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| 1 | Discovering small molecules as Wnt inhibitors that promote heart regeneration and injury repair显示文摘There are intense interests in discovering pro regenerative medicine leads that can promote cardiac differentiation and regeneration,as well as repair damaged heart tissues.We have combined zebrafish embryo-based screens with cardiomyogenesis assays to discover selective small molecules that modulate heart development and regeneration with minimal adverse effects.Two related compounds with novel structures,named as Cardiomogen 1 and 2(CDMG1 and CDMG2),were identified for their capacity to promote myocardial hyperplasia through expansion of the cardiac progenitor cell population.We find that Cardiomogen acts as a Wnt inhibitor by targeting p-catenin and reducing Tcf/Lef-mediated transcription in cultured cells.CDMG treatment of amputated zebrafish hearts reduces nuclear p-catenin in injured heart tissue,increases cardiomyocyte(CM)proliferation,and expedites wound healing,thus accelerating cardiac muscle regeneration.Importantly,Cardiomogen can alleviate the functional deterioration of mammalian hearts after myocardial infarction.Injured hearts exposed to CDMG1 display increased newly formed CMs and reduced fibrotic scar tissue,which are in part attributable to the^-catenin reduction.Our findings indicate Cardiomogen as a Wnt inhibitor in enhancing injury-induced CM proliferation and heart regeneration,highlighting the values of embryo-based small molecule screens in discovery of effective and safe medicine leads. | Shuying Xie Wenbin Fu Guangju Yu Xueli Hu Kaa Seng Lai Xiangwen Peng Yating Zhou Xuejiao Zhu Ptamen Christov Leah Sawyer Terri T.Ni Gary A.Sulikowski Zhongzhou Yang Ethan Lee Chunyu Zeng Wei E.Wang Tao P.Zhong | 2020 | Journal of Molecular Cell Biology2020，12，1： | 4 |
| 2 | The spinel phase of LiMn2O4 as a cathode in secondary lithium cells显示文摘 | J.M.Tarascon E.Wang F.K.Shokoohi W.R.MacKinnon S.Colson | | 0，，： | 1 |
| 3 | A different chemical route to synthesize ZnO nanoparticles显示文摘 | C.Wang Q.Li B.Mao E.Wang and C.Tian | | 0，，： | 1 |
| 4 | 查看详情显示文摘 | R.Yang L.Zhang Y.Wang Z.Shi D.Shi H.Gao E.Wang and G.Zhang | | 0，，36： | 1 |
| 5 | Satellite cell-derived exosome-mediated delivery of microRNA-23a/27a/26a cluster ameliorates the renal tubulointerstitial fibrosis in mouse diabetic nephropathy显示文摘Renal tubulointerstitial fibrosis(TIF)is considered as the final convergent pathway of diabetic nephropathy(DN)without effective therapies currently.MiRNAs play a key role in fibrotic diseases and become promising therapeutic targets for kidney diseases,while miRNA clusters,formed by the cluster arrangement of miRNAs on chromosomes,can regulate diverse biological functions alone or synergistically.In this study,we developed clustered miR-23a/27a/26a-loaded skeletal muscle satellite cells–derived exosomes(Exos)engineered with RVG peptide,and investigated their therapeutic efficacy in a murine model of DN.Firstly,we showed that miR-23a-3p,miR-26a-5p and miR-27a-3p were markedly decreased in serum samples of DN patients using miRNA sequencing.Meanwhile,we confirmed that miR-23a-3p,miR-26a-5p and miR-27a-3p were primarily located in proximal renal tubules and highly negatively correlated with TIF in db/db mice at 20 weeks of age.We then engineered RVG-miR-23a/27a/26a cluster loaded Exos derived from muscle satellite cells,which not only enhanced the stability of miR-23a/27a/26a cluster,but also efficiently delivered more miR-23a/27a/26a cluster homing to the injured kidney.More importantly,administration of RVG-miR-23a/27a/26a-Exos(100μg,i.v.,once a week for 8 weeks)significantly ameliorated tubular injury and TIF in db/db mice at 20 weeks of age.We revealed that miR-23a/27a/26a-Exos enhanced antifibrotic effects by repressing miRNA cluster-targeting Lpp simultaneously,as well as miR-27a-3p-targeting Zbtb20 and miR-26a-5p-targeting Klhl42,respectively.Knockdown of Lpp by injection of AAV-Lpp-RNAi effectively ameliorated the progression of TIF in DN mice.Taken together,we established a novel kidney-targeting Exo-based delivery system by manipulating the miRNA-23a/27a/26a cluster to ameliorate TIF in DN,thus providing a promising therapeutic strategy for DN. | Jia-ling Ji Hui-min Shi Zuo-lin Li Ran Jin Gao-ting Qu Hui Zheng E.Wang Yun-yang Qiao Xing-yue Li Ling Ding Da-fa Ding Liu-cheng Ding Wei-hua Gan Bin Wang Ai-qing Zhang | 2023 | Acta Pharmacologica Sinica2023，44，12： | 0 |
| 6 | Fluorine-thiol displacement probes for acetaminophen's hepatotoxicity显示文摘Chemicals possessing reactive electrophiles can denature innate proteins leading to undesired toxicity,and the overdose-induced liver injury by drugs containing electrophiles has been one of the major causes of non-approval and withdraw by the US Food and Drug Administration(FDA).Elucidating the associated proteins could guide the future development of therapeutics to circumvent these drugs’toxicities,but was largely limited by the current probing tools due to the steric hindrance of chemical tags including the common“click chemistry”labels.Taking the widely used non-steroidal anti-inflammatory drug acetaminophen(APAP)as an example,we hereby designed and synthesized an APAP analogue using fluorine as a steric-free label.Cell toxicity studies indicated our analogue has similar activity to the parent drug.This analogue was applied to the mouse hepatocellular proteome together with the corresponding desthiobiotinSH probe for subsequent fluorine-thiol displacement reactions(FTDRs).This set of probes has enabled the labeling and pull-down of hepatocellular target proteins of the APAP metabolite as validated by Western blotting.Our preliminary validation results supported the interaction of APAP with the thioredoxin protein,which is an important redox protein for normal liver function.These results demonstrated that our probes confer minimal steric perturbation and mimic the compounds of interest,allowing for global profiling of interacting proteins.The fluorine-thiol displacement probing system could emerge as a powerful tool to enable the investigation of drug-protein interactions in complex biological environments. | Benjamin L.Prather Shuyue Ji Yue Zhao Femil Joseph Shajan Mi Zhao Zakey Yusuf Buuh Robert Maloney Rui Zhang Carson Cohen Rongsheng E.Wang | 2023 | Acta Pharmaceutica Sinica B2023，13，1： | 0 |
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