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Sphingosine-1-phosphate signaling and the gut-liver axis in liver diseases

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Liver Research 2019年第1期3卷 19-24页

作者： Eric K.Kwong Huiping Zhou Department of Microbiology and Immunology Virginia Commonwealth UniversityRichmondVAUSA McGuire va medical center RichmondVAUSA

The liver is the central organ involved in lipid metabolism and the gastrointestinal(GI)tract is responsible for nutrient absorption and ***,dyslipidemia and metabolic disorders are of increasing public health concern worldwide,and novel therapeutics that target both the liver and the GI tract(gut-liver axis)are much *** addition to aiding fat digestion,bile acids act as important signaling molecules that regulate lipid,glucose and energy metabolism via activating nuclear receptor,G protein-coupled receptors(GPCRs),Takeda G protein receptor 5(TGR5)and sphingosine-1-phosphate receptor 2(S1PR2).Sphingosine-1-phosphate(S1P)is synthesized by two sphingosine kinase isoforms and is a potent signaling molecule that plays a critical role in various diseases such as fatty liver,in-flammatory bowel disease(IBD)and colorectal *** this review,we will focus on recent findings related to the role of S1P-mediated signaling pathways in the gut-liver axis.

关键词： Sphingosine-1-phosphate(S1P) Sphingosine kinase 2(SphK2) Sphingosine-1-phosphate receptor 2 (S1PR2) Gut-liver axis Liver diseases

Colorectal cancer and dysplasia in inflammatory bowel disease

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World Journal of Gastroenterology 2008年第17期14卷 2662-2669页

作者： Timothy L Zisman David T Rubin Clinical Research Fellow in Gastro-enterology the University of Chicago Medical Center The University of chicago medical center

Both ulcerative colitis and Crohn’s disease carry an increased risk of developing colorectal cancer. Established risk factors for cancer among patients with inflammatory bowel disease (IBD) include the younger age at diagnosis, greater extent and duration of disease, increased severity of inflammation, family history of colorectal cancer and coexisting primary sclerosing cholangitis. Recent evidence suggests that current medical therapies and surgical techniques for inflammatory bowel disease may be reducing the incidence of this complication. Nonetheless heightened vigilance and a careful, comprehensive approach to prevent or minimize the complications of invasive cancer are warranted in this unique cohort of patients. Current guidelines for the prevention and early detection of cancer in this high risk population are grounded in the concept of an inflammation-dysplasia- carcinoma sequence. A thorough understanding of the definition and natural history of dysplasia in IBD, as well as the challenges associated with detection and interpretation of dysplasia are fundamental to developing an effective strategy for surveillance and prevention, and understanding the limitations of the current approach to prevention. This article reviews the current consensus guidelines for screening and surveillance of cancer in IBD, as well as presenting the evidence and rationale for chemoprevention of cancer and a discussion of emerging technologies for the detection of dysplasia.

关键词： Cancer Dysplasia Inflammatory Bowel Disease Ulcerative Colitis Crohn's Disease Chemoprevention

Optimized protocol of multiple post-processing techniques improves diagnostic accuracy of multidetector computed tomography in assessment of small bowel obstruction compared with conventional axial and coronal reformations

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World Journal of Gastroenterology 2019年第9期25卷 1100-1115页

作者： Lian-Qin Kuang Wei Tang Ran Li Cheng Cheng Shuang-Yue Tang Yi Wang Department of Radiology Army Medical Center of PLA Army Medical University Sichuan Key Laboratory of medical Imaging Department of Radiology Affiliated Hospital of North Sichuan Medical College

BACKGROUND Axial and coronal reformations have been a widely used image post-processing protocol for the ordinary multidetector computed tomography(MDCT)examination of patients with small bowel obstruction(SBO) or other abdominal diseases. The diagnostic accuracy of MDCT for assessing SBO is expected to be further improved through the use of multiple post-processing *** To systemically evaluate the diagnostic accuracy and efficiency of an optimized protocol using multiple post-processing techniques for MDCT assessment of SBO and secondary bowel *** This retrospective cross-sectional study included 106 patients with clinically suspected SBO. Two readers applied three protocols to image post-processing and interpretation of patients' MDCT volume data. We compared the three protocols based on time spent, number of images, diagnostic self-confidence,agreement, detection rate, and accuracy of detection of SBO and secondary bowel *** Protocol 2 resulted in more time spent and number of images than protocols 1 and 3(P 0.05). Using protocol 3, both readers added multiple postprocessing techniques at frequencies of 29.2% and 34.9%, respectively, for obstruction cause, and 32.1% and 30.2%, respectively, for secondary bowel ischemia. Protocols 2 and 3 had higher total detection rates of obstruction cause and secondary bowel ischemia than protocol 1(P 0.05). The accuracy, sensitivity,specificity, positive predictive value and negative predictive value of protocols 2 and 3 were superior to those of protocol 1 for evaluating obstruction cause and secondary bowel *** Our optimized protocol of multiple post-processing techniques can both guarantee efficiency and improve diagnostic accuracy of MDCT for assessing SBO and secondary bowel ischemia.

关键词： Intestine Intestinal obstruction Multidetector computed tomography Diagnostic techniques and procedures

Paeoniflorin Attenuates Myocardial Fibrosis in Isoprenaline-induced Chronic Heart F ailure Rats via Inhibiting P38 MA PK Pathway

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Current medical Science 2020年第2期40卷 307-312页

作者： Mao LIU Jie FENG Qian DU Jiao AI Zhan LV Department of Cardiology Cardiovascular Research CenterAfiliated Hospital of North Sichuan Medical CollegeNanchong 637000China Department of Clinical Medicine North Sichuan Medical CollegeNanchong 637000China

Paconiflorin(Pae)is a monoterpenoid glycoside compound and has many biological activitics,such as immunosuppression,anti-inflammation and anti-cell ***,the effects and mechanisms of Pae on chronic heart failure(CHF)remain *** study was conducted to assess the effects and mechanisms of Pae on myocardial fibrosis in isoprenaline(Iso)-induced CHF ***(20 mgkg)was intragastrically administrated to CHF rats for 6 *** structure and function were *** protein and mRNA levels of transforming growth factorβ1(TGF-β1)and p38 were detected.C ompared to Iso group,Pae could alleviate myocardial fbrosis and improve cardiac function in CHF *** levels of collagen volume fraction(13.75%+3.77%vs.30.97%+4.22%,Pvascular collagen volume area(14.32%+2.50%v8.28.31%+3.16%,P<0.001)were significantly reduced in Pae group as compared with those in Iso *** expression of TGF-BI protein(0.30+0.07 vs.0.66+0.07,P<0.05)and mRNA(3.51+0.44 vs.7.58+0.58,P<0.05)decreased significantly in Pac group as compared with that in Iso *** expression of p38 protein(0.36+0.12 vs.0.81+0.38,P<0.05)and mRNA(3.84+0.05 vs.4.40+0.17,P<0.05)also decreased markedly in Pae group as compared with that in Iso *** could attenuate myocardial fibrosis and improve cardiac function in CHF rats by down-regulating the p38 MAPK signaling pathway.

关键词： chronic heart failure paconiflorin myocardial fibrosis p38 transforming growth factorβ1

Sox9 augments BMP2-induced chondrogenic differentiation by downregulating Smad7 in mesenchymal stem cells(MSCs)

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Genes & Diseases 2017年第4期4卷 229-239页

作者： Chen Zhao Wei Jiang Nian Zhou Junyi Liao Mingming Yang Ning Hu Xi Liang Wei Xu Hong Chen Wei Liu Lewis L.Shi Leonardo Oliveira Jennifer Moriatis Wolf Sherwin Ho Aravind Athiviraham H.M.Tsai Tong-Chuan He Wei Huang Department of Orthopedic Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Radiology The University of ChicagoChicagoIL 60637USA

Cartilage injuries caused by arthritis or trauma pose formidable challenges for effective clinical management due to the limited intrinsic proliferative capability of *** stem cell-based therapies and transgene-enhanced cartilage tissue engineering may open new avenues for the treatment of cartilage *** morphogenetic protein 2(BMP2)induces effective chondrogenesis of mesenchymal stem cells(MSCs)and can thus be explored as a potential therapeutic agent for cartilage defect ***,BMP2 also induces robust endochondral *** the precise mechanisms through which BMP2 governs the divergence of chondrogenesis and osteogenesis remain to be fully understood,blocking endochondral ossification during BMP2-induced cartilage formation may have practical significance for cartilage tissue ***,we investigate the role of Sox9-donwregulated Smad7 in BMP2-induced chondrogenic differentiation of *** find that overexpression of Sox9 leads to a decrease in BMP2-induced Smad7 expression in ***9 inhibits BMP2-induced expression of osteopontin while enhancing the expression of chondrogenic marker Col2a1 in *** expression of Sox9 in MSCs promotes BMP2-induced chondrogenesis and suppresses BMP2-induced endochondral *** Smad7 expression inhibits BMP2-induced chondrogenesis in stem cell implantation *** limb explant assay reveals that Sox9 expands BMP2-stimulated chondrocyte proliferating zone while Smad7 promotes BMP2-intitated hypertrophic zone of the growth *** cycle analysis indicates that Smad7 induces significant early apoptosis in BMP2-stimulated *** together,our results strongly suggest that Sox9 may facilitate BMP2-induced chondrogenesis by downregulating Smad7,which can be exploited for effective cartilage tissue engineering.

关键词： Bone morphogenetic protein 2(BMP2) Cartilage tissue engineering Chondrogenic differentiation Endochondral ossification Mesenchymal stem cells(MSCs) Smad7 Sox9

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

Microglia lactylation in relation to central nervous system diseases

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Neural Regeneration Research 2025年第1期20卷 29-40页

作者： Hui Yang Nan Mo Le Tong Jianhong Dong Ziwei Fan Mengxian Jia Juanqing Yue Ying Wang School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Clinical Laboratory The Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine(Hangzhou First People’s Hospital)HangzhouZhejiang ProvinceChina College of medical Veterinary and Life SciencesUniversity of GlasgowGlasgowUK Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina Department of Clinical Research center Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina

The development of neurodegenerative diseases is closely related to the disruption of central nervous system ***,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative *** has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of *** is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various *** review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting ***,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

关键词： brain central nervous system glycolysis immune response inflammation lactate metabolism lactate lactylation microglia neurodegenerative diseases

Management of gastrointestinal bleed in the intensive care setting,an updated literature review

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World Journal of Critical Care Medicine 2025年第1期14卷 20-41页

作者： Vignesh K Nagesh Sai Priyanka Pulipaka Ruchi Bhuju Emelyn Martinez Shruthi Badam Gomathy Aarthy Nageswaran Hadrian Hoang-Vu Tran Daniel Elias Charlene Mansour Jaber Musalli Sanket Bhattarai Lokeash Subramani Shobana Tannishtha Sethi Ritvik Sethi Namrata Nikum Chinmay Trivedi Amer Jarri Colin Westman Nazir Ahmed Shawn Philip Simcha Weissman Jonathan Weinberger Ayrton I Bangolo Department of Internal Medicine Palisades Medical CenterNorth BergenNJ 07047United States Department of Internal Medicine University of Arkansas for Medical SciencesLittle RockAR 72205United States Department of Internal Medicine Hackensack Palisades Medical CenterNorth BergenNJ 07047United States Department of Gastroenterology Hackensack University Medical CenterHackensackNJ 07061United States Department of Pulmonology and Critical Care HCA Florida Bayonet Point HospitalHudsonFL 34667United States Department of Hematology&Oncology John Theurer Cancer Center at Hackensack University Medical CenterHackensackNJ 07601United States

Gastrointestinal(GI)bleeding is a critical and potentially life-threatening condition frequently observed in the intensive care unit(ICU).This literature review consolidates current insights on the epidemiology,etiology,management,and outcomes of GI bleeding in critically ill *** bleeding remains a significant concern,especially among patients with underlying risk factors such as coagulopathy,mechanical ventilation,and renal *** GI bleeding in the ICU requires a multidisciplinary approach,including resuscitation,endoscopic intervention,pharmacologic therapy,and sometimes surgical *** with enhanced management strategies,GI bleeding in the ICU is associated with considerable morbidity and mortality,particularly when complicated by multi-organ *** review reiterates the need for adequate resuscitation and interventions in managing GI bleeding in critically ill patients,aiming to enhance survival rates and improve the quality of care within the ICU setting.

关键词： Gastrointestinal bleed varices variceal bleeding Diverticular bleed Angiodysplasia Ulcer Hemorrhoids Endoscopy Enteroscopy Embolization

Risk of post-operative complications associated with anti-TNF therapy in inflammatory bowel disease

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World Journal of Gastroenterology 2012年第3期18卷 197-204页

作者： Tauseef Ali Laura Yun David T Rubin University of Oklahoma Health Sciences center & va medical center. Section of Digestive Diseases and Nutrition University of chicago Inflammatory Bowel Disease Center

There have been increasing concerns regarding the safety of perioperative anti-tumour necrosis factor (anti-TNF) α agents. We performed a literature review to evaluate the post-operative complications associated with perioperative anti-TNF use in patients with inflammatory bowel disease. A comprehensive review was performed with a literature search utilizing Pub Med, Cochrane, OVID and EMBASE databases according to published guidelines. To date, there are only data for infliximab. There are three published studies which have assessed post-operative complications with perioperative infliximab use in patients with Crohn' s disease (CD), four studies in ulcerative colitis (UC) patients, and one study on both CD and UC patients. Two out of the three studies in CD patients showed no increased post-operative complications associated with perioperative infliximab. Two out of four studies in UC patients also did not show an increase in post-operative complications, and the combined study with CD and UC patients did not show an increased risk as well. Studyresults could not be combined secondary to significant differences in study designs, patient population and definition of their endpoints. There appears to be a risk of post-operative complications associated with TNF therapy in some patients. Based on these data, careful patient selection and prospective data collection should be performed.

关键词： Crohn's disease Ulcerative colitis Colectomy Post-operative complications