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
Objective: Despite the existence of several therapeutic strategies, the management of cervical cancer remains challenging. Our region has very little data on the interaction between the immune system and the clinical ...Objective: Despite the existence of several therapeutic strategies, the management of cervical cancer remains challenging. Our region has very little data on the interaction between the immune system and the clinical response to chemotherapy. This work examines plasma levels of galectin-3 (Gal-3) and percentages of activated T cells in patients with cervical cancer treated with chemotherapy and investigates if there is a relationship between the rates of these two elements. Methods: We compared data from 37 patients with cervical cancer undergoing chemotherapy and 42 controls with normal cervical cytology. Plasma Gal-3 concentrations were assessed by ELISA and expression of activation markers by T cells (CD69 and HLA-DR) was assessed by flow cytometry at three different time points during chemotherapy. Results: Our results showed that patients had a significantly higher concentration of Gal-3 compared to controls (4.025 vs. 1.340, p 0.001), similarly, they had a significantly high percentage of activated lymphocytes (2.610 vs. 0.731;p 0.0001). According to the response to treatment, patients with no response to treatment had a lower concentration of circulating Gal-3 but had approximately the same percentage of activated CD4 and CD8 lymphocytes as patients with a partial or total response. In addition, we found a positive correlation between the Gal-3 level and CD4 T cells expressing the activation marker CD69 (p 0.05;rho = 0.44). Conclusion: In conclusion, our results show that there would be a relationship between circulating galectin-3 and the percentage of peripheral CD4+</sup>CD69+</sup> cells in cervical cancer.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
<strong>Background:</strong><span style="font-family:;" "=""><span style="font-family:Verdana;"> Acute coronary syndrome (ACS) is a very common cause</span...<strong>Background:</strong><span style="font-family:;" "=""><span style="font-family:Verdana;"> Acute coronary syndrome (ACS) is a very common cause</span><b><span style="font-family:Verdana;"> </span></b><span style="font-family:Verdana;">of hospitalizations worldwide each year. Despite Troponin is considered the gold standard in diagnosis of ACS</span></span><span style="font-family:Verdana;">.</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> Several molecules have been investigated to identify predictive biomarkers of diagnosis. Among these, Galectin-3 has emerged as a promising diagnostic biomarker of (ACS). We aimed to evaluate galectin-3 levels in patients with acute coronary syndrome (ACS) and its relation to severity of coronary artery disease. </span><b><span style="font-family:Verdana;">Methods: </span></b><span style="font-family:Verdana;">Seventy two patients with ACS who underwent primary</span><b></b><span style="font-family:Verdana;">percutaneous coronary intervention (PCI) and 20 age-matched healthy controls were enrolled in our study .The severity of coronary artery disease and the burden of atherosclerosis was assessed with Gensini score and with the number of affected vessels. Galectin-3 levels were measured on admission by using ELISA with a commercially kit. </span><b><span style="font-family:Verdana;">Result: </span></b><span style="font-family:Verdana;">The mean age of the observational case control study was 55.9 ±</span><b><span style="font-family:Verdana;"> </span></b><span style="font-family:Verdana;">11.9 and 68 patients (73.9%) of the study were male. Median galectin-3 levels were significantly higher in ACS patients (20.25 ng/mL [11.9 - 39.0] vs. 8.9 ng/mL [4.6 - 24.0], P = 0.001). Patients were classified into three groups according to the number of involved vessels. Median galectin-3 levels were also significantly differen</span></span><span style="font-family:Verdana;">t</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> among groups (one vessel: 18.9 (12 - 35.2) ng/mL, two vessels: 19 (11.9 - 35) ng/mL, three vessels 32 (12 - 39) ng/mL, P = 0.007). There was a strong correlation between galectin-3 levels and Gensini score (r = 0.500, P = 0.001). </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Galectin-3 levels were elevated in patients with ACS and there</span><b><span style="font-family:Verdana;"> </span></b><span style="font-family:Verdana;">was a strong correlation between galectin-3 and severity of coronary artery disease.</span></span>展开更多
目的通过阻断小鼠体内T细胞免疫球蛋白黏蛋白分子-3(Tim3)/Galectin9通路,研究Tim3/Galectin9通路在结核菌感染中的调控作用。方法利用Tim3和Galectin9功能性单抗阻断Tim3/Galectin9通路,1.0×10~6CFUH37Rv经腹腔注射感染C57BL/6雌...目的通过阻断小鼠体内T细胞免疫球蛋白黏蛋白分子-3(Tim3)/Galectin9通路,研究Tim3/Galectin9通路在结核菌感染中的调控作用。方法利用Tim3和Galectin9功能性单抗阻断Tim3/Galectin9通路,1.0×10~6CFUH37Rv经腹腔注射感染C57BL/6雌性小鼠,感染4周后观察肺部大体情况和肺组织病理改变;流式细胞术检测小鼠外周血中Th1细胞干扰素-γ(IFN-γ)等细胞因子的表达情况;采用平板计数法计算脾脏和肺脏组织荷菌数CFUs。结果小鼠感染后,经Tim3、Galectin9功能性单抗阻断Tim3/Galectin9通路的小鼠肺部肉芽肿病变明显减轻,脾脏和肺脏的荷菌量均较Ig G control对照组低,流式细胞术结果显示CD4^+T细胞的IFN-γ表达量相比Ig Gcontrol感染对照组增多,差异有统计学意义(P<0.05)。结论结核分枝杆菌感染中,通过功能性单抗阻断Tim3/Galectin9通路可缓解结核病理状态,有效提高机体免疫水平,抑制结核的发生发展。展开更多
Background Galectin-3 is the most recently identified advanced glycosylation end products （AGEs） binding protein. This study aimed to investigate the effects of AGEs and rosiglitazone on the expression and secretion...Background Galectin-3 is the most recently identified advanced glycosylation end products （AGEs） binding protein. This study aimed to investigate the effects of AGEs and rosiglitazone on the expression and secretion of galectin-3 in cultured human renal mesangial cells （HRMCs）. Methods HRMCs were incubated with different concentrations of AGE-bovine serum albumin （BSA） （0, 50, 100, 200, and 400 mg/L） for different time （0, 24, 36, 48, and 72 hours）, and exposed to AGE-BSA in the presence of different concentrations of rosiglitazone （1, 10, and 100 μmol/L）. The mRNA and protein expression of galectin-3 in HRMCs were analyzed by reverse transcription polymerase chain reaction （RT-PCR） and Western blotting. The culture medium of HRMCs was collected and concentrated, and the content of galectin-3 in the medium was detected by Western blotting. Results Both RT-PCR and Western blotting revealed that AGE-BSA up-regulated the expression of galectin-3 in HRMCs in a concentration- （P 〈0.05） and time-dependent （P 〈0.05） manner compared with the control. Compared with the control, AGE-BSA elevated the content of galectin-3 in the culture medium of HRMCs time- and concentrationdependently （P 〈0.05, respectively）. Both protein and mRNA expression of galectin-3, and its content in the medium of HRMCs exposed to different concentrations of rosiglitazone in the presence of AGE-BSA were increased compared with those of cells exposed to AGE-BSA alone （P 〈0.05）. Rosiglitazone increased the expression and secretion of galectin-3 in a dose-dependent manner （P 〈0.05）. Conclusions AGEs up-regulates the expression and secretion of galectin-3 in HRMCs. Rosiglitazone further enhances the upregulation of galectin-3 in HRMCs induced by AGEs, which suggests that rosiglitazone may play a role of reno-protection via up-regulation of galectin-3.展开更多
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Objective: Despite the existence of several therapeutic strategies, the management of cervical cancer remains challenging. Our region has very little data on the interaction between the immune system and the clinical response to chemotherapy. This work examines plasma levels of galectin-3 (Gal-3) and percentages of activated T cells in patients with cervical cancer treated with chemotherapy and investigates if there is a relationship between the rates of these two elements. Methods: We compared data from 37 patients with cervical cancer undergoing chemotherapy and 42 controls with normal cervical cytology. Plasma Gal-3 concentrations were assessed by ELISA and expression of activation markers by T cells (CD69 and HLA-DR) was assessed by flow cytometry at three different time points during chemotherapy. Results: Our results showed that patients had a significantly higher concentration of Gal-3 compared to controls (4.025 vs. 1.340, p 0.001), similarly, they had a significantly high percentage of activated lymphocytes (2.610 vs. 0.731;p 0.0001). According to the response to treatment, patients with no response to treatment had a lower concentration of circulating Gal-3 but had approximately the same percentage of activated CD4 and CD8 lymphocytes as patients with a partial or total response. In addition, we found a positive correlation between the Gal-3 level and CD4 T cells expressing the activation marker CD69 (p 0.05;rho = 0.44). Conclusion: In conclusion, our results show that there would be a relationship between circulating galectin-3 and the percentage of peripheral CD4+</sup>CD69+</sup> cells in cervical cancer.
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.
文摘<strong>Background:</strong><span style="font-family:;" "=""><span style="font-family:Verdana;"> Acute coronary syndrome (ACS) is a very common cause</span><b><span style="font-family:Verdana;"> </span></b><span style="font-family:Verdana;">of hospitalizations worldwide each year. Despite Troponin is considered the gold standard in diagnosis of ACS</span></span><span style="font-family:Verdana;">.</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> Several molecules have been investigated to identify predictive biomarkers of diagnosis. Among these, Galectin-3 has emerged as a promising diagnostic biomarker of (ACS). We aimed to evaluate galectin-3 levels in patients with acute coronary syndrome (ACS) and its relation to severity of coronary artery disease. </span><b><span style="font-family:Verdana;">Methods: </span></b><span style="font-family:Verdana;">Seventy two patients with ACS who underwent primary</span><b></b><span style="font-family:Verdana;">percutaneous coronary intervention (PCI) and 20 age-matched healthy controls were enrolled in our study .The severity of coronary artery disease and the burden of atherosclerosis was assessed with Gensini score and with the number of affected vessels. Galectin-3 levels were measured on admission by using ELISA with a commercially kit. </span><b><span style="font-family:Verdana;">Result: </span></b><span style="font-family:Verdana;">The mean age of the observational case control study was 55.9 ±</span><b><span style="font-family:Verdana;"> </span></b><span style="font-family:Verdana;">11.9 and 68 patients (73.9%) of the study were male. Median galectin-3 levels were significantly higher in ACS patients (20.25 ng/mL [11.9 - 39.0] vs. 8.9 ng/mL [4.6 - 24.0], P = 0.001). Patients were classified into three groups according to the number of involved vessels. Median galectin-3 levels were also significantly differen</span></span><span style="font-family:Verdana;">t</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> among groups (one vessel: 18.9 (12 - 35.2) ng/mL, two vessels: 19 (11.9 - 35) ng/mL, three vessels 32 (12 - 39) ng/mL, P = 0.007). There was a strong correlation between galectin-3 levels and Gensini score (r = 0.500, P = 0.001). </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Galectin-3 levels were elevated in patients with ACS and there</span><b><span style="font-family:Verdana;"> </span></b><span style="font-family:Verdana;">was a strong correlation between galectin-3 and severity of coronary artery disease.</span></span>
文摘目的通过阻断小鼠体内T细胞免疫球蛋白黏蛋白分子-3(Tim3)/Galectin9通路,研究Tim3/Galectin9通路在结核菌感染中的调控作用。方法利用Tim3和Galectin9功能性单抗阻断Tim3/Galectin9通路,1.0×10~6CFUH37Rv经腹腔注射感染C57BL/6雌性小鼠,感染4周后观察肺部大体情况和肺组织病理改变;流式细胞术检测小鼠外周血中Th1细胞干扰素-γ(IFN-γ)等细胞因子的表达情况;采用平板计数法计算脾脏和肺脏组织荷菌数CFUs。结果小鼠感染后,经Tim3、Galectin9功能性单抗阻断Tim3/Galectin9通路的小鼠肺部肉芽肿病变明显减轻,脾脏和肺脏的荷菌量均较Ig G control对照组低,流式细胞术结果显示CD4^+T细胞的IFN-γ表达量相比Ig Gcontrol感染对照组增多,差异有统计学意义(P<0.05)。结论结核分枝杆菌感染中,通过功能性单抗阻断Tim3/Galectin9通路可缓解结核病理状态,有效提高机体免疫水平,抑制结核的发生发展。
文摘Background Galectin-3 is the most recently identified advanced glycosylation end products （AGEs） binding protein. This study aimed to investigate the effects of AGEs and rosiglitazone on the expression and secretion of galectin-3 in cultured human renal mesangial cells （HRMCs）. Methods HRMCs were incubated with different concentrations of AGE-bovine serum albumin （BSA） （0, 50, 100, 200, and 400 mg/L） for different time （0, 24, 36, 48, and 72 hours）, and exposed to AGE-BSA in the presence of different concentrations of rosiglitazone （1, 10, and 100 μmol/L）. The mRNA and protein expression of galectin-3 in HRMCs were analyzed by reverse transcription polymerase chain reaction （RT-PCR） and Western blotting. The culture medium of HRMCs was collected and concentrated, and the content of galectin-3 in the medium was detected by Western blotting. Results Both RT-PCR and Western blotting revealed that AGE-BSA up-regulated the expression of galectin-3 in HRMCs in a concentration- （P 〈0.05） and time-dependent （P 〈0.05） manner compared with the control. Compared with the control, AGE-BSA elevated the content of galectin-3 in the culture medium of HRMCs time- and concentrationdependently （P 〈0.05, respectively）. Both protein and mRNA expression of galectin-3, and its content in the medium of HRMCs exposed to different concentrations of rosiglitazone in the presence of AGE-BSA were increased compared with those of cells exposed to AGE-BSA alone （P 〈0.05）. Rosiglitazone increased the expression and secretion of galectin-3 in a dose-dependent manner （P 〈0.05）. Conclusions AGEs up-regulates the expression and secretion of galectin-3 in HRMCs. Rosiglitazone further enhances the upregulation of galectin-3 in HRMCs induced by AGEs, which suggests that rosiglitazone may play a role of reno-protection via up-regulation of galectin-3.
