Objective:Wallerian degeneration is a pathological process closely related to peripheral nerve regeneration following injury,and includes the disintegration and phagocytosis of peripheral nervous system cells.Traditio...Objective:Wallerian degeneration is a pathological process closely related to peripheral nerve regeneration following injury,and includes the disintegration and phagocytosis of peripheral nervous system cells.Traditionally,morphological changes are observed by performing immunofluorescence staining after sectioning,which results in the loss of some histological information.The purpose of this study was to explore a new,nondestmetive,and systematic method for observing axonal histological changes during Wallerian degeneration.Methods:Thirty male Thy1-YFP-16 mice(SPF grade,6 weeks old,20±5 g)were randomly selected and divided into clear,unobstructed brain imaging cocktails and computational analysis(CUBIC)optical clearing(n=15)and traditional method groups(n=15).Five mice in each group were sacrificed at 1st,3rd,and 5th day following a crush operation.The histological axon changes were observed by CUBIC light optical clearing treatment,direct tissue section imaging,and HE staining.Results:The results revealed that,compared with traditional imaging methods,there was no physical damage to the samples,which allowed for three-dimensional and deep-seated tissue imaging through CUBIC.Local image information could be nicely obtained by direct fluorescence imaging and HE staining,but it was difficult to obtain image information of the entire sample.At the same time,the image information obtained by fluorescence imaging and HE staining was partially lost.Conclusion:The combining of CUBIC and Thy1-YFP transgenic mice allowed for a clear and comprehensive observation of histological changes of axons in Wallerian degeneration.展开更多
Dr.George Chiou is Professor and Director of the Institute of Ocular Pharmacology and Professor of Neuroscience and Experimental Therapeutics at Texas A&M University System Health Science Center.He has served as H...Dr.George Chiou is Professor and Director of the Institute of Ocular Pharmacology and Professor of Neuroscience and Experimental Therapeutics at Texas A&M University System Health Science Center.He has served as Head of Department of Medical Pharmacology and Toxicology for 27.5 years until the department was reorganized in 2006.He also is an Adjunct Professor of Surgery and Ophthalmology at Texas A&M University College of Medicine,展开更多
Published by The WJG Press and Elsevier Inc．,PO Box 23451 Beijing 100023,China Fax:+86-(0)10-85381893 E-mail:wjg@wjgnet．com http://www．wjgnet．com The World Journal of Gastroenterology Editorial Board consists of 5...Published by The WJG Press and Elsevier Inc．,PO Box 23451 Beijing 100023,China Fax:+86-(0)10-85381893 E-mail:wjg@wjgnet．com http://www．wjgnet．com The World Journal of Gastroenterology Editorial Board consists of 519 members,representing a team of worldwide experts in gastroenterology and hepatology．They are from 51 countries,including Albania(1),Algeria(1),Argentina(1),Australia(8), Austria(5),Belarus(1),Belgium(6),Brazil(1),Bulgaria(1),Canada(7),China(50),Costa Rica(1),Croatia(1),Denmark(6), Egypt(1),Finland(1),France(18),Germany(35),Greece(2),Hungary(2),Iceland(1),India(5),Iran(1),Ireland(1),Israel(2),Italy(41),Japan(132),Lithuania(1),Macedonia(1),Malaysia(3),Monaco(1),Netherlands(13),Norway(2),Pakistan(1),Philippines(1),Poland(2),Portugal(1),Russia(3),Singapore(2),Slovakia(1),South Africa(2),South Korea(6),Spain(20), Sri Lanka(1),Swaziland(1),Sweden(4),Switzerland(4),Turkey(3),United Kingdom(20),United States(90),Yugoslavia(1)． HONORARY EDITORS-IN-CHIEF Ke-Ji Chen,Professor Xiyuan Hospital,Chinese Tranditional Medicine University,Beijing 100091,China. kjchen@public．bta．net．展开更多
Background:Clear cell renal carcinoma(ccRCC),the leading histological subtype of RCC,lacks any targeted therapy options.Although some studies have shown that early growth response factor 1(EGR1)has a significant role ...Background:Clear cell renal carcinoma(ccRCC),the leading histological subtype of RCC,lacks any targeted therapy options.Although some studies have shown that early growth response factor 1(EGR1)has a significant role in cancer development and progression,its role and underlying mechanisms in ccRCC remain poorly understood.Methods:The Cancer Genome Atlas(TCGA)database was utilized to examine the expression of EGR1 in ccRCC.The expression of EGR1 in 55 ccRCC tissues was evaluated using immunohistochemistry.The link between EGR1 expression and clinicopathological variables was examined through an analysis.Gain-of-function assays were employed to investigate EGR1’s biological functions in ccRCC cells,involving proliferation,colony formation,invasion assays,and tumorigenesis in nude mice.In order to assess the protein expression of mitogen-activated protein kinase 15(MAPK15),E-cadherin,matrix metalloproteinase-9/-2(MMP-9 and MMP-2),Western blot technique was applied.Results:The results revealed a decrease in EGR1 expression in ccRCC tissues.This decrease was strongly linked to TNM stage,lymphatic metastasis,tumor size,histological grade,and unfavorable prognosis in ccRCC patients.It has been demonstrated that overexpressing EGR1 inhibits the growth of xenograft tumors in vivo and inhibits cell colony formation,motility,and invasion in vitro.Furthermore,EGR1 can prevent the development and movement of ccRCC cells by controlling the expression of MMP-2,MMP-9,E-cadherin,and MAPK15.Conclusions:The EGR1/MAPK15 axis may represent a promising target for drug development,with EGR1 serving as a possible target for ccRCC therapy.展开更多
Background:Clear cell renal cell carcinoma(ccRCC)is an aggressive malignancy associated with limited treatment options and poor prognosis.Emerging studies suggest that the actin-regulating protein actin-related protei...Background:Clear cell renal cell carcinoma(ccRCC)is an aggressive malignancy associated with limited treatment options and poor prognosis.Emerging studies suggest that the actin-regulating protein actin-related protein 2/3 complex subunit 1B(ARPC1B),a key regulatory protein within the actin cytoskeleton,could play a pivotal role in ccRCC progression.The current study aimed to uncover the biological functions of ARPC1B and the molecular mechanisms driving its effects in ccRCC.Methods:ARPC1B expression and prognostic implications were analyzed using data sourced from the Gene Expression Profiling Interactive Analysis(GEPIA)platform,immunohistochemical(IHC)staining on 150 tumor samples along with 30 corresponding normal tissues,and Western blotting(WB)analyses across multiple ccRCC-derived cell lines.Functional assays assessing cell proliferation,colony formation capability,migration,invasion,and in vivo tumorigenicity were conducted following either ARPC1B suppression or upregulation.Additionally,WB analysis was utilized to evaluate proteins linked to epithelial-to-mesenchymal transition(EMT)and the Wnt/β-catenin pathway.Results:The findings revealed a substantial elevation of ARPC1B in ccRCC tissues and cell lines,significantly associated with advanced TNM stages,higher Fuhrman grades,and reduced overall survival(OS)(p<0.001).Multivariate statistical analysis identified ARPC1B as a standalone prognostic factor.Silencing ARPC1B notably impaired ccRCC cellular activities,and tumorigenesis in animalmodels,whereas augmented ARPC1B expression enhanced these malignant phenotypes.Mechanistically,downregulation of ARPC1B suppressed Wnt/β-catenin signaling and disrupted EMT,indicated by reducedβ-catenin,c-Myc,cyclin D1,and ZEB-1 levels,and concurrently increased E-cadherin expression.Additionally,reactivation of theWnt/β-catenin pathway partly reversed the inhibitory effects of ARPC1B depletion on tumor growth and invasiveness.Conclusions:ARPC1B emerges as an essential oncogenic factor in ccRCC by stimulating EMT and activating the Wnt/β-catenin pathway,ultimately enhancing tumor aggressiveness and metastatic potential.Thus,targeting ARPC1B represents a promising therapeutic strategy,warranting further exploration in ccRCC management.展开更多
基金supported by grants from the National Key Research and Development Program of China(No.2016YFC1101604)the Fundamental Research Funds for the Central Universities+2 种基金Clinical Medicine Plus X-Young Scholars Project of Peking University China(No.PKU2020LCXQ020)Guangdong Basic and Applied Basic Research Foundation(No.2019A1515110983,No.2021A1515012586)Bethune Charitable Foundation and CSPC Osteoporosis Research Foundation Project(No.G-X-2020-1107-21).
文摘Objective:Wallerian degeneration is a pathological process closely related to peripheral nerve regeneration following injury,and includes the disintegration and phagocytosis of peripheral nervous system cells.Traditionally,morphological changes are observed by performing immunofluorescence staining after sectioning,which results in the loss of some histological information.The purpose of this study was to explore a new,nondestmetive,and systematic method for observing axonal histological changes during Wallerian degeneration.Methods:Thirty male Thy1-YFP-16 mice(SPF grade,6 weeks old,20±5 g)were randomly selected and divided into clear,unobstructed brain imaging cocktails and computational analysis(CUBIC)optical clearing(n=15)and traditional method groups(n=15).Five mice in each group were sacrificed at 1st,3rd,and 5th day following a crush operation.The histological axon changes were observed by CUBIC light optical clearing treatment,direct tissue section imaging,and HE staining.Results:The results revealed that,compared with traditional imaging methods,there was no physical damage to the samples,which allowed for three-dimensional and deep-seated tissue imaging through CUBIC.Local image information could be nicely obtained by direct fluorescence imaging and HE staining,but it was difficult to obtain image information of the entire sample.At the same time,the image information obtained by fluorescence imaging and HE staining was partially lost.Conclusion:The combining of CUBIC and Thy1-YFP transgenic mice allowed for a clear and comprehensive observation of histological changes of axons in Wallerian degeneration.
文摘Dr.George Chiou is Professor and Director of the Institute of Ocular Pharmacology and Professor of Neuroscience and Experimental Therapeutics at Texas A&M University System Health Science Center.He has served as Head of Department of Medical Pharmacology and Toxicology for 27.5 years until the department was reorganized in 2006.He also is an Adjunct Professor of Surgery and Ophthalmology at Texas A&M University College of Medicine,
文摘Published by The WJG Press and Elsevier Inc．,PO Box 23451 Beijing 100023,China Fax:+86-(0)10-85381893 E-mail:wjg@wjgnet．com http://www．wjgnet．com The World Journal of Gastroenterology Editorial Board consists of 519 members,representing a team of worldwide experts in gastroenterology and hepatology．They are from 51 countries,including Albania(1),Algeria(1),Argentina(1),Australia(8), Austria(5),Belarus(1),Belgium(6),Brazil(1),Bulgaria(1),Canada(7),China(50),Costa Rica(1),Croatia(1),Denmark(6), Egypt(1),Finland(1),France(18),Germany(35),Greece(2),Hungary(2),Iceland(1),India(5),Iran(1),Ireland(1),Israel(2),Italy(41),Japan(132),Lithuania(1),Macedonia(1),Malaysia(3),Monaco(1),Netherlands(13),Norway(2),Pakistan(1),Philippines(1),Poland(2),Portugal(1),Russia(3),Singapore(2),Slovakia(1),South Africa(2),South Korea(6),Spain(20), Sri Lanka(1),Swaziland(1),Sweden(4),Switzerland(4),Turkey(3),United Kingdom(20),United States(90),Yugoslavia(1)． HONORARY EDITORS-IN-CHIEF Ke-Ji Chen,Professor Xiyuan Hospital,Chinese Tranditional Medicine University,Beijing 100091,China. kjchen@public．bta．net．
基金supported by grants from the Shenzhen Basic Research Project(JCYJ20210324125803008)the Shenzhen Longhua District Science and Innovation Bureau Fund for Medical Institutions(2022143).
文摘Background:Clear cell renal carcinoma(ccRCC),the leading histological subtype of RCC,lacks any targeted therapy options.Although some studies have shown that early growth response factor 1(EGR1)has a significant role in cancer development and progression,its role and underlying mechanisms in ccRCC remain poorly understood.Methods:The Cancer Genome Atlas(TCGA)database was utilized to examine the expression of EGR1 in ccRCC.The expression of EGR1 in 55 ccRCC tissues was evaluated using immunohistochemistry.The link between EGR1 expression and clinicopathological variables was examined through an analysis.Gain-of-function assays were employed to investigate EGR1’s biological functions in ccRCC cells,involving proliferation,colony formation,invasion assays,and tumorigenesis in nude mice.In order to assess the protein expression of mitogen-activated protein kinase 15(MAPK15),E-cadherin,matrix metalloproteinase-9/-2(MMP-9 and MMP-2),Western blot technique was applied.Results:The results revealed a decrease in EGR1 expression in ccRCC tissues.This decrease was strongly linked to TNM stage,lymphatic metastasis,tumor size,histological grade,and unfavorable prognosis in ccRCC patients.It has been demonstrated that overexpressing EGR1 inhibits the growth of xenograft tumors in vivo and inhibits cell colony formation,motility,and invasion in vitro.Furthermore,EGR1 can prevent the development and movement of ccRCC cells by controlling the expression of MMP-2,MMP-9,E-cadherin,and MAPK15.Conclusions:The EGR1/MAPK15 axis may represent a promising target for drug development,with EGR1 serving as a possible target for ccRCC therapy.
文摘Background:Clear cell renal cell carcinoma(ccRCC)is an aggressive malignancy associated with limited treatment options and poor prognosis.Emerging studies suggest that the actin-regulating protein actin-related protein 2/3 complex subunit 1B(ARPC1B),a key regulatory protein within the actin cytoskeleton,could play a pivotal role in ccRCC progression.The current study aimed to uncover the biological functions of ARPC1B and the molecular mechanisms driving its effects in ccRCC.Methods:ARPC1B expression and prognostic implications were analyzed using data sourced from the Gene Expression Profiling Interactive Analysis(GEPIA)platform,immunohistochemical(IHC)staining on 150 tumor samples along with 30 corresponding normal tissues,and Western blotting(WB)analyses across multiple ccRCC-derived cell lines.Functional assays assessing cell proliferation,colony formation capability,migration,invasion,and in vivo tumorigenicity were conducted following either ARPC1B suppression or upregulation.Additionally,WB analysis was utilized to evaluate proteins linked to epithelial-to-mesenchymal transition(EMT)and the Wnt/β-catenin pathway.Results:The findings revealed a substantial elevation of ARPC1B in ccRCC tissues and cell lines,significantly associated with advanced TNM stages,higher Fuhrman grades,and reduced overall survival(OS)(p<0.001).Multivariate statistical analysis identified ARPC1B as a standalone prognostic factor.Silencing ARPC1B notably impaired ccRCC cellular activities,and tumorigenesis in animalmodels,whereas augmented ARPC1B expression enhanced these malignant phenotypes.Mechanistically,downregulation of ARPC1B suppressed Wnt/β-catenin signaling and disrupted EMT,indicated by reducedβ-catenin,c-Myc,cyclin D1,and ZEB-1 levels,and concurrently increased E-cadherin expression.Additionally,reactivation of theWnt/β-catenin pathway partly reversed the inhibitory effects of ARPC1B depletion on tumor growth and invasiveness.Conclusions:ARPC1B emerges as an essential oncogenic factor in ccRCC by stimulating EMT and activating the Wnt/β-catenin pathway,ultimately enhancing tumor aggressiveness and metastatic potential.Thus,targeting ARPC1B represents a promising therapeutic strategy,warranting further exploration in ccRCC management.
