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甲状腺纤维化的中医治疗思路 预览
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作者 柏力萄 赵静 +3 位作者 李俊 吴瑞 魏璠 魏军平 《世界科学技术:中医药现代化》 CSCD 北大核心 2019年第2期267-271,共5页
甲状腺纤维化是各种因素刺激下,出现的纤维性改变,是多种甲状腺疾病共有的病理过程。甲状腺纤维化严重影响患者生存质量,故针对纤维化治疗具有重要意。中药辨证治疗甲状腺纤维化以疏肝行气、健脾补肾、活血化瘀、祛痰除湿、软坚散结为... 甲状腺纤维化是各种因素刺激下,出现的纤维性改变,是多种甲状腺疾病共有的病理过程。甲状腺纤维化严重影响患者生存质量,故针对纤维化治疗具有重要意。中药辨证治疗甲状腺纤维化以疏肝行气、健脾补肾、活血化瘀、祛痰除湿、软坚散结为总原则。根据纤维化早、中、晚三期分别采用半夏厚朴汤,补中益气汤,桂附地黄汤合真武汤加丹参、地龙、贝母等方药治疗。并加入穿山龙、夏枯草、雷公藤、山慈菇、黄药子、人参皂甙等具有抗甲状腺纤维化的中药及单体,以期为临床治疗提供一种新的思路。 展开更多
关键词 甲状腺 纤维化 中医药治疗 抗纤维化
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Current therapies and novel approaches for biliary diseases 预览
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作者 Indu G Rajapaksha Peter W Angus Chandana B Herath 《世界胃肠病理生理学杂志:英文版(电子版)》 2019年第1期1-10,共10页
Chronic liver diseases that inevitably lead to hepatic fibrosis, cirrhosis and/or hepatocellular carcinoma have become a major cause of illness and death worldwide. Among them, cholangiopathies or cholestatic liver di... Chronic liver diseases that inevitably lead to hepatic fibrosis, cirrhosis and/or hepatocellular carcinoma have become a major cause of illness and death worldwide. Among them, cholangiopathies or cholestatic liver diseases comprise a large group of conditions in which injury is primarily focused on the biliary system. These include congenital diseases (such as biliary atresia and cystic fibrosis), acquired diseases (such as primary sclerosing cholangitis and primary biliary cirrhosis), and those that arise from secondary damage to the biliary tree from obstruction, cholangitis or ischaemia. These conditions are associated with a specific pattern of chronic liver injury centered on damaged bile ducts that drive the development of peribiliary fibrosis and, ultimately, biliary cirrhosis and liver failure. For most, there is no established medical therapy and, hence, these diseases remain one of the most important indications for liver transplantation. As a result, there is a major need to develop new therapies that can prevent the development of chronic biliary injury and fibrosis. This mini-review briefly discusses the pathophysiology of liver fibrosis and its progression to cirrhosis. We make a special emphasis on biliary fibrosis and current therapeutic options, such as angiotensin converting enzyme-2 (known as ACE2) over-expression in the diseased liver as a novel potential therapy to treat this condition. 展开更多
关键词 Chronic liver disease BILIARY FIBROSIS CURRENT THERAPIES for BILIARY FIBROSIS ANGIOTENSIN CONVERTING enzyme-2 Gene therapy
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Novel non-invasive score to predict cirrhosis in the era of hepatitis C elimination:A population study of ex-substance users in Singapore 预览
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作者 Yue Zhao Prem Harichander Thurairajah +3 位作者 Rahul Kumar Jessica Tan Eng Kiong Teo John Chen Hsiang 《国际肝胆胰疾病杂志:英文版》 SCIE CAS CSCD 2019年第2期143-148,共6页
Background:Chronic hepatitis C infection is common among people with history of substance use.Liver fibrosis assessment is a barrier to linkage to care,particularly among those with history of substance users.The use ... Background:Chronic hepatitis C infection is common among people with history of substance use.Liver fibrosis assessment is a barrier to linkage to care,particularly among those with history of substance users.The use of non-invasive scores can be helpful in predicting liver cirrhosis in the era of HCV elimination,especially in countries where transient elastography(TE)is not available.We compared the commonly used non-invasive scores with a novel non-invasive score in predicting liver cirrhosis in this population.Methods:HCV patients with history of substance use between 2011 and 2016 were analyzed.All patients had TE for liver fibrosis assessment.Clinical performance of established non-invasive scores for fibrosis assessment and novel score were compared.Youden’s index was used to determine optimal cut-off of the novel score.Results:A total of 579 patients were included.In multivariate logistic regression,cirrhosis on TE was associated with age(P=0.002),aspartate aminotransferase(AST)(P=0.004),and platelet count(P<0.001),but not alanine aminotransferase(ALT)(P=0.896).These form the components of modified AST-toplatelet ratio index(APRI)score.Modified APRI was superior to APRI in predicting cirrhosis(AUROC,0.796 vs.0.770,P=0.007),but not fibrosis-4 score(FIB-4)(P=1.00).Modified APRI at cut-off of 4 has sensitivity,specificity and negative predictive value(NPV)of 94.4%,26.9%and 92.6%,respectively,and at 19,has sensitivity,specificity and positive predictive value(PPV)of 33.3%,96.2%and 77.1%,respectively.FIB-4 has a NPV and PPV of 88.6%,41.8%and 78.5%,77.6%,at cut-off of 1.45 and 3.25,respectively.Using the cut-off of 4 and 14 for modified APRI,32.5%of patients can be correctly classified and misses out only 5.6%of cirrhosis patients.Conclusions:Modified APRI score is superior in predicting cirrhosis in HCV population,with 32.5%of the population being correctly classified using cut-off of 4 and 14.Further studies are required to validate the findings. 展开更多
关键词 Hepatitis C Cirrhosis Fibrosis assessment AST-to-platelet ratio index Modified APRI Fibrosis-4 SCORE
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c.753_754delAG,a novel CFTR mutation found in a Chinese patient with cystic fibrosis:A case report and review of the literature 预览
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作者 Yu-Qing Wang Chuang-Li Hao +4 位作者 Wu-Jun Jiang Yan-Hong Lu Hui-Quan Sun Chun-Yan Gao Min Wu 《世界临床病例杂志》 2019年第15期2110-2119,共10页
BACKGROUND Cystic fibrosis(CF)is rare in Asian populations relative to the Caucasian population.In this paper,we report the cystic fibrosis transmembrane conductance regulator(CFTR)variation in a family of Chinese CF ... BACKGROUND Cystic fibrosis(CF)is rare in Asian populations relative to the Caucasian population.In this paper,we report the cystic fibrosis transmembrane conductance regulator(CFTR)variation in a family of Chinese CF patients,and systematically review the previous literature.CASE SUMMARY Here we report a 30-month-old Chinese girl who was diagnosed with CF based on her history and symptoms such as recurrent productive cough,wheezing with repeated infection of Pseudomonas aeruginosa,and parasinusitis.Chest computed tomography(CT)scanning revealed obvious exudative lesions and bilateral bronchiectasis.Liver CT scanning revealed a low-density lesion in the left lobe of the liver.A diagnosis of CF was made based upon CFTR gene tests.The CFTR gene was sequenced using the blood samples of her and her parents and showed a heterozygous novel missense mutation of c.753_754delAG in exon 7.In addition,a heterozygous c.1240 C>T mutation was found in exon 10 of the CFTR.The mutation c.753_754delAG was verified to have been inherited from her mother,and the c.1240 C>T mutation was from her father who was diagnosed with congenital absence of vas deferens.CONCLUSION A novel mutation of CFTR,c.753_754delAG,was found in a Chinese CF child.c.2909G>A is the most common mutation among Chinese CF patients. 展开更多
关键词 CYSTIC FIBROSIS CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE regulator MUTATION CHINESE children Case report
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Contribution of pancreatic enzyme replacement therapy to survival and quality of life in patients with pancreatic exocrine insufficiency 预览
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作者 Peter Layer Nataliya Kashirskaya Natalya Gubergrits 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第20期2430-2441,共12页
The objective of this study was to analyze the current evidence for the use of pancreatic enzyme replacement therapy (PERT) in affecting survival and quality of life in patients with pancreatic exocrine insufficiency ... The objective of this study was to analyze the current evidence for the use of pancreatic enzyme replacement therapy (PERT) in affecting survival and quality of life in patients with pancreatic exocrine insufficiency (PEI). Systematic searches of the literature were performed using the PubMed database. Articles were selected for inclusion if they reported findings from trials assessing the effects of PERT on quality of life, survival, malabsorption, growth parameters (such as height, body weight and body mass index), or gastrointestinal symptoms (such as abdominal pain, stool consistency and flatulence). PERT improved PEI-related malabsorption and weight maintenance in patients with cystic fibrosis, chronic pancreatitis, pancreatic cancer, and post-surgical states. In patients with chronic pancreatitis, PERT improved PEI-related symptoms and quality of life measures. Several small retrospective studies have also suggested that PERT may have a positive impact on survival, but long-term studies assessing this effect were not identified. PERT is effective for treating malnutrition and supporting weight maintenance, and it is associated with improved quality of life and possibly with enhanced survival in patients with PEI. However, there is evidence that not all patients with PEI receive adequate PERT. Future work should aim to assess the long-term effects of PERT on the survival of patients with PEI. 展开更多
关键词 PANCREATIC EXOCRINE INSUFFICIENCY PANCREATIC enzyme replacement therapy SURVIVAL Quality of life MALABSORPTION CYSTIC fibrosis Chronic pancreatitis PANCREATIC cancer Post-surgical states
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胆道闭锁发生与肝纤维化的分子机制研究进展 预览
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作者 孙雪 任红霞 《临床小儿外科杂志》 CAS 2019年第5期432-436,共5页
胆道闭锁(biliary atresia,BA)的典型表现为肝内外胆管持续性炎症和迅速进展的肝纤维化,目前国内外对于胆道闭锁的病因尚无定论。因此,本文通过查阅、分析、总结近10年来的胆道闭锁相关文献,对胆道闭锁发生及其致肝纤维化的分子机制研... 胆道闭锁(biliary atresia,BA)的典型表现为肝内外胆管持续性炎症和迅速进展的肝纤维化,目前国内外对于胆道闭锁的病因尚无定论。因此,本文通过查阅、分析、总结近10年来的胆道闭锁相关文献,对胆道闭锁发生及其致肝纤维化的分子机制研究进展作一综述。 展开更多
关键词 胆道闭锁/病因学 纤维化 肝/病因学
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Hepatocellular carcinoma:Therapeutic advances in signaling,epigenetic and immune targets 预览
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作者 Daniel Neureiter Sebastian Stintzing +1 位作者 Tobias Kiesslich Matthias Ocker 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第25期3136-3150,共15页
Hepatocellular carcinoma(HCC)remains a global medical burden with rising incidence due to chronic viral hepatitis and non-alcoholic fatty liver diseases.Treatment of advanced disease stages is still unsatisfying.Besid... Hepatocellular carcinoma(HCC)remains a global medical burden with rising incidence due to chronic viral hepatitis and non-alcoholic fatty liver diseases.Treatment of advanced disease stages is still unsatisfying.Besides first and second generation tyrosine kinase inhibitors,immune checkpoint inhibitors have become central for the treatment of HCC.New modalities like epigenetic therapy using histone deacetylase inhibitors(HDACi)and cell therapy approaches with chimeric antigen receptor T cells(CAR-T cells)are currently under investigation in clinical trials.Development of such novel drugs is closely linked to the availability and improvement of novel preclinical and animal models and the identification of predictive biomarkers.The current status of treatment options for advanced HCC,emerging novel therapeutic approaches and different preclinical models for HCC drug discovery and development are reviewed here. 展开更多
关键词 Liver cancer IMMUNOTHERAPY CHECKPOINT inhibitors Targeted therapy Mouse model Biomarker Next-generation sequencing Non-alcoholic STEATOHEPATITIS Fibrosis Clinical trial
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多回声T2^*加权序列和核磁共振扩散加权成像对肝纤维化和肝硬化的量化对比初步实验 预览
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作者 顾均玉 赵虹 +3 位作者 张晶 林锦仕 林晓瑞 贝金玲 《中国医学创新》 CAS 2019年第4期14-18,共5页
目的:比较多回声T2^*加权序列与扩散加权成像(DWI)鉴别慢性肝病病患纤维化阶段的效力。方法:选取慢性肝病肝纤维化患者42例为试验组,24名健康成人志愿者为对照组。均进行MRI检查,比较肝纤维化各阶段的肝T2^*值与ADC值,分析T2^*值和ADC值... 目的:比较多回声T2^*加权序列与扩散加权成像(DWI)鉴别慢性肝病病患纤维化阶段的效力。方法:选取慢性肝病肝纤维化患者42例为试验组,24名健康成人志愿者为对照组。均进行MRI检查,比较肝纤维化各阶段的肝T2^*值与ADC值,分析T2^*值和ADC值对S1~4期纤维化分期的诊断效果,以及T2^*值和ADC值在预测纤维化0期患者出现纤维化1期或更高阶段(≥S1),纤维化1期和以下患者出现2期或更高阶段(≥S2),纤维化2期或以下患者出现3期或更高阶段(≥S3)的效力。结果:每个纤维化阶段的T2^*值和ADC值在2~4期均有明显的重叠,纤维化期和T2^*及ADC值均呈显著正相关(r=0.389、0.665,P<0.001),T2^*值和ADC值在不同纤维化阶段比较差异均有统计学意义(H=19.904、28.954,P<0.001);ROC分析显示,T2^*值和ADC值的AUC分别为0.814和0.762,比较差异有统计学意义(P<0.001),且与ADC值比较,T2^*值在区分≥S1、≥S2、≥S3时的AUC值均有更好的表现(P<0.05),另外在识别≥S1期时,T2^*值和ADC值的AUC、敏感性和特异性为0.988、100%和89.7%。结论:多回声呼吸控制T2^*加权梯度回波序列对肝纤维化期的快速、无创和准确评估有重要意义,可以作为一种技术用于判定抗病毒治疗和监测慢性肝炎患者的治疗反应,并替代部分患者的肝活检。 展开更多
关键词 慢性肝炎 纤维化 肝脏 多回声T2^*加权序列 扩散加权成像
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p53 upregulated by HIF-la promotes hypoxiainduced G2/M arrest and renal fibrosis in vitro and in vivo
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作者 Limin Liu Peng Zhang +10 位作者 Ming Bai Lijie He Lei Zhang Ting Liu Zhen Yang Menglu Duan Minna Liu Baojian Liu Rui Du Qi Qian Shiren Sun 《分子细胞生物学报:英文版》 SCIE CAS CSCD 2019年第5期371-382,共12页
Hypoxia plays an important role in the genesis and progression of renal fibrosis.The underlying mechanisms, however, have not been sufficiently elucidated. We examined the role of p53 in hypoxia-induced renal fibrosis... Hypoxia plays an important role in the genesis and progression of renal fibrosis.The underlying mechanisms, however, have not been sufficiently elucidated. We examined the role of p53 in hypoxia-induced renal fibrosis in cell culture (human and rat renal tubular epithelial cells) and a mouse unilateral ureteral obstruction (UUO) model. Cell cycle of tubular cells was determined by flow cytometry, and the expression of profibrogenic factors was determined by RT-PCR, immunohistochemistry, and western blotting. Chromatin immunoprecipitation and luciferase reporter experiments were performed to explore the effect of HIF-lα on p53 expression. We showed that, in hypoxic tubular cells, p53 upregulation suppressed the expression of CDK1 and cyclins Bl and DI, leading to cell cycle (G2/M) arrest (or delay) and higher expression of TGF-β, CTGF, collagens, and fibronectin. p53 suppression by siRNA or by a specific p53 inhibitor (PIF-α) triggered opposite effects preventing the G2/M arrest and profibrotic changes. In vivo experiments in the UUO model revealed similar antifibrotic results following intraperitoneal administration of PIF-α(2.2 mg/kg). Using gain-of-function, loss-of-function, and luciferase assays, we further identified an HRE3 region on the p53 promoter as the HIF-lα-binding site. The HIF-la-HRE3 binding resulted in a sharp transcriptional activation of p53. Collectively, we show the presence of a hypoxia-activated, p53-responsive profibrogenic pathway in the kidney. During hypoxia, p53 upregulation induced by HIF-la suppresses cell cycle progression, leading to the accumulation of G2/M cells, and activates profibrotic TGF-β and CTGF-mediated signaling pathways, causing extracellular matrix production and renal fibrosis. 展开更多
关键词 RENAL tubulointerstitial FIBROSIS HYPOXIA cell cycle (G2/M) ARREST P53 HIF-lα TGF-β
长期静脉注射羧基化单壁碳纳米管对大鼠肾脏的毒性作用研究 预览
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作者 谢雪平 成晓静 +3 位作者 秦悦 李苏宁 刘华钢 赖泽锋 《广西医科大学学报》 CAS 2019年第4期501-506,共6页
目的:评价静脉注射羧基化单壁碳纳米管(c-SWNTs)对大鼠肾脏的毒性作用。方法:将64只SD大鼠随机分为空白对照组(Control组)和实验组(c-SWNTs组),每组32只,Control组经尾静脉注射5%葡萄糖溶液,c-SWNTs组经尾静脉注射c-SWNTS葡萄糖溶液。... 目的:评价静脉注射羧基化单壁碳纳米管(c-SWNTs)对大鼠肾脏的毒性作用。方法:将64只SD大鼠随机分为空白对照组(Control组)和实验组(c-SWNTs组),每组32只,Control组经尾静脉注射5%葡萄糖溶液,c-SWNTs组经尾静脉注射c-SWNTS葡萄糖溶液。分别在干预30d、60d、90d及c-SWNTs组停止染毒30d后(共120d),每组随机取8只大鼠,麻醉处死后采集肾脏标本,透射电子显微镜(TEM)观察肾组织超微结构,苏木精—伊红(HE)染色和Masson染色观察肾组织病理学改变,Western blotting法检测Ⅲ型胶原(Col Ⅲ)蛋白的表达。结果: TEM结果显示,与Control组比较,30d后c-SWNTs组大鼠肾小球体积明显缩小,细胞核固缩,线粒体增大。HE和Masson染色结果显示,与Control组相比,c-SWNTs组大鼠肾脏血管壁局部增厚,肾小球毛细血管襻与球囊壁发生黏连,毛细血管襻内发生炎症细胞浸润,并随着染毒时间延长而向肾小球旁的间质扩散,肾小管管腔明显扩张,肾小球旁和肾髓质间质纤维组织增生;90d后c-SWNTs组大鼠肾脏炎症和纤维化程度最严重,但停止染毒30d后,炎症反应和纤维化程度有所减轻。与Control组比较,c-SWNTs组在连续染毒90 d后肾组织Col Ⅲ蛋白表达显著上调(P<0.05),而停止染毒30d后下调,与Control组相比差异无统计学意义(P>0.05)。结论:长期静脉注射c-SWNTs会损伤大鼠肾脏肾皮质、肾髓质和肾血管,引起可逆性的炎性反应和肾纤维化。 展开更多
关键词 单壁碳纳米管 静脉注射 肾脏 炎性反应 纤维化
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微小RNA在心房颤动中作用机制的研究进展 预览
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作者 曹敏 姚亚丽 《中国心血管杂志》 2019年第3期297-300,共4页
微小RNA具有很强的生物特性与治疗价值,可以作为心血管疾病的生物标记物。近期多项基因研究显示,微小RNA在一定程度上参与了心房颤动的发生发展,并推测出与心房颤动有关的作用机制,这有望为心房颤动的诊断和治疗带来新方向。
关键词 微小RNA 心房颤动 纤维化 生物学标记
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气管瘢痕狭窄动物模型的研究进展 预览
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作者 王志鹏 张春林 刘兆辉 《海南医学》 CAS 2019年第10期1326-1328,共3页
气管狭窄是气管切开严重的术后并发症,严重影响患者生存质量,临床处理棘手。气管狭窄的发病机制复杂,目前仍未完全清楚,本文将近年来学者关于气管狭窄的动物模型及发生机制的研究做一综述。
关键词 气管狭窄 动物模型 机制 瘢痕 纤维化
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子宫内膜损伤修复与宫腔粘连形成机制研究进展
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作者 郭罗培 隋龙 《中国实用妇科与产科杂志》 CAS CSCD 北大核心 2019年第6期706-709,共4页
宫腔粘连(IUA)又称Asherman Syndrome,自1894年首次由Heinrich Fritsch报道,54年之后,才经以色列妇科医生Joseph Asherman详细介绍了这一疾病,主要表现为闭经、不孕、盆腔疼痛等。同时,他发现子宫内膜损伤极有可能是本病的发病原因[1]... 宫腔粘连(IUA)又称Asherman Syndrome,自1894年首次由Heinrich Fritsch报道,54年之后,才经以色列妇科医生Joseph Asherman详细介绍了这一疾病,主要表现为闭经、不孕、盆腔疼痛等。同时,他发现子宫内膜损伤极有可能是本病的发病原因[1]。那么,宫腔粘连的发病机制与子宫内膜损伤修复有什么联系,具体是如何发生的呢?本文就此问题进行综述。 展开更多
关键词 损伤修复 宫腔粘连 纤维化 上皮间质转化
姜黄素类似物J7对2型糖尿病大鼠肾脏的保护作用 预览
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作者 姬秀焕 章琼莹 +3 位作者 池琛 吴谷 李慧敏 陈国荣 《浙江医学》 CAS 2019年第13期1342-1347,I0004共7页
目的探讨姜黄素(CUR)类似物J7对2型糖尿病(T2DM)大鼠肾脏的保护作用及其可能机制。方法将雄性SD大鼠随机分成5组:正常对照(NC)组、模型组、CUR治疗组、J7低剂量(LJ7)治疗组和J7高剂量(HJ7)治疗组。后4组采用高脂高糖饮食喂养4周,单次腹... 目的探讨姜黄素(CUR)类似物J7对2型糖尿病(T2DM)大鼠肾脏的保护作用及其可能机制。方法将雄性SD大鼠随机分成5组:正常对照(NC)组、模型组、CUR治疗组、J7低剂量(LJ7)治疗组和J7高剂量(HJ7)治疗组。后4组采用高脂高糖饮食喂养4周,单次腹腔注射链脲佐菌素(30mg/kg)诱导T2DM模型。CUR组、LJ7组和HJ7组分别按20mg/kg CUR、10mg/kg J7、20mg/kg J7灌胃8周,1次/d;每次灌胃量按1ml/100g计算得出,其余组予同等容积羧甲基纤维素钠灌胃。在光镜和电镜下观察各组大鼠肾脏组织形态改变;测量各组大鼠体重、肾重,计算肾重指数;检测各组大鼠空腹血糖(FBG)、血肌酐(Scr)、尿素氮(BUN)水平;硫代巴比妥酸法检测各组大鼠肾脏组织丙二醛(MDA)水平;羟胺法检测各组大鼠肾脏组织超氧化物歧化酶(SOD)活性;免疫组化染色法检测各组大鼠肾脏转化生长因子β1(TGF-β1)蛋白表达;Western blot法检测各组大鼠肾脏组织TGF-β1、人信号转导因子7(Smad7)、B淋巴细胞瘤-2基因相关X蛋白(Bax)、B淋巴细胞瘤-2基因(Bcl-2)蛋白相对表达量及Bcl-2/Bax。结果与NC组比较,模型组大鼠肾小球肥大,胶原纤维增多,细胞外基质沉积,足突融合;体重、SOD活性和Bcl-2、Smad7蛋白相对表达量及Bcl-2/Bax均明显降低(均P<0.05),肾重指数、FBG、Scr、BUN、MDA水平和Bax、TGF-β1蛋白相对表达量均明显升高(均P<0.05);经CUR或J7治疗后,相应病理学改变减轻,体重略有上升,SOD活性和Bcl-2、Smad7蛋白相对表达量及Bcl-2/Bax均明显升高(均P<0.05),FBG、MDA水平和Bax、TGF-β1蛋白相对表达量均明显降低(均P<0.05)。结论CUR类似物J7对T2DM大鼠的肾脏具有保护作用,可能与其具有抑制氧化应激、抗细胞凋亡、抑制TGF-β/Smad通路及纤维化作用有关。 展开更多
关键词 糖尿病 肾脏 姜黄素类似物J7 氧化应激 纤维化
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脂多糖刺激的骨髓间充质干细胞来源外泌体改善小鼠心肌梗死后炎症和纤维化 预览
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作者 傅小媚 霍然 +7 位作者 邓赛 林潮金 范景皓 王萍 李松沛 秦爱萍 邹明辉 余细勇 《中国临床药理学与治疗学》 CAS CSCD 2019年第8期841-851,共11页
目的:探讨脂多糖(LPS)刺激下的骨髓间充质干细胞(BMSCs)来源的外泌体对小鼠心肌梗死(MI)后的治疗作用。方法:流式成像细胞分析术鉴定BMSCs的表面标记分子,油红O和茜素红染色于镜下观察成骨成脂分化能力。LPS刺激BMSCs48h,提取细胞培养... 目的:探讨脂多糖(LPS)刺激下的骨髓间充质干细胞(BMSCs)来源的外泌体对小鼠心肌梗死(MI)后的治疗作用。方法:流式成像细胞分析术鉴定BMSCs的表面标记分子,油红O和茜素红染色于镜下观察成骨成脂分化能力。LPS刺激BMSCs48h,提取细胞培养上清外泌体,用透射电镜和粒度分析仪捕捉其形态和粒径大小,流式细胞术和Western blot检测特异性表面标记分子及蛋白表达。建构小鼠MI模型并予以外泌体心脏局部注射,利用心脏超声、组织病理切片和PCR评价治疗结果。结果:分离的BMSCs表达CD29、CD44、CD90、CD73、CD105,未表达HLA-DR、CD14、CD34、CD45,具有成骨成脂分化能力。Western blot检测到外泌体表达Alix、HSP70、Flotillin-1蛋白,流式成像仪检测到外泌体膜表面的CD63、CD9和CD81标记分子,粒径众数为69.2nm。LPS刺激下BMSCs产生的外泌体注射小鼠心脏后,与PBS注射的MI对照组比较,心脏超声评价7天和28天的射血分数(EF)和短轴缩短率(FS)都显著增大(P<0.01,P<0.05),在第28天的舒张末期容积(LVEDV)和收缩末期容积(LVESV)均显著减小(P<0.05),Masson染色显示纤维化面积减小(P<0.01),PCR检测到炎症因子IL-6、IL-1β、转化生长因子β(TGF-β)和趋附因子CCL2表达减少,CX3CL1表达增多,术后第14天最为明显。结论:LPS刺激的BMSCs来源外泌体可以改善小鼠MI后心肌收缩功能和纤维化,降低炎症因子表达量。 展开更多
关键词 骨髓间充质干细胞 外泌体 脂多糖 心肌梗死 纤维化 炎症
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Effect of NLRC5 on activation and reversion of hepatic stellate cells by regulating the nuclear factor-κB signaling pathway 预览
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作者 Yan-Zhen Zhang Jian-Ning Yao +3 位作者 Lian-Feng Zhang Chun-Feng Wang Xue-Xiu Zhang Bing Gao 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第24期3044-3055,共12页
BACKGROUND The formation of liver fibrosis is mainly caused by the activation of hepatic stellate cells(HSCs)and the imbalance of extracellular matrix(ECM)production and degradation.The treatment of liver fibrosis mai... BACKGROUND The formation of liver fibrosis is mainly caused by the activation of hepatic stellate cells(HSCs)and the imbalance of extracellular matrix(ECM)production and degradation.The treatment of liver fibrosis mainly includes removing the cause,inhibiting the activation of HSCs,and inhibiting inflammation.NOD-like receptor(NLR)family,caspase activation and recruitment domain(CARD)domain containing 5/NOD27/CLR16.1(NLRC5)is a highly conserved member of the NLR family and is involved in inflammation and immune responses by regulating various signaling pathways such as nuclear factor-κB(NF-κB)signaling.It has been found that NLRC5 plays an important role in liver fibrosis,but its specific effect and possible mechanism remain to be fully elucidated.AIM To investigate the role of NLRC5 in the activation and reversion of HSCs induced with transforming growth factor-β(TGF-β)and MDI,and to explore its relationship with liver fibrosis.METHODS A total of 24 male C57BL/6 mice were randomly divided into three groups,including normal,fibrosis,and recovery groups.Twenty-four hours after a liver fibrosis and spontaneous reversion model was established,the mice were sacrificed and pathological examination of liver tissue was performed to observe the degree of liver fibrosis in each group.LX-2 cells were cultured in vitro and treated with TGF-β1 and MDI.Real-time quantitative PCR(qPCR)and Western blot were used to analyze the expression levels of NLRC5,α-smooth muscle actin(α-SMA),and collagen type I alpha1(Col1a1)in each group.The activity of NF-κB in each group of cells transfected with NLRC5-siRNA was detected.RESULTS Compared with the normal mice,the expression level of NLRC5 increased significantly(P<0.01)in the fibrosis group,but decreased significantly in the recovery group(P<0.01).In in vitro experiments,the content of NLRC5 was enhanced after TGF-β1 stimulation and decreased to a lower level when treated with MDI(P<0.01).The expression ofα-SMA and Col1a1 proteins and mRNAs in TGF-β1-mediated cells was suppr 展开更多
关键词 NLRC5 HEPATIC stellate cells Liver FIBROSIS RECOVERY
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Decrease of Matrix Plasticity Promotes Fibroblast Activation in Fibrosis
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作者 Yuanbo Jia Yanzhong Wang +8 位作者 Lele Niu Hang Zhang Jin Tian Dengfeng Gao Xiaohui Zhang Tian Jian Lu Jin Qian Guoyou Huang Feng Xu 《医用生物力学》 CAS CSCD 北大核心 2019年第A01期126-127,共2页
This work identified the important role of matrix mechanical plasticity in mediating fibroblast activation.Many existing studies have highlighted the important effects of biochemical cues(e.g.,transforming growth fact... This work identified the important role of matrix mechanical plasticity in mediating fibroblast activation.Many existing studies have highlighted the important effects of biochemical cues(e.g.,transforming growth factor-β1)and mechanicalstiffness on fibroblast activation.Our results indicated that self-assembled collagen hydrogels showed high plasticity and in which fibroblasts remain undifferentiated.However,when we decreased the plasticity of collagen hydrogels by increasing covalent crosslinking,fibroblasts showed a significant fibrotic response as reflected by the increasedα-SMA expression.Since the material systems we constructed have low and the same initial modulus,this process is stiffness independent.Although it has been reported that covalently crosslinked hydrogels are more difficult to degrade and matrix degradability has an important impact on cell behaviors,no significant changes of fibroblast activation were observed when proteases were broadly inhibited in our experiments.Importantly,the hydrogels we constructed showed similar plastic behaviors under creep and recovery tests compared to native normal and fibrotic tissues.These highlight the importance of matrix plasticity in mimicking the mechanical microenvironment of native fibrotic tissues.Mechanistically,we found that the enhanced fibroblast activation in low plastic matrix is mediated through integrin-actin pathway and nuclear localization of YAP.In high plastic collagen,matrix cannot provide effective resistance to actin contraction because of the rupture of weak crosslinks and the slippage of local fibers.On the contrary,in low plastic collagen,deformation energy can be stored in the network due to the existence of strong covalent crosslinks,thus enabling the build-up of cell traction and the formation of a robust cell-matrix interaction.Experiments of inhibiting or promoting cytoskeletal contractility and CGMD simulation both verified the above points.Our results clarify plasticity changes on the development of fibrotic diseases and high 展开更多
关键词 DECREASE MATRIX PLASTICITY PROMOTES FIBROBLAST Activation FIBROSIS MATRIX
Iron and liver fibrosis:Mechanistic and clinical aspects 预览
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作者 Kosha J Mehta Sebastien Je Farnaud Paul A Sharp 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第5期521-538,共18页
Liver fibrosis is characterised by excessive deposition of extracellular matrix that interrupts normal liver functionality.It is a pathological stage in several untreated chronic liver diseases such as the iron overlo... Liver fibrosis is characterised by excessive deposition of extracellular matrix that interrupts normal liver functionality.It is a pathological stage in several untreated chronic liver diseases such as the iron overload syndrome hereditary haemochromatosis,viral hepatitis,alcoholic liver disease,non-alcoholic fatty liver disease,non-alcoholic steatohepatitis and diabetes.Interestingly,regardless of the aetiology,iron-loading is frequently observed in chronic liver diseases.Excess iron can feed the Fenton reaction to generate unquenchable amounts of free radicals that cause grave cellular and tissue damage and thereby contribute to fibrosis.Moreover,excess iron can induce fibrosis-promoting signals in the parenchymal and non-parenchymal cells,which accelerate disease progression and exacerbate liver pathology.Fibrosis regression is achievable following treatment,but if untreated or unsuccessful,it can progress to the irreversible cirrhotic stage leading to organ failure and hepatocellular carcinoma,where resection or transplantation remain the only curative options.Therefore,understanding the role of iron in liver fibrosis is extremely essential as it can help in formulating iron-related diagnostic,prognostic and treatment strategies.These can be implemented in isolation or in combination with the current approaches to prepone detection,and halt or decelerate fibrosis progression before it reaches the irreparable stage.Thus,this review narrates the role of iron in liver fibrosis.It examines the underlying mechanisms by which excess iron can facilitate fibrotic responses.It describes the role of iron in various clinical pathologies and lastly,highlights the significance and potential of iron-related proteins in the diagnosis and therapeutics of liver fibrosis. 展开更多
关键词 IRON LIVER PATHOLOGIES LIVER FIBROSIS Hepatic stellate cells Cirrhosis
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慢性乙型肝炎合并肝脂肪变性患者的临床及病理特征分析
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作者 郑伟 潘宏义 +3 位作者 吴青青 尹乔乔 戴伊宁 潘红英 《中华临床感染病杂志》 CSCD 2019年第2期87-92,共6页
目的分析慢性乙型肝炎(Chronic hepatitis B,CHB)合并肝脂肪变性患者的临床特点,并对其病理特征进行分析。方法回顾性分析2015年9月至2018年9月在浙江省人民医院行肝穿刺检查的CHB患者共841例,根据肝脏病理组织中脂肪变性程度,分为脂肪... 目的分析慢性乙型肝炎(Chronic hepatitis B,CHB)合并肝脂肪变性患者的临床特点,并对其病理特征进行分析。方法回顾性分析2015年9月至2018年9月在浙江省人民医院行肝穿刺检查的CHB患者共841例,根据肝脏病理组织中脂肪变性程度,分为脂肪变性组和非脂肪变性组,采用倾向值匹配法按照性别相同、年龄相近(≤1岁)的原则进行配对,共获得135对CHB患者,采用秩和检验和多因素Logistic回归分析CHB患者合并肝脂肪变性的临床特征及其危险因素,采用Spearman秩相关分析肝脂肪变性的程度与HBV DNA水平和肝脏炎症及纤维化的关系。结果多因素Logistic回归分析显示,超重/肥胖(χ^2=3.947,OR=1.436,95%CI 1.005~2.051,P<0.05)及高脂血症(χ^2=4.277,OR=1.803,95%CI 1.031~3.151,P<0.05)为CHB患者发生肝脂肪变性的危险因素。肝脂肪变性程度与血清HBeAg、HBV DNA均无相关性(Z=-1.762,r=-0.011,P>0.05),但与肝脏炎症活动度分级及纤维化程度分期呈负相关(r=-0.146和-0.192,P<0.05)。结论超重/肥胖及高脂血症的CHB患者容易发生脂肪变性,肝脂肪变性并不会加重CHB患者肝脏炎症及纤维化程度。 展开更多
关键词 乙型肝炎 慢性 肝脂肪变性 肝脏炎症 纤维化 倾向值匹配法
Crosstalk network among multiple inflammatory mediators in liver fibrosis 预览
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作者 Han-Jing Zhangdi Si-Biao Su +4 位作者 Fei Wang Zi-Yu Liang Yu-Dong Yan Shan-Yu Qin Hai-Xing Jiang 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第33期4835-4849,共15页
Liver fibrosis is the common pathological basis of all chronic liver diseases,and is the necessary stage for the progression of chronic liver disease to cirrhosis.As one of pathogenic factors,inflammation plays a pred... Liver fibrosis is the common pathological basis of all chronic liver diseases,and is the necessary stage for the progression of chronic liver disease to cirrhosis.As one of pathogenic factors,inflammation plays a predominant role in liver fibrosis via communication and interaction between inflammatory cells,cytokines,and the related signaling pathways.Damaged hepatocytes induce an increase in proinflammatory factors,thereby inducing the development of inflammation.In addition,it has been reported that inflammatory response related signaling pathway is the main signal transduction pathway for the development of liver fibrosis.The crosstalk regulatory network leads to hepatic stellate cell activation and proinflammatory cytokine production,which in turn initiate the fibrotic response.Compared with the past,the research on the pathogenesis of liver fibrosis has been greatly developed.However,the liver fibrosis mechanism is complex and many pathways involved need to be further studied.This review mainly focuses on the crosstalk regulatory network among inflammatory cells,cytokines,and the related signaling pathways in the pathogenesis of chronic inflammatory liver diseases.Moreover,we also summarize the recent studies on the mechanisms underlying liver fibrosis and clinical efforts on the targeted therapies against the fibrotic response. 展开更多
关键词 CROSSTALK NETWORK INFLAMMATORY cell CYTOKINE signal pathway Liver FIBROSIS
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