The Effect of Altered Mucin1, FGF2, and HBEGF Gene Expression at The Ectopic Implantation Site and Endometrial Tissues in The Tubal Pregnancy Pathogenesis: A Case-Control Study.

BACKGROUND: Ectopic pregnancy (EP) is defined as implantation and development of an embryo outside of the uterine tissue. Women undergoing assisted reproductive technologies (ART), particularly frozen embryo transfer (FET), are in high-risk populations for EP. Mucin1 (MUC1), fibroblast growth factor-2 (FGF2), and Heparin-binding epidermal growth factor (HBEGF) genes are involved in the endometrial receptivity pathway, leading to normal eutopic implantation; Although, their relevance in the tubal pregnancy after FET is unknown. We aimed evaluation of Mucin1, FGF2, and HBEGF expression fold as endometrial receptive markers in the EP patients following the FET cycle. MATERIALS AND METHODS: A case-control study was conducted on ten patients (five EP patients and five women in the pseudo-pregnancy group, as the control samples). Pseudo-pregnancy group was established in women who were candidates for hysterectomy for benign diseases. Fallopian tube biopsies and corresponding endometrial tissues from these patients were taken during the hysterectomy. However, the fallopian tube and endometrial tissues of EP patients were obtained during salpingectomy. The mRNA expressions of Mucin1, FGF2, and HBEGF genes in the fallopian tube and endometrial tissues were measured by real-time polymerase chain reaction (PCR) assay. RESULTS: MUC1 mRNA expression level in the endometrium of the case group was higher than in the control group (P=0.04); however, its mRNA expression in the fallopian samples of the case group in comparison with the control group was significantly decreased (P=0.001). The HBEGF mRNA expression level was not significantly different between the case and control endometrium, whereas its expression was significantly increased in the case fallopian samples compared with the control ones (P=0.001). The same pattern was observed for FGF2 mRNA expression level in the fallopian samples of the case group but was significantly reduced in the endometrial samples in comparison with the control samples (P=0.03). CONCLUSION: Mucin1, FGF2, and HBEGF gene mRNA expression changes may explain the embryo rejection from the uterus and the establishment of a receptive phenotype in fallopian cells.

Investigating the impact of metformin on severity of COVID-19 in patients with Type 2 diabetes mellitus: Focusing on laboratory findings.

BACKGROUND: In the terrifying pandemic caused by SARS-CoV-2, diabetic patients exhibiting more severe outcomes and mortality rate is high among them. Based on recent studies, metformin as the most prescribed drug for T2DM treatment may improve severe outcomes in diabetic patients infected with SARS-CoV-2. On the other hand, abnormal laboratory findings can help to differentiate between the severe and non-severe form of COVID-19. According to the mentioned issues, the effect of metformin on severity of COVID-19 was examined in T2DM patients with SARS-CoV-2 infection. METHODS: The study included 187 individuals diagnosed with COVID-19, 104 patients were diabetic and divided into two groups according to their anti-diabetic drugs: patients who were treated only with metformin and patients who were treated with other anti-diabetic drugs. The other participants were non-diabetic and diagnosed with COVID-19. Biochemical parameters were measured by routine laboratory methods before, during and after SARS-CoV-2 infection. RESULTS: During infection, FBS, creatinine, ALT, AST, Ferritin and LDH were significantly lower in metformin users than non-users (p-value: .02, .01, .03, .04, .0009 and .01, respectively). Also, after recovery, there were statistically significant differences between metformin users and non-users with respect to most of the study parameters, except FBS, BUN and ALP (p-value: .51, .28 and .35, respectively). CONCLUSION: Our result suggested that metformin might be associated with better outcomes in diabetic patients infected with SARS-CoV-2.

The association study between changes in HbA1C with rs2250486 and rs67238751 genetic variants for SLC47A1 in newly diagnosed Iranian patients with type 2 diabetes mellitus: 6 months follow-up study.

OBJECTIVES: One of the most well-known oral medications for the treatment of T2DM is metformin. Variants have been found in studies to be useful in detecting new genes connected to T2DM aetiology and affecting metformin's mechanism of action. In this research, we aimed to study two variations of the SLC47A1 gene; rs2250486 and rs67238751, in T2DM patients who had been taking metformin for the first 6 months after the diagnosis in the Iranian population for the first time. DESIGN AND METHODS: A total of 200 individuals were recruited for the study. According to their glycosylated haemoglobin (HbA1c) levels, the patients were divided into two groups: responders (HbA1c levels were reduced by at least 1% after 6 months of metformin treatment.) and non-responders. DNA was extracted from whole blood and genotyped by Tetra ARMS PCR. High-performance liquid chromatography (HPLC) was used to measure HbA1c levels at the start of the treatment and again 6 months later. RESULTS: rs2250486 variant in the dominant model reduces the HbA1C levels after 6 months of metformin treatment. In fact, when compared to the T/C + C/C genotypes, the T/T genotype improves HbA1C levels (p-value = .014). Furthermore, in the allelic model, the T allele improves HbA1C levels in comparison to the C allele (p-value = .008). After 6 months of metformin treatment, serum levels of HbA1C in responders were reduced significantly in both groups (T/T and T/C + C/C), (p-value = <.0001). However, the rs67238751 variant did not reveal a meaningful relationship with lower HbA1C levels in any of the models. CONCLUSIONS: This study found that the rs2250486 variant could be associated with reducing HbA1C levels while the rs67238751 variant, had no relationship.

Can circulating miR-7-1-5p, and miR-33a-5p be used as markers of T2D patients?

PURPOSE: Recent evidence has indicated that miRNAs play an important role in both initiation and progression of many pathologic processes such as diabetes and can be used as an important and more sensitive tool to predict the development of the disease than the currently used biomarkers. This research aimed at comparing miR-7-5p and miR-33a-5p expression levels in the diabetics and pre-diabetics with the control group. METHODS: In this study, we compared expression of miR-7-5p and miR-33a-5p in plasma of three groups including pre-diabetic patients (n = 20), T2D patients (n = 20) and control group (n = 20), using RT-qPCR. Biochemical parameters were measured by auto-analyser. In silico analysis was performed to identify potential target genes of these miRNAs. RESULTS: Compared to the controls, miR-7-1-5p expression was down regulated in the pre-diabetics and the T2D patients; whereas, miR-33a-5p was expressed at higher levels in the T2D patients compared to the control group. Both miRs were correlated with glycaemic status such as FBS and HbA1c levels. The ROC analysis indicated a significant ability for miR-33a-5p in discriminating between the diabetics and the healthy individuals. In silico analysis suggests that both miRs affect biological pathways related to T2DM pathogenesis, such as MAPK, and insulin signalling pathway. CONCLUSION: Our results demonstrated that the miR-7-1-5p and miR-33a-5p expression levels are deregulated in the diabetics and pre-diabetics. Furthermore, miR-33a-5p showed significant ability in discriminating between diabetics and healthy individuals, suggesting a potential diagnostic use of miRNAs in type-2 diabetes detection.

Novel Derivatives of Tetrahydrobenzo (g) Imidazo[α-1,2] Quinoline Induce Apoptosis Via ROS Production in the Glioblastoma Multiforme Cells, U-87MG.

BACKGROUND: Despite newer therapeutic approaches against glioblastoma multiforme (GBM), the severely poor prognosis and treatment resistance are still disadvantages that slow down the patient's recovery process. Consistent with the need to develop more effective and optimized therapies to control GBM cell growth, the effects of a new series of tetrahydrobenzo(g)imidazo[α-1,2]quinolone derivatives on GBM cell growth and the underlying mechanism is investigated in the current study. METHODS: U-87MG cell line, glioblastoma multiforme and normal skin fibroblast cell line, AGO1522 were used to study the anticancer effects of 5 derivatives of tetrahydrobenzo(g)imidazo[α-1,2]quinolone and paclitaxel as a standard drug. The cytotoxic effect on cell growth was assessed using the MTT assay. Annexin V FITC staining and PI staining were applied to detect apoptosis and cell cycle distribution using flow cytometry. The extent of reactive oxygen species (ROS) formation was assessed using the fluorescent probe 7-dichlorofluorescin diacetate and caspase-3 activity using the colorimetric assay kit. RESULTS: Among the 5 derivatives of tetrahydrobenzo(g)imidazo[α-1,2]quinolone, the 5c derivative (5-(6-bromo-2-chloroquinolin-3-yl)-9a-hydroxy-8,8-dimethyl-4-Nitro-2,3,5,5a,7,8,9,9a-octahydroimidazo[α-1,2]quinoline-6(1H)) showed the strongest cytotoxic effect on U-87MG cells in a time and Dose-dependent manner compared to the other derivatives and paclitaxel. The IC50 (11.91 M) of the 5c derivative induced apoptosis accompanied by a significant increase in sub-G1 and super-G2 phases of U-87MG cells. The increased level of cellular ROS and caspase 3 activity after treatment of U-87MG cells with 5c derivative was significant compared to untreated cells. CONCLUSION: Our data provide insights into the potent anticancer effects of the 5c-derivative of tetrahydrobenzo(g)imidazo[α-1,2]quinolone on GBM cells via the caspase-dependent apoptotic pathway, which may merit further attention.

Circulating miR-148b-3p and miR-27a-3p can be potential biomarkers for diagnosis of pre-diabetes and type 2 diabetes: integrating experimental and in-silico approaches.

BACKGROUND: In view of the growing global prevalence of type 2 diabetes (T2D), detection of prediabetes and type 2 diabetes in the early stages is necessary to reduce the risk of developing diabetes, prevent the progression of the disease, and dysfunction of different organs. Since miRNAs are involved in the initiation and progression of numerous pathogenic processes, including diabetes, in the present study, we aimed to investigate the expression of miR-148b-3p and miR-27a-3p in prediabetic and T2D patients and to evaluate the diagnostic potential of these miRNAs. METHODS: We evaluated the expression of miR-148b-3p and miR-27a-3p in the plasma of three groups: 20 prediabetic patients, 20 T2D patients, and 20 healthy controls. The biochemical parameters were determined by the auto-analyzer. The possible target genes of these miRNAs were identified using an in-silico approach. RESULTS: Our results showed that, as compared to the healthy controls, there was a significant up regulation and down regulation in the expression of miR-148b-3p and miR-27a-3p in the T2D patients, respectively. The results of receiver operating characteristic curve analysis also suggested that miR-148b-3p acted successfully in discriminating the prediabetic and diabetic patients from the control group. According to in-silico analysis, miRs influence biological pathways involved in T2DM development, such as insulin signaling. CONCLUSIONS: The miR148b-3p and miR-27a-3p expression levels were deregulated in diabetes and pre-diabetes. Furthermore, miR-148b-3p showed significant ability in discriminating between diabetic and healthy individuals, suggesting a potential diagnostic use of miR-148b-3p in the detection of T2D.

The influence of SLC22A3 rs543159 and rs1317652 genetic variants on metformin therapeutic efficacy in newly diagnosed patients with type 2 diabetes mellitus: 25 weeks follow-up study.

BACKGROUND AND AIMS: Among anti-diabetic medications, metformin has been proven to be the preferred initial pharmacologic agent for type 2 diabetes mellitus (T2DM) treatment. Despite its safety and efficacy, the response to metformin varies between individuals. Genetic variations, especially within genes involved in pharmacokinetics and pharmacodynamics of metformin (e.g SLC22A3), have been suggested to be responsible for the observed inter-individual differences. By considering the undeniable role of organic cation transporter 3 in hepatic uptake of metformin, this study was aimed to investigate the association of rs543159 and rs1317652 variants in SLC22A3 gene with response to metformin monotherapy in newly diagnosed patients with T2DM. METHODS: The study included 200 T2DM patients who received metformin monotherapy for 25 weeks. The patients were classified into 2 groups according to their HbA1c values: the responders (reduction in HbA1c levels by at least 1% after 25 weeks treatment with metformin) and non-responders (less than 1% reduction in HbA1c levels after 25 weeks treatment with metformin). We used tetra ARMS-PCR method to determine genotypes of the target variants. RESULTS: For the rs543159, CA and AA genotypes were more frequent in responders as compared to non-responders (OR = 2.48; 95% CI = 1.28-4.78, P-value = 0.0057) under the dominant model. In case of rs1317652 CC and CT genotypes were more frequent in metformin responders as compared to non-responder group (OR = 2.49; 95% CI = 1.32-4.70, P-value = 0.0043) under the dominant model. Parameters such as fasting blood sugar (FBS), HbA1c, and total cholesterol (TC) levels were significantly lower in the responder group after 25 weeks of metformin monotherapy. Moreover, according to the result of multiple linear regression rs543159 and base line HbA1c values are significantly associated with response to metformin monotherapy. CONCLUSION: Our results suggested that rs543159 and rs1317652 in SLC22A3 gene might be associated with variability in response to metformin therapy in T2DM patients.

The impact of DAPK1 and mTORC1 signaling association on autophagy in cancer.

BACKGROUND: The autophagy pathway is used by eukaryotic cells to maintain metabolic homeostasis. Autophagy has two functions in cancerous cells which could inhibit tumorigenesis or lead to cancer progression by increasing cell survival and proliferation. METHODS AND RESULTS: In this review article, Web of Science, PubMed, Scopus,  and Google Scholar were searched and summarized published studies to explore the relationship between DAPK1 and mTORC1 signaling association on autophagy in cancer. Autophagy is managed through various proteins including the mTOR, which is two separated structural and functional complexes known as mTORC1 and mTORC2. MTORC1 is an important component of the regulatory pathway affecting numerous cellular functions including proliferation, migration, invasion, and survival. This protein plays a key role in human cancers. The activity level of mTORC1 is regulated by the death-associated protein kinases (DAPks) family, especially DAPK1. In many cancers, DAPK1 acts as a tumor suppressor which can be attributed to its ability to suppress cellular transformation and to inhibit metastasis. CONCLUSIONS: A deep investigation not only will reveal more about the function of DAPK1 but also might provide insights into novel therapies aimed to modulate the autophagy pathway in cancer and to achieve better cancer therapy.

Can miR-145-5p be used as a marker in diabetic patients?

In the light of emerging global epidemics of type 2 diabetes mellitus significant efforts are continuing to discover novel biomarkers for early detection of the disease. Since miRNAs play an important role in both the initiation and progress of many pathologic processes such as diabetes, in this study we aimed to evaluate expression level of plasma miR-145-5p in diabetics and pre-diabetics in comparison to the control group and assess its use as a biomarker in diagnosis of T2D. The plasma level of miR-145-5p was assessed in three groups including 20 prediabetic patients, 20 T2D patients and 20 healthy controls using RT-qPCR. Biochemical parameters were also measured by the auto-analyzer. Expression level of miR-145-5p was down-regulated in the prediabetics and the T2D patients compared to the controls. In the control group miR-145-5p showed a borderline correlation with FBS (p = .06), while in the prediabetic group miR-145 showed a significant negative correlation with FBS and finally in the T2D patients miR-145 was negatively correlated with HbA1c and TC and showed a negative borderline correlation with FBS. The ROC analysis indicated a significant ability for miR-145-5p in discriminating between the diabetics and pre-diabetics from the healthy subjects. Our results demonstrated that the miR-145-5p expression level is deregulated in the diabetics and the prediabetics. Furthermore miR-145-5p displayed a significant ability to discriminate the diabetics from the healthy subjects. These results suggest that miR-145-5p may be a useful biomarker for the diagnosis of T2DM.

The effect of A1298c polymorphism of the MTHFR gene on anti-Müllerian hormone levels: experimental and Web-based analysis.

BACKGROUND: The 5,10-methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionine metabolism, which is expressed in human oocytes and preimplantation. Due to the involvement of MTHFR in female reproduction, we tend to evaluate the influence of MTHFR A1298C polymorphism on ovarian marker reserves such as serum anti-Müllerian hormone (AMH) levels in women after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). METHODS: A total of 100 women, who underwent ART treatment due to male factor infertility, were recruited into this study. MTHFR A1298C polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, and serum AMH concentrations were measured by an ultrasensitive enzyme-linked immunosorbent assay (ELISA). RESULTS: Women with the CC genotype had higher AMH levels (4.15 ± 1.67 ng/ml), albeit not significant, than carriers with other genotypes after ovarian stimulation. No significant differences existed in terms of miscarriage and live birth rates among different genotype groups. CONCLUSION: The presence of the C mutant allele of the 1298 polymorphism in the MTHFR gene led to an increasing trend in serum AMH concentrations; however, the numbers of oocytes retrieved decreased in women with mutated genotypes. The influence of the MTHFR C677T polymorphism on embryo quality and pregnancy rate after ART cycles remains unclear.

Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468.

BACKGROUND: Triple-negative breast cancer accounts for approximately 15-20% of all breast carcinomas and is associated with earlier age of onset, aggressive clinical course, and dismal prognosis. A series of 1,3-diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1 H-Pyrazole and 1,3-diaryl-5- (3,4,5-trimethoxyphenyl)- 1 H-Pyrazole were evaluated for their anticancer activity against MDA-MB-468, human triple negative breast cancer cell line. METHODS: The cytotoxic effects of Pyrazole derivatives on the growth of MDA-MB-468 and AGO1522 were determined using MTT assay. Annexin-V-FITC and PI staining were performed to detect apoptosis and cell cycle distribution using Flow cytometry. The level of Reactive oxygen species (ROS) formation and caspase 3 activity were determined accordingly. RESULTS: Pyrazole derivatives induced a dose and time-dependent cell toxicity in MDA-MB-468 compared with untreated cells. The results showed that 3-(4-methoxyphenyl)-1-(p-tolyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-Pyrazole (3f) was the most active compound with IC50 values 14.97 µM and 6.45 µM compared with Paclitaxel with IC50 values 49.90 µM and 25.19 µM, after 24 and 48 hours, respectively. Upon treatment with 14.97 µM of 3f after 24 h, the compound induced cell cycle arrest in S phase. 3f provoked apoptosis was accompanied by the elevated level of ROS and increased caspase 3 activity in MDA-MB-468 cells compared with untreated cells. CONCLUSION: The overall results of the present study provided evidence for the cytotoxicity of compound 3f against MDA-MB-468 cells in comparison to reference standard, Paclitaxel. It proves that compound 3f can trigger apoptosis through ROS production and caspase 3 activation. These bring supportive data for future investigations that will lead to their use in cancer therapy. 
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Type2 diabetes mellitus prediction using data mining algorithms based on the long-noncoding RNAs expression: a comparison of four data mining approaches.

BACKGROUND: About 90% of patients who have diabetes suffer from Type 2 DM (T2DM). Many studies suggest using the significant role of lncRNAs to improve the diagnosis of T2DM. Machine learning and Data Mining techniques are tools that can improve the analysis and interpretation or extraction of knowledge from the data. These techniques may enhance the prognosis and diagnosis associated with reducing diseases such as T2DM. We applied four classification models, including K-nearest neighbor (KNN), support vector machine (SVM), logistic regression, and artificial neural networks (ANN) for diagnosing T2DM, and we compared the diagnostic power of these algorithms with each other. We performed the algorithms on six LncRNA variables (LINC00523, LINC00995, HCG27_201, TPT1-AS1, LY86-AS1, DKFZP) and demographic data. RESULTS: To select the best performance, we considered the AUC, sensitivity, specificity, plotted the ROC curve, and showed the average curve and range. The mean AUC for the KNN algorithm was 91% with 0.09 standard deviation (SD); the mean sensitivity and specificity were 96 and 85%, respectively. After applying the SVM algorithm, the mean AUC obtained 95% after stratified 10-fold cross-validation, and the SD obtained 0.05. The mean sensitivity and specificity were 95 and 86%, respectively. The mean AUC for ANN and the SD were 93% and 0.03, also the mean sensitivity and specificity were 78 and 85%. At last, for the logistic regression algorithm, our results showed 95% of mean AUC, and the SD of 0.05, the mean sensitivity and specificity were 92 and 85%, respectively. According to the ROCs, the Logistic Regression and SVM had a better area under the curve compared to the others. CONCLUSION: We aimed to find the best data mining approach for the prediction of T2DM using six lncRNA expression. According to the finding, the maximum AUC dedicated to SVM and logistic regression, among others, KNN and ANN also had the high mean AUC and small standard deviations of AUC scores among the approaches, KNN had the highest mean sensitivity and the highest specificity belonged to SVM. This study's result could improve our knowledge about the early detection and diagnosis of T2DM using the lncRNAs as biomarkers.

Evaluation of Neutrophil Gelatinase-Associated Lipocalin and Cystatin C in Early Diagnosis of Chronic Kidney Disease in the Absence of the Gold Standard.

BACKGROUND: Glomerular filtration rate (GFR) is considered as a gold standard of kidney function. However, using GFR as the gold standard is not common in clinical practice, because its direct measurement is usually expensive, cumbersome, and invasive. In the present study, we assessed the predictive power of two other biomarkers, Cystatin-C (Cys-C) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) for early detection of chronic kidney diseases (CKD) in the absence of a gold standard. MATERIALS AND METHODS: In this study, 72 patients who referred to the Shohadaye Tajrish Hospital of Tehran, Iran, for measuring their kidney function were studied. The ELISA method was utilized for measuring plasma NGAL (PNGAL) and serum Cys-C (SCys-C). The Bayesian latent class modeling approach was applied to asses the predictive power of these biomarkers. RESULTS: While both the biomarkers had rather high sensitivities (PNGAL=91%, SCys-C= 89%), the specificity of SCys-C biomarker was very lower than the one of PNGAL (SCys-C=56%, PNGAL=94%). The estimated area under the receiver operating characteristic (ROC) curve for SCys-C as the single biomarker for the diagnosis of CKD was about 0.76, while a similar estimate for PNGAL was 0.93. The added value of PNGAL to SCys-C for the diagnosis of CKD in terms of the ROC curve was about 0.19, while the added value of SCys-C to PNGAL was less than 0.02. CONCLUSION: In general, our findings suggest that PNGAL can be utilized as a single reliable biomarker for early detection of CKD. In addition, results showed that when a perfect gold standard is not available, Bayesian approaches to latent class models could lead to more precise sensitivity and specificity estimates of imperfect tests.

High-intensity interval training (HIIT) effectively enhances heart function via miR-195 dependent cardiomyopathy reduction in high-fat high-fructose diet-induced diabetic rats.

Aims: Regarding the fact that up-regulation of miR-195 in diabetic hearts has a potential role in diabetic cardiomyopathy, the present study investigated whether continuous endurance training (CET) and high-intensity interval training (HIIT) reduces miR-195 expression and which exercise is effective in this regard.Methods: Diabetes was induced by high-fat high-fructose diet (HFHFD). Then, the rats were sub-divided into three categories; sedentary (HFHFD + SED), continuous endurance training (HFHFD + CET), and high-intensity interval training group (HFHFD + HIIT). After eight weeks of running, expression of miR-195 and myocardial function were evaluated.Results: HIIT effectively decreases the expression of miR-195 and increases the expression of Sirt1 and BCL-2 in diabetic rats compared with CET. Our results showed that HIIT compared with CET increases left ventricular ejection fraction (LVEF%) and fractional shortening (FS%).Conclusions: Our results indicated that exercise, especially HIIT is an appropriate strategy for reducing miR-195 and improving myocardial function in diabetic rats compared with CET.

Deregulation of long noncoding RNA SNHG17 and TTC28-AS1 is associated with type 2 diabetes mellitus.

Long noncoding RNAs (lncRNAs) have emerged as key players in several biological processes and complex diseases including type 2 diabetes mellitus (T2DM). The purpose of this study was to investigate the expression levels of SNHG17 and TTC28-AS1 in T2DM patients. Quantitative real-time RT-PCR analysis was performed using peripheral blood mononuclear cells (PBMCs) samples from patients diagnosed with T2DM and healthy controls. Binary logistic regression analysis was carried out to determine the odds of development of T2DM based on expression levels of lncRNAs and clinical characteristic of the subjects. Spearman's correlation analysis was used to clarify the correlation between SNHG17 and TTC28-AS1 expressions to metabolic features. We found that SNHG17 and TTC28-AS1were down-regulated in the T2DM group compared to the healthy control group. The logistic regression revealed that body mass index (BMI), systolic blood pressure (SBP), fasting blood glucose (FBG) and TTC28-AS1 expression substantially affect T2DM susceptibility. Furthermore, expression of SNHG17 was negatively correlated with high-density lipoprotein cholesterol (HDL-C) and expression of TTC28-AS1 was positively correlated with low-density lipoprotein cholesterol (LDL-C). Decreased expressions of lncRNAs TTC28-AS1 and SNHG17 in T2DM are possibly associated with the development of T2DM.

Circulating miR-625 as an Emerging Biomarker for Liver Cirrhosis.

BACKGROUND: Sensitive and specific diagnostic indicators are essential for liver cirrhosis. This study aims to analyze two plasma microRNAs (miR-625 and miR-920) as possible biomarkers for liver cirrhosis. METHODS: miR-625 and miR-920 expressions were analyzed in the plasma of 40 patients with liver cirrhosis and 41 healthy controls. Plasma levels of miR-625 and miR-920 were assessed by qRT-PCR. Analysis of the results was performed by the Mann-Whitney U-test. Spearman's test was used to show correlations between the miR-625 and clinical parameters. Receiver operating characteristic (ROC) analysis was performed to assess sensitivity and specificity. RESULTS: miR-625 is downregulated in patients with liver cirrhosis. Expression of miR-625 correlated with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. ROC curve analysis revealed that miR-625 had a sensitivity of 82.4% and specificity of 88.9% (area under the curve (AUC): 0.902) which indicated a high diagnostic power for cirrhosis. CONCLUSIONS: This study demonstrates for the first time that, miR-625 may be considered as a potential noninvasive biomarker for diagnosis of liver cirrhosis in patients, irrespective of etiology.

Clinical significance of long noncoding RNA VIM-AS1 and CTBP1-AS2 expression in type 2 diabetes.

BACKGROUND/AIMS: The risk of type 2 diabetes (T2D) is determined by a combination of genetic and environmental factors. Multiple studies have proposed that long noncoding RNAs (lncRNAs) are crucial molecules in regulating several biological processes and complex diseases. The study was aimed at investigating the association between the expression levels of lncRNA VIM-AS1, lncRNA CTBP1-AS2, and T2D susceptibility. METHODS: lncRNA VIM-AS1 and lncRNA CTBP1-AS2 in the peripheral blood mononuclear cell (PBMC) of 100 healthy individuals and 100 T2D patients were collected for Quantitative Real-Time RT-PCR analysis. A logistic regression was performed to understand whether the likelihood of T2D can be predicted based on the expression levels of lncRNA VIM-AS1 and lncRNA CTBP1-AS2. Receiver operating characteristic (ROC) analysis was also performed to determine the statistical analysis of VIM-AS1 and CTBP1-AS2 levels in 200 samples. RESULTS: Our results display that decreased levels of VIM-AS1 and CTBP1-AS2 in PBMC were associated with diabetes in Iranian population. The logistic regression revealed that Systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), Fasting blood glucose (FBG) and CTBP1-AS2 are substantial predictors of T2D. The ROC analysis of CTBP1-AS2 revealed the area under the ROC curve (AUC) of 0.68 with a sensitivity of 58.7% and specificity of 75.3% in distinguishing nondiabetic from diabetic subjects. The ROC analysis of VIM-AS1 determined AUC of 0.63 with a sensitivity of 56.1% and specificity of 68.37% in distinguishing the two diagnostic groups. CONCLUSION: lncRNA VIM-AS1 and lncRNA CTBP1-AS2 expression levels are associated with T2D susceptibility.

Long non-coding RNA LY86-AS1 and HCG27_201 expression in type 2 diabetes mellitus.

Long non-coding RNAs (LncRNAs) are non-coding RNAs. The potential roles of lncRNAs in type 2 diabetes mellitus (T2DM) are not well-known. In this study, we aim to assess the expression levels of LY86-AS1 and HCG27_201 in T2DM patients and a healthy control group. We obtained whole blood and serum samples from 100 T2DM and 100 non-diabetic subjects. Peripheral blood mononuclear cells (PBMCs) were extracted from whole blood samples using Ficoll. Total RNA was isolated from PBMCs obtained from patients with type 2 diabetes mellitus and healthy control individuals using TRIzol LS reagent (GeneAll Biotechnology Co., LTD.). Extracted RNA was used to synthesize complementary DNA (cDNA) with a Reverse Transcription Kit (Takara). Real-time was performed with SYBR Green (Takara) and monitored by a Rotor-Gene (Qiagen) system. We performed quantitative PCR analysis of the LY86-AS1 and HCG27_201 lncRNA expression levels in the 200 samples. Here we found that the expression of LY86-AS1 and HCG27_201 were down regulated in the T2DM group compared with the control group. We further identify that the expression of both lncRNAs was negatively correlated with fasting blood sugar (FBS) levels. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of LY86-AS1 and HCG27_201 as biomarkers for T2DM. ROC analysis demonstrated that LY86-AS1 with an area under the ROC curve (AUC) of 0.747 (P < 0.0001, sensitivity: 64.6, and specificity: 79.8) might be the potential novel diagnostic biomarkers for T2DM. Lower expression of our two studied long non-coding RNAs LY86-AS1 and HCG27_201 in type 2 diabetes mellitus patients indicates their role in the pathogenesis of T2DM. Furthermore, LY86-AS1 could possibly be used as a diagnostic marker for T2DM.

Downregulation of long non-coding RNAs LINC00523 and LINC00994 in type 2 diabetes in an Iranian cohort.

Long non-coding RNAs (lncRNAs) are a subclass within the non-coding RNA repertoire that have potential roles in type 2 diabetes mellitus (T2DM). However, the biological function and molecular mechanisms of lncRNAs in T2DM remain largely unknown. The purpose of this study is to investigate the association between LINC00523 and LINC00994 expressions and T2DM susceptibility in an Iranian cohort. In this case-control study, we obtained whole blood and serum samples from 100 T2DM patients and 100 healthy subjects. We extracted peripheral blood mononuclear cells (PBMCs) from whole blood samples using Ficoll-Hypaque density-gradient centrifugation. Total RNA was extracted from the PBMC lysates by using the TRIzol-LS reagent (GeneAll). Finally, a quantitative real-time PCR (qPCR) assay was used to detect LINC00523 and LINC00994 lncRNA expression levels in the 200 samples. LINC00523 and LINC00994 expressions significantly decreased in patients with T2DM compared to the healthy participants, with a fold change for LINC00523 of 0.157 and 0.159 for LINC00994. We observed a significant inverse correlation between the expressions of these lncRNAs with FBS. Receiver operating characteristic (ROC) curve analysis revealed that LINC00523 has a higher area under the ROC curve (AUC) of 0.7430 and a lower P-value (P < 0.0001), in addition to a sensitivity of 81.44% and specificity of 61.11%. Therefore, LINC00523 could be considered a potential diagnostic biomarker for T2DM. Decreased expressions of LncRNAs LINC00523 and LINC00994 in T2DM is possibly associated with pathogenicity of T2DM in Iranian population. Moreover, LINC00523 can perhaps be considered as effective diagnostic biomarkers for T2DM.

Anti-Müllerian Hormone: genetic and environmental effects.

Anti-Müllerian hormone (AMH) is a homodimeric glycoprotein produced by granulosa cells of growing ovarian follicles. AMH appears to have an inhibitory effect on both primordial follicle recruitment and responsiveness of growing follicles to follicle-stimulating hormone (FSH). This hormone is considered to be a reliable marker of ovarian reserve; therefore, it is crucial to determine which factors influence AMH levels for prognostic and diagnostic purposes. In this review we intend to discuss the effect of genetic and environmental factors which may lead to AMH interindividual variability.