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LPA_(1) antagonist-derived LNPs deliver A20 mRNA and promote anti-fibrotic activities

Nano Research 2024年第10期17卷 9095-9102页

作者： Jingyue Yan Diana D.Kang Chang Wang Xucheng Hou Shi Du Siyu Wang Yonger Xue Zhengwei Liu Haoyuan Li Yichen Zhong Binbin Deng David W.McComb Yizhou Dong division of Pharmaceutics&Pharmacology College of PharmacyThe Ohio State UniversityColumbusOH 43210USA Icahn Genomics Institute Precision Immunology InstituteDepartment of Immunology and ImmunotherapyDepartment of Oncological SciencesTisch Cancer InstituteBiomedical Engineering and Imaging InstituteFriedman Brain InstituteIcahn School of Medicine at Mount SinaiNew YorkNY 10029USA center for Electron Microscopy and Analysis The Ohio State UniversityColumbusOH 43212USA Department of Materials Science and Engineering The Ohio State UniversityColumbusOH 43210USA

Activated fibroblasts are major mediators of pulmonary *** are generally found in the connective tissue but upon activation can generate excess extracellular matrix(ECM)in the lung interstitial ***,fibroblasts are one of the most targeted cells for treating idiopathic pulmonary fibrosis(IPF).Here,we develop an anti-fibrotic platform that can modulate both the lysophosphatidic acid receptor 1(LPA_(1))and the inflammatory pathway through tumor necrosis factorα-induced protein 3(TNFAIP3,also known as A20)in ***,we synthesized a series of LPA_(1) antagonists,AM095 and AM966,derived amino lipids(LA lipids)which were formulated into LA-lipid nanoparticles(LA-LNPs)encapsulating ***,LA5-LNPs,with AM966 head group and biodegradable acetal lipid tails,showed efficient A20 mRNA delivery to lung fibroblasts in vitro(80.2%±1.5%)and ex vivo(17.2%±0.4%).When treated to primary mouse lung fibroblasts(MLF),this formulation inhibited fibroblast migration and collagen production,thereby slowing the progression of ***,LA5-LNPs encapsulated with A20 mRNA is a novel platform offering a potential approach to regulate fibroblast activation for the treatment of IPF.

关键词： lysophosphatidic acid receptor 1(LPA_(1))antagonist tumor necrosis factorα-induced protein 3(A20) lung fibrosis lipid nanoparticles mRNA

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Targeting uridine diphosphate glucuronosyltransferase 1A1 in liver disease:Current research and future directions

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World Journal of Gastroenterology 2024年第39期30卷 4305-4307页

作者： Seok-Chan Park Yu Ji Kim Jong-Won Kim Department of Microbiology Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States division of Endocrinology and Metabolism Department of Internal MedicineMedical SchoolJeonbuk National UniversityResearch Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University HospitalJeonju 54907South Korea center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15216United States

The current letter to the editor pertains to the manuscript entitled'Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury'.Increased levels of uridine diphosphate glucuronosyltransferase 1A1 during liver injury could mitigate damage by reducing endoplasmic reticulum stress,oxidative stress,and dysregulated lipid metabolism,impeding hepatocyte apoptosis and necroptosis.

关键词： Uridine diphosphate glucuronosyltransferase 1A1 Liver injury Endoplasmic reticulum stress Oxidative stress Lipid metabolism disorders

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晚发性结直肠癌患者亲属的结肠镜筛查时间间隔:一项全国性匹配队列研究

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Science Bulletin 2024年第6期69卷 732-736页

作者：梁群风 Kristina Sundquist Jan Sundquist Hermann Brenner Elham Kharazmi Mahdi Fallah division of Preventive Oncology National Center for Tumor DiseasesGerman Cancer Research CenterHeidelberg 69120Germany medical Faculty Heidelberg Heidelberg UniversityHeidelberg 69120Germany center for Primary Health Care Research Lund UniversityMalmö20213Sweden Department of Family Medicine and Community Health Department of Population Health Science and PolicyIcahn School of Medicine at Mount SinaiNew YorkNY10029USA center for Community-based Healthcare Research and Education Department of Functional PathologySchool of MedicineShimane UniversityIzumo 693-8501Japan division of Clinical Epidemiology and Aging Research German Cancer Research CenterHeidelberg 69120Germany German Cancer Consortium German Cancer Research CenterHeidelberg 69120Germany Institute of Primary Health Care University of BernBern 3012Switzerland

Colorectal cancer(CRC)is a major global cancer burden,ranking third in terms of incidence,but second in terms of mortality[1].Early detection of CRC through screening combined with subsequent removal of polyps remains a predominant strategy for CRC *** history is a known risk factor for CRC[2-4].However,only a few screening guidelines provide recommendations for individuals with familial CRC risk[5].

关键词：队列研究时间间隔晚发性

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Re-re-treatment of hepatitis C virus: Eight patients who relapsed twice after direct-acting-antiviral drugs

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World Journal of Gastroenterology 2015年第43期21卷 12430-12438页

作者： Joshua Hartman Kian Bichoupan Neal Patel Sweta Chekuri Alyson Harty Douglas Dieterich Ponni Perumalswami Andrea D Branch Department of Medicine Icahn School of Medicine at the Mount Sinai Medical Center division of Liver Disease Icahn School of Medicine at the Mount Sinai Medical Center

AIM: To determine risk factors associated with hepatitis C virus(HCV) treatment failure after direct acting antivirals in patients with complex treatment ***: All HCV mono-infected patients who received treatment at our institution were *** was restricted to patients who previously failed treatment with boceprevir(BOC) or telaprevir(TVR) and started simeprevir(SMV) and sofosbuvir(SOF) ± ribavirin(RBV) between December 2013 and June 2014. Patients with human immunodeficiency virus(HIV)/HCV co-infection or patients who received a liver transplant in the past were excluded. Viral loads were recorded while on treatment and after treatment. Data collection continued until December,31 st 2014 when data analysis was initiated. Patients missing virologic outcomes data were not included in the analysis. Analysis of 35 patients who had virologic outcome data available resulted in eight patients who were viral load negative at the end of treatment with SMF/SOF but later relapsed. Data related to patient demographics,HCV infection,and treatment history was collected in order to identify risk factors shared among patients who failed treatment with SMF/***: Eight patients who were treated with the first generation HCV protease inhibitors BOC or TVR in combination with pegylated-interferon(PEG) and RBV who failed this triple therapy were subsequently retreated with an off-label all-oral regimen of SMV and SOF for 12 wk,with RBV in seven cases. Treatment was initiated before the Food and Drug Administration approved a 24-wk SMV/SOF regimen for patients with liver cirrhosis. All eight patients had an end of treatment response,but later relapsed. Eight(100%) patients were male. Mean age was 56(range,49-64). Eight(100%) patients had previously failed PEG/RBV dual therapy at least once in addition to prior failure with triple therapy. Total number of times treated ranged from 3-6(mean 3.8). Eight(100%) patients were male had liver cirrhosis as determi

关键词： Hepatitis C Protease inhibitor Relapse Simeprevir

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Clostridium diffi cile associated infection,diarrhea and colitis

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World Journal of Gastroenterology 2009年第13期15卷 1554-1580页

作者： Perry Hookman Jamie S Barkin University of Miami Miller School of Medicine division of Gastroenterology Mount Sinai Medical Center

A new, hypervirulent strain of Clostridium difficile, called NAP1/BI/027, has been implicated in C. difficile outbreaks associated with increased morbidity and mortality since the early 2000s. The epidemic strain is resistant to fluoroquinolones in vitro, which was infrequent prior to 2001. The name of this strain reflects its characteristics, demonstrated by different typing methods： pulsed-field gel electrophoresis （NAP1）, restriction endonuclease analysis （BI） and polymerase chain reaction （027）. In 2004 and 2005, the US centers for Disease Control and Prevention （CDC） emphasized that the risk of C. difficile-associated diarrhea （CDAD） is increased, not only by the usual factors, including antibiotic exposure, but also gastrointestinal surgery/manipulation, prolonged length of stay in a healthcare setting, serious underlying illness, immune-compromising conditions, and aging. Patients on proton pump inhibitors （PPIs） have an elevated risk, as do peripartum women and heart transplant recipients. Before 2002, toxic megacolon in C. dif/icile-associated colitis （CDAC）, was rare, but its incidence has increased dramatically. Up to two- thirds of hospitalized patients may be infected with C. difficile. Asymptomatic carriers admitted to healthcare facilities can transmit the organism to other susceptible patients, thereby becoming vectors. Fulminant colitis is reported more frequently during outbreaks of C. difficile infection in patients with inflammatory bowel disease （IBD）. C. diff/cile infection with IBD carries a higher mortality than without underlying IBD. This article reviews the latest information on C. difficile infection, including presentation, vulnerable hosts and choice of antibiotics, alternative therapies, and probiotics and immunotherapy. We review contact precautions for patients with known or suspected C. difficile- associated disease. Healthcare institutions require accurate and rapid diagnosis for early detection of possible outbreaks, to initiate s

关键词： Clostridium difficile Colitis Diarrhea Gastroenterology Nosocomial infection Iatrogenicinfection

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Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity

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World Journal of Gastroenterology 2024年第4期30卷 332-345页

作者： Yi-Jie Li Brittney O Baumert Nikos Stratakis Jesse A Goodrich Hao-Tian Wu Jing-Xuan He Yin-Qi Zhao Max T Aung Hong-Xu Wang Sandrah P Eckel Douglas I Walker Damaskini Valvi Michele A La Merrill Justin R Ryder Thomas H Inge Todd Jenkins Stephanie Sisley Rohit Kohli Stavra A Xanthakos Andrea A Baccarelli Rob McConnell David V Conti Lida Chatzi Department of Population and Public Health Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90032United States Barcelona Institute of Global Health Barcelona Institute of Global HealthBarcelona 08036Spain Department of Environmental Health Sciences Mailman School of Public HealthColumbia UniversityNew YorkNY 10032United States Gangarosa Department of Environmental Health Rollins School of Public HealthEmory UniversityAtlantaGA 30329United States Department of Environmental Medicine and Public Health Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States Department of Environmental Toxicology University of CaliforniaDavisCA 95616United States Department of Surgery Lurie Children’s Hospital of ChicagoChicagoIL 60611United States Northwestern University Feinberg School of Medicine Northwestern UniversityChicagoIL 60611United States division of Biostatistics and Epidemiology Cincinnati Children's Hospital Medical CenterCincinnatiOH 45229United States Department of Pediatrics University of Cincinnati College of MedicineCincinnatiOH 45229United States Department of Pediatrics Children’s Nutrition Research Center USDA/ARSBaylor College of MedicineHoustonTX 77030United States Department of Gastroenterology Children’s Hospital Los AngelesLos AngelesCA 90027United States division of Gastroenterology Hepatology and NutritionCincinnati Children's Hospital Medical CenterCincinnatiOH 45229United States

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and *** ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with *** microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains *** analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in *** To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with *** This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery ***-operative core liver biopsies were collected from participants and used to characterize histological features of *** samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq *** examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key *** Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of *** We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with ***,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,***,16 miRNAs were associated with two or more histological features of *** those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and posi

关键词： MicroRNA Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Liver fibrosis Lobular inflammation Ballooning degeneration

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Endoscopic treatment of non-variceal gastrointestinal bleeding:hemoclips and other hemostatic techniques

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World Journal of Gastroenterology 2000年第1期6卷 42-44页

作者： Moura RM Barkin JS University of Miami School of Medicine & Mount Sinai Medical Center Division of GastroenterologyMiamiFloridaUSA

Although the number of hospitalizations for non-variceal gastrointestinal bleeding has decreased inrecent years,acute upper gastrointestinalhemorrhage continues to be a common reason forhospital admission,and peptic ulcers account for atleast fifty percent of all *** the fact thatbleeding from ulcers ceases spontaneously inapproximately 80% of patients,it is still a

关键词： Subject headings gastrointestinal bleeding/therapy endoscopic/therapy hemoclip/therapy hemostatic technique

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Predictors of acute gastrointestinal bleeding in diabetic ketoacidosis:a retrospective observational study in minority population

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Gastroenterology Report 2017年第4期5卷 293-297,I0002页

作者： Kanthi Rekha Badipatla Preeti Jadhav Sushma Vaddigiri Bharat Bajantri Amandeep Singh Chaitanya Chandrala Vijay S Are Suresh Kumar Nayudu Department of Medicine Bronx Lebanon Hospital CenterIcahn School of Medicine at Mount SinaiBronxNew YorkNYUSA division of Gastroenterology Bronx Lebanon Hospital CenterIcahn School of Medicine at Mount SinaiBronxNew YorkNYUSA division of Pulmonary and Critical Care Bronx Lebanon Hospital CenterIcahn School of Medicine at Mount SinaiBronxNew YorkNYUSA division of cardiology Bronx Lebanon Hospital CenterIcahn School of Medicine at Mount SinaiBronxNew YorkNYUSA

Background:Diabetic ketoacidosis(DKA)is a common acute complication of diabetes mellitus requiring aggressive medical *** attempted to study the incidence and various clinical and laboratory variables associated with acute gastrointestinal bleeding(AGIB)and acute upper AGIB(AUGIB)in patients with ***:We conducted a retrospective chart review of all the patients admitted to our hospital with DKA between January 2010 and December *** collected demographic,clinical,laboratory,endoscopy and hospitalization details using an electronicmedical-record *** were divided into two groups based on the occurrence of gastrointestinal ***:A total of 234 patients with DKA were admitted during this period,of which 27(11.5%)patients had documented *** majority of patients had hematemesis(n=22,9.4%)except two had rectal and three had occult *** did not notice any difference in age,gender and ethnicity distribution between the two *** was no difference in the serum levels of electrolytes,anion gap,pH and hemoglobin A1C between the two ***,patients with AGIB had significantly higher initial blood glucose levels(738 vs 613 mg/dL,p=0.014).There was also increased mortality(7.4%vs 4.8%)in patients with AGIB,but this did not reach statistical ***:We conclude that higher initial serum blood glucose was associated with increased incidence of AGIB in patients admitted with *** also noted increased in-patient mortality in patients with DKA who had AGIB,even though statistically *** aggressive measures to correct blood glucose levels may result in decreased incidence of AGIB,thereby reducing mortality during hospitalization in patients with DKA.

关键词： diabetic ketoacidosis gastrointestinal bleeding mortality

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Left and right ventricular diastolic dysfunction and diastolic heart failure: does one lead to the other?

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Journal of Geriatric cardiology 2009年第1期6卷 3-10页

作者： Faramarz Tehrani Anita Phan Ernst R. Schwarz division of cardiology Department of Medicine Cedars-Sinai Medical Center and University of California Los Angeles Los Angeles California Division of Cardiology Department of Medicine Cedars-Sinai Medical Center and University of California Los Angeles Los Angeles California Division of Cardiology Department of Medicine Cedars-Sinai Medical Center and University of California Los Angeles Los Angeles California

Background and Objective Diastolic dysfunction of the left ventricle is a mechanical abnormality diagnosed primarily by echocardiogram, and can be distinguished into three separate degrees based on the severity of reduction in passive compliance and active myocardial relaxation. Methods A literature search was performed for basic science studies, clinical studies and major practice guidelines on the subject of diastolic dysfunction and diastolic heart failure. Important findings were analyzed and correlated with regard to clinical relevance. Results Left ventricular diastolic dysfunction appears to compromise exercise tolerance and is believed to contribute to the pathophysiology in patients with diastolic heart failure. In the clinical setting, however, oftentimes no clear distinction is made between echocardiographically diagnosed diastolic dysfunction and diastolic heart failure, and adequate treatment recommendations are sparse and aimed to prevent worsening and progression of clinical symptoms. To date, there is a lack of high powered trials assessing the possible progression rate from echocardiographically diagnosed diastolic dysfunction to the clinical diagnosis of diastolic heart failure. Furthermore, there are no solid indices to assess the degree of severity of diastolic dysfunction or its progression. Pure right ventricular diastolic dysfunction appears to be even less understood and under-recognized, although it may play a role in the development of both right and left heart failure. Currently there are few but interesting data on the possible interaction between ventricles with diastolic dysfunction and the overall affect on the development of heart failure. Conclusions The timeline and progression of diastolic dysfunction to diastolic heart failure have not been well established and warrant further investigation.

关键词： Diastolic dysfunction diastolic heart failure left ventricular dysfunction heart failure cardiomyopathy

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Improved scoring system for the electrocardiographic diagnosis of left ventricular hypertrophy

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World Journal of cardiology 2019年第3期11卷 94-102页

作者： Eric D Braunstein Lori B Croft Jonathan L Halperin Steve L Liao division of cardiology Department of Medicine Montefiore Medical Center/Albert Einstein College of Medicine division of cardiology Icahn School of Medicine at Mount Sinai Mount Sinai Medical Center

BACKGROUND Left ventricular hypertrophy(LVH) is a common manifestation of cardiovascular disease and a risk factor for cardiovascular morbidity and mortality, but available methods for its electrocardiographic(ECG) diagnosis have limited *** To investigate findings associated with LVH on ECG and developed an improved system for the diagnosis of *** A cohort study comparing ECG data acquired within 30 days of transthoracic echocardiography(TTE) was performed. Multivariate regression analysis identified ECG findings associated with increased LV mass and mass index. A scoring system was derived and performance compared to established criteria for *** Data from 5486 outpatients with TTEs and corresponding ECGs were included in the derivation cohort, 333(6.1%) of whom had LVH by TTE. In the primary regression analysis, findings associated with LVH were amplitudes of Q in V3, R in V6, S in V3, T in V6, P' in V1, P in V6, as well as R and T-axis discordance, R peak time in V6, QRS duration, weight, height, sex, and age. From this we derived a score consisting of 5 criteria, and validated it in an independent cohort of 910 patients. With a threshold of 1.5 points, sensitivity and specificity were67.9% and 81.4%, and 62.5% and 83.2% in the derivation and validation cohorts,respectively. With a threshold of 2 points, sensitivity and specificity were 42.3% and 93.0%, and 37.5% and 93.4% in these *** This score had superior sensitivity for detection of LVH by ECG while making a modest sacrifice in specificity compared to conventional criteria.

关键词： Left ventricular hypertrophy Electrocardiogram Echocardiogram Diagnostic criteria Scoring system

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