Background: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause of end-stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. Mesenchymal stem cell (MSC)-derived exosomes are currently considered as a new promising therapy for chronic renal injury. However, the renal-protective mechanism of exosomes on DN is not completely understood. We examined the potential role of MSC-derived exosomes for enhancement of autophagy activity and their effect on DN. In our study, we used five groups of rats: control; DN; DN treated with exosomes; DN treated with 3-methyladenine (3-MA) and chloroquine (inhibitors of autophagy); and DN treated with 3-methyladenine (3-MA), chloroquine, and exosome groups. We assessed renal function, morphology, and fibrosis. Moreover, ratios of the autophagy markers mechanistic target of rapamycin (mTOR), Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I were detected. Additionally, electron microscopy was used for detection of autophagosomes. Results: Exosomes markedly improved renal function and showed histological restoration of renal tissues, with significant increase of LC3 and Beclin-1, and significant decrease of mTOR and fibrotic marker expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitors chloroquine and 3-MA. Conclusion: We conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus.

Mesenchymal stem cells (MSCs) have diverse functions in regulating injury and inflammation through the secretion of extracellular vesicles (EVs). In this study, we investigated the systemic administration of extracellular vesicles derived from human umbilical cord mesenchymal stem cells (UCMSCs-EVs) as a therapeutic agent for intrauterine adhesions (IUAs) caused by endometrial injury. Additionally, we investigated the therapeutic impact of both UCMSCs-EVs and estrogen either separately or in combination in a rat model. The inflammation, vascularization, proliferation, and extent of fibrosis were assessed by a histopathological and immunohistochemical assessment using transforming growth factor (TGF)-β as a fibrotic marker and vascular endothelial growth factor (VEGF) as a vascular marker. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 (inflammatory cytokines), CD140b (a marker of endometrial stem cells), and RUNX2 (an antifibrotic factor). Finally, Western blotting was used to evaluate collagen I and β-actin expression. The therapeutic groups treated with either UCMSCs-EVs alone or combined with estrogen exhibited a significant decrease in inflammation and fibrosis (TNF-α, TGF-β, IL-1, IL-6, RUNX2, and collagen-I) as well as a significant decrease in vascularization (VEGF) compared with the untreated rats with IUAs. The most significant results were obtained in animals with IUAs that received a combined therapy of UCMSCs-EVs and estrogen. We conclude that the synergistic action of human UCMSCs-EVs combined with estrogen provides a highly effective alternative regenerative agent in IUA treatment.

Background: Loss of normal function is an inevitable effect of aging. Several factors contribute to the aging process, including cellular senescence and oxidative stress. Methods: We investigate how Arthrospira platensis Nanoparticles (NSP) protect against aging injury induced by d-galactose (D-gal) in the rat. So, we subcutaneously (S/C) injected D-gal at 200 mg/kg BW to see if Arthrospira platensis Nanoparticles (NSP) might protect against the oxidative changes generated by D-gal. NSP (0.5 mg/kg body weight once daily by gastric gavage) was given to all groups apart from the control and D-gal groups. The d-gal + NSP group was supplemented with 200 mg of D-gal per kg BW once a day and NSP 0.5 mg/kg BW given orally for 45 days. Biochemical, mRNA expression, and histological investigations of brain tissues were used to evaluate the oxidative alterations caused by d-gal and the protective role of NSP. Results: Our data demonstrated that d-gal was causing significant reductions in relative brain and body weight with increased malondialdehyde (MDA) and redox oxygen species (ROS) levels and increases in serum creatine phosphokinase (CPK) and creatine phosphokinase isoenzyme BB (CPK-BB) with marked decreases in the level of antioxidant enzyme activity in the brain and acetylcholinesterase activity augmented with a phosphorylated H2A histone family member X (γ-H2AX) level increased. The D-gal group had considerably higher phosphorylated p38 mitogen-activated protein kinases (P38MAPK) and C-Jun N-terminal (JNK) kinases. The d-gal administration stimulates the apoptotic gene expression by downregulating the brain superoxide dismutase (SOD), catalase (CAT), and nuclear factor erythroid 2–related factor 2 (Nrf2). The NSP administration saved these parameters in the direction of the control. The brain histopathologic and immunohistochemistry analysis findings support our findings on NSP’s protective role. Conclusion: The NSP may be a promising natural protective compound that can prevent aging and preserve health.

Signal joint T cell receptor excision circles (sjTRECs) are a promising marker for age estimation and immunosenescence in different ethnic groups. Several limitations are expected to overshadow their use as accurate markers for age prediction. The current study was conducted to determine the influence of immunologic disorders, such as autoimmune diseases and COVID-19, on the accuracy of sjTRECs as molecular markers for age estimation and immunosenescence among living Egyptians. Peripheral blood sjTRECs level was measured by qPCR in 90 autoimmune patients, 58 COVID-19 patients, and 85 healthy controls. The mean dCt values were significantly (p = 0.0002) different between the three groups, with the highest values in healthy subjects, followed by autoimmune and COVID-19 patients. A significant negative correlation was identified between the sjTRECs levels and ages in all studied cases. There were significant positive correlations between chronological age and predicted age for healthy individuals, autoimmune, and COVID-19 patients with mean absolute deviations (MAD) of 9.40, 11.04, and 9.71, respectively. The two patients’ groups exhibited early immunosenescence, which was more noticeable among the young adults with COVID-19 and autoimmune patients of age range (18–49 years). Autoimmunity may represent a critical factor impacting the accuracy of sjTRECs quantitation for age prediction.

Host genetic variation has been recognized as a key predictor of diverse clinical sequelae among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. Insights into the link between the Interleukin-6 receptor (IL-6R) and Interleukin-1 beta (IL-1β) genetic variation and severe coronavirus disease 2019 (COVID-19) are crucial for developing new predictors and therapeutic targets. We aimed to investigate the association of IL-6R rs12083537, IL-1β rs16944, and IL-1β rs1143634 SNPs with the severity of COVID-19. Our study was conducted on 300 COVID-19-negative individuals (control group) and 299 COVID-19-positive cases, classified into mild, moderate, and severe subgroups. Analyses of IL-1β (rs16944, rs1143634) and IL-6R (rs12083537) SNPs’ genotypes were performed using qPCR genotyping assays. The IL-1β (rs16944) CC genotype and IL-6R (rs12083537) GG genotype were substantially related to COVID-19 severity, which was also associated with comorbidities and some laboratory parameters (p < 0.001). The IL-1β (rs1143634) TT genotype was found to be protective. Likewise, the IL-1β (rs16944) CC genotype was associated with increased mortality. IL-1β rs16944 and IL-6R rs12083537 SNPs are promising potential predictors of SARS-CoV-2 disease severity. Meanwhile, the rs1143634 SNP T allele was protective against severity and mortality risk.