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  • Intestinal hypoxia and hypoxia-induced signalling as therapeutic targets for IBD
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-08-30
    Sophie Van Welden, Andrew C. Selfridge, Pieter Hindryckx

    Tissue hypoxia occurs when local oxygen demand exceeds oxygen supply. In chronic inflammatory conditions such as IBD, the increased oxygen demand by resident and gut-infiltrating immune cells coupled with vascular dysfunction brings about a marked reduction in mucosal oxygen concentrations. To counter the hypoxic challenge and ensure their survival, mucosal cells induce adaptive responses, including the activation of hypoxia-inducible factors (HIFs) and modulation of nuclear factor-κB (NF-κB). Both pathways are tightly regulated by oxygen-sensitive prolyl hydroxylases (PHDs), which therefore represent promising therapeutic targets for IBD. In this Review, we discuss the involvement of mucosal hypoxia and hypoxia-induced signalling in the pathogenesis of IBD and elaborate in detail on the role of HIFs, NF-κB and PHDs in different cell types during intestinal inflammation. We also provide an update on the development of PHD inhibitors and discuss their therapeutic potential in IBD.

    更新日期:2017-08-31
  • Liver cancer: Translating '–omics' results into precision medicine for hepatocellular carcinoma
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-08-02
    Daniela Sia, Josep M. Llovet

    A large-scale comprehensive analysis of hepatocellular carcinoma (HCC) based on the integration of six distinct data platforms has pinpointed novel oncogenic processes and prognostic subgroups. These findings confirm previously identified molecular subclasses and fuel the need for a clear strategy of precision medicine in HCC.

    更新日期:2017-08-31
  • Oesophageal cancer: RNA editing of SLC22A3 mRNAs: causative relevance to familial ESCC?
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-07-26
    Kazuko Nishikura

    A new study reveals an involvement of SLC22A3 in the development of familial oesophageal squamous cell carcinoma (ESCC). Reduced expression of SLC22A3 is detected not only in ESCC tumours but also in non-tumour tissues of patients with familial ESCC. Interestingly, adenosine-to-inosine editing of SLC22A3 mRNA is proposed to drive early tumour invasion and metastasis, by inhibiting SLC22A3 expression.

    更新日期:2017-08-31
  • Perianal fistulizing Crohn's disease: pathogenesis, diagnosis and therapy
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-08-09
    Julián Panés, Jordi Rimola

    Perianal fistulizing Crohn's disease has a major negative effect on patient quality of life and is a predictor of poor long-term outcomes. Factors involved in the pathogenesis of perianal fistulizing Crohn's disease include an increased production of transforming growth factor β, TNF and IL-13 in the inflammatory infiltrate that induce epithelial-to-mesenchymal transition and upregulation of matrix metalloproteinases, leading to tissue remodelling and fistula formation. Care of patients with perianal Crohn's disease requires a multidisciplinary approach. A complete assessment of fistula characteristics is the basis for optimal management and must include the clinical evaluation of fistula openings, endoscopic assessment of the presence of proctitis, and MRI to determine the anatomy of fistula tracts and presence of abscesses. Local injection of mesenchymal stem cells can induce remission in patients not responding to medical therapies, or to avoid the exposure to systemic immunosuppression in patients naive to biologics in the absence of active luminal disease. Surgery is still required in a high proportion of patients and should not be delayed when criteria for drug failure is met. In this Review, we provide an up-to-date overview on the pathogenesis and diagnosis of fistulizing Crohn's disease, as well as therapeutic strategies.

    更新日期:2017-08-31
  • Direct-acting antiviral agents for HCV infection affecting people who inject drugs
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-08-23
    Jason Grebely, Behzad Hajarizadeh, Gregory J. Dore

    Globally, 12 million people are estimated to have injected drugs in the past year, 50% of whom have chronic HCV infection, with people who have previously injected drugs presenting an additional large reservoir of infection. The availability of simple and tolerable interferon-free direct-acting antiviral agents (DAAs) for HCV infection, which have a cure rate of >95% represents one of the most exciting advances in clinical medicine in the past few decades. Adherence and response to DAA therapy among people who inject drugs (PWID) receiving opioid substitution therapy (OST) in clinical trials are comparable to populations without a history of injecting drugs. Further data are required among current PWID not receiving OST. Given the potential prevention benefits of treatment, DAAs have enhanced cost-effectiveness among PWID. As HCV therapy is expanded to populations of PWID with high-risk behaviours for re-exposure, acknowledgement that HCV reinfection will occur is crucial, and appropriate strategies must be in place to maximize prevention of reinfection and offer retreatment for reinfection. This Review will also discuss essential components for broadening access to HCV care for PWID as we strive for the global elimination of HCV infection.

    更新日期:2017-08-31
  • Gut microbiota and IBD: causation or correlation?
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-07-19
    Josephine Ni, Gary D. Wu, Lindsey Albenberg, Vesselin T. Tomov

    A general consensus exists that IBD is associated with compositional and metabolic changes in the intestinal microbiota (dysbiosis). However, a direct causal relationship between dysbiosis and IBD has not been definitively established in humans. Findings from animal models have revealed diverse and context-specific roles of the gut microbiota in health and disease, ranging from protective to pro-inflammatory actions. Moreover, evidence from these experimental models suggest that although gut bacteria often drive immune activation, chronic inflammation in turn shapes the gut microbiota and contributes to dysbiosis. The purpose of this Review is to summarize current associations between IBD and dysbiosis, describe the role of the gut microbiota in the context of specific animal models of colitis, and discuss the potential role of microbiota-focused interventions in the treatment of human IBD. Ultimately, more studies will be needed to define host–microbial relationships relevant to human disease and amenable to therapeutic interventions.

    更新日期:2017-08-31
  • Regenerative medicine and cell-based approaches to restore pancreatic function
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-08-16
    Cara Ellis, Adam Ramzy, Timothy J. Kieffer

    The pancreas is a complex organ with exocrine and endocrine components. Many pathologies impair exocrine function, including chronic pancreatitis, cystic fibrosis and pancreatic ductal adenocarcinoma. Conversely, when the endocrine pancreas fails to secrete sufficient insulin, patients develop diabetes mellitus. Pathology in either the endocrine or exocrine pancreas results in devastating economic and personal consequences. The current standard therapy for treating patients with type 1 diabetes mellitus is daily exogenous insulin injections, but cell sources of insulin provide superior glycaemic regulation and research is now focused on the goal of regenerating or replacing β cells. Stem-cell-based models might be useful to study exocrine pancreatic disorders, and mesenchymal stem cells or secreted factors might delay disease progression. Although the standards that bioengineered cells must meet before being considered as a viable therapy are not yet established, any potential therapy must be acceptably safe and functionally superior to current therapies. Here, we describe progress and challenges in cell-based methods to restore pancreatic function, with a focus on optimizing the site for cell delivery and decreasing requirements for immunosuppression through encapsulation. We also discuss the tools and strategies being used to generate exocrine pancreas and insulin-producing β-cell surrogates in situ and highlight obstacles to clinical application.

    更新日期:2017-08-31
  • A clinician's guide to microbiome analysis
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-08-09
    Marcus J. Claesson, Adam G. Clooney, Paul W. O'Toole

    Microbiome analysis involves determining the composition and function of a community of microorganisms in a particular location. For the gastroenterologist, this technology opens up a rapidly evolving set of challenges and opportunities for generating novel insights into the health of patients on the basis of microbiota characterizations from intestinal, hepatic or extraintestinal samples. Alterations in gut microbiota composition correlate with intestinal and extraintestinal disease and, although only a few mechanisms are known, the microbiota are still an attractive target for developing biomarkers for disease detection and management as well as potential therapeutic applications. In this Review, we summarize the major decision points confronting new entrants to the field or for those designing new projects in microbiome research. We provide recommendations based on current technology options and our experience of sequencing platform choices. We also offer perspectives on future applications of microbiome research, which we hope convey the promise of this technology for clinical applications.

    更新日期:2017-08-31
  • The IBD interactome: an integrated view of aetiology, pathogenesis and therapy
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-08-23
    Heitor S. P. de Souza, Claudio Fiocchi, Dimitrios Iliopoulos

    IBD is a complex disease characterized by multiple interacting pathogenic components. In this Perspectives, the authors advocate studying the 'IBD interactome' to build a molecular network of IBD, and discuss new concepts and tools to implement an unbiased systems approach that could facilitate development of novel therapies.

    更新日期:2017-08-31
  • In the news
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-08-09
    Hugh Thomas

    From BSG 2017Manchester played host to the annual meeting of the British Society of Gastroenterology (BSG) this year, which took in 4 days of symposia, hands-on training, lectures and industry exhibits. After a Gastroenterology Master Class on the first day of the meeting, which

    更新日期:2017-08-31
  • Liver: Cholangiocytes regenerate hepatocytes during severe liver injury
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-07-26
    Iain Dickson

    New mouse models of hepatocyte regeneration have identified cholangiocytes as the cellular source of regeneration in the injured adult liver, according to research published in Nature. These findings could help reveal regenerative signalling pathways in the liver and ultimately aid the development of new

    更新日期:2017-08-31
  • NAFLD: Type 2 immunity drives progression of NAFLD
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-07-19
    Katrina Ray

    A new study reveals contrasting effects of polarized immune responses in different tissues during obesity. According to research published in Science Translational Medicine, a type 2 immune response, characterized by accumulation of eosinophils, exacerbates progression of NAFLD and NASH yet is protective in metabolic

    更新日期:2017-08-31
  • Regenerative medicine: Bioengineering the common bile duct
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-07-12
    Hugh Thomas

    Extrahepatic cholangiocyte organoids (ECOs) derived from primary human tissue can successfully repair common bile duct defects in mice, a new study shows.Bile duct disorders are a major cause of morbidity and mortality, with reconstruction of affected tissue limited by the availability of healthy donors.

    更新日期:2017-08-31
  • Pancreatic cancer: Biomarkers for the early detection of PDAC
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-08-02
    Katrina Ray

    A new study reports a novel biomarker panel for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC). Measured using conventional ELISAs, the test combines the detection of two blood-based biomarkers, thrombospondin-2 (THBS2) and carbohydrate antigen 19-9 (CA19-9).Lack of diagnostic tests for the early detection

    更新日期:2017-08-31
  • NAFLD: PNPLA3 and obesity: a synergistic relationship in NAFLD
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-06-14
    Jake P. Mann, Quentin M. Anstee

    NAFLD, the hepatic manifestation of the metabolic syndrome, is a multifactorial condition — environmental factors influence an inherited genetic risk. Stender et al. now describe the additive effect of obesity and NAFLD-associated genetic polymorphisms on steatosis, elevated serum alanine aminotransferase levels and cirrhosis, remarkably illustrating the principle of gene–environment interactions.

    更新日期:2017-08-31
  • Intestinal lymphatic vasculature: structure, mechanisms and functions
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-06-28
    Jeremiah Bernier-Latmani, Tatiana V. Petrova

    The mammalian intestine is richly supplied with lymphatic vasculature, which has functions ranging from maintenance of interstitial fluid balance to transport of antigens, antigen-presenting cells, dietary lipids and fat-soluble vitamins. In this Review, we provide in-depth information concerning the organization and structure of intestinal lymphatics, the current view of their developmental origins, as well as molecular mechanisms of intestinal lymphatic patterning and maintenance. We will also discuss physiological aspects of intestinal lymph flow regulation and the known and emerging roles of intestinal lymphatic vessels in human diseases, such as IBD, infection and cancer.

    更新日期:2017-08-31
  • IBD: To switch or not to switch: that is the biosimilar question
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-07-05
    Silvio Danese, Laurent Peyrin-Biroulet

    Biosimilar monoclonal antibodies are now being accepted in clinical practice by IBD specialists. However, switching patients already undergoing originator biologic treatment to biosimilars has been debated due to lack of controlled studies. The NOR-SWITCH study now provides novel clinical evidence in switching from originator to biosimilar in patients with IBD.

    更新日期:2017-08-31
  • The gut microbiome and liver cancer: mechanisms and clinical translation
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-07-05
    Le-Xing Yu, Robert F. Schwabe

    Hepatocellular carcinoma (HCC) is the third leading cause of worldwide cancer mortality. HCC almost exclusively develops in patients with chronic liver disease, driven by a vicious cycle of liver injury, inflammation and regeneration that typically spans decades. Increasing evidence points towards a key role of the bacterial microbiome in promoting the progression of liver disease and the development of HCC. Here, we will review mechanisms by which the gut microbiota promotes hepatocarcinogenesis, focusing on the leaky gut, bacterial dysbiosis, microbe-associated molecular patterns and bacterial metabolites as key pathways that drive cancer-promoting liver inflammation, fibrosis and genotoxicity. On the basis of accumulating evidence from preclinical studies, we propose the intestinal-microbiota–liver axis as a promising target for the simultaneous prevention of chronic liver disease progression and HCC development in patients with advanced liver disease. We will review in detail therapeutic modalities and discuss clinical settings in which targeting the gut-microbiota–liver axis for the prevention of disease progression and HCC development seems promising.

    更新日期:2017-08-31
  • The extracellular matrix of the gastrointestinal tract: a regenerative medicine platform
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-07-12
    George S. Hussey, Timothy J. Keane, Stephen F. Badylak

    The synthesis and secretion of components that constitute the extracellular matrix (ECM) by resident cell types occur at the earliest stages of embryonic development, and continue throughout life in both healthy and diseased physiological states. The ECM consists of a complex mixture of insoluble and soluble functional components that are arranged in a tissue-specific 3D ultrastructure, and it regulates numerous biological processes, including angiogenesis, innervation and stem cell differentiation. Owing to its composition and influence on embryonic development, as well as cellular and organ homeostasis, the ECM is an ideal therapeutic substrate for the repair of damaged or diseased tissues. Biologic scaffold materials that are composed of ECM have been used in various surgical and tissue-engineering applications. The gastrointestinal (GI) tract presents distinct challenges, such as diverse pH conditions and the requirement for motility and nutrient absorption. Despite these challenges, the use of homologous and heterologous ECM bioscaffolds for the focal or segmental reconstruction and regeneration of GI tissue has shown promise in early preclinical and clinical studies. This Review discusses the importance of tissue-specific ECM bioscaffolds and highlights the major advances that have been made in regenerative medicine strategies for the reconstruction of functional GI tissues.

    更新日期:2017-08-31
  • Medical devices for the treatment of obesity
    Nat. Rev. Gastroenterol. Hepatol. (IF 13.678) Pub Date : 2017-07-12
    Phong Ching Lee, John Dixon

    Obesity is a major public health concern that leads to numerous metabolic, mechanical and psychological complications. Although lifestyle interventions are the cornerstone of obesity management, subsequent physiological neurohormonal adaptations limit weight loss, strongly favour weight regain and counteract sustained weight loss. A range of effective therapies are therefore needed to manage this chronic relapsing disease. Bariatric surgery delivers substantial, durable weight loss but limited access to care, perceived high risks and costs restrict uptake. Medical devices are uniquely positioned to bridge the gap between more conservative lifestyle intervention and weight-loss pharmacotherapy and more disruptive bariatric surgery. In this Review, we examine the range of gastrointestinal medical devices that are available in clinical practice to treat obesity, as well as those that are in advanced stages of development. We focus on the mechanisms of action as well as the efficacy and safety profiles of these devices. Many of these devices are placed endoscopically, which provides gastroenterologists with exciting opportunities for treatment.

    更新日期:2017-08-31
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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