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Adenosine A1 receptor activation inhibits histamine release in gastric enterochromaffin-like cells

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BIOCELL 2015年第2期39卷 5-8页

作者： Rafael Martins de OLIVEIRA Carolina Bernardi STEFANI Angélica Aparecida Antoniellis SILVEIRA marcelo lima ribeiro Alessandra GAMBERO Clinical Pharmacology and Gastroenterology Unit São Francisco University Medical SchoolBragança PaulistaSPBrazil.

Adenosine acts as a gastroprotective factor decreasing inflammation and reducing gastric acid secretion. Quantitative RT-PCR was used to determine the expression of the adenosine receptor genes (A1AR, A2AAR, A2BAR and A3AR) and that of the gastrin receptor B gene (CCKBR) in isolated, short-term cultured enterochromaffin-like (ECL) cells. Both the A1AR and the CCKBR genes were expressed at a level high-er than the other genes. Also, the effect of 2-chloroadenosine, a stable agonist of A1 and A2A receptors, was explored on ECL cells, with a resulting inhibition of both basal and gastrin-stimulated histamine release. Also, dipropylcyclopentylxanthine (DPCPX), a selective A1 antagonist, prevented the inhibitory effects of 2-chloro-adenosine, suggesting the effect of 2-chloroadenosine is mediated by A1 receptors. It is concluded that isolated, short-term cultured ECL cells are a suitable model for studies relating gene expression and function, and that the gastroprotective actions of adenosine are at least partly mediated through A1 receptors.

关键词： Gastrin 2-chloroadenosine DPCPX

Hepcidin expression in colon during trinitrobenzene sulfonic acid-induced colitis in rats

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World Journal of Gastroenterology 2014年第15期20卷 4345-4352页

作者： Erica Martins Ferreira Gotardo Gilberto de Almeida ribeiro Thayane Rodrigues Leite Clemente Camila Henrique Moscato Renata Bortolin Guerra Tome Thalita Rocha Jose Pedrazzoli Jr marcelo lima ribeiro Alessandra Gambero Clinical Pharmacology and Gastroenterology Unit Sao Francisco University Medical SchoolBraganca PaulistaSP 12916-900Brazil

AIM:To investigate hepcidin expression,interleukin-6(IL-6)production and iron levels in the rat colon in the presence of trinitrobenzene sulfonic acid(TNBS)-induced ***:In rats,we evaluated the severity of colitis induced by repeated TNBS administration using macroscopic and microscopic scoring systems and myeloperoxidase activity *** colonic levels of hepcidin,tumor necrosis factor alpha(TNF-α),IL-10 and IL-6 were measured by Enzyme-Linked Immunosorbent Assay,and hepcidin-25 expression and iron deposition were analyzed by immunohistochemistry and the Prussian blue reaction,***-3 phosphorylation was assessed by Western blot *** parameters,iron and transferrin levels,and transferrin saturation were also ***,the ability of iron,pathogen-derived molecules and IL-6 to induce hepcidin expression in HT-29 cells was ***:Repeated TNBS administration to rats resulted in macroscopically and microscopically detectable colon lesions and elevated colonic myeloperoxidase ***-25 protein levels were increased in colonic surface epithelia in colitic rats(10.2±4.0pg/mg protein vs 71.0±8.4 pg/mg protein,P<0.01).Elevated IL-6 levels(8.2±1.7 pg/mg protein vs 14.7±0.7 pg/mg protein,P<0.05),TNF-αlevels(1.8±1.2pg/mg protein vs 7.4±2.1 pg/mg protein,P<0.05)and Stat-3 phosphorylation were also *** alterations in iron homeostasis,hepcidin levels and anemia were not detected in colitic *** deposition in the colon was only observed during *** gene expression was increased in HT-29 cells after IL-6 and lipopolysaccharide[a toll-like receptor 4(TLR-4)ligand]***,ferric citrate and peptidoglycan(a TLR-2 ligand)were unable to alter the in vitro expression of hepcidin in HT-29 ***:Colitis increased local hepcidin-25 expression,which was associated with the IL-6/Stat-3 signaling *** increase in local iron sequestration was also

关键词： Hepcidin-25, Interleukin-6, Iron, Stat-3, Anemia, Toll-like receptor 4

Downregulation of TNFR2 decreases survival gene expression,promotes apoptosis and affects the cell cycle of gastric cancer cells

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World Journal of Gastroenterology 2022年第24期28卷 2689-2704页

作者： Ana Flávia Teixeira Rossi Fernanda da Silva Manoel-Caetano Joice Matos Biselli Ágata Silva Cabral Marilia de Freitas Calmon Saiki marcelo lima ribeiro Ana Elizabete Silva Department of Biological Sciences Sao Paulo State University(UNESP)São Josédo Rio Preto 15054-000São PauloBrazil Clinical Pharmacology and Gastroenterology Unit São Francisco University(USF)Bragança Paulista 12916-900São PauloBrazil

BACKGROUND Chronic inflammation due to Helicobacter pylori(***)infection promotes gastric *** necrosis factor-α(TNF-α),a key mediator of inflammation,induces cell survival or apoptosis by binding to two receptors(TNFR1 and TNFR2).TNFR1 can induce both survival and apoptosis,while TNFR2 results only in cell *** dysregulation of these processes may contribute to *** To evaluate the effects of TNFR1 and TNFR2 downregulation in AGS cells treated with *** extract on the TNF-α*** AGS cell lines containing TNFR1 and TNFR2 receptors downregulated by specific shRNAs and nonsilenced AGS cells were treated with *** extract for 6 ***,quantitative polymerase chain reaction with TaqMan®assays was used for the relative quantification of the mRNAs(TNFA,TNFR1,TNFR2,TRADD,TRAF2,CFLIP,NFKB1,NFKB2,CASP8,CASP3)and miRNAs(miR-19a,miR-34a,miR-103a,miR-130a,miR-181c)related to the TNF-αsignalling *** cytometry was employed for cell cycle analysis and apoptosis *** In nonsilenced AGS cells,*** extract treatment increased the expression of genes involved in cell survival and inhibited both apoptosis(NFKB1,NFKB2 and CFLIP)and the TNFR1 ***1 downregulation significantly decreased the expression of the TRADD and CFLIP genes,although no change was observed in the cellular process or miRNA *** contrast,TNFR2 downregulation decreased the expression of the TRADD and TRAF2 genes,which are both important downstream mediators of the TNFR1-mediated pathway,as well as that of the NFKB1 and CFLIP genes,while upregulating the expression of miR-19a and ***,a reduction in the number of cells in the G0/G1 phase and an increase in the number of cells in the S phase were observed,as well as the promotion of early *** Our findings mainly highlight the important role of TNFR2 in the TNF-αpathway in gastric cancer,indicating that silencing it can reduce the

关键词： Gastric cancer Helicobacter pylori Tumour necrosis factor-αsignalling pathway TNFR1 TNFR2 miRNAs

Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice

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World Journal of Hepatology 2015年第24期7卷 2551-2558页

作者： Simone Coghetto Acedo Cintia Rabelo e Paiva Caria érica Martins Ferreira Gotardo José Aires Pereira José Pedrazzoli marcelo lima ribeiro Alessandra Gambero Clinical Pharmacology and Gastroenterology Unit Sao Francisco University Medical School

AIM:To study pentoxifylline effects in liver and adipose tissue inflammation in obese mice induced by high-fat diet(HFD).METHODS: Male swiss mice(6-wk old) were fed a highfat diet(HFD; 60% kcal from fat) or AIN-93(control diet; 15% kcal from fat) for 12 wk and received pentoxifylline intraperitoneally(100 mg/kg per day) for the last 14 d. Glucose homeostasis was evaluated by measurements of basal glucose blood levels and insulin tolerance test two days before the end of the protocol. Final body weight was assessed. Epididymal adipose tissue was collected and weighted for adiposity evaluation. Liver and adipose tissue biopsies were homogenized in solubilization buffer and cytokines were measured in supernatant by enzyme immunoassay or multiplex kit, respectively. Hepatic histopathologic analyses were performed in sections of paraformaldehyde-fixed, paraffin-embedded liver specimens stained with hematoxylin-eosin by an independent pathologist. Steatosis(macrovesicular and microvesicular), ballooning degeneration and inflammation were histopathologically determined. Triglycerides measurements were performed after lipid extraction in liver tissue. RESULTS: Pentoxifylline treatment reduced microsteatosis and tumor necrosis factor(TNF)-α in liver(156.3 ± 17.2 and 62.6 ± 7.6 pg/mL of TNF-α for non-treated and treated obese mice, respectively; P < 0.05). Serum aspartate aminotransferase levels were also reduced(23.2 ± 6.9 and 12.1 ± 1.6 U/L for nontreated and treated obese mice, respectively; P < 0.05) but had no effect on glucose homeostasis. In obese adipose tissue, pentoxifylline reduced TNF-α(106.1 ± 17.6 and 51.1 ± 9.6 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) and interleukin-6(340.8 ± 51.3 and 166.6 ± 22.5 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) levels; however, leptin(8.1 ± 0.7 and 23.1 ± 2.9 ng/mL for non-treated and treated lean mice, respectively; P < 0.05) and plasminogen activator inhibitor-1(600.2 ± 32.3

关键词： Pentoxifylline Steatosis Obesity Adipose tissue Adipokine Tumor necrosis factor-α

Giant squamous cell carcinoma of the gallbladder: A case report

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World Journal of Clinical Cases 2019年第18期7卷 2787-2793页

作者： marcelo AF ribeiro Junior Murillo de lima Favaro Stephanie Santin Cintia Magalhaes Silva Ana Paula Marconi Iamarino Department of Acute Care and Trauma Surgery Hospital MoriahSao Paulo 04081000Brazil Department of Surgery University of Santo AmaroSao Paulo 04829- 300Brazil Department of Surgery Hospital MoriahUniversity of Santo AmaroSao Paulo 04829-300Brazil Medical Student University of Santo AmaroSao Paulo 04829-300Brazil Department of Surgery Hospital MoriahHospital MoriahSao Paulo 04829-300Brazil

BACKGROUND Gallbladder cancer is the most common malignant tumor of the biliary tract. The majority of cases are adenocarcinoma. Squamous cell carcinoma is the histological type present in 12% of all neoplasias accounting for approximately 12% of gallbladder neoplasms. It can occur in its pure form reaching 1%-3% of the tumors. Many patients are at an advanced stage when diagnosed and have bad therapeutic efficacy. CASE SUMMARY A 45-year-old male patient presented with left flank pain for 1 year and irradiated to the mesogastric region. He denied fever, vomiting, and any other intestinal changes. He reported a weight loss of 10 kg in a period of 7 mo. He denied alcoholism, smoking, drug use, or prior illness. Computed tomography of the abdomen showed in the gallbladder fossa a voluminous mesogastric heterogeneous collection that had a thick and irregular capsule with liquid and gaseous contents. A predominantly hypoattenuating rounded material with partially calcified margins measuring about 2.0 cm related to gallstone was also emphasized. No lymphadenomegalies or free fluid was observed in the abdominal cavity. Patient underwent laparotomy where a huge tumor was observed affecting the transverse colon and gallbladder. This mass was resected en bloc removing gallbladder and transverse colon together with corresponding mesocolon and regional lymphadenectomy. There were no complications in the postoperative period. Although oncological treatment was performed, the patient died 6 mo after surgery. CONCLUSION Squamous cell carcinoma represents a rare disease. Patients often present with large, bulky tumors with involvement of adjacent organs. In spite of progress in surgical techniques and adjuvant chemotherapy, the prognosis remains poor.

关键词： Squamous cell Carcinoma Gallbladder neoplasm Treatment Case report

Perspectives for the association between olfactory disturbances and depression in Parkinson's disease

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Neural Regeneration Research 2019年第4期14卷 591-592页

作者： Jessica L.Ilkiw marcelo M.S.lima Neurophysiology Laboratory Department of PhysiologyFederal University of Paraná

Non-motor disturbances in Parkinson’s disease:Globally,population aged 60 or over is growing and considering the World Bank predictions for the next 20 years it is expected that the number of Parkinson’s disease(PD)cases will double at the end of this period thus,reaching an impressive 13–39 million patients *** scenario is potentially associated with a significant global negative impact on public health systems particularly in countries with increased ageing populations such as the European countries,Asia and *** pathophysiology of PD involves the progressive degeneration of dopaminergic neurons of the substantia nigra pars compacta(SNpc)that triggers denervation of the nigrostriatal pathway and consequent significant reduction of dopamine in the dorsal *** process leads to a critical motor impairment scenario characterized by bradykinesia,rigidity,resting tremor,and postural instability(Emamzadeh and Surguchov,2018).However,several other non-motor disturbances develop earlier,thus,being considered as prodromal signs of the *** this sense,the literature is increasingly emphasizing the importance of investigating mood and olfactory disruptions as high sensitive benchmarks of the early-phase *** fact,the need for innovative early-phase diagnostic tools,as well as the elucidation of the pathophysiological mechanisms of such disturbances,is essential priority in the field of investigation of ***,in the year of 2015,a woman was known for an intriguing ability of“smell PD”.Her husband had lived with the disease for twenty years and during this process she noticed that his odor slowly changed to a musky ***,this woman could associate this particular smell with PD after meeting different people with this distinct odor in a charity for PD *** fact,this clever observation is aligned with studies showing that hyposmia is found decades before the motor *** type of anecdotal story,

关键词： Parkinson olfactory disturbances association

Distribution of trace metals and Pb isotopes in bottom sediments of the Murucupi River,North Brazil

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International Journal of Sediment Research 2016年第3期31卷 226-236页

作者： Diomar Cavalcante Oliveira Jean Michel Lafon marcelo de Oliveira lima Institute of Geosciences Federal University of Pára Environmental Section Evandro Chagas Institute

The Murucupi River belongs to the hydrographic network of the Para River estuary,at the southern portion of the Amazon River mouth,which consists of a fluvial-marine transitional zone under strong impact of both tidal and fluvial *** geochemical results obtained for bottom sediments from the Murucupi River,the Arrozal Channel,and the Para River indicate a natural variation of Pb,Cr,Cu,Zn,and Ni content among these water ways with no significant anthropogenic *** to the threshold effects level(TEL),the contents of trace metals do not offer risk to the local *** contrast,the differences in the Pb isotopic composition of sediments in the Murucupi River,the Arrozal Channel,and the Para River are *** isotopic signatures indicate an anthropogenic contribution of Pb in the Murucupi River originating from the domestic effluents of urban centers;industrial waste represented by red mud is not *** results demonstrate that the Pb isotopic signature is a prospective indicator for future contamination of bottom sediments by trace metals and is useful for identifying contaminants among the possible anthropogenic sources.

关键词： Bottom sediments Pb isotopes Trace metals Murucupi River Barcarena

Probe-based confocal endomicroscopy is accurate for differentiating gastric lesions in patients in a Western center

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Chinese Journal of Cancer Research 2018年第5期30卷 546-552页

作者： adriana vaz safatle-ribeiro elisa ryoka baba rodrigo corsato scomparin sheila friedrich faraj marcelo simas de lima luciano lenz bruno costa martins carla gusmon fábio shiguehissa kawaguti caterina pennacchi bruno zilberstein ulysses ribeiro jr. fauze maluf-filho Endoscopy Unit of Department of Gastroenterology Sao Paulo Cancer Institute University of Sao Paulo Medical School (ICESP-HCFMUSP) Sao Paulo 01246-000 Brazil

Objective： Probe-based confoeal laser endomicroscopy （pCLE） technique may improve the diagnosis of gastric mucosal lesions allowing acquisition of high-resolution in vivo images at the cellular and mierovaseular levels. This study aims to evaluate the accuracy of pCLE for the differential diagnosis of non-neoplastic and neoplastic gastric ***： Twenty gastric mucosal lesions from 10 patients were evaluated during endoscopic procedure and were examined by pCLE. Diagnostic pCLE was followed by biopsies or endoscopic resection of suspected lesions. A senior pathologist evaluated the specimens and was blinded to the pCLE ***： Patients＇ mean age was 68.3 （range, 42-83） years and six were men. Thirteen suspicious flat or elevated lesions （classified as 0-Is, 0-IIa or 0-IIa ＋ IIc） and seven pre-malignant lesions （atrophy and intestinal metaplasia） were evaluated. One patient was studied during his long-term follow-up after partial gastrectomy and presented severe atrophy, intestinal metaplasia, and xanthomas at the stump mucosa. The location of gastric lesions was in the body （n=10 lesions）, the antrum （n=9） and the incisura angularis （n=1）. All neoplastic lesions and all but one benign lesion were properly diagnosed by pCLE. pCLE incorrectly diagnosed one small antrum lesion as adenoma, however the final diagnosis was intestinal metaplasia. The final histological diagnosis was neoplastic in 9 and benign lesions in 11. In this small case series, pCLE accuracy was 95% （19/20 lesions）.Conclusions： pCLE is accurate for real time histology of gastric lesions, pCLE may change the management of patients with gastric mucosal lesions, guiding biopsies and endoscopic resection, and avoiding further diagnostic workup or unnecessary therapy.

关键词： Probe-based confocal endomieroscopy gastric cancer intestinal metaplasia atrophy gastric adenoma endoscopic resection

Progeny selections of coffee cultivar'Mundo Novo'with potential for the specialty coffee market

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Beverage Plant Research 2023年第1期3卷 1-11页

作者： Gabriela Ester Ferraz Marlon Enrique López Flávia Maria Avelar Gonçalves marcelo ribeiro Malta Renato ribeiro de lima Gladyston Rodrigues de Carvalho Lyndel WMeinhardt Dapeng Zhang Antonio Chalfun-Junior Institute of Natural Sciences Department of BiologyFederal University of LavrasLavrasMinas Gerais 37200900Brazil Honduran Foundation for Agricultural Research(FHIA) La LimaCortés 2067Honduras Empresa de Pesquisa Agropecuária de Minas Gerais(EPAMIG) Laboratory of Coffee QualityFederal University of Lavras CampusLavrasMinas Gerais 37200000Brazil Department of Statistics Federal University of LavrasLavrasMinas Gerais 37200900Brazil Empresa de Pesquisa Agropecuária de Minas Gerais(EPAMIG) Federal University of Lavras CampusLavrasMinas Gerais 37200900Brazil Sustainable Perennial Crops Laboratory United States Department of AgricultureAgricultural Research ServiceUSDAWest BeltsvilleMD 20705USA Institute of Natural Sciences Laboratory of Plant Molecular PhysiologyDepartment of BiologyFederal University of LavrasLavrasMinas Gerais 37200900Brazil

Coffee is one of the most popular beverages in the world with a global market worth over$USD 100 *** Brazil,the Arabica coffee(Coffea arabica)cultivar'Mundo Novo'is one of the most planted cultivars due to its high yield,growth vigor and ***,this traditional cultivar is generally not considered a good production source for specialty *** intra-cultivar variation and selecting'Mundo Novo'progenies with superior sensory quality may provide a viable option for coffee producers targeting the rapidly expanding specialty coffee *** present study analyzed cup quality attributes,agronomic characteristics and genetic identities of 14 genotypes selected from the putative progenies of'Mundo Novo'and assessed their potential as specialty coffee in *** quality was assessed using chemical and sensory analysis according to the methodology proposed by the Specialty Coffee Association(SCA)in six selected *** sensory quality,with sensory scores above 80 points was observed which qualified them in the very good and excellent quality *** identities of the 14 selections were verified using 96 SNP markers,based on 57 reference cultivars from the coffee collection of EPAMIG(Empresa de Pesquisa Agropecuária de Minas Gerais),*** and Bayesian clustering analysis generated consistent results and confirmed that all the 14 selections were progenies of'Mundo Novo'.Among them,the top three genotypes(SGAB 1,SGAB 7 and SGAB 8)were selected as promising genotypes,either for future genetic improvement or for direct use in the production of specialty coffee.

关键词： market potential Brazil