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1.
Croat Med J ; 61(4): 319-325, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32881429

RESUMO

AIM: To assess the relationship between Helicobacter pylori (H. pylori) infection and atrophic gastritis (AG) and intestinal metaplasia (IM) development and to assess the rate of dysplasia or gastric cancer development in patients with AG and/or IM. METHODS: This retrospective endoscopic follow-up study enrolled 2214 patients. The patients were followed for at least five years between 2007 and 2017 at the Department of Endoscopy at Antalya Ataturk Government Hospital. The results of third-year and five-year surveillance biopsy were assessed. RESULTS: The mean follow-up time was 7.77 ± 2.78 years. H. pylori was histologically assessed in 1417 (64.6%) patients. Of 198 patients with severe H. pylori infection, 32 (16%) and 139 (70.3%) developed extensive AG and extensive IM, respectively. There was a significant relationship between H. pylori density and AG and IM degrees. High grade dysplasia, early gastric cancer, and advanced gastric cancer were diagnosed in 73 patients with median age 58.2 (28-80) years, and the incidence rate was 3.29% (73/2214). The annual incidence of gastric neoplastic lesions was 0.46% in total, 0.08% for early GC, and 0.02% for advanced gastric cancer. CONCLUSIONS: H. pylori infection has an important role in the development of AG and IM. H. pylori density is directly related to atrophy and metaplasia degree.


Assuntos
Gastrite Atrófica/epidemiologia , Infecções por Helicobacter/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Endoscopia Gastrointestinal , Feminino , Seguimentos , Mucosa Gástrica/patologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Humanos , Incidência , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Turquia/epidemiologia
2.
Ann Surg ; 272(2): 319-325, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32675545

RESUMO

OBJECTIVE: To stratify the postsurgical computed tomography (CT) surveillance based on a risk-scoring system for predicting extragastric recurrence after surgical resection of early gastric cancer (EGC). SUMMARY OF BACKGROUND DATA: Postsurgical CT surveillance should not be routinely performed in all patients because of the low incidence of extragastric recurrence and potential risk of radiation exposure. METHODS: Data from 3162 patients who underwent surgical resection for EGC were reviewed to develop a risk-scoring system to predict extragastric recurrence. Risk scores were based on the predictive factors for extragastric recurrence, which were determined using Cox proportional hazard regression model. The risk-scoring system was validated by Uno censoring adjusted C-index. External validation was performed using an independent dataset (n = 430). RESULTS: The overall incidence of extragastric recurrence was 1.4% (44/3162). Five risk factors (lymph node metastasis, indications for endoscopic resection, male sex, positive lymphovascular invasion, and elevated macroscopic type), which were significantly associated with extragastric recurrence, were incorporated into the risk-scoring system, and the patients were categorized into 2 risk groups. The 10-year extragastric recurrence-free survival differed significantly between low- and high-risk groups (99.7% vs 96.5%; P < 0.001). The predictive accuracy of the risk-scoring system in the development cohort was 0.870 [Uno C-index; 95% confidence interval (95% CI), 0.800-0.939]. Discrimination was good after internal (0.859) and external validation (0.782, 0.549-1.000). CONCLUSION: This risk-scoring system might be useful to predict extragastric recurrence of EGC after curative surgical resection. We suggest that postsurgical CT surveillance to detect extragastric recurrence should be avoided in the low-risk group.


Assuntos
Gastrectomia/métodos , Metástase Linfática/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios X/métodos , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Detecção Precoce de Câncer , Feminino , Gastrectomia/efeitos adversos , Mucosa Gástrica/patologia , Gastroscopia/métodos , Humanos , Metástase Linfática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , República da Coreia , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida
3.
Life Sci ; 256: 117977, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603822

RESUMO

AIMS: Silibinin is the major component of flavonolignans complex mixture (Silymarin), which is obtained from Silybum marianum (L.) Gaertn. Despite several reports about silibinin, little is known about its effects on gastric diseases. Then, the present study aims to evaluate the silibinin effect against Helicobacter pylori infection, gastric tumor cells and immunomodulation. MAIN METHODS: The anti-H. pylori effect was performed on 43504 and 43629 strains by minimum inhibitory concentration (MIC) determination, observing morphological alterations by scanning electron microscopy and in silico evaluation by molecular docking. Immunomodulatory activity (Interleukins-6 and 10, TNF-α and NO inhibition) was determined in H. pylori-stimulated macrophages and the cytotoxic activity on gastric adenocarcinoma cells prior and after metabolization by S9 fraction. KEY FINDINGS: Silibinin showed anti-H. pylori activity with MIC of 256 µg/mL, promoted important morphological changes in the bacterial cell wall, as blebs and clusters, suggesting interaction with Penicillin Binding Protein (PBP) subunits. Immunomodulatory potential was observed at 50 µg/mL with the inhibition of produced cytokines and NO by H. pylori-stimulated macrophages of 100% for TNF-ɑ, 56.83% for IL-6, and 70.29% for IL-10 and 73.33% for NO. Moreover, silibinin demonstrated significant cytotoxic activity on adenocarcinoma cells (CI50: 60.17 ± 0.95 µg/mL) with a higher selectivity index (SI: 1.52) compared to cisplatin. After metabolization silibinin showed an increase of cytotoxicity with a CI50 six-fold decrease (10.46 ± 0.25). SIGNIFICANCE: The use of silibinin may become an important alternative tool in the prevention and treatment of H. pylori infection and, consequently, in gastric cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/efeitos dos fármacos , Simulação de Acoplamento Molecular/métodos , Silibina/farmacologia , Neoplasias Gástricas/prevenção & controle , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/fisiologia , Camundongos , Testes de Sensibilidade Microbiana/métodos , Células RAW 264.7 , Silibina/química , Silibina/uso terapêutico , Neoplasias Gástricas/patologia
4.
Chem Biol Interact ; 327: 109166, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32531310

RESUMO

Boldine is the main alkaloid of Peumus boldus Molina, widely used in the traditional medicine for the treatment of digestive disorders. It is a compound with excellent antioxidant and anti-inflammatory properties already described. Despite the widespread use of P. boldus for digestive disorders treatment, the gastroprotective effect of Boldine remains unknown. Considering the need for new approaches to treat gastric ulcers with fewer side effects than current therapy, this study aimed to investigate the gastroprotective effect of Boldine in mice, as well as the mechanisms underlying this effect. The gastroprotective effect of Boldine was evaluated on gastric ulcer induced by 60% ethanol/0.3 M HCl or indomethacin (100 mg/kg) in mice. Histological analysis and the mucin-like glycoprotein content were evaluated in ethanol-ulcerated tissue, as well as, oxidative stress and inflammatory parameters. The mechanisms involved in the effect of Boldine were evaluated by pretreating mice with NEM (a sulfhydryl group chelator, 10 mg/kg, i.p.), l-NAME (a non-selective nitric oxide synthase inhibitor, 70 mg/kg, i.p.), yohimbine (an alpha-adrenergic receptor antagonist, 2 mg/kg, i.p.) and indomethacin (a cyclooxygenase inhibitor, 10 mg/kg, i.p.). In addition, the in vitro effect of Boldine on H+/K+-ATPase activity was determined. Boldine was able to protect gastric mucosa against the damage induced by ethanol/HCl and indomethacin, as evidenced by reduced lesion area and histological analysis. Moreover, the alkaloid reduced oxidative stress and inflammatory mediators in ethanol-ulcerated tissue, beyond has increased mucin-like glycoprotein amount. Finally, Boldine effect is dependent on non-protein sulfhydryl groups and prostanoids but does not involve the inhibition of H+/K + -ATPase activity, being a promising natural resource for gastric ulcer treatment.


Assuntos
Antiulcerosos/farmacologia , Aporfinas/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Etanol , Feminino , Mucosa Gástrica/patologia , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Indometacina , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Prostaglandinas/metabolismo , Coelhos , Úlcera Gástrica/induzido quimicamente , Compostos de Sulfidrila/metabolismo
5.
Arch Biochem Biophys ; 689: 108466, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32590067

RESUMO

Nuclear factor erythroid-derived 2-like 2 (Nrf-2) is transcription factor implicated in the antioxidant response element-mediated induction of endogenous antioxidant enzyme such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase, and NAD(P)H quinone dehydrogenase 1, among which HO-1 is an enzyme catalyzing the degradation of heme.producing biliverdin, ferrous iron, and carbon monoxide. In the stomach, as much as regulating gastric acid secretions, well-coordinated establishment of defense system stands for maintaining gastric integrity. In previous study, author et al. for the first time discovered HO-1 induction was critical in affording faithful gastric defense against various irritants including Helicobacter pylori infection, stress, alcohol, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and toxic bile acids. In this review article, we can add the novel evidence that dietary walnut intake can be reliable way to rescue from NSAIDs-induced gastrointestinal damages via the induction of HO-1 transcribed with Nrf-2 through specific inactivation of Keap-1. From molecular exploration to translational animal model of indomethacin-induced gastrointestinal damages, significant induction of HO-1 contributed to rescuing from damages. In addition to HO-1 induction action relevant to walnut, we added the description the general actions of walnut extracts or dietary intake of walnut regarding cytoprotection and why we have focused on to NSAID damages.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Alimento Funcional , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/terapia , Juglans , Animais , Alimento Funcional/análise , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Gastroenteropatias/patologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Juglans/química , Juglans/metabolismo
7.
Nat Genet ; 52(6): 594-603, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32451460

RESUMO

Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,103 unsorted single cells from 23 Korean and 6 Belgian patients. Cancer cells displayed transcriptional features reminiscent of normal differentiation programs, and genetic alterations that apparently fostered immunosuppressive microenvironments directed by regulatory T cells, myofibroblasts and myeloid cells. Intercellular network reconstruction supported the association between cancer cell signatures and specific stromal or immune cell populations. Our collective view of the cellular landscape and intercellular interactions in colorectal cancer provide mechanistic information for the design of efficient immuno-oncology treatment strategies.


Assuntos
Linhagem da Célula , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias Colorretais/patologia , Mucosa Gástrica/imunologia , Mucosa Gástrica/patologia , Humanos , Análise de Sequência de RNA , Análise de Célula Única , Células Estromais/patologia , Linfócitos T/imunologia , Linfócitos T/patologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
8.
Virchows Arch ; 477(4): 489-496, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32356024

RESUMO

Pyloric metaplasia (PM) and pseudopyloric metaplasia (PPM) are metaplastic changes resulting in pyloric-type glands in the gastric oxyntic mucosa that mainly occur in chronic gastritis caused by Helicobacter pylori (H. pylori) infection. Focusing on PM and PPM, we classified the histological changes in gastric mucosa according to the Updated Sydney System, using 314 biopsy specimens of gastric greater curvature of the middle body before H. pylori eradication (HPE). Next, the numbers of PM and PPM glands were counted in 47 specimens, and subjects were followed up over 10 years after HPE. PPM was recognized jointly with inflammation, activity, atrophy, and intestinal metaplasia, but PM was recognized more frequently than PPM as atrophy and intestinal metaplasia progressed. Both PM and PPM regressed significantly within 6 years after HPE. Additionally, we demonstrated that PM and PPM are not always coincident with spasmolytic polypeptide-expressing metaplasia (SPEM). In conclusion, PM and PPM are considered different modulations of the same line of differentiation, which are both reversible, with PM potentially emerging from PPM upon progression.


Assuntos
Mucosa Gástrica/patologia , Gastrite/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Biópsia , Diferenciação Celular , Doença Crônica , Mucosa Gástrica/química , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Gastrite/tratamento farmacológico , Gastrite/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Metaplasia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
9.
Braz J Med Biol Res ; 53(4): e9290, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294703

RESUMO

This study was designed to investigate the expression of RBM8A protein in patients with gastric cancer (GC) and to explore its correlation with clinical pathological features as well as prognosis. One hundred pairs of gastric carcinoma tissues and adjacent tissues from patients undergoing gastrectomy for GC were included in this study. The protein expression level of RBM8A was determined by immunohistochemistry using tissue microarrays. We also detected the mRNA expression level of RBM8A in 16 pairs of gastric carcinoma tissues and adjacent tissues. Meanwhile, we predicted the potential correlation between RBM8A and tumor stages as well as survival condition in patents with GC based on The Cancer Genome Atlas (TCGA) database. The correlation of RBM8A with the clinical pathological features and prognosis of the 100 patients with GC was also elucidated. The expression level of RBM8A was significantly higher in gastric carcinoma tissues compared to the adjacent tissues. The protein level of RBM8A was correlated with tumor size (P=0.031), depth of invasion (P<0.001), lymph node metastasis (P<0.001), TNM stage (<0.001), and distant metastasis (P=0.001). Patients with increased RBM8A expression (P<0.0018, 95%CI=0.322-0.871), higher TNM stage (P<0.001, 95%CI=4.990-11.283), and lymph node metastasis (P<0.001, 95%CI=2.873-4.002) had a lower overall survival. Taken together, our study demonstrated that RBM8A may act as a proto-oncogene, which could be a promising biomarker and therapeutic target in the diagnosis and treatment of GC.


Assuntos
Proteínas de Ligação a RNA/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Feminino , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas/metabolismo , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Análise de Sobrevida
10.
Int J Nanomedicine ; 15: 2529-2539, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32346290

RESUMO

Background: Peptic ulcer disease, a painful lesion of the gastric mucosa, is considered one of the most common gastrointestinal disorders. This study aims to investigate the formulation of pumpkin seed oil (PSO)-based nanostructured lipid carriers (NLCs) to utilize PSO as the liquid lipid component of NLCs and to achieve oil dispersion in the nano-range in the stomach. Methods: Box-Behnken design was utilized to deduce the optimum formula with minimum particle size. The optimized PSO-NLCs formula was investigated for gastric ulcer protective effects in Wistar rats by evaluating ulcer index and determination of gastric mucosa oxidative stress parameters. Results: PSO was successfully incorporated as the liquid lipid (LL) component of NLCs. The prepared optimum PSO-NLCs formula showed a size of 64.3 nm. Pretreatment of animals using the optimized PSO-NLCs formula showed significantly (p< 0.001) lower ulcer index compared to indomethacin alone group and significantly (p<0.05) less mucosal lesions compared to the raw oil. Conclusion: These results indicated great potential for future application of optimized PSO-NLCs formula for antiulcer effect in non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcer.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Cucurbita/química , Portadores de Fármacos/química , Lipídeos/química , Nanoestruturas/química , Óleos Vegetais/química , Úlcera Gástrica/tratamento farmacológico , Animais , Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Indometacina/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos Wistar , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de Fourier , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/patologia
11.
Medicine (Baltimore) ; 99(17): e19839, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332633

RESUMO

The present study was designed to investigate the expression of tumor-associated macrophages (TAMs) in gastric cancer and its clinicopathological relationship. In addition, we also aimed to analyze the relationship between helicobacter pylori (HP) infection and TAMs in gastric cancer.The protein expression of CD16 and CD163 in 90 gastric cancer tissues and 30 margin tissues was detected by immunohistochemistry. HP infection was detected in 90 gastric cancer tissues and 30 margin tissues by gram staining and immunohistochemistry.There was no clear correlation between CD16 macrophages and gastric cancer. The density of CD163 macrophages was not correlated with the general condition of tumor patients, but with tumor size, tumor differentiation, lymphatic metastasis, depth of invasion and TNM stage. Additionally, the infection rate of HP in gastric cancer tissues was significantly higher.In summary, TAMs are associated with tumor size, degree of differentiation, depth of invasion, lymph node metastasis and TNM stage, suggesting their critical role in the invasion and metastasis of gastric cancer.


Assuntos
Macrófagos/patologia , Neoplasias Gástricas/patologia , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Contagem de Células , Feminino , Proteínas Ligadas por GPI/análise , Mucosa Gástrica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Receptores de Superfície Celular/análise , Receptores de IgG/análise , Estudos Retrospectivos , Neoplasias Gástricas/complicações , Carga Tumoral
12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(2): 157-163, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32314714

RESUMO

Objective To investigate the effect of matrine on gastric mucosal injury induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in rats and its mechanism. Methods A total of 75 Wister rats were randomly divided into a control group, a model group and three matrine-treated groups (100, 150 and 200 mg/kg). Except for the control group, the other groups were treated with MNNG to establish the models of gastric mucosal injury in the rats. After the models were successfully established, the rats in the three matrine-treated groups were administrated 100, 150, 200 mg/kg matrine, respectively, for successive 45 days. After the last administration, the body mass, daily intake of drinking water and dietary of rats were measured. And then the tissue samples were collected after the rats were sacrificed. The levels of interleukin 1ß (IL-1ß), IL-4, interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) were measured by ELISA in gastric mucosa. HE staining was used to observe the pathological changes of gastric mucosa tissue. Immunohistochemical staining was performed to evaluate the expression of vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor receptor 3 (VEGFR3) in gastric mucosa. The protein levels of Bcl2, BAX, caspase-3, cytochrome C (Cyt-C), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor κB p65 (NF-κB p65) were determined by Western blotting. Results The body mass, daily intake of drinking water and dietary increased in matrine-treated rats in comparison with the model group. In addition, compared with the model group, matrine significantly reduced the expression levels of VEGF-C, VEGFR3, BAX, caspase-3, Cyt-C, TLR4, MyD88 and NF-κB p65, and increase Bcl2 protein level in the gastric mucosa tissues. Conclusion Matrine can reduce gastric mucosal damage induced by MNNG in rats, which is related to the down-regulation of VEGF-C/VEGFR3 and NF-κB/TLR4 signaling pathway.


Assuntos
Alcaloides/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Metilnitronitrosoguanidina/efeitos adversos , Quinolizinas/farmacologia , Animais , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Receptor 4 Toll-Like/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo
13.
Zhongguo Zhen Jiu ; 40(3): 279-84, 2020 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-32270641

RESUMO

OBJECTIVE: To observe the effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum growth hormone (GH) and pepsinogen (PG) in chronic atrophic gastritis (CAG) rats, and to explore the potential mechanism of heat-sensitive moxibustion for CAG. METHODS: A total of 66 male SD rats were randomized into a blank group (12 rats) and a model establishment group (54 rats). No intervention was given in the blank group. Rats in the model establishment group were intervented with compound pathogeny method for 12 weeks to establish CAG model, which were further divided into a model group (11 rats), a vitacoenzyme group (11 rats) and a moxibustion group (22 rats). In the moxibustion group, suspending moxibustion was applied at "Zhongwan" (CV 12) for 40 min. After the intervention of moxibustion, 0.9% sodium chloride solution was given by gavage (2 mL·kg-1·d-1). According to the changes of tail temperature, rats in the moxibustion group were divided into a heat-sensitive moxibustion group (11 rats) and a non-heat-sensitive moxibustion group (8 rats). The vitacoenzyme group was given vitacoenzyme as the same dose by gavage. The intervention was adopted once a day for 28 days. Changes of body weight were observed among the groups. Expressions of serum GH, PGⅠand PGⅡwere detected by ELISA, and the ratio of PGⅠand PGⅡ (PGR) was calculated. The morphological changes of gastric mucosa were observed by macroscopy and light microscope. RESULTS: ①After modeling, the body weight of rats in the model establishment group was lower than the blank group (P<0.01). Compared with the model group, the body weight of rats in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group was increased after intervention (P<0.05), and there were no significant differences among the intervention groups (P>0.05). ②Under macroscopy and light microscope, gastric tissue of rats after modeling showed dark red and pale gastric mucosa, lower plica and mucosal congestion. The glands of lamina propria were atrophied or disappeared with sparse and disordered arrangement, in which, lymphoid follicles and inflammatory cells could be observed. After intervention, morphology of gastric mucosa was improved in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group. ③Compared with the blank group, the serum levels of GH, PGⅠ, PGⅡ and PGR were decreased in the model group (P<0.05, P<0.01). Compared with the model group, the serum levels of GH, PGⅠand PGⅡwere increased in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group (P<0.05, P<0.01), the levels of PGR were increased without statistical difference (P>0.05). Compared with the vitacoenzyme group and the non-heat-sensitive moxibustion group, the serum levels of GH and PGⅠwere increased in the heat-sensitive moxibustion group (P<0.05). CONCLUSION: Heat-sensitive moxibustion at "Zhongwan" (CV 12) can improve the morphology of gastric mucosa in chronic atrophic gastritis rats, its mechanism may be related to the up-regulation of serum GH and PGⅠ.


Assuntos
Gastrite Atrófica/terapia , Moxibustão , Pontos de Acupuntura , Animais , Mucosa Gástrica/patologia , Hormônio do Crescimento/sangue , Masculino , Pepsinogênio A/sangue , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
14.
Arq Gastroenterol ; 57(1): 74-78, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294739

RESUMO

BACKGROUND: The role of Helicobacter pylori infection on eosinophilic infiltration in duodenal mucosa is poorly studied. An increase in the number of eosinophils in duodenum has been associated with functional dyspepsia. OBJECTIVE: To evaluate the influence of H. pylori infection on duodenal eosinophil count and the role of eosinophilic infiltrate of duodenum in functional dyspepsia. METHODS: Positive and negative H. pylori individuals were included. Both functional dyspeptic patients according to Rome III criteria (cases) and individuals without gastrointestinal symptoms (controls) were enrolled. They were submitted to upper endoscopy and H. pylori infection was verified by gastric histopathology and urease test. Eosinophils in the duodenal mucosa were counted in five high-power fields, randomly selected on slides of endoscopic biopsies. RESULTS: Thirty-nine H. pylori positive (mean age 40.5 and 69.2% women) and 24 negative patients (mean age 37.3 and 75% women) were included. The influence of the infection was observed in the duodenal eosinophil count, which was higher in infected individuals: median 13.2 vs 8.1 in non-infected individuals (P=0.005). When we analyzed patients according to symptoms, cases - mean age 39.6; 71.4% women - and controls - mean age 38.7; 71.4% women - had similar duodenal eosinophil count: median 11.9 and 12.6 respectively (P=0.19). CONCLUSIONS: We did not demonstrate association of duodenal eosinophil count with functional dyspepsia but found association with H. pylori infection.


Assuntos
Duodeno/patologia , Dispepsia/microbiologia , Eosinofilia/patologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori , Adulto , Biópsia , Estudos de Casos e Controles , Duodeno/microbiologia , Dispepsia/patologia , Feminino , Mucosa Gástrica/microbiologia , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade
15.
Am J Surg Pathol ; 44(9): 1251-1258, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32301754

RESUMO

Malakoplakia is an inflammatory process related to defective macrophage response to bacterial infection. To further characterize the clinicopathologic manifestations of gastrointestinal malakoplakia, 26 cases were identified from 6 institutions. Hematoxylin and eosin-stained slides and available stains were reviewed, and pertinent clinicopathologic features analyzed. Sixteen patients were women (62%). Mean patient age was 64 (range: 24 to 83). Sites included the colorectum (n=23), appendix (n=1), and stomach (n=2). Clinical indications for tissue procurement included screening (n=14), tumor resection (n=5), diarrhea (n=1), adenoma surveillance (n=1), ulcerative colitis flare (n=1), abdominal pain (n=1), and appendicitis (1). All cases featured histiocytes with abundant, pale, eosinophilic cytoplasm focally containing Michaelis-Gutmann bodies. The process frequently involved the mucosa (n=19), with architectural distortion in 13 cases. Lymphoid aggregates were present in 18 cases, which were prominent or obscuring in 11 (all colon biopsies) and provoked concern for lymphoma in 2. Associated findings included adenocarcinoma (n=5), adenoma (n=2), gastric hyperplastic polyps (n=1), chemical gastritis (n=1), collagenous colitis (n=1), and active chronic colitis (n=2). In cases with available stains, Michaelis-Gutman bodies were highlighted by Periodic Acid-Schiff with diastase, Von Kossa, and iron stains. Although 2 cases were positive for Tropheryma whipplei antibody, no T. whipplei transcripts were detected on real-time polymerase chain reaction. All patients with available follow-up are alive and well with no additional instances of malakoplakia. Malakoplakia of the gastrointestinal tract is a benign, incidental finding. Although histologic features in the stomach and colon resections are similar to those at other sites, exuberant lymphocytic response in colon biopsies and immunoreactivity with T. whippleii antibody may provoke initial confusion and lead to unnecessary time and resource investment.


Assuntos
Gastroenteropatias/patologia , Trato Gastrointestinal/patologia , Achados Incidentais , Malacoplasia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Mucosa Gástrica/patologia , Gastroenteropatias/microbiologia , Trato Gastrointestinal/microbiologia , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Tropheryma/genética , Estados Unidos , Adulto Jovem
16.
Cancer Sci ; 111(5): 1596-1606, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32198795

RESUMO

Chronic infection with Helicobacter pylori cagA-positive strains is causally associated with the development of gastric diseases, most notably gastric cancer. The cagA-encoded CagA protein, which is injected into gastric epithelial cells by bacterial type IV secretion, undergoes tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) segments (EPIYA-A, EPIYA-B, EPIYA-C, and EPIYA-D), which are present in various numbers and combinations in its C-terminal polymorphic region, thereby enabling CagA to promiscuously interact with SH2 domain-containing host cell proteins, including the prooncogenic SH2 domain-containing protein tyrosine phosphatase 2 (SHP2). Perturbation of host protein functions by aberrant complex formation with CagA has been considered to contribute to the development of gastric cancer. Here we show that SHIP2, an SH2 domain-containing phosphatidylinositol 5'-phosphatase, is a hitherto undiscovered CagA-binding host protein. Similar to SHP2, SHIP2 binds to the Western CagA-specific EPIYA-C segment or East Asian CagA-specific EPIYA-D segment through the SH2 domain in a tyrosine phosphorylation-dependent manner. In contrast to the case of SHP2, however, SHIP2 binds more strongly to EPIYA-C than to EPIYA-D. Interaction with CagA tethers SHIP2 to the plasma membrane, where it mediates production of phosphatidylinositol 3,4-diphosphate [PI(3,4)P2 ]. The CagA-SHIP2 interaction also potentiates the morphogenetic activity of CagA, which is caused by CagA-deregulated SHP2. This study indicates that initially delivered CagA interacts with SHIP2 and thereby strengthens H. pylori-host cell attachment by altering membrane phosphatidylinositol compositions, which potentiates subsequent delivery of CagA that binds to and thereby deregulates the prooncogenic phosphatase SHP2.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Células Epiteliais/metabolismo , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/metabolismo , Motivos de Aminoácidos , Animais , Antígenos de Bactérias/química , Antígenos de Bactérias/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Linhagem Celular , Membrana Celular/metabolismo , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Fosfatos de Fosfatidilinositol/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/química , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/genética , Fosforilação , Ligação Proteica , Transporte Proteico , Proteína Tirosina Fosfatase não Receptora Tipo 11/química , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Domínios de Homologia de src
17.
Klin Lab Diagn ; 65(2): 131-136, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32159312

RESUMO

The lack of specific symptoms for the early detection of gastric cancer leads to the fact that it is often diagnosed at a late stage, when the prognosis is unfavorable. The analysis of molecular markers in addition to standard diagnostic procedures is a promising approach for improving the preoperative diagnosis of both gastric cancer and precancerous changes in the mucosa. Therefore, the aim of our study was to analyze the diagnostic significance of using miRNA expression to diagnosis gastric cancer and precancerous conditions (dysplasia) in histological material. In this work, 122 samples of archival histological material in the form of paraffin blocks were used: 34 samples of gastric adenocarcinoma, 54 samples of gastric ulcers with dysplasia and 34 samples of normal gastric mucosa obtained from patients after bariatric surgery. The expression level of miRNA-145-5p, -150-5p, -20a-5p, -21-5p, -31-5p, -34a-5p, -375 was determined using real-time RT-PCR. Samples were stratified into different groups using the C-RT decision tree algorithm. All miRNAs, except miRNA-20a, were included in the decision tree, which allows stratification of samples for normal mucosa, dysplasia, and gastric cancer. Normal mucosa can be distinguished from gastric cancer only by miRNA-34a, -21, -375. Diagnostic characteristics for the detection of dysplasia: specificity - 97%, sensitivity - 87%; for the detection of gastric cancer: specificity - 91%, sensitivity - 93%. The sufficiently high values of the diagnostic characteristics for detecting dysplasia of the gastric mucosa and gastric cancer obtained in our study indicate the possibility of using expression data of a small amount of miRNAs for the effective separation of samples with tumor and precancerous changes in the stomach tissue.


Assuntos
MicroRNAs/genética , Lesões Pré-Cancerosas/diagnóstico , Neoplasias Gástricas/diagnóstico , Biomarcadores Tumorais/genética , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Inclusão em Parafina , Lesões Pré-Cancerosas/genética , Sensibilidade e Especificidade , Neoplasias Gástricas/genética
18.
Aliment Pharmacol Ther ; 51(8): 770-780, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32133670

RESUMO

BACKGROUND: Incidence and mortality of gastric cancer (GC) are high in Mongolia despite Helicobacter pylori in the Mongolian population being less virulent. AIM: To evaluate gastric bacterial microbiota profiles in patients with GC and its precursor histological conditions. METHODS: We conducted a case-control study among 48 GC and 120 noncancer patients (20 normal gastric mucosa [control], 20 gastritis, 40 with atrophy and 40 intestinal metaplasia [IM]). We performed 16S rRNA gene amplicon sequencing and compared taxonomic and functional prediction profiles based on the diagnosis group and H pylori infection status. RESULTS: The highest overall bacterial alpha diversity metrics were observed in the control group, followed by the IM and cancer groups. The gastritis and atrophy groups had the least diversity. Lactobacilli and Enterococci were the dominant genus in several cancer patients especially in the absence of H pylori. In addition, Carnobacterium, Glutamicibacter, Paeniglutamicibacter, Fusobacterium and Parvimonas were associated with GC regardless of H pylori infection. Firmicutes were decreased in the gastritis and atrophy groups and increased in the IM and cancer groups. The functional metabolic activity of the Embden-Meyerhof-Parnas pathway and the utilization of sugar, were significantly increased in cancer group compared with the noncancer group. CONCLUSION: Microbial factors other than H pylori may play a role in Mongolian GC. We identified novel associations between GC and the genera Enterococcus, Lactobacillus, Carnobacterium, Glutamicibacter, Paeniglutamicibacter, Fusobacterium, and Parvimonas.


Assuntos
Mucosa Gástrica/patologia , Microbioma Gastrointestinal , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/microbiologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/microbiologia , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Estudos de Casos e Controles , Estudos Transversais , Feminino , Mucosa Gástrica/microbiologia , Gastrite/epidemiologia , Gastrite/microbiologia , Microbioma Gastrointestinal/genética , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/genética , Humanos , Incidência , Masculino , Metaplasia/complicações , Metaplasia/epidemiologia , Metaplasia/patologia , Pessoa de Meia-Idade , Mongólia/epidemiologia , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/genética , Neoplasias Gástricas/patologia
19.
PLoS One ; 15(3): e0230220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32163505

RESUMO

Helicobacter pylori is a Gram-negative bacterium that causes chronic atrophic gastritis and peptic ulcers and it has been associated with the development of gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT). One of the more remarkable characteristics of H. pylori is its ability to survive in the hostile environment of the stomach. H. pylori regulates the expression of specific sets of genes allowing it to survive high acidity levels and nutrient scarcity. In the present study, we determined the expression of virulence associated protein D (VapD) of H. pylori inside adenocarcinoma gastric (AGS) cells and in gastric biopsies. Using qRT-PCR, VapD expression was quantified in intracellular H. pylori-AGS cell cultures at different time points and in gastric mucosa biopsies from patients suffering from chronic atrophic gastritis, follicular gastritis, peptic ulcers, gastritis precancerous intestinal metaplasia and adenocarcinoma. Our results show that vapD of H. pylori presented high transcription levels inside AGS cells, which increased up to two-fold above basal values across all assays over time. Inside AGS cells, H. pylori acquired a coccoid form that is metabolically active in expressing VapD as a protection mechanism, thereby maintaining its permanence in a viable non-cultivable state. VapD of H. pylori was expressed in all gastric biopsies, however, higher expression levels (p = 0.029) were observed in gastric antrum biopsies from patients with follicular gastritis. The highest VapD expression levels were found in both antrum and corpus gastric biopsies from older patients (>57 years old). We observed that VapD in H. pylori is a protein that is only produced in response to interactions with eukaryotic cells. Our results suggest that VapD contributes to the persistence of H. pylori inside the gastric epithelial cells, protecting the microorganism from the intracellular environment, reducing its growth rate, enabling long-term infection and treatment resistance.


Assuntos
Proteínas de Bactérias/genética , Gastrite Atrófica/etiologia , Helicobacter pylori/genética , Glicoproteínas de Membrana/genética , Estômago/microbiologia , Estômago/patologia , Adenocarcinoma/etiologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Técnicas de Cocultura/métodos , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Gastroscopia/métodos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Humanos , Intestinos/microbiologia , Intestinos/patologia , Masculino , Metaplasia/microbiologia , Metaplasia/patologia , Pessoa de Meia-Idade , Úlcera Péptica/metabolismo , Úlcera Péptica/patologia , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Antro Pilórico/microbiologia , Antro Pilórico/patologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Virulência/genética , Adulto Jovem
20.
Am J Pathol ; 190(6): 1256-1270, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32201262

RESUMO

Gastric cancer is associated with chronic inflammation (gastritis) triggered by persistent Helicobacter pylori (H. pylori) infection. Elevated tyrosine phosphorylation of the latent transcription factor STAT3 is a feature of gastric cancer, including H. pylori-infected tissues, and aligns with nuclear transcriptional activity. However, the transcriptional role of STAT3 serine phosphorylation, which promotes STAT3-driven mitochondrial activities, is unclear. Here, by coupling serine-phosphorylated (pS)-STAT3-deficient Stat3SA/SA mice with chronic H. felis infection, which mimics human H. pylori infection in mice, we reveal a key role for pS-STAT3 in promoting Helicobacter-induced gastric pathology. Immunohistochemical staining for infiltrating immune cells and expression analyses of inflammatory genes revealed that gastritis was markedly suppressed in infected Stat3SA/SA mice compared with wild-type mice. Stomach weight and gastric mucosal thickness were also reduced in infected Stat3SA/SA mice, which was associated with reduced proliferative potential of infected Stat3SA/SA gastric mucosa. The suppressed H. felis-induced gastric phenotype of Stat3SA/SA mice was phenocopied upon genetic ablation of signaling by the cytokine IL-11, which promotes gastric tumorigenesis via STAT3. pS-STAT3 dependency by Helicobacter coincided with transcriptional activity on STAT3-regulated genes, rather than mitochondrial and metabolic genes. In the gastric mucosa of mice and patients with gastritis, pS-STAT3 was constitutively expressed irrespective of Helicobacter infection. Collectively, these findings suggest an obligate requirement for IL-11 signaling via constitutive pS-STAT3 in Helicobacter-induced gastric carcinogenesis.


Assuntos
Mucosa Gástrica/metabolismo , Gastrite/metabolismo , Infecções por Helicobacter/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Mucosa Gástrica/patologia , Gastrite/patologia , Helicobacter , Infecções por Helicobacter/patologia , Humanos , Camundongos , Mitocôndrias/metabolismo , Fosforilação , Transdução de Sinais
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