Large-scale mtDNA deletions as genetic biomarkers for susceptibility to male infertility: A systematic review and meta-analysis.

Several complex rearrangements such as deletions in mitochondrial DNA (mtDNA) have been identified in sperm deficiencies. This study aimed to investigate the association of common mtDNA deletions with male infertility using a meta-analysis approach. Standard databases were systematically searched to discover relevant studies. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CI) were estimated to analyze the association of mtDNA deletions with male infertility. Our data revealed a significant association between a common 4977-bp deletion and an increased risk of male infertility. A similar association was observed in an Asian population. Stratified analysis by infertility phenotype showed significant associations between the 4977-bp deletion and increased risk of asthenozoospermia, oligoasthenoteratozoospermia, and asthenoteratozoospermia. In addition, significant associations were found in studies with sample sizes >100, age of participants <45 years, subject selection according to WHO criteria, and studies of moderate to high quality. Regarding the other common mtDNA deletions, significant associations were observed between 7436-bp, 7599-bp, and 4866-bp deletions and the risk of male infertility. Our findings suggest that the 4977-bp deletion might be a risk factor for male infertility, especially in an ethnic and infertility phenotype dependent manner.

Evaluation of Cisplatin Efficacy on HepG2 and E. coli Cells under Acidic Conditions

Background: Cisplatin (Cispt) is a common anticancer drug for the treatment of several malignancies, including hepatocarcinoma. However, this drug suffers from instability in aqueous solutions. The study aimed to evaluate cisplatin efficacy on HepG2 and E. coli cells under an acidic condition. Methods: Acidic Cispt was prepared via incubation in acidic condition (pH=2) for a month duration. The chemical structure of the acidic Cispt was evaluated by using Fourier Transform Infrared Spectroscopy (FTIR) method. The cytotoxicity of the standard and acidic Cispt were then determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and minimum inhibitory concentration (MIC) assays on HepG2 and E. coli cells, respectively. Results: After preparing of acidic Cispt, its chemical structure was determined by FTIR method. In addition, cytotoxicity effects of Cispt in the standard and acidic forms were calculated 58 ± 2.9 and 65 ± 3.25 µM, respectively. MIC results also confirmed the results of MTT assay. MIC results for the standard and acidic Cispt were estimated 9.5 ± 0.47 and 9.8 ± 0.49 µM, respectively. Conclusion: Preparing Cispt in acidic condition not only did not degrade the drug, but also kept the potency of the drug approximately equal to parent drug. Regarding the instability issues of Cispt, keeping Cispt in acidic condition could be a promising approach to preserve its efficacy.

Fast Biodegradation of Diesel Hydrocarbons at High Concentration by the Sophorolipid-Producing Yeast Candida catenulata KP324968.

In the last decades, biodegradation as an environmentally friendly approach has raised interest in connection with the removal of hydrocarbon pollutants. Its capacity for removing pollutants strongly depends on the type of living cell and environmental conditions. The degradative activity of a new sophorolipid-producing yeast, Candida catenulata KP324968, in the removal of high concentrations of diesel from effluents was statistically evaluated considering the initial pH, the agitation speed, and the initial diesel concentration. The optimal setting of the operational variables at an initial pH of 4.7, an agitation speed of 204 rpm, and an initial diesel concentration of 93.4 g L-1 resulted in the highest total petroleum hydrocarbon removal efficiency: about 82.1% after 6 days (biodegradation rate: 0.378 g gcell-1 h-1). During the cell growth phase, the emulsification index in the medium increased and reached its highest level at 64.6% after 48 h. Further tests indicated that the emulsification capacity was obtained by in situ production of two sophorolipid molecules with an m/z of 533 and 583. In summary, its effective diesel removal and high emulsification capacity makes C. catenulata KP324968 an attractive candidate yeast for the degradation of hydrocarbons from aqueous environments.

Androgen receptor (AR)-CAG trinucleotide repeat length and idiopathic male infertility: a case-control trial and a meta-analysis.

CAG trinucleotide repeats in androgen receptor (AR) gene encode a polyglutamine tract in AR N-terminal transactivation domain. Studies have been conducted to evaluate the effect of CAG repeat length on male infertility, which have yielded contradictory results. This study aimed to explore the number of AR-CAG repeats in 150 fertile controls and 150 idiopathic infertile men, divided into four azoospermia, oligozoospermia, asthenozoospermia, and teratozoospermia subgroups. In addition, a meta-analysis was conducted based on previous studies to assess the association of the mentioned variation with male infertility in recent years. Polymerase chain reaction (PCR) targeting followed by an electrophoresis on polyacrylamide gel was used for AR-CAG genotype detecting. Moreover, a systematic search was performed in PubMed, Web of Science, Science Direct, and Google Scholar databases to collect eligible studies for meta-analysis purpose. According to the results, a significant association was observed between increased length of AR-CAG polymorphism and male infertility (p< 0.0001). Furthermore, there were similar significant associations in the azoospermia (p= 0.048), asthenozoospermia (p= 0.013) and teratozoospermia (p= 0.002) subgroups. In addition, meta-analysis on forty studies showed a significant association between AR-CAG polymorphism in the overall analysis (SMD= 0.199, 95 % CI= 0.112-0.287, p<0.001) and the Caucasian subgroup (SMD= 0.151, 95 % CI= 0.040-0.263, p= 0.008). Our results elucidated that long stretches of CAG repeat might lead to AR dysfunction, contributing to male infertility especially in the Caucasian population.

Survivin polymorphisms and susceptibility to prostate cancer: A genetic association study and an in silico analysis.

Survivin is a member of the apoptosis inhibitor protein family and its polymorphisms may lead to susceptibility to cancer. The aim of this study was to investigate the possible association of c.-31G>C (rs9904341), c.454G>A (rs2071214), c.*148T>C (rs2239680) and c.*571T>C (rs1042489) polymorphisms of survivin gene with prostate cancer risk and provide some justification using in silico analysis. The 157 men with prostate cancer and 145 healthy controls were included in a case-control study. The studied polymorphisms were genotyped using PCR-RFLP method. An in silico approach was employed to show the possible effects of the polymorphisms on the survivin gene function. The study revealed that there are significant associations between c.-31CC genotype (OR= 2.29, 95 % CI= 1.20-4.37, p= 0.012), c.-31C allele (OR= 1.62, 95 % CI= 1.17-2.26, p= 0.004), c.454AG genotype (OR= 2.03, 95 % CI= 1.02-4.04, p= 0.043), and c.*148C allele (OR= 1.49, 95 % CI= 1.04-2.15, p= 0.031) with prostate cancer. Using stratified analysis, we found also significant effects of age distribution on the association of c.-31G>C with prostate cancer risk (OR= 2.10, 95 % CI= 1.08-4.10, p= 0.030). Also as a preliminary study, it was shown that smoking status has significant effects on the association of c.-31G>C (OR= 1.94, 95 % CI= 1.08-3.49, p= 0.027) and c.*148T>C (OR= 2.60, 95 % CI= 1.47-4.60, p= 0.001) polymorphisms with prostate cancer risk. Finally, in silico analysis revealed that c.-31G>C, which is located in a CpG island of the promoter may change transcriptional regulation of survivin gene and c.454G>A and *148T>C could affect protein structure and possible miRNA interaction with 3'-UTR of survivin transcript respectively. According to the results, c.-31G>C, c.454G>A, and c.*148T>C polymorphisms could be genetic risk factors for prostate cancer in an Iranian population. However, further studies with larger sample size and different ethnicities are required to obtain more comprehensive results.