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Azathioprine does not reduce adenoma formation in a mouse model of sporadic intestinal tumorigenesis

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World Journal of Gastroenterology 2014年第44期20卷 16683-16689页

作者： Mattheus CB Wielenga Jooske F van Lidth de Jeude Sanne L Rosekrans Alon D Levin Monique Schukking Geert RAM D'Haens Jarom Heijmans Marnix Jansen Vanesa Muncan Gijs R van den Brink Tytgat Institute for Liver and intestinal Research and Department of Gastroenterology and Hepatology Academic Medical Center Department of Pathology Academic Medical Center

AIM: To investigate if azathioprine could reduce adenoma formation in ApcMin/+, a mouse model of sporadic intestinal tumorigenesis.

关键词： Azathioprine Thiopurine intestinal adenoma Polyp ApcMin Chemoprevention Lymphoma Colon cancer

Enteromorpha prolifera polysaccharide-Fe(Ⅲ) complex promotes intestinal development as a new iron supplement

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Science China Life Sciences 2025年第1期 219-231页

作者： Yingying Feng Yuying Wu Jialu Wang Zhenglin Dong Qian Yu Shuangshuang Xia Chunxue Liu Haihua Wang Xin Wu Tianjin Institute of Industrial biotechnology Chinese Academy of Sciences CAS Key Laboratory of Agro-ecological Processes in Subtropical Region Institute of Subtropical AgricultureChinese Academy of Sciences ANYOU biotechnology Group Co.Ltd Qingdao Seawin biotech Group Co. LTD

Iron is a crucial micronutrient, and its deficiency can have detrimental effects on the health of infants. Dietary polysaccharide-iron(Ⅲ) complexes(PICs) are promising for addressing iron deficiency due to their minimal adverse reactions and high iron absorption rate. This study aimed to investigate the effects of dietary Enteromorpha prolifera polysaccharide-Fe(Ⅲ) complex(EP-Fe) on newborns, using 3-day weaned piglets as the iron-deficiency model. Results showed that EP-Fe improved iron levels and promoted intestinal development in piglets. Transcriptome sequencing revealed that EP-Fe increased the survival of intestinal epithelial cells under hypoxia by upregulating the expression of genes that promote the development of the vascular system. Additionally, EP-Fe enhanced the mucosal barrier functions by inhibiting myosin light chain kinase(MLCK)/phosphorylated myosin light chain(p-MLC) signaling pathway to increase the expression of intestinal tight junction proteins. Furthermore, the 16S r RNA gene sequencing of gut microbiota showed that EP-Fe promoted the enrichment of Bacteroides＿fragilis and other gut microbes that can metabolize carbohydrates. In conclusion, EP-Fe is an effective iron supplement for newborns, and it can be developed as a comprehensive nutritional supplement.

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Current stage in inflammatory bowel disease: What is next?

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World Journal of Gastroenterology 2015年第40期21卷 11282-11303页

作者： Gonzalo Jesús Gómez-Gómez ángeles Masedo Carmen Yela Maria del Pilar Martínez-Montiel Begona Casís Unidad de Enfermedad Inflamatoria intestinal Hospital 12 de Octubre

In recent years,the incidence of inflammatory bowel disease(IBD) has been on the rise,extending to countries where it was infrequent in the past. As a result,the gap between high and low incidence countries is decreasing. The disease,therefore,has an important economic impact on the healthcare system. Advances in recent years in pharmacogenetics and clinical pharmacology have allowed for the development of treatment strategies adjusted to the patient profile. Concurrently,new drugs aimed at inflammatory targets have been developed that may expand future treatment options. This review examines advances in the optimization of existing drug treatments and the development of novel treatment options for IBD.

关键词： Inflammatory bowel disease Future directions Pharmacogenetic Pharmacokinetics New drugs

Laparoscopic liver resection:Wedge resections to living donor hepatectomy, are we heading in the right direction?

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World Journal of Gastroenterology 2014年第37期20卷 13369-13381页

作者： P Thomas Cherian Ashish Kumar Mishra Palaniappen Kumar Vijayant Kumar Sachan Anand Bharathan Gadiyaram Srikanth Baiju Senadhipan Mohamad S Rela Department of HPB Surgery and Liver Transplantation Global Hospital Department of Gastro-intestinal Surgery BGS-Global Hospital Department of Gastro-intestinal Surgery SUT-Royal Hospital

Despite inception over 15 years ago and over 3000 completed procedures, laparoscopic liver resection has remained mainly in the domain of selected centers and enthusiasts. Requirement of extensive open liver resection(OLR) experience, in-depth understanding of anatomy and considerable laparoscopic technical expertise may have delayed wide application. However healthy scepticism of its actual benefits and presence of a potential publication bias; concern about its safety and technical learning curve, are probably equally responsible. Given that a large proportion of our work, at least in transplantation is still OLR, we have attempted to provide an entirely unbiased, mature opinion of its pros and cons in the current invited review. We have dividedthis review into two sections as we believe they merit separate attention on technical and ethical grounds. The first part deals with laparoscopic liver resection(LLR) in patients who present with benign or malignant liver pathology, wherein we have discussed its overall outcomes; its feasibility based on type of pathology and type of resection and included a small section on application of LLR in special scenarios like cirrhosis. The second part deals with the laparoscopic living donor hepatectomy(LDH) experience to date, including its potential impact on transplantation in general. Donor safety, graft outcomes after LDH and criterion to select ideal donors for LLR are discussed. Within each section we have provided practical points to improve safety in LLR and attempted to reach reasonable recommendations on the utilization of LLR for units that wish to develop such a service.

关键词： Liver Laparoscopic Transplantation Resection Living donor Minimally invasive Technique Hepatocellular Hepatectomy Cirrhosis

Plasma matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 as biomarkers of ulcerative colitis activity

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World Journal of Gastroenterology 2003年第12期9卷 2843-2845页

作者： Alicja Wiercinska-Drapalo Jerzy Jaroszewicz Robert Flisiak Danuta Prokopowicz Department of Infectious Diseases Intestinal Diseases UnitMedical University of BialystokPoland

AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel *** activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of this study was to evaluate the effect of ulcerative colitis(UC)on MMP- 1 and TIMP-1 plasma concentrations,as two possible biomarkers of the disease activity. METHODS:MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 16 patients with endoscopically confirmed active UC. RESULTS:Plasma concentrations of both MMP-1(13.7±0.2 ng/ml)and TIMP-1(799±140 ng/ml)were significantly elevated in UC patients in comparison to healthy controls (11.9±0.9 ng/ml and 220±7 ng/ml respectively).There was no correlation between TIMP-1 and MMP-1 concentrations (r=0.02).TIMP-1 levels revealed significant positive correlations with scored endoscopic degree of mucosal injury, disease activity index and clinical activity index values as well as C-reactive protein *** was no correlation between MMP-1 and laboratory,clinical or endoscopic indices of the disease ***: These results confirm the role of both MMP- 1 and TIMP-1 in the pathogenesis of ulcerative colitis. However only TIMP-1 can be useful as a biomarker of the disease activity, demonstrating association with clinical and endoscopic pictures.

关键词： Adult Aged Biological Markers C-Reactive Protein Colitis, Ulcerative Comparative Study Female Humans Interstitial Collagenase Male Middle Aged Reference Values Tissue Inhibitor of Metalloproteinase-1

Management of intestinal failure in inflammatory bowel disease:Small intestinal transplantation or home parenteral nutrition?

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World Journal of Gastroenterology 2014年第12期20卷 3153-3163页

作者： Elizabeth Harrison Philip Allan Amrutha Ramu Anil Vaidya Simon Travis Simon Lal intestinal Failure Unit Salford Royal NHS Foundation Trust Translational Gastroenterology Unit Oxford University Hospitals NHS Trust Transplant Centre Oxford University Hospitals NHS Trust

Inflammatory bowel disease and Crohn’s disease in particular, is a common cause of intestinal failure. Current therapeutic options include home parenteral nutrition and intestinal transplantation. For most patients, home intravenous therapy including parenteral nutrition, with a good probability of long-term survival, is the favoured choice. However, in selected patients, with specific features that may shorten survival or complicate home parenteral nutrition, intestinal transplantation presents a viable alternative. We present survival, complications, quality of life and economic considerations that currently influence individualised decision-making between home parenteral nutrition and intestinal transplantation.

关键词： Inflammatory bowel disease, Crohn’ s disease, intestinal failure, intestinal transplantation, Home parenteral nutrition, Survival, Complications, Quality of life

Mycophenolate mofetil toxicity mimicking acute cellular rejection in a small intestinal transplant

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World Journal of Transplantation 2017年第1期7卷 98-102页

作者： Ross Apostolov Khashayar Asadi Julie Lokan Ning Kam Adam Testro Australian intestinal Transplant Service Austin Health

Mycophenolate mofetil(MMF) is an important medication used for maintenance immunosuppression in solid organ transplants. A common gastrointestinal(GI) side effect of MMF is enterocolitis, which has been associated with multiple histological features. There is little data in the literature describing the histological effects of MMF in small intestinal transplant(SIT) recipients. We present a case of MMF toxicity in a SIT recipient, with histological changes in the donor ileum mimicking persistent acute cellular rejection(ACR). Concurrent biopsies of the patient's native colon showed similar changes to those from the donor small bowel, suggesting a non-graft specific process, raising suspicion for MMF toxicity. The MMF was discontinued and complete resolution of these changes occurred over three weeks. MMF toxicity should therefore be considered as a differential diagnosis for ACR and graftversus-host disease in SITs.

关键词： Small intestinal transplantation Drug toxicity Mycophenolate mofetil Acute cellular rejection Immunosuppression

Role of the gut microbiota in inflammatory bowel disease pathogenesis: What have we learnt in the past 10 years?

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World Journal of Gastroenterology 2014年第5期20卷 1192-1210页

作者： Georgina L Hold Megan Smith Charlie Grange Euan Robert Watt Emad M El-Omar Indrani Mukhopadhya Gastro-intestinal Research Group Division of Applied Medicine University of Aberdeen Foresterhill

Our understanding of the microbial involvement in inflammatory bowel disease (IBD) pathogenesis has increased exponentially over the past decade. The development of newer molecular tools for the global assessment of the gut microbiome and the identification of nucleotide-binding oligomerization domain-containing protein 2 in 2001 and other susceptibility genes for Crohn’s disease in particular has led to better understanding of the aetiopathogenesis of IBD. The microbial studies have elaborated the normal composition of the gut microbiome and its perturbations in the setting of IBD. This altered microbiome or “dysbiosis” is a key player in the protracted course of inflammation in IBD. Numerous genome-wide association studies have identified further genes involved in gastrointestinal innate immunity (including polymorphisms in genes involved in autophagy: ATG16L1 and IGRM), which have helped elucidate the relationship of the local innate immunity with the adjacent luminal bacteria. These developments have also spurred the search for specific pathogens which may have a role in the metamorphosis of the gut microbiome from a symbiotic entity to a putative pathogenic one. Here we review advances in our understanding of microbial involvement in IBD pathogenesis over the past 10 years and offer insight into how this will shape our therapeutic management of the disease in the coming years.

关键词： Inflammatory bowel disease, Crohn’ s disease, Ulcerative colitis, Gut microbiota, Innate immune response, Probiotics, Prebiotics, Faecal transplant

Changes in the colon microbiota and intestinal cytokine gene expression following minimal intestinal surgery

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World Journal of Gastroenterology 2015年第14期21卷 4150-4158页

作者： Susan Lapthorne Julie E Bines Fiona Fouhy Nicole L Dellios Guineva Wilson Sarah L Thomas Michelle Scurr Catherine Stanton Paul D Cotter Prue M Pereira-Fantini intestinal Failure and Clinical Nutrition group Murdoch Childrens Research InstituteRoyal Children’s Hospital intestinal Failure and Clinical Nutrition group Murdoch Childrens Research Institute Department of Paediatrics the University of Melbourne Department of Gastroenterology and Clinical Nutrition Royal Children’s Hospital Teagasc Food Research Centre MooreparkFermoyCorkIreland Department of Microbiology University College Cork Department of Surgery Monash Medical Centre Alimentary Pharmabiotic Centre University College Cork

AIM: To investigate the impact of minor abdominal surgery on the caecal microbial population and on markers of gut ***: Four week old piglets were randomly allocated to a no-surgery "control" group(n = 6) or a "transection surgery" group(n = 5).During the transection surgery procedure, a conventional midline incision of the lower abdominal wall was made and the small intestine was transected at a site 225 cm proximal to the ileocaecal valve, a 2 cm segment was removed and the intestine was *** received a polymeric infant formula diet throughout the study period and were sacrificed at two weeks *** outcomes including weight, stool consistency and presence of stool fat globules were *** throughput DNA sequencing of colonic content was used to detect surgery-relateddisturbances in microbial composition at phylum, family and genus *** and richness estimates were calculated for the control and minor surgery *** disturbances in the gut microbial community are linked to inflammation we compared the gene expression of key inflammatory cytokines(TNF, IL1 B, IL18, IL12, IL8, IL6 and IL10) in ileum, terminal ileum and colon mucosal extracts obtained from control and abdominal surgery groups at two weeks ***: Changes in the relative abundance of bacterial species at family and genus level were confined to bacterial members of the Proteobacteria and Bacteroidetes *** level compositional shifts included a reduction in the relative abundance of Enterobacteriaceae(22.95 ± 5.27 vs 2.07 ± 0.72, P < 0.01), Bacteroidaceae(2.54 ± 0.56 vs 0.86 ± 0.43, P < 0.05) and Rhodospirillaceae(0.40 ± 0.14 vs 0.00 ± 0.00, P < 0.05) following transection ***, at the genus level, changes associated with transection surgery were restricted to members of the Proteobacteria and Bacteroidetes phyla and included decreased relative abundance of Enterobacteriaceae(29.20 ± 6.74 vs 2.88 ±

关键词： Surgery intestinal Microbiota Dysbiosis Inflammati