Potential advantages of genetically modified mesenchymal stem cells in the treatment of acute and chronic liver diseases.

Liver damage caused by toxicity can lead to various severe conditions, such as acute liver failure (ALF), fibrogenesis, and cirrhosis. Among these, liver cirrhosis (LC) is recognized as the leading cause of liver-related deaths globally. Unfortunately, patients with progressive cirrhosis are often on a waiting list, with limited donor organs, postoperative complications, immune system side effects, and high financial costs being some of the factors restricting transplantation. Although the liver has some capacity for self-renewal due to the presence of stem cells, it is usually insufficient to prevent the progression of LC and ALF. One potential therapeutic approach to improving liver function is the transplantation of gene-engineered stem cells. Several types of mesenchymal stem cells from various sources have been suggested for stem cell therapy for liver disease. Genetic engineering is an effective strategy that enhances the regenerative potential of stem cells by releasing growth factors and cytokines. In this review, we primarily focus on the genetic engineering of stem cells to improve their ability to treat damaged liver function. We also recommend further research into accurate treatment methods that involve safe gene modification and long-term follow-up of patients to increase the effectiveness and reliability of these therapeutic strategies.

Extracellular vesicles as a new horizon in the diagnosis and treatment of inflammatory eye diseases: A narrative review of the literature.

Extracellular vesicles include exosomes, microvesicles, and apoptotic bodies. Their cargos contain a diverse variety of lipids, proteins, and nucleic acids that are involved in both normal physiology and pathology of the ocular system. Thus, studying extracellular vesicles may lead to a more comprehensive understanding of the pathogenesis, diagnosis, and even potential treatments for various diseases. The roles of extracellular vesicles in inflammatory eye disorders have been widely investigated in recent years. The term "inflammatory eye diseases" refers to a variety of eye conditions such as inflammation-related diseases, degenerative conditions with remarkable inflammatory components, neuropathy, and tumors. This study presents an overview of extracellular vesicles' and exosomes' pathogenic, diagnostic, and therapeutic values in inflammatory eye diseases, as well as existing and potential challenges.

Protective effects of melatonin against physical injuries to testicular tissue: A systematic review and meta-analysis of animal models.

Background: Modern societies face infertility as a global challenge. There are certain environmental conditions and disorders that damage testicular tissue and may cause male infertility. Melatonin, as a potential antioxidant, may protect testicular tissue. Therefore, we conducted this systematic review and meta-analysis to evaluate the effects of melatonin in animal models against physical, heat, and ischemic damage to the testicular tissue. Methods: PubMed, Scopus, and Web of Science were systematically searched to identify animal trials evaluating the protective effect of melatonin therapy on rodent testicular tissue when it is exposed to physical, thermal, ischemic, or hypobaric oxygen stress. Random-effect modeling was used to estimate the standardized mean difference and 95% confidence intervals based on the pooled data. Additionally, the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool was used to assess the risk of bias. The study protocol was prospectively registered in PROSPERO (CRD42022354599). Results: A total of 41 studies were eligible for review out of 10039 records. Studies employed direct heat, cryptorchidism, varicocele, torsion-detorsion, testicular vascular occlusion, hypobaric hypoxia, ischemia-reperfusion, stress by excessive or restraint activity, spinal cord injury, and trauma to induce stress in the subjects. The histopathological characteristics of testicular tissue were generally improved in rodents by melatonin therapy. Based on the pooled data, sperm count, morphology, forward motility, viability, Johnsen's biopsy score, testicular tissue glutathione peroxidase, and superoxide dismutase levels were higher in the melatonin treatment rodent arms. In contrast, the malondialdehyde level in testicular tissue was lower in the treatment rodent arms. The included studies suffered from a high risk of bias in most of the SYRCLE domains. Conclusion: This study concludes that melatonin therapy was associated with improved testicular histopathological characteristics, reproductive hormonal panel, and tissue markers of oxidative stress in male rodents with physical, ischemic, and thermal testicular injuries. In this regard, melatonin deserves scientific investigations as a potential protective drug against rodent male infertility. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022354599.

The role of the immune system in the pathogenesis of NAFLD and potential therapeutic impacts of mesenchymal stem cell-derived extracellular vesicles.

Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by intra-hepatocyte triglyceride accumulation and concomitant involvement of the immune system with subsequent histological changes, tissue damage, and clinical findings. There are various molecular pathways involved in the progression of NAFLD including lipotoxicity, endoplasmic reticulum stress, and the immune response. Both innate and adaptive immune systems are involved in the NAFLD pathogenesis, and crosstalk between the immune cells and liver cells participates in its initiation and progression. Among the various treatments for this disease, new cell based therapies have been proposed. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSC) (MSC-EVs) are new cell-free vehicles with low immunogenicity, which can suppress detrimental immune responses in inflamed tissues. This review aimed to express the immune system's molecular pathways associated with the initiation and progression of NAFLD. Then, the possible role of MSC-EVs in the treatment of this entity through immune response modulation was discussed. Finally, engineered EVs enhanced by specific therapeutic miRNA were suggested for alleviating the pathological cellular events in liver disease.