AIM： To investigate whether the function of hepatocytes co-cultured with bone marrow mesenchymal stem cells （MSCs） could be maintained in serum from acute-on- chronic liver failure （ACLF） patients.METHODS： Hepat...AIM： To investigate whether the function of hepatocytes co-cultured with bone marrow mesenchymal stem cells （MSCs） could be maintained in serum from acute-on- chronic liver failure （ACLF） patients.METHODS： Hepatocyte supportive functions and cy- totoxicity of sera from 18 patients with viral hepatitis B-induced ACLF and 18 healthy volunteers were evalu- ated for porcine hepatocytes co-cultured with MSCs and hepatocyte mono-layered culture, respectively. Chemo- kine profile was also examined for the normal serum and liver failure serum.RESULTS： Hepatocyte growth factor （HGF） and Tumor necrosis factor; tumor necrosis factor （TNF）-a were re- markably elevated in response to ACLF while epidermal growth factor （EGF） and VEGF levels were significantly decreased. Liver failure serum samples induced a higher detachment rate, lower viability and decreased liver sup- port functions in the homo-hepatocyte culture. Hepato-cytes co-cultured with MSCs could tolerate the cytotoxic- ity of the serum from ACLF patients and had similar liver support functions compared with the hepatocytes cul- tured with healthy human serum in vitro. In addition, co- cultured hepatocytes maintained a proliferative capability despite of the insult from liver failure serum.CONCLUSION： ACLF serum does not impair the cell morphology, viability, proliferation and overall metabolic capacities of hepatocyte co-cultured with MSCs in vitro.展开更多
Wnt/β-catenin regulates cellular functions related to tumor initiation and progression, cell proliferation, differ- entiation, survival, and adhesion, β-Catenin-independent Wnt pathways have been proposed to regulat...Wnt/β-catenin regulates cellular functions related to tumor initiation and progression, cell proliferation, differ- entiation, survival, and adhesion, β-Catenin-independent Wnt pathways have been proposed to regulate cell polarity and migration, including metastasis. In this review, we discuss the possible roles of both β-catenin-dependent and -independent signaling pathways in tumor progression, with an emphasis on their regulation of Rho-family GTPases, cytoskeletal remodeling, and relationships with cell-cell adhesion and cilia/ciliogenesis.展开更多
Voltage-gated calcium channels(VGCCs) play critical roles in cardiac and skeletal muscle contractions,hormone and neurotransmitter release,as well as slower processes such as cell proliferation,differentiation,migrati...Voltage-gated calcium channels(VGCCs) play critical roles in cardiac and skeletal muscle contractions,hormone and neurotransmitter release,as well as slower processes such as cell proliferation,differentiation,migration and death.Mutations in VGCCs lead to numerous cardiac,muscle and neurological disease,and their physiological function is tightly regulated by kinases,phosphatases,G-proteins,calmodulin and many other proteins.Fifteen years ago,RGK proteins were discovered as the most potent endogenous regulators of VGCCs.They are a family of monomeric GTPases(Rad,Rem,Rem2,and Gem/Kir),in the superfamily of Ras GTPases,and they have two known functions: regulation of cytoskeletal dynamics including dendritic arborization and inhibition of VGCCs.Here we review the mechanisms and molecular determinants of RGK-mediated VGCC inhibition,the physiological impact of this inhibition,and recent evidence linking the two known RGK functions.展开更多
Cell communication affects all aspects of cell structure and behavior,such as cell proliferation,differentiation,division,and coordination of various physiological functions.The moving RNA in plants and mammalian cell...Cell communication affects all aspects of cell structure and behavior,such as cell proliferation,differentiation,division,and coordination of various physiological functions.The moving RNA in plants and mammalian cells indicates that nucleic acid could be one of the various types of messengers for cell communication.The microvesicle is a critical pathway that mediates RNA moving and keeps moving RNA stable in body fluids.When moving miRNA enters the target cell,it functions by altering the gene expression profile and significantly inhibiting mRNA translation in recipient cells.Thus,moving RNA may act as a long-range modulator during development,organogenesis,and tumor metastasis.展开更多
Viruses replicate and proliferate in host cells while continuously adjusting to and modulating the host environment.They encode a wide spectrum of multifunctional proteins,which interplay with and modify proteins in h...Viruses replicate and proliferate in host cells while continuously adjusting to and modulating the host environment.They encode a wide spectrum of multifunctional proteins,which interplay with and modify proteins in host cells.Viral genomes were chronologically the first to be sequenced.However,the corresponding viral proteomes,the alterations of host proteomes upon viral infection,and the dynamic nature of proteins,such as post-translational modifications,enzymatic cleavage,and activation or destruction by proteolysis,remain largely unknown.Emerging high-throughput techniques,in particular quantitative or semi-quantitative mass spectrometry-based proteomics analysis of viral and cellular proteomes,have been applied to define viruses and their interactions with their hosts.Here,we review the major areas of viral proteomics,including virion proteomics,structural proteomics,viral protein interactomics,and changes to the host cell proteome upon viral infection.展开更多
Aerobic glycolysis,also known as the Warburg effect,is a hallmark of cancer and essential for metabolism in malignancies,but its regulation and modulation in cancer cells remain poorly understood.Here,using large-scal...Aerobic glycolysis,also known as the Warburg effect,is a hallmark of cancer and essential for metabolism in malignancies,but its regulation and modulation in cancer cells remain poorly understood.Here,using large-scale functional screening,we identified a tumor-associated and broadly expressed oncogenic long noncoding RNA LINC00973.Notably,knocking down LINC00973 significantly inhibits the proliferation of multiple types of cancer cells and reduces tumor growth in vivo.Mechanistically,LINC00973 directly binds to lactate dehydrogenase A(LDHA),an essential glycolytic enzyme,and enhances its enzymatic activity,thereby promoting glycolysis.Clinically,high expression of LINC00973 is significantly associated with poor prognosis in many types of human cancers.This work demonstrates that LINC00973 modulates cancer-specific regulation of the Warburg effect,and may represent a potential target for broad-acting anti-cancer therapies.展开更多
基金Supported by the National Natural Science Foundation of China,No.30772129Jiangsu Provincial Key Medical Center for Hepatobiliary Disease,No.ZX200605
文摘AIM： To investigate whether the function of hepatocytes co-cultured with bone marrow mesenchymal stem cells （MSCs） could be maintained in serum from acute-on- chronic liver failure （ACLF） patients.METHODS： Hepatocyte supportive functions and cy- totoxicity of sera from 18 patients with viral hepatitis B-induced ACLF and 18 healthy volunteers were evalu- ated for porcine hepatocytes co-cultured with MSCs and hepatocyte mono-layered culture, respectively. Chemo- kine profile was also examined for the normal serum and liver failure serum.RESULTS： Hepatocyte growth factor （HGF） and Tumor necrosis factor; tumor necrosis factor （TNF）-a were re- markably elevated in response to ACLF while epidermal growth factor （EGF） and VEGF levels were significantly decreased. Liver failure serum samples induced a higher detachment rate, lower viability and decreased liver sup- port functions in the homo-hepatocyte culture. Hepato-cytes co-cultured with MSCs could tolerate the cytotoxic- ity of the serum from ACLF patients and had similar liver support functions compared with the hepatocytes cul- tured with healthy human serum in vitro. In addition, co- cultured hepatocytes maintained a proliferative capability despite of the insult from liver failure serum.CONCLUSION： ACLF serum does not impair the cell morphology, viability, proliferation and overall metabolic capacities of hepatocyte co-cultured with MSCs in vitro.
文摘Wnt/β-catenin regulates cellular functions related to tumor initiation and progression, cell proliferation, differ- entiation, survival, and adhesion, β-Catenin-independent Wnt pathways have been proposed to regulate cell polarity and migration, including metastasis. In this review, we discuss the possible roles of both β-catenin-dependent and -independent signaling pathways in tumor progression, with an emphasis on their regulation of Rho-family GTPases, cytoskeletal remodeling, and relationships with cell-cell adhesion and cilia/ciliogenesis.
基金supported by the Dyson College 2014 Faculty Summer Research Grant Program (Zafir Buraei)Dyson College 2014 Summer Undergraduate Student-Faculty Research Award (Zafir Buraei and Sukhjinder Kaur)+2 种基金the National Key Basic Research Program of China (2014CB910301 to Yang Jian)the Top Talents Program of Yunnan Province, China (Yang Jian)the US National Institutes of Health (NS053494 to Yang Jian)
文摘Voltage-gated calcium channels(VGCCs) play critical roles in cardiac and skeletal muscle contractions,hormone and neurotransmitter release,as well as slower processes such as cell proliferation,differentiation,migration and death.Mutations in VGCCs lead to numerous cardiac,muscle and neurological disease,and their physiological function is tightly regulated by kinases,phosphatases,G-proteins,calmodulin and many other proteins.Fifteen years ago,RGK proteins were discovered as the most potent endogenous regulators of VGCCs.They are a family of monomeric GTPases(Rad,Rem,Rem2,and Gem/Kir),in the superfamily of Ras GTPases,and they have two known functions: regulation of cytoskeletal dynamics including dendritic arborization and inhibition of VGCCs.Here we review the mechanisms and molecular determinants of RGK-mediated VGCC inhibition,the physiological impact of this inhibition,and recent evidence linking the two known RGK functions.
基金supported by the National Basic Research Program of China(2009CB825603,2012CB517605)National Natural Science Foundation of China(81272392)
文摘Cell communication affects all aspects of cell structure and behavior,such as cell proliferation,differentiation,division,and coordination of various physiological functions.The moving RNA in plants and mammalian cells indicates that nucleic acid could be one of the various types of messengers for cell communication.The microvesicle is a critical pathway that mediates RNA moving and keeps moving RNA stable in body fluids.When moving miRNA enters the target cell,it functions by altering the gene expression profile and significantly inhibiting mRNA translation in recipient cells.Thus,moving RNA may act as a long-range modulator during development,organogenesis,and tumor metastasis.
基金supported by the National Project on Major Infectious Diseases Prevention (Grant No. 2008ZX10002-009)the National Basic Research Program of China (Grant No. 2011CB910703)
文摘Viruses replicate and proliferate in host cells while continuously adjusting to and modulating the host environment.They encode a wide spectrum of multifunctional proteins,which interplay with and modify proteins in host cells.Viral genomes were chronologically the first to be sequenced.However,the corresponding viral proteomes,the alterations of host proteomes upon viral infection,and the dynamic nature of proteins,such as post-translational modifications,enzymatic cleavage,and activation or destruction by proteolysis,remain largely unknown.Emerging high-throughput techniques,in particular quantitative or semi-quantitative mass spectrometry-based proteomics analysis of viral and cellular proteomes,have been applied to define viruses and their interactions with their hosts.Here,we review the major areas of viral proteomics,including virion proteomics,structural proteomics,viral protein interactomics,and changes to the host cell proteome upon viral infection.
基金This work was supported by the National Natural Science Foundation of China(31371314 and 81673460)Sichuan Youth Science and Technology Innovation Research Team of Experimental Formulology(2020JDTD0022).
文摘Aerobic glycolysis,also known as the Warburg effect,is a hallmark of cancer and essential for metabolism in malignancies,but its regulation and modulation in cancer cells remain poorly understood.Here,using large-scale functional screening,we identified a tumor-associated and broadly expressed oncogenic long noncoding RNA LINC00973.Notably,knocking down LINC00973 significantly inhibits the proliferation of multiple types of cancer cells and reduces tumor growth in vivo.Mechanistically,LINC00973 directly binds to lactate dehydrogenase A(LDHA),an essential glycolytic enzyme,and enhances its enzymatic activity,thereby promoting glycolysis.Clinically,high expression of LINC00973 is significantly associated with poor prognosis in many types of human cancers.This work demonstrates that LINC00973 modulates cancer-specific regulation of the Warburg effect,and may represent a potential target for broad-acting anti-cancer therapies.
