Salidroside Pretreatment to Mesenchymal Stem Cells Improves Cell Survival and Migration to Promote Diabetic Wound Healing

Objective Diabetic patients pose a greater challenge in managing chronic wound healing,leading to a higher amputation risk compared to non-diabetic patients.Due to their paracrine function by secreting various cytokines and angiogenic factors,mesenchymal stem cells(MSCs)have been acknowledged to be a potential agent in modulating wound healing process.However,post-transplanted MSCs are vulnerable to death,indicating poor survival and migration ability in the wound site of the host,especially under hyperglycemia.As hyperglycemia induces reactive oxygen species(ROS)generation and cellular apoptosis,improvement of MSCs survival and migration potentials under hyperglycemia could contribute to a more efficient MSCs-based wound healing therapy.Salidroside(Sa),a small-molecule drug derived from Rhodiola plant,has been proved to enhance the paracrine function of skeletal muscle cells,as well as their migration even under hypoxichyperglycemia.Herein,we investigated whether Sa could improve the survival and migration potentials of MSCs,subsequently enhance the wound healing process under hyperglycemia.Methods MSCs were cultured under three conditions:low glucose,high glucose,and high glucose+Sa.qPCR analysis and western blotting were done to examine the mRNA and protein expression level of several factors which are important in upregulating the wound healing process.MTT colorimetric assay,intracellular ROS detection,and flow cytometry assay were employed to examine the effect of Sa in MSCs survival.Transwell chamber assay,scratch assay,and phalloidin staining were done to elucidate the role of Sa in regulating MSCs migration potential.For in vivo experiment,diabetic wound healing mice model was generated to elucidate the effect of Sa-pretreated MSCs transplantation in wound closure rate,as well as re-epithelization status,observed with hematoxylin and eosin staining.The diabetic wound healing mice model were divided into three groups:1)mice injected with PBS,2)mice transplanted with PBS-pretreated MSCs,and 3)mice transplanted with Sa-pretreated MSCs.Results(1)Hyperglycemic condition induced the generation of ROS and suppressed total cell number of MSCs,while Sa treatment into MSCs restored these hyperglycemia-induced alterations.In line with this,total apoptotic cells were also suppressed by treating MSCs with Sa.The expression level of cell survival factor,heme-oxygenase 1(HO-1),was enhanced in Sa-pretreated MSCs.Further treatment of HO-1 inhibitor into Sa-pretreated MSCs nullified the ROS level and total apoptotic cells,indica-ting the importance of HO-1 in mediating the Sa-induced survival of MSCs under hyperglycemia.(2)Transwell chamber and scratch assay results showed that Sa-pretreated MSCs have a higher migration potential under hyperglycemia,supported by higher F-actin polymerization fractal dimension.Fibroblast growth factor 2(FGF2)and hepatocyte growth factor(HGF)expression level,which are essential factors for cell migration,were also improved in Sa-pretreated MSCs under hyperglycemia.(3)In diabetic wound healing mice model,transplantation of Sa-pretreated MSCs resulted in significantly improved wound closure rate and re-epithelization.The protein levels of HO-1,FGF2,and HGF were also enhanced in the tissues obtained from the wound site of diabetic wound healing mice model which were transplanted with Sa-pretreated MSCs.Conclusions Salidroside pretreatment on MSCs could improve their survival and migration potentials,subsequently promoting wound healing process under hyperglycemia.This prospective MSC-based therapy could serve as a novel strategy to improve diabetic wound healing.

Encapsulation of metal layers within metal-organic frameworks as hybrid thin films for selective catalysis

A facile encapsulation strategy for the preparation of metal layer/metal-organic framework （metal/MOF） hybrid thin films, by alternately growing MOF thin films and sputter-coating metal layers, is reported. The controlled species of the MOF thin films and metal layers, as well as the designed thickness of MOF thin films, endow the resulting hybrid thin films with improved functional and design flexibility. Importantly, the metaL/MOF hybrid thin films, with well-defined sandwich structures, exhibit excellent selective catalytic activity, derived from MOFs acting as molecular sieves and the metal layers providing active sites.

Spatial compartmentalization of metal nanoparticles within metal-organic frameworks for tandem reaction

Fabrication of multifunctional catalysts has always been the pursuit of synthetic chemists due to their efficiency,cost-effectiveness,and environmental friendliness.However,it is difficult to control multi-step reactions in one-pot,especially the spatial compartmentalization of incompatible active sites.Herein,we constructed metal-organic framework(MOF)composites which regulate the location distribution of metal nanoparticles according to the reaction path and coupled with the diffusion of substrates to achieve tandem reaction.The designed UiO-66-Pt-Au catalyst showed good activity and selectivity in hydrosilylation-hydrogenation tandem reaction,because the uniform microporous structures can control the diffusion path of reactants and intermediates,and Pt and Au nanoparticles were arranged in core-shell spatial distribution in UiO-66.By contrast,the low selectivity of catalysts with random deposition and physical mixture demonstrated the significance of artificial control to the spatial compartmentalization of active sites in tandem catalytic reactions,which provides a powerful approach for designing high-performance and multifunctional heterogeneous catalysts.

Role of endothelial cells in the regulation of mechanical microenvironment on tumor progression

Majority of cancer patients die from cancer metastases.The physical stimulation produced by microenvironment regulates invasive behavior of cancer cells.Blood vessel is one of the“pathways”for cancer to metastasize,in which tumor cells need to cross the endothelial barrier for intravasation and extravasation.Tumor vessels are arranged in untraditional hierarchies and characterized with rupture,bend,swell and high permeability that are beneficial to intravasation of cancer cell.Abnormal vessels are accompanied with uneven blood flow,increased compression and interstitial fluid pressure.Meanwhile,excessive proliferation of tumor leads to low oxygen pressure in solid tumor.The aberrant tumor mechanical microenvironment changes the biochemical and mechanical signal transduction of endothelial cells and participates in tumor progression.Many current researches focus on how chemical signals regulate endothelial cell function while the role of physical cues is unclear.In this review,the role of endothelial cells in the regulation of shear stress,intercellular force,extracellular matrix and pressure on tumor progression is summarized.