|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Hepatocellular carcinoma in nonalcoholic fatty liver: Role of environmental and genetic factors显示文摘Hepatocellular carcinoma(HCC) is the fourth cause of cancer related mortality, and its incidence is rapidly increasing. Viral hepatitis, alcohol abuse, and exposure to hepatotoxins are major risk factors, but nonalcoholic fatty liver disease(NAFLD) associated with obesity, insulin resistance, and type 2 diabetes, is an increasingly recognized trigger, especially in developed countries. Older age, severity of insulin resistance and diabetes, and iron overload have been reported to predispose to HCC in this context. Remarkably, HCCs have been reported in non-cirrhotic livers in a higher proportion of cases in NAFLD patients than in other etiologies. Inherited factors have also been implicated to explain the different individual susceptibility to develop HCC, and their role seems magnified in fatty liver, where only a minority of affected subjects progresses to cancer. In particular, the common I148 M variant of the PNPLA3 gene influencing hepatic lipid metabolism influences HCC risk independently of its effect on the progression of liver fibrosis. Recently, rare loss-of-function mutations in Apolipoprotein B resulting in very low density lipoproteins hepatic retention and in Telomerase reverse transcriptase influencing cellular senescence have also been linked to HCC in NAFLD. Indeed, hepatic stellate cells senescence has been suggested to bridge tissue aging with alterations of the intestinal microbiota in the pathogenesis of obesity-related HCC. A deeper understanding of the mechanisms mediating hepatic carcinogenesis during insulin resistance, and the identification of its genetic determinants will hopefully provide new diagnostic and therapeutic tools. | Paola Dongiovanni Stefano Romeo Luca Valenti | 2014 | World Journal of Gastroenterology2014，20，36： | 38 |
| 2 | PNPLA3 I148M polymorphism and progressive liver disease显示文摘The 148 Isoleucine to Methionine protein variant(I148M)of patatin-like phospholipase domain-containing 3(PNPLA3),a protein is expressed in the liver and is involved in lipid metabolism,has recently been identified as a major determinant of liver fat content.Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver:from simple steatosis to steatohepatitis and progressive fibrosis.Furthermore,the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis,and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis,and possibly chronic hepatitis B virus hepatitis,hereditary hemochromatosis and primary sclerosing cholangitis.All in all,studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases.Remarkably,the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation,suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes,directly promoting fibrogenesis.Therefore,PNPLA3 is a key player in liver disease progression.Assessment of the I148M polymorphism will possibly inform clinical practice in the future,whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis. | Paola Dongiovanni Benedetta Donati Roberta Fares Rosa Lombardi Rosellina Margherita Mancina Stefano Romeo Luca Valenti | 2013 | World Journal of Gastroenterology2013，19，41： | 17 |
| 3 | Diagnostic and therapeutic implications of the association between ferritin level and severity of nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD),defined by excessive liver fat deposition related to the metabolic syndrome,is a leading cause of progressive liver disease,for which accurate non-invasive staging systems and effective treatments are still lacking.Evidence has shown that increased ferritin levels are associated with the metabolic insulin resistance syndrome,and higher hepatic iron and fat content.Hyperferritinemia and iron stores have been associated with the severity of liver damage in NAFLD,and iron depletion reduced insulin resistance and liver enzymes.Recently,Kowdley et al demonstrated in a multicenter study in 628 adult patients with NAFLD from the NAFLD-clinical research network database with central re-evaluation of liver histology and iron staining that the increased serum ferritin level is an independent predictor of liver damage in patients with NAFLD,and is useful to identify NAFLD patients at risk of non-alcoholic steatohepatitis and advanced fibrosis.These data indicate that incorporation of serum ferritin level may improve the performance of noninvasive scoring of liver damage in patients with NAFLD,and that iron depletion still represents an attractive therapeutic target to prevent the progression of liver damage in these patients. | Luca Valenti Paola Dongiovanni Silvia Fargion | 2012 | World Journal of Gastroenterology2012，18，29： | 15 |
| 4 | NLRP3 inflammasome blockade reduces adipose tissue inflammation and extracellular matrix remodeling显示文摘The NLRP3-IL-1β pathway plays an important role in adipose tissue(AT)-induced inflammation and the development of obesityassociated comorbidities.We aimed to determine the impact of NLRP3 on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and extracellular matrix(ECM)remodeling.Samples obtained from 98 subjects were used in a case-control study.The expression of different components of the inflammasome as well as their main effectors and inflammation-and ECM remodeling-related genes were analyzed.The impact of blocking NLRP3 using siRNA in lipopolysaccharide(LPS)-mediated inflammation and ECM remodeling signaling pathways was evaluated.We demonstrated that obesity(P<0.01),obesity-associated T2D(P<0.01)and NAFLD(P<0.05)increased the expression of different com ponents of the inflammasome as well as the expression and release of IL-1β and IL-18 in AT.We also found that obese patients with T2D exhibited increased(P<0.05)hepatic gene expression levels of NLRP3,IL1B and IL18.We showed that NLRP3,but not NLRP1,is regulated by inflammation and hypoxia in visceral adipocytes.We revealed that the inhibition of NLRP3 in human visceral adipocytes significantly blocked(P<0.01)LPS-induced inflammation by downregulating the mRNA levels of CCL2,IL1B,IL6,IL8,S100A8,S100A9,TLR4 and TNF as well as inhibiting(P<0.01)the secretion of IL1-β into the culture medium.Furthermore,blocking NLRP3 attenuated(P<0.01)the LPS-induced expression of important molecules involved in AT fibrosis(COL1A1,COL4A3,COL6A3 and MMP2).These novel findings provide evidence that blocking the expression of NLRP3 reduces AT inflammation with significant fibrosis attenuation. | Xabier Unamuno Javier Gomez-Ambrosi Beatriz Ramirez Amaia Rodriguez Sara Becerril Victor Valenti Rafael Moncada Camilo Silva Javier Salvador Gema Fruhbeck Victoria Catalan | 2021 | Cellular & Molecular Immunology2021，18，4： | 9 |
| 5 | A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia显示文摘AIM:To compare iron depletion to lifestyle changes alone in patients with severe nonalcoholic fatty liver disease(NAFLD)and hyperferritinemia,a frequent feature associated with more severe liver damage,despite at least 6 mo of lifestyle changes.METHODS:Eligible subjects had to be 18-75 years old who underwent liver biopsy for ultrasonographically detected liver steatosis and hyperferritinemia,ferritin levels≥250 ng/mL,and NAFLD activity score>1.Iron depletion had to be achieved by removing 350 cc of blood every 10-15 d according to baseline hemoglobin values and venesection tolerance,until ferritin<30 ng/mL and/or transferrin saturation(TS)<25%.Thirty-eight patients were randomized 1:1 to phlebotomy(n=21)or lifestyle changes alone(n=17).The main outcome of the study was improvement in liver damage according to the NAFLD activity score at 2 years,secondary outcomes were improvements in liver enzymes[alanine aminotransferases(ALT),aspartate aminotransferase(AST),and gamma-glutamyl-transferases(GGT)].RESULTS:Phlebotomy was associated with normalization of iron parameters without adverse events.In the21 patients compliant to the study protocol,the rate of histological improvement was higher in iron depleted vs control subjects(8/12,67%vs 2/9,22%,P=0.039).There was a better improvement in steatosis grade in iron depleted vs control patients(P=0.02).In patients followed-up at two years(n=35),ALT,AST,and GGT levels were lower in iron-depleted than in control patients(P<0.05).The prevalence of subjects with improvement in histological damage or,in the absence of liver biopsy,ALT decrease≥20%(associated with histological improvement in biopsied patients)was higher in the phlebotomy than in the control arm(P=0.022).The effect of iron depletion on liver damage improvement as assessed by histology or ALT decrease≥20%was independent of baseline AST/ALT ratio and insulin resistance(P=0.0001).CONCLUSION:Iron depletion by phlebotomy is likely associated with a higher rate of improvement of histological liver damage than lifestyle changes alone in patients with NAFLD and hyperferritinemia,and with amelioration of liver enzymes. | Luca Valenti Anna Ludovica Fracanzani Paola Dongiovanni Serena Rovida Raffaela Rametta Erika Fatta Edoardo Alessandro Pulixi Marco Maggioni Silvia Fargion | 2014 | World Journal of Gastroenterology2014，20，11： | 8 |
| 6 | The use of choline in association with the Bangerter filters for the treatment of amblyopia显示文摘The study investigated the effects of choline combined with Bangerter filter in the treatment of amblyopia. All amblyopic subjects used a Bangerter filter on the corrective spectacle lens(1 d over the left eye, 1 d over the right eye). Choline was then administered orally to 39 patients once daily, five days per week for the entire study period. Subjects treated with the Bangerter filter showed a mean visual acuity of 0.27 logM AR; at 12 mo of treatment, the mean visual acuity reached 0.09 log MAR. Patients treated with the Bangerter filter and citicoline showed a mean visual acuity of 0.35 log MAR; at 12 mo of treatment, the mean visual acuity reached 0.01 logMAR. No significant changes in the angle of deviation were observed in both groups. Subjects in both forms of amblyopia therapies demonstrated an increase in visual acuity. However, these effects were markedly enhanced when coupled with the administration of choline. Findings suggest that the effects are particularly relevant in the more severe amblyopic cases. | Lelio Sabetti Francesco Masedu Chiara Tresca Federica Bianchi Marco Valenti | 2017 | International Journal of Ophthalmology(English edition)2017，10，11： | 5 |
| 7 | Hepcidin and HFE protein: Iron metabolism as a target for the anemia of chronic kidney disease?显示文摘The anemia of chronic kidney disease and hemodialysis is characterized by chronic inflammation and release of cytokines,resulting in the upregulation of the iron hormone hepcidin,also increased by iron therapy and reduced glomerular filtration,with consequent reduction in iron absorption,recycling,and availability to the erythron.This response proves advantageous in the short-term to restrain iron availability to pathogens,but ultimately leads to severe anemia,and impairs the response to erythropoietin(Epo)and iron.Homozygosity for the common C282Y and H63D HFE polymorphisms influence iron metabolism by hampering hepcidin release by hepatocytes in response to increased iron stores,thereby resulting in inadequate inhibition of the activity of Ferroportin-1,inappropriately high iron absorption and recycling,and iron overload.However,in hemodialysis patients,carriage of HFE mutations may confer an adaptive benefit by decreasing hepcidin release in response to iron infusion and inflammation,thereby improving iron availability to erythropoiesis,anemia control,the response to Epo,and possibly survival.Therefore,anti-hepcidin therapies may improve anemia management in hemodialysis.However,HFE mutations directly favor hemoglobinization independently of hepcidin,and reduce macrophages activation in response to inflammation,whereas hepcidin might also play a beneficial anti-inflammatory and anti-microbic action during sepsis,so that direct inhibition of HFEmediated regulation of iron metabolism may represent a valuable alternative therapeutic target.Genetic studies may offer a valuable tool to test these hypotheses and guide the research of new therapies. | Elena Canavesi Carlo Alfieri Serena Pelusi Luca Valenti | 2012 | World Journal of Nephrology2012，1，6： | 5 |
| 8 | Carotid Artery Intima-media Thickness in Nonalcoholic Fatty Liver Disease显示文摘 | Anna Ludovica Fracanzani Larry Burdick Sara Raselli Paola Pedotti Liliana Grigore Gennaro Santorelli Luca Valenti Alessandra Maraschi Alberico Catapano Silvia Fargion | 2008 | The American Journal of Medicine2008，，1： | 5 |
| 9 | Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis显示文摘AIM: To investigate whether the patatin-like phospholipase domain containing-3 gene (PNPLA3 ) I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis (HH). METHODS: We studied 174 consecutive unrelated homozygous for the C282Y HFE mutation of HH (C282Y+/+ HH) patients from Northern Italy, for whom the presence of cirrhosis could be determined based on histological or clinical criteria, without excessive alcohol intake (< 30/20 g/d in males or females) or hepatitis B virus and hepatitis C virus viral hepatitis. Steatosis was evaluated in 123 patients by histology (n = 100) or ultrasound (n = 23). The PNPLA3 rs738409 single nucleotide polymorphism, encoding for the p.148M protein variant, was genotyped by a Taqman assay (assay on demand, Applied Biosystems). The association of the PNPLA3 I148M protein variant (p.I148M) with steatosis, fibrosis stage, and cirrhosis was evaluated by logistic regression analysis. RESULTS: PNPLA3 genotype was not associated with metabolic parameters, including body mass index (BMI), the presence of diabetes, and lipid levels, but the presence of the p.148M variant at risk was independently associated with steatosis [odds ratio (OR) 1.84 per p.148M allele, 95% confidence interval (CI): 1.05-3.31; P = 0.037], independently of BMI and alanine amino-transaminase (ALT) levels. The p.148M variant was also associated with higher aspartate aminotransferase (P = 0.0014) and ALT levels (P = 0.017) at diagnosis, independently of BMI and the severity of iron overload. In patients with liver biopsy, the 148M variant was independently associated with the severity (stage) of fibrosis (estimated coefficient 0.56 ± 0.27, P = 0.041). In the overall series of patients, the p.148M variant was associated with cirrhosis in lean (P = 0.049), but not in overweight patients (P = not significant). At logistic regression analysis, cirrhosis was associated with BMI ≥ 25 (OR 1.82, 95% CI: 1.02-3.55), ferritin > 1000 ng/mL at diagnosis (OR 19.3, 95% CI: 5.3-125), and with the G allele in patients with BMI < 25 (OR 3.26, 95% CI: 1.3-10.3). CONCLUSION: The PNPLA3 I148M polymorphism may represent a permissive factor for fibrosis progression in patients with C282Y+/+ HH. | Luca Valenti Paolo Maggioni Alberto Piperno Raffaela Rametta Sara Pelucchi Raffaella Mariani Paola Dongiovanni Anna Ludovica Fracanzani Silvia Fargion | 2012 | World Journal of Gastroenterology2012，18，22： | 4 |
| 10 | HFE Genotype, Parenchymal Iron Accumulation, and Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Disease显示文摘 | Luca Valenti Anna Ludovica Fracanzani Elisabetta Bugianesi Paola Dongiovanni Enrico Galmozzi Ester Vanni Elena Canavesi Ezio Lattuada Giancarlo Roviaro Giulio Marchesini Silvia Fargion | 2010 | Gastroenterology2010，，3： | 4 |
| 11 | Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis C virus-infected patients: A retrospective study显示文摘BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(HCC)and mortality is less well established.AIM To examine the occurrence of HCC or death from any cause in a retrospectiveprospective study of patients treated with DAAs.METHODS Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy.The study was conducted in 380 patients(age:60±13 years,224 males,32%with cirrhosis)treated with DAAs with or without SVR(95/5%),with a median follow up of 58 wk(interquartile range:38-117).The baseline anthropometric features,HCV viral load,severity of liver disease,presence of extra-hepatic complications,coinfection with HIV and/or HBV,alcohol consumption,previous interferon use,alphafetoprotein levels,and renal function were considered to be confounders.RESULTS The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years,respectively(incidence rate ratio:44,95%CI:15-136,P<0.001).Considering the combined endpoint of HCC or death from any cause,the hazard ratio(HR)for the SVR patients was 0.070(95%CI:0.025-0.194,P<0.001).Other independent predictors of HCC or death were low HCV viremia(HR:0.808,P=0.030),low platelet count(HR:0.910,P=0.041),and presence of mixed cryoglobulinemia(HR:3.460,P=0.044).Considering SVR in a multi-state model,the independent predictors of SVR achievement were absence of cirrhosis(HR:0.521,P<0.001)and high platelet count(HR:1.019,P=0.026).Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR(HR:5.982,P=0.028 and HR:5.633,P=0.047,respectively).CONCLUSION DAA treatment is effective in inducing SVR and protecting against HCC or death.A residual risk of HCC persists in patients with advanced liver disease or with complications,such as mixed cryoglobulinemia or renal failure. | Gian Luca Colussi Debora Donnini Rosario Francesco Brizzi Silvia Maier Luca Valenti Cristiana Catena Alessandro Cavarape Leonardo Alberto Sechi Giorgio Soardo | 2019 | World Journal of Gastroenterology2019，25，40： | 4 |
| 12 | Dietary Iron Overload Induces Visceral Adipose Tissue Insulin Resistance显示文摘 | Paola Dongiovanni Massimiliano Ruscica Raffaela Rametta Stefania Recalcati Liliana Steffani Stefano Gatti Domenico Girelli Gaetano Cairo Paolo Magni Silvia Fargion Luca Valenti | 2013 | The American Journal of Pathology2013，，6： | 3 |
| 13 | 澳大利亚全科医学近几十年的变化显示文摘全科医学一直是澳大利亚医疗体系的基石,几乎所有的澳大利亚人每年至少看1次全科医生。本文试图概述1990—2015年澳大利亚全科医生队伍、全科医生接诊的患者以及患者疾病的复杂性所发生的主要变化,发现在过去的25年里,全科医生群体、接诊的患者情况和就诊内容均发生了变化,全科医生的临床工作重点更倾向于老年人保健、慢性病管理、临床和治疗程序、转诊和检查。 | Helena Britt Graeme C Miller Lisa Valenti Joan Henderson Clare Bayram Julie Gordon 本刊编辑部 | 2016 | 中国全科医学2016，19，33： | 3 |
| 14 | A 360-Degree Overview Of Paediatric Nafld: Recent Insights显示文摘 | Valerio Nobili Gianluca Svegliati-Baroni Anna Alisi Luca Miele Luca Valenti Pietro Vajro | 2012 | Journal of Hepatology2012，，： | 3 |
| 15 | Epidemiological network analysis in HIV-1 B infected patients diagnosed in Italy between 2000 and 2008显示文摘 | Annapaola Callegaro Valentina Svicher Claudia Alteri Alessandra Lo Presti Daniela Valenti Antonio Goglio Marco Salemi Eleonora Cella Carlo Federico Perno Massimo Ciccozzi Franco Maggiolo | 2011 | Infection, Genetics and Evolution2011，，3： | 2 |
| 16 | Ectopic expression of the osteogenic master gene RUNX2 in melanoma显示文摘The transcription factor RUNX2 is the osteogenic master gene expressed in mesenchymal stem cells during osteogenic commitment as well as in pre-osteoblasts and early osteoblasts.However,RUNX2 is also ectopically expressed in melanoma and other cancers.Malignant melanoma(MM)is a highly metastatic skin cancer.The incidence of MM has increased considerably in the past half-century.The expression levels and mutation rates of genes such as BRAF,KIT,NRAS,PTEN,P53,TERT and MITF are higher in melanoma than in other solid malignancies.Additionally,transcription factors can affect cellular processes and induce cellular transformation since they control gene expression.Recently,several studies have identified alterations in RUNX2 expression.In particular,the regulation of KIT by RUNX2 and the increased expression of RUNX2 in melanoma specimens have been shown.Melanocytes,whose transformation results in melanoma,arise from the neural crest and therefore show'stemness'features.RUNX2 plays an important role in the re-activation of the MAPK and PI-3K/AKT pathways,thus endowing melanoma cells with a high metastatic potential.In melanoma,the most frequent metastatic sites are the lung,liver,brain and lymph nodes.In addition,bone metastatic melanoma has been described.Notably,studies focusing on RUNX2may contribute to the identification of an appropriate oncotarget in melanoma. | Maria Teresa Valenti Luca Dalle Carbonare Monica Mottes | 2018 | World Journal of Stem Cells2018，10，7： | 2 |
| 17 | The SOD2 C47T polymorphism influences NAFLD fibrosis severity: Evidence from case-control and intra-familial allele association studies显示文摘 | Ahmad Al-Serri Quentin M. Anstee Luca Valenti Valerio Nobili Julian B.S. Leathart Paola Dongiovanni Julia Patch Anna Fracanzani Silvia Fargion Christopher P. Day Ann K. Daly | 2011 | Journal of Hepatology2011，，2： | 2 |
| 18 | Iron in fatty liver and in the metabolic syndrome: A promising therapeutic target显示文摘 | Paola Dongiovanni Anna Ludovica Fracanzani Silvia Fargion Luca Valenti | 2011 | Journal of Hepatology2011，，4： | 2 |
| 19 | Carotid Artery Intima-media Thickness in Nonalcoholic Fatty Liver Disease显示文摘 | Anna Ludovica Fracanzani Larry Burdick Sara Raselli Paola Pedotti Liliana Grigore Gennaro Santorelli Luca Valenti Alessandra Maraschi Alberico Catapano Silvia Fargion | 2008 | The American Journal of Medicine2008，，1： | 2 |
| 20 | Importance and performance of streetscapes at a tourism destination in Indonesia:The residents’perspectives显示文摘The present study examined the importance and performance of streetscapes at a tourism destination in Makassar,Indonesia,from the residents’perspectives using the importance-performance analysis method.Thus,six attributes of the streetscapes in four segments of the old city district were identified and presented to 400 participants.The participants were then asked to rate the perception and preference of each attribute.Results of the attribute values were illustrated in a Cartesian diagram.Findings indicate notable discrepancies between the perceptions and preferences of the respondents.Thus,these attributes were inconsistent with their expectations.Moreover,the results showed that each segment should have different priorities for specific attributes to improve the performance of the streetscapes.Overall,such data can be used by stakeholders,such as tourism developers and government policymakers,to make appropriate and informed decisions that will improve the attractiveness of this tourism destination and increase the number of visitors. | Marly Valenti Patandianan Hiroyuki Shibusawa | 2020 | Frontiers of Architectural Research2020，9，3： | 2 |
您所在的机构暂未开通此部分的功能，请联系管理员