Interplay of miRNAs and lncRNAs in STAT3 signaling pathway in colorectal cancer progression.

In recent decades, colorectal cancer (CRC) has turned into one of the most widespread malignancies, and the incidence of this malignancy is expected to increase. Despite considerable improvements in therapeutic approaches, the prognosis, and the management of CRC face many problems. Likely, the main limitation in the successful treatment of CRC is the lack of appropriate clinical therapeutic targets. As an effective target, the signal transducer and activator of transcription 3 (STAT3) are regulated by a wide range of genes and involved in cellular processes, including cell growth, migration, invasion, immunosuppression, and angiogenesis. Aberrant regulation of STAT3 signaling leads to cellular dysfunction, diseases, and malignancies, including CRC. Consequently, targeting this signaling pathway is considered one of the therapeutic strategies used in CRC treatment. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are non-coding RNA molecules with partial or no protein-coding activity that participate in gene regulation at epigenetic, transcriptional, and post-transcriptional levels and regulate multiple signaling pathways, including STAT3 signaling (especially JAK/STAT). Therefore, these regulatory molecules are suggested to be very promising targets to present new insights into overcoming the limitations of conventional therapeutic strategies. Therefore, the current review study aimed to summarize the therapeutic and diagnostic significance of miRNAs and lncRNAs and their therapeutic and diagnostic significance related to the expression and activity of STAT3 in CRC.

Assessing the possible association between MTHFR (rs1801133) and GPx-1 (rs1050450) polymorphisms with the risk of type 2 diabetes, diabetic neuropathy, and diabetic retinopathy.

PURPOSE: Oxidative stress in chronic hyperglycemia could injure the tissues and onset of diabetes-related complications like retinopathy and neuropathy. This study investigates the association between methylenetetrahydrofolate reductase (MTHFR) and glutathione peroxidase (GPx) genetic variants with these complications. METHODS: In this case-control study, 400 individuals, including 100 healthy subjects and 300 patients with type 2 diabetes mellitus (T2DM) in three subgroups: with retinopathy(n = 100), with neuropathy(n = 100), and without complication (n = 100) from West Iran, were studied. MTHFR (rs1801133) and GPx-1 (rs1050450) variants were identified by the PCR-RFLP method. The plasma levels of GPx activity, glutathione, malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative stress (TOS) were measured by chemical methods. RESULTS: Higher BMI, TOS and MDA levels were observed in patients with neuropathy compared to other patients and controls. Diabetic patients with neuropathy had lower levels of glutathione (7.8 ± 4.5; P < 0.001), GPx activity (39.5 ± 8.5; P < 0.001), and TAC (703.1 ± 129.1; P = 0.0001) in comparison with other groups. The patients without complication and retinopathic patients had higher plasma levels of glutathione (12.2 ± 2.4; p = 0.02) and TAC (793.4 ± 124.6; P < 0.001), respectively. MTHFR TT genotype significantly correlated with lower levels of TOS (3.5 ± 1.1; P < 0.001) and OSI (0.0050 ± 0.001; P < 0.001). Subjects with the GPx-1 TT genotype had higher levels of MDA (6.8 ± 2.5; P = 0.02) and lower levels of TOS (3.7 ± 1.6; P < 0.001), which is statistically significant. TT genotype of MTHFR was associated with 3.9 fold (95% CI 1.04-4.76; P = 0.0436) increased risk of neuropathy. Also, GPx-1 CT genotype increased the risk of retinopathy [OR = 2.7 (95% CI = 1.38-5.44; P = 0.0039)]. CONCLUSION: The MTHFR TT genotype increased the risk of neuropathy in diabetic patients significantly. The GPx-1 CT genotype is related to increased retinopathy risk among diabetic patients. Both MTHFR and Gpx-1 TT genotypes were associated with higher BMI levels.

Association of angiotensin-converting enzyme (ACE) I/D variation with biochemical parameters and oxidative stress markers in systemic lupus erythematosus patients in west of Iran.

PURPOSE: We aimed to study insertion/deletion (I/D) variation (rs4646994) of ACE gene in a group of SLE patients in west of Iran and its possible relationship with oxidative stress. METHOD AND RESULTS: Genotypes and allele frequencies related to ACE (I/D) variation were determined in 108 SLE patients and 110 gender and age-matched healthy controls using PCR. Neopterin, malondialdehyde (MDA), and serum lipid concentrations were determined by HPLC and enzyme assay respectively. The overall distribution of ACE I/D genotypes in SLE patients was different from that of the control group (P = 0.005). DD genotype compared to ID genotype increased the risk of SLE (OR = 2.57, 95% CI 1.4-4.8, P = 0.003). ID genotype compared to the II genotype decreased the risk of disease (OR = 0.45, 95% CI 0.2-0.99, p = 0.042). SLE patients with DD, ID, and II genotypes had lower paraoxonase (PON) activity and higher serum levels of MDA and neopterin versus control patients. We also detected a significant protective effect against SLE in presence of ACE I alleles and lack of angiotensin II receptor, type 1 (AGTR1) A1166C (NCBI reference SNP id: rs5186), C alleles in this study (OR = 0.31, 95% CI 0.14-0.68, P = 0.002). CONCLUSIONS: Carriers of the DD genotype of ACE gene with higher serum concentrations of neopterin and MDA, and lower PON activity had a high risk to develop SLE, while ID genotype decreased the risk of disease development by 2.22 times compared to II genotype.

Tobacco smoking and blood parameters in the kurdish population of Iran.

OBJECTIVE: This study investigates the relationship between smoking and blood parameters in the Iranian Kurdish population. METHOD: The current study was conducted based on the recruitment phase of the Ravansar Non-Communicable Disease (RaNCD) cohort study. RESULTS: Current smokers had higher levels of RBC count, HCT, HGB, MCV, MCH, MCHC, WBC count, and GR%, than in other groups significantly. Passive smokers had higher levels of PLT count and PCT statistically. The increasing exposure time of smoking positively affected WBC count, GR%, PLT count, PCT, and RDW in female passive smokers. In addition, heavy smokers, as well as participants with a higher duration time of smoking, had the same results for significantly lower levels of lymphocyte and monocyte and a higher level of RBC indices. CONCLUSION: According to the present study, along with the current smokers, the intensity of smoking, as well as the duration time of the smoke, could have a positive correlation with blood parameters. Furthermore, passive smokers and specifically secondhand female smokers were more vulnerable to smoke.

Contribution of NOS3AS Variants to Susceptibility to Essential Hypertension: A Study in Kermanshah Province, Western Iran.

Hypertension (HTN) is a global health challenge and increase the risk of cardiovascular disease. Hypertension has a multifactorial course of evolution, with both genetic and environmental factors playing an important role. To date, a number of genes and pathways have been proposed to be associated with HTN, among which is Nitric Oxide pathway. NO levels can be regulated by reactive oxygen species (ROS), superoxide and post-transcriptional mechanisms, including sense-anti sense interactions. NOS3AS gene encodes an antisense RNA (sONE) which is complementary to NOS3 transcript in 662 nucleotides and may regulate NOS3 in a post-transcriptional manner. In this study, we sought to define the role of NOS3AS in the pathophysiology of essential HTN. A total of 131 cases with hypertension and 115 controls were enrolled in the study. Peripheral blood was drawn from all study participants after signing the informed consent form. Three variants (rs71539868, rs12666075 and rs7830) were investigated by Tetra-ARMS PCR method. The results were then statistically analyzed. We found statistically significant association between rs7830 TT genotype, rs12666075 GT and TT genotypes with susceptibility to HTN. We failed to observe association between rs71539868 and susceptibility to HTN. The present study showed a strong association between NOS3AS variants and susceptibility to hypertension in the population of Kermanshah province. Our results may shed more light on the mechanisms of disease development and may also help to better identify genetic predispositions and individuals at risk.

Variants and Haplotypes of SIRT1 (rs7895833, rs7069102, and rs2273773) are Associated with the Risk of Preeclampsia and Affect the Trace Elements and Antioxidant Enzymes Levels.

Preeclampsia is the most common and serious complication of pregnancy. Variants of Sirtuin-1 (SIRT1) as a key player in the regulation of oxidant/antioxidant signaling pathways might be involved in the pathogenesis of preeclampsia. In the present case-control study 300 women with and without preeclampsia were studied for SIRT1 variants (rs7895833, rs7069102, and rs2273773) and haplotypes. Also, the relationship of glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities and Zn, Cu, and Se levels to the polymorphisms were investigated. The SIRT1 rs7895833 A > G, rs7069102 C > G, and the rs2273773 C > T polymorphisms were associated with the risk of preeclampsia. We found the haplotypes G (rs7895833) C (rs7069102) C (rs2273773), GCC, and ACC compared to the AGT decreased the risk of preeclampsia. The risk haplotype of AGT was associated with higher GPx activity compared to the GCC haplotype. A significantly higher level of Cu and lower levels of Zn and Se in patients with preeclampsia compared to controls were detected. Also, a significantly lower SOD and higher GPx activity in preeclamptic patients compared to controls were found. The three risk genotypes of AA (rs7895833), GG (rs7069102), and TT (rs2273773) significantly decreased the Zn level and SOD activity, and the TT genotype (rs2273773) increased the Cu level in all studied women. The presence of rs7069102 polymorphism was associated with enhanced systolic blood pressure. For the first time, we indicated three SIRT1 polymorphisms and the AGT haplotype are risk factors for preeclampsia development. Also, SIRT1 variants and haplotypes affect the levels of antioxidant enzymes and their cofactors, complicating the pregnancy outcome.

Demographics, clinical characteristics, and outcomes of 27,256 hospitalized COVID-19 patients in Kermanshah Province, Iran: a retrospective one-year cohort study.

BACKGROUND: Since the first official report of SARS-CoV-2 infection in Iran on 19 February 2020, our country has been one of the worst affected countries by the COVID-19 epidemic in the Middle East. In addition to demographic and clinical characteristics, the number of hospitalized cases and deaths is an important factor for evidence-based decision-making and disease control and preparing the healthcare system to face the future challenges of COVID-19. Therefore, this cohort study was conducted to determine the demographics, clinical characteristics, and outcomes of hospitalized COVID-19 patients in Kermanshah Province, west of Iran. METHODS: This multicenter retrospective cohort study included all suspected, probable, and confirmed cases of COVID-19 hospitalized in Kermanshah Province, Iran during the first year of the COVID-19 pandemic. Demographics, clinical characteristics, outcomes and other additional information of hospitalized patients were collected from the COVID-19 database of the Medical Care Monitoring Center (MCMC) of Kermanshah Province. RESULTS: Kermanshah Province experienced three waves of COVID-19 infection considering the hospitalization and mortality rates between February 20, 2020 and February 19, 2021. A total of 27,256 patients were included in the study: 5203 (19.09%) subjects were suspected, 9136(33.52%) were probable, and 12,917 (47.39%) were confirmed COVID-19 cases. The mean age of the patients was 53.34 ± 22.74 years and 14,648 (53.74%) were male. The median length of hospital stay among COVID-19 survivors and non-survivors patients were 4 (interquartile range [IQR] 1-6) and 4 (IQR 1-8) days, respectively. Among patients with COVID-19, 2646 (9.71%) died during hospitalization. A multivariable logistic regression revealed that odds of death among patients ≥ 85 years was significantly greater than among patients < 15 years (adjusted odds ratio [aOR] 4.79, 95% confidence interval [CI] = 3.43-6.71, p≤ 0.001). Patients with one (aOR 1.38, 95% CI 1.21-1.59, p = 0.04), two (aOR 1.56, 95% CI 1.27-1.92, p = 0.001) or more (aOR 1.50, 95% CI 1.04-2.17, p = 0.03) comorbidities had higher odds of in-hospital death compared to those without comorbidities. The male sex (aOR 1.20, 95% CI 1.07- 1.35, p = 0.002), ICU admission (aOR 4.35, 95% CI 3.80-4.97, p < 0.001), intubation (aOR 11.09, 95% CI 9.58-12.84, p < 0.001), respiratory distress (aOR 1.40, 95% CI 1.22-1.61, p < 0.001), loss of consciousness (aOR 1.81, 95% CI 1.45-2.25, p < 0.001), anorexia (aOR 1.36, 95% CI 1.09-1.70, p = 0.006) and peripheral oxygen saturation (SpO2) < 93(aOR 2.72, 95% CI 2.34-3.16, p < 0.001) on admission were associated with increased risk of death in patients with SARS-CoV-2 infection. Having cough (aOR 0.82, 95% CI 0.72-0.93, p = 0.003) and headache (aOR 0.70, 95% CI 0.50-0.97, p = 0.03) decreased the odds of death. CONCLUSION: The mortality rate of the patients admitted to the general wards and ICU can be a guide for allocating resources and making appropriate plans to provide better medical interventions during the COVID-19 pandemic. Several risk factors are associated with the in-hospital mortality of COVID-19, including advanced age, male sex, ICU admission, intubation, having comorbidity, SpO2 < 93, respiratory distress, loss of consciousness, headache, anorexia, and cough. These risk factors could help clinicians identify patients at high risk for death.

Oxidative stress parameters and keap 1 variants in T2DM: Association with T2DM, diabetic neuropathy, diabetic retinopathy, and obesity.

INTRODUCTION: Chronic hyperglycemia activates the inflammatory pathways and oxidative stress mechanisms with consequent damage to nerve tissue and retina. The Keap1-Nrf2 pathway acts as one of the most important antioxidant pathways of the organism. Variants of Keap1 could affect susceptibility to diabetes and its complications. METHODS: In a case-control study, 400 individuals included type 2 diabetes mellitus (T2DM) patients without complication, with neuropathy, with retinopathy, and healthy individuals were investigated. The levels of glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured using chemical methods. Using the PCR-RFLP method, the Keap1 (rs11085735) variants were identified. RESULTS: Neuropathic patients had significantly lower levels of GSH, GPx, and TAC and higher levels of total oxidative status (TOS), MDA, and oxidative stress index (OSI) compared to T2DM patients without complication and controls. Lower levels of GSH and GPx and a higher level of MDA were observed in patients with retinopathy compared with controls. Obesity was associated with significantly lower GPx activity and higher TOS. A significantly higher Keap1 AA genotype was found in patients with neuropathy than T2DM without complication and controls. The presence of Keap1 AA genotype correlated with lower GPx activity compared to CC genotype. CONCLUSIONS: Our study suggests the role of reduced antioxidant system and Keap1 variants in the pathogenesis of T2DM and its complications of neuropathy and retinopathy and also obesity in enhanced oxidative stress. Monitoring oxidative stress parameters in diabetic patients, especially those with complication and their treatment with antioxidants is suggested.

Efficacy and safety of sofosbuvir/velpatasvir versus the standard of care in adults hospitalized with COVID-19: a single-centre, randomized controlled trial.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. The majority of patients experience asymptomatic to mild self-limited disease, but some cases progress to respiratory and multi-organ failure. However, so far, no approved antiviral therapy has been available for treatment of COVID-19. Sofosbuvir/velpatasvir (SOF/VEL) is an approved anti-HCV drug that is capable of suppressing other families of positive-sense RNA viruses with conserved polymerase and may be effective against SARS-CoV-2. This study was conducted to evaluate the efficacy of the SOF/VEL combination in addition to the national standard of care versus the national standard of care alone (hydroxychloroquine and lopinavir/ritonavir as well as supportive care) in patients with moderate to severe COVID-19 infection. METHODS: This single-centre, randomized, open-labelled, prospective clinical trial was done in patients with moderate to severe COVID-19 admitted to Farabi Hospital in Kermanshah Province, Iran. Eligible patients were randomly assigned in a 1:1 ratio to the SOF/VEL arm (SOF/VEL plus the national standard of care) or the control arm (the national standard of care alone). The main outcome of the study was the mortality on Day 28 after randomization. Secondary outcomes were time from the start of medication to clinical improvement, hospital length of stay, need for mechanical ventilation, duration of mechanical ventilation and conversion of RT-PCR results from positive to negative from the time of randomization to discharge. Adverse events were evaluated in all patients who started their assigned treatment. RESULTS: Between 11 April and 8 June 2020, 80 patients were recruited and randomly assigned into the SOF/VEL (n = 40) and control (n = 40) arms. The primary outcome was not significantly different between the two arms (P = 1.00). Secondary outcomes, including time to clinical improvement, hospital length of stay, need for mechanical ventilation, duration of mechanical ventilation and RT-PCR conversion, were not significantly different between arms either (P > 0.05). SOF/VEL treatment and the national standard of care were tolerated similarly. CONCLUSIONS: Although treatment with SOF/VEL was safe, adding SOF/VEL to the standard of care did not improve the clinical status or reduce mortality in patients with moderate to severe COVID-19. However, larger randomized clinical trials including more parameters are needed for accurate estimation of the efficacy of SOF/VEL.

The role of caveolin-1 and endothelial nitric oxide synthase polymorphisms in susceptibility to prostate cancer.

Caveolin-1(cav-1) is overexpressed in prostate cancer (PC) and is associated with progression of the disease. We investigated the effects of CAV1-T29107A and endothelial nitric oxide synthase (eNOS) G894T polymorphisms on the serum levels of testosterone, NO and prostate-specific antigen (PSA) in patients with PC. We genotyped cav-1 and eNOS genes in 112 PC patients and 150 healthy controls by PCR-RFLP. Serum levels of NO2- and NO3- were measured using spectrophotometry, and serum levels of testosterone and PSA were measured by ELISA. The frequencies of CAV1 genotypes A/T vs. A/A according to the dominant model AT + TT vs. AA genotype and T allele were significantly higher in PC patients in comparison with the control group and considerably increased the risk of disease by 2.19-, 1.44- and 1.6-fold, respectively. AT + TT genotypes were associated significantly with the increased risk of PC in those with smoking or diabetes by 3.08-fold (P = .004). Individuals carrying concurrently the T allele of CAV1 A29107T and the T allele of eNOS G894T genes had a significantly increased risk of PC by 2.52-fold (P = .009). We did not find any significant relationship between eNOS G894T genotypes and alleles with susceptibility to PC. Our results highlighted the significance of CAV1-T29107A SNP but not (eNOS) G894T in the susceptibility to PC in our the population that we have studied.

Sickle cell disease and COVID-19: Susceptibility and severity.

We surveyed published papers and an international sickle cell disease (SCD) registry to detect susceptibility and clinical course of coronavirus disease 2019 (COVID-19) in SCD patients. COVID-19 presentation was mild in children and moderate in many SCD adults. Regarding increased comorbidities with age, it seems severe COVID-19 to be more common in older SCD patients. Although the overall outcome of COVID-19 was favorable in SCD children, a high rate of pediatric intensive care unit admission should be considered in managing these patients. To explain COVID-19 outcome in SCD patients, the possible benefits of hydroxyurea therapy could be considered. The obtained results should be interpreted, considering low cases from sub-Saharan people, younger age of SCD patients compared to general population, a bias toward registry of the more severe form of disease, the effect of pre-existing comorbidities with multisystem organ damage, and the role of health socio-economic determinants.

Vitamin D level, lipid profile, and vitamin D receptor and transporter gene variants in sickle cell disease patients from Kurdistan of Iraq.

INTRODUCTION: Sickle cell disease (SCD) patients are susceptible to the development of vitamin D deficiency (VDD). Vitamin D through binding to vitamin D receptor (VDR) exerts its function and affects gene transcription in target tissues. VDR gene variants affect bone mineral density. METHODS: In a case-control study, 101 SCD patients including 61 sickle cell anemia (SCA), 39 S/ß-thalassemia, and 1 HbS/HbD (SD) along with 110 healthy individuals from Kurdistan of Iraq were studied. The lipid profile, vitamin D level, FokI, and TaqI variants of VDR and group-specific component (GC) were detected using the standard enzymatic method, the immunodiagnostic systems limited EIA kit and PCR-RFLP methods, respectively. RESULTS: Around 93% and 82% of SCA and S/ß-thalassemia patients, respectively, had VDD compared to 83% of healthy individuals. Severe VDD (<10 ng/ml) was detected in 78.7% of patients with HbSS. Plasma levels of total cholesterol, HDL-C, and LDL-C in SCD patients were significantly lower compared to controls. Vitamin D levels were negatively correlated to TG and positively correlated to total cholesterol and HDL-C. The frequencies of the C allele of FokI were 81.7% (p = 0.003), 80.3% (p = 0.034), and 84.6% (p = 0.011) in all SCD, SCA, and S/ß-thalassemia patients, respectively, compared to 69.1% in controls. However, no significant difference was detected comparing the frequencies of VDR TaqI and GC polymorphisms between SCD patients and controls. CONCLUSION: In the present study, we found hypocholesterolemia, high prevalence of VDR FokI C allele, and low vitamin D levels among children and adults with SCD from Kurdistan of Iraq.

The clinical significance of circulating DSCAM-AS1 in patients with ER-positive breast cancer and construction of its competitive endogenous RNA network.

Long Non-Coding RNAs (lncRNAs), with diagnostic and therapeutic applications in malignancies, are newly described tumour-related molecules. Here, we reported the importance of circulating DSCAM-AS1 as the biomarker to detect Estrogen Receptor (ER)-positive breast cancer (BC) cases. Moreover, the expression of a BC-associated lncRNAs, namely DSCAM-AS1, was measured in tumoural and Paired Adjacent Non-Tumoral (PANT) tissue, as well as plasma, using Real-Time Polymerase Chain Reaction (RT-PCR). Besides, the correlations between gene expression and the clinicopathological features were analyzed. The diagnostic power of circulating DSCAM-AS1 in BC was estimated using the Area Under the Curve (AUC) value. Furthermore, we studied the DSCAM-AS1 associated with the network of competitive endogenous RNA (ceRNA) in BC using the literature review and in silico analysis. We found a significant increase in the expression levels of lncRNA in the tumour (P < 0.001) and in plasma (P < 0.001) of ER-positive BC patients. The sensitivity and specificity of DSCAM-AS1 in plasma for detection of BC from healthy controls were 100 and 97%, respectively (AUC = 0.98, P < 0.001). Accordingly, we suggest an elevated level of circulating DSCAM-AS1 as a candidate biomarker of ER-positive BC patients. Moreover, perturbation of DSCAM-AS1, as a ceRNA, acts in the tumor progression and drug resistance by affecting different cell signaling.

Activities and polymorphisms of MMP-2 and MMP-9, smoking, diabetes and risk of prostate cancer.

Matrix metalloproteinases (MMPs) are a group of zinc dependent enzymes that are involved in tumor cell invasion and metastasis. The role of MMP-2 and -9 genetic polymorphism in different malignancies has been the subject of numerous studies. The present research has attempted to discover any positive correlation between MMP-2 and MMP-9 SNPs and prostate cancer (PCa) in patients with a history of either diabetes or smoking habits. 112 PCa-patients and 150 unrelated healthy-controls that matched for age and sex were selected for present case-control study. MMP-2 -1575G/A and MMP-9 -1562 C/T polymorphisms detected by PCR-RFLP, serum tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), testosterone, prostate-specific antigen (PSA), free-prostate-specific-antigen (fPSA), and fPSA/PSA levels were detected by ELISA and enzyme assay, respectively. MMP-2 and MMP-9 activities were measured by gelatin-zymography. Covariates were considered as age, status of cigarette smoking, and a possible history of diabetes mellitus (DM). The frequency of -1575 MMP-2 A/A + A/G and -1562 MMP-9 C/T + T/T genotypes were higher in PCa-patients with DM (74.3%,p = 0.003) and with smoking habits (72.5%,p = 0.005). These genotypes were associated with the increased risk of prostate cancer in smokers (3.52-folds) and in individuals with history of DM (4.34-folds). A significant positive association was found between level of TIMPs (TIMP -1 and TIMP-2) and BMI in PCa-patients and also between testosterone levels and MMP-9 activity in healthy control subjects. For the first time, this study demonstrated that activities of MMP-2 -1575G/A and MMP-9 -1562C/T variants in association with smoking and diabetes are considered significant risk factors for PCa.

A case-control study on the SNP309T → G and 40-bp Del1518 of the MDM2 gene and a systematic review for MDM2 polymorphisms in the patients with breast cancer.

OBJECTIVE: The current research was conducted to study the association between the SNP309 and del1518 polymorphisms with the breast cancer in the patients with the Kurdish ethnic background from western Iran. Also, a systematic review of the relevant case-control studies on the MDM2 polymorphisms in the patients with breast cancer was performed. METHODOLOGY: Two mL of peripheral blood was taken from 100 patients with breast cancer and 100 healthy individuals. The frequencies of MDM2 SNP309 and del1518 genotypes and alleles were determined using the PCR-RFLP and PCR methods, respectively. RESULTS: The frequency of the TT, TG, and GG of MDM2-SNP309 genotypes in the patients was obtained as 23%, 52%, and 25%, and they were equal to 22%, 40%, and 38% in the control group, respectively. Also, considering the MDM2-del1518 polymorphism, the frequencies of ins/ins, ins/del, and del/del genotypes were equal to 52%, 41%, and 7% in the breast cancer group and they were equal to 62, 30, and 8% in the control group, respectively. Analysis of the results indicated that the GG genotype plays a protective role for the breast cancer in the recessive model (GG vs TT + TG) of SNP309 (χ2  = 3.916, P = .048, and OR = 0.54). CONCLUSION: Our findings revealed that the GG genotype of MDM2-SNP309 can play a protective role in the breast cancer disease. Also, our systematic review indicated that the SNP309, SNP285, and del1518 of MDM2 gene in different populations mostly did not have a significant association with the risk of breast cancer.

Interaction of long noncoding RNA MEG3 with miRNAs: A reciprocal regulation.

The competitive endogenous RNA (ceRNA) hypothesis suggests that a long noncoding RNA (lncRNA) can function as sinks for pools of microRNAs (miRNAs); thereby, in the presence of ceRNA, messenger RNAs (mRNAs) targeted by specific miRNAs can liberate and translate to protein. Maternally expressed gene 3 (MEG3) is a lncRNA, which its expression has been detected in various normal tissues, while it is lost or downregulated in human tumors. The MEG3 is an imprinted gene which, is methylated and suppressed by DNA methyltransferases (DNMTs) family. Also, miRNAs are involved in the regulation of MEG3 gene expression. Interestingly, the lncRNA MEG3 (lnc-MEG3), as a ceRNA affects various cell processes such as proliferation, apoptosis, and angiogenesis by sponging miRNAs. These miRNAs, in turn, regulate different mRNAs in different pathways. This review focuses on the interaction between lnc-MEG3 and experimentally validated miRNAs. In addition, the discussion supplemented by some data obtained from mirPath (v.3) and TarBase (v.8) databanks to provide more details about the pathways affected by this ceRNA.

The effect of VDR gene polymorphisms and vitamin D level on blood pressure, risk of preeclampsia, gestational age, and body mass index.

We investigated the influence of vitamin D receptor (VDR) polymorphisms and vitamin D level on the blood pressure and the risk of preeclampsia. In a case-control study, 200 pregnant women, including 100 individuals with preeclampsia along with 100 healthy pregnant women, were studied for VDR FokI, TaqI, and BmsI polymorphisms and serum 25 (OH)-D level using polymerase chain reaction-restriction fragment length polymorphism method and commercial kit, respectively. The mean level of 25 (OH)-D in preeclamptic patients was significantly lower (16.6 ± 4.2 ng/mL, P < 0.001) compared with controls (19.6 ± 3.8 ng/mL). Among all women, a significantly higher systolic blood pressure and before-pregnancy body mass index and also lower gestational age were observed in the presence of 25 (OH)-D level < 20 ng/mL compared with the 20 to 30 ng/mL. A significantly higher frequency of VDR FokI C allele in preeclamptic patients (83%) than controls (74%) was associated with a 1.72-fold increased risk of preeclampsia. In all the studied individuals, the systolic and diastolic blood pressures were significantly higher in the presence of the FokI CC genotype compared with the TC and TT+TC genotypes. Neither VDR Taq1 nor VDR BmsI was associated with the risk of preeclampsia. The haplotype FokI C, TaqI C and BmsI A (CCA) compared with haplotype CTG increased the risk of preeclampsia by 1.4-fold (P = 0.33). Our study suggests an association between VDR FokI polymorphism and an insufficient serum level of 25 (OH)-D with the risk of preeclampsia and also the influence of insufficient 25 (OH)-D level and VDR FokI polymorphism on maternal factors, including blood pressure.

Angiotensin-converting enzyme insertion/deletion (rs106180) and angiotensin type 1 receptor A1166 C (rs106165) genotypes and psoriasis: Correlation with cellular immunity, lipid profile, and oxidative stress markers.

Psoriasis is a chronic inflammatory skin condition and angiotensin-converting enzyme (ACE) is a key circulating enzyme converting angiotensin (Ang) I to the vasoactive peptide Ang II. The exact role of ACE insertion (I)/deletion (D) polymorphism (rs106180) in psoriasis is not clear. We aimed to examine whether the ACE I/D and Ang II type 1 receptor (AT1R) A1166 C-polymorphisms (rs106165), lipid profile, and stress oxidative are associated with susceptibility to psoriasis. One hundred patients with psoriasis and 100 sex- and age-matched unrelated healthy controls were recruited for this case-control study. ACE I/D and AT1R A1166 C polymorphisms were identified by the polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively, malondialdehyde (MDA) was detected by the high-performance liquid chromatography, serum arylesterase (ARE) activity of paraoxonase and catalase activities were detected by the spectrophotometry, superoxide dismutase (SOD) activity and vascular adhesion protein (VAP)-1 were measured by ELISA. The presence of C allele of AT1R A1166 C and I allele of ACE considerably increased the risk of psoriasis by 6.42-fold (P < 0.001). The distribution of II-genotype of ACE was significantly higher in psoriasis patients than in control group and increased the risk of disease by 3.11-times (P = 0.023). The higher levels of MDA in patients and the higher activity of SOD, ARE, and CAT was observed in healthy controls with I/D+I/I-genotype of ACE I/D. This study for the first time demonstrated that the ACE I/D and AT1R A 1166 C genes polymorphisms robustly increases the risk of developing psoriasis in population from west of Iran. In addition, these individuals had significantly higher VAP-1 and MDA concentration and lower enzymatic and nonenzymatic antioxidant-status, suggesting that psoriatic patients carrying C allele of AT1R1166 polymorphism may be more susceptible to cardiovascular disease and myocardial infarction compared with A allele.

Association between the -11377 C/G and -11391 G/A polymorphisms of adiponectin gene and adiponectin levels with susceptibility to type 1 and type 2 diabetes mellitus in population from the west of Iran, correlation with lipid profile.

Adipose tissue, an endocrine organ, secretes bioactive factors including adiponectin. Adiponectin is a protein hormone that enhances insulin sensitivity through increased fatty acid oxidation and inhibition of hepatic glucose production. We assessed the association of the adiponectin promoter region polymorphisms -11391 G/A and -11377 C/G with susceptibility to type 1 (T1DM) and type 2 (T2DM) diabetes mellitus in the population of west Iran. Also, we investigated the effect of adiponectin level and lipid profile on T1DM and T2DM development. In this case-control study, we recruited 189 patients with diabetes (100 T2DM and 89 T1DM) and 161 sex and age-matched unrelated healthy controls. Adiponectin mutations were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the protein level was measured by the enzyme-linked immunosorbent assay. Other biochemical parameters were determined by routine laboratory methods. The G allele of adiponectin gene at -11377 position (C/G) significantly increased the risk of T1DM. With respect to genotype models, codominant (2.97 times), dominant (3.6-fold), and over-codominant (2.9-fold) patients with T1DM who carried -11377 C > G single-nucleotide polymorphisms were significantly susceptible to the development of the disease. A significantly higher level of adiponectin in T1DM was oberved compared with the control group. In contrast, patients with T2DM had lower adiponectin levels compared with healthy controls. The genotype distributions of -11391 G/A polymorphisms were the same for patients with diabetes and control groups. The presence of G allele at -11377 C/G adiponectin gene significantly increased serum adiponectin level and may be a risk factor for T1DM susceptibility among the western Iranian population.

Vitamin D-binding protein and vitamin D receptor genotypes and 25-hydroxyvitamin D levels are associated with development of aortic and mitral valve calcification and coronary artery diseases.

To assess the association between vitamin D-Binding Protein (VDBP rs7041T>G) and vitamin D receptor (VDR rs1544410G>A) gene polymorphisms with susceptibility to cardiovascular diseases in population from west of Iran. Two hundred forty-nine individuals with cardiovascular disease (92 with aortic and Mitral Valves Calcification (AMVC) and 157 with Coronary Artery Diseases (CAD) that their diseases were confirmed by echocardiography and angiography and unrelated 182 healthy controls (gender and age-matched) were selected for this case-control study. The VDR 1544410G>A, and VDBP 7041T>G genotyping were detected by PCR-RFLP, serum vitamin D and lipid concentrations were measured by ELISA and enzyme assay, respectively. The VDR rs1544410G>A gene is a strong risk factor for CAD (OR = 1.28, p = 0.002) and the dominant genotype (T/G+G/G) of VDBP 7041 T>G SNP plays a protective role (OR = 0.67, p = 0.003) in AMVC development in studied population. In addition, lower level of vitamin D strongly increased the risk of CAD (15 ± 11.02 vs. 21.3 ± 18 µg/L, p = 0.043) and AMVC (12.1 ± 13.1 vs.21.3 ± 18 µg/L, p = 0.014) development in individuals carrying T/T genotype of VDBP 7041 T>G gene polymorphism. There was a strong interaction between A allele VDR rs1544410 and G allele of VDBP rs7041 genes in a protective role (OR = 0.74, p = 0.044) in AMVC patients). CAD and AMVC patients were deficient in vitamin D, i.e. their level of vitamin D was strongly lower than that in the control group. Our findings for the first time indicated that there is a strong association between vitamin D deficiency, lipid profile and the VDR rs1544410G>A and rs7T41>G VDBP genes polymorphisms. These interactions may be one of the important factors for CAD and AMVC incidence.