Unraveling the dark matter, long non-coding RNAs, in male reproductive diseases: A narrative review

Recent advances in human transcriptome have revealed the fundamental and functional roles of long non-coding RNA in the susceptibility to diverse diseases and pathological conditions. They participate in wide range of biological processes such as the modulating of chromatin structure, transcription, translation, and posttranslation modification. In addition, based on their unique expression profiles and their association with clinical abnormalities such as those of related to male reproductive diseases, they can be used to develop therapeutic methods and biomarkers for screening of the diseases. In this study, we will review the identified lncRNAs and their molecular functions in the pathogenesis of male reproductive diseases such as prostate cancer, benign prostatic hyperplasia, prostatitis, testicular cancer, varicocele, and sperm abnormalities. Key words: Long noncoding RNA, Prostate cancer, Prostatic hyperplasia, Prostatitis, Varicocele, Sperm abnormalities

Association study of ESR1 rs9340799, rs2234693, and MMP2 rs243865 variants in Iranian women with premature ovarian insufficiency: A case-control study

Background: Primary ovarian insufficiency (POI) is a rare disease clinically characterized by ovarian follicles depletion or dysfunction and menopause before the age of 40 yr as the cut-off age for POI. It is a complex disease, and its etiology involves several factors. However, genetic factors have a predominant role in the susceptibility to the disease. Objective: This study aims to investigate the polymorphisms of rs243865 in the matrix metallopeptidase 2 (MMP2) gene and rs2234693 and rs9340799 in the estrogen receptor 1 (ESR1) gene with susceptibility to POI in Iranian women under 35 yr. Materials and Methods: This case-control study was performed on 150 women with POI and 150 healthy women who were referred to Yazd Reproductive Sciences Institute, Yazd, Iran between May-October 2020. The genotyping of ESR1 rs9340799, rs2234693, and MMP2 rs243865 polymorphism was done using tetra-amplification refractory mutation system-polymerase chain reaction. In addition, haplotype analysis and linkage disequilibrium were investigated by SNPanalyzer software. Results: Our study revealed the frequency of rs243865 TT, CC genotypes in the MMP2 gene and rs2234693 CC, TT; and rs9340799 GG, AA in the ESR1 gene were more prevalent in the case group compared to the control group. In addition, ESR1 rs2234693 and rs9340799 genotypes showed significant association with the development of the disease in our population. Among 4 haplotypes for 2 polymorphisms in the ESR1 gene, rs2234693T/rs9340799A haplotype was associated with conferring risk to POI. Conclusion: ESR1 rs2234693 and rs9340799 polymorphism were strongly associated with our population’s POI. Key words: Matrix metalloproteinase-2, Estrogen receptor alpha, Primary ovarian insufficiency, Female infertility

Association of HLA-DRB1 Alleles in Juvenile-onset Systemic Lupus Erythematosus (SLE) in Iranian Children

Introduction Systemic Lupus Erythematosus (SLE) is a complex autoimmune and inflammatory disease. Many studies show HLA alleles can be associated with SLE. The aim of this study was to determine the association of HLA-DRB1 alleles with juvenile- onset in Iranian children. Materials and Methods At a case – control study, 31 children with systemic lupus erythematosus (case group) who referred to Mofid Children’s Hospital, Shahid Behehsti University of Medical Sciences, Tehran, and 56 healthy children (control group) were participant.  Genomic  DNA  was  extracted  and  HLA  typing  was performed by Polymerase Chain Reaction (PCR) with Sequence - Specific Primers (SSP) technique. Results HLA- DRB1*01, HLA- DRB1*04, HLA- DRB1*11 and HLA- DRB1*13 were detected to as most frequent alleles associated with SLE in Iranian children. The frequency of HLA DRB1*08 was not significantly different in both groups (P>0.05(.  HLA- DRB1*07 had a higher rate of repetition in the control group than patients with SLE. Conclusion There was a significant difference in the frequency of some alleles between patients and controls group, which could be related to susceptibility to SLE. These differences between frequencies of some alleles in both groups may help to determine the onset of lupus in children

A nanostructured suitable platform based on multi wall carbon nanotubes and graphene nano sheets composite for determination of mefenamic acid

A mefenamic acid sensor was prepared by the modification of a glassy carbon electrode (GCE) with graphene nano-sheets (Gr) and multi wall carbon nanotubes (MWCNT). The designed sensor (MWCNT/Gr/GCE) indicated an electrocatalytic behaviour when applied for mefenamic acid (MFA) oxidation due to good conductivity, low electron transfer resistance and catalytic effect. The suggested sensor revealed a lower overvoltage and enhanced current compared with bare GCE for the oxidation of MFA. The observations indicated that the oxidation potential of MFA is decreased more than 200 mV using the designed sensor. The percentages of MWCNTs and Gr nano materials, and pH solution were optimized. Under the optimum conditions, some kinetic parameters, such as surface coverage in a 0.5 mM [Fe(CN)6]3-/4- solution was obtained by cyclic voltammetric method. The diffusion coefficient of MFA (D) was calculated to be 2.88×10-6 cm2 s-1 by chronoamperometeric technique. The MWCNT/Gr/GCE sensor exhibited a linear dynamic range for MFA (2– 100 μM) with a detection limit of 0.66 μM by differential pulse voltammetry (DPV) technique. This sensor revealed a suitable applicability for determination of MFA in real samples (drug samples and serum solutions)

Genetic Susceptibility to Transient and Permanent Neonatal Diabetes Mellitus

Neonatal diabetes mellitus (NDM) is a rare kind of diabetes characterized by hyperglycemia and low levels of insulin. Clinically, it is categorized into two main types: transient NDM (TNDM) and permanent NDM (PNDM). These types are diagnosed based on duration of insulin dependence early in the disease. In TNDM, diabetes begins in the first few weeks of life with remission in a few months. However, infant with PNDM have insulin secretory failure in the late fetal or early post-natal period with no remission. Mutation in the KCNJ11 and ABCC8 genes can cause both TNDM and PNDM, and infant with this mutation can respond to transition from insulin to sulfonylureas making identification of genes involved in the disease important for appropriate treatment

Frequency of TNFR1 36 A/G gene polymorphism in azoospermic infertile men: A case-control study

Background: Tumor necrosis factor-alpha (TNF-&alpha;) is a multifunctional cytokine that regulates different cellular activities related to spermatogenesis. Tumor necrosis factor-alpha receptor 1 (TNFR1) mediates TNF-&alpha; activity and polymorphism in TNFR1 could lead to gene dysfunction and male infertility. Objective: The aim of this study is to determine the association of TNFR1 36 A/G polymorphism with the idiopathic azoospermia in Iranian population. Materials and Methods: This case-control study included 108 azoospermic and 119 fertile men. This research investigated the frequency of TNFR1 36 A/G polymorphism in cases who were idiopathic azoospermic men referred to Yazd Research and Clinical Center for Infertility, Iran in comparison with controls. polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method was used to investigate the polymorphism in both case and control groups. PCR fragments were digested by Mspa1I enzyme and products were appeared by gel electrophoresis. The abundance of A&rarr;G was calculated in the azoospermic and healthy men. Results: According to the present study, GG and AG genotypes frequency in the azoospermic men group were higher than the control group (OR= 2.298 (1.248-4.229), p=0.007), (OR=1.47 (0.869-2.498, p=0.149). Our findings also showed that G allele frequency in azoospermic men had significant difference compared to the control group (OR=2.302 (1.580-3.355), p<0.001). Conclusion: It seems that the GG genotype and G allele have an association with increased risk of non-obstructive azoospermi

Glutathione S-transferase M1-T1 null genotypes and susceptibility to Hodgkin’s lymphoma

Hodgkin’s Lymphoma (HL) is a heterogeneous malignant disease of lymph node. The glutathione S-transferases (GSTs) have an important role in the detoxification of a wide variety of toxins and carcinogens. Studies have been indicated that genetic variation in the GST gene family may lead to susceptibility in HL. Hereby, we investigated the association of GSTT1 and GSTM1 null genotypes with HL in the Iranian population. This case-control study consisted of 76 patients suffering from HL and 120 healthy individuals as a control group. Genomic DNA was extracted and genotyping of GSTT1 and GSTM1 genes for the identification of their null genotypes was carried out using multiplex PCR method. Our findings indicated that GSTM1 null genotype is associated with risk of developing HL in our population (P=0.025; OR=2.00; 95%CI=1.110- 3.602); however, no association was found for GSTT1 null genotype. Our study also showed that the GSTM1 null genotype increased the risk of disease in the individuals younger than 45 years, and it had a positive association with low ESR. GSTM1 null genotype may have the key role in increasing the risk of HL in the Iranian population