ObjectiveTo investigate the effects of berberine (BBR) as a treatment on intestinal microecological alterations and enteritis in mice produced by TNBS.MethodsThere were seven mice per group: seven in the healthy group (Ctrl), seven in the TNBS-induced enteritis group (TNBS), and seven in the berberine treatment group (BBR). The mice were weighed, slaughtered after 7 days, and subjected to high-throughput intestinal microecological analysis by Illumina, as well as haematological detection and imaging evaluation of colon pathology.ResultsThe alterations in colon length, immune cell subpopulations, inflammatory factors, and intestinal microecology of mice induced by BBR were refined using a battery of experiments and observations. According to intestinal microecological studies, BBR can increase the number of bacteria, including Lactobacillus, Verrucomicrobia, Bacteroides, and Akkermansia muciniphila.ConclusionBBR has a therapeutic effect on TNBS-induced colitis in mice, which is associated with modifications in immune cell subpopulations and intestinal microecology. It also offers a viable approach as a prospective probiotic (like Akkermansia muciniphila) to IBD therapy in clinical settings.

Abstract Background The aim was to analyze the association between the TME and NER factors, and further to explore the effect of miRNAs on the gene expression of NER factors. This was to reveal the regulatory mechanism between DNA damage repair and the TME of GC.Methods ESTIMATE and CIBERSORT-based algorithms were used to assess the relationship between DDR scores and infiltration of immune cells in a TCGA-GC cohort. Eight databases were used to predict miRNAs regulating NER factors and qRT-PCR experiments were used to validate the regulatory relationship between key miRNAs and NER factors.Results (1) GC patients were divided into two groups with high and low DDR capacity; (2) DDR score was correlated with the proportion of immune cell infiltration; (3) DDR score was negatively correlated with FOXO3A but positively correlated with PDL1; (4) GO functional enrichment analysis between DDR subgroups was mainly about rRNA; (5) has-miR-3163, has-miR-944, has-miR-590-3P, miR-551b-5p,has-miR-548c-3p targeted many NER genes; (7) NER factors, RAD23B, POLR2A, ERCC8, CUL3, CUL5, GTF2H5, ERCC4 POLR2H, POLR2D, and GTF2H1, are predicted to be regulated by upstream miRNAs, thereby influencing the immune microenvironment and even the progression of GC.Conclusions NER factors may influence GC progression by working on the TME.

目的 利用网络药理学和实时荧光定量聚合酶链式反应(Quantitative Real-time PCR,qRT-PCR)法研究鬼臼毒素对胃癌的作用机制.方法 利用TCMSP、Pubchem、Swiss Target Prediction、Similarity ensemble approach、Pharmapper数据库预测鬼臼毒素作用于胃癌的潜在靶标,通过蛋白互作网络和富集分析法找到关键节点和作用的主要通路,并采用qRT-PCR实验验证潜在靶基因.结果 通过查询多个数据库筛选获得 15 个胃癌特征基因(可能为鬼臼毒素的潜在靶标).PPI网络图谱进一步显示,15 个基因所对应的蛋白是鬼臼毒素作用于胃癌的关键靶标.通过GO富集分析和KEGG通路富集分析确定PI3K/AKT通路为主要作用通路.通过qRT-PCR验证发现,鬼臼毒素可以抑制与 PI3K/AKT 信号通路相关基因(CCND1、TP53、MET、RELA、EGFR、BCL2L1、IGF1R)的表达.结论 鬼臼毒素可能通过PI3K/AKT信号通路发挥抗胃癌细胞生长的作用.

目的 观察SNRPA1在胃癌中的表达情况及对胃癌细胞生长的影响.方法 通过高通量差异基因增殖筛选技术(High Content Screening,HCS)分析发现,干扰SNRPA1基因可抑制胃癌细胞AGS增殖.利用TCGA数据库分析SNRPA1基因在胃癌中的表达情况.进一步构建SNRPA1慢病毒载体并转染到胃癌细胞系AGS中(shSNRPA1),采用CCK-8技术和克隆形成技术来分析SNRPA1对胃癌细胞生长增殖的影响.结果 (1)在胃癌组织中,SNRPA1的表达水平明显高于正常组织,SNRPA1基因在胃癌等组织中呈现高表达(P＜0.05);(2)通过细胞生物学实验发现,shSNRPA1组与阴性对照病毒组相比,shSNRPA1组的胃癌细胞AGS的增殖被抑制(P＜0.05),由shSNRPA1组胃癌细胞AGS形成的可见集落数量明显少于阴性对照病毒组(P＜0.05).结论 SNRPA1在胃癌中高表达;干扰SNRPA1可以抑制胃癌细胞AGS的生长增殖能力和集落形成能力.

The sperm-associated antigen 5 (SPAG5) is an important protein in mitosis and cell cycle checkpoint regulation, with more attention as a novel oncogene in various cancers. High level of SPAG5 expression has been detected in our clinical gastric cancer (GC) samples and The Cancer Genome Atlas GC data. However, the bio-function and potential mechanism of SPAG5 in GC remain unclear. In this study, we investigated the role of SPAG5 in GC development and the correlation between SPAG5 and 5-fluorouracil (5-FU) treatment. SPAG5 expression was increased in GC samples compared with that in normal tissues (80.8% vs. 22.0%), which was apparently associated with a worse outcome. Biological experiments showed that knockdown of SPAG5 induced apoptosis and suppressed proliferation in cells and animal models. Downregulation of SPAG5 enhanced the sensitivity of 5-FU in GC cells. Gene microarray chip identified 856 upregulated and 787 downregulated genes in SPAG5 silencing cells. Furthermore, 12 significant genes, including CDKN1A, CDKN1B, EIF4E, MAPK1, and HSP90B1, belonged to the PI3K/AKT signaling pathway using ingenuity pathway analysis. Meanwhile, real-time PCR and Western blotting results showed that knockdown of SPAG5 inhibited PI3K/AKT signaling pathway. Collectively, SPAG5 promotes the growth of GC cells by regulating PI3K/AKT signaling pathway, which could be the promising target gene in GC therapy.

目的 探讨NF2、EZR和p53基因甲基化与青海汉族、撒拉族、回族胃癌易感关系.方法 采用亚硫酸氢盐亚克隆测序法检测青海地区汉族、撒拉族、回族胃癌组织(各30例)、正常胃组织(各20例)中NF2、EZR、p53基因的甲基化程度.结果 NF2、EZR和p53基因在青海汉族、撒拉族、回族胃癌组织中的甲基化程度均高于其正常胃组织(P＜0.05),NF2、EZR和p53基因甲基化程度在三个民族胃癌中无差异性.结论 青海地区汉族、撒拉族、回族NF2、EZR和p53基因的甲基化与胃癌易感性有关,但无民族差异性.

Background Previous clinical studies and randomized controlled trials have revealed that low serum vitamin D levels are associated with the risk of developing insulin resistance. Magnesium has been reported to be a protective factor for insulin resistance, and magnesium has been considered an important co-factor for vitamin D activation. However, the effect of dietary magnesium intake on the relationship between vitamin D and the risk of developing insulin resistance has not been comprehensively investigated. Therefore, we designed this cross-sectional analysis to assess whether dietary magnesium intake modifies the association of vitamin D and insulin resistance. Methods A total of 4,878 participants (male: 48.2%) from 4 consecutive cycles of the National Health and Nutrition Examination Survey (2007–2014) were included in this study after a rigorous screening process. Participants were stratified by their dietary magnesium intake into low-intake (<267 mg/day) and high-intake (≥267 mg/day) groups. We assessed differences between serum vitamin D levels and the risk of developing insulin resistance (interaction test), using a weighted multivariate logistic regression to analyze differences between participants with low and high magnesium intake levels. Results There was a negative association between vitamin D and insulin resistance in the US adult population [OR: 0.93 (0.88–0.98)], P < 0.001. Dietary magnesium intake strengthened the association ( P for interaction < 0.001). In the low dietary magnesium intake group, vitamin D was negatively associated with the insulin resistance [OR: 0.94 (0.90–0.98)]; in the high dietary magnesium intake group, vitamin D was negatively associated with insulin resistance [OR: 0.92 (0.88–0.96)]. Conclusion Among adults in the United States, we found an independent association between vitamin D level and insulin resistance, and this association was modified according to different levels of magnesium intake.

Abstract Objective: This study aimed to screen and identify the differentially-expressed circRNAs (DE-circRNAs) in multiple microarray data sets of gastric cancer (GC), predict their corresponding miRNAs, and explore their regulatory relationship, thereby identifying potential molecular markers for early diagnosis of GC. Results : Seven DE-circRNAs were screened and identified: hsa_circ_0007991, hsa_circ_0013048, hsa_circ_0048607, hsa_circ_0050745, hsa_circ_0054971, hsa_circ_0059802 and hsa_circ_0067934. The host genes of these DE-circRNAs are enriched in cancer-related signaling pathways, including ERb signaling, mTOR signaling, chemokine signaling, and B cell receptor signaling. Moreover, these seven DE-circRNAs were all down-regulated in GC tissues. The 7 miRNAs predicted by DE-circRNAs were expressed in GC tissues, namely hsa-miR-1182, hsa-miR-1225-3p, hsa-miR-1275, hsa-miR-193a-5p, hsa-miR-543, hsa-miR-622 and hsa-miR-630. Among them, miR-193a targets were abundant and highly enriched in cancer-related pathways (ERb signaling and mTOR signaling), which was highly consistent with the enrichment of the host gene where the DEcircRNA was located. These results suggested that circRNA may regulate the occurrence and development of GC through the regulation of the expression of the host genes and miRNA. In clinical samples, DE-circRNAs were less expressed in GC tissues when compared to normal tissues. Conclusion : Seven down-regulated DE-circRNAs and 7 targeted miRNAs were identified in GC, which contributed to the understand of the underlying molecular mechanism of GC and provided a basis for the early diagnosis of GC and the development of targeted drugs. Methods: Four sets of circRNA microarray data and one set of miRNA microarray data in GC and adjacent tissues were downloaded from the Gene Expression Omnibus (GEO) and analyzed using GEO2R tool to identify DE-circRNAs and differentially-expressed miRNAs (DE-miRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the enrichment pathway of host mRNAs of DE-circRNAs. Miranda and TargetScan were used to predict miRNA-binding DE-circRNAs. The predicted DE-circRNA interacting miRNAs were intersected with DE-miRNAs, and KEGG and Reactome analyzed the targeted mRNAs corresponding to the obtained miRNAs. DE-circRNAs in GC tissues and adjacent tissues was verified in clinical samples.