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endotoxins enhance hepatocarcinogenesis induced by oral intake of thioacetamide in rats

World Journal of Gastroenterology 1998年第2期4卷 36-40页

AIM To clarify whether endotoxin is of pathogenic importance for hepatocarcinogenesis, or the increased cancer risk results solely from the cirrhotic process. METHODS The rat model of hepatoma was treated by the intake of 0 03% thioacetamide in drinking water for six months. During induction of hepatoma, rats were additionally treated with splenectomy and/or lipopolysaccharide administration. The liver nuclear DNA index and proliferation index were quantitatively analyzed by flow cytometry. Hepatic histology was examined with light and electron microscopes. Plasmic endotoxin concentration and γ glutamyl transpeptidase activity were measured, and hepatoma incidence was recorded. RESULTS Thioacetamide induced cirrhosis and hepatoma in Wistar rats with histology or regenerative nodule, fibrosis and neoplastic foci were quite similar to the pathogenic process of human cirrhosis leading to hepatoma. In comparison with TAA controls (DNA index: 1 15±0 21), exo endotoxin increased the DNA index by 7 8% (1 24±0 25, P <0 02) and hepatoma rate by 16 7. Splenectomy induced enteric endotoxemia increased the DNA index by 25% (1 44±0 15, P <0 01) and hepatoma rate by 33%. A summation of the effects of these two factors increased the DNA index by 36% ( P <0 01)and hepatoma incidence by 50%, moreover, the level of endotoxemia showed a close relation with DNA index ( r =0 96, P <0 01), as well as with the occurrence rate of hepatoma ( r =0 00, P <0 01). Histological findings further verified such alterations. CONCLUSION Lipopolysaccharide administration and/or splenectomy induced enterogenic endotoxemia may enhance rat hepatocarcinogenesis induced by oral intake of thioacetamide.

关键词： liver neoplasms carcinoma, hepatocellular endotoxins thioacetamide glutamyl transpeptidase/metabolism flow cytometry DNA, neoplasm rats, Wistar

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The Antagonistic Action of Heat-Clearing and Detoxifying Chinese Drugs on endotoxins

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Journal of Traditional Chinese Medicine 2001年第1期21卷 72-77页

作者：张霞崔乃杰王家泰毛树章 Tianjin Medical University Tianjin 300070

In the recent decade, interest in treatment and prevention of many critical, severe and acute diseases caused by bacterial endotoxins has been aroused along with the advance of the knowledge on the nature of the endotoxin and the conditions involved. In abroad, attention has been mainly payed to raising antisera and monocolonal antibodies against the endotoxin and the induced mediators. However, the allergic reactions and the cost are still the problems. Till now, there is no drug that can antagonize endotoxin with high effectiveness and low toxicity. Clinical treatments are still confined in inhibiting or killing the pathogen, and correcting the internal environmental disturbance. Being less toxic and rich in resources with low cost and less side-effects, screening of effective Chinese drugs for antagonizing endotoxin is of important and practical significance. Endotoxin belongs to the category of toxic evils, or more precisely, the heat toxin in TCM. Therefore the application of heat-clearing and detoxifying Chinese drugs to antagonizing endotoxins is consistent with the theory of TCM. Some achievements in this field are reported as follows.

关键词： Drug Therapy, Combination Drugs, Chinese Herbal Endotoxemia endotoxins Humans Materia Medica

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endotoxins in the prostatic secretions of chronic prostatitis patients:a need for further biomarkers through the use of proteomics

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Asian Journal of Andrology 2006年第1期8卷 123-124页

作者： Sashi S.Kommu Stewart Reiss The Royal Marsden NHS Foundation Trust Fulham RoadLondon SW3 6JJUK Brighton and Sussex Medical School University of SussexBrighton BN1 9PXUK

Dear Sir,Dai et al.[1] must be commended on their useful investigation of the clinical significance of endotoxins in the expressed prostatic secretions （EPS） of chronic prostatitis （CP） patients. However, we take issue with their conclusion. The conclusion that EPS endotoxin determination is helpful in diagnostic confirmation is plausible,

关键词： Proteomics Bacterial Infections Biological Markers Chronic Disease endotoxins Humans Male Prostate Prostatitis

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Distribution of endotoxins in tissues and circulation and its effects following hemorrhagic shock

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Chinese Medical Journal 1998年第2期000卷 22-26页

作者：蒋建新陈惠孙刁有芳田昆仑朱佩芳王正国 Research Institute of Surgery The Third Military Medical College Chongqing 400042 China

Objective To systemically investigate 1) distribution of endogenous endotoxin (ET) in tissues and circulation; 2) its relationship with shock duration and organ damage; and 3) its possible mechanism after hemorrhagic shock. Methods To further elucidate the intrinsic relationship between endogenous endotoxin translocation and hemorrhagic shock, the present study systematically investigated the distribution of endogenous ET into the liver, lungs, kidneys and circulation, and the relationship between ET levels and the corresponding organ dysfunction with limulus amebocyte lysate (LAL) chromogenic assay following hemorrhagic shock in rats. Results It was found that ET levels in hepatic homogenate markedly increased (P=0.09) 1.5 hours following shock compared with that in the sham group. After resuscitation, ET levels in hepatic, pulmonary and renal tissues were all significantly elevated. The levels kept increasing with the prolonged experimental time, and reached as high as 3.88±0.95 EU (endotoxin unit)/g in the livers, 2.53±1.46 EU/g in the lungs and 2.51±0.89 EU/g in the kidneys 12 hours after shock. ET levels in plasma reached a peak of 1.13 ±0.42 EU/ml at 1 hour following resuscitation, then rapidly decreased to the sham levels 3 hours following resuscitation. There was a close relationship between endotoxin translocation and shock duration. Correlation analysis further indicated that the changes in glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN) in plasma and angiotensin Ⅰ converting exzyme (ACE) in pulmonary homogenate were significantly and positively correlated with the ET levels in the liver, kidneys and lungs after hemorrhagic shock. Conclusions Hemorrhagic shock can induce obvious endogenous ET translocation, which is closely related to the shock duration. Although only transient endotoxemia occurs after hemorrhagic shock, ET can massively accumulate in tissues (liver, lungs and kidneys), and may play an impo

关键词：蒋建 tissues following hemorrhagic circulation endotoxins effects its Distribution and

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Effect of hepatocyte apoptosis induced by TNF-α on acute severe hepatitis in mouse models

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World Journal of Gastroenterology 2000年第5期6卷 688-692页

作者： Guo Qing Zang Xia Qiu Zhou Hong Yu Qing Xie Guo Ming Zhao Bin Wang Qing Guo Yue Qin Xiang Dan Liao Department of Infectious Diseases,Rujin Hospital,Shanghai Second Medical University,Shanghai 200025,China Guo Qing Zang Xia Qiu Zhou Hong Yu Qing Xie Guo Ming Zhao Bin Wang Qing Guo Yue Qin Xiang Dan Liao Department of Infectious Diseases Rujin Hospital Shanghai Second Medical University Shanghai 200025 China Guo Qing Zang graduated from Xian Medical University as a postgraduate in 1990 associate professor of lemology engaged in diagnosis and treatment of viral hepatitis and hemorrahgic fever with renal syndrome having 12 papers published.

AIM To study the effect of hepatocyteapoptosis and necrosis induced by TNF-α on thepathogenesis of acute severe hepatitis(ASH).METHODS The model of ASH was prepared inD-galactosamine(GAIN)sensitized BALB/c miceby injection of either endotoxin(ET)or tumornecrosis factor-α(TNF-α).Morphologicalchanges of apoptotic hepatocytes were studiedby both light and electron microscope and in siteend labeling method(ISEL).Molecular biologicalchanges of DNA ladder were observed byelectrophoresis of extract from liver *** changes were measured by alanineaminotransferase(ALT),asparticaminotransferase(AST)and TNF-α.The relationbetween apoptosis and necrosis was *** The sequence of hepatocyteapoptosis,necrosis,and final death from ASHwas observed both in GAIN/ET and GAIN/*** was prominent at 3.5 h and 5 hafter injection of inducer,while necrosis becamedominant at 9 h after *** appearanceof apoptosis was earlier in GAIN/TNF-α groupthan that in GAIN/ ET *** ofmice with antiTNF IgG1 may completely preventthe liver injury induced by GalN/*** TNF-α can cause liver damageby inducing hepatic apoptosis and necrosis inmice with endotoxemia.

关键词： tumor necrosis factor hepatitis apoptosis alanine transaminase aspartate transaminase endotoxins mice

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Diet high in fructose leads to an overexpression of lipocalin-2 in rat fatty liver

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World Journal of Gastroenterology 2014年第7期20卷 1807-1821页

作者： Salamah Mohammad Alwahsh Min Xu Hatice Ali Seyhan Shakil Ahmad Sabine Mihm Giuliano Ramadori Frank Christian Schultze Department of Gastroenterology and Endocrinology University Medical Center Goettingen37075 GoettingenGermany Department of General Visceral and Pediatric SurgeryUniversity Medical Center Goettingen37075 GoettingenGermany

AIM: To explore lipocalin-2 (LCN-2) expression and its possible role and mechanism(s) of production in rat models of diet-inducible fatty liver.

关键词： Non-alcoholic fatty liver disease Inflammation endotoxins Lipopolysaccharide Oxidative stress Mitochondrial dysfunction Metabolic syndrome

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Potential roles of functional bacterial amyloid proteins,bacterial biosurfactants and other putative gut microbiota products in the etiopathogeny of Parkinson’s Disease

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BIOCELL 2021年第1期45卷 1-16页

作者： EMILIA MANOLE LAURA DUMITRESCU CRISTINA NICULIȚE BOGDAN OVIDIU POPESCU LAURA CRISTINA CEAFALAN Victor Babeș”National Institute of Pathology Bucharest050088Romania Colentina Clinical Hospital Bucharest020125Romania Carol Davila”University of Medicine and Pharmacy Bucharest020021Romania

An increasing number of studies provide evidence for the existence of a microbiota-gut-brain axis and its potential involvement in the development of sporadic Parkinson’s disease and other neurodegenerative *** neuropathologic hallmark of Parkinson’s disease is the presence of brain intraneuronal aggregates of misfolded alpha-synuclein,known as Lewy *** gut microbiota products may trigger alpha-synuclein conformational changes in the neurons of the enteric nervous system,which can then spread to the brain in a prion-like fashion through the vagus *** may interfere with neuroinflammatory pathways and susceptibility to *** this review,we assess the potential role of putative gut microbiota products in the etiopathogeny of Parkinson’s disease,with a special emphasis on functional bacterial amyloid proteins,bacterial biosurfactants,endotoxins and short-chain fatty *** possible roles of molecular hydrogen,a common byproduct of bacterial fermentation,are also addressed.

关键词： Alpha-synuclein endotoxins Short-chain fatty acids

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Possible relationship between intestinal barrier function and formation of pigment gallstones in hamsters

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Hepatobiliary & Pancreatic Diseases International 2008年第5期7卷 529-532页

作者： Fan, Ying Wu, Shuo-Dong Sun, Lei Fu, Bei-Bei Su, Yang China Med Univ Shengjing Hosp Dept Gen Surg Shenyang 110004 Peoples R China

BACKGROUND: The presence of bacteria in bile is an important factor in the formation of pigment gallstones. The bile of healthy people is sterile and bacteria in the biliary system come from endogenous infection from the gut. Yet, the route of bacterial translocation into the bile duct is still unclear. Theoretically, two routes exist: one is through the intestinal barrier and the other is by direct reflux from the sphincter of Oddi. This study was undertaken to explore the relationship between the effectiveness of intestinal barrier and the formation of pigment gallstones in hamsters. METHODS: Thirty-two hamsters were divided into an experimental and a control group, with 16 hamsters in each group. A low protein and high cellulose diet was given for 6 weeks to induce the formation of pigment gallstones in the experimental group (PS) and a normal diet was given to the control group (CON). Morphological changes, changes in the levels of serum endotoxin and diamine oxidase, and changes in the numbers of B lymphocytes, plasma cells and secretory immunoglobin A (sIgA) in the intestinal mucosa were assessed after 6 weeks. RESULTS: Four hamsters died during lithogenesis and body weight decreased in the PS group. Pigment gallstones were found in 11 hamsters at the end of the experiment, giving a lithogenesis rate of 91.67%. The serum endotoxin level before and after gallstone formation in the PS group was 0.2960 +/- 0.1734 U/ml and 8.2964 +/- 4.6268 U/ml, respectively (P<0.05). The blood diamine oxidase level before and after gallstone formation in the PS group was 2.6333 +/- 0.8037 U/ml and 3.3642 +/- 0.9545 U/ml, respectively (P<0.05). The numbers of B lymphocytes, plasma cells and sIgA in the intestinal mucosa in the PS group were 71.56 +/- 2.89, 68.65 +/- 2.09 and 27.56 +/- 1.07, respectively, and were significantly decreased compared with the corresponding values in the CON group (94.25 +/- 3.69, 93.47 +/- 3.98 and 42.57 +/- 1.96, respectively, P<0.05). CONCLUSIONS: A

关键词： endotoxins diamine oxidase B lymphocytes plasma cells secretory immunoglobin A

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Fatty Liver Disease and Gut Microbiota:A Comprehensive Update

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Journal of Clinical and Translational Hepatology 2019年第1期7卷 56-60页

作者： Lyna Campo Sara Eiseler Tehilla Apfel Nikolaos Pyrsopoulos Division of Gastroenterology and Hepatology University HospitalRutgers New Jersey Medical SchoolNewarkNJUSA

Nonalcoholic fatty liver disease(NAFLD)is the accumulation of fat in the liver in the absence of secondary *** is a multifactorial disease that results from the interaction of genetic predisposition and metabolic,inflammatory and environmental *** these factors,dysregulation of gut microbiome has been linked to the development of fatty liver *** microbiome composition can be modified by dietary habits leading to gut microbiome dysbiosis,especially when a diet is rich in saturated fats,animal products and fructose *** species of bacteria in the gut metabolize nutrients differently,triggering different pathways that contribute to the accumulation of fat within the liver and triggering inflammatory cascades that promote liver *** this review,we summarize the current understanding of the roles of gut microbiota in mediating NAFLD development and discuss possible gut microbiota-targeted therapies for *** summarize experimental and clinical evidence,and draw conclusions on the therapeutic potential of manipulating gut microbiota to decrease the incidence and prevalence of fatty liver disease.

关键词： Nonalcoholic fatty liver disease Gut microbiome Dysbiosis endotoxins Choline metabolism

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ISOLATION OF ENDOTOXIN-SPECIFIC ANTIBODIES BY SELECTION OF AN SINGLE CHAIN PHAGE ANTIBODY LIBRARY

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Chinese Journal of Cancer Research 2002年第2期14卷 118-121页

作者：陈鸣俞丽丽张雪府伟灵 Department of Laboratory Diagnosis South-western Hospital the Third Military Medical University Chongqing China

Objective: To isolate murine anti endotoxin single chain phage antibody from a constructed library. Methods: Total RNA was firstly extracted from murine splenic cells and mRNA was reverse-transcribed into cDNA. Then the designed primers were used to amplify the variable region genes of the heavy and light chain (VH, VL) with polymerase chain reaction. The linker was used to assemble the VH and VL into ScFv, and the NotI and SfiI restriction enzymes were used to digest the ScFv in order to ligate into the pCANTAB5E phagemid vector that was already digested with the same restriction enzymes. The ligated vector was then introduced into competent *** TG1 cells to construct a single-chain phage antibody library. After rescued with M13KO7 helper phage, recombinant phages displaying ScFv fragments were harvested from the supernatant and selected with endotoxin. The enriched positive clones were reinfected into TG1 cells. Finally, 190 clones were randomly selected to detect the anti endotoxin antibody with indirect ELISA. Results: The titer of anti endotoxin in murine sera was 1:12,800. The concentration of total RNA was 12.38 μg/ml. 1.9×107 clones were obtained after transformed into TG1. 3×104 colonies were gotten after one round panning. Two positive colonies were confirmed with indirect ELISA among 190 randomly selected colonies. Conclusion: A 1.9×107 murine anti endotoxin single chain phage antibody library was successfully constructed. Two anti endotoxin antibodies were obtained from the library.

关键词： endotoxins Phage antibody library E.coli

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