Diallyl trisulfide improves spinal cord ischemia-reperfusion injury damage by activating AMPK to stabilize mitochondrial function.

BACKGROUND: Spinal cord ischemia-reperfusion injury (SCII) is a catastrophic event, which can cause paraplegia in severe cases. In the reperfusion stage, oxidative stress was up-regulated, which aggravated the injury and apoptosis of neurons. As the main active ingredient of garlic, diallyl trisulfide (DATS) displays strong antioxidant capacity. However, it is unknown whether DATS can protect the neurons of SCII. MATERIALS AND METHODS: In this study, the descending aorta at the distal end of the left subclavian artery was ligated and perfused again after 14 min. Samples including blood and spinal cord (L2-L5) were taken 24 h later for morphological and biochemical examination. RESULTS: After SCII, the rats showed motor dysfunction, increase apoptosis, malondialdehyde content, mitochondrial biogenesis and dynamic balance disorder. After the application of DATS, the adenosine monophosphate activated protein kinase (AMPK) was activated, the mitochondrial damage was improved, the oxidative stress was weakened, and the neuronal damage was recovered to some extent. However, the addition of compound C significantly weakened the protective effect of DATS. CONCLUSION: Oxidative stress caused by mitochondrial damage was one of the important mechanisms of neuronal damage in SCII. DATS could activate AMPK, stabilize mitochondrial biogenesis and dynamic balance, and reduce neuronal damage caused by oxidative stress.

Investigation on repairing diabetic foot ulcer based on 3D bio-printing Gel/dECM/Qcs composite scaffolds.

Diabetic foot ulcers are one of the most serious of the numerous complications of diabetes mellitus, causing great physical trauma and financial stress to patients, and accelerating wound healing in diabetic patients remains one of the major clinical challenges. Exosomes from adipose-derived stem cells can directly and indirectly promote wound healing. However, due to the low retention rate of exosomes in the wound, exosome treatment is difficult to achieve the expected effect. Therefore, it is of great significance to synthesize a composite scaffold that can stably load exosomes and has antibacterial properties. In this study, fresh pig skin was decellularized to obtain decellularized matrix (dECM). Secondly, quaternized chitosan (Qcs) was modified with quaternary ammonium salt to make it soluble in water after quaternization. Finally, Gel-dECM-Qcs (GDQ) bioink was prepared by adding acellular matrix and quaternized chitosan with temperature sensitive gelatin (Gel) as carrier. Tissue engineered composite scaffolds were then prepared by extrusion 3D printing technology. Subsequently, the physicochemical properties, biocompatibility and antimicrobial capacity of the composite scaffolds were determined, and the data showed that the composite scaffolds had good mechanical properties, biocompatibility and antimicrobial capacity, and the maximum stress of the composite scaffolds was 1.16 ± 0.05 MPa, the composite scaffolds were able to proliferate and adhered to the L929 cells, and the kill rates of composite scaffolds against E. coli and S. aureus after incubation for 24 h were 93.24 ± 1.22 % and 97.34 ± 0.23 %, respectively. Overall, the GDQ composite scaffolds have good mechanical properties adapted to skin bending, its good biocompatibility can promote the growth and migration of fibroblasts, reshape injured tissues, accelerate the wound healing, and excellent antimicrobial ability can inhibit the growth of E. coli and S. aureus, reducing the impact of bacterial infections on wounds. Moreover, the composite scaffolds have the potential to be used as exosom-loaded hydrogel dressings, which provides a basis for the subsequent research on the repair of diabetic foot ulcers.

Notoginsenoside R1 promotes MC3T3-E1 differentiation by up-regulating miR-23a via MAPK and JAK1/STAT3 pathways.

Growing evidence have probed a stimulatory influence of Notoginsenoside R1 (NGR1) with osteoblastic probability. miR-23a plays a crucial role in osteoblast differentiation. Whereas whether there exists a miRs-related mechanism by which NGR1 promotes preosteoblast differentiation remains unexplored. We pre-treated MC3T3-E1 with NGR1 to anatomize Runx-2 and Osx expression as well as ALP activity. Phosphorylation of regulators was evaluated by Western blot. SB203580 and Ruxolitinib were used to reduce the phosphorylation of regulators. The effects of NGR1 on miR-23a were verified by qRT-PCR. We analyzed the expression of Runx-2 and Osx, ALP activity as well as phosphorylation of regulators in MC3T3-E1 stimulated with NGR1 and transfected with miR-23a inhibitor. We found that NGR1 enhanced Runx-2 and Osx expression as well as ALP activity in a concentration-dependent manner. NGR1 might exhibit an efficacious promotion on Runx-2, Osx and ALP activity by increased phosphorylation of MAPK, JAK1, and STAT3. NGR1 resulted in miR-23a overexpression which positively modulated Runx-2 and Osx expression as well as ALP activity. Our results showed that miR-23a inhibitor reduced the phosphorylation of MAPK, JAK1 and STAT3 in MC3T3-E1 pre-treated with NGR1. In conclusion, NGR1 exhibited an efficacious promotion on preosteoblast differentiation by up-regulating miR-23a through MAPK and JAK1/STAT3 pathways. Highlights: NGR1 induces MC3T3-E1 differentiation; miR-23a is positively regulated by NGR1; NGR1 regulates MAPK/JAK1/STAT3 through miR-23a.