检索结果-南通市图书馆

Targeting PDE4 as a promising therapeutic strategy in chronic ulcerative colitis through modulating mucosal homeostasis

引用

Acta Pharmaceutica Sinica B 2022年第1期12卷 228-245页

作者： Heng Li Yao Zhang Moting Liu Chen Fan Chunlan Feng Qiukai Lu Caigui Xiang Huimin Lu Xiaoqian Yang Bing Wu Duowu Zou Wei Tang Laboratory of Anti-inflammation and Immunopharmacology Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Pharmacy University of Chinese Academy of SciencesBeijing 100049China Department of Gastroenterology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

Phosphodiesterase-4(PDE4) functions as a catalyzing enzyme targeting hydrolyzation of intracellular cyclic adenosine monophosphate(c AMP) and inhibition of PDE4 has been proven to be a competitive strategy for dermatological and pulmonary inflammation. However, the pathological role of PDE4 and the therapeutic feasibility of PDE4 inhibitors in chronic ulcerative colitis(UC) are less clearly understood. This study introduced apremilast, a breakthrough in discovery of PDE4 inhibitors,to explore the therapeutic capacity in dextran sulfate sodium(DSS)-induced experimental murine chronic UC. In the inflamed tissues, overexpression of PDE4 isoforms and defective c AMP-mediating pathway were firstly identified in chronic UC patients. Therapeutically, inhibition of PDE4 by apremilast modulated c AMP-predominant protein kinase A(PKA)-c AMP-response element binding protein(CREB)signaling and ameliorated the clinical symptoms of chronic UC, as evidenced by improvements on mucosal ulcerations, tissue fibrosis, and inflammatory infiltrations. Consequently, apremilast maintained a normal intestinal physical and chemical barrier function and rebuilt the mucosal homeostasis by interfering with the cross-talk between human epithelial cells and immune cells. Furthermore, we found that apremilast could remap the landscape of gut microbiota and exert regulatory effects on antimicrobial responses and the function of mucus in the gut microenvironment. Taken together, the present studyrevealed that intervene of PDE4 provided an infusive therapeutic strategy for patients with chronic and relapsing UC.

关键词： Ulcerative colitis PDE4 mucosal homeostasis Gut microbiota Epithelial barrier

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Gut microbiota-derived metabolites as key mucosal barrier modulators in obesity

引用

World Journal of Gastroenterology 2021年第33期27卷 5555-5565页

作者： Yan-Xia Wei Kui-Yang Zheng Yu-Gang Wang Laboratory of Infection and Immunity Jiangsu Key Laboratory of Immunity and MetabolismDepartment of Pathogenic Biology and ImmunologyXuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina

A significant breakthrough in the field of obesity research was the demonstration that an obese phenotype could be manipulated by modulating the gut *** important next step is to elucidate a human-relevant"map"of microbiota-host interactions that regulate the metabolic health of the *** improved understanding of this crosstalk is a prerequisite for optimizing therapeutic strategies to combat *** mucosal barrier dysfunction is an important contributor to metabolic diseases and has also been found to be involved in a variety of other chronic inflammatory conditions,including cancer,neurodegeneration,and *** mechanistic basis for intestinal barrier dysfunction accompanying metabolic disorders remains poorly *** the molecular and cellular modulators of intestinal barrier function will help devise improved strategies to counteract the detrimental systemic consequences of gut barrier *** in the composition and function of the gut microbiota,i.e.,dysbiosis,are thought to drive obesity-related pathogenesis and may be one of the most important drivers of mucosal barrier *** effects of the microbiota on the host are mediated by microbiota-derived *** this review,we focus on several relatively well-studied microbial metabolites that can influence intestinal mucosal homeostasis and discuss how they might affect metabolic *** design and use of microbes and their metabolites that are locally active in the gut without systemic side effects are promising novel and safe therapeutic modalities for metabolic diseases.

关键词： Obesity Metabolic diseases Microbiota mucosal homeostasis Gut Microbial metabolites

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases

引用

Precision Clinical Medicine 2021年第4期4卷 246-257页

作者： Huimin Chen Xiaohan Wu Chunjin Xu Jian Lin Zhanju Liu Center for Inflammatory Bowel Disease Research the Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200072China Department of Gastroenterology the First People’s Hospital of Shangqiu City Affiliated to Xinxiang Medical UniversityShangqiu 476100China Department of Gastroenterology Affiliated Hospital of Putian UniversityPutian 351106China

Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal *** exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation,but paradoxically,they also limit exogenousmicrobial invasion and facilitate mucosal *** or dysfunction of neutrophils results in abnormal immune responses,leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus,rheumatoid arthritis,and inflammatory bowel diseases(IBD).As a refractory intestinal inflammatory disease,the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly ***,the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully *** infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis,aggravated intestinal architectural damage,compromised resolution of intestinal inflammation and increased risk of thrombosis during ***,activated neutrophils are also associated with effective elimination of invaded microbiota,promoted angiogenesis and tissue restoration of gutmucosa in ***,we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinalmucosal inflammation,hoping to provide a precise overview of neutrophil functions in the pathogenesis of IBD.

关键词： neutrophil innate immune cell inflammatory bowel disease intestinal inflammation mucosal homeostasis immune response microbial dysbiosis

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：