The development of Meizhou Hakka cuisine relies on the role of professional cooking talents.Higher vocational colleges serve as the platform for cultivating cooking talents.Among various training models,the implementa...The development of Meizhou Hakka cuisine relies on the role of professional cooking talents.Higher vocational colleges serve as the platform for cultivating cooking talents.Among various training models,the implementation of the progressive talent training model featuring the integration of industry and education and work-study alternation is conducive to carrying out talent cultivation activities,improving the effectiveness of professional talent development,and effectively meeting the needs of market development.From the perspective of Meizhou Hakka cuisine cooking talents,this paper analyzes the problems existing in the implementation of the industry-education integration and work-study alternation model,and puts forward specific practical strategies for talent cultivation.The purpose is to enhance the training effect of Hakka cuisine cooking talents and provide reference for the subsequent optimization of professional teaching.展开更多
Alcoholic liver disease(ALD) causes insulin resistance, lipid metabolism dysfunction, and inflammation. We investigated the protective effects and direct regulating target of S-allylmercaptocysteine(SAMC) from aged ga...Alcoholic liver disease(ALD) causes insulin resistance, lipid metabolism dysfunction, and inflammation. We investigated the protective effects and direct regulating target of S-allylmercaptocysteine(SAMC) from aged garlic on liver cell injury. A chronic ethanol-fed ALD in vivo model(the NIAAA model) was used to test the protective functions of SAMC. It was observed that SAMC(300 mg/kg, by gavage method) effectively ameliorated ALD-induced body weight reduction, steatosis,insulin resistance, and inflammation without affecting the health status of the control mice, as demonstrated by histological, biochemical, and molecular biology assays. By using biophysical assays and molecular docking, we demonstrated that SAMC directly targeted insulin receptor(INSR) protein on the cell membrane and then restored downstream IRS-1/AKT/GSK3 b signaling. Liver-specific knock-down in mice and siRNA-mediated knock-down in AML-12 cells of Insr significantly impaired SAMC(250 mmol/L in cells)-mediated protection. Restoration of the IRS-1/AKT signaling partly recovered hepatic injury and further contributed to SAMC’s beneficial effects. Continuous administration of AKT agonist and recombinant IGF-1 in combination with SAMC showed hepato-protection in the mice model.Long-term(90-day) administration of SAMC had no obvious adverse effect on healthy mice. We conclude that SAMC is an effective and safe hepato-protective complimentary agent against ALD partly through the direct binding of INSR and partial regulation of the IRS-1/AKT/GSK3 b pathway.展开更多
The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis(NASH)remain largely unknown.We aimed to elucidate the roles of hepatic cyclooxygenase 1(COX1)in autophagy and the pathogenesis of diet-induc...The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis(NASH)remain largely unknown.We aimed to elucidate the roles of hepatic cyclooxygenase 1(COX1)in autophagy and the pathogenesis of diet-induced steatohepatitis in mice.Human nonalcoholic fatty liver disease(NAFLD)liver samples were used to examine the protein expression of COX1 and the level of autophagy.Cox1^(Δhepa)mice and their wildtype littermates were generated and fed with 3 different NASH models.We found that hepatic COX1 expression was increased in patients with NASH and diet induced NASH mice models accompanied by impaired autophagy.COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy.Mechanistically,COX1 directly interacted with WD repeat domain,phosphoinositide interacting 2(WIPI2),which was crucial for autophagosome maturation.Adeno-associated virus(AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1^(Δhepa)mice,indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy.In conclusion,we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2.Targeting the COX1 WIPI2 axis may be a novel therapeutic strategy for NASH.展开更多
Background:Since boosting stem cell resilience in stressful environments is critical for the therapeutic efficacy of stem cell-based transplantations in liver disease,this study aimed to establish the efficacy of a tr...Background:Since boosting stem cell resilience in stressful environments is critical for the therapeutic efficacy of stem cell-based transplantations in liver disease,this study aimed to establish the efficacy of a transient plasmid-based preconditioning strategy for boosting the capability of mesenchymal stromal cells(MSCs)for anti-inflammation/antioxidant defenses and paracrine actions in recipient hepatocytes.Methods:Human adipose mesenchymal stem cells(hADMSCs)were subjected to transfer,either with or without the nuclear factor erythroid 2-related factor 2(Nrf2)/Dickkopf1(DKK1)genes,followed by exposure to TNF-a/H2O2.Mouse models were subjected to acute chronic liver failure(ACLF)and subsequently injected with either transfected or untransfected MSCs.These hADMSCs and ACLF mouse models were used to investigate the interaction between Nrf2/DKK1 and the hepatocyte receptor cytoskeleton-associated protein 4(CKAP4).Results:Activation of Nrf2 and DKK1 enhanced the anti-stress capacity of MSCs in vitro.In a murine model of ACLF,transient co-overexpression of Nrf2 and DKK1 via plasmid transfection improved MSC resilience against inflammatory and oxidative assaults,boosted MSC transplantation efficacy,and promoted recipient liver regeneration due to a shift from the activation of the anti-regenerative IFN-c/STAT1 pathway to the pro-regenerative IL-6/STAT3 pathway in the liver.Importantly,the therapeutic benefits of MSC transplantation were nullified when the receptor CKAP4,which interacts with DKK1,was specifically removed from recipient hepatocytes.However,the removal of the another receptor low-density lipoprotein receptor-related protein 6(LRP6)had no impact on the effectiveness of MSC transplantation.Moreover,in long-term observations,no tumorigenicity was detected in mice following transplantation of transiently preconditioned MSCs.Conclusions:Co-stimulation with Nrf2/DKK1 safely improved the efficacy of human MSC-based therapies in murine models of ACLF through CKAP4-dependent paracrine mechanisms.展开更多
基金2025 Meizhou Municipal Planning Project of Philosophy and Social Sciences(Project No.:mzsklx2025101)。
文摘The development of Meizhou Hakka cuisine relies on the role of professional cooking talents.Higher vocational colleges serve as the platform for cultivating cooking talents.Among various training models,the implementation of the progressive talent training model featuring the integration of industry and education and work-study alternation is conducive to carrying out talent cultivation activities,improving the effectiveness of professional talent development,and effectively meeting the needs of market development.From the perspective of Meizhou Hakka cuisine cooking talents,this paper analyzes the problems existing in the implementation of the industry-education integration and work-study alternation model,and puts forward specific practical strategies for talent cultivation.The purpose is to enhance the training effect of Hakka cuisine cooking talents and provide reference for the subsequent optimization of professional teaching.
基金supported by National Natural Science Foundation of China (81970515)Guangdong Natural Science Funds for Distinguished Young Scholar (2019B151502013, China)。
文摘Alcoholic liver disease(ALD) causes insulin resistance, lipid metabolism dysfunction, and inflammation. We investigated the protective effects and direct regulating target of S-allylmercaptocysteine(SAMC) from aged garlic on liver cell injury. A chronic ethanol-fed ALD in vivo model(the NIAAA model) was used to test the protective functions of SAMC. It was observed that SAMC(300 mg/kg, by gavage method) effectively ameliorated ALD-induced body weight reduction, steatosis,insulin resistance, and inflammation without affecting the health status of the control mice, as demonstrated by histological, biochemical, and molecular biology assays. By using biophysical assays and molecular docking, we demonstrated that SAMC directly targeted insulin receptor(INSR) protein on the cell membrane and then restored downstream IRS-1/AKT/GSK3 b signaling. Liver-specific knock-down in mice and siRNA-mediated knock-down in AML-12 cells of Insr significantly impaired SAMC(250 mmol/L in cells)-mediated protection. Restoration of the IRS-1/AKT signaling partly recovered hepatic injury and further contributed to SAMC’s beneficial effects. Continuous administration of AKT agonist and recombinant IGF-1 in combination with SAMC showed hepato-protection in the mice model.Long-term(90-day) administration of SAMC had no obvious adverse effect on healthy mice. We conclude that SAMC is an effective and safe hepato-protective complimentary agent against ALD partly through the direct binding of INSR and partial regulation of the IRS-1/AKT/GSK3 b pathway.
基金partly supported by National Natural Science Foundation of China(82125026 and 82122009)Natural Science Foundation of Shandong Province(ZR2022QH241 and ZR2020ZD11,China)Seed Fund for Basic Research of University Research Committee of The University of Hong Kong(20161159263,Hong Kong,China)。
文摘The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis(NASH)remain largely unknown.We aimed to elucidate the roles of hepatic cyclooxygenase 1(COX1)in autophagy and the pathogenesis of diet-induced steatohepatitis in mice.Human nonalcoholic fatty liver disease(NAFLD)liver samples were used to examine the protein expression of COX1 and the level of autophagy.Cox1^(Δhepa)mice and their wildtype littermates were generated and fed with 3 different NASH models.We found that hepatic COX1 expression was increased in patients with NASH and diet induced NASH mice models accompanied by impaired autophagy.COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy.Mechanistically,COX1 directly interacted with WD repeat domain,phosphoinositide interacting 2(WIPI2),which was crucial for autophagosome maturation.Adeno-associated virus(AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1^(Δhepa)mice,indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy.In conclusion,we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2.Targeting the COX1 WIPI2 axis may be a novel therapeutic strategy for NASH.
基金funded by grants from the National Natural Science Foundation of China[nos 82122009,81970515,82170605,and 81873573]the Guangdong Natural Science Funds for Distinguished Young Scholar[no.2019B151502013]the Guangdong Basic and Applied Research Foundation[no.2021B1515120069].
文摘Background:Since boosting stem cell resilience in stressful environments is critical for the therapeutic efficacy of stem cell-based transplantations in liver disease,this study aimed to establish the efficacy of a transient plasmid-based preconditioning strategy for boosting the capability of mesenchymal stromal cells(MSCs)for anti-inflammation/antioxidant defenses and paracrine actions in recipient hepatocytes.Methods:Human adipose mesenchymal stem cells(hADMSCs)were subjected to transfer,either with or without the nuclear factor erythroid 2-related factor 2(Nrf2)/Dickkopf1(DKK1)genes,followed by exposure to TNF-a/H2O2.Mouse models were subjected to acute chronic liver failure(ACLF)and subsequently injected with either transfected or untransfected MSCs.These hADMSCs and ACLF mouse models were used to investigate the interaction between Nrf2/DKK1 and the hepatocyte receptor cytoskeleton-associated protein 4(CKAP4).Results:Activation of Nrf2 and DKK1 enhanced the anti-stress capacity of MSCs in vitro.In a murine model of ACLF,transient co-overexpression of Nrf2 and DKK1 via plasmid transfection improved MSC resilience against inflammatory and oxidative assaults,boosted MSC transplantation efficacy,and promoted recipient liver regeneration due to a shift from the activation of the anti-regenerative IFN-c/STAT1 pathway to the pro-regenerative IL-6/STAT3 pathway in the liver.Importantly,the therapeutic benefits of MSC transplantation were nullified when the receptor CKAP4,which interacts with DKK1,was specifically removed from recipient hepatocytes.However,the removal of the another receptor low-density lipoprotein receptor-related protein 6(LRP6)had no impact on the effectiveness of MSC transplantation.Moreover,in long-term observations,no tumorigenicity was detected in mice following transplantation of transiently preconditioned MSCs.Conclusions:Co-stimulation with Nrf2/DKK1 safely improved the efficacy of human MSC-based therapies in murine models of ACLF through CKAP4-dependent paracrine mechanisms.
