Curcumin Encapsulated into Biocompatible Co-Polymer PLGA Nanoparticle Enhanced Anti-Gastric Cancer and Anti-Helicobacter Pylori Effect

Background: The current disadvantages (high cost, toxicity, resistance) of chemotherapy for gastric cancer opted people for alternative therapy from natural source. Curcumin (natural product) possess multiple biological activities but low bio-availability limits their uses as therapeutic. The Nano-formulation of curcumin increased the bioavailability and productivity of anti-cancer and anti-bacterial properties. The present study was initiated to determine the anti-cancer and anti-bacterial effect of Nano curcumin against gastric cancer and H. pylori. Methods: Curcumin loaded PLGA nanoparticles (CUR-NPs) was prepared by single emulsion solvent evaporation method. The MIC were determined using agar dilution method to find the anti-H. Pylori activity of Nano curcumin. The cytotoxicity of Nano curcumin was evaluated by MTT assay and the apoptotic effect (cell cycle arrest and morphology change) was shown by PI staining and microscopy. Results: The MIC of nanocurcumin and curcumin for all four H. pylori strains were 8 µg/ml and 16 µg/ml respectively. The inhibition rate of gastric cancer cells after treatment with curcumin was increased from 6% to 67% for 24h, from 8% to 75% for 48h, from 10% to 83% for 72h. In case of nanocurcumin, the inhibition rate increased from 7% to 69% for 24h, 11% to 87% for 48h and 16% to 97% for 72h. The IC50 of curcumin and Nano-curcumin were 24.20 µM and 18.78 µM respectively for 72 h. The population of cells in sub-G0 population increased from 4.1% in the control group to 24.5% and 57.8% when treated with curcumin and nanocurcumin respectively. After 72h of treatment with nanocurcumin, the apoptotic cells population increased as compared to native curcumin treated cells. Conclusion: The Nano curcumin might be used as a potential therapeutics against gastric cancer and H. Pylori. There is need of further in vivo study in order to validate CUR-NPs activity.     

Analysis of the correlation between P27 expression and Helicobacter pylori infection in gastric cancer

We aimed to explore the correlation between P27 expression and Helicobacter pylori (H. pylori) infection in gastric cancer, so as to provide evidence for understanding the pathogenesis of gastric cancer caused by H. pylori infection. A total of 82 samples of gastric cancer tissues and 56 samples of tumor-adjacent normal tissues collected from the gastrectomy were enrolled in this study. Then, 14C-urease breathing test was carried out to evaluate the infection of H. pylori in gastric cancer tissues, the expression of P27 in the tissue samples was detected by the immunohistochemistry staining, and the correlation between the H. pylori infection and P27 expression in gastric cancer was analyzed. Of 82 gastric cancer patients, there were 53 patients with H. pylori infection (64.63%). Among the patients with highly or moderately differentiated gastric cancer, the expression of P27 was much higher than that of patients with poorly differentiated gastric cancer (p < 0.01). Besides, comparison of the P27 expression between males and females, among different age groups, tumor sizes, TNM stages, tumor infiltration degrees, or lymph node metastasis, showed no significant differences (p > 0.05). Analysis of the correlation revealed that P27 expression was negatively correlated with the infection of H. pylori (p < 0.01). Multifactorial logistics regression analysis indicated that tumor differentiation was a risk factor of P27-positive expression in gastric cancer tissues (p < 0.01). In addition, P27 expression in the gastric cancer tissues was lower than that in the tumor-adjacent normal tissues (p < 0.01). In gastric cancer patients, expression of P27 is correlated with H. pylori infection which, via downregulating P27, can cause the cancerization of gastric mucosa, and P27, for its role in the development and progression of gastric cancer, is a potential auxiliary indicator for clinical diagnosis whether gastric cancer is complicated with H. pylori infection. So, P27 is a key indicator for diagnosis, treatment, and prognostic evaluation of disease in the advanced stage.     

幽门螺杆菌感染相关因素的研究进展

幽门螺杆菌（HP）是革兰阴性微需氧的螺旋样杆菌，主要通过口-口途径在人-人之间感染传播。HP的发现加深了人类对慢性感染、炎症和癌症之间关系的认识。其特定的螺旋形体型、鞭毛及动力、尿素酶和黏附素活性，以及细胞毒素基因A（cagA）、空泡细胞毒素基因A（vacA）等是影响HP感染研究较多的相关致病因素。HP感染在胃癌的发生、发展中可能具有重要作用，但尚未确切证实HP感染是导致胃癌的主因。文章概述了HP感染相关致病因素的研究进展。     

白光胃镜下内镜征象诊断幽门螺杆菌感染的临床研究

ObjectiveTo investigate the clinical value of endoscopic signs for diagnosing Helicobacter pylori(Hp) infection by white light endoscopy.     

基于网络药理学研究黄连解毒汤抗幽门螺杆菌感染作用机制

目的运用网络药理学方法预测黄连解毒汤抗Hp感染的主要有效成分、靶点及信号通路,挖掘其潜在作用机制,为后续实验研究提供依据。方法应用TCMSP筛选黄连解毒汤中黄连、黄芩、黄柏、栀子4味中药的主要有效成分及其潜在作用靶点。通过GeneCards数据库和人类孟德尔遗传数据库(OMIM)筛选Hp感染相关靶点,并取药物和疾病的交集靶点。将交集靶点导入Cytoscape 3.7.2构建有效成分和Hp感染相关靶点网络,并进行拓扑学分析。应用STRING在线分析平台构建靶蛋白相互作用(PPI)网络并进行分析。运用R语言在线检索Bioconductor平台对靶点进行GO功能富集;通过DAVID数据库对靶点进行KEGG通路富集分析。结果黄连解毒汤中共筛选出85个有效成分,主要包括槲皮素、小檗碱、山柰酚、汉黄芩素、黄芩素等。对应靶点112个,疾病相关靶点1960个,药物疾病共同靶点71个。网络中度值最高的有效成分为槲皮素,度值最高的靶点为环加氧酶1(PTGS1)。PPI网络中69个节点中度值较高的靶蛋白包括半胱氨酸蛋白酶3(CASP3)、IL6、MAPK8、原癌基因(MYC)、VEGFA、表皮生长因子受体(EGFR)等。GO功能富集分析共获得89个条目,KEGG通路富集分析共筛选12条存在显著差异的信号通路,其中发挥主要作用的有癌症通路、ErbB信号通路、p53信号通路、凋亡、黏附斑等。结论黄连解毒汤可通过多成分、多靶点、多通路发挥对Hp的治疗作用,可通过抗肿瘤机制调控胃癌进程,本研究可为其有效成分研究和抗Hp机制研究提供依据。     

Helicobacter pylori CagA oncoprotein interacts with SHIP2 to increase its delivery into gastric epithelial cells

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.     

降逆胃舒汤治疗萎缩性胃炎疗效及对患者病理评分的影响

目的:研究降逆胃舒汤对幽门螺杆菌感染致萎缩性胃炎病理评分的功效。方法:选取238例幽门螺杆菌感染致萎缩性胃炎患者作为本次研究观察对象,入选患者遵循随机数字表法平均分配入对照组与治疗组,对照组以常规西药四联疗法治疗,治疗组在对照组疗法的基础上给予降逆胃舒汤治疗; 治疗3个月后,观察两组患者HP清除率并随访6个月统计复发率,观察两组患者中医证候积分、胃黏膜胃镜征象积分、胃黏膜病理评分及血清胃泌素-17(G-17)、血清胃蛋白酶原Ⅰ、Ⅱ(PGⅠ、PGⅡ)、PGⅠ/PGⅡ比值(PGR)治疗前、后的变化情况。结果:治疗前两组患者各项中医证候、胃黏膜胃镜积分、病理评分及血清指标表达水平比较,差异无统计学意义(P>0.05); 治疗后两组患者各项中医证候、胃黏膜胃镜积分、病理评分及血清指标表达水平比较,差异有统计学意义(P<0.05),治疗组均优于对照组(P<0.05); 治疗后3个月时治疗组HP清除率为88.24%、对照组为73.11%,随访6个月治疗组复发率为3.81%,对照组为18.39%,两组HP根除率、复发率比较,差异有统计学意义(P<0.05)。结论:降逆胃舒汤能够提高幽门螺杆菌清除率并降低复发,更有效缓解幽门螺杆菌感染致萎缩性胃炎的各项中医证候,进一步改善患者胃黏膜病理评分与胃镜征象,更良好的调节患者血清指标。