AIM:To investigate the effects of urolithin A on motor function and muscle fibrosis in dystrophin-deficient mdx mice,a model of Duchenne muscular dystrophy.METHODS:Twelve 26-week-old SPF male dystrophin gene deficient C57BL/10ScSnJNju-Dmdem3Cd4/Gpt(mdx)mice were randomly divided into model group and urolithin A treatment group,with 6 mice in each group.Additionally,six wild-type SPF male mice were selected as the normal con-trol.The motor ability of the mice was evaluated by pole climbing test,inverted suspension test,grip strength test and en-durance test.The body mass,mitochondrial relative copy number,ATP level and malondialdehyde(MDA)level were compared among the mice in different groups.Hematoxylin-eosin staining,Masson staining and immunohistochemistry were performed to analyze the atrophy and pathological changes of the gastrocnemius muscle.RESULTS:Compared with normal control group,the mdx mice in model group exhibited significantly impaired motor function,as evidenced by pro-longed pole-climbing time(P<0.01),reduced suspension time and forelimb/hindlimb grip strength(P<0.01),and in-creased number of electrical stimuli required to induce movement(P<0.01).Additionally,mitochondrial relative copy number and ATP level were significantly decreased(P<0.01),while MDA level was significantly elevated(P<0.01).Histological analysis revealed marked inflammatory cell infiltration and extensive tissue fibrosis in the gastrocnemius mus-cle.In contrast,urolithin A treatment significantly improved motor performance(P<0.01),attenuated inflammatory cell infiltration and muscle fibrosis,increased mitochondrial copy number,restored ATP level(P<0.05),and reduced MDA level(P<0.01).CONCLUSION:Urolithin A ameliorates motor dysfunction and alleviates muscle fibrosis in mdx mice,suggesting its potential therapeutic benefits for Duchenne muscular dystrophy.

AIM:To investigate the effects of urolithin A on motor function and muscle fibrosis in dystrophin-deficient mdx mice,a model of Duchenne muscular dystrophy.METHODS:Twelve 26-week-old SPF male dystrophin gene deficient C57BL/10ScSnJNju-Dmdem3Cd4/Gpt(mdx)mice were randomly divided into model group and urolithin A treatment group,with 6 mice in each group.Additionally,six wild-type SPF male mice were selected as the normal con-trol.The motor ability of the mice was evaluated by pole climbing test,inverted suspension test,grip strength test and en-durance test.The body mass,mitochondrial relative copy number,ATP level and malondialdehyde(MDA)level were compared among the mice in different groups.Hematoxylin-eosin staining,Masson staining and immunohistochemistry were performed to analyze the atrophy and pathological changes of the gastrocnemius muscle.RESULTS:Compared with normal control group,the mdx mice in model group exhibited significantly impaired motor function,as evidenced by pro-longed pole-climbing time(P<0.01),reduced suspension time and forelimb/hindlimb grip strength(P<0.01),and in-creased number of electrical stimuli required to induce movement(P<0.01).Additionally,mitochondrial relative copy number and ATP level were significantly decreased(P<0.01),while MDA level was significantly elevated(P<0.01).Histological analysis revealed marked inflammatory cell infiltration and extensive tissue fibrosis in the gastrocnemius mus-cle.In contrast,urolithin A treatment significantly improved motor performance(P<0.01),attenuated inflammatory cell infiltration and muscle fibrosis,increased mitochondrial copy number,restored ATP level(P<0.05),and reduced MDA level(P<0.01).CONCLUSION:Urolithin A ameliorates motor dysfunction and alleviates muscle fibrosis in mdx mice,suggesting its potential therapeutic benefits for Duchenne muscular dystrophy.

Aim Toinvestigatethepro-angiogenic effects of Danshensu derivative ADTM and explore its underlying possible signaling pathway using zebrafish embryosasinvivomodels.Methods Theangiogenesis activities of ADTM were determined in experimental models of normal and VEGFR tyrosine kinase inhibitorⅡ(VRI )-induced vascular defective zebrafish embry-os.Embryos were treated with various concentrations (50,100,200 μmol · L-1 ) of ADTM for indicated time.The diameter and the numbers of endothelial cells of zebrafish SIVs were evaluated,respectively.In VRI model,the number of intact and defective ISVs in each zebrafish embryo was counted.The total RNA of zebrafish embryos was extracted and transcriptional profiling was analyzed by deep sequencing.Quantita-tive real-time PCR(qPCR)was performed to 4 genes selected from transcriptional profiling to validate the data collected from transcriptome analysis.Results ADTMsignificantlyincreasedsubintestinalvessels (SIVs)diameter in a concentration-dependent manner in normal zebrafish as well as restored VRI-induced blood vessels defect in VRI-exposed zebrafish. The transcriptome data analysis demonstrated that 19 signif-icantly changed genes were mapped to insulin signaling pathway.The qPCR data are in good agreement with those obtained by deep sequencing and support the consistency between the two methods for determining relative expression levels in the zebrafish model.Con-clusion Inzebrafishmodel,ADTMexhibitsthe effects of angiogenesis and blood vessel restoration. The underlying mechanism may be involved in the acti-vation of insulin signaling pathway.