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Gastroenteritis in an adult female revealing hemolytic uremic syndrome: case report

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World Journal of Gastroenterology 2018年第6期24卷 763-766页

作者： Paulina Chinchilla-López Vania Cruz-Ramón Oscar Ramírez-Pérez Nahum Méndez-Sánchez Liver research Unit Medica Sur Clinic and Foundation

Nowadays acute gastroenteritis infection caused by Escherichia coli(E. coli) O157:H7 is frequently associated with hemolytic uremic syndrome(HUS), which usually developed after prodromal diarrhea that is often bloody. The abdominal pain accompanied by failure kidney is a suspicious symptom to develop this disorder. Their pathological characteristic is vascular damage which manifested as arteriolar and capillary thrombosis with abnormalities in the endothelium and vessel walls. The major etiological agent of HUS is enterohemorragic(E coli) strain belonging to serotype O157:H7. The lack of papers about HUS associated to gastroenteritis lead us to report this case for explain the symptoms that are uncommon. Furthermore, this report provides some strategies to suspect and make an early diagnosis, besides treatment approach to improving outcomes and prognosis for patients with this disorder.

关键词： Gastroenteritis Gastrointestinal hemorrhage Hemolytic-uremic syndrome Escherichia coli O157 Shiga-toxigenic Escherichia coli

A small molecule UPR modulator for diabetes identified by high throughput screening

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3983-3993页

作者： Valeria Marrocco Tuan Tran Siying Zhu Seung Hyuk Choi Ana M.Gamo Sijia Li Qiangwei Fu Marta Diez Cunado Jason Roland Mitch Hull Van Nguyen-Tran Sean Joseph Arnab K.Chatterjee Nikki Rogers Matthew S.Tremblay Weijun Shen Calibr at scripps research The Scripps Research InstituteLa JollaCA 92037USA

Unfolded protein response(UPR) is a stress response that is specific to the endoplasmic reticulum(ER).UPR is activated upon accumulation of unfolded(or misfolded) proteins in the ER's lumen to restore protein folding capacity by increasing the synthesis of *** addition,UPR also enhances degradation of unfolded proteins and reduces global protein synthesis to alleviate additional accumulation of unfolded proteins in the ***,we describe a cell-based ultra-high throughput screening(uHTS) campaign that identifies a small molecule that can modulate UPR and ER stress in cellular and in vivo disease *** asialoglycoprotein receptor 1(ASGR) fused with Cypridina luciferase(CLuc) as reporter assay for folding capacity,we have screened a million small molecule library and identified APC655 as a potent activator of protein folding,that appears to act by promoting chaperone ***,APC655 improved pancreatic β cell viability and insulin secretion under ER stress conditions induced by thapsigargin or ***655 was also effective in preserving β cell function and decreasing lipid accumulation in the liver of the leptin-deficient(ob/ob) mouse *** results demonstrate a successful uHTS campaign that identified a modulator of UPR,which can provide a novel candidate for potential therapeutic development for a host of metabolic diseases.

关键词： βcells Unfolded protein response Small molecules Protein folding Endoplasmic reticulum Chaperones Cell signaling Diabetes ER stress Liver Pancreas Metabolic diseases

Hepatocellular Carcinoma:Downstaging to Liver Transplantation as Curative Therapy

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Journal of clinical and Translational Hepatology 2021年第2期9卷 220-226页

作者： Leana Frankul Catherine Frenette scripps Center for Organ Transplant Scripps Clinic/Green HospitalLa JollaCAUSA

Hepatocellular carcinoma(HCC)ranks among the leading cancer-related causes of morbidity and mortality *** of HCC has prevailed as a key method to curative therapy for patients who present with unresectable HCC outside of the listing criteria for liver transplantation(LT).Even though LT paves the way to lifesaving curative therapy for HCC,perpetually severe organ shortage limits its broader *** over the optimal protocol and assessment of response to downstaging treatment has fueled immense research activity and is pushing the boundaries of LT candidate selection *** implicit obligation of refining downstaging protocol is to ensure the maximization of the transplant survival benefit by taking into account the waitlist life *** the following review,we critically discuss strategies to best optimize downstaging HCC to LT on the basis of existing literature.

关键词： Downstaging Milan criteria Hepatocellular carcinoma Liver transplantation

Mitochondrial DNA from hepatocytes as a ligand for TLR9: Drivers of nonalcoholic steatohepatitis?

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World Journal of Gastroenterology 2016年第31期22卷 6965-6971页

作者： Priya Handa Akhila Vemulakonda Kris V Kowdley Misael Uribe Nahum Méndez-Sánchez Senior research Scientist Organ Care Research and Liver Care Network Swedish Medical Center Liver research Unit Medica Sur Clinic and Foundation

Nonalcoholic fatty liver disease(NAFLD) is the most common liver disease worldwide, affecting approximately one third of the Western world. It consists of a wide spectrum of liver disorders, ranging from fatty liver to nonalcoholic steatohepatitis(NASH), which consists of steatosis, ballooning injury and inflammation. Despite an alarming growth in the statistics surrounding NAFLD, there are as yet no effective therapies for its treatment. Innate immune signaling has been thought to play a significant role in initiating and augmenting hepatic inflammation, contributing to the transition from nonalcoholic fatty liver to NASH. An immune response is triggered by countless signals called damage-associated molecular patterns(DAMPs) elicited by lipid-laden and damaged hepatocytes, which are recognized by pattern recognition receptors(PRRs) on hepatic immune cells to initiate inflammatory signaling. In this editorial, in addition to summarizing innate immune signaling in NAFLD and discussing potential therapies that target innate immune pathways, we have described a recent study that demonstrated that mitochondrial DNA serves as a DAMP activating a hepatic PRR, TLR9, in mice and in the plasma of NASH patients. In addition to identifying a new ligand for TLR9 during NASH progression, the study shows that blocking TLR9 reverses NASH, paving the way for the development of future NASH therapy.

关键词： TLR9 Damage-associated molecular patterns Products of microbial metabolism produced by pathogens Mitochondrial DNA Hepatocytes Nonalcoholic steatohepatitis Nonalcoholic fatty liver disease Inflammation Innate immune signaling Kupffer cells Therapy

Non-surgical porto-mesenteric vein thrombosis is associated with worse long-term outcomes in inflammatory bowel diseases

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Gastroenterology Report 2016年第3期4卷 210-215,I0002页

作者： Zubin Arora Xianrui Wu Udayakumar Navaneethan Bo Shen Department of Internal Medicine The Cleveland Clinic FoundationClevelandOHUSA Department of Gastroenterology and Hepatology The Cleveland Clinic FoundationCleveland OHUSA

Objective:Our aim was to assess the risk factors for non-surgery-related portal and mesenteric vein thrombosis(PMVT)and its impact on the outcomes of inflammatory bowel diseases(IBD).Methods:All patients with a concurrent diagnosis of IBD and PMVT between January 2004 and October 2013 were identified from the electronic medical record(study group;n=20).Patients were matched for age,sex,and IBD phenotype with control IBD patients who had no PMVT,with a ratio of 1:3(control group;n=60).Risk factors for PMVT and IBD-related outcomes at one year after diagnosis of PMVT were compared between the two ***:Of the 20 patients in the Study group,6(30%)had UC,14(70%)had CD and 11(55%)were *** multivariable analysis,inpatient status(odds ratio[OR]6.88;95%confidence interval[CI]1.88-25.12)and baseline corticosteroid use(OR 4.39;95%CI 1.27-15.19)were found to be independent risk factors for the development of *** one-year follow-up,PMVT patients were more likely to have an adverse outcome of IBD,including subsequent emergency room visit(26.3%vs.1.7%;P=0.003),hospitalization for medical management(60.0%vs.20.0%;P=0.001)or IBD-related surgery(65.0%vs.26.7%;P=0.003)than the non-PMVT *** multivariable analysis,PMVT(OR 5.19;95%CI 1.07-25.28)and inpatient status(OR 8.92;95%CI 1.33-59.84)were found to be independent risk factors for poor outcome,whereas baseline immunomodulator use(OR 0.07;95%CI 0.01-0.51)was found to be a protective ***:IBD patients who were inpatients or receiving corticosteroid therapy had an increased risk of the development of *** presence of PMVT was associated with poor clinical outcomes in IBD.

关键词： inflammatory bowel diseases portal vein thrombosis outcomes risk factors

Human intestinal and biliary cryptosporidiosis

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World Journal of Gastroenterology 1999年第5期5卷 424-429页

作者： Chen XM LaRusso NF The Center for Basic research in Digestive Diseases Diversion of Gastroenterology and Hepatology Mayo Medical School Clinic and Foundation Rochester MN 55905 USA

Cryptosporidium parvum (C. parvum) is a coccidian parasite of the phylum Apicomplexa that infects the gastrointestinal, biliary and respiratory epithelium of humans and animals[1]. Early reports described a disease in humans characterized by protracted, watery diarrhea occurring in immunosuppressed patients, many with acquired immunodeficiency syndrome (AIDS). Recent epidemiologic studies indicate that cryptosporidiosis may also present as an acute, self-limited diarrheal disease in immunocompetent individuals and may account for 1%-10% of diarrheal disease worldwide[2,3]. Despite the magnitude and severity of cryptosporidial infection, the pathogenesis is poorly understood, and there is currently no effective therapy[3]. In this review, we provide a concise summary of what is known about cryptosporidial infection of the intestinal and biliary tract.

关键词： Cryptosporidium parivum cryptosporidiosis /epidemiology cryptosporidiosis/immunology cryptosporidiosis/diagnosis cryptosporidiosis /therapy

Mechanistic insights of rapid liver regeneration after associating liver partition and portal vein ligation for stage hepatectomy

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World Journal of Gastroenterology 2016年第33期22卷 7613-7624页

作者： Demetrios Moris Spyridon Vernadakis Alexandros Papalampros Michail Vailas Nikolaos Dimitrokallis Athanasios Petrou Dimitrios Dimitroulis Department of Immunology Lerner Research InstituteCleveland Clinic Foundation Laikon General hospital National and Kapodistrian University of Athens

AIM To highlight the potential mechanisms of regeneration in the Associating Liver Partition and Portal vein ligation for Stage hepatectomy models(clinical and experimental) that could unlock the myth behind the extraordinary capability of the liver for regeneration,which would help in designing new therapeutic options for the regenerative drive in difficult setup,such as chronic liver diseases. Associating Liver Partition and Portal vein ligation for Stage hepatectomy has been recently advocated to induce rapid future liver remnant hypertrophy that significantly shortens the time for the second stage hepatectomy. The introduction of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in the surgical armamentarium of therapeutic tools for liver surgeons represented a real breakthrough in the history of liver surgery. METHODS A comprehensive literature review of Associating Liver Partition and Portal vein ligation for Stage hepatectomy and its utility in liver regeneration is performed. RESULTS Liver regeneration after Associating Liver Partition and Portal vein ligation for Stage hepatectomy is a combination of portal flow changes and parenchymal transection that generate a systematic response inducing hepatocyte proliferation and remodeling. CONCLUSION Associating Liver Partition and Portal vein ligation for Stage hepatectomy represents a real breakthrough in the history of liver surgery because it offers rapid liver regeneration potential that facilitate resection of liver tumors that were previously though unresectable. The jury is still out though in terms of safety,efficacy and oncological outcomes. As far as Associating Liver Partition and Portal vein ligation for Stage hepatectomy-induced liver regeneration is concerned,further research on the field should focus on the role of nonparenchymal cells in liver regeneration as well as on the effect of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in liver regener

关键词： Liver regeneration Associating liver partition with portal vein ligation for staged hepatectomy Portal vein embolization Portal vein ligation Liver transection

Links between donor macrosteatosis,interleukin-33 and complement after liver transplantation

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World Journal of Transplantation 2020年第5期10卷 117-128页

作者： Kelley Núñez Mohammad Hamed Daniel Fort David Bruce Paul Thevenot Ari Cohen Institute of Translational research Ochsner Clinic FoundationNew OrleansLA 70121United States Center for Outcomes and Health Services research Research AdministrationOchsner Clinic FoundationNew OrleansLA 70121United States Multi-Organ Transplant Program Ochsner Clinic FoundationNew OrleansLA 70121United States

BACKGROUND As prevalence of nonalcoholic fatty liver disease increases in the population,livers with steatosis will continue to infiltrate the donor *** utilization of these extended criteria grafts is paramount given the increased risk associated with their use in *** factors that can predict liver dysfunction immediately after transplantation with macrosteatotic grafts are *** To understand the relationship between interleukin-33(IL-33)and complement in recipients immediately following liver reperfusion as a marker of liver *** Cohort consisted of patients who received a liver transplant from September 2016–September 2019 at our *** variables were retrospectively extracted from the electronic medical ***-table donor biopsies were obtained with donor steatosis percentage retrospectively determined by a boardcertified *** samples were available immediately following liver *** of plasma IL-33 and complement proteins,C3a and C5a,were determined by enzyme-linked immunosorbent *** mRNA expression,RNA was extracted from donor biopsies and used against a 780 gene *** Cohort consisted of 99 donor and *** median age was 45 years and 55%*** had a median age of 59 years with 62%*** main etiologies were alcoholic hepatitis,nonalcoholic steatohepatitis,and hepatocellular *** MELD-Na at transplant was *** were grouped based on moderate macrosteatosis(≥30%).Recipients implanted with moderate macrosteatotic grafts had significantly higher peak alanine aminotransferase/aspartate aminotransferase(P<0.001 and P<0.004),and increased incidence of early allograft dysfunction(60%compared to 18%).Circulating IL-33 levels were significantly elevated in recipients of≥30%macrosteatotic grafts(P<0.05).Recipients with detectable levels of circulating IL-33 immediately following reperfusion had significantly highe

关键词： Liver transplantation Interleukin-33 Donor macrosteatosis Complement Early allograft dysfunction Reperfusion

Sperm DNA damage and its clinical relevance in assessingreproductive outcome

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Asian Journal of Andrology 2004年第2期6卷 139-148页

作者： R. K. Sharma T. Said A. Agarwal Centerfor Advanced research in Human Reproduction Infertility and Sexual Function Glickman Urological Institute The Cleveland Clinic Foundation Cleveland Ohio 44195 USA

The routine examination of semen, which assesses sperm concentration, percentage motility and morphology, does not identify subtle defects in sperm chromatin architecture. The focus on the genomic integrity of the male gamete has intensified recently due to the growing concern that genetic diseases may be transmitted via assisted reproductive techniques (ART). Accordingly, the intent of this review is to describe the details of the information pertaining to mitochondrial/nuclear sperm DNA damage with an emphasis on its clinical significance and its relation ship with male infertility. Assessment of sperm DNA damage appears to be a potential tool for evaluating semen samples prior to their use in ART. Testing DNA integrity may help select spermatozoa with intact DNA or with the least amount of DNA damage for use in assisted conception. In turn, this may alleviate the financial, social and emotional problems associated with failed ART attempts.

关键词： DNA damage human male infertility sperm