Bone marrow mesenchymal stem cells repair hexavalent chromium-induced testicular injury by regulating autophagy and ferroptosis mediated by the AKT/mTOR pathway in rats.

There is no ideal therapy for testicular damage induced by Cr(VI); however, bone marrow mesenchymal stem cells (BMSCs) transplantation may be a promising therapy. A Cr(VI) solution was administered to rats by intraperitoneal injection for 30 days, then BMSCs from donor rats were transplanted. Two weeks later, decreased activity and appetite, along with other pathological changes, were improved in the BMSCs group. The location of BMSCs in damaged testes was observed via laser confocal microscopy. Chromium content in the Cr(VI) and BMSCs groups significantly increased compared with that in the control group, but there was no significant difference between the two groups, as revealed by atomic absorption spectrometry. The ferrous iron and the total iron content of testes in the BMSCs group were significantly lower than those in the Cr(VI) group, as observed by Lillie staining and a tissue iron assay kit. Western blotting and immunohistochemical analyses revealed that the expression of Beclin 1, LC3B, 4-hydroxynonenal, and transferrin receptor 1 was decreased in the BMSCs group, compared with the Cr(VI) group. The expression of glutathione peroxidase 4 (GPX4), SLC7A11, p-AKT, mammalian target of rapamycin (mTOR), and p-mTOR in the BMSCs group was higher than that in the Cr(VI) group. Taken together, we propose that BMSCs repair Cr(VI)-damaged testes by alleviating ferroptosis and downregulating autophagy-associated proteins through the upregulation of AKT and mTOR phosphorylation.

Effect of non-invasive brain stimulation on neuropathic pain following spinal cord injury: A systematic review and meta-analysis.

BACKGROUND: In recent years, some studies indicated that repetitive transcranial magnetic stimulation (rTMS) could relieve neuropathic pain (NP) following a spinal cord injury (SCI), whereas some studies showed no pain relief effect. In addition, some studies showed the analgesic effect of transcranial direct current stimulation (tDCS) on NP post SCI, whereas other studies showed no effect. METHODS: We systematically searched on the PubMed, Web of Science, EMBASE, Medline, Google Scholar for studies exploring the analgesic effect of rTMS or tDCS on NP post SCI until November 2019. Meta-analysis was conducted to summarize results of these studies. RESULTS: The present quantitative meta-analysis indicated no significant difference in the effect of treatment on NP following SCI between rTMS and sham rTMS over the motor cortex at about 1 week after the end of the rTMS period (standardized mean difference (SMD) = 2.89, 95% confidence interval (CI) = -0.27 to 6.04). However, the study indicated that rTMS showed significantly better pain relief of treatment compared with sham rTMS between 2 and 6 weeks after the end of the rTMS period (SMD = 3.81, 95%CI: 0.80-7.52). However, no sufficient evidence could be provided to make a meta-analysis for the analgesic effect of tDCS on NP following SCI over the primary motor area (M1). CONCLUSIONS: In conclusion, the present meta-analysis suggested that rTMS did not show early analgesic effect on NP after SCI, but showed better middle-term analgesic effect, compared with sham rTMS. More large scale, blinded randomized controlled trials (RCTs) were needed to explore the analgesic effect of rTMS and tDCS on NP following SCI.

Bone marrow mesenchymal stem cells could reduce the toxic effects of hexavalent chromium on the liver by decreasing endoplasmic reticulum stress-mediated apoptosis via SIRT1/HIF-1α signaling pathway in rats.

This study focused on the effect of bone marrow mesenchymal stem cells (BMSCs) on the repair of rat liver injury induced by Cr (VI). Twenty-four Wistar rats were randomly divided into the control, model and cell therapy group, with 8 rats in each group. Potassium dichromate solution containing 0, 0.4 and 0.4 mg/kg·bw Cr (VI) was administered 5 times a week for 30 days. At the end of treatment, rats in the cell therapy group were administered 1 × 107 BMSCs. Two weeks later, serum alanine and aspartate aminotransferase levels in the cell therapy group were significantly improved compared with those in the model group, CM-Dil-labeled BMSCs were localized in rat livers. Compared with the model group, in the cell therapy group the number of apoptotic hepatocytes by TUNEL assay, MDA content, the expression of HIF-1α, endoplasmic reticulum (ER) stress-mediated apoptosis-related proteins including Grp78, CHOP, Cleaved-Caspase-12, ATF6, and Bax was significantly lower, and SOD activity, the expression of SIRT1 and Bcl-2 was significantly higher. It is suggested that BMSCs are localized in livers and reduce the toxic effects of Cr (VI) on the liver, and the possible mechanism may be related to the mechanisms of BMSCs decreasing ER stress-mediated hepatocyte apoptosis via the SIRT1/HIF-1α signaling pathway.