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1.
J Cancer Res Clin Oncol ; 146(1): 75-86, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31754833

RESUMO

PURPOSE: The enzymes gamma-glutamyl hydrolase (GGH) and folylpolyglutamate synthetase (FPGS) regulate intracellular folate concentrations needed for cell proliferation, DNA synthesis, and repair. High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1. METHODS: Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection. RESULTS: While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29-5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/low FPGS and low GGH/high FPGS. Patients without adjuvant treatment showed no significant difference. CONCLUSION: GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. High GGH and low FPGS expression is a useful independent predictor of poor outcomes in stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/biossíntese , Peptídeo Sintases/biossíntese , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/enzimologia , gama-Glutamil Hidrolase/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Quimioterapia Adjuvante , Combinação de Medicamentos , Feminino , Mucosa Gástrica/enzimologia , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Peptídeo Sintases/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem , gama-Glutamil Hidrolase/genética
2.
J Agric Food Chem ; 67(34): 9591-9600, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31414795

RESUMO

Process conditions that are applied to make structured soy-protein-based food commonly include high temperatures. Those conditions can induce protein oxidation, leading to a decrease in their susceptibility to proteolysis by digestive enzymes. We aimed to investigate the effects of thermomechanical processing on oxidation and in vitro gastric digestion of commercial soy protein ingredients. Samples were sheared at 100 to 140 °C and characterized for acid uptake, carbonyl content, electrophoresis, and surface hydrophobicity. The enzymatic hydrolysis was determined in simulated gastric conditions. Protein ingredients were already oxidized and showed higher surface hydrophobicity and hydrolysis rate compared with those of the processed matrices. However, no clear correlation between the level of carbonyls and the hydrolysis rate was found. Therefore, we conclude that gastric digestion is mostly driven by the matrix structure and composition and the available contact area between the substrate and proteolytic enzymes.


Assuntos
Digestão , Mucosa Gástrica/metabolismo , Proteínas de Soja/metabolismo , Mucosa Gástrica/enzimologia , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Interações Hidrofóbicas e Hidrofílicas , Modelos Biológicos , Oxirredução , Proteínas de Soja/química
3.
Cell Mol Biol (Noisy-le-grand) ; 65(3): 76-83, 2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30942158

RESUMO

The aim of this study is an investigation the protective effects of vitamin C (Vit C), vitamin E (Vit E), ß-carotene, sodium selenate combination in indomethacin-induced gastric mucosal damage in rats. Rats were divided into 6 groups. Group I: Intact animals (control). Group II: Control animals receiving Vit C (100 mg/kg/day), Vit E (100 mg/kg/day), ß-carotene (15 mg/kg/day) and sodium selenate (0.2 mg/kg/day) for 3 days. Group III: Animals receiving 25 mg/kg indomethacin. Group IV: Animals receiving Vit C, Vit E, ß-carotene and sodium selenate (in same doses) for 3 days 2 h before the administration of indomethacin. Group V: Animals receiving ranitidine (150 mg/kg) for 3 days. Group VI: Animals receiving ranitidine for 3 days 2 h before to the administration of indomethacin (in same dose and time). The administration of indomethacin caused a decrease in the levels of glutathione, mucus, hexosamine and in the activities of glutathione-S-transferase, sodium-potassium ATPase, thromboplastic activity and an increase in the aspartate and alanine amino transferase, alkaline phosphatase, catalase, lactate dehydrogenase, myeloperoxidase activities and sialic acid, lipid peroxidation and protein carbonyl levels.  Stomach caspase-8 immun+ cell numbers showed a slight increase while caspase-9 immun+ cell numbers reduced in indomethacin given group compared to control animals. Our results findings suggest that the combination of Vit C, Vit E, ß-carotene, sodium selenate and ranitidine has a protective effect on indomethacin-induced gastric mucosal injury of rats.


Assuntos
Antioxidantes/farmacologia , Mucosa Gástrica/lesões , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Caspases/metabolismo , Catalase/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/enzimologia , Mucosa Gástrica/patologia , Glutationa/sangue , Glutationa Transferase/metabolismo , Hexosaminas/metabolismo , Indometacina , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Mucinas/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Peroxidase , Ratos Sprague-Dawley , ATPase Trocadora de Sódio-Potássio/metabolismo
4.
J Biol Chem ; 294(20): 8238-8258, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-30940726

RESUMO

The subcellular mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in gastric cancer and normal mucosal cells is elusive because of the diverse cyclooxygenase-independent effects of these drugs. Using human gastric carcinoma cells (AGSs) and a rat gastric injury model, here we report that the NSAID indomethacin activates the protein kinase Cζ (PKCζ)-p38 MAPK (p38)-dynamin-related protein 1 (DRP1) pathway and thereby disrupts the physiological balance of mitochondrial dynamics by promoting mitochondrial hyper-fission and dysfunction leading to apoptosis. Notably, DRP1 knockdown or SB203580-induced p38 inhibition reduced indomethacin-induced damage to AGSs. Indomethacin impaired mitochondrial dynamics by promoting fissogenic activation and mitochondrial recruitment of DRP1 and down-regulating fusogenic optic atrophy 1 (OPA1) and mitofusins in rat gastric mucosa. Consistent with OPA1 maintaining cristae architecture, its down-regulation resulted in EM-detectable cristae deformity. Deregulated mitochondrial dynamics resulting in defective mitochondria were evident from enhanced Parkin expression and mitochondrial proteome ubiquitination. Indomethacin ultimately induced mitochondrial metabolic and bioenergetic crises in the rat stomach, indicated by compromised fatty acid oxidation, reduced complex I- associated electron transport chain activity, and ATP depletion. Interestingly, Mdivi-1, a fission-preventing mito-protective drug, reversed indomethacin-induced DRP1 phosphorylation on Ser-616, mitochondrial proteome ubiquitination, and mitochondrial metabolic crisis. Mdivi-1 also prevented indomethacin-induced mitochondrial macromolecular damage, caspase activation, mucosal inflammation, and gastric mucosal injury. Our results identify mitochondrial hyper-fission as a critical and common subcellular event triggered by indomethacin that promotes apoptosis in both gastric cancer and normal mucosal cells, thereby contributing to mucosal injury.


Assuntos
Apoptose/efeitos dos fármacos , GTP Fosfo-Hidrolases/metabolismo , Mucosa Gástrica/enzimologia , Indometacina/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/enzimologia , Dinâmica Mitocondrial/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Proteínas de Neoplasias/metabolismo , Proteína Quinase C/metabolismo , Neoplasias Gástricas/enzimologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Apoptose/genética , Linhagem Celular Tumoral , GTP Fosfo-Hidrolases/genética , Mucosa Gástrica/patologia , Humanos , Sistema de Sinalização das MAP Quinases/genética , Proteínas Associadas aos Microtúbulos/genética , Mitocôndrias/genética , Dinâmica Mitocondrial/genética , Proteínas Mitocondriais/genética , Proteínas de Neoplasias/genética , Proteína Quinase C/genética , Ratos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética
5.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(2): 215-221, 2019 02 28.
Artigo em Chinês | MEDLINE | ID: mdl-30890511

RESUMO

OBJECTIVE: To investigate the differentially expressed genes between gastric cancer and normal gastric mucosa by bioinformatics analysis, identify the important gene participating in the occurrence and progression of gastric cancer, and predict the functions of these genes. METHODS: The gene expression microarray data GSE100935 (including 18 gastric cancer samples and normal gastric mucosal tissues) downloaded from the GEO expression profile database were analyzed using Morpheus to obtain the differentially expressed genes in gastric cancer, and a cluster analysis heat map was constructed. The online database UALCAN was used to obtain the expression levels of these differentially expressed genes in gastric cancer and normal gastric mucosa. The prognostic value of the differentially expressed genes in gastric cancer was evaluated with Kaplan-Meier survival analysis. GO functional enrichment analysis was performed using Fun-Rich software, and the STRING database was exploited to establish a PPI network for the differentially expressed genes. RESULTS: A total of 45119 differentially expressed genes were identified from GSE100935 microarray data. Analysis with UALCAN showed an obvious high expression of EXD3 gene in gastric cancer, and survival analysis suggested that a high expression level of EXD3 was associated with a poorer prognosis of the patients with gastric cancer. GO functional enrichment analysis found that the differentially expressed genes in gastric cancer were involved mainly in the regulation of nucleotide metabolism and the activity of transcription factors in the cancer cells. CONCLUSIONS: EXD3 may be a potential oncogene in gastric cancer possibly in relation to DNA damage repair. The up-regulation of EXD3 plays an important role in the development and prognosis of gastric cancer, and may serve as an important indicator for prognostic evaluation of the patients.


Assuntos
Biologia Computacional , Exonucleases/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Neoplasias Gástricas/genética , Bases de Dados Genéticas , Mucosa Gástrica/química , Mucosa Gástrica/enzimologia , Perfilação da Expressão Gênica , Humanos , Prognóstico , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/mortalidade
6.
J Pathol ; 247(1): 35-47, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30168144

RESUMO

Chronic inflammation and intestinal metaplasia are strongly associated with gastric carcinogenesis. Kras activation and Pten deletion are observed in intestinal-type gastric cancer, and Cdh1 mutation is associated with diffuse-type gastric cancer. Although various mouse models of gastric carcinogenesis have been reported, few mouse lines enable gene manipulation selectively in the stomach. Here we established a Tff1-Cre bacterial artificial chromosome transgenic mouse line in an attempt to induce gene modification specifically in the gastric pit lineage. In the stomach, Tff1-Cre-mediated recombination was most evident in the pit lineage in the corpus and in entire antral glands; recombination was also observed in a few gastric chief and parietal cells. Outside the stomach, recombination was patchy throughout the intestines, and particularly frequently in the duodenum (Brunner glands), cecum, and proximal colon. In the stomachs of Tff1-Cre;LSL-KrasG12D mice, proliferating cell clusters expanded throughout the corpus glands, with foveolar cell expansion with ectopic Alcian blue-positive mucins, oxyntic atrophy, and pseudopyloric changes with spasmolytic polypeptide-expressing metaplasia; however, gastric cancer was not observed even at 12 months of age. Corpus-derived organoids from Tff1-Cre;LSL-KrasG12D mice exhibited accelerated growth and abnormal differentiation with a loss of chief and parietal cell markers. Tff1-Cre;Ptenflox/flox mice displayed similar changes to those seen in Tff1-Cre;LSL-KrasG12D mice, both with aberrant ERK activation within 3 months. In contrast, Tff1-Cre;Cdh1flox/flox mice initially showed signet ring-like cells that were rapidly lost with disruption of the mucosal surface, and later developed gastric epithelial shedding with hyperproliferation and loss of normal gastric lineages. Eventually, the glandular epithelium in Tff1-Cre;Cdh1flox/flox mice was completely replaced by squamous epithelium which expanded from the forestomach. Tff1-Cre mice offer an additional useful tool for studying gastric carcinogenesis both in vivo and in vitro. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Caderinas/deficiência , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Mucosa Gástrica/enzimologia , Gastrite/enzimologia , PTEN Fosfo-Hidrolase/deficiência , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias Gástricas/enzimologia , Animais , Caderinas/genética , Linhagem da Célula , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Cromossomos Artificiais Bacterianos , Mucinas Gástricas/genética , Mucinas Gástricas/metabolismo , Mucosa Gástrica/patologia , Gastrite/genética , Gastrite/patologia , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Integrases/genética , Metaplasia , Camundongos Transgênicos , PTEN Fosfo-Hidrolase/genética , Fenótipo , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Técnicas de Cultura de Tecidos , Fator Trefoil-1/genética
7.
Histochem Cell Biol ; 151(1): 21-28, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30159783

RESUMO

Parietal cells in the gastric mucosa are known not only as cells playing major roles in food digestion but also as cells bearing endocrine function. In addition to their production of gastrin and ghrelin, it has been recently revealed that these cells are also involved in the synthesis and secretion of estrogens with their expression of aromatase in experimental animals. Although aromatase activity has been detected in human gastric cancer cells and related cell lines, much less study has been done to ascertain the expression of the enzymatic activity in normal gastric mucosa. It has not been established which cell type is responsible for estrogen production in human gastric glands consisting of epithelial cells of several types. The aim of this study is to define the expression of aromatase by parietal cells in human gastric glands using immunohistochemical techniques. We retrieved formalin-fixed paraffin embedded materials of gastric biopsies from 16 patients (nine men, seven women). Colocalization of aromatase and H+/K+-ATPase ß-subunit indicated that positive cells are parietal cells, but not chief cells and mucous cells. Furthermore, immunoreactivity of aromatase was detected within gastric glands irrespective of age or sex. These results suggest that human parietal cells synthesize estrogens within gastric mucosa and subsequently secrete them to the portal vein via gastric vein, as they do in rats. These estrogens might influence liver functions in humans. The estrogenic effects related to liver dysfunction might also be attributed to them.


Assuntos
Aromatase/análise , Aromatase/biossíntese , Mucosa Gástrica/enzimologia , Células Parietais Gástricas/enzimologia , Aromatase/metabolismo , Biópsia , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Células Parietais Gástricas/metabolismo , Células Parietais Gástricas/patologia
8.
Exp Biol Med (Maywood) ; 243(15-16): 1161-1164, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30541347

RESUMO

IMPACT STATEMENT: Tissue transglutaminase (t-TG) is unique among TG enzymes because of its additional role in several physiological and pathological activities, including inflammation, fibrosis, and wound healing. The presence of t-TG has previously been described in the intestine of human and animal models, yet studies on t-TG activity in human gastric mucosa are missing. Helicobacter pylori infection is the major cause of gastritis and peptic ulcers. For the first time, our results show that t-TG activity was significantly higher in antral specimens of patients with chronic active gastritis associated with H. pylori infection compared to H. pylori negative chronic gastritis and normal antral mucosa. These findings suggest that t-TG has a role in the natural history of human gastritis, which requires further investigation but may be an avenue for new therapeutic options.


Assuntos
Dispepsia/patologia , Proteínas de Ligação ao GTP/metabolismo , Mucosa Gástrica/enzimologia , Gastrite/patologia , Infecções por Helicobacter/patologia , Transglutaminases/metabolismo , Adulto , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Dispepsia/microbiologia , Feminino , Mucosa Gástrica/metabolismo , Gastrite/microbiologia , Helicobacter pylori , Humanos , Itália , Masculino , Pessoa de Meia-Idade
9.
Gen Comp Endocrinol ; 267: 167-171, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29966658

RESUMO

Ghrelin is implicated in the regulation of gastric functional development. The octanoylation of ghrelin is critical for its physiological functions which dependent upon ghrelin O-acyltransferase (GOAT) catalyzation. To investigate the effect of GOAT on gastric acid secretion and expression of ghrelin in vitro. Primary cultures of gastric mucosal cells were challenged with 1.5 × 10-5, 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (The GOAT inhibitor), respectively, for 24 h in order to further clarify the effect of GOAT on H+-K+-ATPase activity. In vitro, GO-CoA-Tat significantly increased ghrelin and GOAT mRNA expression at 1.5 × 10-5, 1.5 × 10-4 and 1.5 × 10-3 mol/mL, and augmented cell total ghrelin secretion at 1.5 × 10-3 mol/mL. But cell acylated ghrelin secretion was reduced at 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). And cell acylated ghrelin synthesis was reduced at 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). In accordance with acylated ghrelin level, H+-K+-ATPase activity were decreased with 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). These results indicated that GOAT inhibitor decreases the acylated ghrelin level and H+-K+-ATPase activity in vitro.


Assuntos
Aciltransferases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Mucosa Gástrica/citologia , Mucosa Gástrica/enzimologia , Grelina/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Peptídeos/farmacologia , Aciltransferases/genética , Aciltransferases/metabolismo , Animais , Linhagem Celular , Meios de Cultura , Proteínas de Membrana , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
10.
FASEB J ; 32(10): 5378-5389, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29688807

RESUMO

Gastric epithelial cells infected with Helicobacter pylori acquire highly invasive and metastatic characteristics. The seven in absentia homolog (Siah)2, an E3 ubiquitin ligase, is one of the major proteins that induces invasiveness of infected gastric epithelial cells. We find that p300-driven acetylation of Siah2 at lysine 139 residue stabilizes the molecule in infected cells, thereby substantially increasing its efficiency to degrade prolyl hydroxylase (PHD)3 in the gastric epithelium. This enhances the accumulation of an oncogenic transcription factor hypoxia-inducible factor 1α (Hif1α) in H. pylori-infected gastric cancer cells in normoxic condition and promotes invasiveness of infected cells. Increased acetylation of Siah2, Hif1α accumulation, and the absence of PHD3 in the infected human gastric metastatic cancer biopsy samples and in invasive murine gastric cancer tissues further confirm that the acetylated Siah2 (ac-Siah2)-Hif1α axis is crucial in promoting gastric cancer invasiveness. This study establishes the importance of a previously unrecognized function of ac-Siah2 in regulating invasiveness of H. pylori-infected gastric epithelial cells.-Kokate, S. B., Dixit, P., Das, L., Rath, S., Roy, A. D., Poirah, I., Chakraborty, D., Rout, N., Singh, S. P., Bhattacharyya, A. Acetylation-mediated Siah2 stabilization enhances PHD3 degradation in Helicobacter pylori-infected gastric epithelial cancer cells.


Assuntos
Células Epiteliais , Mucosa Gástrica , Infecções por Helicobacter , Helicobacter pylori , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Proteólise , Neoplasias Gástricas , Ubiquitina-Proteína Ligases/metabolismo , Acetilação , Linhagem Celular Tumoral , Estabilidade Enzimática , Células Epiteliais/enzimologia , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Mucosa Gástrica/enzimologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/enzimologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Humanos , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
11.
Histol Histopathol ; 33(8): 815-823, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29451295

RESUMO

Gastrointestinal ischemia/reperfusion (I/R) generates pathological alterations that could lead to death. Early ischemic damage markers could be used to guide therapy and improve outcomes. AIM: To relate hypoxia-inducible factor 1α (HIF-1α) activation and inducible nitric oxide synthase (iNOS) expression to gastric impedance changes due to I/R damage. METHODS: Experimental animals were randomly distributed into 3 groups: control, ischemia (30 min) and I/R (60 min). Gastric ischemia was generated by celiac artery clamping for 30 min, and then blood flow was restored for 60 min. Impedance spectra and biopsies of the glandular portion were obtained for histological and immunohistochemical analyses. Immunodetection of both HIF-1α and iNOS was performed. RESULTS: Under ischemia and I/R conditions, there was an increase (p<0.05) in the impedance parameters. Histologically, under ischemic conditions, edema and necrosis were observed in epithelium and significant vascular congestion. In I/R condition, alterations of the glandular and luminal integrity were found, which generated areas of epithelial erosion. Immunohistochemical analysis of HIF-1α revealed an increase (p<0.01) in the number of immunoreactive cells in the ischemia (35.7±13.9) and I/R (119.9±18.8) conditions compared to the control (0.8±1.2). Immunodetection of iNOS showed an increase (p<0.01) in the number of cells expressing iNOS under the ischemia (5.4±2.9) and I/R conditions (27.4±11.3) was observed compared to the control (0.4±0.8). CONCLUSION: Early changes in impedance in response to I/R is related to histopathological changes, the nuclear stabilization and translocation of HIF-1α as well as expression of iNOS.


Assuntos
Mucosa Gástrica/enzimologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Óxido Nítrico Sintase Tipo II/metabolismo , Traumatismo por Reperfusão/enzimologia , Gastropatias/enzimologia , Transporte Ativo do Núcleo Celular , Animais , Biópsia , Modelos Animais de Doenças , Edema/enzimologia , Edema/patologia , Impedância Elétrica , Mucosa Gástrica/patologia , Masculino , Necrose , Estabilidade Proteica , Ratos Wistar , Traumatismo por Reperfusão/patologia , Gastropatias/patologia , Fatores de Tempo
12.
Eur J Nutr ; 57(1): 319-325, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27785565

RESUMO

PURPOSE: The term bioaccessibility refers to the proportion of a nutrient released from a complex food matrix during digestion and, therefore, becoming potentially available for absorption in the gastrointestinal tract. In the present study, we assessed the starch and protein bioaccessibility from a range of wheat endosperm products differing in particle size. METHODS: Five porridge meals (size A, flour, mean particle size 0.11 mm, size B, small, mean particle size 0.38 mm, size C, semolina, mean particle size 1.01 mm, size D, medium, mean particle size 1.44 mm, size E, large, mean particle size 1.95 mm) with theoretically different postprandial glycaemic responses were subjected to oral processing in vitro, followed by simulated gastric and duodenal digestion. RESULTS: A significant increase (P < 0.001) in starch degradation was observed in size A (52%) compared with size E (25%). Both sizes C and D gave less, although not significantly, digestible starch (32 and 28%, respectively). The glucose release significantly decreased as the particle size of the meal increased (92.16% detected for size A vs 47.39% for size E). In agreement with starch degradation and glucose release, size A gave the most digestible protein. CONCLUSIONS: This data provide further evidence that, by decreasing the size of wheat endosperm, starch release and glycaemic response are enhanced. We also showed that protein bioaccessibility followed a similar trend as for starch digestion. Finally, these results support the hypothesis that different degrees of starch encapsulation elicit different blood glucose responses.


Assuntos
Digestão , Grão Comestível/química , Tamanho da Partícula , Proteínas de Plantas/metabolismo , Amido/metabolismo , Triticum , Amilases/metabolismo , Bile/metabolismo , Disponibilidade Biológica , Glicemia/metabolismo , Duodeno/metabolismo , Mucosa Gástrica/enzimologia , Glucose/metabolismo , Humanos , Lipase/metabolismo , Pâncreas/enzimologia , Pepsina A/metabolismo , Saliva/imunologia , Amido/farmacocinética
13.
J Coll Physicians Surg Pak ; 27(11): 678-681, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29132476

RESUMO

OBJECTIVE: To assess whether helicobacter pylori was associated with CDX2 expression in intestinal metaplasia, atrophic gastritis, dysplasia and gastric cancer. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Pathology, The First Hospital of Jilin University, Changchun, China, from August 2016 to January 2017. METHODOLOGY: CDX2 expression was evaluated in 62 gastric antral biopsies; including 32 cases of intestinal metaplasia (IM) and 10 cases each of atrophic gastritis (AG), dysplasia and gastric cancer. Hematoxylin and Eosin staining was used to detect H.pyloriand immunohistochemistry was performed to observe CDX2 in the samples. RESULTS: Of the 62 patients inducted in the study, CDX2 expression was observed in 53 (85.5%). Mean age of these patients was 59 years (s.d.:11.3; range: 38-87) and included 32 males (60.38%) and 21 females (39.62%). However, age and gender were not found to be significantly associated with expression of CDX2 (p >0.05). CDX2 was very frequently expressed in individuals with IM (90.6%). Most of the patients with IM were males (17/29) as compared to females (12/29). However, the difference was not statistically significant (p=0.568). Only 4 out of 29 IM CDX2 positive specimens tested positive for H.pylori(p=1.0). CONCLUSION: CDX2 is highly expressed along the atrophic gastritis-metaplasia-dysplasia-cancer sequential. Though CDX2 expression is quite dominant in IM, but its expression is not associated with H.pyloriinfection.


Assuntos
Fator de Transcrição CDX2/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Proteínas de Homeodomínio/metabolismo , Intestinos/patologia , Metaplasia/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Endoscopia , Feminino , Mucosa Gástrica/enzimologia , Mucosa Gástrica/patologia , Gastrite/enzimologia , Gastrite/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/enzimologia , Infecções por Helicobacter/patologia , Humanos , Mucosa Intestinal/metabolismo , Masculino , Metaplasia/microbiologia , Metaplasia/patologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia
14.
Scand J Gastroenterol ; 52(12): 1320-1325, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28927301

RESUMO

OBJECTIVE: This study aimed to evaluate the optimal biopsy site for Helicobacter pylori detection by comparing the results of rapid urease test (RUT) between the gastric corpus and the antrum. METHODS: A biopsy specimen from each subject was obtained from the corpus and from the antrum. For each subject, the two specimens were separately immersed in two different RUT kits. Positive reaction times were measured at 20 minutes and 1, 3, and 24 hours. If either of the two RUT kits showed a positive reaction, H. pylori infection was confirmed. RESULTS: A total of 310 H. pylori-infected subjects were eligible for study inclusion. Compared with the antrum, positive RUT reaction times in the corpus were shorter when the degree of gastric atrophy was moderate or severe (p = .001 and p < .001, respectively). A multivariate analysis revealed that the factors resulting in a faster positive RUT reaction in the corpus were age ≥50 years (odds ratio [OR] = 1.84; 95% confidence interval [CI] = 1.10-3.08; p = .021) and severe gastric atrophy (OR = 2.41; 95% CI = 1.13-5.13; p = .023). Also, severe gastric atrophy was an independent factor associated with positive RUT reaction only in the corpus (OR = 5.12; 95% CI = 1.55-16.88; p = .007). CONCLUSIONS: In subjects aged ≥50 years or with severe gastric atrophy, biopsy of the corpus mucosa optimized the efficiency of H. pylori detection through a faster positive RUT reaction.


Assuntos
Mucosa Gástrica/enzimologia , Infecções por Helicobacter/diagnóstico , Antro Pilórico/patologia , Urease/análise , Adulto , Atrofia , Biópsia , Feminino , Mucosa Gástrica/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos
15.
Pharm Biol ; 55(1): 2110-2115, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28874080

RESUMO

CONTEXT: Aloe has been used for the prevention and cure of various diseases and symptoms including burns, injuries, oedema and pain. OBJECTIVE: This study determines the specific inhibitory activity of matrix metalloproteinase (MMP)-9 induced by the low molecular-weight gel fraction of Aloe vera (L.) Burm.f. (lgfAv) on alcohol-induced acute gastric lesions. MATERIALS AND METHODS: We examined the protective effects of oral (p.o.) administration of lgfAv (molecular weight cutoff <50.0 kDa, 150.0 mg/kg body weight) in a Balb/c mouse model of alcohol-induced acute gastritis for 1 h exposure. By measuring ulcer index, we compared the antiulcerative activity of the fraction. mRNA expression and immunohistochemical analysis of various biomarkers were performed. RESULTS: The lgfAv-treated mice exhibited drastically fewer ulcer lesions than the untreated control mice did. It featured that lgfAv lessened the ulcer lesions than their relevant controls. Moreover, the transcriptional level of MMP-9 was completely alleviated by lgfAv treatment in alcohol-treated gastritis-induced mice. DISCUSSION: The transcriptional level of MMP-9 was significantly alleviated by lgfAv treatment of the model. However, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry experiments revealed that lgfAv treatment in mucosal tissues had the potential to inhibit the mRNA and protein expression levels of MMP-9, respectively. The protein expression of MMP-9 was closely associated with lgfAv-induced gastroprotection against alcohol-induced gastric lesions. CONCLUSIONS: The present findings suggest that lgfAv has the potential to alleviate alcohol-induced acute gastric lesions, which is mediated in part, mainly by the suppression of the mRNA expression of MMP-9.


Assuntos
Aloe , Etanol/toxicidade , Metaloproteinase 9 da Matriz/biossíntese , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Animais , Indução Enzimática/efeitos dos fármacos , Indução Enzimática/fisiologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/enzimologia , Gastrite/induzido quimicamente , Gastrite/enzimologia , Gastrite/prevenção & controle , Géis , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Úlcera Gástrica/enzimologia
16.
Bull Exp Biol Med ; 163(1): 6-9, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28577107

RESUMO

Neuronal NO synthase blocker 7-nitroindazole suppressed bicarbonate secretion in rat gastric mucosa induced by mild local irritation with 1 M NaCl (pH 2.0). Non-selective blocker of neuronal and endothelial synthases, Nω-nitro-L-arginine (L-NNA), did not affect HCO3- production, but inhibited secretion after pretreatment with omeprazole. Non-selective cyclooxygenase blocker indomethacin inhibited HCO3- production under conditions of normal synthase activity and in the presence of L-NNA, but was ineffective when co-administered with 7-nitroindazole. It was concluded that neuronal and endothelial synthases are involved in different mechanisms of regulation of HCO3- secretion in the gastric mucosa induced by mild irritation. Activation of neuronal synthase stimulated HCO3- production, which is mediated mainly through activation of cyclooxygenase. Theoretically, activation of endothelial synthase should suppress HCO3- production. The effect of endothelial synthase depends on acid secretion in the stomach and bicarbonate concentration in the submucosa, as it was demonstrated in experiments with intravenous NaHCO3 infusion.


Assuntos
Bicarbonatos/metabolismo , Mucosa Gástrica/enzimologia , Mucosa Gástrica/metabolismo , Óxido Nítrico Sintase/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Animais , Indazóis/farmacologia , Indometacina/farmacologia , Masculino , Óxido Nítrico Sintase/antagonistas & inibidores , Omeprazol/farmacologia , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Cloreto de Sódio/farmacologia
17.
J Vet Med Sci ; 79(7): 1253-1260, 2017 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-28579582

RESUMO

Extragonadal tissues are known to produce estrogens. At these sites, the C19 precursor is important for aromatase expression for the production of estrogen. Aromatase expression is tissue-specific and is controlled by hormones. Recent studies have shown that rat gastric parietal cells expressed aromatase. Our first objective was to investigate steroidogenic enzyme expression in estrogen biosynthesis; the second objective was to investigate which site(s) of the GI tract expressed steroidogenic enzymes; and the third objective was to assess the effects of castration on steroidogenic enzyme expression. CYP19A1, 17ß-HSD3, CYP17A1, 3ß-HSD and P450scc were quantified in the GI tract by real-time PCR. CYP19A1 was detected mainly in the body and pyloric regions of the abomasum, while we detected weak expression of CYP19A1 in other parts of GI tract. In addition, the expression of 17ß-HSD3 and CYP17A1 was detected in abomasum. 3ß-HSD expression was observed in duodenum and jejunum, while P450scc was not detectable in any part of GI tract. Immunohistochemical results showed immunolocalization of aromatase in parietal cells. Aromatase expression was observed to increase after castration. Furthermore, immunohistochemical results demonstrated that parietal cells also produced luteinizing hormone receptor (LHR). These results indicate steroidogenic enzymes required for the biosynthesis of estrogen were expressed, and the abomasum appeared to be the responsible organ for estrogen biosynthesis in the goat GI tract. In addition, parietal cells were responsible for estrogen production and the expression of LHR. Castration increased aromatase expression in abomasum through LH mediation.


Assuntos
Estrogênios/biossíntese , Trato Gastrointestinal/metabolismo , Cabras/metabolismo , Orquiectomia/veterinária , Abomaso/enzimologia , Abomaso/metabolismo , Animais , Aromatase/metabolismo , Mucosa Gástrica/enzimologia , Mucosa Gástrica/metabolismo , Trato Gastrointestinal/enzimologia , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Receptores do LH/metabolismo
18.
Medicine (Baltimore) ; 96(19): e6865, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28489783

RESUMO

Triosephosphate isomerase (TPI) is highly expressed in many human cancers and is involved in migration and invasion of cancer cells. However, TPI clinicopathological significance and prognostic value in gastric cancer (GC) are not yet well defined. The aim of the present work was to evaluate TPI expression in GC tissue and its prognostic value in GC patients.TPI expression was analyzed in 92 primary GC tissues and 80 adjacent normal mucosa tissues from GC patients undergoing gastrectomy by immunohistochemical analysis of tissue microarrays (TMAs). Univariate and multivariate analyses were performed to investigate TPI prognostic significance in GC patients.Immunohistochemical staining score showed that TPI expression in cancer tissues was significantly higher than in adjacent normal mucosa (P < .001). Univariate analysis revealed that TPI expression, depth of invasion, lympho node metastasis, tumor node metastasis (TNM) stage, and tumor diameter were associated with negative prognostic predictors for overall survival in GC patients (P < .05). High TPI expression represented a significant predictor of shorter survival in GC patients with positive lymphatic metastasis (P = .022) and tumor diameter >5 cm (P = .018). Cox multivariate analysis identified TPI expression, TNM stage, and tumor diameter as independent prognostic factors in GC patients.TPI expression might be considered as a novel prognostic factor to evaluate GC patients' survival.


Assuntos
Mucosa Gástrica/enzimologia , Neoplasias Gástricas/enzimologia , Biomarcadores Tumorais/metabolismo , Feminino , Seguimentos , Gastrectomia , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Análise Serial de Tecidos , Triose-Fosfato Isomerase , Carga Tumoral
19.
Biochem Cell Biol ; 95(2): 243-250, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28177773

RESUMO

Trypsin and chymotrypsin inhibitors from Erythrina velutina seeds have been previously isolated by our group. In previous studies using a sepsis model, we demonstrated the antitumor and anti-inflammatory action of these compounds. This study aimed to evaluate the gastroprotective and antielastase effects of protein inhibitors from E. velutina seeds in an experimental stress-induced ulcer model. Two protein isolates from E. velutina seeds, with antitrypsin (PIAT) and antichymotrypsin (PIAQ) activities, were tested. Both protein isolates showed a high affinity and inhibitory effect against human neutrophil elastase, with 84% and 85% inhibition, respectively. Gastric ulcer was induced using ethanol (99%) in 6 groups of animals (female Wistar rats, n = 6). Before ulcer induction, these animals were treated for 5 days with one of the following: (1) PIAT (0.2 mg·kg-1), (2) PIAT (0.4 mg·kg-1), (3) PIAQ (0.035 mg·kg-1), (4) ranitidine hydrochloride (50 mg·kg-1), (5) saline solution (0.9%), or (6) no intervention (sham). Both PIAT and PIAQ protected gastric mucosa, preventing hemorrhagic lesions, edema, and mucus loss. No histologic toxic effects of PIAT or PIAQ were seen in liver and pancreatic cells. Our results show that protein isolates from E. velutina seeds have potential gastroprotective effects, placing these compounds as natural candidates for gastric ulcer prevention.


Assuntos
Anti-Inflamatórios/farmacologia , Inibidores Enzimáticos/farmacologia , Erythrina/química , Fármacos Gastrointestinais/farmacologia , Fitoterapia , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios/isolamento & purificação , Modelos Animais de Doenças , Inibidores Enzimáticos/isolamento & purificação , Etanol , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/enzimologia , Mucosa Gástrica/patologia , Fármacos Gastrointestinais/isolamento & purificação , Humanos , Elastase de Leucócito/antagonistas & inibidores , Elastase de Leucócito/metabolismo , Extratos Vegetais/química , Ranitidina/farmacologia , Ratos , Ratos Wistar , Sementes/química , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/enzimologia , Úlcera Gástrica/patologia
20.
Bioorg Med Chem ; 25(2): 665-676, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27916468

RESUMO

The inhibition of gastric cyclooxygenase 1 (COX-1) enzyme was believed to be the major cause of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcer. Recent studies disproved this belief and showed that the gastric tissues vulnerability is not solely connected to COX-1 inhibition. This work aimed at exploring and rationalizing the differential analgesic and anti-inflammatory activities of novel selective COX-1 inhibitors with improved gastric profile. Two novel series of 4,5-diarylthiazole and diarylimidazole were designed, synthesized in analogy to selective COX-1 inhibitors (mofezolac and FR122047) which lack gastric damaging effects. The new compounds were evaluated in vitro for their COXs inhibitory activity and in vivo for their anti-inflammatory and analgesic potentials. Four compounds; diphenylthiazole glycine derivatives (15a, 15b) and diphenylimidazolo acetic acid derivatives (19a, 19b), which possess carboxylic acid group exhibited significant activity and selectivity against COX-1 over COX-2. Of these compounds, (4,5-bis(4-methoxyphenyl)thiazol-2-yl)glycine 15b was the most potent compound against COX-1 with an inhibitory half maximal concentration (IC50) of 0.32µM and a selectivity index (COX-2 IC50/COX-1 IC50) of 28.84. Furthermore, an ulcerogenicity study was performed where the tested compounds demonstrated a significant gastric tolerance. Interestingly, the most selective COX-1 inhibitor showed higher analgesic activity in vivo as expected compared to their moderate anti-inflammatory activity. This study underscores the need for further design and development of novel analgesic agents with low tendency to cause gastric damage based on improving their COX-1 affinity and selectivity profile.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/farmacologia , Desenho de Drogas , Imidazóis/farmacologia , Tiazóis/farmacologia , Ácido Acético , Analgésicos/síntese química , Analgésicos/química , Animais , Anti-Inflamatórios não Esteroides/química , Carragenina , Bovinos , Ciclo-Oxigenase 1/metabolismo , Inibidores de Ciclo-Oxigenase/química , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Mucosa Gástrica/enzimologia , Humanos , Imidazóis/síntese química , Imidazóis/química , Masculino , Simulação de Acoplamento Molecular , Estrutura Molecular , Dor/induzido quimicamente , Dor/tratamento farmacológico , Ratos , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/química
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