Background:EMP2 is a tumor-associated membrane protein belonging to the GAS-3/PMP22 gene family.EMP2 expression demonstrates significant tissue specificity and heterogeneity in various human tissues and tumor tissues,...Background:EMP2 is a tumor-associated membrane protein belonging to the GAS-3/PMP22 gene family.EMP2 expression demonstrates significant tissue specificity and heterogeneity in various human tissues and tumor tissues,where it may play a role in either promoting or inhibiting tumor growth.This study aimed to investigate the expression level,biological functions,and molecular mechanisms of EMP2 in liver cancer.Methods:we analyzed the mRNA expression levels of EMPs family genes in hepatocellular carcinoma(HCC)tissues and normal liver tissues based on the TCGA database and immunohistochemical analysis of tissue microarrays.Subsequently,we constructed HCC cell lines with either knockdown or overexpression of EMP2 to examine the biological functions and molecular mechanisms of EMP2 in tumorigenesis in vivo and in vitro.Results:Bioinformatic and immunohistochemical analysis of tissue microarrays have confirmed the significant upregulation of EMP2 in HCC tissues.In vitro and in vivo studies have shown that downregulation of EMP2 results in a moderate reduction in the proliferation and invasive capacity of HCC cells.Conversely,overexpression of EMP2 enhances the invasive capacity of HCC cells and induces autophagy.Initial investigations into the molecular mechanisms underlying EMP2-mediated enhancement of HCC cell invasion have revealed the dual regulation of EMP2-induced autophagy and the integrin pathway,which synergistically influence the invasive and metastatic potential of HCC cells.Conclusion:EMP2 holds promise as a diagnostic marker for HCC metastasis and a potential target for targeted therapy.展开更多
Some novel peptide dendrimers bearing four amino acids, GD and RGD peptides on their surface were synthesized from tetrakis[(carboxyethoxy)methyl]-methane using DCC method.
THE Chinese knot is a decorative handicraft that is intricately woven with one single colored rope.Knot tying in China harks back to ancient times.Before Chinese writing appeared,people tied knots to make records of t...THE Chinese knot is a decorative handicraft that is intricately woven with one single colored rope.Knot tying in China harks back to ancient times.Before Chinese writing appeared,people tied knots to make records of their lives.The size and shape indicated the significance and nature of an event.展开更多
THAT China invented the compass is well known to all.The very first was known as a chariot compass,or"south-pointing chariot."Legend has it that when the mythical Huangdi(Yellow Emperor)and tribal leader Chi...THAT China invented the compass is well known to all.The very first was known as a chariot compass,or"south-pointing chariot."Legend has it that when the mythical Huangdi(Yellow Emperor)and tribal leader Chi You were at war,the former ordered his Minister Feng Hou to invent a chariot compass that would enable him to find his way through dense fog and defeat his foe.Third century BC thinker Han Fei explained in one of his books the motivation for inventing the compass:"It was easy to get lost due to poor orientation,which is why kings in ancient times invented an instrument that points south and so shows in which direction West and East lie."展开更多
Interferon Regulatory Factors(IRFs),a family of transcription factors,profoundly influence the immune system,impacting both physiological and pathological processes.This review explores the diverse functions of nine m...Interferon Regulatory Factors(IRFs),a family of transcription factors,profoundly influence the immune system,impacting both physiological and pathological processes.This review explores the diverse functions of nine mammalian IRF members,each featuring conserved domains essential for interactions with other transcription factors and cofactors.These interactions allow IRFs to modulate a broad spectrum of physiological processes,encompassing host defense,immune response,and cell development.Conversely,their pivotal role in immune regulation implicates them in the pathophysiology of various diseases,such as infectious diseases,autoimmune disorders,metabolic diseases,and cancers.In this context,IRFs display a dichotomous nature,functioning as both tumor suppressors and promoters,contingent upon the specific disease milieu.Post-translational modifications of IRFs,including phosphorylation and ubiquitination,play a crucial role in modulating their function,stability,and activation.As prospective biomarkers and therapeutic targets,IRFs present promising opportunities for disease intervention.Further research is needed to elucidate the precise mechanisms governing IRF regulation,potentially pioneering innovative therapeutic strategies,particularly in cancer treatment,where the equilibrium of IRF activities is of paramount importance.展开更多
A series of spirooxindole-ferrocene hybrids bearing five or four contiguous chiral centers were designed and synthesized via organocatalysis.In vitro protein binding and cellular proliferation assays suggested that co...A series of spirooxindole-ferrocene hybrids bearing five or four contiguous chiral centers were designed and synthesized via organocatalysis.In vitro protein binding and cellular proliferation assays suggested that compound 5 d was the most potent mouse double minute 2 homolog(MDM2)inhibitor.In addition,mechanistic studies indicated that compound 5 d suppressed MDM2-mediated p53 degradation,induced apoptosis and promoted oxidative damage.Molecular docking studies have suggested that 5 d binds to MDM2 by mimicking the Trp23 and Leu26 residues of p53.This work can provide a basis for the development of novel multifunctional MDM2 inhibitors.The further exploration of more derivatives from this library and additional investigation of organocatalysis application in the development of new molecules may generate new potential lead compounds for cancer-targeted therapy.展开更多
基金supported by the Fundamental Research Funds for the National Natural Science Foundation of China(Nos.22177084 and 82104373)the Fundamental Research Funds of Science&Technology Department of Sichuan Province(No.2022YFQ0054).
文摘Background:EMP2 is a tumor-associated membrane protein belonging to the GAS-3/PMP22 gene family.EMP2 expression demonstrates significant tissue specificity and heterogeneity in various human tissues and tumor tissues,where it may play a role in either promoting or inhibiting tumor growth.This study aimed to investigate the expression level,biological functions,and molecular mechanisms of EMP2 in liver cancer.Methods:we analyzed the mRNA expression levels of EMPs family genes in hepatocellular carcinoma(HCC)tissues and normal liver tissues based on the TCGA database and immunohistochemical analysis of tissue microarrays.Subsequently,we constructed HCC cell lines with either knockdown or overexpression of EMP2 to examine the biological functions and molecular mechanisms of EMP2 in tumorigenesis in vivo and in vitro.Results:Bioinformatic and immunohistochemical analysis of tissue microarrays have confirmed the significant upregulation of EMP2 in HCC tissues.In vitro and in vivo studies have shown that downregulation of EMP2 results in a moderate reduction in the proliferation and invasive capacity of HCC cells.Conversely,overexpression of EMP2 enhances the invasive capacity of HCC cells and induces autophagy.Initial investigations into the molecular mechanisms underlying EMP2-mediated enhancement of HCC cell invasion have revealed the dual regulation of EMP2-induced autophagy and the integrin pathway,which synergistically influence the invasive and metastatic potential of HCC cells.Conclusion:EMP2 holds promise as a diagnostic marker for HCC metastasis and a potential target for targeted therapy.
基金the financial support of the National Natural Science Foundation of China (Project No. 20472055).
文摘Some novel peptide dendrimers bearing four amino acids, GD and RGD peptides on their surface were synthesized from tetrakis[(carboxyethoxy)methyl]-methane using DCC method.
文摘THE Chinese knot is a decorative handicraft that is intricately woven with one single colored rope.Knot tying in China harks back to ancient times.Before Chinese writing appeared,people tied knots to make records of their lives.The size and shape indicated the significance and nature of an event.
文摘THAT China invented the compass is well known to all.The very first was known as a chariot compass,or"south-pointing chariot."Legend has it that when the mythical Huangdi(Yellow Emperor)and tribal leader Chi You were at war,the former ordered his Minister Feng Hou to invent a chariot compass that would enable him to find his way through dense fog and defeat his foe.Third century BC thinker Han Fei explained in one of his books the motivation for inventing the compass:"It was easy to get lost due to poor orientation,which is why kings in ancient times invented an instrument that points south and so shows in which direction West and East lie."
基金supported by the Fundamental Research Funds for the National Natural Science Foundation of China(Nos.82103757,82273559,82104373 and 82304063)Sichuan Natural Science Foundation Project(2023NSFSC1554 and 24NSFSC5087).
文摘Interferon Regulatory Factors(IRFs),a family of transcription factors,profoundly influence the immune system,impacting both physiological and pathological processes.This review explores the diverse functions of nine mammalian IRF members,each featuring conserved domains essential for interactions with other transcription factors and cofactors.These interactions allow IRFs to modulate a broad spectrum of physiological processes,encompassing host defense,immune response,and cell development.Conversely,their pivotal role in immune regulation implicates them in the pathophysiology of various diseases,such as infectious diseases,autoimmune disorders,metabolic diseases,and cancers.In this context,IRFs display a dichotomous nature,functioning as both tumor suppressors and promoters,contingent upon the specific disease milieu.Post-translational modifications of IRFs,including phosphorylation and ubiquitination,play a crucial role in modulating their function,stability,and activation.As prospective biomarkers and therapeutic targets,IRFs present promising opportunities for disease intervention.Further research is needed to elucidate the precise mechanisms governing IRF regulation,potentially pioneering innovative therapeutic strategies,particularly in cancer treatment,where the equilibrium of IRF activities is of paramount importance.
基金supported by grants from the National Natural Science Foundation(Nos.21772131,81672552,81773890,82073997)the Fundamental Research Funds of Science&Technology Department of Sichuan Province(Nos.2019YFSY0004,2017JY0226,2019YFS0298)Project First-Class Disciplines Development supported by CDUTCM。
文摘A series of spirooxindole-ferrocene hybrids bearing five or four contiguous chiral centers were designed and synthesized via organocatalysis.In vitro protein binding and cellular proliferation assays suggested that compound 5 d was the most potent mouse double minute 2 homolog(MDM2)inhibitor.In addition,mechanistic studies indicated that compound 5 d suppressed MDM2-mediated p53 degradation,induced apoptosis and promoted oxidative damage.Molecular docking studies have suggested that 5 d binds to MDM2 by mimicking the Trp23 and Leu26 residues of p53.This work can provide a basis for the development of novel multifunctional MDM2 inhibitors.The further exploration of more derivatives from this library and additional investigation of organocatalysis application in the development of new molecules may generate new potential lead compounds for cancer-targeted therapy.