Tarek Khamis

While ultraviolet C (UVC) radiation has beneficial applications, it can also pose risks to living organisms. Nevertheless, a detailed assessment of UVC radiation’s effects on mammalian male reproductive physiology, including the underlying mechanisms and potential protective strategies, has not yet been accomplished. This study aimed to examine the critical roles of oxidative stress, autophagy, reproductive hormonal axis, and microRNAs in UVC-induced reproductive challenges in male rats. Semen, biochemical, molecular, and in silico analyses revealed significant dysregulation of testicular steroidogenesis, impaired spermatogenesis, deteriorated sperm quality, and altered reproductive hormonal profiles, which ultimately lead to a decline in fertility in male rats exposed to UVC radiation. Our data indicated that the suppression of autophagy, stimulation of gonadotropin-inhibiting hormone (GnIH), and alteration of microRNAs serve as key mediators of UVC-induced stress effects in mammalian reproduction, potentially contributing to male infertility. Targeting these pathways, particularly through pretreatment with hesperidin (HES), offers a promising strategy to counteract UVC-induced male infertility. In conclusion, the present findings emphasize the importance of understanding the molecular mechanisms behind UVC-induced male infertility and offer valuable insights into the protective mechanisms and prospective role of HES in safeguarding male reproductive health.

Ovarian insufficiency is one of the common reproductive disorders affecting women with limited therapeutic aids. Mesenchymal stem cells have been investigated in such disorders before yet, the exact mechanism of MSCs in ovarian regeneration regarding their epigenetic regulation remains elusive. The current study is to investigate the role of the bone marrow-derived mesenchymal stem cells (BM-MSCs) lncRNA (Neat-1 and Hotair1) and miRNA (mir-21-5p, mir-144-5p, and mir-664-5p) in mitigating ovarian granulosa cell apoptosis as well as searching BM-MSCs in altering the expression of ovarian and hypothalamic IGF-1 – kisspeptin system in connection to HPG axis in a cyclophosphamide-induced ovarian failure rat model. Sixty mature female Sprague Dawley rats were divided into 3 equal groups; control group, premature ovarian insufficiency (POI) group, and POI + BM-MSCs. POI female rat model was established with cyclophosphamide. The result revealed that BM-MSCs and their conditioned media displayed a significant expression level of Neat-1, Hotair-1, mir-21-5p, mir-144-5p, and mir-664-5p. Moreover, BM-MSCs transplantation in POI rats improves; the ovarian and hypothalamic IGF-1 – kisspeptin, HPG axis, ovarian granulosa cell apoptosis, steroidogenesis, angiogenesis, energy balance, and oxidative stress. BM-MSCs expressed higher levels of antiapoptotic lncRNAs and microRNAs that mitigate ovarian insufficiency.

One of the main causes of renal impairment and failure is acute kidney injury (AKI), which has few treatment options that can preserve kidney function. Stem cells represent a promising regenerative tool, among these are stem cells derived from breast milk (Br-dSCs), which have demonstrated greater potential for regenerative capacity and plasticity in several diseases than other types of stem cells (SCs). However, their application in kidney injury disorders still needs to be fully studied, and their underlying regenerative mechanisms still need to be discovered. Thus, the current investigation aimed to examine the Br-dSCs' capacity for regeneration in acute renal injury and address the possible molecular mechanisms implicated in the reparative modalities of these cells regarding cellular autophagy. Eighteen adult male Sprague Dawley rats were assigned into 3 equal groups 10 rats each: control, AKI, and AKI + Br-dSCs groups. The kidney function tests' serum level, oxidative stress in the kidneys, histopathological examination, immunohistochemical expression of the renal receptor of insulin growth factor 1 (IGF-1r), epidermal growth factor 1 (EGF-1r), autophagy promoting factor beclin-1, and renal collagen deposition were performed. The results illustrated that Br-dSCs improved the serum level of blood urea nitrogen, uric acid, as well as creatinine rendering them to the ordinary physiological tone of the group of control. Moreover, the administration of Br-dSCs markedly increased the IGF-1r, EGF-1r, beclin-1, and downregulated collagen synthesis and deposition. We could conclude that Br-dSCs regenerate the injured kidney tissue via a modulating growth factor receptor that potentially promote the renal autophagy process.

Canine diabetes mellitus (DM) is a common metabolic endocrine condition, characterized by persistent hyperglycemia and insulin insufficiency. DM has severe irreversible pathological disorders including retinopathy, neuropathy, hepatopathy, and nephropathy. The search for alternative approaches for restoring pancreatic endocrine function is therefore of paramount clinical interest. Umbilical cord blood mesenchymal stem cells (UCB-MSCs) were isolated and identified as one of Mesenchymal stem cells (MSCs) which have a regenerative role by enhancing resident stem cells and soluble factors that stimulate the internal repairing process. Nine mongrel dogs were randomly allocated into three equal groups, 3 dogs each: control, diabetic, and diabetic-UCB-MSCs treated group. The isolated cells displayed surface markers of MSCs cluster of differentiations (CD) CD90, CD105, and CD73. Moreover, the findings showed that UCB-MSCs transplantation in diabetic dogs induced a remarkable decrease in fasting blood glucose (FBG) level, AST, ALT, ALP, γ-GT, total protein (TP), albumin, blood urea nitrogen (BUN), and serum creatinine than the diabetic group. Additionally, UCB-MSCs administration markedly improves hepatic and renal oxidative status besides improving the histopathological changes with appearing multiple regenerative signs. Therefore, MSCs provide a promising therapeutic strategy for DM-associated disorders in dogs.

[This corrects the article DOI: 10.3389/fphar.2023.1265230.].

Introduction: Diabetic nephropathy (DN), a chronic kidney disease, is a major cause of end-stage kidney disease worldwide. Mesenchymal stem cells (MSCs) have become a promising option to mitigate several diabetic complications.Methods: In this study, we evaluated the therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model of STZ-induced DN. After the confirmation of diabetes, rats were treated with BM-MSCs and sacrificed at week 12 after treatment.Results: Our results showed that STZ-induced DN rats had extensive histopathological changes, significant upregulation in mRNA expression of renal apoptotic markers, ER stress markers, inflammatory markers, fibronectin, and intermediate filament proteins, and reduction of positive immunostaining of PCNA and elevated P53 in kidney tissue compared to the control group. BM-MSC therapy significantly improved renal histopathological changes, reduced renal apoptosis, ER stress, inflammation, and intermediate filament proteins, as well as increased positive immunostaining of PCNA and reduced P53 in renal tissue compared to the STZ-induced DN group.Conclusion: In conclusion, our study indicates that BM-MSCs may have therapeutic potential for the treatment of DN and provide important insights into their potential use as a novel therapeutic approach for DN.

Introduction: Optic neuropathy is an affection of the optic neurons, which ends with blindness and occurs either primarily due to direct affection of the optic nerve or secondarily as a complication of chronic diseases and/or adverse effects of their therapy. The search for novel therapeutic tools is crucial in addressing the limited therapeutic approaches for optic neuropathy. Therefore, the present study was developed to investigate the possible ameliorative effect of tempol against cisplatin-induced optic neuropathy and its underlying mechanism.Methods: Forty-eight adult male albino Wistar rats were divided into four equal groups—control, tempol (TEM), cisplatin (CIS), and tempol and cisplatin combined (TEM+CIS). Optic nerve oxidative stress (MDA, SOD, and GPx), gene expression of endoplasmic reticulum stress (ATF-6, XBP-1, BIP, CHOP, and JNK), autophagy 6 (LC3, Beclin-1, and p62) markers, nerve growth factor-1, immunohistochemical expression of (LC3 and p62), histopathological, and electron microscopic examination were performed.Results: Histopathological and ultrastructure examination validated that cisplatin caused optic neuropathy by inducing oxidative stress, upregulating ER stress markers, and downregulating autophagy markers, and NGF-1 expression. TEM + CIS showed improvement in optic nerve structure and ultrastructure along with oxidative stress, ER stress mRNA, autophagy (immunohistochemical proteins and mRNA) markers, and nerve growth factor mRNA expression.Conclusions: Based on previous findings, tempol represents a valid aid in cisplatin-induced optic neuropathy by implicating new molecular drug targets (ER stress and autophagy) for optic neuropathy therapy.