation test revealed miRNAs related to ABI, claudication distance, and length of arterial occlusion. In the DESeq2 analysis, five miRNAs were found to be dysregulated in patients with Rutherford category 3 compared to patients with Rutherford category 2. No miRNAs were found to be differentially expressed between patients with different plaque localizations. Functional analysis performed using the miRNet 2.0 website tool determined associations of selected miRNAs with processes underlying vascular pathology, such as vascular smooth muscle cell differentiation, endothelial cell apoptosis, response to hypoxia, inflammation, lipid metabolism, and circadian rhythm. The most enriched functional terms for genes targeted by associated miRNAs were linked to regulation of the cell cycle, regulation of the transcription process, and nuclear cellular compartment. In conclusion, dysregulations of miRNA expression in PBMCs of patients with LEAD are indicative of the disease and could potentially be used in the prediction of LEAD progression. [ABSTRACT FROM AUTHOR]

Introduction: Wilms tumor is the most common renal malignancy in children and difficult to differentiate from other paediatric abdominal tumors radiologically, necessitating an invasive procedure for diagnosis. Previous studies have shown the potential role of miRNA as biomarkers for diagnosis, histological subtyping and prognosis. In this study, we are exploring the role of miRNA in the histological subtyping of Wilms tumor in the Indian population. Materials and methods: A total of 15 cases of Wilms tumor were evaluated for global miRNA expression analysis by microarray. Total RNA was extracted from fresh frozen tumor and miRNA expression analysis was performed using Agilent platform. Unsupervised clustering was done to analyse the data. Results: Using unpaired student T test, top 10 significantly differentially expressed miRNA were selected which could differentiate among different histological subtypes by unsupervised hierarchical clustering and principal component analysis. The presence of necrosis, heterologous differentiation led to change in miRNA expression profile and led to a distinct cluster formation. Conclusions: A panel of 5 miRNAs (miR1, 133b, 299-3p, 499a-5p, 491-3p) could differentiate among different histological subtypes of Wilms tumor, thus avoiding an invasive procedure in children, however, further confirmation using real time PCR analysis will be needed. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA) are small, noncoding RNA sequences that post-transcriptionally regulate the proliferation, activity and apoptosis of human gastric cancer cells by controlling various signaling cascades. Processes that involve miRNA molecules can create a specific network of interactions in a cell, and disruption of its functioning may contribute to the transformation of normal cells into cancerous cells. Aims of our survey were: 1) study the relationship between the expression of selected miRNA types (let-7a, miR-106b, miR-29b, miR-21, miR-155, miR-222) in the gastric mucosa and pathomorphological changes determined by classical histopathological methods, 2) perform in silico analysis to select target genes for selected miRNAs and to perform functional analysis of these genes. Eighty-three subjects (45 women, 38 men; mean age 39±14 years, range: 21-80 years, were examined). Among them were 18 (21.5%) patients with chronic active gastritis, 42 (50.6%) people with chronic inactive gastritis, 9 (10.8%) patients with gastric cancer and 14 (16.9%) patients without histopathological changes. The study demonstrated that mainly the expression of 3 (miR-29b, let-7a miR-106b) out of 6 selected miRNAs are significantly different depending on the site of biopsy (body of the stomach or antrum) and the group of patients. Expression of miR-106b in the antrum and body was the highest in the group of cancer patients and the lowest in patients with chronic active gastritis. The expression of let-7a differed depending on group of patients and location. The highest expression was in the body in the group with inactive gastritis and the lowest in gastric cancer. Patients with cancer had the lowest expression of miR-29b in stomach body and it was the highest in the patients with inactive gastritis in this location. Expression of miR-21 and miR-155 determinations were not statistically significant in comparison to groups or locations, and of miR-222 was not different between the groups, but only in the control group was higher in the antrum than in the body. We conclude that identification of miRNAs may represent a promising modern complementary method in the diagnosis of gastric diseases, especially cancer. [ABSTRACT FROM AUTHOR]

Background: Madin–Darby canine kidney (MDCK) cells are widely used for vaccine production, however, the safety of MDCK cells needs to be considered seriously because of high tumorigenicity. Micro RNAs (miRNAs) that are involved in the tumorigenicity of MDCK cells have been never been reported. Objective: To reveal the role of miRNA in the tumorigenic phenotype of MDCK cell line. Methods: The miRNA expression profiles of two monoclonal MDCK cells (M09CL and M35CL) with low tumorigenicity and one MDCK cell line (M73P) with high tumorigenicity were characterized and investigated by using small RNA-seq technology. Results: A total of 5 known miRNAs and 5 novel miRNAs were highly expressed in M73P. In addition, 4 known miRNAs and 4 novel miRNAs were highly expressed in M09CL and M35CL. The target genes of the differentially expressed miRNAs were significantly enriched in several biological processes, and the majority of these genes were involved in pathways in cancer and the MAPK signaling pathway. Through interaction analysis, 4 up-regulated miRNAs (cfa-miR-452, cfa-miR-8826, cfa-miR-224, and cfa-miR-2387) and their crucial target genes related to the tumor regulation network were identified. Results indicated these 4 miRNAs might play crucial roles in the tumorigenesis of MDCK cells. Conclusion: Our findings, which were based on the functional prediction of miRNAs and target genes, suggested that miRNAs might influence the tumorigenicity of MDCK cells by regulating target genes. Moreover, the results provided important data for understanding the miRNA-mediated regulatory networks that control the tumorigenicities of MDCK cells. [ABSTRACT FROM AUTHOR]