Objective:Buyinqianzheng Formula(BYQZF)is clinically employed in traditional Chinese medicine to treat Parkinson's disease(PD)by improving mitochondrial dysfunction.However,the underlying mechanisms by which BYQZF...Objective:Buyinqianzheng Formula(BYQZF)is clinically employed in traditional Chinese medicine to treat Parkinson's disease(PD)by improving mitochondrial dysfunction.However,the underlying mechanisms by which BYQZF affects mitochondrial morphology remain unknown.Therefore,we observed the effects of BYQZF on mitochondria from the perspective of the PINK1/Parkin pathway.Methods:Cell survival rates were assessed by Cell Counting Kit-8 assay.Expression levels of PINK1 and Parkin mRNA were examined by qRT-PCR.Protein expression levels of PINK1,PINK1-Ser228,Parkin,Parkin-Ser65,Drp1,and Drp1-Ser637 were examined by western blotting.PINK1,Parkin,and MitoTracker?Red CMXRos(MTR)were stained by triple-labeled immunofluorescence,and observed under laser confocal microscopy.Results:Cell survival rate,mitochondrial form factor,mean length and number of mitochondrial network branches,mitochondrial activity,m RNA expression levels of PINK1 and Parkin,and protein expression levels of PINK1,Parkin,and Drp1-Ser637 were reduced after 1-methyl-4-phenylpyridinium(MPP^(+))intervention.In contrast,Pearson's correlation coefficients between PINK1 and Parkin,and between Parkin and MTR,as well as protein expression levels of PINK1-Ser228,Parkin-Ser65,and Drp1 increased significantly after MPP^(+) intervention.Treatment with BYQZF increased cell survival rate,mitochondrial form factor,mean length and number of mitochondrial network branches,mitochondrial activity,m RNA expression levels of PINK1 and Parkin,and expression of PINK1,Parkin,and Drp1-Ser637 proteins.Pearson's correlation coefficients between PINK1 and Parkin,and between Parkin and MTR,as well as protein expression levels of PINK1-Ser228,Parkin-Ser65,and Drp1 decreased after BYQZF treatment.Conclusion:These results demonstrate that BYQZF has a protective effect on mitochondrial molecular mechanisms in the PD cell model,and the mechanism is related to the PINK1/Parkin pathway.展开更多
ATP depletion is one of the pathological bases in cerebral ischemia.Electro-acupuncture(EA)is widely used in clinical practice for ischemia.However,the mechanism of EA remains unclear.The purpose of this study was to ...ATP depletion is one of the pathological bases in cerebral ischemia.Electro-acupuncture(EA)is widely used in clinical practice for ischemia.However,the mechanism of EA remains unclear.The purpose of this study was to investigate whether EA could activate the AMPK/PGC-1α/TFAM signaling pathway and,consequently,increase the preservation of ATP in rats with ischemia.In this study,48 rats were randomly divided into four groups as a sham-operation control group(sham group),a middle cerebral artery occlusion group(MCAO group),an EA group,and an EA group blocked by the AMPK inhibitor compound C(EA+CC group)(N=12/group).The rats of the EA group and EA+CC group received the EA treatment for 7 days.The rats that belonged in the two remaining groups were only grasped in the same condition.Then,their brain tissues were collected for further detection.When compared with other groups,EA significantly reduced neurological deficits score and increased motor function.The cerebral infarction volume was significantly reduced in the EA group according to TTC staining.With western blot,we found that EA improved the ratio of p-AMPKα/AMPKα(P<0.05),however,there is no difference between the MCAO group and sham group(P>0.05).In addition,EA also increased the expression of PGC-1αand TFAM(all P<0.05).By Elisa,we observed that EA increased the preservation of ATP(P<0.05)and mitochondrial respiratory enzymes,including Complex I(P<0.05),Complex IV(P<0.05),but not Complex III(P>0.05).In summary,we conclude that EA may protect against ischemic damage in MCAO rats,improve the preservation of ATP and mitochondrial respiratory enzymes.This effect may be positively regulated by the activation of the PGC-1α/TFAM signaling pathway.展开更多
Rheumatoid arthritis(RA)is a chronic inflammatory autoimmune disease that affects millions of people worldwide.Current therapeutic drugs for RA are often limited by poor solubility,unresponsive to monotherapy,low bioa...Rheumatoid arthritis(RA)is a chronic inflammatory autoimmune disease that affects millions of people worldwide.Current therapeutic drugs for RA are often limited by poor solubility,unresponsive to monotherapy,low bioavailability,and severe side effects.To address these challenges,we developed a pH-responsive,biodegradable,and multifunctional oral hydrogel delivery system(GTPM Gel)based on the major active ingredients(glycyrrhizic acid(GA),total alkaloids of FZ(TAC),pseudoephedrine(PE),Mg^(2+))from Mahuang Fuzi decoction for the treatment of RA in clinic.In this system,all four components synergistically contributed to gel formation and pharmacodynamics,making each component indispensable.Notably,Mg2+in GTPM Gel promoted the gelation of GA via coordination bonds while exhibiting anti-inflammatory properties and facilitating osteochondral regeneration.Moreover,GTPM Gel enhanced the solubility of TAC and reduced its toxicity,leading to improved anti-RA effects.In vitro and In vivo studies demonstrated that GTPM Gel effectively inhibited the polarization of inflammatory macrophages,reduced pannus formation,and inhibited bone and cartilage erosion by downregulating the PI3K/AKT/NF-κB signaling pathway.This study suggested that the magnesium ion-mediated natural multi-component hydrogel,with its remarkable efficacy and biocompatibility,holds promise as a potential therapeutic candidate for RA treatment.展开更多
The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells,as well as acts as the"mucus layer-soil"for intestinal flora adhesion and colonization.Its structural and funct...The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells,as well as acts as the"mucus layer-soil"for intestinal flora adhesion and colonization.Its structural and functional integrity is crucial to human health.Intestinal mucus is regulated by factors such as diet,living habits,hormones,neurotransmitters,cytokines,and intestinal flora.The mucus layer’s thickness,viscosity,porosity,growth rate,and glycosylation status affect the structure of the gut flora colonized on it.The interaction between"mucus layer-soil"and"gut bacteria-seed"is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease(NAFLD).Probiotics,prebiotics,fecal microbiota transplantation(FMT),and wash microbial transplantation are efficient methods for managing NAFLD,but their long-term efficacy is poor.FMT is focused on achieving the goal of treating diseases by enhancing the"gut bacteria-seed".However,a lack of effective repair and management of the"mucus layer-soil"may be a reason why"seeds"cannot be well colonized and grow in the host gut,as the thinning and destruction of the"mucus layer-soil"is an early symptom of NAFLD.This review summarizes the existing correlation between intestinal mucus and gut microbiota,as well as the pathogenesis of NAFLD,and proposes a new perspective that"mucus layer-soil"restoration combined with"gut bacteria-seed"FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.展开更多
基金the National Natural Science Foundation of China(Grant Nos.81573773 and 81774110)。
文摘Objective:Buyinqianzheng Formula(BYQZF)is clinically employed in traditional Chinese medicine to treat Parkinson's disease(PD)by improving mitochondrial dysfunction.However,the underlying mechanisms by which BYQZF affects mitochondrial morphology remain unknown.Therefore,we observed the effects of BYQZF on mitochondria from the perspective of the PINK1/Parkin pathway.Methods:Cell survival rates were assessed by Cell Counting Kit-8 assay.Expression levels of PINK1 and Parkin mRNA were examined by qRT-PCR.Protein expression levels of PINK1,PINK1-Ser228,Parkin,Parkin-Ser65,Drp1,and Drp1-Ser637 were examined by western blotting.PINK1,Parkin,and MitoTracker?Red CMXRos(MTR)were stained by triple-labeled immunofluorescence,and observed under laser confocal microscopy.Results:Cell survival rate,mitochondrial form factor,mean length and number of mitochondrial network branches,mitochondrial activity,m RNA expression levels of PINK1 and Parkin,and protein expression levels of PINK1,Parkin,and Drp1-Ser637 were reduced after 1-methyl-4-phenylpyridinium(MPP^(+))intervention.In contrast,Pearson's correlation coefficients between PINK1 and Parkin,and between Parkin and MTR,as well as protein expression levels of PINK1-Ser228,Parkin-Ser65,and Drp1 increased significantly after MPP^(+) intervention.Treatment with BYQZF increased cell survival rate,mitochondrial form factor,mean length and number of mitochondrial network branches,mitochondrial activity,m RNA expression levels of PINK1 and Parkin,and expression of PINK1,Parkin,and Drp1-Ser637 proteins.Pearson's correlation coefficients between PINK1 and Parkin,and between Parkin and MTR,as well as protein expression levels of PINK1-Ser228,Parkin-Ser65,and Drp1 decreased after BYQZF treatment.Conclusion:These results demonstrate that BYQZF has a protective effect on mitochondrial molecular mechanisms in the PD cell model,and the mechanism is related to the PINK1/Parkin pathway.
基金supported by the National Natural Science Foundation of China(No.81574048 and No.81904268)Key personnel training project of Health Care in middle-aged and young people in Fujian province(No.2019-ZQN-81).
文摘ATP depletion is one of the pathological bases in cerebral ischemia.Electro-acupuncture(EA)is widely used in clinical practice for ischemia.However,the mechanism of EA remains unclear.The purpose of this study was to investigate whether EA could activate the AMPK/PGC-1α/TFAM signaling pathway and,consequently,increase the preservation of ATP in rats with ischemia.In this study,48 rats were randomly divided into four groups as a sham-operation control group(sham group),a middle cerebral artery occlusion group(MCAO group),an EA group,and an EA group blocked by the AMPK inhibitor compound C(EA+CC group)(N=12/group).The rats of the EA group and EA+CC group received the EA treatment for 7 days.The rats that belonged in the two remaining groups were only grasped in the same condition.Then,their brain tissues were collected for further detection.When compared with other groups,EA significantly reduced neurological deficits score and increased motor function.The cerebral infarction volume was significantly reduced in the EA group according to TTC staining.With western blot,we found that EA improved the ratio of p-AMPKα/AMPKα(P<0.05),however,there is no difference between the MCAO group and sham group(P>0.05).In addition,EA also increased the expression of PGC-1αand TFAM(all P<0.05).By Elisa,we observed that EA increased the preservation of ATP(P<0.05)and mitochondrial respiratory enzymes,including Complex I(P<0.05),Complex IV(P<0.05),but not Complex III(P>0.05).In summary,we conclude that EA may protect against ischemic damage in MCAO rats,improve the preservation of ATP and mitochondrial respiratory enzymes.This effect may be positively regulated by the activation of the PGC-1α/TFAM signaling pathway.
基金funded by the National Natural Science Foundation of China(Nos.82274072 and 82474059)the Beijing Municipal Natural Science Foundation(Nos.7242221 and 7254503)+2 种基金Beijing Nova Programme Interdisciplinary Cooperation Project(No.20240484578)the Fundamental Research Funds for the Central Universities(China,Nos.2023-JYB-JBZD-049,2022-XJKYQD-008,and 2024-JYB-XJSJJ004)Beijing Key Laboratory for Basic and Development Research on Chinese Medicine(Beijing,No.100102).
文摘Rheumatoid arthritis(RA)is a chronic inflammatory autoimmune disease that affects millions of people worldwide.Current therapeutic drugs for RA are often limited by poor solubility,unresponsive to monotherapy,low bioavailability,and severe side effects.To address these challenges,we developed a pH-responsive,biodegradable,and multifunctional oral hydrogel delivery system(GTPM Gel)based on the major active ingredients(glycyrrhizic acid(GA),total alkaloids of FZ(TAC),pseudoephedrine(PE),Mg^(2+))from Mahuang Fuzi decoction for the treatment of RA in clinic.In this system,all four components synergistically contributed to gel formation and pharmacodynamics,making each component indispensable.Notably,Mg2+in GTPM Gel promoted the gelation of GA via coordination bonds while exhibiting anti-inflammatory properties and facilitating osteochondral regeneration.Moreover,GTPM Gel enhanced the solubility of TAC and reduced its toxicity,leading to improved anti-RA effects.In vitro and In vivo studies demonstrated that GTPM Gel effectively inhibited the polarization of inflammatory macrophages,reduced pannus formation,and inhibited bone and cartilage erosion by downregulating the PI3K/AKT/NF-κB signaling pathway.This study suggested that the magnesium ion-mediated natural multi-component hydrogel,with its remarkable efficacy and biocompatibility,holds promise as a potential therapeutic candidate for RA treatment.
基金National Natural Science Funds of China(Nos.82204827,81970545,and 82170609)Zhejiang Provincial Basic Public Welfare Research Project(Nos.LQ23H270016 and LGF20H030010)+1 种基金Hangzhou Major Science and Technology Plan Project(No.20172016A02)Major Projects of Hangzhou Medical and Health Science and Technology Plan(No.0020191059)
文摘The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells,as well as acts as the"mucus layer-soil"for intestinal flora adhesion and colonization.Its structural and functional integrity is crucial to human health.Intestinal mucus is regulated by factors such as diet,living habits,hormones,neurotransmitters,cytokines,and intestinal flora.The mucus layer’s thickness,viscosity,porosity,growth rate,and glycosylation status affect the structure of the gut flora colonized on it.The interaction between"mucus layer-soil"and"gut bacteria-seed"is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease(NAFLD).Probiotics,prebiotics,fecal microbiota transplantation(FMT),and wash microbial transplantation are efficient methods for managing NAFLD,but their long-term efficacy is poor.FMT is focused on achieving the goal of treating diseases by enhancing the"gut bacteria-seed".However,a lack of effective repair and management of the"mucus layer-soil"may be a reason why"seeds"cannot be well colonized and grow in the host gut,as the thinning and destruction of the"mucus layer-soil"is an early symptom of NAFLD.This review summarizes the existing correlation between intestinal mucus and gut microbiota,as well as the pathogenesis of NAFLD,and proposes a new perspective that"mucus layer-soil"restoration combined with"gut bacteria-seed"FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.
