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Context. MicroRNAs (miRNAs) are short noncoding RNAs involved in posttranscriptional regulation of gene expression that influence various cellular functions including glucose and lipid metabolism and adipocyte differentiation. Objective. The aim of this study was to evaluate the levels of miR-34a and miR-149 and their relationship with metabolic parameters in obese children and adolescents. Design. Seventy children and adolescents were enrolled in the study. Plasma levels of microRNAs were evaluated by real-time PCR using SYBR green and analyzed by ΔCt method. Plasma concentrations of visfatin and insulin were measured by ELISA method. Glucose and lipid profile were determined colorimetrically. HOMA-IR was calculated and used as an index of insulin resistance (IR). Results. miR-34a was significantly lower in subjects with insulin resistance compared to obese children with normal insulin sensitivity. There was an inverse relationship between miR-34a levels and both insulin and HOMA-IR. On the other hand, miR-149 was significantly correlated with visfatin. There was no significant difference in miR-34a and miR-149 between obese and normal weight subjects. Conclusions. miR-34a is associated with insulin and HOMA-IR and thus seems to be involved in IR. miR- 149 is inversely associated with visfatin levels which could be indicative of anti-inflammatory effect of this miRNA. [ABSTRACT FROM AUTHOR]

Neurodevelopmental disorders are major indications for genetic referral and have been linked to more than 1500 loci including genes encoding transcriptional regulators. The dysfunction of transcription factors often results in characteristic syndromic presentations; however, at least half of these patients lack a genetic diagnosis. The implementation of machine learning approaches has the potential to aid in the identification of new disease genes and delineate associated phenotypes. Next generation sequencing was performed in seven affected individuals with neurodevelopmental delay and dysmorphic features. Clinical characterization included reanalysis of available neuroimaging datasets and 2D portrait image analysis with GestaltMatcher. The functional consequences of ZSCAN10 loss were modelled in mouse embryonic stem cells (mESCs), including a knockout and a representative ZSCAN10 protein truncating variant. These models were characterized by gene expression and western blot analyses, chromatin immunoprecipitation and quantitative PCR (ChIP-qPCR) and immunofluorescence staining. Zscan10 knockout mouse embryos were generated and phenotyped. We prioritized bi-allelic ZSCAN10 loss-of-function variants in seven affected individuals from five unrelated families as the underlying molecular cause. RNA-sequencing analyses in Zscan10-/- mESCs indicated dysregulation of genes related to stem cell pluripotency. In addition, we established in mESCs the loss-of-function mechanism for a representative human ZSCAN10 protein truncating variant by showing alteration of its expression levels and subcellular localization, interfering with its binding to DNA enhancer targets. Deep phenotyping revealed global developmental delay, facial asymmetry and malformations of the outer ear as consistent clinical features. Cerebral MRI showed dysplasia of the semicircular canals as an anatomical correlate of sensorineural hearing loss. Facial asymmetry was confirmed as a clinical feature by GestaltMatcher and was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations. Our findings provide evidence of a novel syndromic neurodevelopmental disorder caused by bi-allelic loss-of-function variants in ZSCAN10., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Recent studies have implicated dysregulated long non-coding RNA (lncRNA) levels in the pathogenesis of type 2 diabetes (T2D). This study aimed to assess the expression of circulating HOTAIR and uc.48+, examining their correlation with clinical and biochemical variables in T2D patients, pre-diabetic individuals, and healthy controls., Methods: Peripheral blood levels of lncRNAs were quantified using QRT-PCR in 65 T2D patients, 63 pre-diabetic individuals, and 63 healthy subjects. Pathway enrichment analysis was conducted to explore the functional enrichment of lncRNA-miRNA targets., Results: Analysis revealed a significantly elevated circulating level of HOTAIR in both T2D (P < 0.0001) and pre-diabetic patients (P = 0.04) compared to controls. ROC analysis demonstrated that, at a cutoff value of 9.1, with a sensitivity of 80% and specificity of 62%, HOTAIR could distinguish T2D patients from controls (AUC = 0.723, 95% CI 0.637-0.799, P < 0.0001). Spearman correlation analysis identified a significant positive correlation between HOTAIR expression, HbA1c, and insulin resistance (P < 0.005). MiRNA enrichment analysis indicated significant enrichment of diabetes-related pathways among HOTAIR's miRNA targets. Conversely, no significant difference in uc.48+ circulating levels between groups was observed, but a significant positive correlation emerged between uc.48+ and systolic blood pressure., Conclusions: This study provides evidence that elevated HOTAIR expression levels are associated with T2D progression, suggesting their potential as biomarkers for early diagnosis and prognosis., Competing Interests: The authors declare no conflicts of interest.

Background: Circulating microRNAs (miRNAs) can help to predict the chemotherapy response in breast cancer with promising results. The aim of the present study was to investigate the relationships between the miR-199a, miR-663a, and miR-663b expression and chemotherapy response in metastatic breast cancer patients., Methods: This study is a case-control study performed at Yasuj University of Medical Sciences (2018-2021). The expression levels of miR-663a, miR-663b, and miR-199a in the serum of 25 patients with metastatic breast cancer versus 15 healthy individuals were determined by the real-time polymerase chain reaction method. The response to treatment was followed up in a 24-month period. All patients were treated with second-line medications. Two or more combinations of these drugs were used: gemcitabine, Navelbine ® , Diphereline ® , Xeloda ® , letrozole, Aromasin ® , and Zolena ® . Statistical analyses were performed in SPSS 21.0 and GraphPad Prism 6 software. The expression levels were presented as mean±SD and analyzed by Student's t test., Results: The results and clinicopathological features of patients were analyzed by t test. The statistical analysis showed that miR-663a expression was related to human epidermal growth factor receptor 2 (HER2) status and was significantly lower in the HER2 + than HER2 - group (P=0.027). Moreover, the expression of miR-199a and miR-663b was significantly correlated with the response to treatment, in which the expression of miR-199a was higher in the poor-response group (P=0.049), while the higher expression of miR-663b was seen in the good-response group (P=0.009)., Conclusion: These findings state that the high plasma level of miR-199a and the low plasma level of miR-663b may be related to chemoresistance in patients with metastatic breast cancer., Competing Interests: Dr. Mehdi Dehghani, as the Editorial Board Member, was not involved in any stage of handling this manuscript. A team of independent experts were formed by the Editorial Board to review the article without his knowledge., (Copyright: © Iranian Journal of Medical Sciences.)

Background: It has been suggested that the anti-hyperglycemic effect of metformin could be associated with its impact on long non-coding RNA (lncRNA) expression levels. Accordingly, in the current study, we evaluated the effect of metformin on the expression of H19, MEG3, MALAT1, and GAS5 in in vitro and in vivo situations., Methods: The effect of hyperglycemia and metformin treatment on the lncRNAs expression level was evaluated in HepG2 cells. A total of 179 age- and sex-matched subjects, including 88 newly diagnosed patients with type 2 diabetes (T2D) and 91 healthy volunteers, were included in the case-control phase of the study. Moreover, 40 newly diagnosed patients participated in the study's open-labeled non-controlled clinical trial phase. The expression levels of lncRNA in HepG2 cells and whole blood samples were determined using QRT-PCR., Results: In vitro results showed that hyperglycemia induced H19 and MALAT1 and decreased GAS5 expression levels. Moreover, metformin decreased H19 and increased GAS5 expression in high glucose-treated cells. Case-control study findings revealed that the circulating levels of H19, MALAT1, and MEG3 were significantly elevated in T2D patients compared to the control subjects. Finally, results showed that the level of circulating H19 levels decreased while GAS5 increased in T2D patients after taking metformin for 2 months., Conclusion: The results of the current study provided evidence that metformin could exert its effect in the treatment of T2D by altering the expression levels of H19 and GAS5., (© 2022. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Background: Recent investigations suggested that deregulated levels of Circular RNAs (circRNAs) could be associated with type 2 diabetes mellitus (T2DM) pathogenesis. Accordingly, this study aimed to determine the expression levels of circulating CircHIPK3, CDR1as and their correlation with biochemical parameters in patients with T2DM, pre-diabetes and control subjects., Methods and Results: The expression of circRNAs in peripheral blood was determined using QRT-PCR in 70 patients with T2DM, 60 pre-diabetes and in 69 age and sex matched healthy controls. Moreover, bioinformatics tools were applied to explore and predict the potential interactions between circRNAs and other non-coding RNAs (ncRNAs). Our analysis revealed that the expression level of CircHIPK3 was significantly elevated in T2DM patients compared to healthy participants (P < 0.001) and pre-diabetes subjects (P = 0.018). In addition, ROC analysis suggested that at the cutoff value of 0.24 and the sensitivity and specificity of 50% and 88.4%, respectively, CircHIPK3 could distinguish between T2DM patients and control subjects. Furthermore, it was observed that the expression level of CDR1as is higher in pre-diabetic individuals than healthy individuals (P = 0.004). Finally, Spearman correlation analysis showed that there was a significant correlation between CircHIPK3 and CDR1as expression levels and clinical and anthropometrical parameters such as BMI, systolic and diastolic blood pressure, HbA1c and fasting blood glucose (P < 0.005)., Conclusions: The data of this study provided evidence that the expression levels of CircHIPK3, CDR1as increased in T2DM and pre-diabetes subjects, respectively., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Pathogenesis of the beginning and progression of nonalcoholic fatty liver disease (NAFLD) has not been clarified exactly. The osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) axis seems to play an imperative function in the onset and progression of this disease. The goal of the present study was to investigate the peripheral blood mononuclear cell (PBMC) expression and plasma levels of RANKL and OPG cytokines in NAFLD patients and compare them with healthy group. Plasma levels of OPG and RANKL were determined with ELISA kits in 57 men with NAFLD and 25 healthy men as controls. Biochemical and anthropometric parameters tests were also evaluated in the study groups. RANKL and OPG mRNA contents were evaluated by quantitative RT-PCR. OPG contents were markedly decreased in NAFLD patients as compared with healthy patients [1.43 (1.05-5.45)] versus [2.94 (1.76-4.73)] ng/mL; P = 0.007). The levels of RANKL were significantly reduced in NAFLD patients [74.00 (56.26-203.52) ng/mL] than in healthy patients [119.37 (83.71-150.13) ng/mL]; (P = 0.03). Also, OPG and RANKL gene expression were significantly decreased in NAFLD patients in comparison with the control group (P < 0.05). Moreover, receiver operating characteristic curve indicated that OPG may have a good capability to discriminate between NAFLD patients and normal individuals. A positive correlation was observed between OPG and RANKL in plasma sample (r = 0.495) (P = 0.000). Decreased plasma levels and gene expression of RANKL and OPG cytokines in NAFLD patients indicate that there is a relationship between these cytokines and the pathology of NAFLD disease. Confirmation of this association as well as the mechanism and role of these cytokines in NAFLD require further studies., (© 2020 International Union of Biochemistry and Molecular Biology, Inc.)

This study was aimed to investigate the effect of microalgae Chlorella vulgaris (C. vulgaris) on nonalcoholic fatty liver disease (NAFLD)-related complications induced by high-fat diet (HFD). Fifty adult male rats were divided into six groups. Control group and HFD group treated with or without C. vulgaris 5% and 10%. Biochemical parameters in serum were measured by spectrophotometric and enzyme-linked immunosorbent assay (ELISA) methods. The relative gene expression levels of Tumor Necrosis Factor-alpha (TNF-α), NF-kappa B (NF-ƙB), and p38 Mitogen-Activated Protein Kinases (p38 MAPK) in the liver were assessed by using quantitative real-time PCR, while the protein levels of NF-ƙB and TNF-α in the liver homogenate were determined by ELISA. The effects of HFD significantly were reversed by C. vulgaris, especially at a 10% dose. Therefore, it can be concluded that C. vulgaris therapeutically could be useful to improve NAFLD and its complications. PRACTICAL APPLICATIONS: It is established that NAFLD is associated with the resistance to insulin, dyslipidemia, and inflammation. Accordingly, modulating of these conditions may be useful in the management of NAFLD. Our results showed the effectiveness of C. vulgaris against NAFLD-related complication through the alleviating insulin resistance, dyslipidemia and also down-regulation of inflammatory genes in p38 MAPK/TNF-α/NF-ƙB pathway. The results of our study may be useful for scientist to prepare an effective supplement from C. vulgaris to overcoming NAFLD-related complications., (© 2021 Wiley Periodicals LLC.)

Aims: The hereditary spastic paraplegias (HSPs) are a heterogeneous group of inherited neurodegenerative disorders. Although, several genotype-phenotype studies have carried out on HSPs, the association between genotypes and clinical phenotypes remain incomplete since most studies are small in size or restricted to a few genes. Accordingly, this study provides the systematic meta-analysis of genotype-phenotype associations in HSP., Methods and Results: We retrieved literature on genotype-phenotype associations in patients with HSP and mutated SPAST, REEP1, ATL1, SPG11, SPG15, SPG7, SPG35, SPG54, SPG5. In total, 147 studies with 13,570 HSP patients were included in our meta-analysis. The frequency of mutations in SPAST (25%) was higher than REEP1 (3%), as well as ATL1 (5%) in AD-HSP patients. As for AR-HSP patients, the rates of mutations in SPG11 (18%), SPG15 (7%) and SPG7 (13%) were higher than SPG5 (5%), as well as SPG35 (8%) and SPG54 (7%). The mean age of AD-HSP onset for ATL1 mutation-positive patients was earlier than patients with SPAST, REEP1 mutations. Also, the tendency toward younger age at AR-HSP onset for SPG35 was higher than other mutated genes. It is noteworthy that the mean age at HSP onset ranged from infancy to adulthood. As for the gender distribution, the male proportion in SPG7-HSP (90%) and REEP1-HSP (78%) was markedly high. The frequency of symptoms was varied among patients with different mutated genes. The rates of LL weakness, superficial sensory abnormalities, neuropathy, and deep sensory impairment were noticeably high in REEP1 mutations carriers. Also, in AR-HSP patients with SPG11 mutations, the presentation of symptoms including pes cavus, Neuropathy, and UL spasticity was higher., Conclusion: Our comprehensive genotype-phenotype assessment of available data displays that the mean age at disease onset and particular sub-phenotypes are associated with specific mutated genes which might be beneficial for a diagnostic procedure and differentiation of the specific mutated genes phenotype among diverse forms of HSP.

The mitochondrial encephalomyopathies represent a clinically heterogeneous group of neurodegenerative disorders. The clinical phenotype of patients could be explained by mutations of mitochondria-related genes, notably SUCLG1 and SUCLA2. Here, we presented a 5-year-old boy with clinical features of mitochondrial encephalomyopathy from Iran. Also, a systematic review was performed to explore the involvement of SUCLG1 mutations in published mitochondrial encephalomyopathies cases. Genotyping was performed by implementing whole-exome sequencing. Moreover, quantification of the mtDNA content was performed by real-time qPCR. We identified a novel, homozygote missense variant chr2: 84676796 A > T (hg19) in the SUCLG1 gene. This mutation substitutes Cys with Ser at the 60-position of the SUCLG1 protein. Furthermore, the in-silico analysis revealed that the mutated position in the genome is well conserved in mammalians, that implies mutation in this residue would possibly result in phenotypic consequences. Here, we identified a novel, homozygote missense variant chr2: 84676796 A > T in the SUCLG1 gene. Using a range of experimental and in silico analysis, we found that the mutation might explain the observed phenotype in the family.

Background: Recent evidence indicates that TRIB3 and miR-124 levels have been deregulated in type 2 diabetes (T2D); however, the simultaneous evaluation of these markers in diabetic patients has not been investigated to date., Methods: This case-control study included 50 T2D patients and 40 age-gender matched controls. The circulation level of miR-124a was assessed by real-time PCR. TRIB3 plasma level was measured using the enzyme-linked im-munosorbent assay., Results: Our findings revealed that the TRIB3 plasma level was significantly increased (p = 0.025), while miR-124a plasma levels were significantly reduced (p = 0.028) in diabetic patients compared to healthy subjects. ROC analysis showed that TRIB3 and miR-124a levels could discriminate control subjects and diabetic patients. Interestingly, a significant negative correlation was found between the TRIB3 and miR-124a plasma levels. Furthermore, there was a significant positive correlation between the TRIB3 plasma level with fasting blood glucose and insulin resistance., Conclusions: In this study, we showed deregulation of TRIB3 level in diabetic patients and its association with miR-124a circulating level and clinical parameters. These findings suggest that miR-124a may affect T2D incidence and progression by modulating the expression of TRIB3 protein level.

Accumulating evidence has reported that H19 long non-coding RNA (lncRNA) expression level is deregulated in human cancer. It has been also demonstrated that de-regulated levels of H19 could affect cancer biology by various mechanisms including microRNA (miRNA) production (like miR-675), miRNA sponging and epigenetic modifications. Furthermore, lncRNA could act as a potential diagnosis and prognosis biomarkers and also a candidate therapeutic approach for different human cancers. In this narrative review, we shed light on the molecular mechanism of H19 in cancer development and pathogenesis. Moreover, we discussed the expression pattern and diagnostic and therapeutic importance of H19 as a potential biomarker in a range of human malignancies from breast to osteosarcoma cancer.

Objectives: Injectable insulin is the most widely used therapy in patients with type 1 diabetes which has several disadvantages. The present study was aimed to evaluate the efficacy of injectable insulin on diabetes mellitus-related complications in comparison to orally encapsulated insulin nanoparticles., Materials and Methods: This study involved 42 Wistar rats separated into 5 groups, including control (C), diabetic control (D), diabetic receiving regular insulin (INS), diabetic receiving encapsulated insulin nanoparticle (INP), and diabetic receiving chitosan for two months. Biochemical parameters in serum and urine were measured using spectrophotometric or ELISA methods. mRNA levels of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated using quantitative PCR., Results: There were no significant differences between the two forms of insulin in controlling the glycemic condition ( P -value>0.05), but oral INP was more effective in correcting diabetic dyslipidemia in comparison to injectable insulin ( P -value<0.05). Urine volume and creatinine excretion were significantly modulated by insulin and oral INP in diabetic groups ( P -value<0.05), although the effects of INP on the modulation of execration of urea, acid uric, and albumin was more dramatic. Oral INP caused a significant decrease in urine concentration of KIM-1 and NGAL as well as expression of KIM-1 in renal tissue ( P -value<0.05)., Conclusion: Our results suggested that oral INP is more effective than injectable insulin in modulation of urine and serum diabetic-related parameters.

Recent investigations have indicated that altered expression of non-coding RNAs (ncRNAs) could be associated with human diseases such as type 2 diabetes (T2D). Circular RNAs (circRNAs) are a new discovered class of ncRNAs with unique structural characteristics that involved in several molecular and cellular functions. Exploring of the circulating circRNAs as a reliable non-invasive biomarker for monitoring and diagnosing of human diseases has grown significantly. However, the molecular functions and clinical relevance of circRNAs are not yet well clarified in T2D. Accordingly, in this review, the involvement of circRNAs in the β-cell function and T2D-related complications is highlighted. The study also shed light on the possibility of using circRNAs as a biomarker for T2D diagnosis.

BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory disorder of the large intestine. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a member of the immunoglobulin superfamily, which binds B7-1 and B7-2 on APCs (antigen-presenting cells), and induces APCs to produce an inhibitory signal to T cells. The aim of this study was to investigate the effect of vitamin D on CTLA-4 gene expression in whole blood samples of patients with UC. METHODS 90 patients with mild to moderate UC were randomized to receive either a single injection of 7.5 mg vitamin D3 or 1 mL normal saline. 90 days following the intervention fold changes in CTLA-4 mRNA expression were determined and statistical comparisons between the two groups were performed. RESULTS Serum vitamin D increased significantly only in the vitamin D group. CTLA-4 fold changes were significantly higher in the vitamin D group compared with the placebo group (median ± IQR: 1.21 ± 2.3 vs. 1.00 ± 1.5, respectively; p = 0.007). CONCLUSION The results of this study revealed that vitamin D administration in patients with UC enhances the CTLA-4 gene expression., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest related to this work., (© 2019 The Author(s).)

Background: Gastric cancer (GC) is one of the most prevalent cancers with a high rate of mortality in the world. In recent years, microRNAs (miRNAs) have been proposed to be involved in GC development. In this study, we aimed at investigating differential expression level of miR-155-5p, miR-15a, miR-15b, and miR-186 in GC., Methods: For this research, we used qPCR to investigate miR-15b, miR-155, miR-15a, and miR-186 expression levels in a total of 29 normal gastric tissue, 45 gastric dysplasia, and 39 GC samples., Results: We showed significant down-regulation of miR-155-5p (p = 0.0018), miR-15a (p = 0.0159), and miR-186 (p = 0.0005) expression in GC tissue., Conclusion: This study provides evidence for deregulated expression of miR155-5p, miR-186, and miR-15a in GC and is providing new insights into the potential implication of these miRNAs in the pathogenesis of GC.

Introduction: Acetaminophen (APAP) as an analgesic and antipyretic drug can result to liver damages while using more than 4 g/day. Therefore, APAP toxicity causes the liver to dysfunction. This study aims to investigate the hepatoprotective and antioxidant activity of hydroalcoholic extract of watercress (WC) in APAP-induced hepatotoxicity in rats., Materials and Methods: Randomly, twenty-four Wistar rats were divided into four groups of six each. Groups named as control, APAP, APAP + WC and APAP + S for group 1, 2, 3, and 4, respectively. Group 1 received distilled water 1 ml/kg for 7 days. In group 2, 3, and 4, rats pretreated by receiving distilled water (1 ml/kg), WC extract (500 mg/kg), silymarin extract (mg/kg) for 7 days, respectively. Of note, to induce acute hepatotoxicity in groups 2, 3, and 4, rats posttreated by orally intoxicated with single dose of APAP (2 g/kg) on the sixth day. The animals were sacrificed on the seventh day. Alanine amino transferase (ALT), aspartate amino transferase (AST), ferric reducing ability of plasma (FRAP), protein carbonyl (PCO), total thiol (T-SH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were measured in plasma. It should be noted that the chemical composition of WC extract was identified by GC-MS analysis., Results: The results have shown that there was a significant increase in AST, ALT, FRAP and PCO content in APAP group in comparison to control. Also, there was a significant reduction in T-SH levels and GPx activity in APAP group compared to control. However, administration of WC extract and silymarin not only causes a significant decrease in AST activity, but they markedly increased T-SH content and GPx activity compared to APAP group. GC-MS analysis showed the major compositions were found to be benzenepropanenitrile (48.30 %), Phytol (10.10 %), α-cadinene (9.50%) and linolenic acid (8.0)., Conclusions: It is concluded that the WC extract reduces APAP-induced toxicity through its hepatoprotective and antioxidant activity in rats.

The aim of the current study was to investigate the antioxidative effect of metformin (MTF) on bile duct ligation (BDL)-induced hepatic disorder and histological damage in rats. The rats were divided into 4 groups including sham control (SC), BDL alone (BDL surgery), MTF1 (BDL surgery and administration of 250 mg/kg of MFM) and MTF2 (BDL surgery and administration of 500 mg/kg of MTF). After BDL, the animals treated with MTF by gavage for 10 days. Hematoxylin and eosin staining, biochemical analysis and oxidative stress markers were assayed to determine histological alterations, liver functions, and oxidant/antioxidant status. Hepatotoxicity was verified by remarkable increase in plasma levels of aminotransferases and alkaline phosphatase activity and liver histology 10 days after the BDL surgery. Our finding showed that treatment with MTF markedly reduced plasma alkaline phosphatase and alleviated liver injury indices ( P ≤ 0.05). Furthermore, BDL caused a considerable increase in the protein carbonyl and malondialdehyde content ( P ≤ 0.05). However, MTF reduces oxidative stress by constraining the protein oxidation and lipid peroxidation, and increases antioxidant reserve by increasing the ferric reducing ability of plasma and reducing glutathione levels. MTF exerts antioxidative effects in the liver fibrosis and may represent a hepato-protective effect when given to rats with BDL-induced hepatic injury., (Copyright: © 2019 Research in Pharmaceutical Sciences.)

Purpose: The recent researches indicate that differential non-coding RNAs expression signatures could be associated with the pathogenesis of gastric cancer (GC). However, there are few studies focused on lncRNA-miRNAs co-expression profiling in GC patients. Therefore, in the present study the expression of H19 and MEG3 and their related miRNAs including miR-148a-3p, miR-181a-5p, miR-675-5p and miR-141-3p were determined in the plasma samples of GC patients and controls., Materials and Methods: This case-control study included 62 GC patients and 40 age- sex matched controls. The non-coding RNA levels were assessed by real-time PCR. Further, using in silico analysis, we identified shared targets of studied miRNAs and performed GC-associated pathway enrichment analysis., Results: Our results showed that the H19 level was significantly (P = 0.008) elevated and MEG3 expression was significantly (P = 0.002) down-regulated in GC patients compared to healthy participants. Furthermore, it was revealed that the miR-675-5p level was increased, while miR-141-3p plasma levels were significantly reduced in GC patients (P < 0.05). We did not observe a significant difference for miR-148a-3p (P = 0.682) and miR-181a-5p (P = 0.098) expression between groups. In addition, the expression levels of H19, MEG3 and miR-148a-3p were associated with some clinicopathological features of patients (P < 0.05). ROC analysis revealed that a combination of H19, MEG3 and miR-675-5p levels able to discriminate controls and GC subjects with 88.87% sensitivity and 85% specificity (AUC, 0.927; 0.85-0.96 CI, P < 0.0001)., Conclusion: The results of current study demonstrated that combination of H19, MEG3 and miR-675-5p expression levels could provide a potential diagnostic panel for GC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Gastric cancer (GC) is one of the most common types of cancer and the second leading cause of cancer-associated mortality .  Identification of novel biomarkers is critical to prolonging patient survival. MicroRNAs (miRNAs) proved to play diverse roles in the physiological and pathological state in cancers including GC. Herein we aimed at performing a meta-analysis on miRNA profiling studies that used microarray platforms. Relevant studies were retrieved from PubMed and GEO databases. We used the robust rank aggregation to perform the meta-analysis. Moreover, for meta-signature miRNAs target genes, we performed pathway enrichment and GO molecular function enrichment analysis. A total of 19 upregulated miRNAs and seven downregulated miRNAs in GC samples were identified. However, only three upregulated and one downregulated miRNA reached statistical significance after multiple test correction. Here we showed that hsa-miR-21-5p, hsa-miR-93-5p, hsa-miR-25-3p, and hsa-miR-375 are differentially expressed in GC samples.

Full-thickness skin defect is one of the main clinical problems, which cannot be repaired spontaneously. The aim of this study was to evaluate the feasibility of combining nanofibers with ADM as a bilayer scaffold for treatment of full-thickness skin wounds in a single-step procedure. The nanofibrous polycaprolactone/fibrinogen scaffolds were fabricated by electrospinning. Subsequently, mesenchymal stem cells were isolated from rat adipose tissues and characterized by flow cytometry. Cell adhesion, proliferation, and the epidermal differentiation potential of adipose-derived stem cells (ADSCs) on nanofibrous scaffolds were investigated by scanning electron microscopy (SEM), alamarBlue, and real-time PCR, respectively. In animal studies, full-thickness excisional wounds were created on the back of rats and treated with following groups: ADM, ADM-ADSCs, nanofiber, nanofiber-ADSCs, bilayer, and bilayer-ADSCs. In all groups, wounds were harvested on days 14 and 21 after treatment to evaluate re-epithelialization, blood vessel density, and collagen content. The results indicated that ADSCs seeded on ADM, nanofiber, and bilayer scaffolds can promote re-epithelialization, angiogenesis, and collagen remodeling in comparison with cell-free scaffolds. In conclusion, nanofiber-ADSCs showed the best results for re-epithelialization (according to histological scoring), average blood vessel density (92.7 ± 6.8), and collagen density (87.4 ± 4.9%) when compared to the control and other experimental groups.

Purpose: Long-noncoding RNAs (lncRNAs) have been reported to regulate glucose homeostasis and insulin synthesis and secretion. However, the association of genetic variants of lncRNAs and type 2 diabetes (T2D) has not been evaluated. Therefore, in the present study we investigated the association between H19 rs217727 and H19 rs3741219 variants and MEG3 rs7158663 polymorphism with T2D susceptibility., Materials and Methods: The study population consists of 969 subjects including 496 T2D patients and 473 non-diabetic age and sex-matched controls. The H19 and MEG3 variants genotyping were performed by PCR-RFLP method., Results: Our results revealed that the T allele of rs217727 was more frequent in T2D group compared with controls (P = 0.007, OR = 1.1, 95% CI:1.02-1.18). Moreover, the rs217727-TT genotype was significantly associated with T2D after adjustment for age, BMI and lipid levels (P = 0.041, OR = 1.53, 95% CI: 1.01-2.32). However, no significant difference was detected for allele or genotype frequencies of H19 rs3741219 between T2D and controls (P = 0.71). Furthermore, the findings showed that the AA genotype of MEG3 rs7158663 was associated with significantly increased risks of T2D compared with the GG genotype (P = 0.026, OR = 1.79, 95% CI: 1.07-2.99). The results remained significance after analysis by logistic regression (P = 0.033, Adjusted OR = 1.72, 95% CI: 1.04-2.84). Finally, bioinformatics analysis showed that these SNPs could alter local RNA folding structure and also the miRNA-lncRNA interactions., Conclusions: Our findings provided the evidence of significant association between H19 rs217727-TT and MEG3 rs7158663-AA genotypes with T2D susceptibility., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Recent genome-wide association studies (GWAS) identified a list of single-nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD). Replication of GWAS findings in different population corroborated the observed association in the parent GWAS. In this study, we aimed to replicate the association of rs1870634, a GWAS identified SNP, to CAD in an Iranian population. The study population consisted of 267 subjects undergoing coronary angiography coronary angiography including 155 CAD patients and 112 non-CAD age- and gender-matched controls. The genotype determination of rs1870634 SNP performed using high-resolution melting analysis (HRM) technique. Our results revealed that the GG genotype frequency was significantly higher in CAD patients compared with controls (P = 0.03). The results of binary logistic regression suggested that this genotype was significantly associated with CAD risk adjustment for age, BMI, sex, TC, and LDL-C lipid levels (OR of 2.78, 95% CI (1.10-7.01), P = 0.03). Moreover, our results showed that the GG+TG genotypes were 2.52 times more likely to develop CAD (95% CI 1.05-6.03) than TT genotype carriers after adjusting for age, sex, and lipid profiles (P = 0.037). These data showed that the GG genotype could be associated with increased risk of CAD in a sample of Iranian population.

Background: Recently, much attention has been paid to the role of circulating microRNAs (miRNAs) as novel biomarkers for various diseases. The aim of this study was to investigate the level of a subset of miRNAs in serum samples of the diabetic and healthy subjects., Methods: Forty two healthy and 45 T2D subjects participated in this study. Serum miR-21, miR-126, and miR-146a levels were measured using real-time PCR., Results: There was no significant difference in the serum level of miR-21, miR-126, and miR-146a between the diabetic and non-diabetic groups. The level of miR-21 in obese non-diabetic and diabetic subjects was significantly lower than lean subjects. Correlation analyses in non-diabetic and diabetic groups revealed a significant negative correlation between the amount of miR-21 and body mass index, waist circumference, insulin, and HOMA-IR levels., Conclusions: A reduced level of miR-21 might associate with obesity and its related metabolic traits such as hyperinsulinaemia.

Background: Type 2 diabetes is the most common metabolic disease, affecting many of the adult population all around the world. In recent years much attention has been paid to the role of circulating miRNAs as novel biomarkers for various diseases. The aim of this study was to investigate the expression level of miR-155 in serum samples of diabetic and healthy subjects., Methods: 42 healthy and 45 type 2 diabetic subjects participated in the study. Serum miR-155 level of the subjects was measured using real-time PCR. The levels of IL-6 and TNF-α were quantified using ELISA., Results: There was no significant difference in the level of miR-155 between the diabetic and non-diabetic groups. The level of miR-155 in non-diabetic obese group was significantly lower than the non-diabetic lean subjects. Correlation analyses in non-diabetic group revealed a significant negative correlation between the amount of miR155 and body mass index and cholesterol levels after the elimination of the confounding factors. In diabetic group, a negative correlation was found between miR-155 and insulin, HOMA-IR, and waist circumference levels. Furthermore, no significant relationship between miR-155 and inflammatory cytokines (TNF-α and IL-6) was observed in both diabetic and healthy groups., Conclusions: A reduced level of miR-155 might associate with obesity and its related metabolic traits such as hyperinsulinemia and dyslipidemia.

Background: Coronary artery disease (CAD) is the most common cause of mortality and disability from incommunicable disease in the world. Although the association between the single nucleotide polymorphisms (SNPs) in protein-coding genes and the risk of CAD has been investigated extensively, very few heart-disease associated studies concerning the SNPs in miRNA genes have been reported. The present study was performed to elucidate the association between the pre-microRNA-149 (miR-149) SNP rs2292832 and the risk of CAD in an Iranian population., Methods: Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to identify the genotypes of the miR-149 SNP rs2292832 in 421 unrelated subjects (272 with CAD and 149 controls)., Results: Our analysis revealed that the TT genotype was more frequent in CAD patients than control subjects (P=0.02) implying that TT genotype should be considered as a risk factor in CAD development (TT vs. TC+CC p=0.02, OR=1.88)., Conclusions: The present study suggests that rs2292832-TT in pre-miR-149 is associated with CAD in an Iranian population., Competing Interests: Conflict of interest Conflict of interest statement: The authors stated that they have no conflicts of interest regarding the publication of this article.

Although deregulation of miR-146a has been reported in type 2 diabetes repeatedly, the direction of deregulation events (up or down) remained to be inconsistent in literatures. Therefore, in this study we performed a meta-analysis on the possible association between miR-146a expression levels and type 2 diabetes. A systematic literature searching of PubMed, ISI Web of Science and Google Scholar was performed up to the end of September 2016. Finally, a total of 12 studies including 344 diabetic patients and 316 controls were selected for meta-analysis. All statistical analysis was performed using the metafor package with R software. Moreover, publication bias was assessed by Egger's and sensitivity analysis was applied on the meta-analysis. The results are presented as log10 odds ratios (logORs), 95% confidence intervals (CI) with relevant P values. The results revealed that miR-146a was downregulated in type 2 diabetes cases compared with normal subjects (P=0.01, logOR:-4.76, 95% CI:-8.41, -1.11). Furthermore, sub-group analysis showed that the association between miR-146a expression levels and type 2 diabetes in whole blood (P<0.001) and PBMCs (P<0.001) samples were significant. However, this association was not significant in the serum (P=0.67) and plasma (P=0.90) samples. Our finding suggests that miR-146a downregulation could be associated with type 2 diabetes susceptibility. Further investigations with larger sample size are required to evaluate this association in the type 2 diabetes pathogenesis., Competing Interests: The authors declare that they have no conflict of interest.

Background: Recent reports have suggested that single-nucleotide polymorphisms (SNPs) in microRNA genes may contribute to individual susceptibility to coronary artery disease (CAD). The purpose of this study was to evaluate the association between rs3746444 in pre-miR-499 with CAD., Methods: We performed a case-control study including 288 CAD patients and 150 control subjects. DNA was extracted from blood samples and genotyped through the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Meta-analysis was performed under fixed effect and random effect models whenever appropriate., Results: We found that the GG genotype is significantly more frequent in CAD patients than controls (adjusted p = 0.010; OR = 1.99, 95%; CI: 1.18 - 3.38). Additionally, through a meta-analysis, we showed that miR-499rs3746444 has a significant association with cardiovascular disease., Conclusions: Our results suggest that miR-499-rs3746444-GG is associated with CAD susceptibility and development.

Background: Complement-C1q/TNF-related protein 13 (CTRP13) is a novel adipokine involved in the regulation of energy metabolism. Here, we sought to evaluate serum levels of CTRP13 and adiponectin in patients with type 2 diabetes (T2D) (n = 40) and healthy subjects (n = 40) and also to study the association of CTRP13 levels with diabetes-related indices., Methods: Circulating levels of CTRP13 and adiponectin were measured by enzyme-linked immunosorbent assay (ELISA) in T2D patients (n = 40) and in an age and gender-matched control group (n = 40). The anthropometric assessment and biochemical evaluation were done in all subjects., Results: Circulating levels of CTRP13 and adiponectin were significantly lower in T2D patients in comparison with controls ( = 0.025 and p < 0.001, respectively). CTRP13 was inversely correlated with fasting blood sugar (Spearman's  = -0.420, p < 0.001), HbA1C (Spearman's  = -0.554, p < 0.001), and HOMA-IR (Spearman's  = -0.403, p < 0.001). ROC curve analysis showed that CTRP13 might be used as a biomarker for differentiating T2D patients from healthy individuals (area under the curve with 95% confidence intervals = 0.841, 0.752 - 0.929). A CTRP13 level equal to or lower than 0.885 ng/mL was found to be the optimal cutoff (sensitivity = 92.5%, specificity = 70%, Youden Index = 0.625) for differentiating T2D patients from healthy individuals., Conclusions: It appears that CTRP13 is a novel adipokine associated with T2D in humans as its serum level was significantly lower in T2D patients and also was inversely correlated with insulin resistance and FBS in humans.

Background: The deregulation of miRNAs has been implicated in the pathogenesis of type 2 diabetes (T2D). Single nucleotide polymorphisms (SNPs) located within the miRNA sequence could alter miRNA maturation and expression or change the binding affinity of miRNAs to their target mRNAs. In the present study we aimed to elucidate the possible association between the miR-146a rs2910164 and miR-149 rs2292832 variants with the susceptibility to T2D and its related metabolic traits in an Iranian population., Methods: The study population consisted of 183 type 2 diabetic and 192 non-diabetic subjects. The genotyping of the variants was performed by a PCR-RFLP method., Results: The frequency of the CC genotype of the miR-146a rs2910164 variant was significantly higher in diabetic patients than in controls (15.85% vs. 7.81%, p = 0.043). The results of binary logistic regression suggested that this genotype was significantly associated with T2D (OR of 2.43 (95% CI 1.17 - 5.02, p = 0.016). Moreover, subjects carrying the CC genotype had significantly higher values for diastolic blood pressure, triglycerides, total cholesterol, fasting blood glucose and HbAlc levels compared to individuals having the GG and GC genotypes. Our bioinformatic analyses also showed that the miR-146a sequence is conserved across primate taxa and substituting G to C causes the structural instability of pre-miR-146a by changing the minimum free energy. For the rs2292832 variant, no statistically significant difference was detected for allele or genotype frequencies between T2D and control groups., Conclusions: Our findings suggest that miR-146a rs2910164 polymorphism might be associated with T2D and its cardiovascular risk factors in an Iranian population.

The present work is aimed at finding variants associated with Type 1 and Type 2 diabetes mellitus (DM) that reside in functionally validated miRNAs binding sites and that can have a functional role in determining diabetes and related pathologies. Using bioinformatics analyses we obtained a database of validated polymorphic miRNA binding sites which has been intersected with genes related to DM or to variants associated and/or in linkage disequilibrium (LD) with it and is reported in genome-wide association studies (GWAS). The workflow we followed allowed us to find variants associated with DM that also reside in functional miRNA binding sites. These data have been demonstrated to have a functional role by impairing the functions of genes implicated in biological processes linked to DM. In conclusion, our work emphasized the importance of SNPs located in miRNA binding sites. The results discussed in this work may constitute the basis of further works aimed at finding functional candidates and variants affecting protein structure and function, transcription factor binding sites, and non-coding epigenetic variants, contributing to widen the knowledge about the pathogenesis of this important disease.

Aim: This study was designed to examine the effect of Burdock root tea on inflammatory markers and oxidative stress indicators in patients with knee osteoarthritis (OA)., Methods: Thirty-six patients (10 men and 26 women) aged 50-70 years old with knee osteoarthritis referred to the Physical Medicine and Rehabilitation Department of the Tabriz University of Medical Sciences Hospitals, were selected for the study and randomly divided into two groups. Anthropometric measurements, including height, weight and body mass index (BMI) were measured. For all individuals along the 42 days of study period, the same drug treatments, including two lots of 500 mg acetaminophen twice a day and one glucosamine 500 mg once a day,were considered. The intervention group received daily three cups of Burdock root tea (each cup containing 2 g/150 mL boiled water) half-hour after the meal. The control group received three cups containing 150 cc boiled water daily. We assessed inflammatory markers such as high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) and oxidative stress indicators such as total antioxidants capacity (TAC), glutathione peroxidase (GPX), superoxide dismutase (SOD) and thiobarbituric acid reactive substances before and after the intervention., Results: The results showed that burdock root tea significantly decreased the levels of serum IL-6 (P = 0.002), hs-CRP (P = 0.003) and malondialdehyde (P < 0.001), while the levels of serum TAC (P < 0.001) and activities of SOD (P = 0.009) were significantly increased. GPX activities increased but not significantly., Conclusions: The results suggested that Arctium lappa L. root tea improves inflammatory status and oxidative stress in patients with knee osteoarthritis., (© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

It has been suggested that single nucleotide polymorphisms (SNPs) in genes involved in Toll-like receptors (TLRs) pathway may exhibit broad effects on function of this network and might contribute to a range of human diseases. However, the extent to which these variations affect TLR signaling is not well understood. In this study, we adopted a bioinformatics approach to predict the consequences of SNPs in TLRs network. The consequences of non-synonymous coding SNPs (nsSNPs) were predicted by SIFT, PolyPhen, PANTHER, SNPs&GO, I-Mutant, ConSurf and NetSurf tools. Structural visualization of wild type and mutant protein was performed using the project HOPE and Swiss PDB viewer. The influence of 5'-UTR and 3'- UTR SNPs were analyzed by appropriate computational approaches. Nineteen nsSNPs in TLRs pathway genes were found to have deleterious consequences as predicted by the combination of different algorithms. Moreover, our results suggested that SNPs located at UTRs of TLRs pathway genes may potentially influence binding of transcription factors or microRNAs. By applying a pathway-based bioinformatics analysis of genetic variations, we provided a prioritized list of potentially deleterious variants. These findings may facilitate the selection of proper variants for future functional and/or association studies.

Probiotics are live bacteria which have frequently been reported to be beneficial in preventing a wide range of diseases as well as playing a major role in treating the existing ailments. Thus far, a variety of probiotic products have been developed which can be categorized into two groups: probiotic foods and supplements. Both foods and supplements have been able to confer the health benefits claimed for them. However, it is not known which one can be clinically more efficient, and to the best of our knowledge, until now no research has been conducted to investigate this issue. The present review aims to discuss this matter, based on the evidence available in the literature. To do so, articles indexed in PubMed and ScienceDirect between 2000 and 2011 were reviewed. The articles included the clinical trials in which either foods or supplements were used to administer the probiotics to either patients suffering from different diseases or healthy subjects. Although both foods and supplements seem to have been efficient carriers for the beneficial bacteria, to generally promote public health in communities, probiotic foods appear to be preferred to probiotic supplements.

The contribution of microRNAs (miRNAs) to cancer has been extensively investigated and it became obvious that a strict regulation of miRNA-mRNA regulatory network is crucial for safeguarding cell health. Apart from the direct impact of miRNA dysregulation in cancer pathogenesis, genetic variations in miRNAs are likely to disrupt miRNA-target interaction. Indeed, many evidences suggested that SNPs within miRNA regulome are associated with the development of different hematological malignancies. However, a full catalog of SNPs within miRNAs target sites of genes relevant to hematopoiesis and hematological malignancies is still lacking. Accordingly, we aimed to systematically identify and characterize such SNPs and provide a prioritized list of most potentially disrupting SNPs. Although in the present study we did not address the functional significance of these potential disturbing variants, we believe that our compiled results will be valuable for researchers interested in determining the role of target-SNPs in the development of hematological malignancies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Oxidative stress induced by superoxide anion plays critical roles in the pathogenesis of coronary artery disease (CAD) and hence acute myocardial infarction (AMI). The major source of superoxide production in vascular smooth muscle and endothelial cells is the NADPH oxidase complex. An essential component of this complex is p22phox, that is encoded by the cytochrome b-245, alpha polypeptide (CYBA) gene. The aim of this study was to investigate the association of CYBA variants (rs1049255 and rs4673) and premature acute myocardial infarction risk in an Iranian population., Methods: The study population consisted of 158 patients under the age of 50 years, with a diagnosis of premature AMI, and 168 age-matched controls with normal coronary angiograms. Genotyping of the polymorphisms was performed by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP)., Results: There was no association between the genotypes and allele frequencies of rs4673 polymorphism and premature acute myocardial infarction ( P >0.05). A significant statistical association was observed between the genotypes distribution of rs1049255 polymorphism and AMI risk ( P =0.037). Furthermore, the distribution of AA+AG/GG genotypes was found to be statistically significant between the two groups ( P =0.011)., Conclusions: Our findings indicated that rs1049255 but not rs4673 polymorphism is associated with premature AMI.

Considering the high prevalence of osteoarthritis (OA) and since until now there has not been any human studies to evaluate the effect of sesame in OA patients, this study was designed to assess the effect of administration of sesame on inflammation and oxidative stress in patients with knee OA. Fifty patients with knee OA were allocated into two groups namely control and sesame group. 25 patients in the control group received 40 g placebo powder per day while 25 patients in the sesame group received 40 g of sesame seed daily during two months of study along with standard medical therapy. Serum total antioxidant capacity, malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were measured. In the sesame group, a significant decrease in serum MDA and hs-CRP were seen after two months of study (P<0.05). There was no significant difference in post-treatment serum values of MDA, TAC and hs-CRP between two groups (P>0.05). Serum IL-6 decreased significantly in both groups compared with baseline during the two-month study (P<0.05). There was a significant difference in mean serum IL-6 between two groups after treatment (P=0.001). Sesame seed is a natural and safe substance that may have beneficial effects in patients with knee OA, and it may provide new complementary and adjunctive treatment in these patients.

Background: This study was designed to assess the effect of sesame seed on lipid profile and oxidative stress biomarkers in knee osteoarthritis (OA) patients., Methods: Fifty patients with knee OA were allocated into two groups receiving 40 g of sesame seed daily along with standard medical therapy (n=25) or stan-dard treatment (n=25) for two months. Serum total antioxidant capacity, ma-londialdehyde (MDA) and lipid profile (total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, triglycerides) were measured., Results: After the intervention period two months of study, serum TC, LDL-cholesterol and MDA decreased significantly in the sesame group (P<0.05), while no significant difference in serum values of lipid profile and oxidative stress parameters was seen in the control group (P>0.05). There was no signifi-cant difference in pre and post-treatment values of lipid profile and oxidative parameters between the two groups (P>0.05)., Conclusion: Current study showed a positive effect of sesame seed in improv-ing lipid profile and oxidative stress in patients with knee OA and indicated the fact that sesame seed might be of help to reduce oxidative stress in OA patients.

Background: Esophageal, stomach, and colorectal cancers are commonly lethal gastrointestinal tract (GIT) neoplasms, causing almost two million deaths worldwide each year. some environmental risk factors are acknowledged; however, genetic defects can significantly contribute to predisposition to GIT cancers. Accordingly, recent works have shown that single-nucleotide polymorphisms (SNPs) within miRNAs coding sequence (miR-SNPs) and miRNA target sites (target-SNPs) may further contribute to increased risk of developing cancer., Objectives: In this study, we comprehensively identified miRNA-target gene pairs implicated in GIT cancers and catalogued the presence of potentially functional miR-SNPs and target-SNPs that impair the correct functional recognition., Materials and Methods: Using bioinformatics tools, manual literature review, and a highly accurate dataset of experimentally validated miRNA-target gene interactions, we compiled a list of miRNA-target genes pairs related to GIT cancers and prioritized them into different groups based on the levels of experimental support. Functional annotations (gene ontology) were applied to these pairs in each group to gain further information., Results: We identified 97 pairs in which both miRNAs and target genes were implicated in GIT cancers. Several pairs, denoted as highly polymorphic pairs, had both miR-SNPs and target-SNPs. In addition, more than 5000 miRNA-target gene pairs were identified in which, according to the previous reports, either the miRNAs or the target genes had a direct involvement in GIT cancers. More than 800 target-SNPs are located in regulatory regions that were extracted from the ENCODE project through the RegulomeDB database. Of these, 20 were classified as expression quantitative trait loci (eQTLs)., Conclusions: Our work provided a comprehensive source of prioritized and annotated candidate polymorphisms inside miRNAs and their target sites in GIT cancers, which would facilitate the process of choosing right candidate miRNA-target genes and related polymorphisms for future association or functional studies.