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| 1 | New therapeutic options opened by the molecular classification of gastric cancer显示文摘Gastric cancer(GC) is one of the most lethal and aggressive cancers, being the third cause of cancer related death worldwide. Even with radical gastrectomy and the latest generation of molecular chemotherapeutics, the numbers of recurrence and mortality remains high. This is due to its biological heterogeneity based on the interaction between multiple factors, from genomic to environmental factors, diet or infections with various pathogens. Therefore, understanding the molecular characteristics at a genomic level is critical to develop new treatment strategies. Recent advances in GC molecular classification provide the unique opportunity to improve GC therapy by exploiting the biomarkers and developing novel targeted therapy specific to each subtype. This article highlights the molecular characteristics of each subtype of gastric cancer that could be considered in shaping a therapeutic decision, and also presents the completed and ongoing clinical trials addressed to those targets. The implementation of the novel molecular classification system will allow a preliminary patient selection for clinical trials, a mandatory issue if it is desired to test the efficacy of a certain inhibitor to the given target. This will represent a substantial advance as well as a powerful tool for targeted therapy. Nevertheless, translating the scientific results into new personalized treatment opportunities is needed in order to improve clinical care, the survival and quality of life of patients with GC. | Mihaela Chivu-Economescu Lilia Matei Laura G Necula Denisa L Dragu Coralia Bleotu Carmen C Diaconu | 2018 | World Journal of Gastroenterology2018，24，18： | 14 |
| 2 | Acute pancreatitis:The stress factor显示文摘Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications.Etiologies of pancreatitis vary,with gallstones accounting for the majority of all cases,followed by alcohol.Other causes of pancreatitis include trauma,ischemia,mechanical obstruction,infections,autoimmune,hereditary,and drugs.The main events occurring in the pancreatic acinar cell that initiate and propagate acute pancreatitis include inhibition of secretion,intracellular activation of proteases,and generation of inflammatory mediators.Small cytokines known as chemokines are released from damaged pancreatic cells and attract inflammatory cells,whose systemic action ultimately determined the severity of the disease.Indeed,severe forms of pancreatitis may result in systemic inflammatory response syndrome and multiorgan dysfunction syndrome,characterized by a progressive physiologic failure of several interdependent organ systems.Stress occurs when homeostasis is threatened,and stressors can include physical or mental forces,or combinations of both.Depending on the timing and duration,stress can result in beneficial or harmful consequences.While it is well established that a previous acute-short-term stress decreases the severity of experimentally-induced pancreatitis,the worsening effects of chronic stress on the exocrine pancreas have received relatively little attention.This review will focus on the influence of both prior acute-short-term and chronic stress in acute pancreatitis. | Marcelo G Binker Laura I Cosen-Binker | 2014 | World Journal of Gastroenterology2014，20，19： | 10 |
| 3 | Therapies targeting cancer stem cells: Current trends and future challenges显示文摘Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells(CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a longlasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of mi RNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers. | Denisa L Dragu Laura G Necula Coralia Bleotu Carmen C Diaconu Mihaela Chivu-Economescu | 2015 | World Journal of Stem Cells2015，7，9： | 10 |
| 4 | Relationship between adipose tissue dysfunction, vitamin D deficiency and the pathogenesis of non-alcoholic fatty liver disease显示文摘Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide.Its pathogenesis is complex and not yet fully understood.Over the years many studies have proposed various pathophysiological hypotheses,among which the currently most widely accepted is the'multiple parallel hits'theory.According to this model,lipid accumulation in the hepatocytes and insulin resistance increase the vulnerability of the liver to many factors that act in a coordinated and cooperative manner to promote hepatic injury,inflammation and fibrosis.Among these factors,adipose tissue dysfunction and subsequent chronic low grade inflammation play a crucial role.Recent studies have shown that vitamin D exerts an immune-regulating action on adipose tissue,and the growing wealth of epidemiological data is demonstrating that hypovitaminosis D is associated with both obesity and NAFLD.Furthermore,given the strong association between these conditions,current findings suggest that vitamin D may be involved in the relationship between adipose tissue dysfunction and NAFLD.The purpose of this review is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to adipose tissue dysfunction,and in the pathophysiology linking vitamin D deficiency with NAFLD and adiposity,together with an overview of the evidence available on the clinical utility of vitamin D supplementation in cases of NAFLD. | Flavia A Cimini Ilaria Barchetta Simone Carotti Laura Bertoccini Marco G Baroni Umberto Vespasiani-Gentilucci Maria-Gisella Cavallo Sergio Morini | 2017 | World Journal of Gastroenterology2017，23，19： | 9 |
| 5 | High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes显示文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening(HTS) data for 3 762 distinct global gene knockout(KO) mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type(WT) cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging,ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass: 23 previously reported genes(Calcr, Cebpb, Crtap, Dcstamp, Dkk1, Duoxa2, Enpp1, Fgf23, Kiss1/Kiss1 r, Kl(Klotho),Lrp5, Mstn, Neo1, Npr2, Ostm1, Postn, Sfrp4, Slc30a5, Slc39a13, Sost, Sumf1, Src, Wnt10b), five novel genes extensively characterized(Cldn18, Fam20 c, Lrrk1, Sgpl1, Wnt16), five novel genes with preliminary characterization(Agpat2, Rassf5, Slc10a7, Slc26a7, Slc30a10) and three novel undisclosed genes coding for potential osteoporosis drug targets. | Robert Brommage Jeff Liu Gwenn M Hansen Laura L Kirkpatrick David G Potter Arthur T Ss Brian Zambrowicz David R Powell Peter Vogel | 2014 | Bone Research2014，2，3： | 7 |
| 6 | Chronic stress sensitizes rats to pancreatitis induced by cerulein:Role of TNF-α显示文摘AIM:To investigate chronic stress as a susceptibility factor for developing pancreatitis,as well as tumor necrosis factor-α (TNF-α) as a putative sensitizer.METHODS:Rat pancreatic acini were used to analyze the influence of TNF-α on submaximal (50 pmol/L) cholecystokinin (CCK) stimulation.Chronic restraint (4 h every day for 21 d) was used to evaluate the effects of submaximal (0.2 μg/kg per hour) cerulein stimulation on chronically stressed rats.RESULTS:In vitro exposure of pancreatic acini toTNF-α disorganized the actin cytoskeleton.This was further increased by TNF-α/CCK treatment,which additionally reduced amylase secretion,and increased trypsin and nuclear factor-κB activities in a protein-kinase-C δ and ε-dependent manner.TNF-α/CCK also enhanced caspases' activity and lactate dehydrogenase release,induced ATP loss,and augmented the ADP/ATP ratio.In vivo,rats under chronic restraint exhibited elevated serum and pancreatic TNF-α levels.Serum,pancreatic,and lung inflammatory parameters,as well as caspases' activity in pancreatic and lung tissue,were substantially enhanced in stressed/cerulein-treated rats,which also experienced tissues' ATP loss and greater ADP/ATP ratios.Histological examination revealed that stressed/cerulein-treated animals developed abundant pancreatic and lung edema,hemorrhage and leukocyte infiltrate,and pancreatic necrosis.Pancreatitis severity was greatly decreased by treating animals with an anti-TNF-αantibody,which diminished all inflammatory parameters,histopathological scores,and apoptotic/necrotic markers in stressed/cerulein-treated rats.CONCLUSION:In rats,chronic stress increases susceptibility for developing pancreatitis,which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation. | Marcelo G Binker Andres A Binker-Cosen Daniel Richards Herbert Y Gaisano Rodica H de Cosen Laura I Cosen-Binker | 2010 | World Journal of Gastroenterology2010，16，44： | 7 |
| 7 | Thrombotic risk factors in patients with liver cirrhosis: Correlation with MELD scoring system and portal vein thrombosis development显示文摘 | Maria Assunta Zocco Enrico Di Stasio Raimondo De Cristofaro Marialuisa Novi Maria Elena Ainora Francesca Ponziani Laura Riccardi Stefano Lancellotti Angelo Santoliquido Roberto Flore Maurizio Pompili Gian Lodovico Rapaccini Paolo Tondi Giovanni Battista G | 2009 | Journal of Hepatology2009，，4： | 5 |
| 8 | Novel nutraceutic therapies for the treatment of metabolic syndrome显示文摘Nutraceutic therapies such as berberine, bitter melon,Gymnema sylvestre, Irvingia gabonensis, resveratrol and ursolic acid have been shown to help control metabolic syndrome(MetS). The effect of berberine on glucose and lipid metabolism, hypertension, obesity and MetS has been evaluated in animal models and humans. Most clinical trials involving bitter melon have been conducted to evaluate its effect on glucose metabolism; nevertheless, some studies have reported favorable effects on lipids and blood pressure although there is little information about its effect on body weight. Gymnema sylvestre helps to decrease body weight and blood sugar levels; however, there is limited information on dyslipidemia and hypertension. Clinical trials of Irvingia gabonensis have shown important effects decreasing glucose and cholesterol concentrations as well decreasing body weight. Resveratrol acts through different mechanisms to decrease blood pressure, lipids, glucose and weight, showing its effects on the population with Met S. Finally, there is evidence of positive effects with ursolic acid in in vitro and in vivo studies on glucose and lipid metabolism and on body weight and visceral fat. Therefore, a review of the beneficial effects and limitations of the above-mentioned nutraceutic therapies is presented. | Esperanza Martínez-Abundis Miriam Mendez-del Villar Karina G Pérez-Rubio Laura Y Zuniga Marisol Cortez-Navarrete Alejandra Ramírez-Rodriguez Manuel González-Ortiz | 2016 | World Journal of Diabetes2016，7，7： | 3 |
| 9 | Lipotoxicity in the liver显示文摘Obesity due to excessive food intake and the lack of physical activity is becoming one of the most serious public health problems of the 21stcentury. With the increasing prevalence of obesity, non-alcoholic fatty liver disease is also emerging as a pandemic. While previously this pathophysiological condition was mainly attributed to triglyceride accumulation in hepatocytes,recent data show that the development of oxidative stress, lipid peroxidation, cell death, inflammation and fibrosis are mostly due to accumulation of fatty acids,and the altered composition of membrane phospholipids. In fact, triglyceride accumulation might play a protective role, and the higher toxicity of saturated or trans fatty acids seems to be the consequence of a blockade in triglyceride synthesis. Increased membrane saturation can profoundly disturb cellular homeostasis by impairing the function of membrane receptors,channels and transporters. However, it also inducesendoplasmic reticulum stress via novel sensing mechanisms of the organelle's stress receptors. The triggered signaling pathways in turn largely contribute to the development of insulin resistance and apoptosis. These findings have substantiated the lipotoxic liver injury hypothesis for the pathomechanism of hepatosteatosis.This minireview focuses on the metabolic and redox aspects of lipotoxicity and lipoapoptosis, with special regards on the involvement of endoplasmic reticulum stress responses. | Veronika Zámbó Laura Simon-Szabó Péter Szelényi va Kereszturi Gábor Bánhegyi Miklós Csala | 2013 | World Journal of Hepatology2013，5，10： | 3 |
| 10 | Localization and role of metabotropic glutamate receptors subtype 5 in the gastrointestinal tract显示文摘Metabotropic glutamate receptor subtype 5(mGluR5) is a Group I mGlu subfamily of receptors coupled to the inositol trisphosphate/diacylglycerol pathway. Like other m Glu R subtypes, mGluR5 s contain a phylogenetically conserved, extracellular orthosteric binding site and a more variable allosteric binding site, located on the heptahelical transmembrane domain. The mGluR5 receptor has proved to be a key pharmacological target in conditions affecting the central nervous system(CNS) but its presence outside the CNS underscores its potential role in pathologies affecting peripheral organs such as the gastrointestinal(GI) tract and accessory digestive organs such as the tongue, liver and pancreas. Following identification of mGluR5s in the mouth, various studies have subsequently demonstrated its involvement in mechanical allodynia, inflammation, pain and oral cancer. mGluR5 expression has also been identified in gastroesophageal vagal pathways. Indeed, experimental and human studies have demonstrated that mGluR5 blockade reduces transient lower sphincter relaxation and reflux episodes. In the intestine, mGluR5s have been shown to be involved in the control of intestinal inflammation, visceral pain and the epithelial barrier function. In the liver, mGluR5s have a permissive role in the onset of ischemic injury in rat and mice hepatocytes. Conversely, livers from mice treated with selective negative allosteric modulators and mGluR5 knockout mice are protected against ischemic injury. Similar results have been observed in experimental models of free-radical injury and in vivo mouse models of acetaminophen intoxication. Finally, mGluR5s in the pancreas are associated with insulin secretion control. The picture is, however, far from complete as the review attempts to establish in particular as regards identifying specific targets and innovative therapeutic approaches for the treatment of GI disorders. | Andrea Ferrigno Clarissa Berardo Laura G Di Pasqua Veronica Siciliano Plinio Richelmi Mariapia Vairetti | 2017 | World Journal of Gastroenterology2017，23，25： | 3 |
| 11 | Cardiac alterations in cirrhosis: reversibility after liver transplantation显示文摘 | Mireia Torregrosa Santi Aguadé Laura Dos Rosa Segura Antonio Gónzalez Artur Evangelista Joan Castell Carlos Margarit Rafael Esteban Jaume Guardia Joan Genescà | 2004 | Journal of Hepatology2004，，1： | 3 |
| 12 | A Novel Line Immunoassay Based on Recombinant Virulence Factors Enables Highly Specific and Sensitive Serologic Diagnosis of Helicobacter pylori Infection显示文摘 | Luca Formichella Laura Romberg Christian Bolz Michael Vieth Michael Geppert Gereon G?ttner Christina N?lting Dirk Walter Wolfgang Schepp Arne Schneider Kurt Ulm Petra Wolf Dirk H. Busch Erwin Soutschek Markus Gerhard | 2013 | Clinical and Vaccine Immunology2013，，11： | 2 |
| 13 | Thrombotic risk factors in patients with liver cirrhosis: Correlation with MELD scoring system and portal vein thrombosis development显示文摘 | Maria Assunta Zocco Enrico Di Stasio Raimondo De Cristofaro Marialuisa Novi Maria Elena Ainora Francesca Ponziani Laura Riccardi Stefano Lancellotti Angelo Santoliquido Roberto Flore Maurizio Pompili Gian Lodovico Rapaccini Paolo Tondi Giovanni Battista G | 2009 | Journal of Hepatology2009，，4： | 2 |
| 14 | Liver plays a central role in asymmetric dimethylargininemediated organ injury显示文摘Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolytic degradation.ADMA is metabolized to citrulline and dimethylamine,by dimethylarginine dimethylaminohydrolase(DDAH) and enters cells through cationic amino-acid transporters extensively expressed in the liver.The liver plays a crucial role in ADMA metabolism by DDAH-1 and,as has been recently demonstrated,it is also responsible for ADMA biliary excretion.A correlation has been demonstrated between plasma ADMA levels and the degree of hepatic dysfunction in patients suffering from liver diseases with varying aetiologies:plasma ADMA levels are increased in patients with liver cirrhosis,alcoholic hepatitis and acute liver failure.The mechanism by which liver dysfunction results in raised ADMA concentrations is probably due to impaired activity of DDAH due to severe inflammation,oxidative stress,and direct damage to DDAH.High plasma ADMA levels are also relevant as they are associated with the onset of multiorgan failure(MOF).Increased plasma concentration of ADMA was identified as an independent risk factor for MOF in critically-ill patients causing enhanced Intensive Care Unit mortality:a significant reduction in nitric oxide synthesis,leading to malperfusion in various organs,eventually culminating in multi organs dysfunction. | Andrea Ferrigno Laura G Di Pasqua Clarissa Berardo Plinio Richelmi Mariapia Vairetti | 2015 | World Journal of Gastroenterology2015，21，17： | 2 |
| 15 | Oxidative stress with an activation of the renin–angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction显示文摘 | Min-A Yu Laura G Sánchez-Lozada Richard J Johnson Duk-Hee Kang | 2010 | Journal of Hypertension2010，，6： | 2 |
| 16 | Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation显示文摘 | Jose A. Rodríguez-Navarro Laura Rodríguez María J. Casarejos Rosa M. Solano Ana Gómez Juan Perucho Ana María Cuervo Justo García de Yébenes María A. Mena | 2010 | Neurobiology of Disease2010，，3： | 2 |
| 17 | Mitral peak early diastolic filling velocity to deceleration time ratio as a predictor of prognosis in patients with chronic heart failure and preserved or reduced ejection fraction显示文摘ObjectiveDoppler 导出僧帽形的山峰到减速时间比率(E/DT ) 的早心脏舒张的充满速度为在一般人口预言预后作为参数被建议了。这研究有希望地在就医的病人在临床的、常规 echocardiographic 和 mitral-Doppler 变量上调查 E/DT 的增长的预示的值因为患心脏代偿失调的心失败(HF ).MethodsWe 分析了 95 个 HF 病人(吝啬的年龄 64.8 ±12.2 年) 从 2010 年 1 月在我们的机构就医了到 2012 年 3 月。主要端点是心脏的死亡或住院,无论哪个首先发生了。考克斯回归分析被执行识别 outcomes.ResultsDuring 后续的重要预言者(中部 37.7 个月) 13 个病人死了, 44 为一个心脏的事件被就医。在 univariable 分析,纽约心协会(NYHA ) 功能的班, furosemide 剂量,侧面的有三尖的环形的飞机收缩旅行,减速时间和 E/DT 结果是预兆的。在 multivariable 分析, E/DT 是预后的唯一的预言者(危险比率 = 1.02, P = 0.018 ) ,把增长预示的信息给临床并且另外的 echocardio 图形的措施(从 15.4 ~ 25.2 的全球 chi 平方;P = 0.032 ).ConclusionsE/DT 在 HF 病人给独立、增长的预示的信息。 | Flora Pirozzi AntoneUa Paglia Laura Sasso Pasquale Abete Angelo Carlomagno Carlo G Tocchetti Domenico Bonaduce Mario Petretta | 2015 | Journal of Geriatric Cardiology2015，12，4： | 2 |
| 18 | Land -cover change model validation by an ROC method for the lpswichwatershod, Massachusetts,USA显示文摘 | Pontius R G Jr Laura C S | 2001 | Agriculture Ecosystems and Environment2001，8，5： | 1 |
| 19 | Nerve growth factor control of neuronal expression of angiogenetic and vasoactive factors显示文摘 | Laura C Luciana G Alessandro G | 2001 | PNAS2001，98，11： | 1 |
| 20 | The role of root exudates in rhizosphere interactions with plants and other organisms显示文摘 | Harsh P B Tiffany L W Laura G P | 2006 | Plant Biology2006，57，： | 1 |
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