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Thymosinβ4 released by mast cells under stress conditions impairs intestinal epithelial barrier via IL22RA1/JAK1/STAT3 signaling in irritable bowel syndrome
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作者 Yue-Shan Sun Xiao-Qin Bai +6 位作者 Kai-Di Sun Jiao Li Lei Liu Yuan-Yuan Chen Zhao-Yu Zeng Qiong Wang Yuan-Biao Guo 《World Journal of Gastroenterology》 2025年第42期171-196,共26页
Mast cells(MCs)under stress conditions contribute to the development of irritable bowel syndrome(IBS),yet their precise mechanisms in IBS remain unclear.AIM To investigate the role of MC-derived thymosinβ4(Tβ4)in st... Mast cells(MCs)under stress conditions contribute to the development of irritable bowel syndrome(IBS),yet their precise mechanisms in IBS remain unclear.AIM To investigate the role of MC-derived thymosinβ4(Tβ4)in stress-induced intestinal barrier dysfunction.METHODS The colonic mucus Tβ4 levels in IBS patients were determined and their effects on the epithelial barrier were assessed in vitro and in vivo.Specifically,rats genetically deficient in Tβ4(Tβ4^(-/-))or mice deficient in MCs(Kit^(w-sh/w-sh))were used to observe the effects of reintroducing Tβ4 or wild-type peritoneal MCs(wt-PMCs)into these animals.Additionally,the regulatory mechanism underlying Tβ4 secretion in MCs was investigated.RESULTS We demonstrated that high levels of Tβ4 in IBS mucus and intestinal MCs mediate stress-associated disruptive changes to the epithelial barrier.Moreover,Tβ4 treatment of wild-type or MC-deficient Kit^(w-sh/w-sh)mice caused a reduction in tight junction proteins and the interleukin 22 receptor A1(IL22RA1)/Reg3γcascade,but an increase in myosin light chain kinase.Furthermore,Tβ4^(-/-)rats were resistant to stress,though reintroduction of Tβ4 or wt-PMCs restored stress or corticotropin-releasing hormone(CRH)-induced barrier disturbance.Consistently,Tβ4 release from MCs was dependent on the CRH receptor 1,but not degranulation.The effect of Tβ4 was accompanied by IL22RA1/Janus kinase 1(JAK1)/signal transducer and activation of transcription 3(STAT3)pathway inhibition,suggesting a mechanism for physical and immune barrier suppression.CONCLUSION Collectively,these results suggest that Tβ4,which is abundant in IBS mucus and the secretome of MCs,plays a crucial role in the pathogenesis of IBS via IL22RA1/JAK1/STAT3 signaling,with potential implications for diagnostic and therapeutic targeting. 展开更多
关键词 thymosinβ4 Intestinal barrier Mast cell Janus kinase 1/signal transducer and activation of transcription 3 Irritable bowel syndrome
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Thymosin beta 10在不同模式动物或器官中功能的研究进展 被引量:3
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作者 张伟 褚文辉 +2 位作者 路晓 董振 李春义 《基因组学与应用生物学》 CAS CSCD 北大核心 2015年第3期663-668,共6页
Thymosin beta 10(T茁10)是一类小的肌动蛋白结合因子,在不同物种不同组织中具有不同的功能,已知其参与细胞凋亡、细胞增殖、细胞迁移、血管再生、肿瘤发生以及早期器官发育等一系列过程。本文综述了T茁10在不同研究模型动物或器官中的... Thymosin beta 10(T茁10)是一类小的肌动蛋白结合因子,在不同物种不同组织中具有不同的功能,已知其参与细胞凋亡、细胞增殖、细胞迁移、血管再生、肿瘤发生以及早期器官发育等一系列过程。本文综述了T茁10在不同研究模型动物或器官中的功能的研究现状,并结合鹿茸现有研究,提出了鹿茸可作为研究T茁10功能的新优势模型的命题。 展开更多
关键词 thymosin BETA 10(Tβ10) 功能 研究模型 鹿茸
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梅花鹿Thymosin beta 10基因RNAi慢病毒载体的构建及其对鹿茸干细胞增殖的影响 被引量:1
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作者 张伟 褚文辉 +3 位作者 路晓 董振 王权威 李春义 《吉林农业大学学报》 CAS CSCD 北大核心 2016年第1期92-96,106,共6页
利用慢病毒干扰系统,对梅花鹿生茸区骨膜干细胞(Antlerogenic periosteum cells,AP细胞)Thymosin beta 10(Tβ10)基因进行RNA干扰(RNA Interference,RNAi),并初步研究该基因对细胞增殖的影响。结果表明:试验设计的3条针对梅花鹿Tβ10基... 利用慢病毒干扰系统,对梅花鹿生茸区骨膜干细胞(Antlerogenic periosteum cells,AP细胞)Thymosin beta 10(Tβ10)基因进行RNA干扰(RNA Interference,RNAi),并初步研究该基因对细胞增殖的影响。结果表明:试验设计的3条针对梅花鹿Tβ10基因的shRNA序列与载体质粒p LVTHM连接成功,与p SPAX2、p MD2.G质粒共转染HEK 293T细胞,获得的重组慢病毒成功感染了AP细胞;荧光定量PCR检测结果表明,RNA干扰后Tβ10基因的mRNA水平下调,MTT试验结果显示Tβ10基因的下调可以抑制AP细胞增殖。试验成功构建了针对梅花鹿Tβ10基因RNAi载体,并成功干扰了Tβ10基因在AP细胞中的表达,基因下调最高可达35.6%,并初步确定Tβ10基因下调可抑制AP细胞的增殖。 展开更多
关键词 鹿茸 thymosin BETA 10(Tβ10) RNA干扰 增殖
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Preparation and in vitro release studies of thymosin-loaded PLA microspheres 被引量:2
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作者 何熠 肖国民 《Journal of Southeast University(English Edition)》 EI CAS 2007年第2期294-297,共4页
To obtain a kind of convenient oral dosage form of protein, which can be fully absorbed and is efficient and safe, the thymosin-loaded PLA(polylactic acid) microspheres are prepared by the emulsification- solvent ev... To obtain a kind of convenient oral dosage form of protein, which can be fully absorbed and is efficient and safe, the thymosin-loaded PLA(polylactic acid) microspheres are prepared by the emulsification- solvent evaporation method and the orthogonal design is used to optimize the technology of preparation. The form of the medicament microspheres of thymosin are proved by differential thermal analysis (DTA). The drug content is determined by the Lowry method, and the package ratio of medicament microspheres of thymosin and drug release in vitro are calculated. The results show that the average diameter and encapsulation efficiency of the product prepared according to the optimized formulation are 13. 8 μm and 80. 7%, respectively. The in vitro release behavior within 12 h can be described by the Higuchi equation with T1/2 = 295 rain. There are no significant changes in size distribution and residual drug contents after being stored at 25℃ and 40 ℃ for 90 d, respectively. Due to the fact that its thymosin content and package ratio meet the requirement, and its releasing half life is long, the thymosin-loaded PLA microsohere has a favorable application future. 展开更多
关键词 thymosin polylactic acid micro sphere in vitro release
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梅花鹿Thymosin beta 10基因的原核表达、活性鉴定和多克隆抗体制备
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作者 褚文辉 张伟 +2 位作者 赵海平 王大涛 李春义 《中国农业大学学报》 CAS CSCD 北大核心 2018年第11期72-79,共8页
为研究梅花鹿Thymosin beta 10基因(Tβ10)在鹿茸快速生长过程中的作用,利用Gateway技术构建梅花鹿Tβ10基因的原核表达载体—pDEST17-Tβ10并诱导表达,对融合蛋白进行功能检测及多克隆抗体制备。结果表明:1)获得了190bp Tβ10基因开放... 为研究梅花鹿Thymosin beta 10基因(Tβ10)在鹿茸快速生长过程中的作用,利用Gateway技术构建梅花鹿Tβ10基因的原核表达载体—pDEST17-Tβ10并诱导表达,对融合蛋白进行功能检测及多克隆抗体制备。结果表明:1)获得了190bp Tβ10基因开放阅读框序列,并获得重组表达载体pDEST17-Tβ10。2)pDEST17-Tβ10在宿主BL21-SI中诱导表达条件为0.3mol/L NaCL诱导2h,获得产物的最终浓度为0.50mg/mL。3)制备的Tβ10蛋白多克隆抗体血清效价在105之上,该抗体可以特异性结合天然和原核表达的Tβ10蛋白。4)离体检测发现,Tβ10融合蛋白一方面可以促进人脐静脉内皮细胞增殖,另一方面可以抑制鹿茸前成软骨区细胞的增殖。综上所述,本研究获得了具有生物活性的Tβ10融合蛋白,并制备了高度特异性的梅花鹿Tβ10蛋白多克隆抗体,为深入研究Tβ10基因的生物学功能奠定了基础。 展开更多
关键词 梅花鹿 thymosin BETA 10 原核表达 鹿茸 多克隆抗体
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A randomized controlled clinical trial on the treatment of Thymosin-a1 versus interferon-α in patients with hepatitis B 被引量:48
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作者 Jing You Lin Zhuang Bao Zhang Tang Wei Bo Yang Su Ying Ding Wu Li Rong Xue Wu Hong Li Zhang Yan Mei Zhang Shao Ming Yan Lu Zhang ~1Department of Infectious Diseases,The First Affiliated Hospital of Kunming Medical College,Kunming 650032,Yunnan Province,China ~2Departrnent of Hepatology,Kunming Third Municipal People’s Hospital,Kunming 650041,Yunnan Province,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第3期411-414,共4页
INTRODUCTIONChronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse sequelae ,such as cirrhosis and hepatocellular carcinoma .The World Health Organiz... INTRODUCTIONChronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse sequelae ,such as cirrhosis and hepatocellular carcinoma .The World Health Organization estimates that HBV has infected mord than 350 million people worldwide ,and up to 20% of them will become chromic carricrs and will be at significant risk for cirrhosis and HCC .The ultimate goal of the therapy for chronic hepatitis B is to prevent progression to cirrhosis and to prevent development of HCC. 展开更多
关键词 HEPATITIS B/therapy thymosin INTERFERON-ALPHA HEPATITIS B virus randomized controlled trials
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家蝇Thymosin(THY)基因的克隆及原核表达 被引量:5
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作者 王宇 吴高吉 +4 位作者 罗曼 彭传林 修江帆 尚小丽 吴建伟 《生物技术通报》 CAS CSCD 北大核心 2015年第2期143-147,共5页
采用EST测序技术从构建的家蝇(Musca domestica)幼虫c DNA质粒文库中筛选到胸腺肽(Thymosin,THY)基因,以该基因的c DNA文库质粒为模板,设计引物,通过PCR扩增,测序鉴定,获得THY基因完整编码序列。运用生物信息学方法对该基因及其编码蛋... 采用EST测序技术从构建的家蝇(Musca domestica)幼虫c DNA质粒文库中筛选到胸腺肽(Thymosin,THY)基因,以该基因的c DNA文库质粒为模板,设计引物,通过PCR扩增,测序鉴定,获得THY基因完整编码序列。运用生物信息学方法对该基因及其编码蛋白的基本理化性质、信号肽和亚细胞定位等方面进行预测和分析。构建p ET-28a(+)-THY重组质粒,转化到大肠杆菌BL21(DE3)中进行诱导表达。研究结果表明,THY基因ORF全长384 bp,编码127个氨基酸,理论分子量14.3 k D,等电点为5.22,具有THY家族的蛋白保守结构域。构建重组原核质粒p ET-28a(+)-THY,经IPTG诱导,蛋白在大肠杆菌中获得表达,经亲和层析柱纯化获得目的蛋白,Western blot检测发现纯化的目的蛋白大小正确。 展开更多
关键词 家蝇 胸腺肽 克隆 原核表达
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Serum thymosin β4 levels in patients with hepatitis B virus-related liver failure 被引量:21
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作者 Tao Han,Ying Liu,Huan Liu,Zheng-Yan Zhu,Yan Li,Shi-Xiang Xiao,Zhen Guo,Zhen-Gang Zhao,Department of Hepatology,Tianjin Institute of Hepatobiliary Disease,Tianjin Key Laboratory of Artificial Cells,Tianjin Third Central Hospital,Tianjin Medical University,83 Jintang Road,Tianjin 300170, China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2010年第5期625-630,共6页
AIM:To investigate whether serum thymosinβ4 can provide diagnostic or prognostic information in liver failure patients caused by chronic hepatitis B virus(HBV) infection. METHODS:Serum thymosinβ4 levels were measure... AIM:To investigate whether serum thymosinβ4 can provide diagnostic or prognostic information in liver failure patients caused by chronic hepatitis B virus(HBV) infection. METHODS:Serum thymosinβ4 levels were measured in 30 patients with acute-on-chronic liver failure(ACLF), 31 patients with chronic liver failure(CLF),30 patients with compensated liver cirrhosis(CR)and 32 patients with chronic hepatitis B and 30 healthy controls.Serum thymosinβ4 levels were measured by enzyme-linked immunosorbent assay and Child-Pugh and model for end-stage liver disease(MELD)scores were calculated for each patient on admission.RESULTS:Compared with healthy controls,serum thymosinβ4 levels in ACLF,CLF,CR and chronic hepatitis B patients were significantly lower,6.5047 (4.7879-10.5314)μg/mL vs 0.4632(0.2759-0.8768) μg/mL,0.6981(0.5209-1.2008)μg/mL,1.8053 (0.8110-2.3397)μg/mL,3.7803(1.8570-6.4722)μg/mL, respectively(P<0.001).The levels of thymosinβ4 in liver failure(ACLF or CLF)patients were markedly lower than that in CR(P<0.001),and a difference was also found between CLF and ACLF patients(P=0.038).In patients with chronic liver disease,there was a positive relationship between thymosinβ4 levels and albumin, choline esterase,and platelet(P<0.001),and negative relationship with alanine aminotransferase(P=0.020), aspartate aminotransferase,total bilirubin,international normalized ratio of prothrombin time,and Child-Pugh and MELD scores(P<0.001).Of the 61 liver failure patients,the thymosinβ4 levels of non-survivors were significantly lower than that of survivors(P=0.007). Receiver operating characteristics analysis identified a thymosinβ4 cutoff level of 0.5708μg/mL for predicting poor prognosis in all liver failure patients.The serial thymosinβ4 values were observed in 13 liver failure inpatients.Lower initial values were observed in the death.While greater improvement in thymosinβ4 value was found in those who recovered from the disease. CONCLUSION:Serum thymosinβ4 can be used as an important potential predictor for liver failure caused by chronic HBV infection. 展开更多
关键词 thymosinβ4 Liver failure SERUM Hepatitis B virus BIOCHEMISTRY
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Thymosin Alpha-1 Inhibits Complete Freund’s Adjuvant-Induced Pain and Production of Microglia-Mediated Pro-inflammatory Cytokines in Spinal Cord 被引量:5
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作者 Yunlong Xu Yanjun Jiang +10 位作者 Lin Wang Jiahua Huang Junmao Wen Hang Lv Xiaoli Wu Chaofan Wan Chuanxin Yu Wenjie Zhang Jiaying Zhao Yinqi Zhou Yongjun Chen 《Neuroscience Bulletin》 SCIE CAS CSCD 2019年第4期637-648,共12页
Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems.The immunopotentiator thymosin alpha-1(Tal)has recently been... Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems.The immunopotentiator thymosin alpha-1(Tal)has recently been reported to have anti-inflammatory and neuroprotective functions in rodents.However,how Tα1 affects inflammatory pain remains unclear.In the present study,intraperitoneal injection of Tal attenuated complete Freund's adjuvant(CFA)-induced pain hypersensitivity,and decreased the up-regulation of pro-inflammatory cytokines(TNF-α,IL-1β,and IL-6)in inflamed skin and the spinal cord.We found that CFA-induced peripheral inflammation evoked strong microglial activation,but the effect was reversed by Tα1.Notably,Tα1 reversed the CFA-induced up-regulation of vesicular glutamate transporter(VGLUT)and down-regulated the vesicular γ-aminobutyric acid transporter(VGAT)in the spinal cord.Taken together,these results suggest that Tα1 plays a therapeutic role in inflammatory pain and in the modulation of microgliainduced pro-inflammatory cytokine production in addition to mediation of VGLUT and VGAT expression in the spinal cord. 展开更多
关键词 thymosin alpha-1 Cytokine MICROGLIA Vesicular GLUTAMATE TRANSPORTER type 2 Vesicular γ-aminobutyric acid TRANSPORTER
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Efficacy of thymosin alpha-1 and interferon alpha in treatment of chronic viral hepatitis B:A randomized controlled study 被引量:9
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作者 Jing You Lin Zhuang +11 位作者 Hong-Ying Cheng Shou-Ming Yan Lan Yu Jun-Hua Huang Bao-Zhang Tang Meng-Ling Huang Yong-Liang Ma Virasakdi Chongsuvivatwong Hutcha Sriplung Alan Geater Yan-Wei Qiao Rong-Xue Wu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第41期6715-6721,共7页
AIM: To observe the efficiency and safety of thymosin-α1 treatment in patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis. METHODS: Sixty-two patients were randomly divided into gro... AIM: To observe the efficiency and safety of thymosin-α1 treatment in patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis. METHODS: Sixty-two patients were randomly divided into groups A and B. The patients in group A received subcutaneous injection of 1.6 mg thymosin-α1, twice a week (T-α1 group) for six months, and the patients in group B received 5 MU interferon alpha (IFN-α) each day for fifteen days, then three times weekly (IFN-α group) for six months. The results between two groups treated with and the group untreated with IFN-α which was followed up for 12 mo (historical control group consisting of 30 patients) were compared, and three groups were comparable between each other (P 〉 0.05) at baseline (age, sex, clinical history, biochemical, and serological parameters). RESULTS: At the end of treatment, complete response, which was defined as alanine aminotransferase (ALT) normalization and HBV DNA and HBeAg loss, occurred in 9 of 29 (31.0%) patients in the T-α1 group and in 15 of 33 (45.5%) patients in the IFN-α group (χ^2= 1.36, P 〉 0.05). After a follow-up period of six months, a complete response was observed in 14 of 29 (48.3%) patients in the T-α1 group and in 9 of 33 (27.3%) patients in the IFN-α group (χ^2= 2.93, P 〉 0.05). Compared with the results observed in the historical control (HC) group untreated with IFN-α which was followed up for 12 mo, the rate of complete response was significantly higher in IFN-α group at the end of therapy (1 of 30 vs 15 of 33, 7:2 = 14.72, P 〈 0.001) and in the T-α1 group at the end of follow-up (1 of 30 vs 14 of 29,χ^2 = 15.71, P 〈 0.001). In T-α1 and IFN-α treatment groups, the area under (the plasma concentration time) curve (AUC) of negative HBV DNA and HBeAg was 340, 17%, 31% and 19% smaller than that in the HC group. By the end of the follow-up period, the proportions of ALT normalization and negative HBV DNA in the T-α1 group were significantly higher than those in the IFN-α and HC groups. The odds of ALT normalization and negative HBV DNA at the end of the follow-up was three-fold higher in the T-α1 group than in the IFN-α group. Unlike IFN-α, T-α1 was well tolerated by all patients, and no side effects appeared in T-α1 group. CONCLUSION: The results suggest that a 6-too course of T-α1 therapy is effective and safe in patients with chronic hepatitis B. T-α1 is able to reduce HBV replication in patients with chronic hepatitis B. Furthermore, T-α1 is better tolerated than IFN-α and can gradually induce more sustained ALT normalization and HBV DNA and HBeAg loss. However, a response rate of 48.3% is still less ideal. A more effective therapeutic approach warrants further study. 展开更多
关键词 Chronic hepatitis B EFFICACY Interferonalpha thymosin alpha-1
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Recombinant adeno-associated virus carrying thymosin β4 suppresses experimental colitis in mice 被引量:6
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作者 Xiao-Yan Zheng Yi-Fei Lv +4 位作者 Shuang Li Qian Li Qian-Nan Zhang Xue-Ting Zhang Zhi-Ming Hao 《World Journal of Gastroenterology》 SCIE CAS 2017年第2期242-255,共14页
AIMTo investigate the protective effect of a recombinant adeno-associated virus carrying thymosin &#x003b2;<sub>4</sub> (AAV-T&#x003b2;<sub>4</sub>) on murine colitis via intracolonic a... AIMTo investigate the protective effect of a recombinant adeno-associated virus carrying thymosin &#x003b2;<sub>4</sub> (AAV-T&#x003b2;<sub>4</sub>) on murine colitis via intracolonic administration.METHODSAAV-T&#x003b2;<sub>4</sub> was prepared and intracolonically used to mediate the secretory expression of T&#x003b2;<sub>4</sub> in mouse colons. Dextran sulfate sodium (DSS) was applied to induce the murine ulcerative colitis, and 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to establish a mouse colitis model resembling Crohn&#x02019;s disease. The disease severity and colon injuries were observed and graded to reveal the effects of AAV-T&#x003b2;<sub>4</sub> on colitis. The activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were determined using biochemical assays. Colonic levels of tumor necrosis factor-&#x003b1; (TNF-&#x003b1;), interleukin (IL)-1&#x003b2; and IL-10 were measured using ELISA, and mucosal epithelial cell apoptosis and proliferation were detected by TUNEL assay and immunochemistry, respectively.RESULTSRecombinant AAVs efficiently delivered LacZ and T&#x003b2;<sub>4</sub> into the colonic tissues of the mice, and AAV-T&#x003b2;<sub>4</sub> led to a strong expression of T&#x003b2;<sub>4</sub> in mouse colons. In both the DSS and TNBS colitis models, AAV-T&#x003b2;<sub>4</sub>-treated mice displayed distinctly attenuated colon injuries and reduced apoptosis rate of colonic mucosal epithelia. AAV-T&#x003b2;<sub>4</sub> significantly reduced inflammatory cell infiltrations and relieved oxidative stress in the inflamed colons of the mice, as evidenced by decreases in MPO activity and MDA content and increases in SOD activity. AAV-T&#x003b2;<sub>4</sub> also modulated colonic TNF-&#x003b1;, IL-1&#x003b2; and IL-10 levels and suppressed the compensatory proliferation of colonic epithelial cells in DSS- and TNBS-treated mice.CONCLUSIONT&#x003b2;<sub>4</sub> exerts a protective effect on murine colitis, indicating that AAV-T&#x003b2;<sub>4</sub> could potentially be developed into a promising agent for the therapy of inflammatory bowel diseases. 展开更多
关键词 thymosin β 4 MICE COLITIS Dextran sulfate sodium 2 4 6-trinitrobenzene sulfonic acid
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Preliminary results of Thymosin-a1 versus interferon-α treatment in patients with HBeAg negative and serum HBV DNA positive chronic hepatitis B 被引量:24
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作者 Lin Zhuang Jing You Bao Zhang Tang Su Ying Ding Kui Hua Yan Dan Peng Yan Mei Zhang Lu Zhang ~1Department of Hepatology,Kunming Third Municipal Peoples Hospital,Kunming 650041,Yunnan Province,China ~2Department of Infectious Diseases,The First Affiliated Hospital of Kunming Medical College,Kunming 650032,Yunnan Province,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第3期407-410,共4页
INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 a... INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer . 展开更多
关键词 hepatitis B hepatitis B surface antigens INTERFERON-Α thymosin-a1 hepatitis B E antigens SEROLOGY
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Construction, expression and characterization of human interferon α2b-(G4S)n-thymosin α1 fusion proteins in Pichia pastoris 被引量:5
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作者 You-FengYang Han-YingYuan Nan-SongLiu Xiang-LingChen Bu-YuGao HongLu Yu-YangLi 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第17期2597-2602,共6页
AIM:Interferon α2b (IFNα2b) and thymosin α1 (Tα1) exhibit synergic effects in the treatment of hepatitis B and hepatitis C when used together. For developing a fusion protein drug, fusion proteins of IFNα2b and T... AIM:Interferon α2b (IFNα2b) and thymosin α1 (Tα1) exhibit synergic effects in the treatment of hepatitis B and hepatitis C when used together. For developing a fusion protein drug, fusion proteins of IFNα2b and Ta1 linked by different lengths of (G4S)n(n = 1-3) were constructed and expressed in Pichia pastoris. METHODS: Using PCR and molecular clone techniques, the fusion genes of IFNα2b-(G4S)n-Tα1 (n = 1-3) were constructed and subcloned into the eukaryotic expression vector pPIC9. After transformation of these plasmids into P. pastoris, the expressed fusion proteins IFNα2b-(G4S) n-Tα1 (n = 1-3) were obtained. These proteins were purified through diethylaminoethyl (DEAE) affinity chromatography and Superdex?75 gel filtration and analyzed by SDS-PAGE and Western blot. Antiviral and E-rosette assays were used to investigate the bioactivities of these fusion proteins. RESULTS: DNA sequencing confirmed that the fusion genes of IFNa2b-(G4S)n-Tα1 (n= 1-3) were correctly cloned to the pPIC9 vector. The recombinant IFNα2b-(G4S)n-Tα1 (n = 1-3) fusion proteins expressed in P. pastoris were purified with DEAE and Superdex?75 gel filtration chromatography. The fusion proteins could be observed on sodium dodecylsulfate-polyacrylamide gel electrophoresis with molecular weight (MW) of 23.2, 22.9, and 22.6 ku, respectively, and reacted to the IFNa2b monoclonal antibody and Tal polyclonal antibody. The purified fusion proteins exhibit antiviral activity and can enhance the percentage of E-rosette-forming-cell in E-rosette assay. CONCLUSION: The recombinant IFNa2b-(G4S)n-Tα1 (n = 1-3) fusion proteins were successfully expressed in P. pastoris. Purified fusion proteins exhibit both antiviral activity of IFNa2b and immunomodulatory activity of Tal in vitro. These results will be the basis for further evaluation of the fusion proteins' function in vivo. 展开更多
关键词 Fusion protein Interferon α2b thymosin al Antiviral assay E-rosette assay
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Thymosin alpha 1:A comprehensive review of the literature 被引量:21
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作者 Asimina Dominari Donald Hathaway III +14 位作者 Krunal Pandav Wanessa Matos Sharmi Biswas Gowry Reddy Sindhu Thevuthasan Muhammad Adnan Khan Anoopa Mathew Sarabjot Singh Makkar Madiha Zaidi Michael Maher Mourad Fahem Renato Beas Valeria Castaneda Trissa Paul John Halpern Diana Baralt 《World Journal of Virology》 2020年第5期67-78,共12页
Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying,enhancing,and restoring immune function.Thymosin alpha 1 has been utilized in the treatment of immunocompromi... Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying,enhancing,and restoring immune function.Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies,as an enhancer of vaccine response,and as a means of curbing morbidity and mortality in sepsis and numerous infections.Studies have postulated that thymosin alpha 1 could help improve the outcome in severely ill corona virus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how thymosin alpha 1 could prevent the excessive activation of T cells.In this review,we discuss key literature on the background knowledge and current clinical uses of thymosin alpha 1.Considering the known biochemical properties including antibacterial and antiviral properties,timehonored applications,and the new promising findings regarding the use of thymosin,we believe that thymosin alpha 1 deserves further investigation into its antiviral properties and possible repurposing as a treatment against severe acute respiratory syndrome coronavirus-2. 展开更多
关键词 thymosin alpha 1 THYMALFASIN Immunomodulating T lymphocytes Infectious diseases Immune deficiency Oxidative damage
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Immunomodulatory function of orally administered thymosin α1 被引量:1
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作者 陈祥明 蒋汉梁 +5 位作者 周林福 潘小平 胡中荣 刘荣华 陈晓明 陈智 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2005年第9期873-876,共4页
Objective: To investigate the immunological function of a yeast expression system for thymosin α1 (Tα1). Methods: A constructed Tetl yeast expression system was used to investigate the immunological function of ... Objective: To investigate the immunological function of a yeast expression system for thymosin α1 (Tα1). Methods: A constructed Tetl yeast expression system was used to investigate the immunological function of orally administered Tα1. Dried yeast containing three different concentration of Tα1 was fed to normal Balb/c mice and other Balb/c mice whose immunities were inhibited in advance by cyclophosphamide. Synthesized Tα1 peptide was used as positive control and dried yeast with empty plasmid was used as negative control. CD4^+ and CD8^+ levels were detected by flow cytometry assay. TNF-α, IFN-γ, IL-2, IL-6 and IL-10 levels were detected by liquid chip. Results: In normal Balb/c mice or immune inhibition Balb/c mice, CD8^+ levels were significantly increased. Especially in immune inhibition Balb/c mice, CD8^+ levels in synthesized Tα1 group (18.77%±4.72%), small dose group (13.48%±6.17%) and large dose group (22.74%±1.09%) were significantly higher than that in empty yeast control group (7.49%±2.14%). Conclusion: Orally administered Tα1 has its certain immunomodulatory function. 展开更多
关键词 thymosin α1 Yeast expression system Biological activity Orally administered
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Molecular characteristics of three thymosin-repeat proteins from Marsupenaeus japonicus and their responses to WSSV infection 被引量:5
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作者 MA Jinyou RUAN Lingwei +1 位作者 XU Xun GAO Zhaoming 《Acta Oceanologica Sinica》 SCIE CAS CSCD 2016年第4期44-50,共7页
β-thymosins, a family of highly conserved peptides, play a vital role in wound-healing, angiogenesis,antimicrobial process and antiviral immunity. Three novel β-thymosin-repeat proteins, named mjthm4, mjthm3 and mjt... β-thymosins, a family of highly conserved peptides, play a vital role in wound-healing, angiogenesis,antimicrobial process and antiviral immunity. Three novel β-thymosin-repeat proteins, named mjthm4, mjthm3 and mjthm2, were cloned from Marsupenaeus japonicus using expressed sequence tags(EST) from suppression subtractive hybridization. The mjthm4, mjthm3 and mjthm2 c DNAs possessed open reading frames that encoded166, 128 and 90 amino acid residue polypeptides and contained four, three and two β-thymosin actin binding modules, respectively. Blast analysis demonstrated that mjthm4, mjthm3 and mjthm2 shared high homology with known invertebrate multi-repeat β-thymosins. These proteins are ubiquitously expressed in all of the examined tissues, and the transcriptional levels were highest in the intestine. Further investigation revealed that mjthm4,mjthm3 and mjthm2 were remarkably up-regulated 6 h after WSSV infection. Moreover, while mjthm4 transcriptional levels displayed no changes, mjthm3 and mjthm2 levels decreased in the virus-resistant shrimps.The results indicate that mjthm4, mjthm3 and mjthm2 are novel multi-repeat β-thymosin homologues, have a close relationship with WSSV infection, and might contribute to a better understanding of host defense and/or virus invasion interactions in shrimps. 展开更多
关键词 β-thymosin thymosin-repeat proteins white spot syndrome virus(WSSV) Marsupenaeus japonicus
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Thymosinβ4 Impeded Murine Stem Cell Proliferation with an Intact Cardiovascular Differentiation 被引量:1
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作者 Li NIE Shi-jun GAO +7 位作者 Ya-nan ZHAO Jacob Masika Hong-yan LUO Xin-wu HU Liang-pin ZHANG Ying ZENG Jirgen Hescheler Hua-min LIANG 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2016年第3期328-334,共7页
Thymosinβ4(Tβ4)is a key factor in cardiac development,growth,disease,epicardial integrity,blood vessel formation and has cardio-protective properties.However,its role in murine embryonic stem cells(m ESCs)proliferat... Thymosinβ4(Tβ4)is a key factor in cardiac development,growth,disease,epicardial integrity,blood vessel formation and has cardio-protective properties.However,its role in murine embryonic stem cells(m ESCs)proliferation and cardiovascular differentiation remains unclear.Thus we aimed to elucidate the influence of Tβ4 on m ESCs.Target genes during m ESCs proliferation and differentiation were detected by real-time PCR or Western blotting,and patch clamp was applied to characterize the m ESCs-derived cardiomyocytes.It was found that Tβ4 decreased m ESCs proliferation in a partial dose-dependent manner and the expression of cell cycle regulatory genes c-myc,c-fos and c-jun.However,m ESCs self-renewal markers Oct4 and Nanog were elevated,indicating the maintenance of self-renewal ability in these m ESCs.Phosphorylation of STAT3 and Akt was inhibited by Tβ4 while the expression of RAS and phosphorylation of ERK were enhanced.No significant difference was found in BMP2/BMP4 or their downstream protein smad.Wnt3 and Wnt11 were remarkably decreased by Tβ4 with upregulation of Tcf3 and constant?-catenin.Under m ESCs differentiation,Tβ4 treatment did not change the expression of cardiovascular cell markersα-MHC,PECAM,andα-SMA.Neither the electrophysiological properties of m ESCs-derived cardiomyocytes nor the hormonal regulation by Iso/Cch was affected by Tβ4.In conclusion,Tβ4 suppressed m ESCs proliferation by affecting the activity of STAT3,Akt,ERK and Wnt pathways.However,Tβ4 did not influence the in vitro cardiovascular differentiation. 展开更多
关键词 thymosinβ4 murine embryonic stem cells PROLIFERATION CARDIOGENESIS patch clamp
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Thymosin <i>β</i>4 Improves Neurological Outcome and Enhances Induced Oligodendrogenesis in the Rat after ICH 被引量:1
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作者 Dongmei Yang Yuxia Han +1 位作者 Michael Chopp Donald M. Seyfried 《World Journal of Neuroscience》 2014年第5期395-405,共11页
Thymosin β4 (Tβ4), a G-actin binding protein, has diverse biological functions. This study tested the effects of Tβ4 on oligodendrogenesis in a rat model of intracerebral hemorrhage (ICH). ICH was induced by stereo... Thymosin β4 (Tβ4), a G-actin binding protein, has diverse biological functions. This study tested the effects of Tβ4 on oligodendrogenesis in a rat model of intracerebral hemorrhage (ICH). ICH was induced by stereotactic injection of 100 μm of autologous blood into the striatum in 32 male Wistar rats. The rats were randomly divided into four groups: 1) saline control group (n = 8);2) 3 mg/kg Tβ4-treated group (n = 8);3) 6 mg/kg Tβ4-treated group (n = 8);and 4) 12 mg/kg Tβ4treated group (n = 8). Tβ4 or saline was administered intraperitoneally starting at 24 h post ICH and then every 3 days for 4 additional doses. The neurological functional outcome was evaluated by behavioral tests (i.e., modified Neurological Severity Score and corner turn test) at multiple time points after ICH. Animals were sacrificed at 28 days post ICH, and histological studies were completed. Tβ4 treatment improved neurological functional recovery significantly and increased actively proliferating oligodendrocytic progenitor cells and myelinating oligodendrocytes in the ICH-affected brain tissue, compared with the saline-treated group. The high-dose treatment of Tβ4 showed better restorative effects compared with the low-dose treatment. Tβ4 treatment enhanced ICH-induced oligodendrogenesis that may contribute to the enhanced functional recovery after ICH. Further investigation is warranted to determine the associated underlying mechanisms of Tβ4 treatment for ICH. 展开更多
关键词 thymosin β4 NEUROGENESIS OLIGODENDROGENESIS INTRACEREBRAL Hemorrhage
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Hypermethylation of thymosinβ4 predicts a poor prognosis for patients with acute-on-chronic hepatitis B liver failure
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作者 He Wang Yan-Ping Yin +4 位作者 Zhen-Li Wang Yu Qian Yu-Chen Fan Hui-Hui Liu Kai Wang 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2023年第4期373-382,共10页
Background:It has been demonstrated that thymosinβ4(Tβ4)could inflect the severity of acute-on-chronic hepatitis B liver failure(ACHBLF),but the relationship between its methylation status and the prognosis of liver... Background:It has been demonstrated that thymosinβ4(Tβ4)could inflect the severity of acute-on-chronic hepatitis B liver failure(ACHBLF),but the relationship between its methylation status and the prognosis of liver failure is not clear.This study aimed to determine Tβ4 promoter methylation status in patients with ACHBLF and to evaluate its prognostic value.Methods:The study recruited 115 patients with ACHBLF,80 with acute-on-chronic hepatitis B pre-liver failure(pre-ACHBLF),and 86 with chronic hepatitis B(CHB).In addition,there were 36 healthy controls(HCs)from the Department of Hepatology,Qilu Hospital of Shandong University.The 115 patients with ACHBLF were divided into three subgroups:33 with early stage ACHBLF(E-ACHBLF),42 with mid-stage ACHBLF(M-ACHBLF),and 40 with advanced stage ACHBLF(A-ACHBLF).Tβ4 promoter methylation status in peripheral blood mononuclear cells(PBMCs)was measured by methylation-specific polymerase chain reaction,and mRNA was detected by quantitative real-time polymerase chain reaction.Results:Methylation frequency of Tβ4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF,CHB or HCs.However,expression of Tβ4 mRNA showed the opposite trend.In patients with ACHBLF,Tβ4 promoter methylation status correlated negatively with mRNA levels.The 3-month mortality of ACHBLF in the methylated group was significantly higher than that in the unmethylated group.Also,Tβ4 promoter methylation frequency was lower in survivors than in non-survivors.When used to predict the 1-,2-,and 3-month incidence of ACHBLF,Tβ4 methylation status was better than the model for end-stage liver disease(MELD)score.The predictive value of Tβ4 methylation was higher than that of MELD score for the mortality of patients with E-ACHBLF and M-ACHBLF,but not for A-ACHBLF.Conclusions:Tβ4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF. 展开更多
关键词 Acute-on-chronic hepatitis B liver failure Acute-on-chronic hepatitis B pre-liver failure thymosinβ4 METHYLATION PROGNOSIS
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Thymosin as a possible therapeutic drug for COVID-19:A case report
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作者 Qiong Na Zheng Mei Yan Xu +2 位作者 Fang Min Gan Sha Sha Ye Hui Zhao 《World Journal of Clinical Cases》 SCIE 2021年第16期4090-4094,共5页
BACKGROUND There are no effective antiviral therapies for coronavirus disease 2019(COVID-19)at present.Although most patients with COVID-19 have a mild or moderate course of disease,up to 5%-10%of patients may have a ... BACKGROUND There are no effective antiviral therapies for coronavirus disease 2019(COVID-19)at present.Although most patients with COVID-19 have a mild or moderate course of disease,up to 5%-10%of patients may have a serious and potentially life-threatening condition,indicating an urgent need for effective therapeutic drugs.The therapeutic effect of thymosin on COVID-19 has not been previously studied.In this paper,for the first time we report a case of thymosin treatment of COVID-19.CASE SUMMARY A 51-year-old man with imported COVID-19 was admitted with definite symptoms of chest tightness,chest pain,and fatigue.The polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 were negative.The antibody test was positive,confirming the diagnosis of COVID-19.As many orally administered drugs were not well tolerated due to gastrointestinal symptoms,an emergency use of thymosin,a polypeptide consisting of 28 amino acids,was administered by injection.Finally,after the implementation of the treatment program,symptoms and lung imaging improved significantly.CONCLUSION In this case report,it is confirmed that thymosin may help alleviate the severity of COVID-19 symptoms. 展开更多
关键词 COVID-19 thymosin SARS-CoV-2 Treatment Therapeutic drug Case report
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