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| 1 | INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep^(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep^(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass spectrometry.RESULTS INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potential utility of FXR and dual FXR/TGR5 activation as disease intervention strategies in NASH. | Jonathan D Roth Michael Feigh Sanne S Veidal Louise KD Fensholdt Kristoffer T Rigbolt Henrik H Hansen Li C Chen Mathieu Petitjean Weslyn Friley Niels Vrang Jacob Jelsing Mark Young | 2018 | World Journal of Gastroenterology2018，24，2： | 7 |
| 2 | Optimizing hepatitis C virus treatment through pharmacist interventions: Identification and management of drug-drug interactions显示文摘AIM To quantify drug-drug-interactions(DDIs) encountered in patients prescribed hepatitis C virus(HCV) treatment, the interventions made, and the time spent in this process.METHODS As standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral(DAA) HCV treatment between November 2013 and July 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir(LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir(OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV). This retrospective analysis reviewed the work completed by the clinical pharmacist in order to measure the aims identified for the study. The number and type of DDIs identified were summarized with descriptive statistics.RESULTS Six hundred and sixty four patients(83.4% Caucasian, 57% male, average 56.7 years old) were identified; 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. Fifty-one point five per cent of patients were cirrhotic. Overall, 5217 medications were reviewed (7.86 medications per patient) and 781 interactions identified (1.18 interactions per patient). The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex patients. CONCLUSION DDIs are common with HCV medications and management can require medication adjustments and increased monitoring. An interdisciplinary team including a clinical pharmacist can optimize patient care. | Jacob A Langness Matthew Nguyen Amanda Wieland Gregory T Everson Jennifer J Kiser | 2017 | World Journal of Gastroenterology2017，23，9： | 5 |
| 3 | Integrating insulin-like growth factor 1 and sex hormones into neuroprotection:Implications for diabetes显示文摘Brain integrity and cognitive aptitude are often impaired in patients with diabetes mellitus, presumably a result of the metabolic complications inherent to the disease. However, an increasing body of evidence has demonstrated the central role of insulin-like growth factor 1(IGF1) and its relation to sex hormones in many neuroprotective processes. Both male and female patients with diabetes display abnormal IGF1 and sexhormone levels but the comparison of these fluctuations is seldom a topic of interest. It is interesting to note that both IGF1 and sex hormones have the ability to regulate phosphoinositide 3-kinase-Akt and mitogen-activated protein kinases-extracellular signal-related kinasesignaling cascades in animal and cell culture models of neuroprotection. Additionally, there is considerable evidence demonstrating the neuroprotective coupling of IGF1 and estrogen. Androgens have also been implicated in many neuroprotective processes that operate on similar signaling cascades as the estrogen-IGF1 relation. Yet, androgens have not been directly linked to the brain IGF1 system and neuroprotection. Despite the sex-specific variations in brain integrity and hormone levels observed in diabetic patients, the IGF1-sex hormone relation in neuroprotection has yet to be fully substantiated in experimental models of diabetes. Taken together, there is a clear need for the comprehensive analysis of sex differences on brain integrity of diabetic patients and the relationship between IGF1 and sex hormones that may influence brain-health outcomes. As such, this review will briefly outline the basic relation of diabetes and IGF1 and its role in neuroprotection. We will also consider the findings on sex hormones and diabetes as a basis for separately analyzing males and females to identify possible hormone-induced brain abnormalities. Finally, we will introduce the neuroprotective interplay of IGF1 and estrogen and how androgen-derived neuroprotection operates through similar signaling cascades. Future research on both neuroprotection and diabetes should include androgens into the interplay of IGF1 and sex hormones. | Jacob Huffman Christina Hoffmann George T Taylor | 2017 | World Journal of Diabetes2017，8，2： | 4 |
| 4 | Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source显示文摘BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments. | Michelle L Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian Nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James L Trevaskis Henrik H Hansen | 2019 | World Journal of Gastroenterology2019，25，33： | 3 |
| 5 | Rejection of Permacol~ mesh used in abdominal wall repair:A case report显示文摘Permacol mesh has shown promise when used in abdominal wall repair,especially in the presence of a contaminated surgical field.This biomaterial,derived from porcine dermis collagen,has proposed advantages over synthetic materials due to increased biocompatibility and reduced foreign body reaction within human tissues.However,we present a case report describing a patient who displayed rejection to a Permacol mesh when used in the repair of abdominal wound dehiscence following an emergency laparotomy.Review of the English language literature using PubMed and Medline, showed only two previously published cases of explantation of Permacoldue to sepsis or wound breakdown. The authors believe this is the first case of severe foreign body reaction leading to rejection of Permacol.Both animal and human studies show conflicting evidence of biocompatibility.There are several reports of successful use of Permacolto repair complex incisional herniae or abdominal walls in the presence of significant contamination.It appears from the literature that Permacolis a promising material,but as we have demonstrated,it has the potential to evoke a foreign body reaction and rejection in certain subjects. | Franchesca T Wotton Jacob A Akoh | 2009 | World Journal of Gastroenterology2009，15，34： | 2 |
| 6 | Comparative analysis of T-cell receptor gene rearrangements at diagnosis and T-cell acute lymphoblastic leukemia (T-ALL) shows high stability of clonal markers for monitoring of minimal residual disease,and reveals the occurrence of second T-ALl,显示文摘 | Szczepanski T van der Velden VH Raft T Jacobs DC van Wering ER Bruggemann M | 2003 | leukemia2003，17，11： | 1 |
| 7 | Random and site -specific immobilization of catalytic antibodies 显示文摘 | Spitznagel T M Jacobs J W Clark D S | 1993 | Enzyme Microbial Technol1993，15，： | 1 |
| 8 | Synthesis and electrochemical performance of reduced graphene oxide/maghemite composite anode for lithium ion batteries显示文摘 | KIM I T MAGASINSKI A JACOB K | 2013 | Carbon2013，52，： | 1 |
| 9 | The effects of supply chain integration on customer satisfaction and financial performance : An organizational learning perspective 显示文摘 | YU W T JACOBS M A SALISBURY W D ENNS H | 2013 | International Journal of Production Economies2013，146，1： | 1 |
| 10 | Loss of tumor mark er-immunostaining intensity on stored paraffin slides of hreast cancer显示文摘 | Jacobs T W Prioleau J E Schnitt S J | 1996 | NatlCancer Inst1996，88，15： | 1 |
| 11 | Blood flow and vascular permeability during motor dysfunction in a rabbit model of spinal cord ischemia 显示文摘 | Jacobs T P Kempski O Mckinley D | 1992 | Stroke1992，23，3： | 1 |
| 12 | Negtative inotropic effects of cytokines on the heart mediated by nitric oxide显示文摘 | Finkel M Oddis C Jacob T | 1992 | Science1992，257，4： | 1 |
| 13 | Von Hippel-Lindau gene therapy : a novel strategy in limiting endo-thelial cell proliferative activity 显示文摘 | Jacob T Ascher E Hingorani A | 2001 | Ann Vase Surg2001，15，1： | 1 |
| 14 | Identifi- cation and subtyping of Francisella by pyrosequencing and signature matching of 16S rDNA fragments 显示文摘 | Jacob D Wahab T Edvinsson B Peterzon A Boskani T Farhadi L Barduhn A Grunow R Sandstrom G | 2011 | Lett Appl Microbiol2011，53，6： | 1 |
| 15 | GFAP and SIOOB are biomarkers of traumatic brain injury: an observa- tional cohort study显示文摘 | Vos P E Jacobs B Andriessen T M | 2010 | Neurology2010，75，20： | 1 |
| 16 | OMEGA EP high-energy petawatt laser: progress and prospects显示文摘 | D N Maywar J H Kelly L J Waxer S F B Morse I A Begishev J Bromage C Dorrer J L Edwards L Folnsbee M J Guardalben S D Jacobs R Jungquist T J Kessler R W Kidder B E Kruschwitz S J Loucks J R Marciante R L McCrory D D Meyerhofer A V Okishev J B Oliver G Pien | 2008 | Journal of Physics: Conference Series2008，，3： | 1 |
| 17 | Foam processing of poly ( ethylene - co - vinyl acetate ) rubber using supereritical carbon dioxide 显示文摘 | JACOBS M A KEMMERE M F KEURENTJES J T | 2004 | Polymer2004，45，： | 1 |
| 18 | The Influence of Particle Shape on Dielectric Enhancement in Metal-insulator Composites显示文摘 | DOYLE W T JACOBS I S | 1992 | J Appl Phys1992，71，： | 1 |
| 19 | The role of ClC-3 in volume-activated chloride currents and volume regulation in bovine epithelial cells demonstrated by antisense inhibition显示文摘 | Wang L Chen L Jacob T J | 2000 | J Physiol2000，524，： | 1 |
| 20 | Fiber,sex,and colorectal adenoma:results of a pooled analysis显示文摘 | JACOBS E T LANZA E ALBERTS D S | 2006 | Am J Clin Nutr2006，83，2： | 1 |
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