Emerging role of galectin 3 in neuroinflammation and neurodegeneration

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.

Relationship between Circulating Plasma Galectin-3 Levels and T-Cell Activation during Cervical Cancer Chemotherapy

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+CD69+ cells in cervical cancer.

galectin-3和E-cadherin在结肠癌中的表达及与肿瘤淋巴结转移的关系

目的探讨galectin-3和上皮型钙黏蛋白(E-cadherin)在人结肠癌组织中的表达及其与淋巴结转移之间的关系。方法应用免疫组织化学染色技术检测37例结肠癌标本E-cadherin和galectin-3蛋白表达状况,对其中21例新鲜标本应用RT-PCR方法检测E-cadherin和galectin-3 mRNA水平,对其表达与结肠癌临床病理参数的关系进行分析。结果galectin-3在结肠癌组织中的阳性表达率为83.8%(31/37),其中有淋巴结转移的表达率为94.7%(18/19),显著高于无淋巴结转移者的72.2%(13/18)。结肠癌组织中E-cadherin的阳性表达率为59.5%(22/37),有淋巴结转移的表达率为47.4%(9/19),显著低于无淋巴结转移者的72.2%(13/18)。淋巴结转移组E-cadherin mRNA水平显著低于淋巴结未转移组,galectin-3 mRNA水平显著高于淋巴结未转移组(P<0.05)。结论galectin-3和E-cadherin表达与结肠癌患者的淋巴结转移相关,可作为判断预后的一个观测指标。

心力衰竭患者血清中Apelin-12、半乳糖凝集素-3和C反应蛋白表达及意义

目的检测心力衰竭患者血清中Apelin-12、半乳糖凝集素(Galectin)-3和C反应蛋白(CRP)的表达,分析三者的关系及临床意义。方法 61例心力衰竭患者作为观察组,32例体检证实为无明显器质性疾病的成人作为对照组,检测两组血清中Apelin-12、Galectin-3和CRP的表达。结果观察组中Apelin-12的表达明显低于对照组,观察组中Galectin-3和CRP的表达明显高于对照组(P<0.05)。观察组中Apelin-12、Galectin-3和CRP的表达与病变分级、有无心脏不良事件明显相关。观察组中Galectin-3和CRP具有正相关性,而其他指标间未见明显相关性。结论心力衰竭患者血清中Apelin-12低表达、Galectin-3和CRP高表达,三者与病变分级及心血管事件的发生相关,Apelin-12、Galectin-3和CRP异常表达均对病变的形成和进展起重要作用。

Galectin-3在CCl_4致肝损伤及对GRP78调控的作用

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.

鼻息肉组织半乳凝素3和胞间黏附分子1表达在嗜酸细胞浸润中的意义

鼻息肉的发病机制至今尚不清楚,近年研究结果表明,鼻息肉是鼻黏膜的慢性、持续性嗜酸细胞（eosinophil,Eos）性炎症。Bachert等曾指出揭示局部大量Eos浸润机制是了解鼻息肉本质的首要问题。国内、外一些研究,包括我们以前的报道证明鼻息肉组织中Eos大量聚集,

重组人脑利钠肽对急性心力衰竭患者疗效及对血清中半乳糖凝集素3、内皮素1和半胱氨酸蛋白酶抑制剂C的影响

目的观察重组人脑利钠肽对急性心力衰竭的疗效及对血清中半乳糖凝集素(Galectin)-3、内皮素(ET)-1和半胱氨酸蛋白酶抑制剂(Cystatin)C的影响。方法 118例急性心力衰竭〔心功能均为纽约心脏病协会(NYHA)Ⅲ~Ⅳ级〕的患者随机分为对照组59例,应用硝普钠或硝酸甘油等血管扩张药;观察组59例,应用重组人脑利钠肽。治疗前、治疗后抽取静脉血,应用ELISA法检测血清中galectin-3、ET-1和Cystatin C的表达。结果治疗1 w后,观察组心功能改善的总有效率明显高于对照组,两组血清galectin-3、ET-1和Cystatin C的表达均下降,但是观察组galectin-3、ET-1和Cystatin C的下降值明显高于对照组。结论重组人脑利钠肽治疗急性心力衰竭的疗效明显,且能更有效地优化血清中galectin-3、ET-1和Cystatin C的表达,有效调节机体的内环境。

半乳凝集素3在小鼠肺缺血再灌注损伤中的表达

目的:探讨半乳凝集素3(Gal3)在小鼠肺缺血再灌注损伤(LIRI)模型中的表达情况。方法:将20只C57BL/6J雄性小鼠随机分为假手术组和4个实验组(即LIRI后2 h组、LIRI后6 h组、LIRI后12 h组、LIRI后24 h组),每组4只。假手术组只开胸不夹闭肺门,实验组夹闭肺门60 min并分别于松开血管夹后2 h、6 h、12 h、24 h收集左肺标本。采用苏木精—伊红(HE)染色法和肺组织湿干重比(W/D)观察肺组织病理学变化,酶联免疫吸附法(ELISA)检测支气管肺泡灌洗液(BALF)炎性因子白细胞介素-1β(IL-1β)和肿瘤坏死因子α(TNF-α)的表达,分别采用实时荧光定量PCR(RT-qPCR)、western blotting、免疫荧光染色法检测Gal3 mRNA与Gal3蛋白的表达水平。结果:与假手术组相比,LIRI后各实验组出现肺组织损伤,组织结构破坏明显,肺损伤评分和W/D均升高,炎症因子IL-1β和TNF-α水平升高(均P<0.05),在LIRI后6 h肺组织病理学损伤程度和炎性因子水平达到峰值(P<0.05),随后逐渐降低。与假手术组相比,LIRI后各实验组Gal3 mRNA及其蛋白表达水平升高,Gal3免疫荧光染色表达水平升高(P<0.05),均于LIRI后6 h达到高峰(P<0.05),然后逐渐下降。结论:小鼠LIRI后Gal3表达升高,高水平的Gal3可能与LIRI后的肺组织损伤和炎症爆发有关。

缺血性脑卒中患者血清中S100B、半乳糖凝集素-3和神经元特异性烯醇化酶的表达及意义

目的检测缺血性脑卒中患者血清中S100B蛋白(S100B)、半乳糖凝集素(Galectin)-3和神经元特异性烯醇化酶(NSE)的表达,关注其临床价值。方法 59例缺血性脑卒中患者作为观察组,30例经体检成年人血清标本作为对照组,应用酶联免疫吸附法检测两组中S100B、Galectin-3和NSE的表达。结果观察组血清中S100B、Galectin-3和NSE的表达量明显高于对照组,观察组血清中S100B、Galectin-3和NSE的表达量与梗死灶的体积及病变严重程度相关。相关分析显示S100B和NSE具有正相关性,而S100B和Galectin-3、Galectin-3和NSE的表达未见明显相关性。结论缺血性脑卒中患者血清中S100B、Galectin-3和NSE的表达升高,三者不仅可以促进疾病的形成,还对疾病的进展起一定作用。S100B和NSE可能具有一定的协同作用。

Galectin 3 Level in Patients with Acute Coronary Syndrome and its Relation to Severity of Coronary Artery Disease

Background: Acute coronary syndrome (ACS) is a very common cause of hospitalizations worldwide each year. Despite Troponin is considered the gold standard in diagnosis of ACS. 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. Methods: Seventy two patients with ACS who underwent primarypercutaneous 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. Result: The mean age of the observational case control study was 55.9 ± 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 different 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). Conclusion: Galectin-3 levels were elevated in patients with ACS and there was a strong correlation between galectin-3 and severity of coronary artery disease.

CK19、Ki67、galectin3在甲状腺乳头状癌中的表达及临床意义

目的:探究细胞角蛋白19(Cytokeratin 19,CK19)、Ki67、半乳糖凝素-3(galectin3)在甲状腺乳头状癌(Papillary thyroid carcinoma,PTC)中的表达及与病理特征的关系。方法:搜集2021年1月到2023年12月医院收治的68例PTC患者临床资料,免疫组化检查癌组织及癌旁组织中CK19、Ki67、galectin3阳性表达率,分析三者与患者病理特征的关系。结果:PTC癌组织中CK19、Ki67、galectin3阳性表达率明显高于癌旁组织(P<0.05)。不同肿瘤直径、病灶数量、分化类型、临床分期PTC患者癌组织中CK19、Ki67阳性表达率差异有统计学意义(P<0.05)。结论:PTC患者癌组织CK19、Ki67、galectin3阳性表达率高,CK19和Ki67阳性表达与肿瘤大小、数量和分化程度及病理分期有一定关联。

阻断T细胞Tim3/Galectin9通路介导抗结核菌感染免疫保护

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。

Effects of advanced glycosylation end products and rosiglitazone on the expression and secretion of galectin-3 in human renal mesangial cells

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.

甲状腺乳头状癌与乳头状增生的病理研究

目的探讨Galectin3,CK19及Ki-67在甲状腺乳头状癌与乳头状增生中的表达,寻找有助于两者鉴别诊断的标志物。方法运用免疫组化方法检测100例甲状腺乳头状癌、100例良性乳头状增生中Galectin3,CK19及Ki-67的表达。结果Galectin3,CK19及Ki-67在甲状腺乳头状癌阳性表达率分别为100%,97%及93%,而在乳头状增生中表达率分别为13%,30%及1%,3种蛋白在乳头状癌与良性乳头状增生间差异有统计学意义(P<0.05)。在乳头状癌中2种或3种蛋白同时阳性表达为94.3%,而乳头状增生为0。结论Galectin3,CK19及Ki-67是鉴别诊断甲状腺乳头状癌与乳头状增生的有用标志物,尤其联合使用更有价值。