Objective This study aimed to investigate the therapeutic effects and underlying mechanisms of the combination of Yinchenhao decoction(YCHD)and praziquantel(PZQ)in a Schistosoma japonicum(S.japonicum)-induced mouse mo...Objective This study aimed to investigate the therapeutic effects and underlying mechanisms of the combination of Yinchenhao decoction(YCHD)and praziquantel(PZQ)in a Schistosoma japonicum(S.japonicum)-induced mouse model of schistosomiasis.Methods Six-week-old male BALB/c mice were randomly divided into five groups:control group,infected group,infected-PZQ group(I-PZQ),infected-YCHD group(I-YCHD),and infected-PZQ+YCHD group(I-PZQ+YCHD).The mice were infected with S.japonicum cercariae in infected group,I-PZQ group,I-YCHD group,and I-PZQ+YCHD group(n=6 per group)and maintained for 63 days.From day 43 to day 63 postinfection,the mice received PZQ(150 mg/kg,intragastric gavage),YCHD(10 mL/kg,intragastric gavage),or a combination of both.The control and infected groups received equal amounts of sterile double-distilled water for the same period.At the end of the experiment,the mice were anesthetized with pentobarbital sodium and sacrificed.Serum alanine transaminase(ALT)and aspartate transaminase(AST)levels were measured.Network pharmacology analysis was used to predict the targets of YCHD in the treatment of schistosomiasis.Histopathological analysis,Western blotting,immunofluorescence,quantitative polymerase chain reaction and flow cytometry were employed to evaluate liver pathology and molecular changes.Results Compared with the other groups,the I-PZQ+YCHD group presented significantly decreased serum ALT and AST levels(P<0.001).The I-PZQ+YCHD group exhibited improved pathological changes in the liver,as evidenced by reduced area of single granuloma(P<0.01),granuloma area(P<0.01),and Ishak score of liver fibrosis(P<0.01).Network pharmacology analysis suggested that YCHD may alleviate schistosomiasis-related liver injury through the modulation of the endoplasmic reticulum stress(ERS)pathway.Western blot analysis revealed that ERS-related markers,including glucose-regulated protein 78(GRP78),inositol-requiring enzyme 1 alpha(IRE1α),X-box binding protein 1(XBP-1),and C/EBP homologous protein(CHOP),were significantly downregulated in the I-PZQ+YCHD group(P<0.05).Furthermore,the I-PZQ+YCHD group presented reduced hepatocyte apoptosis(P<0.05),diminished hepatic macrophage infiltration(P<0.05)and downregulated expression of proinflammatory cytokines(TNF-α,IL-1βand IL-6)(P<0.05).Conclusion YCHD combined with PZQ reduced schistosomiasis-associated hepatic granulomatous inflammation and fibrosis by inhibiting hepatic apoptosis and ERS.展开更多
Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplanta...Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone.Bone marrow mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles.Small extracellular vesicles derived from bone marrow mesenchymal stem cells,which offer low immunogenicity,minimal tumorigenic risk,and ease of transportation,have been utilized in the treatment of various neurological diseases.These vesicles exhibit various activities,including anti-inflammatory actions,promotion of tissue repair,and immune regulation.Therefore,novel strategies using human retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration.In this study,we developed such an approach utilizing retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats,a genetic model of retinal degeneration.Our findings revealed that the combination of bone marrow mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats.The addition of bone marrow mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival,migration,and differentiation of the exogenous retinal progenitor cells.Concurrently,these small extracellular vesicles inhibited the activation of regional microglia,promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina,and facilitated their differentiation into photoreceptors and bipolar cells.These findings suggest that bone marrow mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.展开更多
INTRODUCTION.On January 7,2025,at 9:05 AM BJT,a MS6.8 earthquake(CENC epicenter:28.50°N,87.45°E)struck Dingri County,Xizang Province(hereinafter referred to as the Dingri mainshock).The inferred moment magni...INTRODUCTION.On January 7,2025,at 9:05 AM BJT,a MS6.8 earthquake(CENC epicenter:28.50°N,87.45°E)struck Dingri County,Xizang Province(hereinafter referred to as the Dingri mainshock).The inferred moment magnitude,based on regional/teleseismic waveform inversion and back-projection,is approximately MW7.1.Focal mechanism solutions,aftershock distribution,and field surveys indicate that the Dingri mainshock was a normal-faulting event,with a nearly north-south strike and a westward-dipping fault plane.展开更多
基金supported by the National Natural Science Foundation of China(No.81802036 and No.81876182).
文摘Objective This study aimed to investigate the therapeutic effects and underlying mechanisms of the combination of Yinchenhao decoction(YCHD)and praziquantel(PZQ)in a Schistosoma japonicum(S.japonicum)-induced mouse model of schistosomiasis.Methods Six-week-old male BALB/c mice were randomly divided into five groups:control group,infected group,infected-PZQ group(I-PZQ),infected-YCHD group(I-YCHD),and infected-PZQ+YCHD group(I-PZQ+YCHD).The mice were infected with S.japonicum cercariae in infected group,I-PZQ group,I-YCHD group,and I-PZQ+YCHD group(n=6 per group)and maintained for 63 days.From day 43 to day 63 postinfection,the mice received PZQ(150 mg/kg,intragastric gavage),YCHD(10 mL/kg,intragastric gavage),or a combination of both.The control and infected groups received equal amounts of sterile double-distilled water for the same period.At the end of the experiment,the mice were anesthetized with pentobarbital sodium and sacrificed.Serum alanine transaminase(ALT)and aspartate transaminase(AST)levels were measured.Network pharmacology analysis was used to predict the targets of YCHD in the treatment of schistosomiasis.Histopathological analysis,Western blotting,immunofluorescence,quantitative polymerase chain reaction and flow cytometry were employed to evaluate liver pathology and molecular changes.Results Compared with the other groups,the I-PZQ+YCHD group presented significantly decreased serum ALT and AST levels(P<0.001).The I-PZQ+YCHD group exhibited improved pathological changes in the liver,as evidenced by reduced area of single granuloma(P<0.01),granuloma area(P<0.01),and Ishak score of liver fibrosis(P<0.01).Network pharmacology analysis suggested that YCHD may alleviate schistosomiasis-related liver injury through the modulation of the endoplasmic reticulum stress(ERS)pathway.Western blot analysis revealed that ERS-related markers,including glucose-regulated protein 78(GRP78),inositol-requiring enzyme 1 alpha(IRE1α),X-box binding protein 1(XBP-1),and C/EBP homologous protein(CHOP),were significantly downregulated in the I-PZQ+YCHD group(P<0.05).Furthermore,the I-PZQ+YCHD group presented reduced hepatocyte apoptosis(P<0.05),diminished hepatic macrophage infiltration(P<0.05)and downregulated expression of proinflammatory cytokines(TNF-α,IL-1βand IL-6)(P<0.05).Conclusion YCHD combined with PZQ reduced schistosomiasis-associated hepatic granulomatous inflammation and fibrosis by inhibiting hepatic apoptosis and ERS.
基金supported by the National Natural Science Foundation of China,Nos.82271132(to YL),82101167(to BB)the Natural Science Foundation of Chongqing,Nos.CSTB2022NSCQ-MSX0020(to BB),cstc2019jcyj-msxmX0473(to FC).
文摘Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone.Bone marrow mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles.Small extracellular vesicles derived from bone marrow mesenchymal stem cells,which offer low immunogenicity,minimal tumorigenic risk,and ease of transportation,have been utilized in the treatment of various neurological diseases.These vesicles exhibit various activities,including anti-inflammatory actions,promotion of tissue repair,and immune regulation.Therefore,novel strategies using human retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration.In this study,we developed such an approach utilizing retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats,a genetic model of retinal degeneration.Our findings revealed that the combination of bone marrow mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats.The addition of bone marrow mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival,migration,and differentiation of the exogenous retinal progenitor cells.Concurrently,these small extracellular vesicles inhibited the activation of regional microglia,promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina,and facilitated their differentiation into photoreceptors and bipolar cells.These findings suggest that bone marrow mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.
基金supported by the“CUG Scholar”Scientific Research Funds at China University of Geosciences(Wuhan)(No.2021230)supported by the National Natural Science Foundation of China(Nos.41922025,42204062)。
文摘INTRODUCTION.On January 7,2025,at 9:05 AM BJT,a MS6.8 earthquake(CENC epicenter:28.50°N,87.45°E)struck Dingri County,Xizang Province(hereinafter referred to as the Dingri mainshock).The inferred moment magnitude,based on regional/teleseismic waveform inversion and back-projection,is approximately MW7.1.Focal mechanism solutions,aftershock distribution,and field surveys indicate that the Dingri mainshock was a normal-faulting event,with a nearly north-south strike and a westward-dipping fault plane.
