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BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.
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BACKGROUND: The optimal sampling techniques for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) remain unclear and have not been standardized. The aim of this study was to compare the wet-suction and dry-suction techniques for sampling solid lesions in the pancreas, mediastinum, and abdomen. METHODS: This was a multicenter, crossover, randomized controlled trial with randomized order of sampling techniques. The 296 consecutive patients underwent EUS-FNA with 22G needles and were randomized in a ratio of 1:1 into two separate groups that received the dry-suction and wet-suction techniques in a different order. The primary outcome was to compare the histological diagnostic accuracy of dry suction and wet suction for malignancy. The secondary outcomes were to compare the cytological diagnostic accuracy and specimen quality. RESULTS: Among the 269 patients with pancreatic (nâ=â161) and non-pancreatic (nâ=â108) lesions analyzed, the wet-suction technique had a significantly better histological diagnostic accuracy (84.9â% [95â% confidence interval (CI) 79.9â%â-â89.0â%] vs. 73.2â% [95â%CI 67.1â%â-â78.7â%]; Pâ=â0.001), higher specimen adequacy (94.8â% vs. 78.8â%; Pâ<â0.001), and less blood contamination (Pâ<â0.001) than the dry-suction technique. In addition, sampling non-pancreatic lesions with two passes of wet suction provided a histological diagnostic accuracy of 91.6â%. CONCLUSIONS: The wet-suction technique in EUS-FNA generates better histological diagnostic accuracy and specimen quality than the dry-suction technique. Furthermore, sampling non-pancreatic lesions with two passes of EUS-FNA with wet suction may provide a definitive histological diagnosis when rapid on-site evaluation is not routinely available.
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Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pancreáticas , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Humanos , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Sucção/métodosRESUMO
OBJECTIVE: Published studies on the association between NCF4 rs4821544T/C polymorphism and inflammatory bowel disease (IBD) risk in Caucasian have yielded conflicting results. The present study aimed to provide more reliable conclusions by conducting a meta-analysis. METHODS: All eligible studies were extracted from Wiley Online Library, Chinese National Knowledge Infrastructure and PubMed databases. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the associations between rs4821544T/C polymorphism and IBD risk in Caucasian. RESULTS: A total of 13 case-control studies comprising 7441 Crohn's disease (CD) patients, 2565 ulcerative colitis (UC) patients and 8315 controls were included in this meta-analysis. Significant associations were found between CD and the rs4821544T/C polymorphism in three genetic models (C vs T: OR = 1.11, 95 % CI: 1.06, 1.16, P = 0.000; CC vs TT: OR = 1.31, 95 % CI: 1.18, 1.45, P = 0.000; CC/TC vs TT: OR = 1.07, 95 % CI: 1.01, 1.13, P = 0.014; CC vs TC/TT: OR = 1.28, 95 % CI: 1.16, 1.42, P = 0.000). However, significant associations were not found in UC under any genetic models (C vs T: OR = 1.04, 95 % CI: 0.97, 1.11, P = 0.264; CC vs TT: OR = 1.10, 95 % CI: 0.93, 1.30, P = 0.284; TC vs TT: OR = 1.04, 95 % CI: 0.95, 1.13, P = 0.429; CC/TC vs TT: OR = 1.04, 95 % CI: 0.95, 1.13, P = 0.390; CC vs TC/TT: OR = 1.07, 95 % CI: 0.91, 1.26, P = 0.409). CONCLUSION: This meta-analysis suggested that the rs4821544T/C polymorphism was associated with CD, but not UC in Caucasian.
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Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , NADPH Oxidases/genética , Estudos de Casos e Controles , Frequência do Gene , Humanos , Polimorfismo Genético , População BrancaRESUMO
INTRODUCTION: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are recommended in kidney disease and heart failure to reduce adverse clinical outcomes, but utilization can vary. To understand potential gaps in clinical practice and identify opportunities for improvement, we aimed to describe the prevalence and factors associated with SGLT2i prescription in patients with reduced kidney function hospitalized for fluid overload and/or heart failure. METHODS: Single-center observational study of patients with reduced kidney function (eGFR 20-59 mL/min/1.73 m2) hospitalized for fluid overload or heart failure between January 2022 and December 2023. Data were retrieved from electronic medical records. The outcome was SGLT2i prescription at discharge. Potential variables affecting SGLT2i prescription were identified during stakeholder engagement and evaluated using multivariable logistic regression. RESULTS: Among 2,543 patients, the median age was 79 (71, 86) years and admission eGFR was 38.7 (28.4, 49.4) mL/min/1.73 m2. SGLT2i was prescribed to 630 (24.8%) patients at discharge. SGLT2i prescription at discharge was independently associated with cardiovascular disease (OR 1.76, 95% CI: 1.31-2.35), diabetes (OR 1.59, 95% CI: 1.19-2.14), fluid overload or heart failure as the primary discharge diagnosis (OR 1.71, 95% CI: 1.29-2.28), SGLT2i pre-hospitalization (OR 104.91, 95% CI: 63.22-174.08), RAS blocker (OR 2.1, 95% CI: 1.65-2.89), and higher eGFR (OR 1.01, 95% CI: 1.003-1.02) at discharge; but inversely associated with older age (OR 0.97, 95% CI: 0.96-0.98). CONCLUSION: SGLT2i prescription at discharge was suboptimal among patients with reduced kidney function hospitalized for fluid overload and/or heart failure, especially in older age and more severe kidney disease. Additionally, cardiovascular disease, diabetes, primary discharge diagnosis of fluid overload or heart failure, prior SGLT2i use, and concurrent RAS blocker at discharge were independently associated with SGLT2i prescription at discharge. Interventions are needed to increase clinicians' knowledge and overcome clinical inertia to increase SGLT2i use in patients with fluid overload and heart failure.
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Taxa de Filtração Glomerular , Insuficiência Cardíaca , Hospitalização , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/complicações , Masculino , Idoso , Feminino , Idoso de 80 Anos ou mais , Taxa de Filtração Glomerular/efeitos dos fármacos , Hospitalização/estatística & dados numéricos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Desequilíbrio Hidroeletrolítico/epidemiologiaRESUMO
OBJECTIVE: To investigate the therapeutic efficacy and safety of aspartate-ornithine granules in patients with nonalcoholic steatohepatitis (NASH). METHODS: Seventy-two patients with NASH were included in this multiple-dose parallel controlled clinical trial and received a 12-week course of aspartate-ornithine granule treatment at either high-dose (6 g bid po; n = 38) or low-dose (3 g bid po; n = 34). Clinical efficacy was assessed by monitoring data from urinalysis, serologic tests (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and triglyceride (TG)), and abdominal computed tomography (CT) scan. Safety was assessed by occurrence of adverse events (fatigue, anorexia, abdominal distension, nausea, and vomiting). Statistical analyses were conducted to determine the significance of differences between parameters before (baseline) and after treatment. RESULTS: After 12 weeks of treatment, the liver and spleen CT ratios in both the high-dose group (0.89 +/- 0.19) and the low-dose group (0.80 +/- 0.15) were significantly higher than at baseline (S = 329, P less than 0.0001 and S = 246, P less than 0.0001); the overall improvement was more robust in the high-dose group (52.63%) than in the low-dose group (38.23%) (Z = -2.1042, P less than 0.05). After 6 and 12 weeks of treatment, the serum ALT levels in both the high-dose group and the low-dose group were significantly lower than at baseline (6 weeks: S = 324.5, P less than 0.0001 and S = 223, P less than 0.0001; 12 weeks: S = 370.5, P less than 0.0001 and S = 297.5, P less than 0.0001); the overall improvement was more robust in the high-dose group (79.0%) than in the low-dose group (53.0%) (Z = -2.0533, P less than 0.05). Similar trends were seen for the serum levels of AST and GGT after 6 and 12 weeks of treatment (all P less than 0.01) and serum levels of TG after 12 weeks of treatment. The rate of adverse reactions was low and similar between the two groups (high-dose: 4.8% and low-dose: 4.4%; all gastrointestinal). CONCLUSION: Aspartate-ornithine granule therapy was an effective and safe treatment of nonalcoholic steatohepatitis, with the higher dose of 6 g bid po providing more robust clinical benefit without affecting the safety profile.
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Dipeptídeos/administração & dosagem , Dipeptídeos/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Triglicerídeos/sangue , gama-Glutamiltransferase/sangueRESUMO
OBJECTIVE: To observe the growth-inhibitory effect of polypeptide P110, designed with G3BP protein targets, plus cisplatin on human colon cancer HCT-116 cells and mouse colon cancer C26 xenotransplanted tumors in mice. METHODS: The proliferation inhibition of HCT-116 cells and HUVEC cells in vitro was evaluated by MTT assay. A mouse model of xenotransplanted C26 mouse colon cancer was established. The inhibitory effects of P110 and cisplatin at different concentrations on C26 xenotransplanted tumors were assessed. RESULTS: P110 enhanced the inhibitory effect of cisplatin on proliferation of HCT-116 cells. By treated with 20 µmol/LP110 + 10, 30, 90 µmol/L cisplatin, the proliferation inhibitory rates were (43.3 ± 3.2)%, (46.4 ± 4.6)% and (47.6 ± 5.8)%, respectively, significantly higher than that in the cisplatin group (P < 0.05). 20 µmol/L P110 + 10 µmol/L cisplatin effectively killed HCT-116 cells, whereas with less toxicity to HUVEC cells. The tumor inhibition rates in mice of P110 (25 mg/kg, 50 mg/kg, 100 mg/kg) plus cisplatin (1 mg/kg) were 23.0%, 30.4% and 34.2%, respectively. While, the tumor inhibition rates in mice of the cisplatin group (1 mg/kg) was 22.7%. Compared with cisplatin at the same concentration, the tumor inhibition rates in mice of the P110 plus cisplatin groups were all increased. CONCLUSIONS: P110 can enhance the growth inhibitory effects of cisplatin on HCT-116 cells and C26 xenotransplanted tumors in mice. P110 plus cisplatin can reduce the effective dose of cisplatin and decrease the toxicity of cisplatin.
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Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Neoplasias do Colo/patologia , Peptídeos/farmacologia , Animais , Linhagem Celular Tumoral , Sinergismo Farmacológico , Células HCT116 , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Distribuição Aleatória , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: The results from previous studies on association between prostaglandin E receptor 4 (PTGER4) polymorphisms and inflammatory bowel disease (IBD) risk in Caucasian were conflict. The present study aimed to investigate the genetic association by conducting a meta-analysis. METHODS: Systematic literature search was conducted through Wiley Online Library, Chinese National Knowledge Infrastructure (CNKI), and PubMed databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to investigate the associations between rs4613763âT/C, 17234657T/G polymorphisms, and IBD risk in Caucasian. RESULTS: Twenty case-control studies consisting of 18,495 Crohn disease (CD) patients and 4203 ulcerative colitis (UC) patients, as well as 26,063 controls were included in this meta-analysis. The rs4613763T/C polymorphism had obvious influence on CD, UC risk in Caucasian. However, rs17234657T/G polymorphism had obvious influence on CD but not UC in Caucasian. CONCLUSION: This meta-analysis suggested that both the rs4613763âT/C, rs17234657T/G polymorphisms had obvious influence on risk of CD in Caucasian. In addition, rs4613763âT/C, polymorphism had obvious influence on risk of UC in Caucasian.
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Doenças Inflamatórias Intestinais/genética , Receptores de Prostaglandina E Subtipo EP4/genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , População BrancaRESUMO
BACKGROUND: Poor habits can worsen gastroesophageal reflux disease (GERD) and reduce treatment efficacy. Few large-scale studies have examined lifestyle influences, particularly eating habits, on GERD in China, and research related to eating quickly, hyperphagia, and eating hot foods is quite limited. The aim of this study was to evaluate the relationship between GERD pathogenesis and lifestyle factors to produce useful information for the development of a clinical reference guide through a national multicenter survey in China. METHODS: Symptom and lifestyle/habit questionnaires included 19 items were designed. The questionnaire results were subjected to correlation analysis relative to GERD symptom onset. A standard proton pump inhibitor (PPI) was advised to correct patients with unhealthful lifestyle habits. RESULTS: A total of 1518 subjects (832 GERD, 686 non-GERD) enrolled from six Chinese hospitals completed symptom and lifestyle/habit questionnaires. The top lifestyle factors related to GERD were fast eating, eating beyond fullness, and preference for spicy food. Univariate analysis showed that 21 factors, including male gender, a supra-normal body mass index (BMI), smoking, drinking alcohol, fast eating, eating beyond fullness, eating very hot foods, and drinking soup, among others, were associated with GERD (p < 0.05). Logistic multivariate regression analysis revealed the following risk factors for GERD [with odds ratios (ORs)]: fast eating (4.058), eating beyond fullness (2.849), wearing girdles or corsets (2.187), eating very hot foods (1.811), high BMI (1.805), lying down soon after eating (1.544), and smoking (1.521). Adjuvant lifestyle interventions improved outcomes over medication alone (z = -8.578, p < 0.001 Mann-Whitney rank sum test). CONCLUSIONS: Lifestyle interventions can improve medication efficacy in GERD patients. Numerous habits, including fast eating, eating beyond fullness, and eating very hot foods, were associated with GERD pathogenesis. The present results may be useful as a reference for preventive education and treatment.
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AIM: To investigate the relationship between the staging by endoscopic ultrasonography (EUS) and the expression of carcinoma metastasis associated gene in the patients with gastric carcinoma. METHODS: Sixty-three patients with gastric cancer were diagnosed by electric gastroscopy and EUS. The preoperative staging of gastric cancer was measured by EUS and compared with pathologic staging and MMP-9 expression. Peripheral serum level of MMP-9 was measured with enzyme-linked immunosorbent assay (ELISA), while the expression of MMP-9 protein was tested with immunohistochemistry and hybridization in situ in the gastric carcinoma tissues. RESULTS: The total accuracy of EUS in estimating invasive depth of gastric cancer was 80.95%, while that in estimating lymphatic metastasis was 73.02%. Serum MMP-9 levels were consistent with the expression of MMP-9 protein and MMP-9 mRNA in tissue, a result closely correlated with invasive degree, staging with EUS and lymphatic metastasis in gastric cancer (P<0.05). The total accuracy of estimating invasive depth in gastric cancer was 95.22% using both EUS and MMP-9. CONCLUSION: The MMP-9 level of preoperative serum presents the reference value for preoperative staging by EUS in the patients with gastric cancer. When serum MMP-9 level in gastric cancer is significantly high, physicians should pay closer attention to the metastasis which reaches the serosa or beyond. Combining EUS and MMP-9 improves the accuracy in deciding the invasion and metastasis in the patients with gastric carcinoma.
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Endossonografia , Metaloproteinase 9 da Matriz/sangue , Estadiamento de Neoplasias/métodos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico por imagem , Adulto , Idoso , Biópsia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico por imagem , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias Gástricas/patologiaRESUMO
AIM: To determine whether the mast cell (MCs) and tumor-associated macrophage (TAMs) counts have any correlation with clinical outcome in colorectal cancer, and to investigate whether MCs undergo phenotypic changes in colorectal cancer. METHODS: The MC and TAM counts were determined immunohistochemically in 60 patients with colorectal cancer and the depth of invasion, lymph node metastasis rate, distant metastasis rates, and survival rates were compared between patients with low (less than the mean number of positive cells) and high (more than the mean number of positive cells) cell counts. RESULTS: Both patients with a low MC count and patients with a low TAM count had significantly deeper depth of invasion than those with a high MC count and those with a high TAM count (P<0.01 and P<0.01 respectively). Patients with a high MC count and patients with a high TAM count were significantly higher showing significantly lower rates of lymph node metastasis, distant metastasis than those with a low MC count and those with a low TAM count. There were significant positive correlation between MC counts and TAM counts (r = 0.852, P<0.01). In both cancerous tissue and normal colorectal tissue, the predominant MC phenotype was MC(TC). The 5-year survival rate estimated was significantly lower in both patients with a low MC count and patients with a low TAM count than in those with a high MC count and those with a high TAM count (P<0.05 and P<0.01 respectively). CONCLUSION: There appears to be a direct relationship between the number of MCs and clinical outcome in patients with colorectal cancer, even though MCs exhibited no significant phenotypic changes. TAM count is of value to predict the clinical outcome or prognosis. It is more beneficial for estimating biological character of colorectal carcinoma to combine MC and TAM counts.
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Neoplasias Colorretais/imunologia , Vigilância Imunológica , Macrófagos/imunologia , Mastócitos/imunologia , Idoso , Idoso de 80 Anos ou mais , Antígenos/metabolismo , Contagem de Células , Quimases , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/secundário , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Macrófagos/citologia , Masculino , Mastócitos/citologia , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Serina Endopeptidases/metabolismo , Análise de Sobrevida , TriptasesRESUMO
Artesunate, a derivative of artemisinin isolated from Artemisia annua L., has been traditionally used to treat malaria, and artesunate has demonstrated cytotoxic effects against a variety of cancer cells. However, there is little available information about the antitumor effects of artesunate on human gastric cancer cells. In the present study, we investigated the antitumor effect of artesunate on human gastric cancer cells and whether its antitumor effect is associated with reduction in COX-2 expression. The effects of artesunate on the growth and apoptosis of gastric cancer cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis of annexin V-fluorescein isothiocyanate/propidium iodide staining, rhodamine 123 staining, and Western blot analysis. Results indicate that artesunate exhibits antiproliferative effects and apoptosis-inducing activities. Artesunate markedly inhibited gastric cancer cell proliferation in a time- and dose-dependent manner and induced apoptosis in gastric cancer cells a dose-dependent manner, which was associated with a reduction in COX-2 expression. Treatment with the selective COX-2 inhibitor celecoxib, or transient transfection of gastric cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Furthermore, the treatment with artesunate promoted the expression of proapoptotic factor Bax and suppressed the expression of antiapoptotic factor Bcl-2. In addition, caspase-3 and caspase-9 were activated, and artesunate induced loss of mitochondrial membrane potential, suggesting that the apoptosis is mediated by mitochondrial pathways. These results demonstrate that artesunate has an effect on anti-gastric cancer cells. One of the antitumor mechanisms of artesunate may be that its inhibition of COX-2 led to reduced proliferation and induction of apoptosis, connected with mitochondrial dysfunction. Artesunate might be a potential therapeutic agent for gastric cancer.
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BACKGROUND/AIMS: Chromogranin A (CgA), a major soluble protein released by the neuroendocrine system, functions as a prohormone by giving rise to several biologically active peptides. Our study aimed to evaluate the relationship between CgA levels and nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: In total, 111 NAFLD patients and 120 healthy controls were enrolled in the trial. The levels of plasma CgA were quantified by an available enzyme-linked immunosorbent assay kit. Pearson's correlation analysis was conducted to detect whether CgA levels correlated with oxidative stress, insulin resistance, and inflammation profile. A multiple stepwise regression model was used to explore independent determinants for plasma CgA levels. Multivariate logistic regression analysis was conducted to assess whether CgA levels were independent predictors of NAFLD. RESULTS: The levels of plasma CgA between the case and control groups were significantly different (70.9±8.1 µg/L vs 47.6±11.3 µg/L). The levels of plasma CgA positively correlated with high-sensitivity C-reactive protein (hs-CRP; p=0.000), fasting blood glucose (FBG; p=0.025), homeostasis model assessment of insulin resistance index (HOMA-IR; p=0.012), and malondialdehyde (MDA; p=0.037) levels, but negatively associated with superoxide dismutase (SOD; p=0.041) levels. The multiple stepwise regression model indicated that hs-CRP, MDA, and HOMA-IR were independent determinants for plasma CgA levels. The logistic regression analysis showed that plasma levels of CgA were independent predictors of NAFLD. CONCLUSION: Increased plasma CgA levels were associated with NAFLD.
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Cromogranina A/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
The plant growth, phosphate acquisition, Cd translocation, phytochelatins (PCs) production and antioxidant parameters [superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (POD), ascorbate peroxidase (APX), glutathione reductase (GR), glutathione (GSH), ascorbate (ASA) and malonaldehyde (MDA)] were investigated in Cd-hyperaccumulator Solanum photeinocarpum inoculated with Glomus versiforme BGC GD01C (Gv) in Cd-added soils (0, 5, 10, 20, 40 mg Cd kg-1 soil). Mycorrhizal colonization rates were generally high (from 77% to 94%), and hardly affected by Cd. Gv colonization significantly enhanced P acquisition, growth and total Cd uptakes in both shoots and roots of S. photeinocarpum at all Cd levels. Meanwhile, Gv symbiosis significantly increased Cd concentration in the roots, and decreased Cd concentration in the shoots at all Cd levels, which indicates that Gv could promote phytostabilization by enhancing Cd accumulation in the roots to inhibit its translocation to shoots and the "dilution effects" linked to an increase in plant dry matter yield and a reduced Cd partitioning to shoots. Moreover, the improvement of CAT, POD and APX activities in the leaves of mycorrhizal plants infers that Gv symbiosis helped S. photeinocarpum to relieve oxidative damage to biomolecules in Cd-contaminated soil. The evident decline of MDA content in the leaves of mycorrhizal plants indicates that Gv symbiosis evidently improved antioxidant activities, and the enhancement of PCs production in the leaves of mycorrhizal plants suggests that Gv-inoculated plant may be more efficient to relieve Cd phytotoxicity. Therefore, the possible mechanisms of Cd phytotoxicity alleviation by Gv can be concluded as the decline of Cd concentration in the shoots and the improvement of P acquisition, PCs production and activities of CAT, POD, APX in mycorrhizal plants.
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Antioxidantes/metabolismo , Cádmio/metabolismo , Glomeromycota/fisiologia , Fitoquelatinas/metabolismo , Solanum/metabolismo , Cádmio/química , Cádmio/toxicidade , Malondialdeído/metabolismo , Micorrizas/enzimologia , Micorrizas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Folhas de Planta/enzimologia , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Poluentes do Solo/química , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade , Solanum/enzimologia , Solanum/crescimento & desenvolvimento , Simbiose/efeitos dos fármacosRESUMO
AIM: To study the expression of CDw75 in patients with gastric carcinoma and to correlate CDw75 expression with progression of the tumor. METHODS: Immunohistochemical method was used to examine the expression of CDw75 in 72 cases of the gastric carcinoma and adjacent normal gastric mucosa, and the percentage of the cells positively stained with CDw75 was calculated using a computer-aided microscopic image analysis system. RESULTS: CDw75 was not expressed in normal gastric mucosa but detected in 37 of the 72 neoplastic gastric lesions. The expression of CDw75 was associated with the tumor progression as indicated by its close correlation with the depth of the tumor infiltration (chi(2)=18.415, P<0.01), TNM stage (chi(2)=10.419, P<0.05) and lymph node metastasis (chi(2)=6.675, P<0.01). The overall survival rate of the patients with positive CDw75 expression (32.4%) was significantly lower than that of the patients without CDw75 expression (71.4%) (P<0.01). There was no significant correlation between the expression of CDw75 and the sex and age and histological type of patients (P>0.05). CONCLUSION: These findings suggest that the expression of CDw75 is a significant histopathological marker for more advanced stage of gastric carcinoma and indicates a poor prognosis for the patients.
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Antígenos CD/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Adulto , Idoso , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Valor Preditivo dos Testes , Prognóstico , Sialiltransferases , Neoplasias Gástricas/mortalidade , Taxa de SobrevidaRESUMO
Cyclooxygenase-2 (COX-2) and its metabolite prostaglandin E2 (PGE2) can potentially affect most of the events in cancer development, including promotion of proliferation, resistance to apoptosis, angiogenesis, immune suppression and invasion. However, worldwide attention has predominantly centered on the cardiovascular toxicity of selective COX-2 inhibitors. Paeonol is a major active extract from the root bark of Paeonia suffruticosa Andrews with antiinflammatory, anti-oxidant, anti-allergic, anti-oxidation and antitumor effects. In the present study, we investigated the underlying mechanisms of paeonol in inducing apoptosis and aimed to ascertain whether its antitumor effect is associated with a reduction in COX-2 expression and a decrease in the levels of PGE2 in colorectal cancer cells. We observed that paeonol inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner in colorectal cancer cells, which was associated with a reduction in COX-2 expression and PGE2 synthesis. Treatment with the selective COX-2 inhibitor, celecoxib, or transient transfection of colorectal cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Western blot analysis showed that paeonol inhibited the activation of NF-κB, an upstream regulator of COX-2, and its translocation to the nucleus. Treatment with increasing doses of paeonol led to increased expression of pro-apoptotic factor Bax and decreased expression of anti-apoptotic factor Bcl-2. Caspase-3 and caspase-9 were activated, and paeonol induced loss of mitochondrial membrane potential, suggesting that the apoptosis induced by paeonol was mediated by mitochondrial pathways. In addition, paeonol significantly suppressed tumor growth in a xenograft tumor mouse model in a dose-dependent manner. Our findings indicate that paeonol exerts an antitumor effect on human colorectal cancer cells by inhibiting PGE2 production and COX-2 expression. We expect that paeonol may replace selective COX-2 inhibitors due to their toxic effects, and may offer a new strategy for the therapy of colorectal cancer.
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Acetofenonas/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Ciclo-Oxigenase 2/biossíntese , Dinoprostona/biossíntese , Animais , Apoptose/efeitos dos fármacos , Caspase 3/biossíntese , Celecoxib , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ciclo-Oxigenase 2/genética , Dinoprostona/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , NF-kappa B/biossíntese , Pirazóis/administração & dosagem , Sulfonamidas/administração & dosagemRESUMO
AIM: To systematically evaluate the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer. METHODS: A comprehensive electronic search was conducted for articles published up until January 27, 2014 in Medline (PubMed), Excerpta Medica Database (Embase), the Cochrane Library and Google Scholar. Only case-control studies published in English that evaluated the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer were included. Furthermore, only studies with sufficient data allowing for calculation of odds ratio (OR) and corresponding 95% confidence interval (CI) were included. These values were used in the quantitative synthesis to assess the strength of the association between the miR-146a rs2910164 polymorphism and risk of gastric cancer. RESULTS: The database search identified 1002 eligible studies, of which seven (comprising 4112 cases and 5811 controls) were included for the meta-analysis. The results indicate that miR-146a rs2910164 polymorphism is more likely to be associated with gastric cancer risk. In the overall analysis, a significantly increased cancer risk was found in the heterozygote (GG vs GC) comparison (OR = 1.14, 95%CI: 1.03-1.27; P = 0.01 for pooled OR). In the ethnicity subgroup analysis, a similar result was found among Caucasians (OR = 1.36, 95%CI: 1.01-1.85; P = 0.04 for pooled OR). In the stratified analysis by quality of studies, a significantly increased cancer risk was found in the heterozygote comparison among high quality studies (OR = 1.12, 95%CI: 1.01-1.26; P = 0.04 for pooled OR). When stratified on the basis of sample size, a significantly increased cancer risk was found among small sample size subgroups for the allelic (G vs C: OR = 1.16, 95%CI: 1.03-1.30; P = 0.01), homozygote (GG vs CC: OR = 1.33, 95%CI: 1.03-1.73; P = 0.03) and recessive model (GG vs GC + CC: OR = 0.05, 95%CI: 0.00-0.10; P = 0.03) comparisons. CONCLUSION: The miR-146a rs2910164 polymorphism is associated with increased gastric cancer risk, particularly evident in high quality studies with small sample sized Caucasian populations.
Assuntos
MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Povo Asiático/genética , Distribuição de Qui-Quadrado , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Razão de Chances , Fenótipo , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/etnologia , População Branca/genéticaRESUMO
OBJECTIVE: There is emerging evidence that the microRNA-146a (miR-146a) rs2910164 polymorphism might be associated with the susceptibility to colorectal cancer (CRC). However, previous published studies have failed to achieve a definitive conclusion. We aimed to address this issue in an updated meta-analysis. METHODS: A comprehensive literature search was conducted in PubMed, Embase, China BioMedicine, the Cochrane Library and Google Scholar to identify eligible studies. Case-control studies written in English that evaluated the association between miR-146a polymorphism and CRC were included. Odds ratio and 95% confidence interval were calculated in the quantitative synthesis. RESULTS: Overall seven case-control studies including a total of 2978 cases and 3576 cancer-free or healthy controls were enrolled in the meta-analysis. The results indicated that there was no association between miR-146a G/C rs2910164 polymorphism and CRC risk either in the overall analysis or among Asians, when stratified on the basis of ethnicity. CONCLUSION: miR-146a G/C genetic polymorphism was not related to the susceptibility to CRC.
Assuntos
Neoplasias Colorretais/genética , MicroRNAs/genética , Povo Asiático , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Polimorfismo GenéticoRESUMO
The present study aimed to investigate the effects of silencing RIP1 by small interfering RNA (siRNA) on the biological behavior of the LoVo human colorectal carcinoma cell line and to provide evidence for the feasibility of colorectal cancer gene therapy. LoVo cells were divided into the RIP1 siRNA group, the blank control group and the negative control group. Chemically synthesized siRNA targeting RIP1 (RIP1 siRNA) was transfected into LoVo cells. Following transfection of the RIP1-targeted siRNA into the LoVo cells, the expression of the RIP1 gene was effectively inhibited. The results demonstrated that RIP1 effectively regulated the malignant biological behavior of the LoVo colon cancer cell line. Furthermore, the proliferation, motility and invasiveness of LoVo cells were inhibited by siRNA knockdown of RIP1. The results revealed that the RIP1 gene has an important role in the regulation of proliferation and apoptosis in colorectal carcinoma cells.
RESUMO
Paeonol, a major phenolic component of the root bark of Paeonia moutan, is known to exhibit antitumor effects. However, the underlying mechanisms remain unknown. In the present study, the effects of paeonol on cell viability, intracellular calcium concentration and the expression of runtrelated transcription factor 3 (RUNX3) were analyzed in LoVo human colon cancer cells. Results revealed that paeonol markedly reduced LoVo cell viability in a time and dosedependent manner. Flow cytometry assays demonstrated that paeonol blocked the cell cycle at the G1 to S transition and significantly induced apoptosis in LoVo cells. Intracellular calcium accumulation occurred following a 48 h treatment with paeonol. Furthermore, RUNX3 gene expression was increased in paeonoltreated cells. These observations indicate that paeonol possesses antiproliferative properties and apoptosisinducing activity. One of the antitumor mechanisms of paeonol may be its apoptosisinducing activity through an increased intracellular calcium concentration and the upregulation of RUNX3 expression. Paeonol may be a promising antitumor agent for colon carcinoma treatment.
Assuntos
Acetofenonas/farmacologia , Cálcio/metabolismo , Neoplasias do Colo/metabolismo , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Espaço Intracelular/metabolismo , Acetofenonas/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Ensaios de Seleção de Medicamentos Antitumorais , Fase G1/efeitos dos fármacos , Fase G1/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Espaço Intracelular/efeitos dos fármacos , Fase S/efeitos dos fármacos , Fase S/genéticaRESUMO
The combined use of currently used anticancer genotoxins with other drugs is a therapeutic tool for potentially increasing the efficacy of the genotoxins. In the present study, the effects of a RasGAP-derived peptide, P110 (RasGAP301-316), designed to target Ras-GTPase activating protein SH3 domain-binding proteins (G3BPs), on the chemotherapeutic agent, cisplatin (DDP), were examined. P110 was demonstrated to enhance the effect of DPP in vitro and in vivo. The results indicate that P110 significantly increased the DDP-induced apoptosis in SGC-7901, HCT-116, HeLa and A-549 cells. Furthermore, P110 combined with DDP significantly suppressed the growth of C26 xenograft tumors in a dose-dependent manner. This synergistic effect may be associated with DDP-induced apoptosis, involving the downregulation of Bcl-2 and the upregulation of Bax, cytochrome c and caspase-3. The results of the present study indicate that P110, in combination with chemotherapeutics, is likely to represent a potential therapeutic strategy for cancer.