Infertility is a multifactorial and polygenic disease. A vast majority of infertility is still unexplained despite modern diagnostic techniques. Oxidative stress is considered a factor for male infertility but etiology in terms of functional gene polymorphism and experimental studies on human subjects is scarcely reported. The aim of the study was to investigate the status of three antioxidant enzymes; catalase, superoxide dismutase (SOD), and glutathione reduced (GSH) in clinically diagnosed infertile males and find the potential association of CAT gene variant in the promoter region −21 A/T (rs7943316). The study consisted of 55 clinically diagnosed infertile males and 50 non‐infertile volunteers. The activity of antioxidant enzymes was measured through a spectrophotometer. Polymerase chain reaction–restriction fragment length polymorphism was performed for genotyping of single‐nucleotide polymorphism. Catalase enzyme activity was significantly decreased while SOD and GSH were substantially increased (p ≤ 0.01) in infertile men in comparison to non‐infertile. CAT gene variant rs7943316 had shown significant association in dominant, recessive model and allelic frequencies. The study concludes that rs7943316 has a substantial role in male infertility. The outcome of the study may help in resolving idiopathic infertility cases and may help in evolving novel diagnostic and therapeutic approaches. Other variants of CAT and antioxidant genes are suggested to ascertain further insight.
Helicobacter cinaedi is a Gram-negative bacterium from the family Helicobacteraceae and genus Helicobacter. The pathogen is a causative agent of gastroenteritis, cellulitis, and bacteremia. The increasing antibiotic resistance pattern of the pathogen prompts the efforts to develop a vaccine to prevent dissemination of the bacteria and stop the spread of antibiotic resistance (AR) determinants. Herein, a pan-genome analysis of the pathogen strains was performed to shed light on its core genome and its exploration for potential vaccine targets. In total, four vaccine candidates (TonB dependent receptor, flagellar hook protein FlgE, Hcp family type VI secretion system effector, flagellar motor protein MotB) were identified as promising vaccine candidates and subsequently subjected to an epitopes’ mapping phase. These vaccine candidates are part of the pathogen core genome: they are essential, localized at the pathogen surface, and are antigenic. Immunoinformatics was further applied on the selected vaccine proteins to predict potential antigenic, non-allergic, non-toxic, virulent, and DRB*0101 epitopes. The selected epitopes were then fused using linkers to structure a multi-epitopes’ vaccine construct. Molecular docking simulations were conducted to determine a designed vaccine binding stability with TLR5 innate immune receptor. Further, binding free energy by MMGB/PBSA and WaterSwap was employed to examine atomic level interaction energies. The designed vaccine also stimulated strong humoral and cellular immune responses as well as interferon and cytokines’ production. In a nutshell, the designed vaccine is promising in terms of immune responses’ stimulation and could be an ideal candidate for experimental analysis due to favorable physicochemical properties.
Male infertility is a complex and polygenic reproductive disease. 10–15% of the males are affected by idiopathic infertility conditions. Acetylcholine (ACh), a major neurotransmitter has been reported to play a non-neuronal role as well. Acetylcholinesterase (AChE) is the primary ACh hydrolyzing enzyme whose over or lower expression influence the availability of ACh for physiological roles. The purpose of the study was to find the possible impact and association of acetylcholinesterase, ACHE gene variant rs 17228602, and pro-inflammatory cytokines in clinically diagnosed infertile males. The study includes clinically diagnosed fifty non-infertile (control) and forty-five infertile males. Whole blood AChE enzymatic activity was measured. Genotyping of rs17228602 was carried out from peripheral blood by standard molecular methods. Pro-inflammatory cytokines were determined by the ELISA method. AChE enzyme was found to be significantly elevated in infertile than non-infertile males. ACHE SNP rs17228602 had shown significant association in dominant model (odd ratio = 0.378, 95% CI = 0.157–0.911, p-value 0.046). Pro-inflammatory cytokine IL-1β was notably increased with statistical significance (p ≤0.05) in male infertile patients. The study concludes and speculates that AChE plays role in the pathogenesis of male infertility through the modulation of inflammatory pathways. Further studies in this direction may resolve the idiopathic cases of male infertility. Other variants of ACHE and the association of miRNA for the regulation of AChE in male infertility are suggested for further insight.
Psychiatric disorders are complex mental conditions that cause significant emotional distress and impairment in a person’s ability to function normally. Globally, there is an alarming rise in the prevalence of psychiatric conditions. Genetic and environmental factors are involved in the pathophysiology of these disorders, but molecular underpinning is still elusive. Cholinergic dysregulation is one of the aetiology of psychiatric condition. This study was aimed to assess the status of hydrolyzing enzyme of cholinergic neurotransmitter, acetylcholinesterase (AChE) from blood and investigate the possible association of a single nucleotide polymorphisms in 3'UTR region of ACHE (rs17228602) with predisposition to psychiatric disorder. Methods: Ninety-five confirmed psychiatric and one hundred thirty healthy individuals were recruited for the study with due consents. AChE was determined by Elman’s method. SNP was studied by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) and sanger sequencing on DNA samples. Results: The results showed notably reduced AChE in psychiatric cohorts with statistical significance (p≤0.05). Genotype and allelic association of the examined SNP was observed with the risk of psychiatric condition in patients.
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