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| 1 | Current concepts on the role of nitric oxide in portal hypertension显示文摘Portal hypertension(PHT) is defined as a pathological increase in portal venous pressure and frequently accompanies cirrhosis.Portal pressure can be increased by a rise in portal blood flow,an increase in vascular resistance,or the combination.In cirrhosis,the primary factor leading to PHT is an increase in intra-hepatic resistance to blood flow.Although much of this increase is a mechanical consequence of architectural disturbances,there is a dynamic and reversible component that represents up to a third of the increased vascular resistance in cirrhosis.Many vasoactive substances contribute to the development of PHT.Among these,nitric oxide(NO) is the key mediator that paradoxically regulates the sinusoidal(intra-hepatic) and systemic/splanchnic circulations.NO deficiency in the liver leads to increased intra-hepatic resistance while increased NO in the circulation contributes to the hyperdynamic systemic/splanchnic circulation.NO mediated-angiogenesis also plays a role in splanchnic vasodilation and collateral circulation formation.NO donors reduce PHT in animals models but the key clinical challenge is the development of an NO donor or drug delivery system that selectively targets the liver. | Liang Shuo Hu Jacob George Jian Hua Wang | 2013 | World Journal of Gastroenterology2013，19，11： | 18 |
| 2 | Role of ethanol in the regulation of hepatic stellate cell function显示文摘Evidence has accumulated to suggest an important role of ethanol and/or its metabolites in the pathogenesis of alcohol-related liver disease. In this review, the fibrogenic effects of ethanol and its metabolites on hepatic stellate cells (HSCs) are discussed. In brief, ethanol interferes with retinoid metabolism and its signaling, induces the release of fibrogenic cytokines such as transforming growth factor β-1 (TGFβ-1) from HSCs, up-regulates the gene expression of collagen I and enhances type I collagen protein production by HSCs. Ethanol further perpetuates an activated HSC phenotype through extracellular matrix remodeling. The underlying pathophysiologic mechanisms by which ethanol exerts these pro-fibrogenic effects on HSCs are reviewed. | Jian-Hua Wang Robert G Batey Jacob George | 2006 | World Journal of Gastroenterology2006，12，43： | 16 |
| 3 | Molecular mechanisms of insulin resistance in chronic hepatitis C显示文摘It is now widely recognized that chronic hepatitis C (CHC)is associated with insulin resistance(IR)and type 2 diabetes,so can be considered a metabolic disease.IR is most strongly associated with hepatitis C virus(HCV)genotype 1,in contrast to hepatic steatosis, which is associated with genotype 3 infection.Apart from the well-described complications of diabetes,IR in CHC predicts faster progression to fibrosis and cirrhosis that may culminate in liver failure and hepatocellular carcinoma.More recently,it has been recognized that IR in CHC predicts a poor response to antiviral therapy. The molecular mechanisms for the association between IR and HCV infection are not well defined.This review will elaborate on the clinical associations between CHC and IR and summarize current knowledge regarding the molecular mechanisms that potentially mediate HCV-associated IR. | Mark W Douglas Jacob George | 2009 | World Journal of Gastroenterology2009，15，35： | 16 |
| 4 | From NAFLD to MAFLD:a“redefining”moment for fatty liver disease显示文摘The term non-alcoholic fatty liver disease(NAFLD)was coined in 1980 to characterize a disease similar to alcoholic fatty liver disease that developed in patients without a history of excessive alcohol intake.[1]Morphologically,NAFLD is characterized by excess fatty infiltration of the liver in the absence of known causes of liver disease(eg,alcohol,autoimmune liver disease,viral hepatitis,etc).The clinical manifestations of NAFLD(both hepatic and extrahepatic)depend on the outcome of complex interactions between its primary drivers including poor lifestyle habits and diet,a dysfunctional microbiota,genetic predisposition,and environmental cues that result in metabolic dysfunction and liver disease.However,bringing all patients with their markedly different clinical courses under the NAFLD umbrella belies its complexity and implies a homogeneous disease state that then negatively impacts clinical management and a deeper understanding of pathogenesis.With advances in current knowledge on the spectrum of fatty liver diseases,it is apparent that the fourdecade-old outdated term NAFLD can no longer serve to usefully describe a highly heterogeneous disease.The disease as we understand it today not only impacts patients who consume alcohol and those who do not,but also potentially impacts all patients with any form of liver disease,by acting as a disease modifier.[2] | Kenneth IZheng Jian-Gao Fan Jun-Ping Shi Vincent Wai-Sun Wong Mohammed Eslam Jacob George Ming-Hua Zheng | 2020 | Chinese Medical Journal2020，，19： | 14 |
| 5 | Combining computer vision and deep learning to enable ultra-scale aerial phenotyping and precision agriculture:A case study of lettuce production显示文摘Aerial imagery is regularly used by crop researchers,growers and farmers to monitor crops during the growing season.To extract meaningful information from large-scale aerial images collected from the field,high-throughput phenotypic analysis solutions are required,which not only produce high-quality measures of key crop traits,but also support professionals to make prompt and reliable crop management decisions.Here,we report AirSurf,an automated and open-source analytic platform that combines modern computer vision,up-to-date machine learning,and modular software engineering in order to measure yield-related phenotypes from ultra-large aerial imagery.To quantify millions of in-field lettuces acquired by fixed-wing light aircrafts equipped with normalised difference vegetation index(NDVI)sensors,we customised AirSurf by combining computer vision algorithms and a deep-learning classifier trained with over 100,000 labelled lettuce signals.The tailored platform,AirSurf-Lettuce,is capable of scoring and categorising iceberg lettuces with high accuracy(>98%).Furthermore,novel analysis functions have been developed to map lettuce size distribution across the field,based on which associated global positioning system(GPS)tagged harvest regions have been identified to enable growers and farmers to conduct precision agricultural practises in order to improve the actual yield as well as crop marketability before the harvest. | Alan Bauer Aaron George Bostrom Joshua Ball Christopher Applegate Tao Cheng Stephen Laycock Sergio Moreno Rojas Jacob Kirwan Ji Zhou | 2019 | Horticulture Research2019，6，1： | 14 |
| 6 | Treatment responses in Asians and Caucasians with chronic hepatitis C infection显示文摘AIM:To conduct a multicentre retrospective review of virological response rates in Asians infected with genotype 1 chronic hepatitis C(CHC) treated with combination interferon and ribavirin and then to compare their responses to that among Caucasians.METHODS:Asian patients infected with genotype 1 CHC treated at 4 Australian centres between 2001 to 2005 were identified through hospital databases.Baseline demographic characteristics,biochemical,virological and histological data and details of treatment were collected.Sustained virological responses(SVR) in this cohort were then compared to that in Caucasian subjects,matched by genotype,age,gender and the stage of hepatic fibrosis.RESULTS:A total of 108 Asians with genotype 1 CHC were identified.The end of treatment response(ETR) for the cohort was 79% while the SVR was 67%.Due to the relatively advanced age of the Asian cohort,only sixty-four subjects could be matched with Caucasians.The ETR among matched Asians and Caucasians was 81% and 56% respectively(P=0.003),while the SVR rates were 73% and 36%(P <0.001) respectively.This difference remained significant after adjusting for other predictive variables. | Kenneth K Yan Marianne Guirgis Amany Zekry Thuy Dinh Anouk Dev Jacob George Alice Lee | 2008 | World Journal of Gastroenterology2008，14，21： | 12 |
| 7 | Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease显示文摘The prevalence of obesity and related conditions like non-alcoholic fatty liver disease(NAFLD) is increasing worldwide and therapeutic options are limited.Alternative treatment options are therefore intensively sought after.An interesting candidate is the natural polyphenol resveratrol(RSV) that activates adenosinmonophosphate-activated protein kinase(AMPK) and silent information regulation-2 homolog 1(SIRT1).In addition,RSV has known anti-oxidant and anti-inflammatory effects.Here,we review the current evidence for RSVmediated effects on NAFLD and address the different aspects of NAFLD and non-alcoholic steatohepatitis(NASH) pathogenesis with respect to free fatty acid(FFA) flux from adipose tissue,hepatic de novo lipogenesis,inadequate FFA β-oxidation and additional intra- and extrahepatic inflammatory and oxidant hits.We review the in vivo evidence from animal studies and clinical trials.The abundance of animal studies reports a decrease in hepatic triglyceride accumulation,liver weight and a general improvement in histological fatty liver changes,along with a reduction in circulating insulin,glucose and lipid levels.Some studies document AMPK or SIRT1 activation,and modulation of relevant markers of hepatic lipogenesis,inflammation and oxidation status.However,AMPK/SIRT1-independent actions are also likely.Clinical trials are scarce and have primarily been performed with a focus on overweight/obese participants without a focus on NAFLD/NASH and histological liver changes.Future clinical studies with appropriate design are needed to clarify the true impact of RSV treatment in NAFLD/NASH patients. | Sara Heebll Karen Louise Thomsen Steen B Pedersen Hendrik Vilstrup Jacob George Henning Grnbk | 2014 | World Journal of Hepatology2014，6，4： | 11 |
| 8 | Lean diabetes mellitus:An emerging entity in the era of obesity显示文摘Much has been published on the characteristics of type 2 diabetes mellitus and its association with the epidemic of obesity.But relatively little is known about the incidence of lean diabetes,progression of disease and fate of the patients with low-normal body mass index(< 25).Studies in developing countries have shown that the clinical characteristics of these patients include history of childhood malnutrition,poor socioeconomic status,relatively early age of onset and absence of ketosis on withdrawal of insulin.In the United States,recent studies showed that the lean,normal weight diabetes is not rare especially among minority populations.They showed that these patients are mainly males,have higher prevalence of insulin use indicating rapid beta cell failure.They might have increased total,cardiovascular and non cardiovascular mortality when compared to obese diabetic patients.In this review,the epidemiologic and clinical features of lean diabetes are presented.The potential causal mechanisms of this emerging diabetes type that may include genetic,autoimmune,acquired and behavioral factors are discussed.The need for studies to further elucidate the causation as well as specific prevention and treatment of lean diabetes is emphasized. | Amrutha Mary George Amith George Jacob Leon Fogelfeld | 2015 | World Journal of Diabetes2015，6，4： | 7 |
| 9 | Australian tertiary care outcomes of entecavir monotherapy in treatment naive patients with chronic hepatitis B显示文摘AIM:To evaluate the long-term treatment outcomes of entecavir monotherapy in treatment naive patients in an Australian tertiary care setting. METHODS:A retrospective analysis of treatment naive patients receiving entecavir monotherapy through Westmead Hospital was performed.Patients were excluded if they had received previous treatment with another nucleoside or nucleotide analogue,were pregnant or less than 18 years old. RESULTS:Out of 336 patients,163 patients fulfilled the selection criteria.Range of follow up was 3-46 mo (mean 26 mo).134 patients(82.2%)had pre-treatment biopsies,with 26 patients(16.0%)demonstrating F3-4 fibrosis.In total,153 patients(93.9%)achieved at least Partial Virological Suppression(PVS),with 134 patients (82.2%)achieving complete virological suppression. The cumulative CVS and PVS rates at 36 mo were 82.1%and 96.4%,respectively.3 patients(1.8%)failed to achieve PVS,while 5 patients(3.0%)developed virological rebound.128 patients(78.5%)maintained CVS throughout follow up.Predictors of CVS included lower baseline DNA level(P=0.001),hepatitis B virus e antigen negative status(P=0.001)and increasing age at treatment(log rank 0.001).No significant adverse effects were reported necessitating cessation of entecavir. CONCLUSION:Entecavir monotherapy is efficacious and safe in an Australian tertiary care setting.Resistance and rebound rates are very low.This is similar to data from controlled and uncontrolled trials around the world. | Farzan Fahrtash-Bahin Viraj C Kariyawasam Timothy Gray Karen Byth Jacob George Mark W Douglas | 2013 | World Journal of Gastroenterology2013，19，5： | 5 |
| 10 | Comparative analysis of the predictive power of different endothelial progenitor cell phenotypes on cardiovascular outcome显示文摘AIM: To compare the predictive power of different endothelial progenitor cell (EPC) phenotypic markers for future cardiovascular events. METHODS: Peripheral blood was collected from 76 consecutive patients with acute coronary syndromes (ACS) who underwent percutaneous coronary intervention in our institute. The various EPC phenotypes of peripheral blood mononuclear cells were CD34+CD133+, CD34+KDR+, and CD 133+KDR+. The outcome endpoint included cardiovascular mortality, recurrent ACS, and hospitalization for decompensated heart failure during a 24-mo follow-up period.RESULTS: CD34+CD133+ cells (P = 0.034), but not CD34+KDR+ (P = 0.35) or CD 133+KDR+ cells (P = 0.19), were found to predict recurrent ACS. We found no correlation between EPCs measured by any of the three phenotypic combinations of accepted CD markers and the total combination of these separate outcomes. CONCLUSION: The EPC CD34+CD133+ phenotype, but not the CD34+KDR+ or the CD 133+KDR+ phenotypes, is predictive of future adverse cardiovascular outcomes. | Shmuel Schwartzenberg Arnon Afek Gideon Charach Ardon Rubinstein Yossi Ben-Shoshan Sarina Kissil Sofia Maisel-Auslender Gad Keren Jacob George | 2010 | World Journal of Cardiology2010，2，9： | 5 |
| 11 | Macrophages in metabolic associated fatty liver disease显示文摘Metabolic associated fatty liver disease(MAFLD),formerly named non-alcoholic fatty liver disease is the most common liver disorder in many countries.The inflammatory subtype termed steatohepatitis is a driver of disease progression to cirrhosis,hepatocellular carcinoma,liver transplantation,and death,but also to extrahepatic complications including cardiovascular disease,diabetes and chronic kidney disease.The plasticity of macrophages in response to various environmental cues and the fact that they can orchestrate cross talk between different cellular players during disease development and progression render them an ideal target for drug development.This report reviews recent advances in our understanding of macrophage biology during the entire spectrum of MAFLD including steatosis,inflammation,fibrosis,and hepatocellular carcinoma,as well as for the extra-hepatic manifestations of MAFLD.We discuss the underlying molecular mechanisms of macrophage activation and polarization as well as cross talk with other cell types such as hepatocytes,hepatic stellate cells,and adipose tissue.We conclude with a discussion on the potential translational implications and challenges for macrophage based therapeutics for MAFLD. | Jawaher Alharthi Olivier Latchoumanin Jacob George Mohammed Eslam | 2020 | World Journal of Gastroenterology2020，26，16： | 5 |
| 12 | 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 |
| 13 | Resistin mediates the hepatic stellate cell phenotype显示文摘AIM: To describe the role of resistin in liver fibrosis. METHODS: For the in vivo animal study, Sprague Dawley rats were subjected to bile duct ligation (BDL) for 4 wk. Rat liver, adipose tissue (epididymal fat) and serum were analyzed for resistin expression. For the in vitro experiment, rat primary hepatic stellate cells (HSCs) and Kupffer cells (KCs) were used. HSCs were exposed to recombinant resistin, and collagenⅠ, transforming growth factor β1, α smooth muscle actin, tissue inhibitor of metalloproteinase 1 and connective tissue growth factor expression were analyzed. Resistin gene and protein expression was quantified as was the expression of pro-inflammatory cytokines including tumor necrosis factor α (TNFα), interleukin (IL)-1, IL-6, IL-8 and monocyte chemotactic protein-1 (MCP-1). The effects of resistin on HSC proliferation, migration and apoptosis were determined. The effects of resistin on KCs were also investigated. RESULTS: Following BDL, rat epididymal fat and serum rather than liver showed higher resistin expression compared to control rats. In liver, resistin was expressed in quiescent HSCs and KCs. Resistin treatment resulted in enhancement of TNFα , IL-6 , IL-8 and MCP-1 gene expression and increased IL-6 and MCP-1 protein in HSCs. Resistin activated HSC phospho-MAPK/p38, and p38 inhibition diminished IL-6 and MCP-1 expression. Furthermore, resistin facilitated HSC proliferation and migration, but decreased apoptosis which was via an IL-6 and MCP-1 mechanism. Finally, resistin-induced transforming growth factor β1 from KCs enhanced HSC collagenⅠexpression. CONCLUSION: Resistin directly and indirectly modulates HSC behavior towards a more pro-fibrogenic phenotype. | Zhi-Xia Dong Lin Su Joanne Brymora Claire Bird Qing Xie Jacob George Jian-Hua Wang | 2013 | World Journal of Gastroenterology2013，19，28： | 4 |
| 14 | Exercise and non-alcoholic fatty liver disease: A systematic review and meta-analysis显示文摘 | Shelley E. Keating Daniel A. Hackett Jacob George Nathan A. Johnson | 2012 | Journal of Hepatology2012，，1： | 4 |
| 15 | Preventive treatment of alveolar pulmonary edema of cardiogenic origin显示文摘Objective To evaluate the efficacy of preventive treatment (PT) on alveolar pulmonary edema (APE) of cardiogenic origin using a monitor based on principles of internal thoracic impedance (ITI) measurements.Methods We conducted blinded clinical trials on patients with ST-elevation myocardial infarction (STEMI) and monitored whether the condition would progress to APE. ITI was measured noninvasively by the Edema Guard Monitor (EGM, model RS-207) every 30 min. The measurement threshold for the diagnosis of APE was fixed at > 12% decrease in ITI from baseline as described in our methodology. The patients were divided into one group that received standard treatment after the appearance of clinical signs of APE without considering the prediction of APE by EGM devise (Group 1), and another group of asymptomatic patients in whom development of APE was predicted by using only EGM measurements (Group 2). The latter participants’PT consisted of furosemide, intravenous nitroglycerine and supplemental oxygen. Results One-hundred and fifty patients with acute STEMI were enrolled into this study. Group 1 included 100 patients (53% males, age 64.1 ±12.6 years). Treatment was started after the clinical appearance of overt signs of APE. Group 2 included 50 patients (54% males, age 65.2 ±11.9 years) who received PT based on EGMmeasurements. Group 2 had significantly fewer cases of APE (n = 4, 8%) than Group 1 (n = 100, 100%) (P > 0.001). While APE was lethal in six (6%) Group 1 patients, PT resulted in prompt resolution of APE in all four (8%) Group 2 patients. Conclusion ITI is a usefulmodality for early diagnosis and PT of pulmonary edema of cardiogenic origin. | Gideon Charach Michael Shochat Alexander Rabinovich Oded Ayzenberg Jacob George Lior Charach Pavel Rabinovich | 2012 | Journal of Geriatric Cardiology2012，9，4： | 3 |
| 16 | Does laser surface texturing really have a negative impact on the fatigue lifetime of mechanical components?显示文摘Laser surface texturing(LST)has been proven to improve the tribological performance of machine elements.The micro-scale patterns manufactured by LST may act as lubricant reservoirs,thus supplying oil when encountering insufficient lubrication.However,not many studies have investigated the use of LST in the boundary lubrication regime,likely due to concerns of higher contact stresses that can occur with the increasing surface roughness.This study aims to examine the influence of LST on the fatigue lifetime of thrust rolling bearings under boundary lubrication.A series of periodic patterns were produced on the thrust rolling bearings,using two geometrically different designs,namely cross and dimple patterns.Base oil ISO VG 100 mixed with 0.05 wt%P of zinc dialkyldithiophosphate(ZDDP)was supplied.The bearings with cross patterns reduce the wear loss by two orders of magnitude.The patterns not only retain lubricant in the textured pockets but also enhance the formation of an anti-wear tribofilm.The tribofilm generation may be improved by the higher contact stresses that occur when using the textured surface.Therefore,in contrast to the negative concerns,the ball bearings with cross patterns were instead found to increase the fatigue life by a factor of three. | Chia-Jui HSU Andreas STRATMANN Simon MEDINA Georg JACOBS Frank MÜCKLICH Carsten GACHOT | 2021 | Friction2021，9，6： | 3 |
| 17 | Omega-3 supplementation and non-alcoholic fatty liver disease: A systematic review and meta-analysis显示文摘 | Helen M. Parker Nathan A. Johnson Catriona A. Burdon Jeffrey S. Cohn Helen T. O’Connor Jacob George | 2011 | Journal of Hepatology2011，，4： | 3 |
| 18 | From MAFLD to hepatocellular carcinoma and everything in between显示文摘Metabolic(dysfunction)associated fatty liver disease(MAFLD),previously known as non-alcoholic fatty liver disease,is the most common cause of chronic liver disease worldwide.Many risk factors contribute to the pathogenesis of MAFLD with metabolic dysregulation being the final arbiter of its development and progression.MAFLD poses a substantial economic burden to societies,which based on current trends is expected to increase over time.Numerous studies have addressed various aspects of MAFLD from its risk associations to its economic and social burden and clinical diagnosis and management,as well as the molecular mechanisms linking MAFLD to end-stage liver disease and hepatocellular carcinoma.This review summarizes current understanding of the pathogenesis of MAFLD and related diseases,particularly liver cancer.Potential therapeutic agents for MAFLD and diagnostic biomarkers are discussed. | Sarah Da Won Bae Jacob George Liang Qiao | 2022 | Chinese Medical Journal2022，，5： | 3 |
| 19 | Simple Non-Invasive Systems Predict Long-Term Outcomes of Patients With Nonalcoholic Fatty Liver Disease显示文摘 | Paul Angulo Elisabetta Bugianesi Einar S. Bjornsson Phunchai Charatcharoenwitthaya Peter R. Mills Francisco Barrera Svanhildur Haflidadottir Christopher P. Day Jacob George | 2013 | Gastroenterology2013，，： | 2 |
| 20 | The role of thiazolidinediones in non-alcoholic steatohepatitis – A systematic review and meta analysis显示文摘 | Suzanne E. Mahady Angela C. Webster Sarah Walker Arun Sanyal Jacob George | 2011 | Journal of Hepatology2011，，6： | 2 |
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