RARS1-related hypomyelinating leukodystrophy-9 (HLD-9) in two distinct Iranian families: Case report and literature review.

BACKGROUND: Hypomyelinating leukodystrophy-9 (HLD-9) is caused by biallelic pathogenic variants in RARS1, which codes for the cytoplasmic tRNA synthetase for arginine (ArgRS). This study aims to evaluate the clinical, neuroradiological, and genetic characteristics of patients with RARS1-related disease and determine probable genotype-phenotype relationships. METHODS: We identified three patients with RARS1 homozygous pathogenic variants. Furthermore, we performed a comprehensive review of the literature. RESULTS: Homozygous variants of RARS1 (c.2T>C (p.Met1Thr)) were identified in three patients with HLD-9. Clinical symptoms were severe in all patients. Following the literature review, thirty HLD-9 cases from eight studies were found. The 33 patients' main symptoms were hypomyelination, language delay, and intellectual disability or developmental delay. The mean age of onset for HLD9 in the group of 33 patients with a known age of onset was 5.8 months (SD = 8.1). The interquartile range of age of onset was 0-10 months. Of the 25 variants identified, c.5A>G (p.Asp2Gly) was identified in 11 patients. CONCLUSION: Pathogenic variants in RARS1 decrease ArgRS activity and cause a wide range of symptoms, from severe, early onset epileptic encephalopathy with brain atrophy to a mild condition with relatively maintained myelination. These symptoms include the classic hypomyelination presentation with nystagmus and spasticity. Furthermore, the pathogenicity of the variation c.2T>C (p.Met1Thr) has been shown.

Genetic Analysis of 27 Y-STR Haplotypes in 11 Iranian Ethnic Groups.

BACKGROUND: The study of Y-chromosomal variations provides valuable insights into male susceptibility in certain diseases like cardiovascular disease (CVD). In this study, we analyzed paternal lineage in different Iranian ethnic groups, not only to identify developing medical etiology, but also to pave the way for gender-specific targeted strategies and personalized medicine in medical genetic research studies. METHODS: The diversity of eleven Iranian ethnic groups was studied using 27 Y-chromosomal short tandem repeat (Y-STR) haplotypes from Y-filer® Plus kit. Analysis of molecular variance (AMOVA) based on pair-wise RST along with multidimensional scaling (MDS) calculation and Network phylogenic analysis was employed to quantify the differences between 503 unrelated individuals from each ethnicity. RESULTS: Results from AMOVA calculation confirmed that Gilaks and Azeris showed the largest genetic distance (RST=0.35434); however, Sistanis and Lurs had the smallest considerable genetic distance (RST=0.00483) compared to other ethnicities. Although Azeris had a considerable distance from other ethnicities, they were still close to Turkmens. MDS analysis of ethnic groups gave the indication of lack of similarity between different ethnicities. Besides, network phylogenic analysis demonstrated insignificant clustering between samples. CONCLUSION: The AMOVA analysis results explain that the close distance of Azeris and Turkmens may be the effect of male-dominant expansions across Central Asia that contributed to historical and demographics of populations in the region. Insignificant differences in network analysis could be the consequence of high mutation events that happened in the Y-STR regions over the years. Considering the ethnic group affiliations in medical research, our results provided an understanding and characterization of Iranian male population for future medical and population genetics studies.

Discriminative features in White-Sutton syndrome: literature review and first report in Iran.

White-Sutton Syndrome is one of the rare neurodevelopmental disorder inherited in an autosomal dominant manner, mainly caused by de novo mutations in the POGZ gene and shows many phenotypic signs such as intellectual disability, Autism Spectrum Disorder and other spectra. About 70 patients with this syndrome have been reported worldwide. In this paper, we have described different phenotypic features of the White-Sutton Syndrome with a brief review of recent literatures. Finally, we have reported an Iranian male with intellectual disability and visual impairment. We have explained the clinical symptoms of the patient and have compared the patient's phenotype with existing data from individuals with White-Sutton Syndrome. The results of Whole Exome Sequencing test, performed for the patient, declared the presence of a de novo mutation in POGZ gene and confirmed the White-Sutton Syndrome diagnosis.

Association of MMP2 and MMP9 gene polymorphisms with nonsyndromic cleft lip/palate in an Iranian population.

Background: Cleft lip/palate (CL/P) is a prevalent congenital disorder. Matrix metalloproteinases (MMPs) play a role in palatogenesis and have been proposed to be associated with nonsyndromic CL/P development. This study aimed to examine the association of MMP2 (rs243866) and MMP9 (rs3918242) gene polymorphism with nonsyndromic CL/P in an Iranian population. Methods: Blood samples were collected from 120 nonsyndromic CL/P patients and 140 healthy newborns in this case-control study. DNA extraction was performed by the salting-out method, and the samples underwent polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), using Pag and SphI enzymes, for genotyping MMP2 and MMP9 gene polymorphisms. Statistical analysis was performed with SPSS 11.5. Univariate and multivariate logistic regression models were used to calculate the odds ratios and 95% confidence intervals (CIs). The level of statistical significance was set at P<0.05. Results: No significant association was found between MMP2 gene polymorphism and nonsyndromic CL/P. However, the MMP9 gene polymorphism had a significant association with nonsyndromic CL/P, with a higher prevalence of the T allele and TT genotype in the case group than the control group. Conclusion: This study indicated a potential link between MMP9 gene polymorphism and nonsyndromic CL/P in an Iranian population. Future investigations with greater sample diversity and larger sample sizes are required to obtain more comprehensive and robust evidence. In-depth analyses and studies involving different ethnic groups can further enhance our understanding of the genetic underpinnings of CL/P.

Whole-exome sequencing revealed a novel homozygous missense variant in OSGEP gene: a case report of Galloway-Mowat syndrome in Iran.

Galloway-Mowat syndrome is a rare autosomal-recessive genetic disorder that is characterized by variety of complications such as neurological abnormalities and early-onset progressive kidney disease. Studies have been shown that pathogenic mutations in genes that belong to the KEOPS complex lead to Galloway-Mowat syndrome. Several pathogenic mutations in OSGEP gene, a member of the KEOPS complex, have been detected in Galloway-Mowat syndrome. Here we describe a 12-year-old male with intellectual disability, poor speech, seizures, microcephaly, and nephrotic syndrome that were in favor of Galloway-Mowat syndrome, born to a healthy Iranian consanguineous parents. Extracted genomic DNA from blood sample was used to perform whole-exome sequencing in the patient. The mutational screening revealed a novel homozygote OSGEP gene missense variant. Our finding established whole-exome sequencing as a valuable technic for the detection of rare variants.

A Panel of Circulating microRNAs as a Potential Biomarker for the Early Detection of Gastric Cancer.

Background: The high mortality rate of Gastric Cancer (GC) is a consequence of delayed diagnosis. The early diagnosis of GC could increase the five-year survival rate among patients. We aimed to find a panel of microRNAs (miRNA) for the detection of GC in the early stages. Methods: In this case-control study, we selected consistently upregulated miRNAs from the results of 12 high-throughput miRNA profiling studies in GC. In the profiling phase, the differential expressions of 13 candidate miRNAs were analyzed by quantitative reverse-transcription PCR (qRT-PCR) in two pooled RNA samples prepared from the plasma of eight GC patients and eight matched controls. In the validation phase, significantly upregulated miRNAs from the profiling phase were further evaluated in the plasma samples of 97 patients with stage I-IV gastric adenocarcinoma and 100 healthy controls. Results: In the profiling phase, six miRNAs (miR-18a, 21, 25, 92a, 125b and 221) were significantly upregulated in the GC patients compared to the controls (p<0.05). However, in the validation phase, only significant up-regulation of miR-18a, 21 and 125b was confirmed (p<0.05). A panel of miR-18a/21/125b was able to detect GC patients with stage I-IV from the controls (p<0.001; AUC=0.92, sensitivity=86%; specificity=85%). In addition, the panel could distinguish the early-stage GC (I+II) from the control group with an AUC of 0.83, a sensitivity of 83%, and a specificity of 75%. Conclusion: A panel of circulating miR18a/21/125b could be suggested as a potential biomarker for the early detection of GC.

Protective effects of Herbal Compound (IM253) on the inflammatory responses and oxidative stress in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a multifactorial chronic inflammatory demyelinating disease of the central nervous system with both immune and neurodegenerative components as the underlying causes. Cytokines are key components of the inflammatory processes and their crucial roles in the inflammatory aspect of MS are undeniable. Several studies have pointed to the apparent change in Cytokines in MS. The aim of this study was to investigate the effects of IM253 treatment on inflammation and antioxidant defense in the cerebral corpus callosum of the C57BL/6 mouse, an Experimental autoimmune encephalomyelitis (EAE) model and as a most commonly used experimental model of MS. During the course of study, clinical evaluation was performed and eventually histological and molecular analysis on brain samples was carried out. Gene expression analyses demonstrated that treatment with IM253 causes a significant reduction in the expression of pro-inflammatory cytokine coding genes including IL-6, TNF-α, IFN-γ, and IL-17 as well as a significant increase in the expression of anti-inflammatory and anti-oxidant enzyme coding genes including TGF-ß, GPX-1, and Cat. Histological studies also show that treatment with IM253 can reduce demyelination and inflammation (p<0.001). In addition, the GPX-1 enzyme activity evaluation also demonstrated that total antioxidant capacity was significantly higher in IM253 treated mice (p<0.001). Overall, our results suggest that IM253 could ameliorate the severity of EAE, probably because of its anti-inflammatory and anti-oxidant properties, and support the preclinical effects of IM253 as a potential therapeutic intervention.

Association of rs2013162 and rs2235375 Polymorphisms in IRF6 Gene with Susceptibility to Non-Syndromic Cleft Lip and Palate.

Background: Non-syndromic cleft lip occurs by the interaction of environmental and genetic factors. The purpose of the current study was to analyze the association of Single Nucleotide Polymorphisms (SNPs) in IRF6 and NSCL/P in an Iranian population. Methods: A group of 105 children with NSCL/P and 185 normal controls were included in the current study. Genotyping of IRF6 rs2013162 and rs2235375 was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results: A substantial association of AA and CA genotypes in rs2013162 with the risk of NSCL/P (AA vs. CC; OR=2.36; 95%CI [1.05-5.29], p=0.004; and CA vs. CC; OR=0.47; 95%CI [0.28-0.79], p=0.018) was found. However, there were no important associations between A allele and risk of NSCL/P (p=0.980). According to logistic regression analysis results, subjects with GG genotype and G allele in rs2235375 polymorphism had increased risk of NSCL/P. Conclusion: The IRF6 polymorphisms are associated with the susceptibility to NSCL/P in Iranian population.

Identification of causative gene mutation in an Iranian family with coloboma and nephropathy using whole exome sequencing.

Pathogenic variants in FAT1 gene have recently been described in association with coloboma, nephropathy, and facial dismorphism. Here we describe a 5-year-old Iranian boy with iris coloboma and nephropathy, born to an Iranian family. Extracted genomic DNA from blood sample was used to perform whole exome sequencing in the patient. The mutational screening revealed a homozygote Fat1 gene mutation c.5320A > G (p.17747Val), not previously reported in homozygote state in Iran. Our findings establish FAT1 as a gene with pleiotropic effects in human, emphasizing it as one of the causative genes in syndromic nephropathies.

Molecular characterization of a large cohort of mucopolysaccharidosis patients: Iran Mucopolysaccharidosis RE-diagnosis study (IMPRESsion).

Mucopolysaccharidoses (MPSs) are rare, heterogeneous inborn errors of metabolism (IEM) diagnosed through a combination of clinical, biochemical, and genetic investigations. The aim of this study was molecular characterization of the largest cohort of Iranian MPS patients (302 patients from 289 unrelated families), along with tracking their ethnicity and geographical origins. 185/289 patients were studied using an IEM-targeted NGS panel followed by complementary Sanger sequencing, which led to the diagnosis of 154 MPS patients and 5 non-MPS IEMs (diagnostic yield: 85.9%). Furthermore, 106/289 patients who were referred with positive findings went through reanalysis and confirmatory tests which confirmed MPS diagnosis in 104. Among the total of 258 MPS patients, 225 were homozygous, 90 harbored novel variants, and 9 had copy number variations. MPS IV was the most common type (34.8%) followed by MPS I (22.7%) and MPS VI (22.5%). Geographical origin analysis unveiled a pattern of distribution for frequent variants in ARSB (c.430G>A, c.962T>C [p.Leu321Pro], c.281C>A [p.Ser94*]), GALNS (c.319G>A [p.Ala107Thr], c.860C>T [p.Ser287Leu], c.1042A>G [p.Thr348Ala]), and IDUA (c.1A>C [p.Met1Leu], c.1598C>G [p.Pro533Arg], c.1562_1563insC [p.Gly522Argfs*50]). Our extensive patient cohort reveals the genetic and geographic landscape of MPS in Iran, which provides insight into genetic epidemiology of MPS and can facilitate a more cost-effective, time-efficient diagnostic approach based on the region-specific variants.

Electrophysiology of Human Gametes: A Systematic Review.

PURPOSE: Oocytes and spermatozoa are electrogenic cells with the ability to respond to electrical stimuli and modulate their electrical properties accordingly. Determination of the ionic events during the gamete maturation helps to design suitable culture media for gametes in assisted reproductive technology (ART). The present systematic review focuses on the electrophysiology of human gametes during different stages of maturation and also during fertilization. MATERIALS AND METHODS: The reports published in the English language between January 2000 and July 2021 were extracted from various electronic scientific databases following the PRISMA checklist using specific MeSH keywords. RESULTS: Subsequent to the screening process with defined inclusion and exclusion criteria, 60 articles have been included in this review. Among them, 11 articles were directly related to the electrophysiology of human oocytes and 49 physiology department to the electrophysiology of human spermatozoa. CONCLUSIONS: Gametes generate electrical currents by ionic exchange, particularly Na+, K+, Cl-, H+, Zn2+, Cu2+, Se2+, Mg2+, HCO3-, and Ca2+ through specific ion channels in different stages of gamete maturation. The ionic concentrations, pH, and other physicochemical variables are modulated during the gametogenesis, maturation, activation, and the fertilization process following gamete function and metabolism. The electrical properties of human gametes change during different stages of maturation. Although it is demonstrated that the electrical properties are significant regulators of cell signaling and are fundamental to gamete maturation and fertilization, their exact roles in these processes are still poorly understood. Further research is required to unveil the intricate electrophysiological processes of human gamete maturation.

Whole Exome Sequencing Identified the Causative Mutation in a 4-Year-Old Female with Mulibrey Nanism: A Case Report.

Mulibrey Nanism is a rare multisystem disorder inherited in an autosomal recessive manner caused by mutations in the TRIM37 gene. Most of the reported cases are from Finland, but this condition has rarely occurred in other countries. Although the clinical diagnosis of Mulibrey nanism is a challenge during the first months of life, the disease can be suspected clinically due to the distinctive features of the patients. A 4-year-old female with pneumonia, cardiomyopathy, growth retardation, peripheral edema, and characteristic craniofacial features was referred to Tehran Hope Generation Foundation Genetic diagnosis Center, in October 2021. Genomic DNA was isolated from peripheral blood samples of the patient and her parents and Whole exome sequencing was performed for the patient. Whole exome sequencing revealed a homozygous G>A splice site variant (TRIM37; c.370-1G>A). Sanger sequencing confirmed the segregation of the variant with phenotype in this family. Whole exome sequencing can be helpful in the diagnosis of the patients suspecting to Mulibrey nanism and lacking sufficient clinical presentation according to the diagnostic algorithm.

Identification of a Novel Homozygous Mutation in BBS10 Gene in an Iranian Family with Bardet-Biedl Syndrome.

BACKGROUND: Bardet-Biedl Syndrome (BBS) is a rare pleiotropic autosomal recessive disease related to ciliopathies with approximately 25 causative genes. BBS is a multisystemic disorder with wide spectrum of manifestations including truncal obesity, retinal dystrophy, male hypogenitalism, postaxial polydactyly, learning difficulties, and renal abnormalities. METHODS: A consanguineous Iranian family with a 28-year-old daughter affected with BBS, resulting from a first cousin marriage, was examined. After clinical examination, Whole Exome Sequencing (WES) was applied. Following the analysis of exome data, Sanger sequencing was used to confirm as well as to co-segregate the candidate variant with the phenotype. RESULTS: A novel homozygous variant [c. 2035G>A (p.E679K)] in exon 2 of the BBS10 gene was found which was categorized as likely pathogenic based on American College of Medical Genetics and Genomics (ACMG) guidelines and criteria. In this study, the variant was fully co-segregated with the phenotype in the family. CONCLUSION: Despite overlapping with other ciliopathies in terms of the phenotype, the BBS has high genetic heterogeneity and clinical variability even among affected members of a family. The symptoms observed in patients are largely related to the genes involved and the type of mutations in the BBS. In this study, in addition to phenotype description of the proband harboring a novel disease-causing variant in BBS10 gene, the spectrum of BBS symptoms was expanded. The findings of this study can be useful in genetic counseling, especially for risk estimation and prenatal diagnosis.

Shikonin ameliorates experimental autoimmune encephalomyelitis (EAE) via immunomodulatory, anti-apoptotic and antioxidative activity.

OBJECTIVES: Multiple sclerosis is a common autoimmune inflammatory disease of the central nervous system. There are several underlying mechanisms for the pathogenesis of the disease, including inflammation, oligodendrocyte apoptosis and oxidative stress. METHODS: The mechanism of action of shikonin was investigated in the C57BL/6 experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. KEY FINDINGS: The results revealed that EAE induction significantly increased the extent of demyelination in the corpus callosum tissues of the animals, while treatment of the mice with shikonin significantly decreased the extent of demyelination. Real-time polymerase chain reaction-based analysis of the brain samples from the EAE mice revealed significant enhancement in the expression levels of tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and Bax genes as well as a reduction in the expression levels of transforming growth factor-ß (TGF-ß) and Bcl2. But, shikonin treatment significantly reduced the expression levels of TNF-α, IFN-γ and Bax. On the other hand, the expression levels of TGF-ß and Bcl2 as well as the activity of glutathione peroxidase-1 (GPX-1) enzyme were significantly increased following the shikonin treatment. CONCLUSIONS: This study emphasized the immune-modulatory and antioxidative effects of shikonin, which may have an important healing effect on the severity of EAE.

Methylation Analysis of P16, RASSF1A, RPRM, and RUNX3 in Circulating Cell-Free DNA for Detection of Gastric Cancer: A Validation Study.

BACKGROUND: Most of Gastric Cancer (GC) patients are diagnosed at an advanced stage with poor prognosis. Hypermethylations of several tumor suppressor genes in cell-free DNA of GC patients have been previously reported. In this study, an attempt was made to investigate the methylation status of P16, RASSF1A, RPRM, and RUNX3 and their potentials for early diagnosis of GC. METHODS: Methylation status of the four tumor suppressor genes in 96 plasma samples from histopathologically confirmed gastric adenocarcinoma patients (Stage I-IV) and 88 healthy controls was determined using methylation-specific PCR method. Receiver operating characteristic curve analysis was performed and Area Under the Curve (AUC) was calculated. Two tailed p<0.05 were considered statistically significant. RESULTS: Methylated P16, RASSF1A, RPRM, and RUNX3 were significantly higher in the GC patients (41.7, 33.3, 66.7, and 58.3%) compared to the controls (15.9, 0.0, 6.8, and 4.5%), respectively (p<0.001). Stratification of patients showed that RPRM (AUC: 0.70, Sensitivity: 0.47, Specificity: 0.93, and p<0.001) and RUNX3 (AUC: 0.77, Sensitivity: 0.59, Specificity: 0.95, and p<0.001) had the highest performances in detection of early-stage (I+II) GC. The combined methylation of RPRM and RUNX3 in detection of early-stage GC had a higher AUC of 0.88 (SE=0.042; 95% CI:0.793-0.957; p<0.001), higher sensitivity of 0.82 and reduced specificity of 0.89. CONCLUSION: Methylation analysis of RPRM and RUNX3 in circulating cell free-DNA of plasma could be suggested as a potential biomarker for detection of GC in early-stages.

Novel Bi-allelic PDE6C Variant Leads to Congenital Achromatopsia.

Background: The clinical phenotyping of patients with achromatopsia harboring variants in phosphordiesterase 6C (PDE6C) has poorly been described in the literature. PDE6C encodes the catalytic subunit of the cone phosphodiesterase, which hydrolyzes the cyclic guanosine monophosphate that proceeds with the hyperpolarization of photoreceptor cell membranes, as the final step of the phototransduction cascade. Methods: In the current study, two patients from a consanguineous family underwent full ophthalmologic examination and molecular investigations including WES. The impact of the variant on the functionality of the protein has been analyzed using in silico molecular modeling. Results: The patients identified with achromatopsia segregated a homozygous missense variant (c.C1775A:p.A592D) in PDE6C gene located on chromosome 10q23. Molecular modeling demonstrated that the variant would cause a protein conformational change and result in reduced phosphodiesterase activity. Conclusion: Our data extended the phenotypic spectrum of retinal disorders caused by PDE6C variants and provided new clinical and genetic information on achromatopsia.

MiR-4485-3p expression reduced in spermatozoa of men with idiopathic asthenozoospermia.

Asthenozoospermia (AZS), which characterised by reduced forward sperm motility, is a common cause of male infertility. Recently, mitochondrial dysfunction reported in AZS men came to attention for finding the molecular aetiology of AZS. Mitochondria-related microRNAs (miRNAs) are the most important regulators of mitochondrial function through post-transcriptionally modulation of gene expression. Therefore, this study aims to evaluate the expression of four recently reported mitochondrial-related miRNAs (miR-4485-3p/4484/4461 and 4463) in the sperm sample of asthenozoospermic men. RNA was extracted from spermatozoa of 74 volunteers (39 patients with idiopathic AZS and 35 controls with normal fertility), and relative gene expression analysis was performed by quantitative PCR. We used SNORD48 as a normaliser gene, and quantification was calculated by 2-ΔΔCt method. The expression of miR-4484 and miR-4461 was not detected in the spermatozoa of cases and controls. However, miR-4485-3p (p = .006) was significantly downregulated in the AZS men compared with the controls, but the miR-4463 expression was not significantly different between the two groups (p = .5). Bioinformatic analysis identified three target genes for miR-4485-3p (DNAH1, KIT and PARK7) that are related to male infertility. In conclusion, the downregulation of miR-4485-3p was associated with idiopathic AZS, which could be a molecular link between mitochondrial dysfunction and AZS.

RPE65 and retinal dystrophy: Report of new and recurrent mutations.

BACHGROUND: Leber congenital amaurosis (LCA) is a severe and congenital or early onset form of inherited retinitis pigmentosa (RP). To date, approximately 25 genes have been introduced in relation to LCA. In this regard, retinal pigment epithelium-specific 65 kDa (RPE65) is a well-known gene mutation that plays a role in the pathogenesis of 5-10% of LCA cases. METHOS: Two individuals fromseparate families were subjected to ehole exome sequencing (WES). Causativevariants were searched further assessed using Sanger sequencing. RESULTS: Here, two families with mutations in the RPE65 gene show severe and early onset LCA, as expected. In addition to the characterization of the phenotype, by reporting a new mutation (c.1451-1G>A), we further expand the mutation spectrum of RPE65. Likewise, as an interesting aspect of our study, we report on a previously reported RP-linked mutation associated with severe early onset LCA (c.T200G:p.L67R). CONCLUSIONS: Considering this variant in different populations, it is likely that it represents a hotspot and affects the function of the coded protein. The variable expressivity of the phenotype can be assumed by the presence of the modifier allele(s) as a result of a different genetic background or the effect of different environments on phenotype expression.

Healing Influence of Melilotus Officinalis Herbal Extract on Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice.

The present study was designed to primarily examine the therapeutic potential of the herbal extract of Melilotus Officinalis for the treatment of multiple sclerosis in the experimental autoimmune encephalomyelitis (EAE) model of the disease. The animal model was induced in C57BL/6 female mice, and then the herbal extract was intraperitoneally administered for a total of 21 days after the first day of post-immunization. The phenotypic signs, a gene expression profile of inflammatory cytokines, antioxidant state, and pathological hallmarks of the disease in the corpus callosum were evaluated. The prophylactic administration of Melilotus Officinalis attenuates the clinical signs of the disease. It significantly declined the gene expression of pro-inflammatory cytokines like IL-6, TNF-α, and IFN-γ. This herbal extract also surged the gene expression, as an anti-inflammatory cytokine. The gene expression of Glutathione peroxidase and Catalase (antioxidant enzymes) was meaningfully higher in the treatment group. Pathological evaluation of corpus callosum cross-sections by Luxol Fast Blue staining revealed preserved myelin sheath in the treated group compared to the EAE mice. The results of our assay confirmed that immunomodulatory and antioxidant features of the herbal extract of Melilotus Officinalis ameliorated the EAE severity. This study finding disclosed the therapeutic efficiency of this compound in MS treatment.

Genetic aspects of idiopathic asthenozoospermia as a cause of male infertility.

Infertility is a worldwide problem affecting about 15% of couples trying to conceive. Asthenozoospermia (AZS) is one of the major causes of male infertility, diagnosed by reduced sperm motility, and has no effective therapeutic treatment. To date, a few genes have been found to be associated with AZS in humans and mice, but in most of cases its molecular aetiology remains unknown. Genetic causes of AZS may include chromosomal abnormalities, specific mutations of nuclear and mitochondrial genes. However recently, epigenetic factors, altered microRNAs expression signature, and proteomics have shed light on the pathophysiological basis of AZS. This review article summarises the reported genetic causes of AZS.