[ABSTRACT]AIM:Toexploretheeffectoftheelasticmodulusandsizesofliquidcrystal(LC)phasesonosteo-genic differentiation based on OPC/PU composite substrate by mimicking the microenvironment in rat bone mesenchymal stem cells (rBMSCs).METHODS: A series of composite substrates with different elastic modulus were constructed via modulation of LC content in the composites .The surface phase structure was observed by polarized microscopy , and the mechanical property was measured by a universal material testing machine .Furthermore, the laser confocal microscope was employed to observe the spreading , polarization and the cytoskeleton arrangement of the rBMSCs .The proliferation of rBM-SCs was evaluated by CCK-8 assay.The specific mRNA expression of osteogenic differentiation such as collagen Ⅰ, and osteopontin on the composite membranes was detected by real-time PCR.RESULTS:The size and number of LC phase in-creased and the elastic modulus of the composite substrates decreased with the increase of the LC content .The rBMSCs ex-hibited better characteristics of initial adhesion , spreading and proliferation on the OPC 10-PU and OPC30-PU in the early and medium culturing .The rBMSCs displayed higher expression of collagen Ⅰ and osteopontin on the OPC10-PU in the early and medium osteogenic induction , while the high expression of these osteogenic genes occured on the OPC 30-PU and OPC50-PU in later osteogenic induction .The emphasis of genetic expression was switched from collagen Ⅰin the early and medium osteogenic induction to osteopontin in the later stage .CONCLUSION:When the content of LC remained low in the composite substrates , rBMSCs mainly responded to the mechanical stimuli induced by substrate stiffness and exhibited distinguished cellular behaviors;with the increase in the LC content , rBMSCs had strong interactions with LC by sensing the viscoelasticity of LC , probably resulted from the contribution of both substrate stiffness and the viscoelasticity of LC phase .

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.

Objective To investigate the effects of Zhoufei Pingchuan Capsules on the balance of peripheral blood helper T lymphocyte 17 cell/regulatory T lymphocyte cell(Th17/Treg)and related inflammatory factors in peripheral blood of patients with stable chronic obstructive pulmonary disease(COPD)with lung-kidney qi deficiency syndrome.Methods Totally 40 COPD patients were randomly divided into the study group and the control group,with 20 cases in each group.Another 20 cases were in the healthy group.The control group was given tiotropium bromide powder inhalation,18 μg/time,1 time/d,inhalation;on the basis of the control group,the study group was given Zhoufei Pingchuan Capsules,3 pills/time,3 times/d,orally.All patients were treated for 8 weeks.The healthy group was not given any intervention.Forced expiratory volume in one second(FEV1),FEV1/forced vital capacity(FEV1/FVC),maximum mid-expiratory flow(MMEF),carbon monoxide diffusing capacity/alveolar ventilation(DLCO/VA),arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),COPD assessment test(CAT)score,Th17/Treg ratio,cytokines interleukin(IL)-17,IL-22,IL-10,and transforming growth factor-β1(TGF-β1)were compared before and after treatment.Results Compared with before treatment,the lung function indexes(FEV1,FEV1/FVC,MMEF,DLCO/VA),blood gas indexes(PaO2,PaCO2)and CAT score in the study group after treatment were significantly improved(P<0.05).After treatment,the mean values of MMEF,DLCO/VA,PaCO2 and CAT score in the study group were better than those in the control group(P<0.05).Compared with before treatment,the levels of Th17,IL-17 and IL-22 in the study group were significantly lower,and the levels of Treg,IL-10 and TGF-β1 were significantly higher(P<0.05).After treatment,there were significant differences in Th17,Treg,IL-17,IL-22,IL-10 and TGF-β1 among the three groups(P<0.01).Further pairwise comparison showed that Th17 ranked in the order of high and low was control group>study group>healthy group,Treg in the order of high and low was healthy group>study group>control group,the levels of IL-17 and IL-22 in the order of high and low were control group>study group>healthy group,and the levels of IL-10 and TGF-β1 in the order of high and low were healthy group>study group>control group,with statistical significance(P<0.05).Conclusion Zhoufei Pingchuan Capsules can improve the lung function,arterial blood gas and symptom score of patients with lung-kidney qi deficiency syndrome in stable stage of COPD.Its mechanism may be related to regulating the balance of Th17/Treg,down-regulating the levels of Th17,IL-17 and IL-22,and up-regulating the levels of Treg,IL-10 and TGF-β1,in order to reduce airway inflammation and regulate immune homeostasis.