Aerobic exercise reverses the NF-κB/NLRP3 inflammasome/5-HT pathway by upregulating irisin to alleviate post-stroke depression.

Background: Post-stroke depression (PSD) is one of the most common and serious sequelae of stroke. The pathogenesis of PSD involves both psychosocial and biological mechanisms, and aerobic exercise is a potential therapeutic target. We conducted an in-depth exploration of the protective mechanisms of aerobic exercise in a PSD mouse model. Methods: In this study, C57BL/6 mice were used as the research objects, and a PSD mouse model was established by combining middle cerebral artery occlusion and chronic unpredictable mild stimulation. Real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assays, adeno-associated virus microinjection technology, co-immunoprecipitation, fluorescence in-situ hybridization, and western blotting were performed. A moderate-load treadmill exercise was used for aerobic exercise intervention. The moderate-intensity aerobic exercise training method adopted 0 slopes and treadmill adaptation training for 5 days. We verified the effects of aerobic exercise on the nuclear factor kappa B (NF-κB)/nucleotide-binding oligomerization domain--like receptor protein 3 (NLRP3) inflammasome/5-hydroxytryptamine (5-HT) pathway. Results: Aerobic exercise effectively alleviated the neurological damage caused by PSD (P<0.01). The results from the PSD mouse model in vivo were consistent with those of the cell experiments. Moreover, overexpression of irisin improves depression-like behavior in PSD mice. We confirmed that aerobic exercise is involved in PSD through 5-HT, which inhibits NF-κB/NLRP3 inflammasome initiation through irisin and alleviates mitochondrial damage under stress by reducing calcium overload, thereby inhibiting NLRP3 inflammasome activation. Conclusions: Aerobic exercise reversed the NF-κB/NLRP3 inflammasome/5-HT pathway by upregulating irisin expression to alleviate PSD.

Ozone alleviates ischemia/reperfusion injury by inhibiting mitochondrion-mediated apoptosis pathway in SH-SY5Y cells.

Cerebral ischemia/reperfusion (I/R) injuries are common and often cause severe complications. Ozone has been applied for protecting I/R injury in animal models of several organs including cerebra, but the detailed mechanism remains unclear. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase measurement were used to determine the influence of ozone on cell activity and damage of SH-SY5Y cells. Some redox items such as catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were measured by enzyme-linked immunosorbent assay. The mitochondrial membrane potential (ΔΨm ) was determined by JC-1 assay. Cytochrome-c (cyt-c) level in the cytoplasm and mitochondrion was measured by western blotting. Apoptosis was determined by flow cytometry, and some apoptosis-related molecules were detected by quantitative real-time polymerase chain reaction and western blotting. Ozone alleviated oxidative damage by increasing GSH-Px, SOD, CAT, and decreasing MDA. Ozone decreased mitochondrial damage caused by I/R injury and inhibited the release of cyt-c from mitochondrion to cytoplasm in SH-SY5Y cells. The cell apoptosis caused by I/R was inhibited by ozone, and ozone could decrease apoptosis by increasing the ratio of Bcl-2/Bax and inhibiting caspase signaling pathway in SH-SY5Y cells. Ozone has the ability of maintaining redox homeostasis, decreasing mitochondrion damage, and inhibiting neurocytes apoptosis induced by I/R. Therefore, ozone may be a promising protective strategy against cerebral I/R injury.

Ginsenoside (Rg-1) promoted the wound closure of diabetic foot ulcer through iNOS elevation via miR-23a/IRF-1 axis.

BACKGROUND: Impaired wound healing in diabetes foot ulcers (DFUs) brings a great burden to diabetic patients. Pro-angiogenesis through elevating nitric oxide (NO) is beneficial to the wound healing process. Ginsenoside Rg1, the main active in Notoginseng, is reported to regulate the angiogenesis in endothelial cells through modulating miR-23a. However, the effect of Rg1 in diabetes remains elusive. METHODS: High fat diet combined with streptozotocin-induced diabetic rats were treated with Rg1. Then incision area and tissue NO level were measured to evaluate the wound closure efficacy of Rg1. Then high glucose cultured HUVECs were employed to mimic diabetic environment in vitro. Overexpression and knockdown plasmids of miR-23a or IRF-1 were constructed and transfected in HUVECs. qPCR and western blot were used to determine the mRNA and protein level, respectively. Dual-luciferase reporter assay was utilized to determine the interaction of IRF-1/miR-23a. RESULTS: Rg1 accelerated the wound closure speed in diabetic rats and increased NO level through elevating iNOS expression. Knockdown of iNOS reversed Rg1-induced VEGF expression, cell proliferation, anti-apoptotic efficacy and cell migration ability in high glucose cultured HUVECs. Further investigation revealed that Rg1 mediated iNOS through miR-23a. miR-23a inhibited the expression of IRF-1, a protein which could directly bind to the iNOS mRNA 3'UTR. CONCLUSION: Rg1 promoted angiogenesis in diabetic wound healing process through NO signaling via miR-23a, providing a novel candidate for DFUs treatment.