Disturbed cholesterol and glucose homeostasis play crucial roles in the development of various diseases such as cardiovascular diseases,cerebrovascular diseases,central nervous system diseases,and cancer.An increasing...Disturbed cholesterol and glucose homeostasis play crucial roles in the development of various diseases such as cardiovascular diseases,cerebrovascular diseases,central nervous system diseases,and cancer.An increasing number of studies have shown that excessive body fat accumulation is associated with type 2 diabetes or insulin resistance in a vicious cycle.This vicious cycle promotes the occurrence and development of the aforementioned diseases.Therefore,stabilizing the blood lipids and blood glucose of patients is the predominant strategy for improving the symptoms of patients with cardiovascular,cerebrovascular,and central nervous system diseases.Traditional Chinese medicine,mainly Chinese herbal medicine(CHM),has a history of more than 2000 years in China,which has established a unique theory and accumulated a great wealth of clinical experience.Moreover,CHM has been widely used in China and other countries for the treatment of cardiovascular and cerebrovascular diseases,with the advantages of preventing and curing hyperlipidemia,diabetes,hypertension,and other diseases.However,the use of CHM in Western countries remains rather limited,partly because of the incomplete understanding of multiple complex components and uncertain pharmacological mechanisms.Herein,we review and discuss the benefits,molecular mechanisms,and clinical research progress of bioactive components of CHM and their preparations as therapeutics for hyperlipidemia and hyperglycemia.展开更多
Liver fibrosis is a pathological response following liver injury induced by various etiologies.Herein,we present the therapeutic potential of a novel anthraquinone compound,kanglexin(KLX),in the treatment of liver fib...Liver fibrosis is a pathological response following liver injury induced by various etiologies.Herein,we present the therapeutic potential of a novel anthraquinone compound,kanglexin(KLX),in the treatment of liver fibrosis.We observed significant suppression of the inflammatory response and extracellular matrix deposition in mice with liver fibrosis induced by CCL4,by bile duct ligation,and by a methionine-cholinedeficient diet.Mechanistically,through screening,we found that KLX interacts with HDAC1.Additionally,KLX facilitates binding between HDAC1 and KCTD11,promoting the ubiquitination-mediated degradation of HDAC1 and consequently reducing its protein level.Moreover,HDAC1 was found to bind to PPARγ,influencing its acetylation level.Following KLX treatment,the level of PPARγdeacetylation mediated by HDAC1 decreases,leading to increased protein expression of PPARγ.This effectively inhibited the NFκB and TGF-β/Smad2/3 signaling pathways,thereby reducing inflammation and extracellular matrix deposition.Ultimately,this intervention can halt the progression of liver fibrosis and ameliorate liver damage.In summary,our study demonstrated that KLX can effectively inhibit the progression of liver fibrosis by modulating the protein level and activity of HDAC1.These findings provide valuable insights for the development of effective drugs and treatment strategies for liver fibrosis.展开更多
Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies.In oral squamous cell carcinoma(OSCC),av integrin is a crucial mediator of multicellular clustering an...Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies.In oral squamous cell carcinoma(OSCC),av integrin is a crucial mediator of multicellular clustering and collective movement in vitro;however,its contribution to metastatic spread remains to be addressed.According to the emerging therapeutic concept,dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas.This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a clusterdissociating therapeutic agent in vitro.Firstly,we found marked enrichment ofαv integrin in collectivelyinvading multicellular clusters in human OSCCs.Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of av integrin in cancerous lesions.Following PEP06treatment,cell clustering on fibronectin,migration,multicellular aggregation,anchorage-independent survival and colony formation of OSCC were significantly inhibited.Moreover,PEP06 suppressed av integrin/FAK/Sre signaling in OSCC cells.PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC in vitro.Overall,these results suggest that PEP06 polypeptide 30 inhibiting av integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.展开更多
Cardiac fibrosis caused by ventricular remodeling and dysfunction such as post-myocardial infarction(MI)can lead to heart failure.RNA N6-methyladenosine(m^(6)A)methylation has been shown to play a pivotal role in the ...Cardiac fibrosis caused by ventricular remodeling and dysfunction such as post-myocardial infarction(MI)can lead to heart failure.RNA N6-methyladenosine(m^(6)A)methylation has been shown to play a pivotal role in the occurrence and development of many illnesses.In investigating the biological function of the m^(6)A reader YTHDF1 in cardiac fibrosis,adeno-associated virus 9 was used to knock down or overexpress the YTHDF1 gene in mouse hearts,and MI surgery in vivo and transforming growth factor-β(TGF-β)-activated cardiac fibroblasts in vitro were performed to establish fibrosis models.Our results demonstrated that silencing YTHDF1 in mouse hearts can significantly restore impaired cardiac function and attenuate myocardial fibrosis,whereas YTHDF1 overexpression could further enhance cardiac dysfunction and aggravate the occurrence of ventricular pathological remodeling and fibrotic development.Mechanistically,zinc finger BED-type containing 6 mediated the transcriptional function of the YTHDF1 gene promoter.YTHDF1 augmented AXL translation and activated the TGF-β-Smad2/3 signaling pathway,thereby aggravating the occurrence and development of cardiac dysfunction and myocardial fibrosis.Consistently,our data indicated that YTHDF1 was involved in activation,proliferation,and migration to participate in cardiac fibrosis in vitro.Our results revealed that YTHDF1 could serve as a potential therapeutic target for myocardial fibrosis.展开更多
基金supported by the National Natural Science Foundation of China(81730012,81970320,and 82270273)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-078)。
文摘Disturbed cholesterol and glucose homeostasis play crucial roles in the development of various diseases such as cardiovascular diseases,cerebrovascular diseases,central nervous system diseases,and cancer.An increasing number of studies have shown that excessive body fat accumulation is associated with type 2 diabetes or insulin resistance in a vicious cycle.This vicious cycle promotes the occurrence and development of the aforementioned diseases.Therefore,stabilizing the blood lipids and blood glucose of patients is the predominant strategy for improving the symptoms of patients with cardiovascular,cerebrovascular,and central nervous system diseases.Traditional Chinese medicine,mainly Chinese herbal medicine(CHM),has a history of more than 2000 years in China,which has established a unique theory and accumulated a great wealth of clinical experience.Moreover,CHM has been widely used in China and other countries for the treatment of cardiovascular and cerebrovascular diseases,with the advantages of preventing and curing hyperlipidemia,diabetes,hypertension,and other diseases.However,the use of CHM in Western countries remains rather limited,partly because of the incomplete understanding of multiple complex components and uncertain pharmacological mechanisms.Herein,we review and discuss the benefits,molecular mechanisms,and clinical research progress of bioactive components of CHM and their preparations as therapeutics for hyperlipidemia and hyperglycemia.
基金supported by the National Natural Science Foundation of China(82104168,U21A20339)。
文摘Liver fibrosis is a pathological response following liver injury induced by various etiologies.Herein,we present the therapeutic potential of a novel anthraquinone compound,kanglexin(KLX),in the treatment of liver fibrosis.We observed significant suppression of the inflammatory response and extracellular matrix deposition in mice with liver fibrosis induced by CCL4,by bile duct ligation,and by a methionine-cholinedeficient diet.Mechanistically,through screening,we found that KLX interacts with HDAC1.Additionally,KLX facilitates binding between HDAC1 and KCTD11,promoting the ubiquitination-mediated degradation of HDAC1 and consequently reducing its protein level.Moreover,HDAC1 was found to bind to PPARγ,influencing its acetylation level.Following KLX treatment,the level of PPARγdeacetylation mediated by HDAC1 decreases,leading to increased protein expression of PPARγ.This effectively inhibited the NFκB and TGF-β/Smad2/3 signaling pathways,thereby reducing inflammation and extracellular matrix deposition.Ultimately,this intervention can halt the progression of liver fibrosis and ameliorate liver damage.In summary,our study demonstrated that KLX can effectively inhibit the progression of liver fibrosis by modulating the protein level and activity of HDAC1.These findings provide valuable insights for the development of effective drugs and treatment strategies for liver fibrosis.
基金funded by the National Natural Science Foundation of China(grant Nos.81730012 and 81673426)the Grant of Republic Bashkortostan for Young Scientists(grant No.26 GR).
文摘Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies.In oral squamous cell carcinoma(OSCC),av integrin is a crucial mediator of multicellular clustering and collective movement in vitro;however,its contribution to metastatic spread remains to be addressed.According to the emerging therapeutic concept,dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas.This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a clusterdissociating therapeutic agent in vitro.Firstly,we found marked enrichment ofαv integrin in collectivelyinvading multicellular clusters in human OSCCs.Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of av integrin in cancerous lesions.Following PEP06treatment,cell clustering on fibronectin,migration,multicellular aggregation,anchorage-independent survival and colony formation of OSCC were significantly inhibited.Moreover,PEP06 suppressed av integrin/FAK/Sre signaling in OSCC cells.PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC in vitro.Overall,these results suggest that PEP06 polypeptide 30 inhibiting av integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.
基金funded by the National Natural Science Foundation of China(Nos.82104168 and U21A20339)the China Postdoctoral Science Foundation(Nos.2021M693832)Heilongjiang Province Postdoctoral Science Foundation(No.LBH-Z20174).
文摘Cardiac fibrosis caused by ventricular remodeling and dysfunction such as post-myocardial infarction(MI)can lead to heart failure.RNA N6-methyladenosine(m^(6)A)methylation has been shown to play a pivotal role in the occurrence and development of many illnesses.In investigating the biological function of the m^(6)A reader YTHDF1 in cardiac fibrosis,adeno-associated virus 9 was used to knock down or overexpress the YTHDF1 gene in mouse hearts,and MI surgery in vivo and transforming growth factor-β(TGF-β)-activated cardiac fibroblasts in vitro were performed to establish fibrosis models.Our results demonstrated that silencing YTHDF1 in mouse hearts can significantly restore impaired cardiac function and attenuate myocardial fibrosis,whereas YTHDF1 overexpression could further enhance cardiac dysfunction and aggravate the occurrence of ventricular pathological remodeling and fibrotic development.Mechanistically,zinc finger BED-type containing 6 mediated the transcriptional function of the YTHDF1 gene promoter.YTHDF1 augmented AXL translation and activated the TGF-β-Smad2/3 signaling pathway,thereby aggravating the occurrence and development of cardiac dysfunction and myocardial fibrosis.Consistently,our data indicated that YTHDF1 was involved in activation,proliferation,and migration to participate in cardiac fibrosis in vitro.Our results revealed that YTHDF1 could serve as a potential therapeutic target for myocardial fibrosis.
