Improving Fertility in Non-obstructive Azoospermia: Results from an Autologous Bone Mar-row-Derived Mesenchymal Stromal/Stem Cell Phase I Clinical Trial.

BACKGROUND: In this phase I clinical trial, our primary objective was to develop an innovative therapeutic approach utilizing autologous bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) for the treatment of nonobstructive azoospermia (NOA). Additionally, we aimed to assess the feasibility and safety of this approach. MATERIALS AND METHODS: We recruited 80 participants in this non-randomized, open-label clinical trial, including patients undergoing NOA treatment using autologous BM-MSCs (n=40) and those receiving hormone therapy as a control group (n=40). Detailed participant characteristics, such as age, baseline hormonal profiles, etiology of NOA, and medical history, were thoroughly documented. Autotransplantation of BM-MSCs into the testicular network was achieved using microsurgical testicular sperm extraction (microTESE). Semen analysis and hormonal assessments were performed both before and six months after treatment. Additionally, we conducted an in-silico analysis to explore potential protein-protein interactions between exosomes secreted from BM-MSCs and receptors present in human seminiferous tubule cells. RESULTS: Our results revealed significant improvements following treatment, including increased testosterone and inhibin B levels, elevated sperm concentration, and reduced levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin. Notably, in nine patients (22.5%) previously diagnosed with secondary infertility and exhibiting azoospermia before treatment, the proposed approach yielded successful outcomes, as indicated by hormonal profile changes over six months. Importantly, these improvements were achieved without complications. Additionally, our in-silico analysis identified potential binding interactions between the protein content of BM-MSC-derived exosomes and receptors integral to spermatogenesis. CONCLUSION: Autotransplantation of BM-MSCs into the testicular network using microTESE in NOA patients led to the regeneration of seminiferous tubules and the regulation of hormonal profiles governing spermatogenesis. Our findings support the safety and effectiveness of autologous BM-MSCs as a promising treatment modality for NOA, with a particular focus on the achieved outcomes in patients with secondary infertility (registration number: IRCT20190519043634N1).

Comprehensive Overview of Innovative Strategies in Preventing Renal Ischemia-reperfusion Injury: Insights from Bibliometric and In silico Analyses.

BACKGROUND: Ischemia-reperfusion Injury (IRI) is a complex pathophysiological process with severe consequences, including irreversible loss of renal function. Various intraoperative prevention methods have been proposed to mitigate the harmful effects of warm ischemia and kidney reperfusion. AIM: This comprehensive analysis provides an overview of pharmacological agents and intraoperative methods for preventing and treating renal IRI. METHODS: Our analysis revealed that eplerenone exhibited the highest binding affinity to crucial targets, including Aldehyde Dehydrogenase (AD), Estrogen Receptor (ER), Klotho protein, Mineralocorticoid Receptor (MR), and Toll-like Receptor 4 (TLR4). This finding indicates eplerenone's potential as a potent preventive agent against IRI, surpassing other available therapeutics like Benzodioxole, Hydrocortisone, Indoles, Nicotinamide adenine dinucleotide, and Niacinamide. In preventing kidney IRI, our comprehensive analysis emphasizes the significance of eplerenone due to its strong binding affinity to key targets involved in the pathogenesis of IRI. RESULTS: This finding positions eplerenone as a promising candidate for further clinical investigation and consideration for future clinical practice. CONCLUSION: The insights provided in this analysis will assist clinicians and researchers in selecting effective preventive approaches for renal IRI in surgical settings, potentially improving patient outcomes.

Genetic and epigenetic factors of arterial hypertension: a bibliometric- and in-silico-based analyses.

Introduction: Arterial hypertension (AH) is a pervasive global health concern with multifaceted origins encompassing both genetic and environmental components. Previous research has firmly established the association between AH and diverse genetic factors. Consequently, scientists have conducted extensive genetic investigations in recent years to unravel the intricate pathophysiology of AH. Methods: In this study, we conducted a comprehensive bibliometric analysis employing VOSviewer software to identify the most noteworthy genetic factors that have been the focal point of numerous investigations within the AH field in recent years. Our analysis revealed genes and microRNAs intricately linked to AH, underscoring their pivotal roles in this condition. Additionally, we performed molecular docking analyses to ascertain microRNAs with the highest binding affinity to these identified genes. Furthermore, we constructed a network to elucidate the in-silico-based functional interactions between the identified microRNAs and genes, shedding light on their potential roles in AH pathogenesis. Results: Notably, this pioneering in silico examination of genetic factors associated with AH promises novel insights into our understanding of this complex condition. Our findings prominently highlight miR-7110-5p, miR-7110-3p, miR-663, miR-328-3p, and miR-140-5p as microRNAs exhibiting a remarkable affinity for target genes. These microRNAs hold promise as valuable diagnostic and therapeutic factors, offering new avenues for the diagnosis and treatment of AH in the foreseeable future. Conclusion: In summary, this research underscores the critical importance of genetic factors in AH and, through in silico analyses, identifies specific microRNAs with significant potential for further investigation and clinical applications in AH management.