Regulated cell death predominantly involves apoptosis,autophagy,and regulated necrosis.It is vital that we understand how key regulatory signals can control the process of cell death.Pin1 is a cis-trans isomerase that...Regulated cell death predominantly involves apoptosis,autophagy,and regulated necrosis.It is vital that we understand how key regulatory signals can control the process of cell death.Pin1 is a cis-trans isomerase that catalyzes the isomerization of phosphorylated serine or threonine-proline motifs of a protein,thereby acting as a crucial molecular switch and regulating the protein functionality and the signaling pathways involved.However,we know very little about how Pin1-associated pathways might play a role in regulated cell death.In this paper,we review the role of Pin1 in regulated cell death and related research progress and summarize Pin1-related pathways in regulated cell death.Aside from the involvement of Pin1 in the apoptosis that accompanies neurodegenerative diseases,accumulating evidence suggests that Pin1 also plays a role in regulated necrosis and autophagy,thereby exhibiting distinct effects,including both neurotoxic and neuroprotective effects.Gaining an enhanced understanding of Pin1 in neuronal death may provide us with new options for the development of therapeutic target for neurodegenerative disorders.展开更多
Objective: To demonstrate whether the expression of silent mating type information regulation 2 homolog 1 (SIRT1) affects the level of TGF-β1 and Smad3 in HEK293 cells through regulating mTOR. Methods: First, recombi...Objective: To demonstrate whether the expression of silent mating type information regulation 2 homolog 1 (SIRT1) affects the level of TGF-β1 and Smad3 in HEK293 cells through regulating mTOR. Methods: First, recombinant plasmids DNA (rSIRT1) and siRNA targeting SIRT1 were constructed which were transfected into Human Embryonic Kidney 293 cell (HEK293) cells, respectively. Then, the generation of intracellular ROS in cells was examined by flow cytometry using the oxidation-sensitive probe. Last, the expressions of TGF-β1, smad3, P53, mTOR, p-mTOR, LC3-I and LC3-II in cells were detected to observe the effect of SIRT1 on TGF-β1 Pathway by western blot analysis. Results: We demonstrated that overexpressing of SIRT1 may decrease TGF-β1 and Smad3 expression in HEK293 cells through regulating mTOR. In addition, the result is the opposite when SIRT1 was silent in HEK293 cells. Conclusions: SIRT1 is closely related to TGF-β1/Smad3 pathway that correlates with the regulation of mTOR and ROS generation and causes diabetic nephropathy. The available evidence implies that SIRT1 has great potential as a clinical target for the prevention and treatment of renal fibrosis in the development of DN.展开更多
It is necessary to develop a new strategy for treatment of lung cancer since it is the main cause of cancer death.Tanshinone IIA(Tan IIA),an active ingredient of a commonly used traditional Chinese herb Salvia miltior...It is necessary to develop a new strategy for treatment of lung cancer since it is the main cause of cancer death.Tanshinone IIA(Tan IIA),an active ingredient of a commonly used traditional Chinese herb Salvia miltiorrhiza,provides a new direction to develop a new strategy for the treatment.It has been found that Tan IIA could inhibit lung cancer in vitro and in vivo by inducing autophagic apoptosis.Tan IIA increased apoptotic cells and the expression of cleaved caspase 3 and cleaved caspase 9,decreased B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax)ratio in human non-small cell lung cancer(NSCLC)cell lines,which was promoted by an autophagy activator Rapamycin,and weaken by autophagy inhibitor 3-methyladenine(3-MA).In addition,Tan IIA induced more autophagosomes,up-regulated light chain 3b(LC-3B)I and LC-3B II conversion and less sequestosome 1(SQSTM1/p62)expression,which cannot be weakened by the caspase 3 antagonist.Moreover,overexpression of LC-3B gene(LC3B)and downregulation of autophagic gene 5(ATG5)further confirmed that Tan IIA induced autophagic apoptosis in NSCLC cell lines.Beclin-1 gene(BECN1)overexpression and silence attenuated the effects of Tan IIA,suggesting autophagic apoptosis that Tan IIA induced was dependent on Beclin-1.Overall,our study demonstrated a new treatment mechanism of Tan IIA and suggested that Tan IIA is a potential new anti-cancer therapeutic option.展开更多
In this editorial,we comment on three articles published in a recent issue of World Journal of Gastroenterology.There is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and al...In this editorial,we comment on three articles published in a recent issue of World Journal of Gastroenterology.There is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains incomplete.Moreover,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further elucidation.Similarly,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly understood.Innovative studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.展开更多
基金supported by the National Natural Science Foundation of China, Nos. 81971891 (to KX), 82101126 (to SCW), 81772134 (to KX), 82172196 (to KX)the Natural Science Foundation of Hunan Province of China, No. 2021JJ40873 (to SCW)
文摘Regulated cell death predominantly involves apoptosis,autophagy,and regulated necrosis.It is vital that we understand how key regulatory signals can control the process of cell death.Pin1 is a cis-trans isomerase that catalyzes the isomerization of phosphorylated serine or threonine-proline motifs of a protein,thereby acting as a crucial molecular switch and regulating the protein functionality and the signaling pathways involved.However,we know very little about how Pin1-associated pathways might play a role in regulated cell death.In this paper,we review the role of Pin1 in regulated cell death and related research progress and summarize Pin1-related pathways in regulated cell death.Aside from the involvement of Pin1 in the apoptosis that accompanies neurodegenerative diseases,accumulating evidence suggests that Pin1 also plays a role in regulated necrosis and autophagy,thereby exhibiting distinct effects,including both neurotoxic and neuroprotective effects.Gaining an enhanced understanding of Pin1 in neuronal death may provide us with new options for the development of therapeutic target for neurodegenerative disorders.
文摘Objective: To demonstrate whether the expression of silent mating type information regulation 2 homolog 1 (SIRT1) affects the level of TGF-β1 and Smad3 in HEK293 cells through regulating mTOR. Methods: First, recombinant plasmids DNA (rSIRT1) and siRNA targeting SIRT1 were constructed which were transfected into Human Embryonic Kidney 293 cell (HEK293) cells, respectively. Then, the generation of intracellular ROS in cells was examined by flow cytometry using the oxidation-sensitive probe. Last, the expressions of TGF-β1, smad3, P53, mTOR, p-mTOR, LC3-I and LC3-II in cells were detected to observe the effect of SIRT1 on TGF-β1 Pathway by western blot analysis. Results: We demonstrated that overexpressing of SIRT1 may decrease TGF-β1 and Smad3 expression in HEK293 cells through regulating mTOR. In addition, the result is the opposite when SIRT1 was silent in HEK293 cells. Conclusions: SIRT1 is closely related to TGF-β1/Smad3 pathway that correlates with the regulation of mTOR and ROS generation and causes diabetic nephropathy. The available evidence implies that SIRT1 has great potential as a clinical target for the prevention and treatment of renal fibrosis in the development of DN.
基金The study was supported by grants from the National Natural Science Foundation of China(81903943 and 82074219)the Natural Science Foundation of Guangdong Province(2017A030310502)+1 种基金The study was also supported by the Key Projects of Educational Commission of Guangdong Province(2018KZDXM020)the Science and Technology Planning Project of Guangzhou(202002030009).
文摘It is necessary to develop a new strategy for treatment of lung cancer since it is the main cause of cancer death.Tanshinone IIA(Tan IIA),an active ingredient of a commonly used traditional Chinese herb Salvia miltiorrhiza,provides a new direction to develop a new strategy for the treatment.It has been found that Tan IIA could inhibit lung cancer in vitro and in vivo by inducing autophagic apoptosis.Tan IIA increased apoptotic cells and the expression of cleaved caspase 3 and cleaved caspase 9,decreased B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax)ratio in human non-small cell lung cancer(NSCLC)cell lines,which was promoted by an autophagy activator Rapamycin,and weaken by autophagy inhibitor 3-methyladenine(3-MA).In addition,Tan IIA induced more autophagosomes,up-regulated light chain 3b(LC-3B)I and LC-3B II conversion and less sequestosome 1(SQSTM1/p62)expression,which cannot be weakened by the caspase 3 antagonist.Moreover,overexpression of LC-3B gene(LC3B)and downregulation of autophagic gene 5(ATG5)further confirmed that Tan IIA induced autophagic apoptosis in NSCLC cell lines.Beclin-1 gene(BECN1)overexpression and silence attenuated the effects of Tan IIA,suggesting autophagic apoptosis that Tan IIA induced was dependent on Beclin-1.Overall,our study demonstrated a new treatment mechanism of Tan IIA and suggested that Tan IIA is a potential new anti-cancer therapeutic option.
基金Supported by the European Union-NextGenerationEU,through The National Recovery and Resilience Plan of The Republic of Bulgaria,No.BG-RRP-2.004-0008。
文摘In this editorial,we comment on three articles published in a recent issue of World Journal of Gastroenterology.There is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains incomplete.Moreover,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further elucidation.Similarly,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly understood.Innovative studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.
