Association of Functional Genetic Variations in Uric Acid Transporters with the Risk of Idiopathic Male Infertility: A Genetic Association Study and Bioinformatic Analysis.

Uric acid plays an important role in sustaining and improving sperm morphology, viability, and motility. It is known that SLC2A9 and ABCG2 protein are the main urate transporter and genetic variations in these genes could be associated with the levels of serum uric acid. This study aimed to investigate the association between single-nucleotide polymorphisms (SNPs) SLC2A9-rs16890979, SLC2A9-rs3733591, ABCG2-rs2231142, and ABCG2-rs2231137 with male infertility. Additionally, the correlation of these SNPs with the uric acid level in seminal plasma of infertile men was examined. Subsequently, an in silico analysis was performed. In a case-control study, 193 infertile and 154 healthy controls were recruited. After semen sample collection, the uric acid level of seminal plasma was measured by a commercial kit. After genomic DNA extraction from sperm samples, SNPs genotyping was performed by PCR-RFLP method. Lastly, the effects of SNPs on the SLC2A9 and ABCG2 gene function were evaluated by bioinformatics tools. The genetic association study revealed that there are significant associations between rs16890979, rs3733591, rs2231142, and rs2231137 genetic variations and increased risk of male infertility. Also, these variations were associated with oligozoospermia and teratozoospermia, and sometimes with asthenozoospermia. Also, we found that four studied SNPs could be associated with a decreased level of uric acid of seminal plasma in teratozoospermia and asthenozoospermia. Bioinformatic analysis revealed that the mentioned polymorphisms could affect molecular aspects of SLC2A9 and ABCG2 genes. In this preliminary study, the rs16890979, rs3733591, rs2231142, and rs2231137 genetic variations could be considered as genetic risk factors for male infertility by interfering with the uric acid level of seminal plasma.

Synergistic effects of dendrosomal nanocurcumin and oxaliplatin on oncogenic properties of ovarian cancer cell lines by down-expression of MMPs.

BACKGROUND: Contrary to the advantageous anticancer activities of curcumin (Cur), limited bioavailability and solubility hindered its efficacy. Here, nontoxic dendrosomal nano carrier with Cur was used to overcome these problems. Despite considerable antitumor properties of Oxaliplatin (Oxa), the limiting factors are drug resistance and adverse side-effects. The hypothesis of this study was to evaluate the possible synergism between dendrosomal nanocurcumin (DNC) and Oxa and these agents showed growth regulatory effects on SKOV3 and OVCAR3 cells. METHODS AND MATERIALS: In the present study, colony formation, wound healing motility, cell adhesion, transwell invasion and migration assay and cell cycle arrest with or without DNC, Oxa and Combination were defined. In addition to, real time PCR and Western blot were used to analyze AKT, PI3K, PKC, JNK, P38 and MMPs mRNAs and proteins expressions. Docking of MMP-2-Cur, MMP-2-DNC and MMP-2-Oxa was performed and the results of all three complexes were simulated by molecular dynamics. RESULTS: Our findings illustrated that DNC had the greatest effect on cell death as compared to the Cur alone. Moreover, the growth inhibitory effects (such as cell death correlated to apoptosis) were more intense if Oxa was added followed by DNC at 4 h interval. However, insignificant effects were observed upon simultaneous addition of these two agents in both cell lines. Besides, a combination of agents synergistically alters the relative expression of MMP-9. CONCLUSIONS: The docking results showed that His70 and Asp100 may play a key role at the MMP-2 binding site. The matrigel invasion as well as cell viability of ovarian cancer cell lines SKOV3 and OVCAR3 by DNC alone or in combination with Oxa was inhibited significantly. The inhibitory effects of these agents were due to the differential expression levels of MMP 2 and MMP 9 regulated by multiple downstream signaling cascades. From the molecular dynamic simulation studies, it was confirmed that DNC established a strong interaction with MMP-2.

The dual interaction of antimicrobial peptides on bacteria and cancer cells; mechanism of action and therapeutic strategies of nanostructures.

Microbial infection and cancer are two leading causes of global mortality. Discovering and developing new therapeutics with better specificity having minimal side-effects and no drug resistance are of an immense need. In this regard, cationic antimicrobial peptides (AMP) with dual antimicrobial and anticancer activities are the ultimate choice. For better efficacy and improved stability, the AMPs available for treatment still required to be modified. There are several strategies in which AMPs can be enhanced through, for instance, nano-carrier application with high selectivity and specificity enables researchers to estimate the rate of drug delivery to a particular tissue. In this review we present the biology and modes of action of AMPs for both anticancer and antimicrobial activities as well as some modification strategies to improve the efficacy and selectivity of these AMPs.

The correlation between IgM and IgG antibodies with blood profile in patients infected with severe acute respiratory syndrome coronavirus.

OBJECTIVES: This study aimed to determine the levels of IgM and IgG antibody response to the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 in coronavirus disease 2019 (COVID-19) patients with different disease severity. METHODS: IgM and IgG antibody levels were evaluated via enzyme-linked immunosorbent assay (ELISA). In total, 100 patients with confirmed SARS-CoV-2 infection were enrolled in this study and viral RNA was detected by using Real-time PCR technique. Clinical and laboratory data were collected and analyzed after hospital admission for COVID-19 and two months post-admission. RESULTS: The level of anti-SARS-CoV-2 antibody IgG was significantly higher in the severe patients than those in moderate and mild groups, 2 months after admission. Also, level of IgG was positively associated with increased WBC, NUT and LYM counts in sever than mild or moderate groups after admission to hospital. CONCLUSION: Our findings suggested that patients with severe illness might experience longer virus exposure times and have a stronger antibody response against viral infection. Thus, they have longer time immunity compared with other groups.

The impact of LncRNA dysregulation on clinicopathology and survival of pancreatic cancer: a systematic review and meta-analysis (PRISMA compliant).

PURPOSE: An increasing number of studies have reported a significant association between long non-coding RNAs (lncRNAs) dysregulation and pancreatic cancers. In the present study, we aimed to gather articles to evaluate the prognostic value of long non coding RNA in pancreatic cancer. EXPERIMENTAL DESIGN: We systematically searched all eligible articles from databases of PubMed, Web of Science, and Scopus to meta-analysis of published articles and screen association of multiple lncRNAs expression with clinicopathology and/or survival of pancreatic cancer. The pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were used to analysis of overall survival, disease-free survival and progression-free survival were measured with a fixed or random effects model. RESULTS: A total of 39 articles were included in the present meta-analysis. Our results showed that dysregulation of lncRNAs were linked to overall survival (39 studies, 4736 patients HR = 0.41, 95% CI 0.25 ± 0.58, random-effects in pancreatic cancer. Moreover, altered lncRNAs were also contributed to progression-free survival (8 studies, 1180 patients HR: 1.88, 95% CI (1.35-2.62) and disease-free survival (2 studies, 285 patients, HR: 6.07, 95% CI 1.28-28.78). In addition, our findings revealed the association between dysregulated RNAs and clinicopathological features in this type of cancer. CONCLUSIONS: In conclusion, dysregulated lncRNAs could be served as promising biomarkers for diagnosis and prognosis of pancreatic cancer.

Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management.

Infertility is a global health problem involving about 15% of couples. Approximately half of the infertility cases are related to male factors. The oxidative stress, which refers to an imbalance in levels of reactive oxygen species (ROS) and antioxidants, is one of the main causes of infertility in men. A small amount of ROS is necessary for the physiological function of sperm including the capacitation, hyperactivation and acrosomal reaction. However, high levels of ROS can cause infertility through not only by lipid peroxidation or DNA damage but inactivation of enzymes and oxidation of proteins in spermatozoa. Oxidative stress (OS) is mainly caused by factors associated with lifestyle. Besides, immature spermatozoa, inflammatory factors, genetic mutations and altering levels of sex hormones are other main source of ROS. Since OS occurs due to the lack of antioxidants and its side effects in semen, lifestyle changes and antioxidant regimens can be helpful therapeutic approaches to overcome this problem. The present study aimed to describe physiological ROS production, roles of genetic and epigenetic factors on the OS and male infertility with various mechanisms such as lipid peroxidation, DNA damage, and disorder of male hormone profile, inflammation, and varicocele. Finally, the roles of oral antioxidants and herbs were explained in coping with OS in male infertility.

Retinoic acid and/or progesterone differentiate mouse induced pluripotent stem cells into male germ cells in vitro.

Numerous reagents were employed for differentiating induced pluripotent stem cells (iPSCs) into male germ cells; however, the induction procedure was ineffective. The aim of this study was to improve the in vitro differentiation of mice iPSCs (miPSCs) into male germ cells with retinoic acid (RA) and progesterone (P). miPSCs were differentiated to embryoid bodies (EBs) in suspension with RA with or without progesterone for 0, 4, and 7 days. Then, the expression of certain genes at different stages of male germ cell development including Ddx4 (pre meiosis), Stra8 (meiosis), AKAP3 (post meiosis), and Mvh protein was examined in RNA and/or protein levels by real-time polymerase chain reaction or flow cytometry, respectively. The Stra8 gene expression increased in the RA groups on all days. But, expression of this gene declined in RA + P groups. In addition, an increased expression of Ddx4 gene was observed on day 0 in the P group. Also, a significant upregulation was observed in the expression of AKAP3 gene in the RA + P group on days 0 and 4. However, gene expression decreased in P and RA groups on day 7. The expression of Mvh protein significantly increased in the RA group on day 7. The Mvh expression was also enhanced in the P group on day 4, but it decreased on day 7, while this protein upregulated on day 0 and 7 in the RA + P group. The miPSCs have the capacity for in vitro differentiation into male germ cells by RA and/or progesterone. However, the effects of these inducers depend on the type of combination and an effective time.

Dual and mutual interaction between microbiota and viral infections: a possible treat for COVID-19.

All of humans and other mammalian species are colonized by some types of microorganisms such as bacteria, archaea, unicellular eukaryotes like fungi and protozoa, multicellular eukaryotes like helminths, and viruses, which in whole are called microbiota. These microorganisms have multiple different types of interaction with each other. A plethora of evidence suggests that they can regulate immune and digestive systems and also play roles in various diseases, such as mental, cardiovascular, metabolic and some skin diseases. In addition, they take-part in some current health problems like diabetes mellitus, obesity, cancers and infections. Viral infection is one of the most common and problematic health care issues, particularly in recent years that pandemics like SARS and COVID-19 caused a lot of financial and physical damage to the world. There are plenty of articles investigating the interaction between microbiota and infectious diseases. We focused on stimulatory to suppressive effects of microbiota on viral infections, hoping to find a solution to overcome this current pandemic. Then we reviewed mechanistically the effects of both microbiota and probiotics on most of the viruses. But unlike previous studies which concentrated on intestinal microbiota and infection, our focus is on respiratory system's microbiota and respiratory viral infection, bearing in mind that respiratory system is a proper entry site and residence for viruses, and whereby infection, can lead to asymptomatic, mild, self-limiting, severe or even fatal infection. Finally, we overgeneralize the effects of microbiota on COVID-19 infection. In addition, we reviewed the articles about effects of the microbiota on coronaviruses and suggest some new therapeutic measures.

Oxidative stress markers in seminal plasma of idiopathic infertile men may be associated with glutathione S-transferase M1 and T1 null genotypes.

This study aimed to investigate the association between glutathione S-transferase (GST) M1 and T1 null genotypes and thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC) and nitric oxide (NO) levels in male infertility. For this purpose, semen samples were collected from fertile and infertile subjects, and then they were genotyped for GSTT1 and GSTM1 genes using multiplex-PCR. The TBARS, TAC and NO levels in seminal plasma were then measured via the ferric-reducing ability of plasma (FRAP). A significant association was observed between GSTT1 null genotype and oligozoospermia, asthenozoospermia and teratozoospermia. But, the GSTM1 null genotype was merely associated with teratozoospermia. Moreover, the GSTT1-/GSTM1+ combined genotype was associated with all subgroups of male infertility. Besides, an association was observed between GSTT1-/GSTM1- genotype and asthenozoospermia and teratozoospermia. Further analysis showed that the GSTT1 null genotype was associated with increased NO in asthenozoospermia. Also, the GSTT1 null genotype was associated with increased TBARS in oligozoospermia and asthenozoospermia. As well, GSTM1 null genotype was associated with decreased TAC and increased NO in asthenozoospermia respectively. As a preliminary conclusion, the GSTM1 and GSTT1 null genotypes could be considered as genetic risk factors for male infertility, interfering with some oxidative stress markers in infertile men.

Retinoic acid and 17ß-estradiol improve male germ cell differentiation from mouse-induced pluripotent stem cells.

This research aimed to explore the impacts of retinoic acid (RA)/17ß-estradiol (E) induction and embryoid body formation to enhance differentiation of mouse-induced pluripotent stem cells (miPSCs) into male germ cells in vitro. Flow cytometry and qPCR were conducted to describe miPSCs differentiation process. Various temporal expression profiles of germ cell-related genes were traced. Stra8 gene expression increased in the RA group on the 4th day compared to other groups. The RA group experienced a more significant increase than E group. The expression of Sycp3 increased in RA + E group on 4th day compared with other groups. Expression of AKAP3 enhanced in the RA + E group than other groups on day 4. Moreover, miPSCs showed that this gene expression in the RA + E group was increased in comparison to RA and E groups on day 7. AKAP3 gene expression on day 7 of miPSCs decreased in RA and E groups. Flow cytometry data indicated that 3%-8% of the cells in sub-G1 stage were haploid after RA and E induction compared to other groups on day 4. This study showed that miPSCs possess the power for differentiating into male germ cells in vitro via formation of embryoid body by RA with/or E induction.

The role of microRNAs in embryonic stem cell and induced pluripotent stem cell differentiation in male germ cells.

New perspectives have been opened by advances in stem cell research for reproductive and regenerative medicine. Several different cell types can be differentiated from stem cells (SCs) under suitable in vitro and in vivo conditions. The differentiation of SCs into male germ cells has been reported by many groups. Due to their unlimited pluripotency and self-renewal, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can be used as valuable tools for drug delivery, disease modeling, developmental studies, and cell-based therapies in regenerative medicine. The unique features of SCs are controlled by a dynamic interplay between extrinsic signaling pathways, and regulations at epigenetic, transcriptional and posttranscriptional levels. In recent years, significant progress has been made toward better understanding of the functions and expression of specific microRNAs (miRNAs) in the maintenance of SC pluripotency. miRNAs are short noncoding molecules, which play a functional role in the regulation of gene expression. In addition, the important regulatory role of miRNAs in differentiation and dedifferentiation has been recently demonstrated. A balance between differentiation and pluripotency is maintained by miRNAs in the embryo and stem cells. This review summarizes the recent findings about the role of miRNAs in the regulation of self-renewal and pluripotency of iPSCs and ESCs, as well as their impact on cellular reprogramming and stem cell differentiation into male germ cells.

Protective effect of oestrogen receptor α-PvuII transition against idiopathic male infertility: a case-control study and meta-analysis.

RESEARCH QUESTION: Is there any genetic association between oestrogen receptor alpha [ERα]-PvuII polymorphism and idiopathic male infertility? DESIGN: A total of 226 infertile and 213 fertile men participated in the present case-control study. ERα-PvuII genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] method. Meta-analysis was also performed by pooling data collected from seven other eligible studies identified by searches of PubMed, Embase, Google Scholar, and Science Direct databases. Summary odds ratios were estimated by fixed- or random-effects models. The molecular effects of ERα-PvuII polymorphism were evaluated by bioinformatics tools. RESULTS: A significant protective association was reported between ERα-PvuII and male infertility in the homozygote model [OR=0.54, 95%CI=0.3-0.98, p=0.042]. Also, a similar association was observed in asthenozoospermia subgroup [OR=0.4, 95%CI=0.18-0.9, p=0.025]. Meta-analysis also revealed that the ER-PvuII polymorphism was significantly associated with the decreased risk of male infertility in the heterozygote co-dominant model [OR=0.80, 95%CI=0.64-0.99, p=0.042]. Moreover, similar protective results were reported in stratified analyses in Caucasian subgroup in the dominant genetic model [OR=0.66, 95%CI=0.45-0.96, p=0.029] and in the heterozygote co-dominant model [OR=0.62, 95%CI=0.41-0.93, p=0.021]. A significant association was also found in studies with sample size of less than 400 subjects in heterozygote co-dominant model [OR=0.69, 95%CI=0.50-0.95, p=0.023]. The bioinformatics data indicated that ER-PvuII polymorphism could significantly affect RNA structure of ERα [p=0.004]. CONCLUSION: The ERα-PvuII polymorphism could be considered as a possible protective factor against male infertility.

Studies on combination of oxaliplatin and dendrosomal nanocurcumin on proliferation, apoptosis induction, and long non-coding RNA expression in ovarian cancer cells.

Drug resistance remains a major challenge in the treatment of patients with ovarian cancer. Therefore, the development of new anticancer drugs is a clinical priority to develop more effective therapies. New approaches to improve clinical outcomes and limit the toxicity of anticancer drugs focus on chemoprevention. The aim of this study was to determine the effects of dendrosomal nanocurcumin (DNC) and oxaliplatin (Oxa) and their combination on cell death and apoptosis induction in human ovarian carcinoma cell lines analyzed by MTT assay and flow cytometry, respectively. The synergism effect of Oxa and DNC was analyzed using the equation derived from Chou and Talalay. In addition, real-time PCR was used to measure the effect of this combination on the expression levels of long non-coding RNAs with different expression in ovarian cancer and normal ovaries. Our data showed that the effect of DNC on cell death is more than curcumin alone in the same concentration. The greatest cell death effect was observed in combination of Oxa with DNC, while Oxa was added first, followed by DNC at 4 h interval (0/4 h). The findings indicated that DNC induced apoptosis significantly in both cell lines as compared to control groups; however, combination of both agents had no significant effect in apoptosis induction. In addition, combination of both agents significantly affects the relative expression of long non-coding RNAs investigated in the study as compared with mono therapy.

Prenatal exposure to diesel exhaust particles causes anxiety, spatial memory disorders with alters expression of hippocampal pro-inflammatory cytokines and NMDA receptor subunits in adult male mice offspring.

Air pollution by Diesel exhaust (DE) consists of gaseous compounds and diesel exhaust particles (DEPs). Previous studies show associations between prenatal exposure to diesel exhaust affects the central nervous system (CNS). However, there was not reported that these effects were caused by gaseous compounds, diesel exhaust particles, or both. A limited number of studies in rodent models have shown that exposure to DEPs can result in CNS. Here, we explored the effects of prenatal exposure to DEPs on anxiety and learning and memory in NMRI mice male offspring. Three groups of pregnant mice were exposed to 350-400 µg DEPs/m3 for 2, 4 and 6 h daily in a closed system room. We examined anxiety and learning and memory in 8-to-9-week-old male offspring using the Elevated plus maze and Morris water maze (MWM) test. Hippocampi were isolated after the behavioral tests and measured pro-inflammatory cytokines and N-methyl-D-aspartate (NMDA) receptor expression by quantitative RT-PCR analysis. Mice exposed to DEPs in utero showed deficits in the Elevated plus maze and Morris water maze test. In addition, DEPs exposed mice exhibited decreased hippocampal NR2A and NR3B expression. Taken together, our data suggest that maternal DEP exposure is associated with anxiety, disrupts learning and memory and reduction hippocampal NR2A and NR3B expression in male offspring.

Application of induced pluripotent stem cell and embryonic stem cell technology to the study of male infertility.

Stem cells (SCs) are classes of undifferentiated biological cells existing only at the embryonic, fetal, and adult stages that can divide to produce specialized cell types during fetal development and remain in our bodies throughout life. The progression of regenerative and reproductive medicine owes the advancement of respective in vitro and in vivo biological science on the stem cell nature under appropriate conditions. The SCs are promising therapeutic tools to treat currently of infertility because of wide sources and high potency to differentiate. Nevertheless, no effective remedies are available to deal with severe infertility due to congenital or gonadotoxic stem cell deficiency in prepubertal childhood. Some recent solutions have been developed to address the severe fertility problems, including in vitro formation of germ cells from stem cells, induction of pluripotency from somatic cells, and production of patient-specific pluripotent stem cells. There is a possibility of fertility restoration using the in vitro formation of germ cells from somatic cells. Accordingly, the present review aimed at studying the literature published on the medical application of stem cells in reproductive concerns.

Arg399Gln substitution in XRCC1 as a prognostic and predictive biomarker for prostate cancer: Evidence from 8662 subjects and a structural analysis.

BACKGROUND: The Arg399Gln polymorphism in the X-ray repair cross-complementing group 1 gene (XRCC1) may alter the risk of prostate cancer (PCa). The present study aimed to investigate the association of the XRCC1-Arg399Gln polymorphism with PCa risk in an Iranian population, as followed by a meta-analysis and an in silico analysis. METHODS: In a case-control study, 360 subjects were included (180 men with PCa and 180 healthy controls). XRCC1-Arg399Gln genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. In the meta-analysis, 14 eligible studies were included to which our case-control data were added to estimate the pooled odds ratios. Some bioinformatics tools were employed to evaluate the effects of Arg399Gln substitution on molecular aspects of the XRCC1 protein. RESULTS: Our case-control study revealed a significant association between the XRCC1-Arg399Gln polymorphism and PCa risk. The data from overall meta-analysis showed significant associations between the mentioned polymorphism and PCa risk in allelic and recessive genetic models. In addition, we observed statistically significant associations in stratified analyses by ethnicity, sample size and source of controls. Our in silico analysis showed that Arg399Gln substitution could be damaging with respect to the function and structure of the XRCC1 protein. CONCLUSIONS: Based on these results, the XRCC1-Arg399Gln polymorphism might be a risk factor for PCa and it could be considered as a prognostic and predictive biomarker for susceptible men.

Derivation of male germ cells from induced pluripotent stem cells by inducers: A review.

Induced pluripotent stem cells (iPSCs) refer to stem cells that are artificially produced using a new technology known as cellular reprogramming, which can use gene transduction in somatic cells. There are numerous potential applications for iPSCs in the field of stem cell biology becauase they are able to give rise to several different cell features of lineages such as three-germ layers. Primordial germ cells, generated via in vitro differentiation of iPSCs, have been demonstrated to produce functional gametes. Therefore, in this review we discussed past and recent advances in the in vitro differentiation of germ cells using pluripotent stem cells with an emphasis on iPSCs. Although this domain of research is still in its infancy, exploring development mechanisms of germ cells is promising, especially in humans, to promote future reproductive and developmental engineering technologies. While few studies have evaluated the ability and efficiency of iPSCs to differentiate toward male germ cells in vitro by different inducers, the given effect was investigated in this review.

The combination of retinoic acid and estrogen can increase germ cells genes expression in mouse embryonic stem cells derived primordial germ cells.

Generation of germ cells from embryonic stem cells in vitro could have great application for treating infertility. The temporal expression profile of several genes was expressed at different stages of germ cell development and examined in differentiation the mouse embryonic stem cells. Cells were treated in three groups of control, with 10-8 M of all-trans retinoic acid and the combination of 10-9 M of 17ß-Estradiol and retinoic acid for 7, 12, 17 or 22 days. Quantitative RT-PCR and Immunofluorescent were used to investigate the possible inductive effects of estrogen on mouse embryonic stem cell-derived primordial germ cells. mRNA expression of Oct4 and Dazl were downregulated in embryonic stem cells by the retinoic acid group, whereas Mvh transcription was reduced by retinoic acid and estrogen group in these cells compared to the control group. But, retinoic acid with estrogen group-treated cells exhibited increased mRNA expression of Stra8, Fragilis, Sycp3, GDF9, and Stella compared to untreated controls. The expression of Stella and Mvh proteins were remarkably increased in cell colonies. This study shows that estrogen affects the expression of specific markers of primordial germ cells. Also, estrogen and retinoic acid speed up and increase the level of expression of specific markers.

IL-1RA VNTR and IL-1α 4845G>T polymorphisms and risk of idiopathic male infertility in Iranian men: A case-control study and an in silico analysis.

This study aimed to investigate the association of IL-1RA VNTR and IL-1α 4845G>T polymorphisms with idiopathic male infertility followed by an in silico analysis. In a case-control study, we collected blood samples from 230 infertile and 230 healthy men. Genotyping of IL-1RA VNTR was performed by PCR whereas IL-1α 4845G>T was genotyped by polymerase chain reaction-restriction fragment length polymorphism. An in silico approach was employed for the detection of IL-1RA VNTR and IL-1α 4845G>T effects on some molecular aspects of IL-1RA and IL-1α respectively. The result of our genetic association study for IL-1α 4845G>T revealed that there was a significant association between GT genotype, TT genotype, T allele and idiopathic male infertility. Although there was no significant association between IL-1RA VNTR and male infertility in the overall analysis. However, subgroup analysis revealed that the subjects with VNTR 4R/5R genotype were at a higher risk of oligozoospermia. Furthermore, 4845TT genotype, and 4845T allele were associated with oligozoospermia, asthenozoospermia and nonobstructive azoospermia. Bioinformatics analysis showed that IL-1RA VNTR may affect the splicing pattern of IL-1RA. Moreover, IL-1α 4845G>T has a significant effect on RNA structure and protein function. Based on our findings, both IL-1RA VNTR and IL-1α 4845G>T polymorphisms could be considered as potential biomarkers for screening of susceptible individuals.

Dysregulated expression of long noncoding RNAs in gynecologic cancers.

Cancers of the female reproductive system include ovarian, uterine, vaginal, cervical and vulvar cancers, which are termed gynecologic cancer. The emergence of long noncoding RNAs (lncRNAs), which are believed to play a crucial role in several different biological processes, has made the regulation of gene expression more complex. Although the function of lncRNAs is still rather elusive, their broad involvement in the initiation and progression of various cancers is clear. They are also involved in the pathogenesis of cancers of the female reproductive system. LncRNAs play a critical physiological role in apoptosis, metastasis, invasion, migration and cell proliferation in these cancers. Different expression profiles of lncRNAs have been observed in various types of tumors compared with normal tissues and between malignant and benign tumors. These differential expression patterns may lead to the promotion or suppression of cancer development and tumorigenesis. In the current review, we present the lncRNAs that show a differential expression between cancerous and normal tissues in ovarian, cervical and endometrial cancers, and highlight the associations between lncRNAs and some of the molecular pathways involved in these cancers.