Andrias davidianus bone peptides alleviates hyperuricemia-induced kidney damage in vitro and in vivo

Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.

A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis

The complex pathogenesis of osteoporosis includes excessive bone resorption,insufficient bone formation and inadequate vascularization,a combination which is difficult to completely address with conventional therapies.Engineered exosomes carrying curative molecules show promise as alternative osteoporosis therapies,but depend on specifically-functionalized vesicles and appropriate engineering strategies.Here,we developed an exosome delivery system based on exosomes secreted by mesenchymal stem cells(MSCs)derived from human induced pluripotent stem cells(iPSCs).The engineered exosomes BT-Exo-siShn3,took advantage of the intrinsic anti-osteoporosis function of these special MSC-derived exosomes and collaborated with the loaded siRNA of the Shn3 gene to enhance the therapeutic effects.Modification of a bone-targeting peptide endowed the BT-Exo-siShn3 an ability to deliver siRNA to osteoblasts specifically.Silencing of the osteoblastic Shn3 gene enhanced osteogenic differentiation,decreased autologous RANKL expression and thereby inhibited osteoclast formation.Furthermore,Shn3 gene silencing increased production of SLIT3 and consequently facilitated vascularization,especially formation of type H vessels.Our study demonstrated that BT-Exo-siShn3 could serve as a promising therapy to kill three birds with one stone and implement comprehensive anti-osteoporosis effects.

Adhesive peptides conjugated PAMAM dendrimer as a coating polymeric material enhancing cell responses

This present work aims to functionalize poly（amidoamine） （PAMAM） dendrimers with various reported adhesive peptides, including Arg-Gly-Asp （RGD）, Tyr-lle-Gly-Ser-Arg （YIGSR）, and Ile-Lys-Val-Ala-Val （IKVAV） for enhancing cell responses. The RGD, YIGSR, or IKVAV functionalized PAMAM coated substrate could promote cell adhesion of bone marrow mesenchymal stem cells （BMSCs） within 1 h after incubation. The neurite differentiation and proliferation of pheochromocytoma （PC12） cells were also significantly enhanced after culturing on the peptide functionalized PAMAM dendrimers for two and foul days. This peptide functionalized PAMAM dendrimers are considered as the potential candidates for various tissue engineering applications.