Diabetes mellitus (DM) patients are at a higher risk of developing brain injury characterized by neuronal death. Melatonin, a hormone produced by the pineal gland, exerts neuroprotective effects against brain damage. However, the effect of melatonin on diabetes‐induced brain injury has not been elucidated. This study was to evaluate the role of melatonin against neuronal death in DM and to elucidate the underlying mechanisms. Herein, we found that melatonin administration significantly alleviated the neuronal death in both streptozotocin (STZ)‐induced diabetic mice and high glucose (HG)‐treated neuronal cells. Melatonin inhibited neuronal pyroptosis and excessive autophagy, as evidenced by decreased levels of NLRP3, cleaved caspase‐1, GSDMD‐N, IL‐1β, LC3, Beclin1, and ATG12 both in vivo and in vitro. MicroRNA‐214‐3p (miR‐214‐3p) was decreased in DM mice and HG‐treated cells, and such a downregulation was corrected by melatonin, which was accompanied by repression of caspase‐1 and ATG12. Furthermore, downregulation of miR‐214‐3p abrogated the anti‐pyroptotic and anti‐autophagic actions of melatonin in vitro. Our results indicate that melatonin exhibits a neuroprotective effect by inhibiting neuronal pyroptosis and excessive autophagy through modulating the miR‐214‐3p/caspase‐1 and miR‐214‐3p/ATG12 axes, respectively, and it might be a potential agent for the treatment of brain damage in the setting of DM.

No abstract

BmK AS is a beta long-chain scorpion peptide from the venom of Buthus martensii Karsch (BmK). It was efficiently expressed as a soluble and functional peptide in Escherichia coli, and purified by metal chelating chromatography. About 4.2 mg/l purified recombinant BmK AS could be obtained. The recombinant BmK AS maintained a similar analgesic activity to the natural one in both the mouse-twisting test and hot-plate procedure. It also exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria. BmK AS is the first long-chain scorpion peptide reported to have antimicrobial activity, and is a valuable molecular scaffold for pharmacological research.

Knee injury is known as a frequently occurred damage related to sports, which may affect the function of cartilage. This study aims to explore whether Insulin‐like growth factor 1 (IGF‐1) and bone morphogenetic protein‐7 (BMP‐7)‐modified bone‐marrow mesenchymal stem cells (BMSCs) affect the repair of cartilage damage found in the knee. Primarily, BMSCs were treated with a series of pEGFP‐C1, IGF‐1, and BMP‐7, followed by determination of IGF‐1 and BMP‐7 expression. A rabbit cartilage defect model was also established. Afterfward, cell morphology, viability, cartilage damage repair effect, and expression of collagen I and collagen II at the 6th and the 12th week were measured. BMSCs treated with pEGFP‐C1/IGF‐1, pEGFP‐C1/BMP‐7, and pEGFP‐C1/BMP‐7‐IGF‐1 exhibited elevated expression of BMP‐7 and IGF‐1. Besides, BMSCs in the P10 generation displayed decreased cell proliferation. Moreover, BMSCs treated with IGF‐1, BMP‐7, and IGF‐1‐BMP‐7 showed reduced histological score and collagen I expression while elevated collagen II expression, as well as better repair effect, especially in those treated with IGF‐1‐BMP‐7. Collectively, these results demonstrated a synergistic effect of IGF‐1 and BMP‐7 on the BMSC chondrogenic differentiation on the articular cartilage damage repair in the rabbit knees, highlighting its therapeutic potential for the treatment of articular cartilage damage.

Taper implants differ greatly from anatomical teeth in shape. In this study, seven three-dimensional finite element models were established, including a conventional taper implant and six root-analog implants with different root numbers and shapes. Vertical, horizontal, and oblique instantaneous loads of 100 N were applied to the models to obtain stress distribution in the implant, mucosa, cortical bone, and cancellous bone. ANSYS was used to perform the analysis under hypothetical experimental conditions. We find the stresses in all the implants and surrounding tissues varied by loading direction, the sequence of stress magnitude is vertical load, oblique load, and then horizontal load. The maximum stress values in root-analog implants were significantly less than in the taper implant. Moreover, stress distribution in the former was equalized contrary to the concentrated stress in the latter. Root-analog implants with different root geometry also revealed a pattern: stresses in multiple-root implant models were lower than those in single-root implants under the same load. The implant with a long and rounded root distributed the stress more uniformly, and it was mainly concentrated on the implant itself and cancellous bone. However, the opposite effect was observed in the short implant on mucosa and cortical bone. The root geometry of anatomical teeth can modify their functions. A uniform-shaped implant can hardly meet their functional requirements. Thus, the root-analog implant could be a possible solution.