Liver cancer remains one of the leading causes of cancer-related mortality worldwide,with hepatocellular carcinoma representing its most prevalent form.This review provides a comprehensive summary of the key factors d...Liver cancer remains one of the leading causes of cancer-related mortality worldwide,with hepatocellular carcinoma representing its most prevalent form.This review provides a comprehensive summary of the key factors driving the initiation and progression of hepatocellular carcinoma,with a particular emphasis on immune-related mechanisms.Furthermore,we delve into the emerging roles of galectins,particularly galectin-1 and galectin-3,in hepatocellular carcinoma pathobiology,underscoring their potential utility as biomarkers for assessing disease severity and progression.These insights contribute to a better understan-ding of the molecular and immunological underpinnings of hepatocellular carcinoma,paving the way for more targeted therapeutic strategies.展开更多
Hepatocellular carcinoma(HCC)represents a global health problem.Infections with hepatitis B or C virus,non-alcoholic steatohepatitis disease,alcohol abuse,or dietary exposure to aflatoxin are the major risk factors to...Hepatocellular carcinoma(HCC)represents a global health problem.Infections with hepatitis B or C virus,non-alcoholic steatohepatitis disease,alcohol abuse,or dietary exposure to aflatoxin are the major risk factors to the development of this tumor.Regardless of the carcinogenic insult,HCC usually develops in a context of cirrhosis due to chronic inflammation and advanced fibrosis.Galectins are a family of evolutionarily-conserved proteins defined by at least one carbohydrate recognition domain with affinity forβ-galactosides and conserved sequence motifs.Here,we summarize the current literature implicating galectins in the pathogenesis of HCC.Expression of"proto-type"galectin-1,"chimera-type"galectin-3 and"tandem repeat-type"galectin-4 is up-regulated in HCC cells compared to their normal counterparts.On the other hand,the"tandemrepeat-type"lectins galectin-8 and galectin-9 are downregulated in tumor hepatocytes.The abnormal expression of these galectins correlates with tumor growth,HCC cell migration and invasion,tumor aggressiveness,metastasis,postoperative recurrence and poor prognosis.Moreover,these galectins have important roles in other pathological conditions of the liver,where chronic inflammation and/or fibrosis take place.Galectin-based therapies have been proposed to attenuate liver pathologies.Further functional studies are required to delineate the precise molecular mechanisms through which galectins contribute to HCC.展开更多
Galectins are sticky molecules that bind toβ-galactoside.Their interactions render them essential players in many cellular processes.The imbalance of galectin expression was reported in many diseases.In cancer,galect...Galectins are sticky molecules that bind toβ-galactoside.Their interactions render them essential players in many cellular processes.The imbalance of galectin expression was reported in many diseases.In cancer,galectins interact with the extracellular matrix,evade the immune system,and potentially have broad interactions with blood components.In the last ten years,since 2010,we did focus on galectin research in different cancer types.Ourfindings showed an interaction between cancer cells and erythrocytes via galectin-4.Moreover,we found that upregulation of galectins was associated with lymph node metastasis in ovarian cancers.Hence,with this,we shortly review some important aspects of galectins and their potential importance in more profound understanding of cancer progression and thefield of cancer biomarkers.展开更多
Protein/carbohydrate interactions through specific protein families termed lectin control essential biological processes. Galectins, a family of animal lectins defined by shared amino acid sequence with affinity for ...Protein/carbohydrate interactions through specific protein families termed lectin control essential biological processes. Galectins, a family of animal lectins defined by shared amino acid sequence with affinity for β-galactosides, appear to be functionally polyvalent in a wide range of biological activity. Recent studies have identified immunoregulatory roles of galectins in intestinal inflammatory disorders. Galectin-1 and galectin -2 contribute to the suppression of intestinal inflammation by the induction of apoptosis of activated T cells, whereas galectin-4 is involved in the exacerbation of this inflammation by specifically stimulating intestinal CD4+ T cells to produce IL-6. We review how different members of the galectins provide inhibitory or stimulatory signals to control intestinal immune response under intestinal inflammation.展开更多
The effects of recombinant galectins of male and female Hemonchus contortus （Hco-gal-m/f） on the mRNA levels of IL-1β, IL-2, IL-4, IL-6, interferon-γ（IFN-γ）, and tumor necrosis factor-γ （TNF-γ） of goat peri...The effects of recombinant galectins of male and female Hemonchus contortus （Hco-gal-m/f） on the mRNA levels of IL-1β, IL-2, IL-4, IL-6, interferon-γ（IFN-γ）, and tumor necrosis factor-γ （TNF-γ） of goat peripheral blood mononuclear cells （PBMCs） were examined in this study. Blood samples were collected from five randomly selected two-year-old healthy goats. PBMCs were separated and cultured in vitro with varying concentration galectins （Hco-gal-m/f） of 0, 10, 20, and 40 lag mL-L Semi-quantitative reverse transcription RT-PCR was employed to test the synthesis of mRNA. The results showed that the mRNA transcriptions of IL-1β, IL-2, IL-4, IL-6, IFN-γ, and TNF-γ in the PBMCs were inhibited by Hco-galm in a dose-dependent manner. Hco-gal-f inhibited mRNA synthesis of IL- 1β, IL-4, IFN-γ, and TNF-γ of the same cells in similar fashion. The findings suggested that the recombinant galectin proteins of H. contortus could decrease the transcription of cytokines in vitro.展开更多
Different forms of programmed cell death have been described to participate in the degeneration of dopaminergic neurons in Parkinson’s disease(PD).Given the critical role that disturbance of mitochondrial homeostasis...Different forms of programmed cell death have been described to participate in the degeneration of dopaminergic neurons in Parkinson’s disease(PD).Given the critical role that disturbance of mitochondrial homeostasis plays in the pathogenesis of PD,apoptosis can be reasonably considered as one of the cell death pathways involved in neuronal loss(Schon and Przedborski,2011).Multiple lines of evidence support that proposal such as the observations in postmortem human brain samples of PD patients including mitochondrial complex I deficiency,reactive oxygen species generation,and oxidative damage to lipids,proteins,and DNA,among others.展开更多
Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological diseases.However,the mechanisms modulating these processes in different diseases remain incomplete...Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological diseases.However,the mechanisms modulating these processes in different diseases remain incompletely understood.Advances in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system(CNS).Lgals3 encodes galectin-3(Gal3),aβ-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological diseases.While Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases,recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis,Alzheimer’s disease,and Parkinson’s disease.In this review,we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological diseases.We also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS.展开更多
目的:探讨Galectin-3对CCl_4致急性肝损伤时GRP78的调控作用.方法:选择ICR系的♂Galectin-3基因敲除型[Gal-3(-/-)]和其野生型[Gal(+/+)1小鼠,一次灌胃给予CCl_4,观察给药后10,24,48和72 h的肝组织病理改变和检测其血清谷草转氨酶(AST)...目的:探讨Galectin-3对CCl_4致急性肝损伤时GRP78的调控作用.方法:选择ICR系的♂Galectin-3基因敲除型[Gal-3(-/-)]和其野生型[Gal(+/+)1小鼠,一次灌胃给予CCl_4,观察给药后10,24,48和72 h的肝组织病理改变和检测其血清谷草转氨酶(AST)和谷丙转氨酶(ALT)活性,并检测肝细胞不同细胞组分中的GRP78蛋白表达.结果:与Gal(+/+)型鼠比较,CCl_4对Gal-3(-/-)型鼠的肝组织病理损伤出现时间早、损伤程度重.Gal-3(-/-)型鼠在CCl_4灌胃后10和24 h的血清ALT活性(1 860±191 U/L vs 1356±177 U/L,t=6.12,P<0.01;2789±236 U/L vs 2468±221 U/L,f=3.14,P<0.01)及CCl_4灌胃后10 h的血清AST活性(946±89 vs 623±73 U/L,t=8.87,P<0.01)与Gal(+/+)型鼠比较显著升高.对照组中Gal-3(+/+)型鼠的微粒体组分(Mic)中的GRP78蛋白表达显著高于Gal-3(-/-)型鼠(140.9±21.1 vs 76.1±9.5,t=8.86,P<0.01).在CCl_4 ig后24 h,Gal-3(+/+)型鼠的肝细胞线粒体组分(Mt)和Mic中的GRP78蛋白表达明显升高,并显著高于Gal-3(-/-)型鼠(Mt:127.0±18.8 vs 49.1±6.3,P<0.01;Mic:166.5±23.4 vs 87.7±11.6,P<0.01).结论:Galectin-3蛋白在CCl_4致急性肝损伤中可能具有一定的保护作用.上调Mic和Mt中的GRP78蛋白表达可能是Galectin-3在CCl_4对肝细胞损伤中发挥保护作用的一个途径.展开更多
文摘Liver cancer remains one of the leading causes of cancer-related mortality worldwide,with hepatocellular carcinoma representing its most prevalent form.This review provides a comprehensive summary of the key factors driving the initiation and progression of hepatocellular carcinoma,with a particular emphasis on immune-related mechanisms.Furthermore,we delve into the emerging roles of galectins,particularly galectin-1 and galectin-3,in hepatocellular carcinoma pathobiology,underscoring their potential utility as biomarkers for assessing disease severity and progression.These insights contribute to a better understan-ding of the molecular and immunological underpinnings of hepatocellular carcinoma,paving the way for more targeted therapeutic strategies.
文摘Hepatocellular carcinoma(HCC)represents a global health problem.Infections with hepatitis B or C virus,non-alcoholic steatohepatitis disease,alcohol abuse,or dietary exposure to aflatoxin are the major risk factors to the development of this tumor.Regardless of the carcinogenic insult,HCC usually develops in a context of cirrhosis due to chronic inflammation and advanced fibrosis.Galectins are a family of evolutionarily-conserved proteins defined by at least one carbohydrate recognition domain with affinity forβ-galactosides and conserved sequence motifs.Here,we summarize the current literature implicating galectins in the pathogenesis of HCC.Expression of"proto-type"galectin-1,"chimera-type"galectin-3 and"tandem repeat-type"galectin-4 is up-regulated in HCC cells compared to their normal counterparts.On the other hand,the"tandemrepeat-type"lectins galectin-8 and galectin-9 are downregulated in tumor hepatocytes.The abnormal expression of these galectins correlates with tumor growth,HCC cell migration and invasion,tumor aggressiveness,metastasis,postoperative recurrence and poor prognosis.Moreover,these galectins have important roles in other pathological conditions of the liver,where chronic inflammation and/or fibrosis take place.Galectin-based therapies have been proposed to attenuate liver pathologies.Further functional studies are required to delineate the precise molecular mechanisms through which galectins contribute to HCC.
文摘Galectins are sticky molecules that bind toβ-galactoside.Their interactions render them essential players in many cellular processes.The imbalance of galectin expression was reported in many diseases.In cancer,galectins interact with the extracellular matrix,evade the immune system,and potentially have broad interactions with blood components.In the last ten years,since 2010,we did focus on galectin research in different cancer types.Ourfindings showed an interaction between cancer cells and erythrocytes via galectin-4.Moreover,we found that upregulation of galectins was associated with lymph node metastasis in ovarian cancers.Hence,with this,we shortly review some important aspects of galectins and their potential importance in more profound understanding of cancer progression and thefield of cancer biomarkers.
基金National Institute of Health Grants, No. DK64289 and DK74454IBD grants from the Eli and Edythe L. Broad Medical Foundation+1 种基金National Institute of Health grant, DK64351IBD grants from the Eli and Edythe L. Broad Medical Foundation
文摘Protein/carbohydrate interactions through specific protein families termed lectin control essential biological processes. Galectins, a family of animal lectins defined by shared amino acid sequence with affinity for β-galactosides, appear to be functionally polyvalent in a wide range of biological activity. Recent studies have identified immunoregulatory roles of galectins in intestinal inflammatory disorders. Galectin-1 and galectin -2 contribute to the suppression of intestinal inflammation by the induction of apoptosis of activated T cells, whereas galectin-4 is involved in the exacerbation of this inflammation by specifically stimulating intestinal CD4+ T cells to produce IL-6. We review how different members of the galectins provide inhibitory or stimulatory signals to control intestinal immune response under intestinal inflammation.
基金the National Natural Science Foundation of China （30071078）.
文摘The effects of recombinant galectins of male and female Hemonchus contortus （Hco-gal-m/f） on the mRNA levels of IL-1β, IL-2, IL-4, IL-6, interferon-γ（IFN-γ）, and tumor necrosis factor-γ （TNF-γ） of goat peripheral blood mononuclear cells （PBMCs） were examined in this study. Blood samples were collected from five randomly selected two-year-old healthy goats. PBMCs were separated and cultured in vitro with varying concentration galectins （Hco-gal-m/f） of 0, 10, 20, and 40 lag mL-L Semi-quantitative reverse transcription RT-PCR was employed to test the synthesis of mRNA. The results showed that the mRNA transcriptions of IL-1β, IL-2, IL-4, IL-6, IFN-γ, and TNF-γ in the PBMCs were inhibited by Hco-galm in a dose-dependent manner. Hco-gal-f inhibited mRNA synthesis of IL- 1β, IL-4, IFN-γ, and TNF-γ of the same cells in similar fashion. The findings suggested that the recombinant galectin proteins of H. contortus could decrease the transcription of cytokines in vitro.
基金supported by the Spanish Ministerio de Ciencia e Innovación/Agencia Española de Investigación(PID2021-124096OB-I00)(to JLV)JGR was granted by Demensfonden,The Royal Physiografic Society of Lund,Neurofonden,The Greta och Johan Kocks stiftelser,and Bertil och Ebon Norlins stiftelse.
文摘Different forms of programmed cell death have been described to participate in the degeneration of dopaminergic neurons in Parkinson’s disease(PD).Given the critical role that disturbance of mitochondrial homeostasis plays in the pathogenesis of PD,apoptosis can be reasonably considered as one of the cell death pathways involved in neuronal loss(Schon and Przedborski,2011).Multiple lines of evidence support that proposal such as the observations in postmortem human brain samples of PD patients including mitochondrial complex I deficiency,reactive oxygen species generation,and oxidative damage to lipids,proteins,and DNA,among others.
文摘Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological diseases.However,the mechanisms modulating these processes in different diseases remain incompletely understood.Advances in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system(CNS).Lgals3 encodes galectin-3(Gal3),aβ-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological diseases.While Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases,recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis,Alzheimer’s disease,and Parkinson’s disease.In this review,we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological diseases.We also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS.
文摘目的:探讨Galectin-3对CCl_4致急性肝损伤时GRP78的调控作用.方法:选择ICR系的♂Galectin-3基因敲除型[Gal-3(-/-)]和其野生型[Gal(+/+)1小鼠,一次灌胃给予CCl_4,观察给药后10,24,48和72 h的肝组织病理改变和检测其血清谷草转氨酶(AST)和谷丙转氨酶(ALT)活性,并检测肝细胞不同细胞组分中的GRP78蛋白表达.结果:与Gal(+/+)型鼠比较,CCl_4对Gal-3(-/-)型鼠的肝组织病理损伤出现时间早、损伤程度重.Gal-3(-/-)型鼠在CCl_4灌胃后10和24 h的血清ALT活性(1 860±191 U/L vs 1356±177 U/L,t=6.12,P<0.01;2789±236 U/L vs 2468±221 U/L,f=3.14,P<0.01)及CCl_4灌胃后10 h的血清AST活性(946±89 vs 623±73 U/L,t=8.87,P<0.01)与Gal(+/+)型鼠比较显著升高.对照组中Gal-3(+/+)型鼠的微粒体组分(Mic)中的GRP78蛋白表达显著高于Gal-3(-/-)型鼠(140.9±21.1 vs 76.1±9.5,t=8.86,P<0.01).在CCl_4 ig后24 h,Gal-3(+/+)型鼠的肝细胞线粒体组分(Mt)和Mic中的GRP78蛋白表达明显升高,并显著高于Gal-3(-/-)型鼠(Mt:127.0±18.8 vs 49.1±6.3,P<0.01;Mic:166.5±23.4 vs 87.7±11.6,P<0.01).结论:Galectin-3蛋白在CCl_4致急性肝损伤中可能具有一定的保护作用.上调Mic和Mt中的GRP78蛋白表达可能是Galectin-3在CCl_4对肝细胞损伤中发挥保护作用的一个途径.
