Insight into the bovine milk peptide LPcin‐YK3 selection in the proteolytic system of Lactobacillus species

Antimicrobial peptides are class of small, positively charged peptides known for their broad‐spectrum antimicrobial activity. Antimicrobial activities for most antimicrobial peptides have largely remained elusive, particularly in the lactic acid bacteria. However, recently our investigation using LPcin‐YK3, an antimicrobial peptide from bovine milk, suggests that in vitro antimicrobial activity was reduced over 100‐fold compared with pathogenic bacteria. Additionally, for the structural study of how antimicrobial peptide undergoes its reaction at the proteolytic pathway of lactic acid bacteria based on degradation assay and propidium iodide staining, we performed molecular docking for interaction between oligopeptide‐binding protein A and LPcin‐YK3 peptide. Given that degradation related to the LPcin‐YK3 peptide in lactic acid bacteria proteolytic system, the inhibitory inactivity of LPcin‐YK3 against beneficial lactic acid bacteria strains may be one of the primary pharmacological properties of recombinant peptide discovered in bovine milk. These results provide structural and functional insights into the proteolytic mechanism and possibility as a putative substrate of oligopeptide‐binding protein A in respect of LPcin‐YK3 peptide.     

Enantioanalysis of tryptophan in whole blood samples using stochastic sensors—A screening test for gastric cancer

Tryptophan is a key amino acid related to metabolomics in gastric cancer. To date, methods were developed only for the assay of l -tryptophan, the role of d -tryptophan being not yet established. Therefore, four stochastic sensors based on different graphene materials modified with β-cyclodextrins, 2,2-diphenyl-1-picrylhydrazyl, and protoporphyrin IX were designed and used for enantioanalysis of tryptophan in whole blood samples. High sensitivities, and reliabilities were recorded when the stochastic sensors were used for the enantioanalysis of tryptophan in whole blood samples. The paper opened a new chapter in early detection of gastric cancer, based on establishing the role of d -tryptophan in metabolomics, and in early diagnosis of gastric cancer.     

硫氧还蛋白还原酶1(TrxR1)在胃癌中的表达及对胃癌细胞生长的影响*

目的: 探讨胃癌组织硫氧还蛋白还原酶1(TrxR1)表达与生存时间的关系及其对胃癌细胞生长的影响。方法: 用Real-time PCR法检测76例胃癌组织及癌旁TrxR1 mRNA表达,并分析其与胃癌患者临床病理特征及预后的关系;随机选取3例胃癌组织及癌旁组织,采用免疫组化法、Western blot法检测TrxR1蛋白表达。采用Western blot法和Real-time PCR法检测胃癌细胞系及人胃粘膜上皮细胞中TrxR1的表达。采用小RNA干扰序列(siRNA)处理AGS细胞,根据处理方法不同将AGS细胞分为3组:阴性对照组:转染NC-siRNA、TRXR1 siRNA干扰1组:转染TRXR1-siRNA1、TRXR1 siRNA干扰2组:转染TRXR1-siRNA2。使用Real-time PCR法检测各组AGS细胞中TrxR1 mRNA的表达,克隆形成试验和MTT法检测AGS细胞生长情况。结果: 胃癌组织中TrxR1 mRNA和蛋白表达量均显著性上调,TrxR1主要定位于细胞质中。TrxR1高表达与患者TNM分期及淋巴结转移有关,且TrxR1高表达组患者的中位生存时间短于低表达组(P＜0.05)。胃癌细胞中TrxR1表达量高于人胃粘膜上皮细胞系中的表达。TRXR1-siRNA1组AGS细胞和TRXR1-siRNA2组AGS细胞中TrxR1 mRNA和蛋白与NC-siRNA组相比均显著性降低(P＜0.05),且AGS细胞克隆形成与增殖能力均降低(P＜0.05)。结论: 胃癌组织中TrxR1高表达提示患者预后不良,沉默TrxR1能抑制胃癌细胞的增殖。     

葛根芩连汤在模拟胃肠液中对微生物生长的影响

目的探究葛根芩连汤在模拟胃肠液中对微生物生长的影响。方法在模拟胃肠液中分别加入消化液10%量的金黄色葡萄球菌、大肠埃希菌、沙门菌、产气杆菌、黑曲霉、米曲霉、青霉和汉逊德巴利酵母,然后加入生药浓度为1 g/mL的葛根芩连汤水煎液,37℃恒温培养。分别在0、1、2和4 h吸取1 mL培养液做稀释平板计数。结果体外模拟肠液中,葛根芩连汤对金黄色葡萄球菌、大肠埃希菌、沙门菌、产气杆菌、黑曲霉、米曲霉和青霉有较强的抑制作用,而对汉逊德巴利酵母的生长则为先促进后抑制,并且在2 h时对黑曲霉、米曲霉、青霉和汉逊德巴利酵母的抑制效果最显著;在模拟胃液中,葛根芩连汤对金黄色葡萄球菌、大肠埃希菌、沙门菌、黑曲霉、青霉和汉逊德巴利酵母均有一定的抑制作用,而对产气杆菌无明显影响。结论葛根芩连汤在模拟胃肠液中对金黄色葡萄球菌、大肠埃希菌、沙门菌、黑曲霉、米曲霉、青霉和汉逊德巴利酵母等均具有一定的抑制作用,在模拟肠液中对产气杆菌抑制作用明显,而在模拟胃液中对其抑制效果不明显。     

精准营养联合生长抑素对胃癌根治术患者的临床疗效

目的探讨生长抑素联合精准营养疗法对胃癌根治术患者术后营养指标水平和肠道菌群的影响。方法选取我院2017年10月至2019年1月收治并拟行胃癌根治术治疗的92例胃癌患者为研究对象,随机分为对照组(46例)和观察组(46例)。两组患者术后均给予常规处理。对照组患者同时给予生长抑素+常规肠外营养支持,观察组患者同时给予生长抑素+精准营养支持。于营养干预前后统计两组患者营养相关指标[体质量、血清白蛋白(ALB)、前白蛋白(PA)、淋巴细胞计数(LC)、肌酐(Ct)以及尿素氮(UN)]水平;对肠道菌群进行alpha分析,并计算肠杆菌、肠球菌、乳杆菌和双歧杆菌数量。结果营养干预前,两组患者营养相关指标水平以及肠道菌群相关指标水平之间差异无统计学意义(均P>0.05)。营养干预后,(1)观察组患者平均体质量以及血清ALB、PA、LC水平分别为(56.98±5.34)kg、(29.98±6.03)mg/L、(137.14±35.17)g/L、(1.15±0.26)×10⁹,对照组分别为(53.29±5.18)kg、(26.12±5.29)mg/L、(104.53±27.66)g/L、(0.82±0.18)×10⁹,两组之间差异有统计学意义(均P<0.05);(2)观察组患者肠道菌群Chao指数和Ace指数水平分别为(397.84±75.23)、(408.26±78.34),对照组分别为(362.13±66.23)、(371.19±70.09),两组之间差异有统计学意义(均P<0.05);(3)观察组患者肠道肠杆菌、肠球菌数量明显低于对照组,而乳杆菌、双歧杆菌数量明显高于对照组(均P<0.05)。结论胃癌根治术患者术后联合生长抑素和精准营养疗法能够显著改善患者的营养状况,保持肠道菌群丰度,平衡肠道菌群分布,值得临床研究和应用。     

The correlation of microRNA-499 rs3746444 T>C locus with the susceptibility of gastric cancer: from a case–control study to a meta-analysis

The relationship between rs3746444 T>C single-nucleotide polymorphism (SNP) in microRNA (mir)-499 and risk of gastric cancer (GC) has been widely investigated. However, the association was still unconfirmed. Here, we first recruited 490 GC patients and 1476 controls, and conducted a case-control study. And we did not find any association between rs3746444 T>C SNP polymorphism and risk of GC. Subsequently, we conducted a meta-analysis to explore the association of mir-499 rs3746444 polymorphism with GC development. Two authors searched the PubMed and EMBASE databases up to October 15, 2019 independently. Finally, nine literatures involving 12 independent studies were included. In total, 3954 GC cases and 9745 controls were recruited for meta-analysis. The results suggested that allele model, homozygote model and recessive model could increase the risk of overall GC (P = 0.002, 0.009 and 0.013, respectively). When we excluded the studies violated HWE, this association was also found in allele model (P = 0.020) and dominant model (P= 0.044). In subgroup analyses, we identified that rs3746444 SNP in mir-499 increased the risk of GC in Asians and gastric cardiac adenocarcinoma (GCA) subgroups. No significant bias of selection was found (all P>0.1). Test of sensitivity analysis indicated that our findings were stable. Additionally, we found that the power value was 0.891 in the allele model, suggesting the reliability of our findings. In summary, our analysis confirmed the association between rs3746444 and the risk of GC, especially in Asians and in patients with GCA.     

ARL4C might serve as a prognostic factor and a novel therapeutic target for gastric cancer: bioinformatics analyses and biological experiments

The ADP-ribosylation factor-like proteins (ARLs) have been proved to regulate the malignant phenotypes of several cancers. However, the exact role of ARLs in gastric cancer (GC) remains elusive. In this study, we systematically investigate the expression status, interactive relations, potential pathways, genetic variations and clinical values of ARLs in GC. We find that ARLs are significantly dysregulated in GC and involved in various cancer-related pathways. Subsequently, machine learning models identify ARL4C as one of the two most significant clinical indicators among ARLs for GC. Furthermore, ARL4C silencing remarkably inhibits the growth and metastasis of GC cells both in vitro and in vivo. Moreover, enrichment analysis indicates that ARL4C is highly correlated with TGF-β1 signalling. Correspondingly, TGF-β1 treatment dramatically increases ARL4C expression and ARL4C knockdown inhibits the phosphorylation level of Smads, downstream factors of TGF-β1. Meanwhile, the coexpression of ARL4C and TGF-β1 worsens the prognosis of GC patients. Our work comprehensively demonstrates the crucial role of ARLs in the carcinogenesis of GC and the specific mechanisms underlying the GC-promoting effects of TGF-β1. More importantly, we uncover the great promise of ARL4C-targeted therapy in improving the efficacy of TGF-β1 inhibitors for GC patients.     

Progress of Gastric Cancer Surgery in the era of Precision Medicine

With the development of genomics, the update of modern imaging technology and the advent of artificial intelligence and big data, the surgical treatment of gastric cancer has gradually stepped into precision medicine. Precision surgery treatment of gastric cancer is based on accurate molecular typing and staging using modern molecular diagnostic technology and imaging, and the formulation of precise and individualized surgical treatment plans, with the concept of minimally invasive and accelerated rehabilitation surgery running through it. For intermediate-stage gastric cancer, we have adopted a comprehensive treatment approach including traditional radiotherapy and chemotherapy, targeted therapy and immunotherapy. Utilize artificial intelligence and big data technology to improve the standardization and interconnectivity of specialty data and realize the transformation of evidence-based medicine. Promoting the standardization, standardization and individualization of gastric cancer surgical treatment, providing patients with precise diagnosis and treatment, and further improving patients'' prognosis are the opportunities and challenges in the development of gastric cancer surgery.     

HER2 testing in gastric and esophageal adenocarcinoma: new diagnostic challenges arising from new therapeutic options

Abstract

Adenocarcinomas of the esophagus and stomach constitute a substantial number of cancer cases worldwide. Most patients in the United States are diagnosed at an advanced or metastatic stage and, therefore, the prognoses have been poor. New treatments are needed to augment standard surgical and medical management. Recent studies have shown that a subset of esophageal and gastric adenocarcinomas overexpress the HER2 protein, similar to the overexpression seen in breast cancer. Because trastuzumab, a monoclonal antibody to the HER2 receptor, has been used with success in primary and HER2 positive metastatic breast cancers, the phase III ToGA trial was designed to assess the impact of trastuzumab in patients with HER2 positive gastric cancers. They have reported an increase in overall survival time for patients treated with chemotherapy and trastuzumab compared to those treated with chemotherapy alone. They have reported an increase in overall survival time for patients treated with chemotherapy and trastuzumab compared to those treated with chemotherapy alone. This means that accurate HER2 testing in gastric and esophageal carcinomas is necessary. While the breast cancer scoring system can be used to determine HER2 status in most cases, modifications are necessary to accommodate the heterogeneity and incomplete membrane staining that are observed more frequently in gastric cancers. An understanding of the scoring modifications is required for proper stratification of gastric cancer patients for treatment.