检索结果-南通市图书馆

Differential role of Hedgehog signaling in human pancreatic(patho-)physiology:An up to date review

在线全文

学校读者我要写书评

暂无评论

World Journal of Gastrointestinal pathophysiology 2016年第2期7卷 199-210页

作者： Eckhard Klieser Stefan Swierczynski Christian Mayr Tarkan Jager Johanna Schmidt Daniel Neureiter Tobias Kiesslich Romana Illig Institute of Pathology Paracelsus Medical UniversitySalzburger Landeskliniken(SALK) Department of Surgery Paracelsus Medical UniversitySalzburger Landeskliniken(SALK) Department of Internal Medicine I Paracelsus Medical UniversitySalzburger Landeskliniken(SALK) laboratory for Tumour Biology and experimental Therapies(TREAT) Institute of Physiology and PathophysiologyParacelsus Medical University

Since the discovery of the Hedgehog(Hh)pathway in drosophila melanogaster,our knowledge of the role of Hh in embryonic development,inflammation,and cancerogenesis in humans has dramatically increased over the last decades.This is the case especially concerning the pancreas,however,real therapeutic breakthroughs are missing until now.In general,Hh signaling is essential for pancreatic organogenesis,development,and tissue maturation.In the case of acute pancreatitis,Hh has a protective role,whereas in chronic pancreatitis,Hh interacts with pancreatic stellate cells,leading to destructive parenchym fibrosis and atrophy,as well as to irregular tissue remodeling with potency of initiating cancerogenesis.In vitro and in situ analysis of Hh in pancreatic cancer revealed that the Hh pathway participates in the development of pancreatic precursor lesions and ductal adenocarcinoma including critical interactions with the tumor microenvironment.The application of specific inhibitors of components of the Hh pathway is currently subject of ongoing clinical trials(phases 1 and 2).Furthermore,a combination of Hh pathway inhibitors and established chemotherapeutic drugs could also represent a promising therapeutic approach.In this review,we give a structured survey of the role of the Hh pathway in pancreatic development,pancreatitis,pancreatic carcinogenesis and pancreatic cancer as well as an overview of current clinical trials concerning Hh pathway inhibitors and pancreas cancer.

关键词： Pancreatic cancer Hedgehog Pancreatitis Pancreas Development

Neonatal Exposure to the Dipeptidyl Peptidase-IV Inhibitors Diprotin A and Sitagliptin Induces Depression-Like Behavior, Anxiety, and Latent Aggression in Adolescent and Adult Rats

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Behavioral and Brain Science 2016年第4期6卷 167-183页

作者： Nataliya A. Krupina Nadezhda N. Khlebnikova laboratory of the General Pathology of Nervous System Federal State Budgetary Scientific Institution “Institute of General Pathology and Pathophysiology” Moscow Russia

Emotional and motivational disorders in adults are often considered to be the result of altered neurodevelopment. Clinical and experimental data provide evidence that serine protease dipeptidyl peptidase-IV (DPP-IV, EC 3.***.14.5) is involved in the pathophysiology of psycho-emotional disorders. Recently, we have shown that adolescent and adult rats exhibit an increase in anxiety and depression-related behaviors after neonatal administration of a synthetic non-competitive inhibitor of DPP-IV, methionyl-2(S)-cyano-pyrrolidine. In the present study, we tested the effects of two competitive, selective DPP-IV inhibitors, sitagliptin (4 mg/kg) and diprotin A (2 mg/kg), administered at postnatal days 5 - 18 on the emotional and motivational behavior of adolescent and adult rats. We observed increased anxiety in one-month-old diprotin A- or sitagliptin-treated rats in the elevated plus maze;diprotin A also enhanced the animals’ anxiety score using a ranked scale for evaluating anxiety and phobias. In the sucrose consumption and preference test, depressive-like behavior was pronounced in both the diprotin A- and sitagliptin-treated one-month-old animals, while only the diprotin A-treated rats exhibited a decrease in sucrose consumption at the age of 2 months. The diprotin A-treated rats also demonstrated behavioral despair and decreased activity in the forced swimming test within 1 - 3 months of age. Increased aggression was observed in 1 - 3-month-old diprotin A-treated rats and in two-month-old sitagliptin-treated rats. These findings support the hypothesis that DPP-IV is involved in the genesis of emotional and motivational disorders. Additionally, the results show that diprotin А impairs the adolescent and adult rats’ behavior more significantly than sitagliptin when the animals were treated with the DPP-IV inhibitors in the early postnatal period.

关键词： Dipeptidyl Peptidase IV Inhibitors Rat Depression Anxiety Aggression

Phenotype and target-based chemical biology investigations in cancers

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

National Science Review 2019年第6期6卷 1111-1127页

作者： Guo-Qiang Chen Ying Xu Shao-Ming Shen Jian Zhang Department of pathophysiology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationShanghai Jiao Tong University School of Medicine (SJTU-SM)

Chemical biology has been attracting a lot of attention because of the key roles of chemical methods and techniques in helping to decipher and manipulate biological systems. Although chemical biology encompasses a broad field, this review will focus on chemical biology aimed at using exogenous chemical probes to interrogate, modify and manipulate biological processes, at the cellular and organismal levels,in a highly controlled and dynamic manner. In this area, many advances have been achieved for cancer biology and therapeutics, from target identification and validation based on active anticancer compounds(forward approaches) to discoveries of anticancer molecules based on some important targets including protein-protein interaction(reverse approaches). Herein we attempt to summarize some recent progresses mainly from China through applying chemical biology approaches to explore molecular mechanisms of carcinogenesis. Additionally, we also outline several new strategies for chemistry to probe cellular activities such as proximity-dependent labeling methods for identifying protein-protein interactions, genetically encoded sensors, and light activating or repressing gene expression system.

关键词： chemical biology chemical compounds target cancer leukemia

Collagen for brain repair:therapeutic perspectives

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Neural Regeneration Research 2018年第4期13卷 595-598页

作者： Buket Ucar Christian Humpel laboratory of Psychiatry and experimental Alzheimer's Research Medical University of Innsbruck

Biomaterials have increasingly become a focus of research on neuroprotection and neuroregeneration.Collagen,in terms of brain repair,presents many advantages such as being remarkably biocompatible,biodegradable,versatile and non-toxic.Collagen can be used to form injectable scaffolds and micro/nano spheres in order to：（i） locally release therapeutic factors with the aim of protecting degenerating neurons in neurodegenerative conditions such as Alzheimer＇s or Parkinson＇s diseases,（ii） encapsulate stem cells for safe delivery,（iii） encapsulate genetically modified cells to provide a long term source of trophic factors,（iv） fill in the voids from injury to serve as a structural support and provide a permissive microenvironment to promote axonal growth.This mini-review summarizes different applications of collagen biomaterial for central nervous system protection and repair,as well as the future perspectives.Overall,collagen is a promising natural biomaterial with various applications which has the potential to progress the development of therapeutic strategies in central nervous system injuries and degeneration.

关键词： biomaterial collagen scaffold microspheres neuroprotection neuroregeneration neurorepair Alzheimer’s disease Parkinson’s disease

Transcriptional regulation of endothelial dysfunction in atherosclerosis:an epigenetic perspective

在线全文

学校读者我要写书评

暂无评论

The Journal of Biomedical Research 2014年第1期28卷 47-52页

作者： Yong Xu Key laboratory of Cardiovascular Disease and Molecular Intervention Department of PathophysiologyNanjing Medical University

Atherosclerosis is a progressive human pathology that encompasses several stages of development. Endothelial dysfunction represents an early sign of lesion within the vasculature. A number of risk factors for atherosclero- sis, including hyperlipidemia, diabetes, and hypertension, target the vascular endothelium by re-programming its transcriptome. These profound alterations taking place on the chromatin rely on the interplay between sequence specific transcription factors and the epigenetic machinery. The epigenetic machinery, in turn, tailor individual transcription events key to atherogenesis to intrinsic and extrinsic insults dictating the development of atheroscle- rotic lesions. This review summarizes our current understanding of the involvement of the epigenetic machinery in endothelial injury during atherogenesis.

关键词： Atherosclerosis transcriptional regulation endothelial injury epigenetics

Hypoxia,angiogenesis and liver fibrogenesis in the progression of chronic liver diseases

在线全文

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2010年第3期16卷 281-288页

作者： Claudia Paternostro Ezio David Erica Novo Maurizio Parola Department of experimental Medicine and Oncology Interuniversity Centre for Hepatic PathophysiologyUniversity of Torino Department of Pathology San Giovanni Battista Hospital

Angiogenesis is a dynamic,hypoxia-stimulated and growth factor-dependent process,and is currently referred to as the formation of new vessels from preexisting blood vessels.experimental and clinical studies have unequivocally reported that hepatic angiogenesis,irrespective of aetiology,occurs in conditions of chronic liver diseases(CLDs) characterized by perpetuation of cell injury and death,inflammatory response and progressive fibrogenesis.Angiogenesis and related changes in liver vascular architecture,that in turn concur to increase vascular resistance and portal hypertension and to decrease parenchymal perfusion,have been proposed to favour fibrogenic progression of the disease towards the end-point of cirrhosis.Moreover,hepatic angiogenesis has also been proposed to modulate the genesis of portal-systemic shunts and increase splanchnic blood flow,thus potentially affecting complications of cirrhosis.Hepatic angiogenesis is also crucial for the growth and progression of hepatocellular carcinoma.Recent literature has identified a number of cellular and molecular mechanisms governing the cross-talk between angiogenesis and fibrogenesis,with a specifi c emphasis on the crucial role of hypoxic conditions and hepatic stellate cells,particularly when activated to the myofibroblast-like pro-fibrogenic.experimental anti-angiogenic therapy has been proven to be effective in limiting the progression of CLDs in animal models.From a clinical point of view,anti-angiogenic therapy is currently emerging as a new pharmacologic intervention in patients with advanced fibrosis and cirrhosis.

关键词： Chronic liver diseases Hepatic myofi broblasts Hypoxia Liver angiogenesis Liver fi brogenesis

Arsenic trioxide inhibits the activity of SphK1 by decreasing the level of phosphatidylserine and phosphatidic acid in the human gastric cancer cell line MGC-803

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

BIOCELL 2022年第3期46卷 737-743页

作者： PEI LIU ZHE CHEN XIAOQIONG MA Key laboratory of Digestive pathophysiology of Zhejiang Province Institute of Cancer ResearchFirst Affiliated HospitalZhejiang Chinese Medical UniversityHangzhou310006China

Sphingosine kinase 1(SphK1)is an important synthetase during the synthesis of sphingosine-1-phosphate(S1P)from sphingosine(Sph).Previous studies demonstrated that arsenic trioxide(As_(2)O_(3))could reduce the level of S1P in human gastric cancer cell line MGC-803,indicating that As_(2)O_(3) may inhibit the activity of SphK1.In this study,the effect of As_(2)O_(3) on the SphK1 activation pathway was investigated.Western blot and quantitative real-time PCR analysis were used to evaluate the changes in protein and mRNA levels.The multi-dimensional mass spectrometry-based shotgun lipidomics method(MDMS-SL)was used for the quantitative detection of phosphatidylserine(PS)and phosphatidic acid(PA).The results revealed that As_(2)O_(3) did not affect the protein and mRNA expression of SphK1 in the MGC-803 cells.However,As_(2)O_(3) increased the levels of p-ERK1/2 and CIB1 in the SphK1 activation pathway and decreased the levels of PS and PA in the MGC-803 cells.The outcomes suggested that As_(2)O_(3) may enhance the activity of SphK1 by increasing the levels of p-ERK1/2 and CIB1 and decrease the activity of SphK1 by decreasing the levels of PS and PA.It was suggested that the inhibition effect is stronger and resulting in an overall decrease in the activity of SphK1.

关键词： As_(2)O_(3) SphK1 PS PA

Intestinal epithelial chemokine (C-C motif) ligand 7 overexpression protects against high fat diet-induced obesity and hepatic steatosis in mice

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Medical Journal 2020年第15期133卷 1805-1814页

作者： Zhi-Hong Luo Meng-Wei Niu Shen-Hai Gong Guang-Yan Wu Teng Wang Fang-Zhao Wang Guo-Quan Wei Zhan-Ke He Yong Jiang Peng Chen Department of pathophysiology Guangdong Provincial Key Laboratory of ProteomicsSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515 China

Background:We previously found that the intestinal epithelial chemokine(C-C motif)ligand 7(CCL7)plays an important role in the development of toxin-induced acute liver damage.The detailed effects of intestinal epithelial CCL7 on chronic diseases;however,are still unclear.Here,we aimed to investigate the impact of intestinal epithelial CCL7 overexpression on high-fat diet(HFD)-induced obesity and steatohepatitis in mice.Methods:Intestinal epithelial CCL7 overexpression(CCL7tgIEC)mice and their wild-type(WT)littermates were fed with normal chow or HFD for 16 weeks to induce obesity and non-alcoholic fatty liver disease.Body weight gain,as well as adipose tissue index were assessed.Liver injury was monitored by histological analysis and real time polymerase chain reaction.Gut microbial composition was analyzed by 16S rRNA gene sequencing.Results:We found that the CCL7tgIEC mice on a HFD had markedly decreased weight gain(8.9 vs.17.0 g,P<0.05)and a lower adipose tissue index that include mesenteric fat(1.0%vs.1.76%,P<0.05),gonadal fat(2.1%vs.6.1%,P<0.05),subcutaneous fat(1.0%vs.2.8%,P<0.05)compared to WT animals.HFD-induced glucose intolerance and insulin resistance were also significantly improved in CCL7tgIEC mice compared to WT.Furthermore,HFD-fed CCL7tgIEC mice displayed less hepatic lipid accumulation and lower expression of inflammatory factors than WT mice.16S rRNA gene sequencing demonstrated that CCL7 overexpression in intestinal epithelial cells improved HFD-induced gut microbial dysbiosis.Conclusions:Our study revealed that CCL7 overexpression in the intestinal epithelium protects mice against the progression of diet-induced obesity,hepatic steatosis,and enteric dysbiosis.

关键词： Chemokine(C-C motif)ligand 7 Gut microbiota High-fat diet Obesity Steatohepatitis

Impaired glucocorticoid receptor expression and mitochondrial metabolism in MDSCs contribute to glucocorticoid resistance in immune thrombocytopenia

在线全文

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2022年第7期19卷 858-860页

作者： Rick Kapur Sanquin Research Department of Experimental ImmunohematologyAmsterdam and Landsteiner LaboratoryAmsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands

In this issue of Cellular&Molecular Immunology,Hou and coworkers provide novel insights into glucocorticoid(GC)treatment refractoriness in immune thrombocytopenia(ITP),reporting that myeloid-derived suppressor cells(MDSCs)contribute to GC resistance in ITP via impairments in their glucocorticoid receptor(GR)expression and mitochondrial metabolism[1].

关键词： metabolism glucocorticoid Immunology