<p>AIMTo evaluate the effect of oxidative stress on the spermatogenesis and lactate dehydrogenase-X (LDH-X) activity in mouse testis.p><p>METHODSFor creating different levels of oxidative stress in mice, three selenium (Se) level diets were fed in separate groups for 8 weeks. Group 1 animals were fed yeast-based Se-deficient (0.02 ppm) diet. Group 2 and Group 3 animals were fed with the same diet supplemented with 0.2 ppm and 1 ppm Se as sodium selenite, respectively. After 8 weeks, biochemical and histopathological observations of the testis were carried out. LDH-X levels in the testis were analyzed by western immunoblot and ELISA.p><p>RESULTSA significant decrease in testis Se level was observed in Group 1 animals, whereas it was enhanced in Group 3 as compared to Group 2. The glutathione peroxidase (GSH-Px) activity was significantly reduced in both the liver and testis in Group 1, but not in Group 2 and 3. A significant increase in the testis glutathione-S-transferase (GST) activity was observed in Group 1, whereas no significant change was seen in Groups 2 and 3. Histological analysis of testis revealed a normal structure in Group 2. A significant decrease in the germ cell population in Group 1 was observed as compared to Group 2 with the spermatids and mature sperm affected the most. Decrease in the lumen size was also observed. In the Se-excess group (Group 3), displacement of germ cell population was observed. Further, a decrease in the LDH-X level in testis was observed in Group 1.p><p>CONCLUSIONExcessive oxidative stress in the Se deficient group, as indicated by changes in the GSH-Px/GST activity, affects the spermatogenic process with a reduction in mature sperm and in turn the LDH-X level.p>
Animals ; Diet ; Glutathione Transferase ; metabolism ; Isoenzymes ; drug effects ; metabolism ; L-Lactate Dehydrogenase ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Oxidative Stress ; drug effects ; physiology ; Selenium ; deficiency ; pharmacokinetics ; pharmacology ; Spermatogenesis ; physiology ; Testis ; drug effects ; enzymology ; pathology ; physiology

Tissue fibrosis, characterized by excessive accumulation of aberrant extracellular matrix (ECM) produced by myofibroblasts, is a growing cause of mortality worldwide. Understanding the factors that induce myofibroblastic differentiation is paramount to prevent or reverse the fibrogenic process. Integrin-mediated interaction between the ECM and cytoskeleton promotes myofibroblast differentiation. In the present study, we explored the significance of integrin alpha 11 (ITGA11), the integrin alpha subunit that selectively binds to type I collagen during tissue fibrosis in the liver, lungs and kidneys. We showed that ITGA11 was co-localized with α-smooth muscle actin-positive myofibroblasts and was correlatively induced with increasing fibrogenesis in mouse models and human fibrotic organs. Furthermore, transcriptome and protein expression analysis revealed that ITGA11 knockdown in hepatic stellate cells (liver-specific myofibroblasts) markedly reduced transforming growth factor β-induced differentiation and fibrotic parameters. Moreover, ITGA11 knockdown dramatically altered the myofibroblast phenotype, as indicated by the loss of protrusions, attenuated adhesion and migration, and impaired contractility of collagen I matrices. Furthermore, we demonstrated that ITGA11 was regulated by the hedgehog signaling pathway, and inhibition of the hedgehog pathway reduced ITGA11 expression and fibrotic parameters in human hepatic stellate cells in vitro, in liver fibrosis mouse model in vivo and in human liver slices ex vivo. Therefore, we speculated that ITGA11 might be involved in fibrogenic signaling and might act downstream of the hedgehog signaling pathway. These findings highlight the significance of the ITGA11 receptor as a highly promising therapeutic target in organ fibrosis.
Animals ; Collagen ; Collagen Type I ; Cytoskeleton ; Extracellular Matrix ; Fibrosis ; Hedgehogs ; Hepatic Stellate Cells ; Humans ; In Vitro Techniques ; Kidney ; Liver ; Liver Cirrhosis ; Lung ; Mice ; Mortality ; Myofibroblasts* ; Phenotype* ; Transcriptome ; Transforming Growth Factors

Introduction: Bone-patellar tendon-bone (BPTB) and semitendinosus–gracilis (STG) are the commonest grafts used for ACL reconstruction. However even after having been debated for years, there is no consensus about the ideal graft. Moreover, the literature is deficient about STG graft with preserved tibial insertion (STGPI) which preserves the proprioception. Our aim is to compare the outcome of BPTB, free STG and STGPI grafts after ACL reconstruction in professional sports persons. We compared the outcome in terms of mechanical stability, functional outcome, return to sports activity and degenerative changes. Materials and Methods: Professional sports persons aged between 16-50 years operated for ACL tear using BPTB, free STG and STGPI grafts with minimum follow-up of two years were identified from hospital records. Patients with associated knee injuries were excluded. Patients, divided in three groups according to graft used, were compared in terms of mechanical stability (arthrometric examination KT-1000 score), functional outcome (Lysholm Score), return to sports activity (Tegner score and difference in thigh circumference) and degenerative changes (KL grading). Results: BPTB graft group was found to be better than free STG and STGPI graft groups in terms of KT-1000 score. There was no statistically significant difference among the groups in terms of Lysholm score, Tegner score, difference in thigh circumference and KL grading. Conclusion: BPTB graft is better than free STG and STGPI grafts in terms of knee stability. When compared for patient reported outcome, return to sports activity, osteoarthritic changes and graft failure there is no significant difference among the three types of grafts.