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.

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.

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.

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.

Increased mRNA Expression of CTRP3 and CTRP9 in Adipose Tissue from Obese Women: Is it Linked to Obesity-Related Parameters and mRNA Expression of Inflammatory Cytokines?

BACKGROUND: Obesity, a medical condition with impaired adipokine secretion and function, has a detrimental effect on insulin and glucose metabolism. CTRP3 and CTRP9 are adipokines with possible roles in energy homeostasis regulation. We sought to compare CTRP3, CTRP9, and inflammatory gene expression in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from obese women who underwent bariatric surgery and non-obese women as controls. METHODS: For this study, the investigators recruited 20 morbidly obese women (BMI> 35) who qualified for bariatric surgery and 20 normal-weight women (BMI< 25) who underwent elective surgeries. Real-time PCR was performed to investigate mRNA expression of CTRP3, CTRP9, and the inflammatory genes IL1-ß, IL-6, MCP-1, and TNF-α in SAT and VAT from both obese patients and controls. RESULTS: We observed that CTRP3 mRNA levels were significantly greater in VAT from obese patients than from controls (P< 0.0003). Also, patient group had higher levels of CTRP9 that control group (P< 0.0026). Inflammatory cytokines were markedly increased in SAT of obese patients compared to controls (P< 0.05). In addition, our results revealed a positive correlation of CTRP9 with HOMA-IR and waist circumference in VAT and CTRP3 with IL-1ß, MCP-1, and TNF-α in SAT. CONCLUSION: Both CTRP3 and CTRP9 expression were significantly higher in VAT from obese patients than from controls, and CTRP3 expression positively correlated with inflammatory parameters. Our findings indicate that CTRP3 and CTRP9 might be important in regulating glucose metabolism and obesity-related conditions such as inflammation.

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.

The gene expression of CTRP12 but not CTRP13 is upregulated in both visceral and subcutaneous adipose tissue of obese subjects.

Obesity is a well-known chronic low-grade inflammation condition characterized by dysregulated adipokine secretion and function. Both CTRP12 and CTRP13 are adipokines that influence glucose and lipid metabolism. We aimed to investigate CTRP12, CTRP13, and inflammatory gene expressions in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from obese women who underwent bariatric surgery in comparison with the normal weight women. This case-control study included 20 obese [body mass index (BMI) > 35-40 kg/m2] candidates for bariatric surgery and 20 normal-weight women (BMI <25 kg/m2) as control group, who underwent elective surgeries. Real-time PCR was used to evaluate mRNA expression levels of CTRP12, CTRP13, and inflammatory genes in SAT and VAT from both groups. We observed significantly higher mRNA expression of CTRP12 in SAT (p = 0.048) and VAT (p = 0.046) from obese patients compared to the controls. There was significantly greater expression of IL-6 and MCP-1 inflammatory genes in SAT (p = 0.013 and p = 0.005 respectively) and VAT (p = 0.000 and p = 0.001 respectively) of obese patients compared to the control group. IL-1ß (p = 0.015) and TNF-α (p = 0.014) expressions significantly increased in VAT from obese patients compared to the control group. Spearman correlation analysis showed that CTRP12 expression significantly correlated with obesity indices. Our findings showed that CTRP12 significantly increased in both VAT and SAT of obese group. More importantly, we observed a positive correlation between CTRP12 with inflammatory parameters. These results indicated that CTRP12 might be part of an intricate network for glucose metabolism and obesity-related inflammation processes.

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.

The Relationship Between the MTHFR C677T Genotypes to Serum Anti-Müllerian Hormone Concentrations and In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcome.

BACKGROUND: The expression of the 5,10-methylentetrahydrofolate reductase (MTHFR) gene in human oocytes and preimplantation embryos suggests that the MTHFR gene is involved in folliculogenesis and female reproduction. Considering the importance of the MTHFR gene on female reproduction, the aim of this study was to evalu- ate the influence of MTHFR C677T polymorphism on ovarian marker reserve, particularly serum anti-Müllerian hormone (AMH) levels, and ovarian response as well as clinical pregnancy rates after in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI). METHODS: A total of 137 women who underwent ART treatment due to male factor infertility enrolled in this study. Genotyping of MTHFR C677T polymorphism and serum AMH concentrations were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and an ultrasensitive enzymelinked immunosorbent assay (ELISA). RESULTS: Women with the TT genotype showed significantly higher AMH levels (4.5 ± 3.2 ng/mL) compared to carriers of other genotypes after ovarian stimulation. We observed a nonsignificant trend towards lower clinical pregnancy rates in patients with the TT (23.1%) versus CT (48.4%) genotypes (p = 0.2). No significant differences existed in terms of miscarriage and live birth rates among the groups. Multivariable logistic regression revealed that the duration of infertility and AFC were important predictive variables for the live birth rate. CONCLUSIONS: Our results confirmed that the presence of the T mutant allele of the 677 polymorphism in the MTHFR gene led to an increased trend in AMH levels. Interestingly, we observed that the numbers of oocytes retrieved decreased in the mutated genotypes. We have not observed this trend in relation to oocyte maturity. The influence of the MTHFR C677T polymorphism on embryo quality and pregnancy rate after ART cycles remains unclear.

The pre-mir-499 Variant rs3746444 May Contribute to Coronary Artery Disease Susceptibility: a Case-Control and Meta-Analysis Study.

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.

The Circulating Levels of Complement-C1q/TNF-Related Protein 13 (CTRP13) in Patients with Type 2 Diabetes and its Association with Insulin Resistance.

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.

Association of MiR-149 (RS2292832) Variant with the Risk of Coronary Artery Disease.

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.

Comparative assessment of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C as early biomarkers for early detection of renal failure in patients with hypertension.

BACKGROUND: Hypertension is one the most common causes of chronic kidney disease (CKD). One of the major concerns in hypertensive patients is early detection of renal disorders. In the past, serum creatinine (Scr) concentration was used as a marker of kidney function, but it proffers a late reflection of reduced glomerular filtration rate. Cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) have been recently proven to be useful for quantification of CKD. Therefore, we compared the diagnostic value of NGAL with cystatin C and creatinine to evaluate kidney function in hypertensive patients. METHODS: In this study, 42 hypertensive patients and 30 healthy volunteers were recruited. Serum cystatin C (Scys C) and plasma NGAL were measured using ELISA method. Creatinine, urea, hemoglobin, fibrinogen, and C-reactive protein were measured according to the routine methods. Estimated glomerular filtration rate (eGFR) was considered as the gold standard method (cut-off value of < 78 ml/min/1.73 m². RESULTS: In the patient group, plasma NGAL, cystatin C, and creatinine were all significantly correlated with eGFR, and plasma NGAL correlated best with eGFR. Receiver-operating characteristics analysis indicated that plasma NGAL was a better indicator than creatinine and cystatin C for predicting a GFR < 78 ml/min/1.73 m2. The sensitivity and specificity for NGAL were 96% and 100%, for cystatin C were 92% and 60% and for creatinine were 76% and 47%, respectively. CONCLUSION: Plasma NGAL demonstrated a higher diagnostic value to detect kidney impairment in the early stages of CKD as compared to Scys C and Scr in hypertensive patients.

Dietary nitrate improves glucose tolerance and lipid profile in an animal model of hyperglycemia.

Reduction in nitric oxide (NO) production and bioavailability contribute to the pathogenesis of type 2 diabetes. Administration of nitrate has strong NO-like outcomes in both animals and humans. In this study, we examined the effects of dietary nitrate on glucose tolerance and lipid profile in type 2 diabetic rats. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Thirty-two male Wistar rats were divided into 4 groups: controls (C), control+nitrate (CN), diabetes (D), and diabetes+nitrate (DN). For 8 weeks, the CN and DN groups consumed sodium nitrate (100 mg/L in drinking water) while the C and D groups consumed tap water. Serum nitrate+nitrite (NOx), glucose, lipid profile, total antioxidant capacity (TAC), and catalase (CAT) activity were measured before and at the end of the study. Systolic blood pressure (SBP) was measured every 10 days. Intravenous glucose tolerance test (IVGTT) was performed at the end of the study. Serum NOx decreased in diabetic rats and dietary nitrate restored it to normal values. Increases in serum glucose levels was significantly lower in the DN group compared to the D group (24.1% vs. 90.2%; p < 0.05). Nitrate therapy in diabetic rats significantly improved lipid profile, glucose tolerance (AUC: 20264 ± 659 vs. 17923 ± 523; p < 0.05 for D and DN groups respectively) and restored elevated SBP to normal values. Diabetic rats had lower TAC and CAT activity and dietary nitrate restored these to normal status. In conclusion, dietary nitrate prevented increase in SBP and serum glucose, improved glucose tolerance and restored dyslipidemia in an animal model of hyperglycemia.

Granzyme h serum levels variations with both reproductive hormone receptors, and related hormone receptors in breast cancer patients.

BACKGROUND: Breast Cancer (BC) is the most common cancer in Iranian women, meanwhile the Iranian patients are relatively young. Granzyme H (GZMH) is a functional cytotoxic serine protease of NK cell granules, which expands the cell death-inducing repertoire of innate immune system. GZMH is constitutively and highly expressed in human NK cells, in order to possess chymotrypsin-like (chymase) enzymatic activity. The purpose of this study was to determine GZMH level, in BC and healthy women. METHODS: 30 breast cancer patients, and 30 control women in premenopausal status, have participated in this study. GZMH, Estrogen levels, and ER, PR have been measured in cancer and healthy women subsequently, as using ELISA, Radioimmunoassay, and Immunohistochemistry methods. RESULTS: Mean GZMH value was lower in BC than healthy women (p<0.0001). CONCLUSION: Our study has implicated existence of suppressor or problem for producing of GZMH in patients group and levels of estrogen couldn't effect on making positive ER, PR.

High ω-3:ω-6 fatty acids ratio increases fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in human ectopic endometrial cells.

BACKGROUND: Endometriosis, a common chronic inflammatory disorder, is defined by the atypical growth of endometrium- like tissue outside of the uterus. Secretory phospholipase A2 group IIa (sPLA2-IIa) and fatty acid binding protein4 (FABP4) play several important roles in the inflammatory diseases. OBJECTIVE: Due to reported potential anti-inflammatory effects of ω-3 and ω-6 fatty acids, the purpose of the present study was to investigate the effects of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) on fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in cultured endometrial cells. MATERIALS AND METHODS: Ectopic and eutopic endometrial tissues obtained from 15 women were snap frozen. After thawing and tissue digestion, primary mixed stromal and endometrial epithelial cell culture was performed for 8 days in culture mediums supplemented with normal and high ratios of ω-3 and ω-6 PUFA. sPLA2-IIa in the culture medium and FABP4 level was determined using enzyme immuno assay (EIA) technique. RESULTS: Within ectopic endometrial cells group, the level of cellular FABP4 and extracellular sPLA2-IIa were remarkably increased under high ω-3 PUFA exposure compared with control condition (p=0.014 and p=0.04 respectively). CONCLUSION: ω-3 PUFAs may increase the level of cellular FABP4 and extracellular sPLA2-IIa in ectopic endometrial cells, since sPLAIIa and FABP4 may affect endometriosis via several mechanisms, more relevant studies are encouraged to know the potential effect of increased cellular FABP4 and extracellular sPLA2-IIa on endometriosis.