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Associations of dietary, lifestyle, and other participant characteristics with APC, β-catenin, E-cadherin, and MSH2 expression in the normal mucosa of sporadic colorectal adenoma patients 散发性结直肠腺瘤患者正常黏膜中APC、β-catenin、E-钙粘蛋白和MSH2表达与饮食、生活方式和其他参与者特征的关系
Pub Date : 2022-11-07 DOI: 10.3389/fgstr.2022.889925
Timothy D. Shu, R. Rutherford, M. Seabrook, E. Barry, R. Bostick
Abnormal expression of Wnt pathway and DNA mismatch repair proteins is common during colorectal carcinogenesis. To investigate cross-sectional associations of lifestyle, dietary, and other participant characteristics with the expression of such proteins, we measured APC, β-catenin, E-cadherin, and MSH2 colorectal crypt expression in biopsies of normal-appearing colorectal mucosa from 104 sporadic colorectal adenoma patients using automated immunohistochemistry and quantitative image analysis. We used multivariable general linear models to compare adjusted mean biomarker expression across categories of participant characteristics. Example findings include that among women relative to men, mean APC expression in whole crypts, the upper 40% of crypts (differentiation zone), and the lower 60% of crypts (proliferation zone) was 322.9% higher (p<0.01), 296.7% higher (p<0.01), and 399.1% higher (p<0.01), respectively. Among participants with higher alcohol consumption, APC expression in the crypt differentiation zone was estimated to be 15.9% lower (p=0.08). Among those with higher total meat consumption, β-catenin expression in whole crypts and the crypt proliferation zone was estimated to be 20.5% higher (p=0.07) and 19.6% higher (p=0.06), respectively, and MSH2 expression in the crypt differentiation zone was estimated to be 64.4% lower (p=0.10). Among those with a higher body mass index, MSH2 expression in the crypt differentiation zone was estimated to be 87.5% lower (p=0.15). These pilot study findings suggest that being male, higher adiposity, and higher alcohol and meat consumption may be unfavorably associated with biomarkers of colorectal carcinogenesis pathway proteins in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients and support further investigation in larger studies.
Wnt通路和DNA错配修复蛋白的异常表达在结直肠癌发生过程中很常见。为了研究生活方式、饮食和其他参与者特征与这些蛋白质表达的横断面相关性,我们使用自动免疫组织化学和定量图像分析,测量了104例散发性结直肠腺瘤患者正常结直肠粘膜活检中APC、β-连环蛋白、E-钙粘蛋白和MSH2结直肠隐窝的表达。我们使用多变量通用线性模型来比较参与者特征类别的调整平均生物标志物表达。示例性发现包括,在女性中,与男性相比,整个隐窝、隐窝上部40%(分化区)和隐窝下部60%(增殖区)的平均APC表达分别高出322.9%(p<0.01)、296.7%(p<0.01。在饮酒量较高的参与者中,隐窝分化区的APC表达估计低15.9%(p=0.08)。在总肉类消费量较高的人中,整个隐窝和隐窝增殖区的β-连环蛋白表达估计分别高20.5%(p=0.07)和19.6%(p=0.06),隐窝分化区的MSH2表达估计低64.4%(p=0.010)。在体重指数较高的人群中,并且较高的酒精和肉类消费可能与散发性结直肠腺瘤患者正常出现的结直肠粘膜中的结直肠致癌途径蛋白的生物标志物不利相关,并支持更大规模研究中的进一步研究。
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引用次数: 0
Akkermansia muciniphila: The state of the art, 18 years after its first discovery 粘蛋白阿克曼菌:首次发现18年后的最新技术
Pub Date : 2022-10-25 DOI: 10.3389/fgstr.2022.1024393
Rim Iwaza, R. M. Wasfy, G. Dubourg, D. Raoult, J. Lagier
Akkermansia muciniphila (A. muciniphila) is an anaerobic, Gram negative and mucin-degrading bacterium of the phylum Verrucomicrobia isolated in 2004 from human feces. Although it is a common resident in the human intestinal tract, it has also been detected in other anatomical sites. Genomic studies have revealed that A. muciniphila can be divided into different phylogroups with distinct metabolic properties. There is growing evidence regarding its beneficial impact on human health. Indeed, A. muciniphila is considered as a promising next-generation probiotic for treating cancer and metabolic disorders. The large-scale production of A. muciniphila is, therefore, a challenge. Beside mucin-based medium, other culture strategies have enabled its isolation. The administration of both live and pasteurized forms of A. muciniphila has shown to be promising in animal models. Alternatively, the administration of various prebiotics has also been assessed for enhancing its abundance in the human gut. Future prospects include human clinical trials, some of which are currently ongoing. This paper provides an overview of what is currently known about A. muciniphila’s phenotypical and genotypic traits, as well as its culture techniques and its connections to a number of human diseases and its potential application as an effective next generation probiotic.
粘蛋白嗜酸性阿克曼菌(A.muciniphila)是一种厌氧、革兰氏阴性和粘蛋白降解菌,于2004年从人类粪便中分离出来。尽管它在人类肠道中很常见,但在其他解剖部位也有发现。基因组学研究表明,粘球菌可分为不同的门组,具有不同的代谢特性。越来越多的证据表明它对人类健康有益。事实上,A.muciniphila被认为是治疗癌症和代谢紊乱的有前景的下一代益生菌。因此,大规模生产A.muciniphila是一个挑战。除了基于粘蛋白的培养基外,其他培养策略也使其得以分离。活的和巴氏灭菌形式的嗜粘酵母都被证明在动物模型中是有前景的。另外,还评估了各种益生元的给药,以提高其在人类肠道中的丰度。未来的前景包括人体临床试验,其中一些试验目前正在进行中。本文概述了目前已知的A.muciniphila的表型和基因型特征,以及它的培养技术及其与许多人类疾病的联系,以及它作为有效的下一代益生菌的潜在应用。
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引用次数: 3
An association study on PSCA rs2294008 polymorphism and gastric cancer: A meta-analysis PSCA rs2294008多态性与胃癌的相关性研究:meta分析
Pub Date : 2022-10-24 DOI: 10.3389/fgstr.2022.944525
Hang-Yu Li, Qiang Zhao, Shuhan Si, Dongkai Wu
Studies have confirmed that prostate stem cell antigen (PSCA) rs2294008 C>T polymorphism is related to gastric cancer susceptibility, but some studies have reached the opposite conclusion. In this meta-analysis, we attempted to clear up these differences and explore the relationship between the different factors that influence susceptibility to gastric cancer. Studies with publication dates that preceded 16 April 2022 were selected from PubMed, Springer, EMBASE, and Web of Science, and the relationship between risk models and gastric cancer was analyzed by odds ratios (ORs) and 95% confidence intervals. Consequently, it was confirmed that PSCA rs2294008 polymorphism leads to an increased risk of gastric cancer. Subgroup analysis found that individuals with diffuse gastric cancer, non-cardia gastric cancer, Helicobacter pylori (HP)-positive or who are from the white or Asian population faced an increased susceptibility to gastric cancer. Those from the white populations faced significantly higher risks than Asians, and the association of PSCA with gastric cancer could be significantly increased by genome-wide association analysis. However, the conclusion that smoking reduces susceptibility to gastric cancer appears to be abnormal. Further prospective investigations that involve smoking and have a larger sample size are required.
研究证实,前列腺干细胞抗原(PSCA)rs2294008C>T多态性与癌症易感性有关,但一些研究得出了相反的结论。在这项荟萃分析中,我们试图澄清这些差异,并探讨影响癌症易感性的不同因素之间的关系。发表日期在2022年4月16日之前的研究选自PubMed、Springer、EMBASE和Web of Science,并通过比值比(OR)和95%置信区间分析风险模型与癌症之间的关系。因此,证实PSCA rs2294008多态性导致癌症风险增加。亚组分析发现,患有弥漫性癌症、非心脏性癌症、幽门螺杆菌(HP)阳性或来自白人或亚洲人的个体对癌症的易感性增加。来自白人群体的人面临的风险明显高于亚洲人,全基因组关联分析可以显著增加PSCA与癌症的关联。然而,吸烟降低癌症易感性的结论似乎是不正常的。需要进一步的前瞻性调查,涉及吸烟,并有更大的样本量。
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引用次数: 0
The integrated landscape of fatty acid metabolism subtypes reveals with prognostic and therapeutic relevance in pancreatic cancer 脂肪酸代谢亚型的综合状况揭示了胰腺癌症的预后和治疗相关性
Pub Date : 2022-10-21 DOI: 10.3389/fgstr.2022.969533
P. Dai, Jing Feng, Yanyan Dong, Shaohua Zhang, Xiaopeng Cui, X. Qin, Shiming Yang, Daguang Fan
Background Pancreatic Cancer (PAAD) is one of the most commonly diagnosed malignancies and the leading cause of cancer-related death worldwide. Aberrantly expressed long noncoding RNAs (lncRNAs) are involved in tumourigenesis of PAAD, and associated with the overall survival and tumor fatty acid metabolism in PAAD patients. Methods The data on gene expression and corresponding clinical characteristics of PAAD patients in TCGA-PAAD (N=177) and GSE62452 (N=65) are taken from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Consensus cluster analysis to identify distinct fatty acid metabolism subtypes in PAAD based on 62 fatty acid metabolism gene. The single sample GSEA (ssGSEA) algorithm was developed for evaluation of tumor infiltrating immune cells between fatty acid metabolism subtypes. As well, the R package “pRRophetic” was used to predict chemotherapeutic response in PAAD patients. Tumor Immune Dysfunction and Exclusion (TIDE) was used to predict immunotherapy response in PAAD patients. Univariate and multivariate Cox analysis were utilized to calculate the prognostic-related lncRNAs. Results Totally, three fatty acid metabolism subtypes were obtained in PAAD based on 62 fatty acid metabolism gene. Kaplan-Meier (K-M) analysis showed that the overall survival rate of cluster3 group was significantly higher than the other two groups. Significant differences were seen between the three subtypes in immune cell infiltration characteristics and the immunotherapy response indicators, including Tumor mutational burden (TMB), immunophenoscore (IPS), and immune checkpoint molecules. The cluster1 group and cluster3 group were speculated to have the higher response to immunotherapy patients in cluster2 gains more benefit from chemotherapy than other groups. A 4-lncRNA signature was constructed based on the value of gene expression and regression coefficients which stratified patients into two risk groups. Patients in the higher-risk group had lower survival probabilities than those in the lower-risk group, based on the Kaplan-Meier analysis and Cox regression analysis. Receiver operating characteristic (ROC) curve analysis confirmed the predictive capability. In GO and KEGG analysis, genes in the high-risk group were linked to PAAD development. Conclusions We constructed a signature that could predict prognosis of PAAD and provide certain theory guidance for novel therapeutic approaches of PAAD.
胰腺癌(PAAD)是最常见的恶性肿瘤之一,也是全球癌症相关死亡的主要原因。异常表达的长链非编码rna (lncRNAs)参与PAAD的肿瘤发生,并与PAAD患者的总生存率和肿瘤脂肪酸代谢相关。方法TCGA-PAAD (N=177)和GSE62452 (N=65)的PAAD患者基因表达及相应临床特征数据来源于美国癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)。基于62脂肪酸代谢基因的共识聚类分析确定PAAD不同的脂肪酸代谢亚型。建立了单样本GSEA (ssGSEA)算法,用于评价肿瘤浸润免疫细胞在脂肪酸代谢亚型之间的差异。同样,R包“prophytic”被用于预测PAAD患者的化疗反应。肿瘤免疫功能障碍和排斥(TIDE)用于预测PAAD患者的免疫治疗反应。采用单因素和多因素Cox分析计算与预后相关的lncrna。结果基于62脂肪酸代谢基因,PAAD共获得3个脂肪酸代谢亚型。Kaplan-Meier (K-M)分析显示,cluster3组总生存率显著高于其他两组。三种亚型在免疫细胞浸润特征及肿瘤突变负荷(Tumor mutational burden, TMB)、免疫表型评分(immunophenoscore, IPS)、免疫检查点分子等免疫治疗应答指标上存在显著差异。推测cluster1组和cluster3组对免疫治疗的反应较高,cluster2组患者比其他组从化疗中获益更多。根据基因表达值和回归系数构建4-lncRNA特征,将患者分为两个危险组。Kaplan-Meier分析和Cox回归分析显示,高危组患者的生存概率低于低危组患者。受试者工作特征(ROC)曲线分析证实了预测能力。在GO和KEGG分析中,高危组的基因与PAAD的发展有关。结论构建了一个能够预测PAAD预后的特征,为PAAD的新治疗方法提供一定的理论指导。
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引用次数: 0
Innovative, complementary and alternative therapy in inflammatory bowel diseases: A broad 2020s update 炎症性肠病的创新、补充和替代疗法:2020年的广泛更新
Pub Date : 2022-10-17 DOI: 10.3389/fgstr.2022.1022530
L. Masi, C. Ciuffini, V. Petito, L. Pisani, L. Lopetuso, C. Graziani, D. Pugliese, L. Laterza, P. Puca, F. Di Vincenzo, M. Pizzoferrato, D. Napolitano, L. Turchini, V. Amatucci, E. Schiavoni, G. Privitera, L. Minordi, M. C. Mentella, A. Papa, A. Armuzzi, A. Gasbarrini, F. Scaldaferri
Inflammatory bowel diseases (IBD) are chronic disabling conditions with a complex and multifactorial etiology, which is still not completely understood. In the last 20 years, anti-TNF-α antagonists have revolutionized the treatment of IBD, but many patients still do not respond or experience adverse events. Therefore, new biological therapies and small molecules, targeting several different pathways of gut inflammation, have been developed of which some have already been introduced in clinical practice while many others are currently investigated. Moreover, therapeutic procedures such as leukocytapheresis, fecal microbiota transplant and stem cell transplantation are currently being investigated for treating IBD. Lastly, complementary and alternative medicine has become a field of interest for gastroenterologist to reduce symptom burden in IBD patients. In this comprehensive and updated review, a novel classification of current and developing drugs is provided.
炎症性肠病(IBD)是一种慢性致残疾病,具有复杂的多因素病因,目前仍未完全了解。在过去的20年里,抗tnf -α拮抗剂已经彻底改变了IBD的治疗,但许多患者仍然没有反应或经历不良事件。因此,针对几种不同肠道炎症途径的新的生物疗法和小分子已经被开发出来,其中一些已经被引入临床实践,而许多其他的正在研究中。此外,目前正在研究白细胞清除、粪便微生物群移植和干细胞移植等治疗方法来治疗IBD。最后,补充和替代医学已成为胃肠病学家感兴趣的领域,以减轻IBD患者的症状负担。在这篇全面和最新的综述中,提供了当前和正在开发的药物的新分类。
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引用次数: 0
Gut microbiota in anxiety and depression: Pathogenesis and therapeutics 焦虑和抑郁的肠道微生物群:发病机制和治疗
Pub Date : 2022-10-12 DOI: 10.3389/fgstr.2022.1019578
S. Bibbò, S. Fusco, G. Ianiro, C. Settanni, D. Ferrarese, Claudio Grassi, G. Cammarota, A. Gasbarrini
Depression and anxiety disorders represent a burdensome clinical issue. Considering the unsatisfactory clinical response of some patients to antidepressant therapy, new personalized approaches are being studied. In recent years, pre-clinical and clinical studies have investigated the role of intestinal microbiota demonstrating the importance of the gut-brain axis in these diseases. Indeed, gut microbes are able to interact with the brain interfering with behavior through some mechanisms such as amino acid metabolism, short–chain fatty acids, vagus nerve, endocrine signaling and immune responses. Experiments of gut microbiota transfer from subjects with major depression to animal models corroborated the causative role of intestinal microbes in mood disorders and anxiety. Furthermore, the incidence of dysbiosis in patients with anxiety and depression suggests a potential role for gut microbiota modulators in the treatment of these disorders. In particular, several probiotics and synbiotics have been shown to be effective in improving clinical symptoms, promising results have emerged also from fecal microbiota transplantation, but the evidence is still limited. These promising results switch on the use of gut microbiota modulators as an adjunctive tool to anti-depressant therapy. Developing pharmaceutical or nutraceutical strategies to modify the composition of gut microbiota may offer novel and personalized therapeutic tools against anxiety and depression.
抑郁症和焦虑症是一个繁重的临床问题。考虑到一些患者对抗抑郁治疗的临床反应不令人满意,正在研究新的个性化方法。近年来,临床前和临床研究已经调查了肠道微生物群的作用,证明了肠脑轴在这些疾病中的重要性。事实上,肠道微生物能够通过氨基酸代谢、短链脂肪酸、迷走神经、内分泌信号和免疫反应等机制与大脑相互作用,干扰行为。从患有严重抑郁症的受试者到动物模型的肠道微生物群转移实验证实了肠道微生物在情绪障碍和焦虑中的致病作用。此外,焦虑和抑郁患者的微生态失调发生率表明肠道微生物群调节剂在治疗这些疾病中具有潜在作用。特别是,几种益生菌和合生元已被证明能有效改善临床症状,粪便微生物群移植也取得了有希望的结果,但证据仍然有限。这些有希望的结果开启了肠道微生物群调节剂作为抗抑郁治疗辅助工具的使用。开发药物或营养品策略来改变肠道微生物群的组成,可能会为对抗焦虑和抑郁提供新的个性化治疗工具。
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引用次数: 0
Transitions from pediatric to adult IBD care: Incorporating lessons from psychogastroenterology 从儿童到成人IBD护理的转变:结合心理胃肠病学的经验教训
Pub Date : 2022-10-12 DOI: 10.3389/fgstr.2022.1037421
Michelle Mendiolaza, Jordyn H. Feingold, Halley P. Kaye-Kauderer, M. Dubinsky, K. Gorbenko, L. Keefer
The transition from pediatric to adult gastroenterology care for adolescents with inflammatory bowel disease (IBD) is a critical period associated with poor disease outcomes and high medical costs. Burdens such as the discontinuity of care when transitioning from one provider to another are amplified by poor coping and psychosocial factors. However, existing research on the topic of health care transitions has centered largely on disease knowledge and competencies that young adults ought to master and self-manage, while largely disregarding the broader psychosocial context and impacts of IBD on daily functioning. Findings from a recent mixed-methods pilot study of transition-aged adolescents with IBD and their parents highlight the importance of acknowledging the psychosocial needs of adolescents with IBD and their families throughout the transition process, which include understanding the gut-brain axis, optimizing social support and mental health resources, and maintaining optimism and positivity. In this review, we expand upon the findings from this pilot study, synthesize the latest research in psychogastroenterology and pediatric-to-adult transitions in IBD, and provide five patient-centered interventions that may be implemented in clinical settings, in anticipation of, and during the patient transition experience. These interventions are rooted in positive psychology and cognitive-behavioral principles and are designed for adolescents with IBD to complete with input from their families and health care professionals.
炎症性肠病(IBD)青少年从儿科胃肠病护理过渡到成人胃肠病护理是一个关键时期,与不良的疾病结果和高昂的医疗费用有关。从一个提供者过渡到另一个提供者时,护理的不连续性等负担因应对不力和心理社会因素而加剧。然而,现有关于医疗保健转型主题的研究主要集中在年轻人应该掌握和自我管理的疾病知识和能力上,而在很大程度上忽视了IBD对日常功能的更广泛的心理社会背景和影响。最近一项针对患有IBD的过渡年龄青少年及其父母的混合方法试点研究的结果强调了在整个过渡过程中承认患有IBD青少年及其家人的心理社会需求的重要性,包括了解肠脑轴、优化社会支持和心理健康资源,以及保持乐观和积极。在这篇综述中,我们扩展了这项试点研究的发现,综合了心理胃肠病学和IBD儿童向成人过渡的最新研究,并提供了五种以患者为中心的干预措施,这些干预措施可以在临床环境中、预期中和患者过渡期间实施。这些干预措施植根于积极的心理学和认知行为原则,旨在为患有IBD的青少年提供家庭和医疗保健专业人员的意见。
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引用次数: 2
Effect of calorie-restriction and rapamycin on autophagy and the severity of caerulein-induced experimental acute pancreatitis in mice 热量限制和雷帕霉素对小白鼠自噬和蓝精灵诱导的实验性急性胰腺炎严重程度的影响
Pub Date : 2022-10-12 DOI: 10.3389/fgstr.2022.977169
M. Sharma, Kumari Priyam, Punit Kumar, P. Garg, T. Roy, T. Jacob
Background Impaired autophagy contributes to development of acute pancreatitis (AP). We studied the effect of inducing autophagy by calorie-restriction and rapamycin, separately, in the caerulein-induced model of severe AP. Methods Adult, male, Swiss albino mice were given eight, hourly, intraperitoneal injections of caerulein (Ce) (50µg/Kg/dose). The interventions were calorie restriction (CR) and rapamycin (2mg/Kg). Mice were sacrificed at the 9th hour. Pancreas was harvested for histopathology and immunoblotting. Amylase activity and the levels of cytokines were measured in plasma. Results The histopathological score and amylase activity were significantly lower in calorie-restricted caerulein-induced AP (CRCeAP) in comparison to animals that had unrestricted access to chow. In the CRCeAP group, levels of IL-6 and GM-CSF in plasma were lower and the expression of LC3II and Beclin-1 were higher. On transmission electron-microscopy, the area occupied by autophagic vacuoles was higher in CRCeAP. The expression of caspase-8 and caspase-9 was also higher in CRCeAP. In rapamycin with caerulein-induced AP (Rapa+CeAP), the histopathological score and amylase activity were significantly lower than caerulein-induced AP (CeAP). In Rapa+CeAP, the expression of LC3II and Beclin-1 were higher, whereas; SQSTM1 was decreased. The number of autophagic vacuoles in Rapa+CeAP group was fewer. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were lower in Rapa+CeAP. Caspase-3 increased and high mobility group box 1 (HMGB1) decreased in Rapa+CeAP. Conclusion Calorie-restriction and rapamycin can individually decrease the severity of injury in the caerulein-induced model of severe AP.
背景自噬受损导致急性胰腺炎(AP)的发展。我们分别研究了热量限制和雷帕霉素在蓝精灵诱导的严重AP模型中诱导自噬的作用。方法成年、雄性、瑞士白化病小鼠每8小时腹膜内注射50µg/Kg/剂的银合欢素(Ce)。干预措施为热量限制(CR)和雷帕霉素(2mg/Kg)。在第9小时处死小鼠。采集胰腺进行组织病理学和免疫印迹。测定血浆淀粉酶活性和细胞因子水平。结果与不限制进食的动物相比,热量限制性盲肠蛋白诱导的AP(CRCeAP)的组织病理学评分和淀粉酶活性显著降低。CRCeAP组血浆IL-6和GM-CSF水平较低,LC3II和Beclin-1表达较高。在透射电子显微镜下,CRCeAP中自噬液泡占据的面积更高。胱天蛋白酶-8和胱天蛋白酶-9在CRCeAP中的表达也较高。雷帕霉素联合蓝精灵诱导的AP(Rapa+CeAP)的组织病理学评分和淀粉酶活性显著低于蓝精灵诱导AP(CeAP)。在Rapa+CeAP中,LC3II和Beclin-1的表达较高,而;SQSTM1降低。Rapa+CeAP组的自噬液泡数量较少。Rapa+CeAP组白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和单核细胞趋化蛋白-1(MCP-1)水平较低。在Rapa+CeAP中,Caspase-3增加,而高迁移率族盒1(HMGB1)降低。结论热量限制和雷帕霉素可分别降低蓝精灵诱导的严重AP模型的损伤程度。
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引用次数: 1
Biomarker identification of chronic atrophic gastritis and its potential drug analysis 慢性萎缩性胃炎的生物标志物鉴定及其潜在药物分析
Pub Date : 2022-09-23 DOI: 10.3389/fgstr.2022.948323
Biao Song, Qinglin Cao, Tingting Li, Yun Liu, Qin Sun, Shanshan Fan, Xuejun Li
Background Chronic atrophic gastritis (CAG) is the first step of gastric precancerous lesions, and the study of the pathogenesis of CAG is helpful for the prevention and treatment of gastric cancer(GC). The purpose of this study is to explore the potential biomarkers and therapeutic drugs of CAG through bioinformatics analysis. Methods The GSE11632 dataset was downloaded from Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were obtained by using GEO2R online tool. We searched GeneCard and DisGeNET databases for genes related to CAG and used the overlapping genes as final DEGs for further functional enrichment analysis and Protein-protein Interaction (PPI) network analysis. Tissue-specific expressed genes were identified by BioGPS database. Cytoscape software was used to identify key hub genes and validated them in GSE27411 data sets. The upstream miRNAs of hub gene was predicted by TargetScan, miRDB and miRWalk. Finally, run the Connectivity Map (CMap) to identify new potential drugs for the treatment of CAG. Results A total of 430 differentially expressed mRNA were identified in this study, including 315 up-regulated genes and 115 down-regulated genes. After intersecting with CAG-related genes in GeneCard and DisGeNET databases, 42 DEGs were obtained. 24 DEGs were identified as tissue-specific expressed genes, most of which were expressed in stomach. GO and KEGG pathway analysis showed that DGEs was mainly enriched in digestion, IL-1 production, gastric acid secretion and so on. A total of 6 hub genes were generated by cytoHubba plug-in, among which ATP4A, CFTR and EPCAM had high diagnostic value. A total of 13 overlapping miRNA were predicted by 6 hub genes. Conclusion ATP4A, CFTR and EPCAM may be potential biomarkers of CAG. hsa-miR-185-5p-CFTR, hsa-miR-4644-CFTR and hsa-miR-4505-CFTR are potential RNA regulatory pathways to control the progression of CAG disease. Finally, amonafide, etoposide, mycophenolate-mofetil, cycloheximide and Emetine may be potential therapeutic drugs for CAG.
背景慢性萎缩性胃炎(CAG)是胃癌前病变的第一步,对其发病机制的研究有助于癌症的预防和治疗。本研究旨在通过生物信息学分析,探索CAG的潜在生物标志物和治疗药物。方法从基因表达综合数据库(GEO)下载GSE11632数据集,利用GEO2R在线工具获得差异表达基因。我们在GeneCard和DisGeNET数据库中搜索与CAG相关的基因,并使用重叠的基因作为最终的DEG进行进一步的功能富集分析和蛋白质相互作用(PPI)网络分析。通过BioGPS数据库鉴定组织特异性表达基因。Cytoscape软件用于识别关键枢纽基因,并在GSE27411数据集中对其进行验证。通过TargetScan、miRDB和miRWalk预测hub基因的上游miRNA。最后,运行连接图(CMap)来确定治疗CAG的新的潜在药物。结果本研究共鉴定出430个差异表达的信使核糖核酸,其中上调基因315个,下调基因115个。在GeneCard和DisGeNET数据库中与CAG相关基因交叉后,获得42个DEG。24个DEG被鉴定为组织特异性表达基因,其中大部分在胃中表达。GO和KEGG通路分析表明,DGEs主要富集在消化、IL-1产生、胃酸分泌等方面。cytoHubba插件共产生6个hub基因,其中ATP4A、CFTR和EPCAM具有较高的诊断价值。6个枢纽基因共预测了13个重叠的miRNA。结论ATP4A、CFTR和EPCAM可能是CAG的潜在生物标志物。hsa-miR-185-5p-CFTR、hsa-miR-4644-CFTR和hsa-miR-4505-CFTR是控制CAG疾病进展的潜在RNA调节途径。最后,阿莫萘、足叶乙甙、霉酚酸酯、环己酰亚胺和埃美汀可能是治疗CAG的潜在药物。
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引用次数: 0
The α-Gal mammalian meat allergy as a cause of isolated gastrointestinal symptoms α-Gal哺乳动物肉类过敏作为孤立性胃肠道症状的原因
Pub Date : 2022-09-23 DOI: 10.3389/fgstr.2022.987713
Nathan E. Richards, T. Makin, Anna R. Smith, T. Platts-Mills, R. Richards, Jeffrey M. Wilson
The α-Gal mammalian meat allergy classically presents with urticaria, with or without gastrointestinal (GI) symptoms or anaphylaxis, but increasingly we are aware of patients with only GI symptoms. Here we describe patients presenting with isolated GI symptoms who had detectable IgE antibodies to α-Gal and reported symptom improvement on a mammal-restricted diet. Forty patients in the practice of a single gastroenterologist, and 35 patients in one allergy clinic were identified, with abdominal pain, diarrhea, and nausea the most common symptoms. Alpha-Gal IgE levels were lower than in a previously described cohort of patients who exhibited classic allergic reactions. This large case series suggests that α-Gal IgE is an important contributor to GI morbidity in areas where lone star tick bites are common. Symptom presentations in GI-AGS can be easily confused with other common GI conditions, and α-Gal IgE levels are often lower than those in patients with classic AGS.
α-Gal哺乳动物肉类过敏通常表现为荨麻疹,伴或不伴胃肠道(GI)症状或过敏反应,但我们越来越多地注意到只有胃肠道症状的患者。在这里,我们描述了出现孤立胃肠道症状的患者,他们检测到α-Gal的IgE抗体,并报告在限制哺乳动物饮食后症状得到改善。一名胃肠病学家的40名患者和一家过敏诊所的35名患者被确定,腹痛、腹泻和恶心是最常见的症状。α - gal IgE水平低于先前描述的表现出典型过敏反应的患者队列。这一大型病例系列表明,α-Gal IgE是孤星蜱叮咬常见地区GI发病率的重要因素。GI-AGS的症状表现很容易与其他常见的胃肠道疾病混淆,α-Gal IgE水平通常低于经典AGS患者。
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引用次数: 1
期刊
Frontiers in gastroenterology (Lausanne, Switzerland)
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