microRNA Expression In Patients Research Articles

БИОЛОГИЧЕСКИЕ МАРКЕРЫ ФИБРОЗООБРАЗОВАНИЯ У БОЛЬНЫХ САРКОИДОЗОМ ЛЕГКИХ

Introduction. Sarcoidosis-associated pulmonary fibrosis still lacks biomarkers to predict progression. Whole-genome association studies and other genetic research over the past few years have identified several single nucleotide polymorphisms that are associated with an increased risk of developing pulmonary fi brosis. In sarcoidosis, relatively reliable predictors of the disease activity include serum angiotensin-converting enzyme, soluble interleukin-2 receptor (sIL-2R) and chitotriosidase. Levels of inetrleukin-5 and, possibly, interleukin-7 were found to be elevated in patients with a fibrotic phenotype. Aim. In the present study, we sought to find the relationship between serum non- coding RNA- microRNA expression in patients with pulmonary sarcoidosis and the likelihood of pulmonary fibrosis developing in these patients. Materials and Methods. A total of 52 research subjects (sarcoidosis patients with/without fibrosis and healthy subjects) were included in the study. RNA samples from two groups of sarcoidosis patients (with and without fibrosis) and the control group were analyzed using the PCR Array. TaqMan QRT-PCR Assay was used for data verification. Results and Discussion. A significant decrease in the lung diffusion capacity was detected in 12 of 15 patients with chest-CT fibrosis signs. Lung diffusion capacity was normal in 17 patients without any fibrosis signs. There was a significant negative correlation among miR-15a, miR-150, and the level of lung diffusion capacity. Сonclusions. A set of non-coding RNA- microRNAs, i. e., miR-15a, miR-22, miR-106b, miR-107, and miR-150, was identified that can be further used as diagnostic markers for sarcoidosis fibrosis.

Plasma miRNA expression in patients with genetically confirmed multiple endocrine neoplasia type 1 syndrome and its phenocopies

MEN-1 is a rare autosomal dominant disease caused by mutations in MEN1 gene encoding the menin protein. This syndrome is characterized by the occurrence of parathyroid tumors, gastroenteropancreatic neuroendocrine tumors, pituitary adenomas, as well as other endocrine and non-endocrine tumors. If a patient with the MEN-1 phenotype carry no mutations in the MEN1 gene, the condition considers a phenocopy of syndrome (phMEN1). The possible cause of this changes could be changes in epigenetic regulation, particularly in microRNA expression that might affect menin signaling pathways. to identify differently expressed circulating miRNAs in plasma in patients with genetically confirmed MEN-1 syndrome, its phenocopies and healthy controls. single-center, case-control study was conducted. We assessed plasma microRNA expression in patients with genetically confirmed MEN-1 (gMEN1), phMEN1 and healthy controls. Morning plasma samples were collected from fasting patients and stored at -80°C. Total RNA isolation was performed using miRNeasy Mini Kit with QIAcube. Thelibraries were prepared by the QIAseq miRNA Library Kit following the manufacturer. Circulating miRNA sequencing was done on Illumina NextSeq 500 (Illumina). Subsequent data processing was performed using the DESeq2 bioinformatics algorithm. we enrolled 21 consecutive patients with gMEN1 and 11 patients with phMEN1, along with 12 gender matched controls. Median age of gMEN1 was 38,0 [34,0; 41,0]; in phMEN1 - 59,0 [51,0; 60,0]; control - 59,5 [51,5; 62,5]. The gMEN1 group differed in age (p<0.01) but not gender (р=0.739) or BMI (р=0.116) compared to phMEN1 and controls group, the last two groups did not differ by these parameters (p>0.05). 25 microRNA were differently expressed in groups gMEN1 and phMEN1 (21 upregulated microRNAs, 4 - downregulated). Comparison of samples from the phMEN-1 group and relatively healthy controls revealed 10 differently expressed microRNAs: 5 - upregulated; 5 - downregulated. In the gMEN-1 and control groups, 26 differently expressed microRNAs were found: 24 - upregulated; 2 - downregulated. The miRNAs most differing in expression among the groups were selected for further validation by RT-qPCR (in the groups of gMEN1 vs phMEN1 - miR-3613-5p, miR-335-5p, miR-32-5p, miR-425-3p, miR-25-5p, miR-576-5p, miR-215-5p, miR-30a-3p, miR-141-3p, miR-760, miR-501-3p; gMEN1 vs control - miR-1976, miR-144-5p miR-532-3p, miR-375; as well as in phMEN1 vs control - miR-944, miR-191-5p, miR-98-5p). In a pilot study, we detected microRNAs that may be expressed differently between patients with gMEN-1 and phMEN-1. The results need to be validated using different measurement method with larger sample size.

Non-invasive diagnostics of endometriosis based on plasma miRNA expression

Aim. To develop a method for noninvasive diagnosis of external genital endometriosis based on plasma microRNA concentrations.Materials and Methods. 80 women of reproductive age who were admitted to the gynecological department for routine laparoscopy were retrospectively examined, according to the results of which and histological examination, the patients were divided into 2 groups: the main group — 54 patients with laparoscopically and histologically confirmed external genital endometriosis (EGE); the control group — 26 patients without EGE. Before laparoscopy, a blood sample was taken from all patients for a molecular-biological study of the expression of 10 microRNAs: miR-183, miR-125b, miR-126, miR-16, miR-15a, miR-200a, miR-20a, miR-21, miR-222 and miR-29b. Identification of the studied and normalizing RNAs (U6 RNA and 103a microRNA) was performed according to the method of Chen et al. The presented values of the expression of the studied microRNAs are given in the form of 2-ΔCt. The expression ratio is given in the form of 2-ΔCt (main)/2-ΔCt (control), if the expression in the group of patients with endometriosis exceeded that in the control group, and in the form of 2-ΔCt (control)/2-ΔCt (main), if vice versa.Results. Comparison of the expression of 10 mi-croRNAs between the two groups revealed statistically significant differences only in miR-183: its expression in patients with EGE was statistically 1.5 times higher than that in women of the control group (p=0.017).We have not detected a difference in the expression of mir-200a, while according to other researchers, representatives of the mir-200 family are among the most frequent whose expression changes with endometriosis. MIR-16 expression also did not differ statistically among the patients we examined, whereas a group of American colleagues revealed its increase in patients with endometriosis and with endometriosis-associated ovarian tumors. We found no difference in mir-21 expression. The results of other researchers are contradictory: some found its increase in endometrioid cysts compared with eutopic endometrium, an increase in the epithelium of the fallopian tubes with their endometriosis compared with unaffected; others did not reveal a difference between the eutopic endometrium of endometriosis patients and healthy women, but showed a decrease in expression in peritoneal foci and foci of deep infiltrative endometriosis compared with eutopic endometrium.The expression of mir-222 was reduced in the patients we examined with endometriosis, which goes against the existing ideas about the pro-oncogenic role of this microRNA. An increase in its expression in cancer of the stomach, bladder, liver, lungs, breast, endometrium, ovaries is described. At the same time, the oncosuppressive effect of mir-222 is also known in prostate cancer, squamous cell carcinoma of the oral cavity.Conclusion. Taking into account the revealed statistically significant difference in microRNA expression by ROC analysis, we determined their effectiveness and specificity in the diagnosis of EGE. Of course, further studies with a large contingent of patients are needed to confirm the diagnostic value of these biomarkers. In addition, our study did not allow us to establish a statistical difference in microRNA expression in patients with impaired fertility. But it is the test that makes it possible to differentiate female infertility — associated with endometriosis and without it, as a rule, tubal-peritoneal genesis — that will become a key tool in the personalized management of patients with infertility.In our work, the distribution of patients by stages of EGE turned out to be uneven (there were no women with stage I at all) and it was not possible to establish a statistical difference in microRNA expression depending on the "length of service" of the disease.

Pattern of Expression of MicroRNA in Patients with Radiation-Induced Bladder Injury

Introduction: Bladder cancer (BC) is sensitive to radiation treatment and a subset of patients experience radiation-induced injuries including shrinkage of bladder due to bladder fibrosis. Methods: This study is a retrospective cohort study. Three Japanese BC patients were randomly selected. Using a microRNA (miRNA) array, comparing their samples with or without radiation-induced injuries, we have checked the clustering of miRNA expression. Results: Hsa-miR-130a, hsa-miR-200c, hsa-miR-141, and hsa-miR-96 were found to be highly expressed (>50 times) in patients with fibrotic bladder shrinkage (FBS) compared to those with intact bladder (IB) function. In patients with FBS, hsa-miR-6835, hsa-miR-4675, hsa-miR-371a, and hsa-miR-6885 were detected to have lesser than half expression to IB patients. We have analyzed the significance of these genes in relation to overall survival of 409 BC patients retrieved from the Cancer Genome Atlas data set. All available cutoff values between the lower and upper quartiles of expression are used for the selected genes, and false discovery rate using the Benjamini-Hochberg method is computed to correct for multiple hypothesis testing. We have run combined survival analysis of the mean expression of these four miRNAs highly expressed in FBS patients. 175 patients with high expression had a longer median survival of 98.47 months than 23.73 months in 233 patients with low expression (hazard ratio [HR]: 0.53; 0.39–0.72, log-rank p value: 7.3e−0.5). Combination analysis of all 8 genes including hsa-miR-6835, hsa-miR-4675, hsa-miR-371a, and hsa-miR-6885 showed the same HR for OS. Target scanning for these miRNAs matched specific cytokines known as an early biomarker to develop radiation-induced fibrosis. Conclusions: BC patients with fibrotic radiation injury have specific miRNA expression profile targeting profibrotic cytokines and these miRNAs possibly render to favorable survival.

Stromal Cell-Derived Factor 1 Alpha (SDF-1α), Cartilage Oligomeric Matrix Protein (COMP) and Circulating microRNAs 208a-3p and 221-3p: Potential Signature Biomarkers of Hemophilic Arthropathy

Introduction. Hemophilia A is a rare constitutional bleeding disorder due to a deficiency in Factor VIII. Recurrent hemarthroses, one of the major complications of the disease, lead to hemophilic arthropathy, a disabling condition difficult to diagnose with current strategies (ultrasound and magnetic resonance imaging [MRI]), with possible delayed diagnosis. MRI, the gold standard, is not of easy access nor cheap and requires sedation in young children. Ultrasound is liable to inter-operator variability and difficult to apply to such joints as ankles, especially in children for whom this is the most frequently involved location of hemophilic arthropathy. Circulating MicroRNAs are a group of endogenous, small, non-coding RNA molecules that regulate gene expression ; and knowledge on the potential roles of miRNAs in haemophilia is very limited. Aim. The aim of this project was to assess plasmatic biomolecules indicative of osteo-cartilaginous damage in patients with hemophilia with or without known arthropathy, in order to improve the diagnosis of this major complication of the disease. We also investigated microRNA expression in patients with haemophilia A with and without inhibitors, compared to healthy controls. Methods In this monocentric retrospective study, 40 patients with hemophilia A or B, for whom a plasma sample was available, provided informed consent for further analyses (multiplex immunoassays and ELISA) and collection of relevant clinical information in their medical files. Correlations were sought for between biomarkers of interest and the severity of joint lesions assessed according to Pettersson radiologic score. For miRNAs analysis, all RNAs were extracted from plasma samples. We synthesised complementary DNA from the RNA samples, and used to quantitative PCR and microarray analysis to allow us to look at changes in expression levels. Results Two biomarkers were identified, respectively SDF-1α and COMP. Their plasmatic levels were significantly increased in patients with arthropathy compared to controls and patients without arthropathy. These values correlated significantly with the Pettersson score in patients under regular prophylaxis. We also identified two microRNAs of interest, the microRNA 208a-3p was significantly downregulated in hemophilia patients with arthropathy but not in patients without arthropathy and the microRNA 221-3p had a clear tendency for statistically significant down regulation in hemophiliacs with arthropathy. Interestingly, miRNA 221-3p has been shown to be involved in rheumatoid arthritis. Dysregulation of this microRNA leads to a reduced anti-inflammatory response and drives macrophages into a pro-inflammatory state. Conclusion Two plasma proteins SDF-1 alfa and COMP and two circulating micro-RNAs have been identified as potential biomarkers that could help physicians to assess the presence and severity of hemophilic arthropathy.

THU081 Differences In Circulating Microrna Levels In Genetically Confirmed Multiple Endocrine Neoplasia Type 1 And Multiple Endocrine Neoplasia Type 1 Phenocopies As Assessed By Next Generation Sequencing

Abstract Disclosure: D.A. Trukhina: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). E.O. Mamedova: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). P.A. Koshkin: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). A.G. Nikitin: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). G.A. Melnichenko: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). Z.E. Belaya: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). Multiple endocrine neoplasia type 1 (MEN1) is a rare disease caused by mutations in the MEN1 gene encoding the menin protein (gMEN1). This syndrome is characterized by the occurrence of parathyroid tumors, gastroenteropancreatic neuroendocrine tumors (GEP-NETs), pituitary adenomas, as well as other endocrine and non-endocrine tumors. Patients with MEN1 phenotype without MEN1 mutations are considered MEN1 phenocopies (phMEN1). It has not been studied whether the development of MEN1 phenocopies is determined by epigenetic changes, particularly by altered microRNA expression, which can affect menin. Materials & methods Single-center, case-control study: assessment of plasma microRNA expression in patients with gMEN1, phMEN1 and healthy controls. Morning plasma samples were collected from fasting patients and gender-matched controls and stored at –80C. Total RNA isolation was performed using miRNeasy Mini Kit with QIAcube. The libraries were prepared by the QIAseq miRNA Library Kit. Circulating miRNA sequencing was performed on Illumina NextSeq 500. Subsequent data processing was performed using DESeq2 bioinformatics algorithm. Results We enrolled 24 patients with gMEN1 and 12 patients with phMEN1, along with 12 gender-matched controls. The median age of gMEN1 patients was 39 [35; 46]; in phMEN1 — 59 [51;60]; control — 59 [51.5; 62.5]. The gMEN1 group differed in age (p<0,01) compared to phMEN1 and control groups. We divided all assessed microRNAs into 3 groups based on the significance of the results: the first group consisted of samples with the highest level of detected microRNAs (>50 counts), the second group — moderate (10–50), the third group — the lowest (<10).98 microRNAs were differently expressed in groups gMEN1 and phMEN1 (84 upregulated microRNAs, 14 — downregulated). We found increased expression of microRNAs in gMEN1 which interact with menin: hsa-miR-421 (p adj = 0.0004362), hsa-miR-664a-5p (p adj = 0.0037814). We found several microRNAs associated with intestinal and pituitary tumors in gMEN1 and phMEN1 groups: up-regulated hsa-miR-7-5p (p adj = 0.0000084); downregulated hsa-miR-423-5p (p adj < 0.000001) and hsa-miR-432-5p (p adj = 0.0087227). 84 microRNA were differently expressed in groups gMEN1 and control (67 up-regulated microRNAs, 17 — downregulated). When comparing gMEN1 with phMEN1 and control a decrease in hsa-let-7a-5p miRNA was found, which, according to the literature, is downregulated in Men1 gene knockout cell lines. The phMEN1 vs control group showed downregulation of hsa-miR-122-5p (p adj = 0.0080138) and upregulation of hsa-miR-191-5p (p adj = 0.0002144), hsa-miR-486-5p (p adj = 0.0491822) that has been detected in GEP-NETs. Conclusion We found microRNAs which could potentially become biomarkers in the differential diagnosis of gMEN1 and phMEN1. The results need to be validated using a different measurement method with a larger sample size. Presentation: Thursday, June 15, 2023

Altered microRNA expression in patients with sarcoidosis.

Background Sarcoidosis is a granulomatous multisystem disease of uncertain aetiology. The disease has major inflammatory and immune components; however, the immunopathogenesis is not well understood. Micro ribonucleic acids (microRNAs) are classes of miniature, single-stranded, non-coding RNAs. Their key recognised role includes mediating the silencing of target genes post-transcriptionally. Recently, the role of miRNAs has gained interest in numerous disorders, suggested as being involved in pathogenesis of those diseases and acting as disease markers. Very little is known about the role of miRNAs in sarcoidosis, with nothing known regarding miRNAs in South African patients. The main objective, therefore, was to investigate the serum expression of approximately 800 miRNAs in patients with sarcoidosis compared with race-, age- and gender-matched healthy controls. Methods A total of six patients and six matched controls participated in this study. Whole blood samples were collected in EDTA tubes, processed and the plasma retained. RNA was extracted from the stored plasma samples using the QIAGEN miRNeasy Mini Kit® and concentrated using a salt-ethanol precipitation. The extracted miRNA was profiled using an nCounter® miRNA human v3 expression assay and data analysed using the nSolver™ Analysis Software. Results After excluding one sample/control pair because of cellular RNA contamination, the remaining five patient and five matched control samples were analysed, and 145 miRNAs were found to be potentially differentially expressed. On applying a Bonferroni correction, the only miRNA that was significantly different was miRNA let-7a-5p, which was significantly overexpressed (141-fold change; p<0.0003) in patients compared with controls. Conclusion This is the first miRNA report of differentially expressed miRNAs in the serum of patients with sarcoidosis and matched healthy controls in South Africa. The results obtained suggest that miRNAs may play a role in sarcoidosis pathogenesis. Whether these molecules have diagnostic or prognostic implications, needs future studies recruiting larger patient cohorts.

MiR-181c targets Parkin and SMAD7 in human cardiac fibroblasts: Validation of differential microRNA expression in patients with diabetes and heart failure with preserved ejection fraction

BackgroundCardiac fibrosis represents a key element in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), a condition highly prevalent amongst geriatric patients, especially if diabetic. The microRNA 181c (miR-181c) has been shown to be associated with the response to exercise training in HFpEF patients and has been also linked to diabetic cardiovascular complications. However, the underlying mechanisms have not been fully elucidated. ObjectiveTo measure circulating miR-181c in elderly patients with HFpEF and diabetes mellitus (DM) and identify gene targets pathophysiologically relevant in HFpEF. MethodsWe quantified circulating miR-181c in frail older adults with a confirmed diagnosis of HFpEF and DM, and, as control, we enrolled age-matched subjects without HFpEF and without DM. We validated in human cardiac fibroblasts the molecular mechanisms linking miR-181c to a pro-fibrotic response. Results51 frail patients were included :34 patients with DM and HFpEF and 17 age-matched controls. We observed that miR-181c was significantly upregulated (p < 0.0001) in HFpEF patients vs controls. We confirmed in vitro that miR-181c is targeting PRKN and SMAD7. ConclusionsWe demonstrate that miR-181c levels are significantly increased in frail elderly adults with DM and HFpEF and that miR-181c targets PRKN and SMAD7 in human cardiac fibroblasts.

Retracted: Effect of EPOC on Serum MicroRNA Expression in Patients with Hypertension.

[This retracts the article DOI: 10.1155/2022/1998445.].

RF25 | PMON147 Plasma MicroRNA Expression in Phenocopy of Multiple Endocrine Neoplasia Type 1 Compared to Patients with Acromegaly and Primary Hyperparathyroidism: Potential Biomarkers of Multiple Endocrine Tumor Growth

Abstract Introduction Changes in the expression of microRNA facilitate in the formation of various tumors. MEN1 is a rare disease caused by mutations in MEN1 gene encoding the menin protein and characterize by the occurrence of parathyroid, pituitary, gastroenteropancreatic and other tumors. If a patient with the MEN1 phenotype carry no mutations in the MEN1 gene, the condition considers a phenocopy of syndrome (phMEN1). We hypothesize that the pathogenic link among the above sporadic tumors might be represented by molecular pathways involving the MEN1 gene and epigenetic regulations — particularly microRNAs. Materials &amp; methods Single-center, case-control study: assessment of plasma microRNA expression in patients with phMEN1, acromegaly (AM), primary hyperparathyroidism (PHPT) and healthy controls. Morning plasma samples were collected from fasting patients and age- and sex-matched controls and stored at –80°C. Total RNA isolation: miRNeasy Mini Kit with QIAcube. The libraries were prepared by the QIAseq miRNA Library Kit following the manufacturer. Circulating miRNA sequencing was done on Illumina NextSeq 500 (Illumina). Subsequent data processing was performed using the DESeq2 bioinformatics algorithm. Results We enrolled 36 consecutive patients (12 patients in each group) with phMEN1, AM, PHPT, along with 12 age and gender matched controls. Median age of phMEN1 group — 59 [52; 60.5]; AM — 59 [52; 63]; PHPT — 60.5 [54; 62.5]; control — 59 [51.5; 62.5]. The groups did not differ in age (p=0.88) and gender – in all groups were 11 women and 1 man (p=1.00). We divided all assessed microRNAs into 3 groups based on the significance of the results; the first group consisted of samples with the highest levels of detected microRNAs (&amp;gt;50), the second group — moderate (10–50), the third group — the lowest (&amp;lt;10). The microRNA expression pattern was almost the same between AM and phMEN1 groups (15 microRNAs upregulated, 10 — downregulated), we found slightly decreased hsa-miR-4301 (padj=0.038); it is interesting that phMEN group when compared to PHPT and control groups showed decline in hsa-miR-4301 too. PHPT and control groups had also quite similar expression profile (4 microRNAs upregulated, 19 — downregulated). 607 microRNA were differently expressed in groups phMEN1 and PHPT (473 upregulated microRNAs, 134 — downregulated). We found increased expression of some microRNAs that interferes with menin: hsa-miR-24-1-5p (padj=0.0008), hsa-miR-24-3p (padj=0.034), hsa-miR-26a-5p (padj=0.0005), hsa-miR-421 (padj=0.018), hsa-miR-762 (padj=0.027). In addition, we found decreased microRNAs with oncogene potential: miR-3182 (padj=0.007), hsa-miR-875-5p (padj&amp;lt;0.001), hsa-miR-6749-5p (padj&amp;lt;0.001). 173 microRNA differed in phMEN1 and control groups (11 microRNAs upregulated, 162 — downregulated). We detected several decreased microRNAs in phMEN1 that participate in tumor genesis: hsa-miR-625-3p (padj&amp;lt;0.005), hsa-miR-3168 (padj=0,028), hsa-miR-302b-3p (padj&amp;lt;0.001). Conclusion We found microRNAs, which could potentially become biomarkers in phMEN1 diagnosis. The results need to be validated using different measurement method with larger sample size. Likewise further assessment of plasma microRNA expression in genetically confirmed MEN1 patients is needed. Presentation: Monday, June 13, 2022 12:30 p.m. - 12:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Role of resveratrol supplementation in regulation of glucose hemostasis, inflammation and oxidative stress in patients with diabetes mellitus type 2: A randomized, placebo-controlled trial

ObjectiveThe objective was to determine the effects of resveratrol supplementation on glucose homeostasis, oxidative stress, inflammation and microRNAs expression in patients with diabetes mellitus type 2 on oral hypoglycemic drugs. MethodThis was a randomized, double blinded placebo-controlled parallel group trial. The diabetic patients (n = 110) were randomly assigned either to resveratrol (n = 55) and placebo (55) groups after informed consent and given once daily resveratrol 200 mg and cellulose capsules respectively for 24 weeks. Fasting glucose, insulin, HbA1c, lipid profile, TNF- α, IL-6, hs-CRP, MDA & circulatory microRNAs were measured at start and end of 24- week intervention. ResultsOut of 110 patients recruited, 94 patients completed the study comprising of 45 in resveratrol and 46 in placebo group. The resveratrol supplementation after 24 weeks was resulted in significant reduction [mean difference (95%CI)] of plasma glucose[− 0.50(−0.94 to −0.06)], insulin[− 1.31(−2.24 to −0.38)], homeostatic model assessment of insulin resistance[− 0.83(−1.37 to −0.29)], malondialdehyde[− 0.36(−0.61 to −0.11)], high sensitive-C-reactive protein[− 0.35(−0.70 to −0.01)], tumor necrosis factor-alpha[− 1.25(−1.90 to −0.61)] and interleukin-6[− 1.99(−3.29 to −0.69)]. More than two-fold down regulation in miRNA-34a, miRNA-375, miRNA-21, miRNA-192 and up regulation in miRNA-126 and miRNA-132 expression was noted in patients receiving resveratrol as compared to placebo. No side effects were reported during the trial. ConclusionResveratrol supplementation contributes in improvement of glycemic control by reducing insulin resistance. It has significant beneficial impact on chronic inflammation, oxidative stress and associated microRNA expression in diabetic patients. Thus, supplementation of resveratrol along with oral hypoglycemic agents may be useful in the reduction of diabetic associated complications.

Effect of EPOC on Serum MicroRNA Expression in Patients with Hypertension.

In order to analyze the effect of EPOC on serum microRNA expression in patients with hypertension, we have carried out an experimental evaluation and presented a dedicated method to improve its effectiveness. For this purpose, 60 patients with hypertension treated in our hospital from January to December 2020 were selected and randomly divided into the EPOC group (30 cases) and the control group (30 cases). Patients in both groups received conventional hypertension medication according to the treatment guidelines, and education and guidance were strengthened to ensure patients' drug compliance. The EPOC group received EPOC training in addition to conventional medication. After the intervention, 6MWD, LVEF, and LVEDD in the control group and the EPOC group were significantly improved compared with that before treatment (P < 0.05). The improvement of cardiac function in the EPOC group was significantly better than that in the control group (P < 0.05). Physiological function, physiological characteristics, body pain, and general health of the control group and the EPOC group were significantly improved compared with that before treatment (P < 0.05). The improvement of quality of life in the EPOC group was significantly better than that in the control group (P < 0.05). The indexes of heart rate, oxygen pulse, minute ventilation, oxygen uptake in kg, and anaerobic threshold in the EPOC group were significantly better than those in the control group before and after treatment (P < 0.05). Full-sample real-time PCR verification of the 8 miRNAs with the highest expression differentiation showed that, compared with the control group, the expression levels of miR-20a-5p, miR-93-5p, and miR-1287-5p in the serum of the EPOC group were significantly increased, while the expression levels of miR-7706, miR-28-5p, and miR-125b-5p were significantly decreased. The expression of miR-20a-5p was the highest, while the expression of miR-125b-5p was the lowest, suggesting that miR-20a-5p and miR-125b-5p might be involved in the process of HIIT to improve hypertension. After EPOC rehabilitation treatment, patients' heart function indexes, lung function indexes, and quality of life have been significantly improved. EPOC rehabilitation can improve exercise tolerance, enhance cardiopulmonary function, and improve the prognosis of patients.

Analysis of inflammation-related microRNA expression in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a complex genetic disease characterized by axial skeletal inflammation. Available scientific evidence suggests that a relationship may exist between miRNA expression levels and the pathogenesis of AS. This study investigated the clinical diagnostic value of miR-146a, miR-15a, miR-20a, miR-125a-3p, miR-125a-5p, miR-125b-5p, miR-148a, miR-149a, miR-499, and miR-155a in AS. A total of 44 AS patients and 56 healthy controls (HCs) were included in the study. MiRNA expression levels were detected using fluorescence quantitative PCR (qPCR). Results showed that the expression levels of miR-146a, miR-125a-3p, miR-125a-5p, miR-125b-5p, and miR-155a decreased, whereas miR-499a expression increased significantly in AS patients compared to that in the controls. Logistic regression analysis with receiver operating characteristic (ROC) curves showed that combined miR-146a/miR-125a-5p/miR-125b-5p/miR-499a/miR-155a (area under curve [AUC] = 0.824, 95% confidence interval [CI] = 0.727-0.921) had high sensitivity and specificity for AS diagnosis. C-reactive protein (CRP) levels were positively correlated with the expression of miR-125a-5p (rs = 0.438, p = 0.005) and miR-155a (rs = 0.414, p = 0.006), which indicates that miR-125a-5p and miR-155a can perhaps aggravate AS-induced inflammation. Our findings suggest the association of miR-125a-5p and miR-155a with disease activity in AS patients. Furthermore, miR-146a, miR-125a-5p, miR-125b-5p, miR-499a, and miR-155a could have potential diagnostic value in AS.

Identification of cluster of differentiation molecule-associated microRNAs as potential therapeutic targets for gastrointestinal cancer immunotherapy.

Cluster of differentiation molecules are markers of immune cells that have been identified as a potential immunotherapeutic target for cancer treatment. MicroRNAs are small non-coding RNAs that act as tumor suppressors or oncogenes whose importance in diagnosis, prognosis, and treatment of gastric and colorectal cancers has been widely reported. However, their association with cluster of differentiation molecules in gastrointestinal cancers has not been well studied. Therefore, our study aimed to analyze the relationship between microRNAs and cluster of differentiation molecules in gastrointestinal cancers, and to identify cluster of differentiation molecule-associated microRNAs as prognostic biomarkers for gastrointestinal cancer patients. Targetscan, Starbase, DIANA microT, and miRDB were used to investigate microRNA profiles that might be correlated with cluster of differentiation molecules in gastrointestinal cancers. Moreover, The Cancer Genome Atlas data analysis was used to investigate the association between cluster of differentiation molecules and microRNA expression in patients with gastric, colon, rectal, pancreatic, and esophageal cancers. The Kaplan-Meier plotter was used to identify the association between overall survival and cluster of differentiation molecule-associated microRNA expression in gastrointestinal cancer patients. miR-200a, miR-559, and miR-1236 were negatively associated with CD86, CD81, and CD160, respectively, in almost all types of gastrointestinal cancers, which were further verified in the in vitro studies by transfecting microRNA mimics in gastric cancer, colon cancer, pancreatic, and esophageal cell lines. Our study showed that miR-200a, miR-1236, and miR-559 are identified as cluster of differentiation-associated microRNAs in gastrointestinal cancers, providing a novel perspective to identify new therapeutic targets for cancer immunotherapy in gastrointestinal cancer patients.

Evaluation of circulating microRNA expression in patients with trigeminal neuralgia: An observational study.

Trigeminal neuralgia (TN) is a chronic neuropathic pain that seriously affects the daily life of patients. There is increasing evidence that microRNAs (miRNAs) play an important role in the development of neuropathic pain.In this study, the TaqMan Low Density Array (TLDA) was used to analyze the serum miRNA levels of 28 TN patients, and 31 healthy people without any neuropathic pain were used as controls.The results showed that the expression profile of serum miRNA in TN patients was different from that in healthy controls. Compared with the control group, 13 miRNAs in the serum of TN patients were up-regulated and 115 miRNAs were down-regulated by >2 times. Quantitative reverse transcription PCR (RT-qPCR) analysis and receiver operating characteristic (ROC) curve were performed. The analysis further confirmed that the expression levels of 4 miRNAs, including miR-132-3p, miR-146b-5p, miR-155-5p, and miR-384, were significantly higher than those of healthy controls, and the difference was statistically significant.This study preliminarily confirmed the changes of serum miRNA expression profile in TN patients. Among them, 4 kinds of serum miRNA are likely to be related to the occurrence and development of TN.

Role of microRNAs in neuroendocrine neoplasms of the stomach

Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare epithelial tumors that arise from cells with a neuroendocrine phenotype. NENs are found in the gastrointestinal tract and pancreas – 60 % of all localities. The incidence of gastric NENs is about 9 % of all neuroendocrine tumors of the gastrointestinal tract and 0.3 % of all stomach tumors. Stomach neuroendocrine tumors (NETs) are classified into three clinico-pathological types, based on etiology, pathogenesis and morphology. There are also separate neuroendocrine cancers: small- and large-cell. The prognosis and approach to treatment of various types of gastric NENs differs significantly. Modern methods of instrumental diagnostics, immunohistochemical methods of morphological research, along with light microscopy, do not always allow us to accurately assess the malignant potential of a tumor and individualize the treatment process. One of the promising directions in the study of NETs is to determine the molecular mechanism underlying their development, in particular the role of microRNAs. This direction can open a new vector of understanding the pathogenesis, determining the prognosis of the disease, as well as finding new application points for the drug treatment of NETs. MicroRNAs are a class of short non-coding RNA molecules (18–25 nucleotides). MicroRNAs can be involved in the regulation of all major cellular processes, including proliferation and differentiation, metabolism, signaling pathways, and apoptosis. A study of microRNA expression in tissues revealed tumor-specific microRNAs. In contrast to a number of other malignant tumors, microRNA expression in patients diagnosed with NENs is poorly understood. MicroRNA-222 and microRNA-202 are among the few microRNAs that have been demonstrated in the NETs of the stomach.

Dysregulated microRNA expression in rheumatoid arthritis families\u2014a comparison between rheumatoid arthritis patients, their first-degree relatives, and healthy controls

ObjectiveRecent studies have demonstrated an altered expression of certain microRNAs in patients with rheumatoid arthritis (RA) as well as their first-degree relatives (FDRs) compared to healthy controls (HCs), suggesting a role of microRNA in the progression of the disease. To corroborate this, a set of well-characterized RA families originating from northern Sweden were analyzed for differential expression of a selected set of microRNAs.MethodMicroRNA was isolated from frozen peripheral blood cells obtained from 21 different families and included 26 RA patients, 22 FDRs, and 21 HCs. Expression of the selected microRNAs miR-22-3p, miR-26b-5p, miR-34a-3p, miR-103a-3p, miR-142-3p, miR-146a-5p, miR-155, miR-346, and miR-451a was determined by a two-step quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis including clinical variables was applied.ResultsOut of the nine selected microRNAs that previously have been linked to RA, we confirmed four after adjusting for age and gender, i.e., miR-22-3p (p = 0.020), miR-26b-5p (p = 0.018), miR-142-3p (p = 0.005), and miR-155 (p = 0.033). Moreover, a significant trend with an intermediate microRNA expression in FDR was observed for the same four microRNAs. In addition, analysis of the effect of corticosteroid use showed modulation of miR-103a-3p expression.ConclusionsWe confirm that microRNAs seem to be involved in the development of RA, and that the expression pattern in FDR is partly overlapping with RA patients. The contribution of single microRNAs in relation to the complex network including all microRNAs and other molecules is still to be revealed.Key Points• Expression levels of miR-22-3p, miR-26b-5p, miR-142-3p, and miR-155 were significantly altered in RA patients compared to those in controls.• In first-degree relatives, a significant trend with an intermediate microRNA expression in FDR was observed for the same four microRNAs.

Outlook for Neurofi bromatosis Type I Research in the Republic of Bashkortostan

Neurofi bromatosis type I (NF1) is a common hereditary tumour syndrome with autosomal dominant type of inheritance. Average worldwide incidence rate of NF1 is 1:3000, equal in men and women. Th e disease develops with a heterozygous mutation in the oncosupressor neurofi bromin-encoding gene NF1. No NF1-associated most common mutations have been found, with over 1400 mutations being described along the gene. No clinical and genetic correlations are observed for NF1, and its symptoms may vary considerably within same inheritance group. Typical NF1 manifestations include pigmented patches and multiple cutaneous or subcutaneous neurofi bromas, oft en disfi guring in degree. Pathogenetic therapy for NF1 is not yet developed, whilst surgical tumourectomy may lead to recurrence and new tumour development in other localities on the body. Molecular genetic research on putative interfaces with epigenetic factors and gene expression patterns may open promising future avenues. Further, establishing a marker NF1 mutation in NF1 patients will allow secondary prevention of the disease. A survey of russian NF1-related literature reveals prevalence of individual clinical case descriptions. In the Russian Federation, studies of NF1-associated mutations in gene NF1 originate from Moscow and Bashkortostan, which sets off advancement of Bashkir medical genetics and urges further developments. In Bashkortostan, 10 NF1-associated mutations were described from 16 patients. Th e reported mutations с.1278G&gt;A (p.Trp426Х), с.1570G&gt;A (p.Glu540Lys), с.1973_1974delTC (р.Leu658ProfsX10), с.3526_3528delAGA (p.Arg1176del), с.3826delC (р.Arg1276GlufsX8), с.4514+5G&gt;A, c.5758_5761delTTGA (p.Leu1920AsnfsX7) in the NF1 gene are new to science. Further research into other genes’ and microRNA expression in patients with various clinical manifestations of NF1 should be aimed at discovering its possible involvement in disease pathogenesis.

Expression of plasma microRNA in patients with acromegaly

microRNA is a class of small non-coding RNA molecules involved in posttranscriptional regulation of gene expression. MicroRNAs are detectable in blood in stable concentrations, which makes them promising biomarkers for various diseases. to assess plasma microRNA expression in patients with active acromegaly compared with healthy controls. single-center, case-control study: assessment of plasma microRNA in patients with acromegaly compared with healthy controls. Fasting blood samples were drawn and centrifuged at +5С temperature and 3000 rpm for 20 minutes, then aliquoted and frozen at 80C until further analysis. MicroRNA extraction and library preparation was done according to manufacturers instructions. Expression analysis was performed on NextSeq sequencer. Bioinformatic analysis using atropos (adapted deletion), STAR (aligning), FastQC (quality control), seqbuster/seqcluster/miRge2 (microRNA annotation, isomiR and new microRNA search, expression analysis). Primary endpoint of the study differential expression of plasma microRNA in patients with acromegaly compared with healthy controls. we included 12 patients with acromegaly age 33.1 [20; 47], BMI 29.3 kg/m2 [24.0; 39.6], IGF-1 686.1 ng/mL [405.9; 1186.0] and 12 healthy subjects age 36.2 [26; 44], BMI 26.7 kg/m2 [19.5; 42.5], IGF-1 210.4 ng/mL [89.76; 281.90]; gender ratio for both groups 4 males, 8 females. The groups did not differ in gender (p=0.666), age (p=0.551) and BMI (p=0.378). We found decreased expression of four microRNAs in patients with acromegaly: miR-4446-3p 1.317 (p=0.001), miR-215-5p 3.040 (p=0.005), miR-342-5p 1.875 (p=0.013) and miR-191-5p 0.549 (p=0.039). However, none of these changes were statistically significant after adjustment for multiple comparisons (q 0.1). we found four microRNAs, which could potentially be downregulated in plasma of patients with acromegaly. The result need to be validated using different measurement method with larger sample size.

Study on the Difference of Plasma microRNA Expression in Patients With Genetic Susceptibility to Mental Disorders

Study on the Difference of Plasma microRNA Expression in Patients With Genetic Susceptibility to Mental Disorders