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| 1 | Cytokeratms and carcinoembryonic antigen in diagnosis,staging and prognosis of colorectal adenocarcinoma显示文摘AIM: To evaluate the serum levels of cytokeratins and carcinoembryonic antigen (CEA) in diagnosis, staging and prognosis of patients with colorectal adenocarcinoma.METHODS: The sample consisted of 169 patients. One hundred blood donors formed the control group. Radical surgery was performed on 120 patients, with an average follow-up duration of 22.3 mo. Relapses occurred in 23individuals after an average of 18.09 mo. CEA was assayed via the Delfia(R) method with a limit of 5 ng/mL. Cytokeratins were assayed via the LIA-mat(R) TPA-M Prolifigen(R) method with a limit of 72 U/L.RESULTS: In the diagnosis of patients with colorectal adenocarcinoma, CEA showed a sensitivity of 56%, a specificity of 95%, a positive predictive value of 94%, a negative predictive value of 50% and an accuracy of 76.8%.TPA-M had a sensitivity of 70%, a specificity of 96%, a positive predictive value of 97%, a negative predictive value of 66% and an accuracy of 93.6%. The elevation of one of the markers was shown to have a sensitivity of 76.9%, a specificity of 91%, a positive predictive value of 93.5%, a negative predictive value of 70% and an accuracy of 83.6%.There was no variation in the levels of the markers according to the degree of cell differentiation while there was an elevation in their concentrations in accordance with the increase in neoplastic dissemination. There was a statistically significant difference between the patients with stage Ⅳ lesions and those with stages Ⅰ, Ⅱ and Ⅲ tumors.With regard to CEA, the averagelevel was 14.2 ng/mL in patients with stage Ⅰ lesions, 8.5 ng/mL in patients with stage Ⅱ lesions, 8.0 ng/mL in patients with stage Ⅲ lesions and 87.7 ng/mL in patients with stage Ⅳ lesions. In relation to TPA-M, the levels were 153.1 U/L in patients with stage Ⅰtumors, 106.5 U/L in patients with stage Ⅱ tumors, 136.3 U/L in patients with stage Ⅲ tumors and 464.3 U/L in patients with stage Ⅳ tumors. There was a statistical difference in patients with a high CEA level in relation to a shorter survival(P<0.05). However, there was no correlation between patients with high TPA-M levels and prognostic indices of patients undergoing radical surgery.CONCLUSION: Cytokeratins demonstrate a greater sensitivity than CEA in the diagnosis of colorectal adenocarcinoma.There is an increase in the sensitivity of the markers with tumor dissemination. Cytokeratins cannot identify the worse prognosis in patients undergoing radical surgery.Cytokeratins constitute an advance in the direction of a perfect tumor marker in the treatment of patients with colorectal cancer. | Luís C.Fernandes Su B.Kim Delcio Matos | 2005 | World Journal of Gastroenterology2005，11，5： | 21 |
| 2 | Biomarkers and subtypes of deranged lipid metabolism in nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD)is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy.NAFLD covers a spectrum that ranges from simple steatosis,nonalcoholic steatohepatitis(NASH)with varying degrees of fibrosis,to cirrhosis,which is a major risk factor for hepatocellular carcinoma.Lifestyle and eating habit changes during the last century have made NAFLD the most common liver disease linked to obesity,type 2 diabetes mellitus and dyslipidemia,with a global prevalence of 25%.NAFLD arises when the uptake of fatty acids(FA)and triglycerides(TG)from circulation and de novo lipogenesis saturate the rate of FAβ-oxidation and verylow density lipoprotein(VLDL)-TG export.Deranged lipid metabolism is also associated with NAFLD progression from steatosis to NASH,and therefore,alterations in liver and serum lipidomic signatures are good indicators of the disease’s development and progression.This review focuses on the importance of the classification of NAFLD patients into different subtypes,corresponding to the main alteration(s)in the major pathways that regulate FA homeostasis leading,in each case,to the initiation and progression of NASH.This concept also supports the targeted intervention as a key approach to maximize therapeutic efficacy and opens the door to the development of precise NASH treatments. | José M Mato Cristina Alonso Mazen Noureddin Shelly C Lu | 2019 | World Journal of Gastroenterology2019，25，24： | 19 |
| 3 | Relationship between Fusobacterium nucleatum,inflammatory mediators and microRNAs in colorectal carcinogenesis显示文摘AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4. | Marcela Alcantara Proenca Joice Matos Biselli Maysa Succi Fábio Eduardo Severino Gustavo Noriz Berardinelli Alaor Caetano Rui Manuel Reis David J Hughes Ana Elizabete Silva | 2018 | World Journal of Gastroenterology2018，24，47： | 15 |
| 4 | Pancreatic ductal system obstruction and acute recurrent pancreatitis显示文摘Acute recurrent pancreatitis is a clinical entity largely associated with pancreatic ductal obstruction. This latter includes congenital variants, of which pancreas divisum is the most frequent but also controversial, chronic pancreatitis, tumors of the pancreaticobiliary junction and sphincter of Oddi dysfunction. This review summarizes current knowledge about diagnostic work-up and therapy of these conditions. | M Delhaye C Matos M Arvanitakis J Devière | 2008 | World Journal of Gastroenterology2008，14，7： | 12 |
| 5 | Engineering nanoparticles for targeting rheumatoid arthritis: Past, present, and future trends显示文摘风湿性关节炎(RA ) 是 synovial 关节发炎和软骨和骨头织物破坏描绘的长期的煽动性的疾病。尽管在那里存在为 RA 的一些处理策略,他们不完全安全、有效。因此,为明确地,目标 inflamed/swollen 连接的 RA 开发并且测试并且同时稀释另外的可能的损坏到健康纸巾新药是重要的。当为对待 RA 想象精确的药时,纳米技术能是一种好选择考虑。通过 nanoparticles 的使用,增加治疗学的 bioavailability 和 bioactivity 并且启用到损坏关节的选择指向是可能的。此处,用为 RA 的处理的 nanoparticles 的最近的研究,也就是与 liposomes,聚合 nanoparticles, dendrimers,和金属性的 nanoparticles,被考察了。这些治疗学的策略在由传统的药在那上改进处理显示出大诺言。这些研究的结果证实 nanoparticles 的使用的可行性主要由于他们的 biocompatibility,低毒性,控制版本,和选择的药交货到在动物 RA 模型的煽动的纸巾。因此,宣称在不久的将来,纳米技术将为象 RA 那样的人的疾病在先进治疗和病人特定的治疗起一个关键作用是可能的。 | Isabel Matos Oliveira Cristiana Goncalves Rui Lufs Reis Joaquim Miguel Oliveira | 2018 | Nano Research2018，11，9： | 11 |
| 6 | Thymosin alpha 1:A comprehensive review of the literature显示文摘Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying,enhancing,and restoring immune function.Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies,as an enhancer of vaccine response,and as a means of curbing morbidity and mortality in sepsis and numerous infections.Studies have postulated that thymosin alpha 1 could help improve the outcome in severely ill corona virus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how thymosin alpha 1 could prevent the excessive activation of T cells.In this review,we discuss key literature on the background knowledge and current clinical uses of thymosin alpha 1.Considering the known biochemical properties including antibacterial and antiviral properties,timehonored applications,and the new promising findings regarding the use of thymosin,we believe that thymosin alpha 1 deserves further investigation into its antiviral properties and possible repurposing as a treatment against severe acute respiratory syndrome coronavirus-2. | Asimina Dominari Donald Hathaway III Krunal Pandav Wanessa Matos Sharmi Biswas Gowry Reddy Sindhu Thevuthasan Muhammad Adnan Khan Anoopa Mathew Sarabjot Singh Makkar Madiha Zaidi Michael Maher Mourad Fahem Renato Beas Valeria Castaneda Trissa Paul John Halpern Diana Baralt | 2020 | World Journal of Virology2020，9，5： | 11 |
| 7 | Methionine adenosyltransferases in liver cancer显示文摘Methionine adenosyltransferases(MATs)are essential enzymes for life as they produce S-adenosylmethionine(SAMe),the biological methyl donor required for a plethora of reactions within the cell.Mammalian systems express two genes,MAT1A and MAT2A,which encode for MATα1 and MATα2,the catalytic subunits of the MAT isoenzymes,respectively.A third gene MAT2B,encodes a regulatory subunit known as MATβwhich controls the activity of MATα2.MAT1A,which is mainly expressed in hepatocytes,maintains the differentiated state of these cells,whilst MAT2A and MAT2B are expressed in extrahepatic tissues as well as non-parenchymal cells of the liver(e.g.,hepatic stellate and Kupffer cells).The biosynthesis of SAMe is impaired in patients with chronic liver disease and liver cancer due to decreased expression and inactivation of MATα1.A switch from MAT1A to MAT2A/MAT2B occurs in multiple liver diseases and during liver growth and dedifferentiation,but this change in the expression pattern of MATs results in reduced hepatic SAMe level.Decades of study have utilized the Mat1a-knockout(KO)mouse that spontaneously develops non-alcoholic steatohepatitis(NASH)and hepatocellular carcinoma(HCC)to elucidate a variety of mechanisms by which MAT proteins dysregulation contributes to liver carcinogenesis.An increasing volume of work indicates that MATs have SAMe-independent functions,distinct interactomes and multiple subcellular localizations.Here we aim to provide an overview of MAT biology including genes,isoenzymes and their regulation to provide the context for understanding consequences of their dysregulation.We will highlight recent breakthroughs in the field and underscore the importance of MAT’s in liver tumorigenesis as well as their potential as targets for cancer therapy. | Ben Murray Lucia Barbier-Torres Wei Fan JoséM Mato Shelly C Lu | 2019 | World Journal of Gastroenterology2019，25，31： | 10 |
| 8 | Toll-like receptor 9 polymorphisms and Helicobacter pylori influence gene expression and risk of gastric carcinogenesis in the Brazilian population显示文摘BACKGROUND Toll-like receptors(TLRs)are the first line of host defense,and are involved in Helicobacter pylori(H.pylori)recognition and activation of both inflammatory and carcinogenic processes.The presence of single nucleotide polymorphisms(SNPs)in genes that activate the immune response may modulate the risk of precancerous lesions and gastric cancer(GC).Among them,Toll-like receptor 9(TLR9)polymorphisms have emerged with a risk factor of infectious diseases and cancer,however the studies are still inconclusive.AIM To evaluate whether TLR9 rs5743836 and rs187084 SNPs contribute to the risk of gastric carcinogenesis,and its influence on mRNA expression.METHODS A case-control study was conducted to evaluate two TLR9 SNPs(TLR9-1237 TCrs5743836 and TLR9-1486 CT-rs187084)in chronic gastritis(CG)and GC patients.A total of 609 DNA samples of peripheral blood[248 CG,161 GC,and 200 samples from healthy individuals(C)]were genotyped by polymerase chain reaction-restriction fragment length polymorphism.All samples were tested for the H.pylori infection using Hpx1 and Hpx2 primers.Quantitative polymerase chain reaction by TaqMan?assay was used to quantify TLR9 mRNA from fresh gastric tissues(48 GC,26 CG,and 14 C).RESULTS For TLR9-1237,the TC+CC or CC genotypes were associated with a higher risk of GC than C[recessive model odds ratio(OR)=5.01,95%confidence interval(CI):2.52-9.94,P<0.0001],and the CG(recessive model OR=4.63;95%CI:2.44-8.79,P<0.0001)groups.For TLR9-1486,an association between the CT+TT genotypes and increased risk of both GC(dominant model OR=2.72,95%CI:1.57-4.72,P<0.0001)and CG(dominant model OR=1.79,95%CI:1.15-2.79,P=0.0094)was observed when compared to the C group.Moreover,the presence of TLR9-1237 TC/CC+TLR9-1486 CC genotypes potentiate the risk for this neoplasm(OR=18.57;95%CI:5.06-68.15,P<0.0001).The TLR9 mRNA level was significantly higher in the GC group(RQ=9.24,P<0.0001)in relation to the CG group(RQ=1.55,P=0.0010)and normal mucosa(RQ=1.0).When the samples were grouped according to the polymorphic genotypes and the presence of H.pylori infection,an influence of TLR9-1237 TC+CC polymorphic genotypes(P=0.0083)and H.pylori infection(P<0.0001)was observed on the upregulation of mRNA expression.CONCLUSION Our findings show that TLR9 rs5743836 and rs187084 polymorphisms are associated with a higher risk of carcinogenesis gastric,and that TLR9 mRNA levels can be modulated by TLR9-1237 TC+CC variant genotypes and H.pylori infection. | Manoela Dias Susi de Matos Lourenco Caroline Lucas Trevizani Rasmussen Spencer Luis Marques Payao Ana Flavia Teixeira Rossi Ana Elizabete Silva Juliana Garcia de Oliveira-Cucolo | 2019 | World Journal of Gastrointestinal Oncology2019，11，11： | 9 |
| 9 | Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review显示文摘BACKGROUND S-adenosylmethionine(AdoMet)is a metabolically pleiotropic molecule used to treat intrahepatic cholestasis(IHC)and chronic liver diseases.While the efficacy of AdoMet has been demonstrated previously,it has not been systematically investigated within the early weeks of treatment.AIM To systematically review the early treatment efficacy of AdoMet in adult patients with IHC.METHODS Studies reporting the efficacy of intravenous,intramuscular,or oral forms of AdoMet within 8 wk of treatment initiation were considered;three randomized and six non-randomized studies were eligible for inclusion(PROSPERO registration number CRD42018090936).Of the three randomized studies,two were double-blind and placebo-controlled,and one was comparator-controlled with unclear blinding and a relatively high risk of bias.Mean serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),and gamma-glutamyl transferase(γGT)following AdoMet treatment vs placebo,comparator,or baseline were summarized to determine differences in liver enzymes.Changes in patient-reported clinical symptoms of cholestasis were also summarized.RESULTS Both placebo-controlled randomized studies reported significant reductions in serum ALT levels with AdoMet vs placebo within 2 wk.One of these also reported significant ALP reductions,and the other reported significant AST andγGT reductions within 2 wk.The comparator-controlled randomized study,which had a number of notable limitations,reported significant reductions in serum ALT and AST levels with AdoMet vs potassium magnesium aspartate within 4 wk,but not within2 wk.All of the non-randomized studies(4/4)that investigated ALT,AST,ALP and/orγGT reported significant reductions in at least two of these parameters within 2 wk.Of the five studies that evaluated fatigue,reductions were observed within 2 wk in one randomized and two nonrandomized studies.The remaining two non-randomized studies reported improvements in fatigue within 6 and 8 wk.Of the four studies reporting symptoms of depression,two non-randomized studies observed improvements within 2 wk and the other two observed improvements within 17 d and 8 wk.CONCLUSION Data from both randomized and non-randomized studies suggest that AdoMet improves some biochemical liver parameters and symptoms of cholestasis within 2 wk,with further improvements observed in some studies after 4 and 8 wk of treatment. | Mazen Noureddin Suntje Sander-Struckmeier JoséM Mato | 2020 | World Journal of Hepatology2020，12，2： | 8 |
| 10 | Is autoimmune hepatitis a frequent finding among HCV patients with intense interface hepatitis?显示文摘AIM:To evaluate the overlap of autoimmune hepatitis in hepatitis C virus(HCV)-infected patients with intense interface hepatitis.METHODS:Among 1759 patients with hepatitis C submitted to liver biopsy,92(5.2%) presented intense interface hepatitis.These patients were evaluated regarding the presence of antinuclear antibody(ANA),anti-smooth muscle antibody(SMA) and anti-liver/kidney microsomal antibody(LKM-1),levels of γ-globulin and histological findings related to autoimmune hepatitis(plasma cell infiltrate and presence of rosettes).RESULTS:Among patients with hepatitis C and intense interface hepatitis there was a low prevalence of autoantibodies(ANA=12%,SMA=5%,LKM-1=0%) and the median γ-globulin level was within the normal range.Typical histological findings of autoimmune disease were observed in only two cases(2%).After applying the score for diagnosis of autoimmune hepatitis,only one patient was classified with a definitive diagnosis of autoimmune hepatitis.Since overlap with autoimmune hepatitis was not the explanation for the intense necroinflammatory activity in patients with chronic hepatitis C we sought to identify the variables associated with this finding.The presence of intense interface hepatitis was associated with more advanced age,both at the time of infection and at the time of the biopsy,and higher prevalence of blood transfusion and alcohol abuse.CONCLUSION:Although possible,overlap with autoimmune hepatitis is a very rare association in HCV-infected patients with intense interface hepatitis,an unusual presentation which seems to be related to other host variables. | Rosilene G Badiani Vitória Becker Renata M Perez Carla AL Matos Lara B Lemos Valéria P Lanzoni Luis Eduardo C Andrade Alessandra Dellavance Antonio Eduardo B Silva Maria Lucia G Ferraz | 2010 | World Journal of Gastroenterology2010，16，29： | 7 |
| 11 | Focal liver lesions:Practical magnetic resonance imaging approach显示文摘With the widespread of cross-sectional imaging, a growth of incidentally detected focal liver lesions(FLL) has been observed. A reliable detection and characterization of FLL is critical for optimal patient management. Maximizing accuracy of imaging in the context of FLL is paramount in avoiding unnecessary biopsies, which may result in post-procedural complications. A tremendous development of new imaging techniques has taken place during these last years. Nowadays, Magnetic resonance imaging(MRI) plays a key role in management of liver lesions, using a radiation-free technique and a safe contrast agent profile. MRI plays a key role in the non-invasive correct characterization of FLL. MRI is capable of providing comprehensive and highly accurate diagnostic information, with the additional advantage of lack of harmful ionizing radiation. These properties make MRI the mainstay for the noninvasive evaluation of focal liver lesions. In this paper we review the state-of-the-art MRI liver protocol, briefly discussing different sequence types, the unique characteristics of imaging non-cooperative patients and discuss the role of hepatocyte-specific contrast agents. A review of the imaging features of the most common benign and malignant FLL is presented, supplemented by a schematic representation of a simplistic practical approach on MRI. | António P Matos Fernanda Velloni Miguel Ramalho Mamdoh AlObaidy Aruna Rajapaksha Richard C Semelka | 2015 | World Journal of Hepatology2015，7，16： | 6 |
| 12 | Definition of the Portuguese frameworks with international relevance as an input for the European geological heritage characterisation显示文摘 | J. Brilha C. Andrade A. Azeredo F.J.A.S. Barriga M. Cachāo2 H. Couto P.P. Cunha J.A. Crispim P. Dantas L. V. Duarte M. C Freitas H.M. Granja M.H. Henriques P. Henriques L. Lopes J. Madeira J.M.X. Matos F. Noronha J. Pais J. Pifarra M.M. Ramalho J.M.R.S. Relvas A. Ribeiro A. Santos V.F.Santos P. Terrinha | 2005 | Episodes2005，28，3： | 5 |
| 13 | Role of sex hormones in gastrointestinal motility in pregnant and non-pregnant rats显示文摘AIM: To correlate gastric contractility, gastrointestinal transit, and hormone levels in non-pregnant(estrous cycle) and pregnant rats using noninvasive techniques. METHODS: Female rats(n = 23) were randomly divided into(1) non-pregnant,(contractility, n =6; transit, n = 6); and(2) pregnant(contractility, n = 5; transit, n = 6). In each estrous cycle phase or at 0, 7, 14, and 20 d after the confirmation of pregnancy, gastrointestinal transit was recorded by AC biosusceptometry(ACB), and gastric contractility was recorded by ACB and electromyography. After each recording, blood samples were obtained for progesterone and estradiol determination. RESULTS: In the estrous cycle, despite fluctuations of sex hormone levels, no significant changes in gastrointestinal motility were observed. Days 7 and 14 of pregnancy were characterized by significant changes in the frequency of contractions(3.90 ± 0.42 cpm and 3.60 ± 0.36 cpm vs 4.33 ± 0.25 cpm) and gastric emptying(168 ± 17 min and 165 ± 15 min vs 113 ± 15 min) compared with day 0. On these same days, progesterone levels significantly increased compared with control(54.23 ± 15.14 ng/m L and 129.96 ± 30.52 ng/mL vs 13.25 ± 6.31 ng/mL). On day 14, we observed the highest level of progesterone and the lowest level of estradiol compared with day 0(44.3 ± 15.18 pg/mL vs 24.96 ± 5.96 pg/mL). CONCLUSION: Gastrointestinal motility was unaffected by the estrous cycle. In our data, high progesterone and low estradiol levels can be associated with decreased contraction frequency and slow gastric emptying. | Juliana Fernandes Matos Madileine Francely Americo Yuri Karen Sinzato Gustavo Tadeu Volpato Luciana Aparecida Corá Marcos Felipe Freitas Calabresi Ricardo Brandt Oliveira Debora Cristina Damasceno Jose Ricardo Arruda Miranda | 2016 | World Journal of Gastroenterology2016，22，25： | 5 |
| 14 | Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation显示文摘BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation. | David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso María Luz Martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato | 2020 | World Journal of Gastroenterology2020，26，34： | 5 |
| 15 | Characterization of the Topography and Wettability of English Weed Leaves and Biomimetic Replicas显示文摘 | Pedro Miguel Matos Pereira Ana Sofia Moita Gabriel Amaro Monteiro Duarte Miguel Franca Prazeres | 2014 | Journal of Bionic Engineering2014，11，3： | 5 |
| 16 | Aging and menopause reprogram osteoclast precursors for aggressive bone resorption显示文摘Women gradually lose bone from the age of〜35 years,but around menopause,the rate of bone loss escalates due to increasing bone resorption and decreasing bone formation levels,rendering these individuals more prone to developing osteoporosis.The increased osteoclast activity has been linked to a reduced estrogen level and other hormonal changes.However,it is unclear whether intrinsic changes in osteoclast precursors around menopause can also explain the increased osteoclast activity.Therefore,we set up a protocol in which CD14f blood monocytes were isolated from 49 female donors(40-66 years old).Cells were differentiated into osteoclasts,and data on differentiation and resorption activity were collected.Using multiple linear regression analyses combining in vitro and in vivo data,we found the following:(1)age and menopausal status correlate with aggressive osteoclastic bone resorption in vitro;(2)the type I procollagen N-terminal propeptide level in vivo inversely correlates with osteoclast resorption activity in vitro;(3)the protein level of mature cathepsin K in osteoclasts in vitro increases with age and menopause;and(4)the promoter of the gene encoding the dendritic cell-specific transmembrane protein is less methylated with age.We conclude that monocytes are'reprogrammed'in vivo,allowing them to'remember'age,the menopausal status,and the bone formation status in vitro,resulting in more aggressive osteoclasts.Our discovery suggests that this may be mediated through DNA methylation.We suggest that this may have clinical implications and could contribute to understanding individual differences in age-and menopause-induced bone loss. | Anais Marie Julie Moller Jean-Marie Delaisse Jacob Bastholm Olesen Jonna Skov Madsen Luisa Matos Canto Troels Bechmann Silvia Regina Rogatto Kent Soe | 2020 | Bone Research2020，8，3： | 4 |
| 17 | Peripheral and mesenteric serum levels of CEA and cytokeratins,staging and histopathological variables in colorectal adenocarcinoma显示文摘瞄准:为了评估在外设和 mes 伤寒浆液之间存在的差别,与颜色在病人 carcinoembryonic 铺平抗原(CEA ) 和 cytokeratins 表面的腺癌。方法:有颜色的 138 个病人表面的腺癌在在 1993 年 12 月和 2000 年 3 月之间的医院 Sao Paulo (UNIFESP-EPM 的外科的肠胃病学的纪律) 经历了外科的人,回顾地被分析。CEA 和 cytokeratin (TPA-M ) 之间的差别在外部血(P) 并且在 mes 伤寒血(M) 的层次被学习。协会在外设和 mes 伤寒层次和阶段和组织病理学说的变量(细胞分化,宏观的外观,肿瘤尺寸和淋巴、静脉的侵略的存在的度) 之间被调查。结果:差别在标记层次的数字价值被观察:CEA (M)(39.10 mg/L +/- 121.19 mg/L ) 对 CEA (P)(38.5 mg/L +/- 122.55 mg/L ) , P <
0.05;TPA-M (M)(325.06 U/L +/- 527.29 U/L ) 对 TPA-M (P)(279.48 U/L +/- 455.81 U/L ) , P <
0.01。mes 伤寒 CEA 层次在更先进的肿瘤是更高的(P <
0.01 ) ,在生长损害(34.44 mg/L +/- 93.07 mg/L )(P <
0.01 ) 并且与静脉的侵略(48.41 mg/L +/- 129.86 mg/L )(P <
0.05 ) 。外部 CEA 与更先进的阶段是更高的(P <
0.01 ) 并且在有静脉的侵略的损害(53.23 mg/L +/- 158.57 mg/L )(P <
0.05 ) 。病人表明了有更多的 TPA-M 层次预付肿瘤的伤寒、外部的增加的 mes (P <
0.01 并且 P <
0.01 ) 并且在非溃烂的损害[530.45 U/L +/- 997.46 U/L (P <
0.05 ) 并且 457.95 U/L +/- 811.36 U/L (P <
0.01 )] 。结论:肿瘤标记 CEA 和 cytokeratins 的 mes 伤寒层次比在这些的外部层次渲染表面的腺癌病人高。这些生物学的肿瘤标记的高水平与癌的传播的一个先进状态被联系。 | Ivan Gregório Ivankovics Luis César Fernandes Sarhan Sydeney Saad Delcio Matos | 2008 | World Journal of Gastroenterology2008，14，43： | 4 |
| 18 | Lymphocyte subsets in alcoholic liver disease显示文摘AIM:To compare lymphocyte subsets between healthy controls and alcoholics with liver disease.METHODS:The patient cohort for this study included individuals who were suspected to have alcoholic liver disease(ALD) and who had undergone liver biopsy(for disease grading and staging,doubts about diagnosis,or concurrent liver disease;n = 56).Normal controls included patients who were admitted for elective cholecystectomy due to non-complicated gallstones(n = 27).Formalin-fixed,paraffin-embedded liver biopsy specimens were sectioned and stained with hematoxylin and eosin and Perls' Prussian blue.The non-alcoholic steatohepatitis score was used to assess markers of ALD.Lymphocyte population subsets were determined by flow cytometry.T lymphocytes were identified(CD3+),and then further subdivided into CD4+ or CD8+ populations.B lymphocytes(CD19+) and natural killer(NK) cell numbers were also measured.In addition to assessing lymphocyte subpopulation differences between ALD patients and controls,we also compared subsets of alcoholic patients without cirrhosis or abstinent cirrhotic patients to normal controls.RESULTS:The patient cohort primarily consisted of older men.Active alcoholism was present in 66.1%.Reported average daily alcohol intake was 164.9 g and the average lifetime cumulative intake was 2211.6 kg.Cirrhosis was present in 39.3% of the patients and 66.1% had significant fibrosis(perisinusoidal and portal/periportal fibrosis,bridging fibrosis,or cirrhosis) in their liver samples.The average Mayo end-stage liver disease score was 7.6.No hereditary hemochromatosis genotypes were found.ALD patients(n = 56) presented with significant lymphopenia(1.5 × 109/L ± 0.5 × 109/L vs 2.1 × 109/L ± 0.5 × 109/L,P < 0.0001),due to a decrease in all lymphocyte subpopulations,except for NK lymphocytes:CD3+(1013.0 ± 406.2/mm3 vs 1523.0 ± 364.6/mm3,P < 0.0001),CD4+(713.5 ± 284.7/mm3 vs 992.4 ± 274.7/mm3,P < 0.0001),CD8+(262.3 ± 140.4/mm3 vs 478.9 ± 164.6/mm3,P < 0.0001),and CD19+(120.6 ± 76.1/mm3 vs 264.6 ± 88.0/mm3,P < 0.0001).CD8+ lymphocytes suffered the greatest reduction,as evidenced by an increase in the CD4+/CD8+ ratio(3.1 ± 1.3 vs 2.3 ± 0.9,P = 0.013).This ratio was associated with the stage of fibrosis on liver biopsy(rs = 0.342,P = 0.01) and with Child-Pugh score(rs = 0.482,P = 0.02).The number of CD8+ lymphocytes also had a positive association with serum ferritin levels(rs = 0.345,P = 0.009).Considering only patients with active alcoholism but not cirrhosis(n = 27),we found similar reductions in total lymphocyte counts(1.8 × 109/L ± 0.3 × 109/L vs 2.1 × 109/L ± 0.5 × 109/L,P = 0.018),and in populations of CD3+(1164.7 ± 376.6/mm3 vs 1523.0 ± 364.6/mm3,P = 0.001),CD4+(759.8 ± 265.0/mm3 vs 992.4 ± 274.7/mm3,P = 0.003),CD8+(330.9 ± 156.3/mm3 vs 478.9 ± 164.6/mm3,P = 0.002),and CD19+(108.8 ± 64.2/mm3 vs 264.6 ± 88.0/mm3,P < 0.0001).In these patients,the CD4+/CD8+ ratio and the number of NK lymphocytes was not significantly different,compared to controls.Comparing patients with liver cirrhosis but without active alcohol consumption(n = 11),we also found significant lymphopenia(1.3 × 109/L ± 0.6 × 109/L vs 2.1 × 109/L ± 0.5 × 109/L,P < 0.0001) and decreases in populations of CD3+(945.5 ± 547.4/mm3 vs 1523.0 ± 364.6/mm3,P = 0.003),CD4+(745.2 ± 389.0/mm3 vs 992.4 ± 274.7/mm3,P = 0.032),CD8+(233.9 ± 120.0/mm3 vs 478.9 ± 164.6/mm3,P < 0.0001),and CD19+(150.8 ± 76.1/mm3 vs 264.6 ± 88.0/mm3,P = 0.001).The NK lymphocyte count was not significantly different,but,in this group,there was a significant increase in the CD4+/CD8+ ratio(3.5 ± 1.3 vs 2.3 ± 0.9,P = 0.01).CONCLUSION:All patient subsets presented with decreased lymphocyte counts,but only patients with advanced fibrosis presented with a significant increase in the CD4+/CD8+ ratio. | Luís Costa Matos Paulo Batista Nuno Monteiro Joo Ribeiro Maria A Cipriano Pedro Henriques Fernando Giro Armando Carvalho | 2013 | World Journal of Hepatology2013，5，2： | 4 |
| 19 | 青少年和年轻成人先天性心脏病的心理社会远期转归显示文摘目的先天性心脏病(CHD)是一种在全球范围内高发的慢性疾病,通常在出生时或出生前确诊。由于诊断以及早期药物和手术治疗的条件较好,患者的生存率达到90%,并且生存时间不断延长,面临着生活中的各种挑战。该研究探讨了不同人口统计学、临床和心理社会变量对CHD青少年和年轻成人患者的生活质量(QOL)感知、心理社会适应和精神障碍患病率的影响,评估CHD青少年和年轻成人患者的生活质量、心理社会适应和精神障碍发病率,确定哪些变量(人口统计学、临床和心理社会变量)对缓解压力、促进恢复起到积极作用,哪些变量起到不良作用。方法该研究入组了150名CHD患者(男87例,女63例),年龄12~26岁(平均年龄:17.45±3.373岁)。对参与者进行了关于社会支持、家庭教育方式、自我形象、人口统计信息和生理限制等方面的访谈。他们对标准化精神病学访谈(SADS-L)中的问题进行了回答,并填写了自我报告问卷,以进行生活质量(WHOQOL-BREF)和心理社会适应(YSR/ASR)的评估。结果所有参与者精神障碍的终身患病率为18.7%(女性25.4%,男性13.8%)。57.1%的参与者有过留级(平均1.53±0.804年)。与整体葡萄牙人相比,CHD患者的生活质量感知在社会关系、环境、身体和总体方面较好。而女性、学习成绩差、较少的社会支持、复杂性CHD、紫绀型CHD、中重度残留病灶、接受过手术和有生理限制患者生活质量感知较差。除了紫绀,所有这些变量也会引起较差的心理社会适应。结论女性CHD患者及学习成绩差且获得社会支持少的CHD患者的心理社会适应和生活质量较差。 | Maria Emlha Gulmaraes Arelas Catarina I. Pinto Patricia F. Vieira Flavio Teixeira Rosalia. Coelho Isabela Freitas Samantha Matos Marta Castro Sofia Sarmento Victor Viana Jorge Quintas Jose C. Areias | 2013 | 中国当代儿科杂志2013，15，10： | 3 |
| 20 | Association of Helicobacter pylori infection and giardiasis: Results from a study of surrogate markers for fecal exposure among children显示文摘AIM: To investigate whether Helicobacter pylori (H pykori)infection is associated with hepatitis A virus (HAV) infection, presence of enteroparasites, and other surrogates of fecal exposure.METHODS: We conducted a cross-sectional study in 121 children consecutively admitted at a pediatric hospital inSalvador, Brazil.H pylori and HAV infection were identified by the presence of serum antibodies. Stool specimens were examined for the presence of ova and parasites. A structured questionnaire inquiring about sanitary conditions and life style was applied to each subject. RESULTS: Fifty-one of the 121 children (42.1%) werefound to be seropositive for H pylori, and 45 (37.2%) for HAV. The seroprevalence ofHpyloriand HAV both increased significantly with age. Cross-tabulation of data showed that 26 (21.5%) were seropositive and 51 (42.1%) were negative for bothHpyloriand HAV antibodies (χ2 = 7.18,OR = 2.8, CI 1.30-5.97). The age adjusted OR for an HAV-infected child being H pylori positive was 2.3 (CI1.02-5.03). The agreement between H pylori and HAVseropositivity was fair (κ = 0.24). After controlling for possible confounding, the variables remaining independently associated with seropositivity to H pyloriwere age,presence of Giardia lamblia in feces (OR = 3.2, 95%CI, 1.1-9.5) and poor garbage disposal quality (OR = 2.4,95%CI, 1.1-5.1).CONCLUSION: Our data suggest that H pylori infection is associated with surrogate markers of fecal exposure. Thus, we conclude that the fecal-oral route is relevant in the transmission of HP among children in an urban setting of a developing country. The association observed between G. lamblia and H pylori infection may have several explanations. Further studies to investigate this relationship are warranted. | Edson Duarte Moreira Jr Victor Bastos Nassri Rafaela Sousa Santos Junísia Ferraz Matos Wilson Andrade de Carvalho Célia Stolve Silvani Círia Santana e Sant'Ana | 2005 | World Journal of Gastroenterology2005，11，18： | 3 |
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