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Microbiome as mediator: Do systemic infections start in the gut?

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World Journal of Gastroenterology 2015年第37期21卷 10487-10492页

作者： Melissa Latorre Suneeta Krishnareddy Daniel E Freedberg division of digestive and liver Diseases Columbia University Medical Center

The intestinal microbiome is emerging as a crucial mediator between external insults and systemic infections. New research suggests that our intestinal microorganisms contribute to critical illness and the development of non-gastrointestinal infectious *** pathways include a loss of fecal intestinal bacterial diversity and a disproportionate increase in toxogenic bacterial species. Therapeutic interventions targeting the microbiome- primarily probiotics- have yielded limited results to date. However, knowledge in this area is rapidly expanding and microbiome-based therapy such as short-chain fatty acids may eventually become a standard strategy for preventing systemic infections in the context of critical illness.

关键词： Clostridium difficile Gut Microbiome Critical illn

Current and future pharmacological therapies for managing cirrhosis and its complications

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World Journal of Gastroenterology 2019年第8期25卷 888-908页

作者： David Kockerling Rooshi Nathwani Roberta Forlano Pinelopi Manousou Benjamin H Mullish Ameet Dhar liver Unit/division of Integrative Systems Medicine and digestive Disease Imperial College London

Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of *** article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications,together with discussion of current controversies and potential future ***/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety,efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of ***-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices,but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced *** observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial *** gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy;recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial *** remain the mainstay of uncomplicated ascites treatment,and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory *** have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental *** initial hepatotoxicity concerns,safety of statin administration has been demonstrated in compensated ***,statins are suggested to have protective effects upon fibrosis progression,decompensation and *** as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is *** evidence indicates that anticoa

关键词： Cirrhosis Beta-blockers Rifaximin Diuretics Statins Proton pump inhibitors Pharmacology

Non-coding RNAs in hepatitis C-induced hepatocellular carcinoma:Dysregulation and implications for early detection,diagnosis and therapy

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World Journal of Gastroenterology 2013年第44期19卷 7836-7845页

作者： Weihong Hou Herbert L Bonkovsky the liver Digestive and Metabolic Disorders Laboratory and the Liver-Biliary-Pancreatic Center Cannon Research Center Carolinas Medical CenterCharlotte NC 28203 United States

Hepatitis C virus(HCV)infection is one of main causes of hepatocellular carcinoma(HCC)and the prevalence of HCV-associated HCC is on the rise *** is particularly important and helpful to identify potential markers for screening and early diagnosis of HCC among high-risk individuals with chronic hepatitis C,and to identify target molecules for the prevention and treatment of *** noncoding RNAs,mainly microRNAs(miRNAs),and long non-coding RNAs(lncRNAs)with size greater than 200nucleotides,are likely to play important roles in a variety of biological processes,including development and progression of *** the most part their underlying mechanisms of action remain largely *** recent years,with the advance of high-resolution of microarray and application of next generation sequencing techniques,a significant number of non-coding RNAs(ncRNAs)associated with HCC,particularly caused by HCV infection,have been found to be differentially expressed and to be involved in pathogenesis of HCVassociated *** this review,we focus on recent studies of ncRNAs,especially miRNAs and lncRNAs related to HCV-induced *** summarize those ncRNAs aberrantly expressed in HCV-associated HCC and highlight the potential uses of ncRNAs in early detection,diagnosis and therapy of HCV-associated *** also discuss the limitations of recent studies,and suggest future directions for research in the ***,lncRNAs and their target genes may represent new candidate molecules for the prevention,diagnosis and treatment of HCC in patients with HCV *** of the potential uses of miRNAs and lncRNAs as diagnostic tools or therapies are still in their infancy.

关键词： MicroRNA Long non-coding RNAs Non-coding RNAs Hepatitis C virus Hepatocellular carcinoma

Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

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Neural Regeneration Research 2025年第6期20卷 1541-1554页

作者： Jinmei Ye Cong Duan Jiaxin Han Jinrong Chen Ning Sun Yuan Li Tifei Yuan Daihui Peng division of Mood Disorder Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Shanghai Key Laboratory of Psychotic disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

关键词： biomarker cytokine exosomes inflammasome major depressive disorder microglia mitochondrial DNA mitochondrial dysfunction neuroinflammation Toll-like receptor

Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment

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World Journal of Gastroenterology 2016年第20期22卷 4794-4801页

作者： Jordan E Axelrad Simon Lichtiger Vijay Yajnik Department of Medicine Division of Digestive and Liver Diseases Columbia University Medical Center Department of Medicine Division of Gastro-enterology The Massachusetts General Hospital

In patients with inflammatory bowel disease(IBD), chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. The pathogenesis of colitis-associated cancer is distinct from sporadic colorectal carcinoma and the critical molecular mechanisms underlying this process have yet to be elucidated. Patients with IBD have also been shown to be at increased risk of developing extra-intestinal malignancies. Medical therapies that diminish the mucosal inflammatory response represent the foundation of treatment in IBD, and recent evidence supports their introduction earlier in the disease course. However, therapies that alter the immune system, often used for long durations, may also promote carcinogenesis. As the population of patients with IBD grows older, with longer duration of chronic inflammation and longer exposure to immunosuppression, there is an increasing risk of cancer development. Many of these patients will require cancer treatment, including chemotherapy, radiation, hormonal therapy, and surgery. Many patients will require further treatment for their IBD. This review seeks to explore the characteristics and risks of cancer in patients with IBD, and to evaluate the limited data on patients with IBD and cancer, including management of IBD after a diagnosis of cancer, the effects of cancer treatment on IBD, and the effect of IBD and medications for IBD on cancer outcomes.

关键词： Inflammatory bowel disease Cancer Antitumor necrosis factor Immunosuppression Chemotherapy Radiation

Clostridium difficile infection in the community:Are proton pump inhibitors to blame?

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World Journal of Gastroenterology 2013年第40期19卷 6710-6713页

作者： Daniel E Freedberg Julian A Abrams division of digestive and liver Diseases Columbia University Medical CenterNew YorkNY 10032United States

Once a nosocomial disease,Clostridium difficile infection(CDI)now appears frequently in the community in the absence of exposure to *** studies have shown that patients with community-acquired CDI are younger,more likely to be female,and have fewer comorbidities compared to patients with hospital-associated *** most studies of CDI are hospitalbased,comparatively little is known about communityacquired *** recent study by Chitnis has received widespread attention because it used active surveillance to capture all cases of community-acquired CDI within a large population and assessed key risk *** authors found that low-level healthcare exposure and proton pump inhibitor use were common among those with non-antibiotics associated,community-acquired *** this commentary,we discuss the changing epidemiology of community-acquired CDI and the evidence basis for the controversial association between proton pump inhibitors and community-acquired CDI.

关键词： Clostridium difficile Pseudomembranous enterocolitis Proton pump inhibitors Anti-bacterial agents Pharmacoepidemiology Public health Disease outbreaks Epidemics

Overview and comparison of guidelines for management of pancreatic cystic neoplasms

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World Journal of Gastroenterology 2019年第31期25卷 4405-4413页

作者： Aws Hasan Kavel Visrodia James J Farrell Tamas A Gonda division of digestive and liver Diseases Department of MedicineColumbia UniversityNew YorkNY 10032United States division of digestive Diseases Department of MedicineYale UniversityNew HavenCT 06520United States

Pancreatic cysts are identified at an increasing *** mucinous cystic neoplasms represent a pre-malignant condition,the majority of these lesions do not progress to *** the last 10 years several societies have established guidelines for the diagnosis,initial evaluation and surveillance of these *** we provide an overview of five commonly used guidelines:2015 American Gastroenterological Association,2017 International Association of Pancreatology,American College of Gastroenterology 2018,European Study Group and American College of *** describe the similarities and differences between the methods used to formulate these guidelines,the population they target and their approaches towards initial evaluation and surveillance of cystic lesions.

关键词： Pancreatic cyst surveillance Cyst malignancy Guidelines

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease

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World Journal of Gastroenterology 2015年第39期21卷 11044-11052页

作者： Rosa Lombardi Elena Buzzetti Davide Roccarina Emmanuel A Tsochatzis Sheila Sherlock liver Unit and UCL Institute for liver and digestive Health Royal Free Hospital and UCL

Alcoholic liver disease(ALD) consists of a broad spectrum of disorders, ranging from simple steatosisto alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current "gold standard" for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of noninvasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence.

关键词： Transient elastography Cirrhosis Prognosis Histolo

1H nuclear magnetic resonance spectroscopy-basedmetabonomic study in patients with cirrhosis and hepaticencephalopathy

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World Journal of Hepatology 2015年第12期7卷 1701-1707页

作者： Konstantinos John Dabos John Andrew Parkinson Ian Howard Sadler John Nicholas Plevris Peter Clive Hayes Centre of liver and digestive disorders Royal Infirmary of Edinburgh Department of Chemistry University of Strathclyde Department of Chemistry University of Edinburgh

AIM: To identify plasma metabolites used as biomarkers in order to distinguish cirrhotics from controls and ***: A clinical study involving stable cirrhotic patients with and without overt hepatic encephalopathy was designed. A control group of healthy volunteers was used. Plasma from those patients was analysed using 1H- nuclear magnetic resonance spectroscopy. We used the Carr Purcell Meiboom Gill sequence to process the sample spectra at ambient probe temperature. We used a gated secondary irradiation field for water signal suppression. Samples were calibrated and referenced using the sodium trimethyl silyl propionate peak at 0.00 ppm. For each sample 128 transients(FID's) were acquired into 32 K complex data points over a spectral width of 6 KHz. 30 degree pulses were applied with an acquisition time of 4.0 s in order to achieve better resolution, followed by a recovery delay of 12 s, to allow for complete relaxation and recovery of the magnetisation. A metabolic profile was created for stable cirrhotic patients without signs of overt hepatic encephalopathy and encephalopathic patients as well as healthy controls. Stepwise discriminant analysis was then used and discriminant factors were created to differentiate between the three ***: Eighteen stabled cirrhotic patients, eighteen patients with overt hepatic encephalopathy and seventeen healthy volunteers were recruited. Patients with cirrhosis had significantly impaired ketone body metabolism, urea synthesis and gluconeogenesis. This was demonstrated by higher concentrations of acetoacetate(0.23 ± 0.02 vs 0.05 ± 0.00, P < 0.01), and b-hydroxybutarate(0.58 ± 0.14 vs 0.08 ± 0.00, P < 0.01), lower concentrations of glutamine(0.44 ± 0.08 vs 0.63 ± 0.03, P < 0.05), histidine(0.16 ± 0.01 vs 0.36 ± 0.04, P < 0.01) and arginine(0.08 ± 0.01 vs 0.14 ± 0.02, P < 0.03) and higher concentrations of glutamate(1.36 ± 0.25 vs 0.58 ± 0.04, P < 0.01), lactate(1.53 ± 0.11 vs 0.42 ± 0.05, P < 0.01),

关键词： Ketone bodies Branch chain amino acids Glutamine Glycolysis