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Is there any predictor for relapse after treatment withdrawal in autoimmune hepatitis patients in the real life? 现实生活中自身免疫性肝炎患者停药后是否有复发的预测因子?
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-01-01 DOI: 10.1177/03946320221077860
Bilger Çavuş, Filiz Akyuz, Raim İliaz, Alp Atasoy, Umit Akyuz, Kadir Demir, Fatih Besisik, Sabahattin Kaymakoglu

Backgrounds and aims: In autoimmune hepatitis, there are uncertainties about whether to discontinue the treatment, when the treatment should be discontinued, and the risks of relapse in the cases where remission is achieved with immunosuppressive therapy. In this study, patients with AIH, whose immunosuppressive treatments were discontinued, were evaluated for the rates of remission and the risk of relapse.

Materials and methods: A total of 119 patients, who were diagnosed with AIH based on the AIHG scoring systems between 1990 and 2015, were evaluated. Patients were receiving standard azathioprine and steroid therapy. The treatment was discontinued in patients, who had been receiving treatment for at least 2 years, who had no clinical complaints, and whose aminotransferases were normal and when an increase occurred in AST values more than two times the normal after the treatment was interrupted, the case was considered as a relapse.

Results: Among the patients, 83%(n = 99) were women. When the patients were diagnosed with AIH, their mean age was 36 ± 16(8-79) years; 70.6%(n = 84) were type 1, 3.4%(n = 4) type 2, and 26%(n = 31) were autoantibody-negative AIH. At the time of discontinuation, liver biopsy was performed in 8 of the patients and minimal-mild abnormalities were detected. Patients whose treatment was discontinued received treatment for an average of 101 ± 75(range: 24-280, median: 68.5) months; and, they were followed up for an average of 19 (1-110) months during the period without medication. Relapse occurred in 67%(n = 12) of the patients with drug withdrawal. Relapse occurred within the first 12 months in 67% of these patients (n = 8) and developed with an acute hepatitis attack in 42%. None of the clinical, laboratory, and histological data were found to be effective on relapse.

Conclusion: In patients with AIH, relapse occurs in two-thirds of patients within an average of 19 month after the discontinuation of the medication. Most relapses occur at the early period and they are accompanied by an acute hepatitis attack.

背景和目的:在自身免疫性肝炎中,是否应该停止治疗,何时应该停止治疗,以及在免疫抑制治疗获得缓解的情况下复发的风险存在不确定性。在这项研究中,对停止免疫抑制治疗的AIH患者的缓解率和复发风险进行了评估。材料与方法:对1990 - 2015年间根据AIHG评分系统诊断为AIH的119例患者进行评估。患者接受标准硫唑嘌呤和类固醇治疗。治疗至少2年,无临床主诉,转氨酶正常,停药后AST升高超过正常2倍者,视为复发。结果:患者中女性占83%(n = 99)。确诊为AIH时,患者平均年龄36±16(8-79)岁;70.6%(n = 84)为1型,3.4%(n = 4)为2型,26%(n = 31)为自身抗体阴性AIH。在停药时,8例患者进行了肝活检,发现了轻微的异常。停止治疗的患者接受治疗的平均时间为101±75个月(范围:24-280,中位数:68.5);在不给药期间,平均随访19个月(1 ~ 110个月)。停药后复发的患者占67%(n = 12)。67%的患者(n = 8)在前12个月内复发,42%的患者出现急性肝炎发作。临床、实验室和组织学资料均未发现对复发有效。结论:在AIH患者中,三分之二的患者在停药后平均19个月内复发。大多数复发发生在早期,并伴有急性肝炎发作。
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引用次数: 1
Epidemiological and clinical characteristics of vaccinated COVID-19 patients: A meta-analysis and systematic review. COVID-19疫苗接种患者的流行病学和临床特征:荟萃分析和系统评价
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-01-01 DOI: 10.1177/03946320221141802
Wen Tian, Xingxiang Ren, Mei Han, Yuanyuan Zhang, Xu Gao, Zhihai Chen, Wei Zhang

Objective: With the global epidemic of coronavirus disease 2019 (COVID-19), vaccination rates are increasing globally. This study evaluated the relevant clinical manifestations of vaccinated COVID-19 patients.

Methods: We searched carefully in 11 databases such as PubMed, Embase, Scopus, Cochrane Library, Web of Science, Ovid, China National Knowledge Infrastructure Database, Wan Fang Data, Sinomed, VIP Database, and Reading Showing Database up to 26 March 2022. To search for articles that have described the characteristics of vaccinated patients including epidemiological and clinical symptoms. Statistical analysis of the extracted data using STATA 14.0.

Results: A total of 58 articles and 263,708 laboratory-confirmed COVID-19 patients were included. Most of the patients in the vaccinated group had more asymptomatic infection and fewer severe illnesses. There were significant differences in ethnicity, and strain infected with COVID-19, and comorbidities (hyperlipidemia, diabetes, obesity, kidney disease, immunocompromised, cardiovascular disease, and tumor) and symptoms (fever, cough, gastrointestinal symptoms, neurological symptoms, and dysgeusia/anosmia) between vaccinated group and unvaccinated group. Oxygen support, use of steroid, days in hospital, hospital treatment, ICU treatment, death, and poor prognosis were also significantly different.

Conclusion: Compared with the vaccinated group, patients in the unvaccinated group had a more severe clinical manifestations. Vaccines are also protective for infected people.

目的:随着2019冠状病毒病(COVID-19)的全球流行,全球疫苗接种率不断上升。本研究评价接种新冠肺炎疫苗患者的相关临床表现。方法:截止到2022年3月26日,我们在PubMed、Embase、Scopus、Cochrane Library、Web of Science、Ovid、中国国家知识基础数据库、万方数据、Sinomed、VIP数据库、Reading show Database等11个数据库中进行了仔细的检索。检索描述接种疫苗患者特征(包括流行病学和临床症状)的文章。使用STATA 14.0对提取的数据进行统计分析。结果:共纳入文献58篇,实验室确诊病例263708例。接种疫苗组的大多数患者无症状感染较多,严重疾病较少。在种族、感染COVID-19的菌株、合并症(高脂血症、糖尿病、肥胖、肾脏疾病、免疫功能低下、心血管疾病和肿瘤)和症状(发烧、咳嗽、胃肠道症状、神经系统症状和嗅觉障碍/嗅觉障碍)方面,接种疫苗组和未接种疫苗组存在显著差异。氧支持、类固醇使用、住院天数、住院治疗、ICU治疗、死亡和预后不良也有显著差异。结论:与接种疫苗组相比,未接种疫苗组患者的临床表现更为严重。疫苗对感染者也有保护作用。
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引用次数: 4
Laboratory biomarker predictors for disease progression and outcome among Egyptian COVID-19 patients 埃及COVID-19患者疾病进展和结局的实验室生物标志物预测指标
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-01-01 DOI: 10.1177/03946320221096207
L. Fathalla, Lamyaa Kamal, Omina Salaheldin, Mahmoud Khalil, Mahmoud M. Kamel, Hagar H. Fahim, Youssef A. S. Abdel-Moneim, Jawaher A. Abdulhakim, A. S. Abdel-Moneim, Yomna M El-Meligui
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in more than five hundred million infected cases worldwide. The current study aimed to screen the correlation of different laboratory findings with disease severity and clinical outcomes of coronavirus disease (COVID-19) among Egyptian patients to obtain prognostic indicators of disease severity and outcome. A total of 112 laboratory-confirmed COVID-19 patients were examined. According to the severity of the disease, these patients were divided into three main groups: mild, moderate and severe cases. In addition, clinical characteristics and laboratory findings, including Hb, platelet count, white blood cell count, lymphocyte percentage, neutrophil percentage, neutrophil lymphocyte ratio (NLR), D-dimer, highly sensitive C-reactive protein (HS-CRP), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatinine, were measured. The presence of hypertension and/or diabetes was found to be a significant risk factor for disease severity and poor outcome. Increased respiratory rate, levels of SpO2, HS-CRP, D-dimer, NLR, ALT, LDH, lymphopenia and neutrophilia, as well as changes in chest computed tomography (CT), were associated with increased disease severity and fatal consequences. Highly sensitive C-reactive protein, D-dimer, NLR and LDH constituted excellent predictors for both disease severity and death. Laboratory biomarkers, such as HS-CRP, D-dimer, NLR and LDH, are excellent predictors for both disease severity and death. They can predict mortality in patients at the time of admission secondary to SARS-CoV-2 infection and can help physicians identify high-risk patients before clinical deterioration.
严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)大流行导致全球感染病例超过5亿例。本研究旨在筛选埃及冠状病毒病(COVID-19)患者不同实验室检查结果与疾病严重程度和临床转归的相关性,获得疾病严重程度和转归的预后指标。共检测实验室确诊病例112例。根据病情的严重程度,将这些患者分为轻、中、重度三组。此外,还测量了临床特征和实验室结果,包括Hb、血小板计数、白细胞计数、淋巴细胞百分比、中性粒细胞百分比、中性粒细胞淋巴细胞比率(NLR)、d -二聚体、高敏c反应蛋白(HS-CRP)、丙氨酸转氨酶(ALT)、乳酸脱氢酶(LDH)和肌酐。发现高血压和/或糖尿病的存在是疾病严重程度和不良预后的重要危险因素。呼吸频率增加、SpO2、HS-CRP、d -二聚体、NLR、ALT、LDH、淋巴细胞减少症和中性粒细胞增多以及胸部计算机断层扫描(CT)的变化与疾病严重程度增加和致命后果相关。高度敏感的c反应蛋白、d -二聚体、NLR和LDH是疾病严重程度和死亡的优秀预测因子。实验室生物标志物,如HS-CRP、d -二聚体、NLR和LDH,是疾病严重程度和死亡的极好预测指标。它们可以预测患者在入院时继发于SARS-CoV-2感染的死亡率,并可以帮助医生在临床恶化之前识别高危患者。
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引用次数: 3
Network pharmacology and bioinformatics analyses identify the intersection genes and mechanism of Huang Bai for recurrent aphthous stomatitis. 网络药理学和生物信息学分析确定了黄柏治疗复发性口腔炎的交叉基因和机制。
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-01-01 DOI: 10.1177/03946320221129134
Lulu Tang, Ling Huang, Yingtao Lai

Recurrent aphthous stomatitis (RAS) are complex inflammatory diseases caused by multi-factors, which severely impact patient quality of life. However, there is still no effective treatment method for RAS without side effects. Traditionally, Cortex Phellodendri known as "Huang Bai" was used to treat RAS for antibacterial and anti-inflammatory properties in China. Network pharmacology methods and bioinformatics analysis were utilized to search and fish incorporating target. Network analysis and silico validation were used to discover the pharmacological mechanisms of "Huang Bai" for the treatment of RAS. A total of 25 active ingredients in HB, 200 drug targets, and 578 differentially expressed genes (DEGs) between Recurrent aphthous stomatitis and normal samples were obtained. The Gene Ontology enrichment analysis revealed that the immune response was the most significantly enriched term within the DEGs. The KEGG pathway analysis identified 60 significant pathways, most of which involved in the inhibition of inflammation and regulation of immunological response. The functions are dependent on a multi-pathway, particularly the TNF signaling pathway and the HIF-1 signaling pathway. We identified six hub genes in the PPI network, most of which were validated as highly expressed in oral ulcers by DiseaseMeth databases. In addition, molecular docking displayed that the primary molecule combined well with the key targets. "Huang Bai" contains potential anti-RAS active compounds. This study reflects the multi-component multi-target multi-pathway action characteristics of "Huang Bai." Our study provides potential biomarkers or treatment targets for further research.

复发性口腔炎(RAS)是一种多因素引起的复杂炎症性疾病,严重影响患者的生活质量。然而,目前尚无无副作用的RAS有效治疗方法。传统上,黄柏被称为“黄柏”,用于治疗RAS的抗菌和抗炎作用。利用网络药理学方法和生物信息学分析对合并靶点进行搜索和捕获。通过网络分析和计算机验证,探索“黄柏”治疗RAS的药理机制。在复发性口腔炎与正常样本中,共获得HB中25种有效成分,200个药物靶点,578个差异表达基因(DEGs)。基因本体富集分析显示,免疫应答是DEGs中最显著富集的项。KEGG通路分析确定了60条重要通路,其中大部分涉及抑制炎症和调节免疫反应。其功能依赖于多通路,特别是TNF信号通路和HIF-1信号通路。我们在PPI网络中确定了6个中心基因,其中大多数在口腔溃疡中被disease - emeth数据库证实为高表达。此外,分子对接表明,一级分子与关键靶点结合良好。“黄柏”含有潜在的抗ras活性化合物。本研究反映了“黄柏”多组分、多靶点、多途径的作用特点。我们的研究为进一步研究提供了潜在的生物标志物或治疗靶点。
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引用次数: 0
Luteolin loaded on zinc oxide nanoparticles ameliorates non-alcoholic fatty liver disease associated with insulin resistance in diabetic rats via regulation of PI3K/AKT/FoxO1 pathway. 木犀草素负载氧化锌纳米颗粒通过调节PI3K/AKT/FoxO1通路改善糖尿病大鼠与胰岛素抵抗相关的非酒精性脂肪性肝病。
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-01-01 DOI: 10.1177/03946320221137435
Esraa Sa Ahmed, Hebatallah E Mohamed, Mostafa A Farrag

Objective: Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem with high prevalence and morbidity associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. Nano-formulation of luteolin with Zn oxide in the form of Lut/ZnO NPs may improve the anti-diabetic property of each alone and ameliorate the insulin resistance thus management of NAFLD. This study aimed to measure the efficiency of Lut/ZnO NPs against insulin resistance coupled with NAFLD and T2DM.

Methods: A diabetic rat model with NAFLD was induced by a high-fat diet and streptozotocin (30 mg/kg I.P). Serum diabetogenic markers levels, lipid profile, and activity of liver enzymes were measured beside liver oxidative stress markers. Moreover, the hepatic expressions of PI3K/AKT/FoxO1/SERBP1c as well as heme oxygenase-1 were measured beside the histopathological examination.

Results: Lut/ZnO NPs treatment effectively reduced hyperglycemia, hyperinsulinemia, and ameliorated insulin resistance. Additionally, Lut/ZnO NPs improved the hepatic functions, the antioxidant system, and reduced the oxidative stress markers. Furthermore, the lipid load in the liver, as well as the circulating TG and TC, was minified via the suppression of lipogenesis and gluconeogenesis. Moreover, Lut/ZnO NPs activated the PI3K/AKT signaling pathway, hence inactivating FoxO1, therefore enhancing the hepatic cells' insulin sensitivity.

Conclusion: Lut/ZnO NPs have a hepatoprotective effect and may relieve the progression of NAFLD by alleviating insulin resistance, ameliorating the antioxidant status, and regulating the insulin signal pathway.

目的:非酒精性脂肪性肝病(NAFLD)是一种高患病率和高发病率的全球性健康问题,与肥胖、胰岛素抵抗、2型糖尿病(T2DM)和血脂异常有关。木犀草素与氧化锌以Lut/ZnO NPs的形式组成的纳米配方可以单独改善各自的抗糖尿病特性,改善胰岛素抵抗,从而控制NAFLD。本研究旨在测量Lut/ZnO NPs对胰岛素抵抗合并NAFLD和T2DM的效率。方法:采用高脂饮食和链脲佐菌素(30 mg/kg I.P)诱导糖尿病大鼠NAFLD模型。除肝氧化应激标志物外,测定血清糖尿病标志物水平、血脂和肝酶活性。在组织病理学检查的同时,检测肝脏PI3K/AKT/FoxO1/SERBP1c及血红素加氧酶-1的表达。结果:Lut/ZnO NPs治疗可有效降低高血糖、高胰岛素血症,改善胰岛素抵抗。此外,Lut/ZnO NPs改善了肝脏功能和抗氧化系统,降低了氧化应激标志物。此外,肝脏中的脂质负荷以及循环中的TG和TC通过抑制脂肪生成和糖异生而减少。此外,Lut/ZnO NPs激活PI3K/AKT信号通路,使fox01失活,从而增强肝细胞的胰岛素敏感性。结论:Lut/ZnO NPs具有保护肝脏的作用,可能通过减轻胰岛素抵抗、改善抗氧化状态、调节胰岛素信号通路等途径缓解NAFLD的进展。
{"title":"Luteolin loaded on zinc oxide nanoparticles ameliorates non-alcoholic fatty liver disease associated with insulin resistance in diabetic rats <i>via</i> regulation of PI3K/AKT/FoxO1 pathway.","authors":"Esraa Sa Ahmed,&nbsp;Hebatallah E Mohamed,&nbsp;Mostafa A Farrag","doi":"10.1177/03946320221137435","DOIUrl":"https://doi.org/10.1177/03946320221137435","url":null,"abstract":"<p><strong>Objective: </strong>Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem with high prevalence and morbidity associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. Nano-formulation of luteolin with Zn oxide in the form of Lut/ZnO NPs may improve the anti-diabetic property of each alone and ameliorate the insulin resistance thus management of NAFLD. This study aimed to measure the efficiency of Lut/ZnO NPs against insulin resistance coupled with NAFLD and T2DM.</p><p><strong>Methods: </strong>A diabetic rat model with NAFLD was induced by a high-fat diet and streptozotocin (30 mg/kg I.P). Serum diabetogenic markers levels, lipid profile, and activity of liver enzymes were measured beside liver oxidative stress markers. Moreover, the hepatic expressions of PI3K/AKT/FoxO1/SERBP1c as well as heme oxygenase-1 were measured beside the histopathological examination.</p><p><strong>Results: </strong>Lut/ZnO NPs treatment effectively reduced hyperglycemia, hyperinsulinemia, and ameliorated insulin resistance. Additionally, Lut/ZnO NPs improved the hepatic functions, the antioxidant system, and reduced the oxidative stress markers. Furthermore, the lipid load in the liver, as well as the circulating TG and TC, was minified <i>via</i> the suppression of lipogenesis and gluconeogenesis. Moreover, Lut/ZnO NPs activated the PI3K/AKT signaling pathway, hence inactivating FoxO1, therefore enhancing the hepatic cells' insulin sensitivity.</p><p><strong>Conclusion: </strong>Lut/ZnO NPs have a hepatoprotective effect and may relieve the progression of NAFLD by alleviating insulin resistance, ameliorating the antioxidant status, and regulating the insulin signal pathway.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/17/e2/10.1177_03946320221137435.PMC9630902.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40447789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
Analysis of TRIM27 prognosis value and immune infiltrates in hepatocellular carcinoma. 肝细胞癌中 TRIM27 的预后价值和免疫浸润分析
IF 3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221132986
Haichuan Wang, Yu Zhang, Li Yan, Qiang Lv, Jie Lu, Bei Yun

Up-regulation of tripartite motif-containing 27 (TRIM27) in varieties of tumors found that TRIM27 advanced tumor metastasis and invasion. Nevertheless, the relation of TRIM27 and immune infiltration in hepatocellular carcinoma (HCC) and the prognostic value of TRIM27 expression is unknown. We assessed TRIM27 association with immune infiltrates and the prognostic value of TRIM27 in HCC. From the Cancer Genome Atlas, we obtained TRIM27 transcriptional expression profiles of HCC and normal tissues. Using the Human Protein Atlas to evaluate the expression TRIM27, protein-protein interaction (PPI) networks were produced using the STRING database. Functional enrichment analysis was performed by using the clusterProfiler package. The tumor immune estimation resource was used to determine the relation of TRIM27 expression and immune infiltrates. We found that the expression of TRIM27 was up-regulated in HCC tissues compared with adjacent normal tissues. High TRIM27 expression correlated with high pathologic stage and high TNM stage. The receiver operating characteristic curve of TRIM27 area was 0.946. Kaplan-Meier analyses showed poor prognosis in HCC patients with high expression of TRIM27. Correlation analysis suggested that the expression of TRIM27 was related to immune infiltrates and tumor purity. This study indicated in HCC up-regulated the expression of TRIM27 is correlated to poor survival and immune infiltration. TRIM27 is an underlying target of immune therapy and is an underlying biomarker for poor prognosis in HCC.

研究发现,含三方基序27(TRIM27)在多种肿瘤中的上调会促进肿瘤的转移和侵袭。然而,TRIM27与肝细胞癌(HCC)免疫浸润的关系以及TRIM27表达的预后价值尚不清楚。我们评估了TRIM27与免疫浸润的关系以及TRIM27在HCC中的预后价值。我们从癌症基因组图谱中获得了HCC和正常组织的TRIM27转录表达谱。利用人类蛋白质图谱评估了TRIM27的表达,并利用STRING数据库生成了蛋白质-蛋白质相互作用(PPI)网络。使用clusterProfiler软件包进行了功能富集分析。利用肿瘤免疫估算资源确定了TRIM27的表达与免疫浸润的关系。我们发现,与邻近的正常组织相比,TRIM27在HCC组织中表达上调。TRIM27的高表达与高病理分期和高TNM分期相关。TRIM27面积的接收者操作特征曲线为0.946。Kaplan-Meier分析显示,TRIM27高表达的HCC患者预后较差。相关性分析表明,TRIM27的表达与免疫浸润和肿瘤纯度有关。这项研究表明,TRIM27在HCC中的上调表达与生存率低和免疫浸润有关。TRIM27是免疫治疗的潜在靶点,也是HCC预后不良的潜在生物标志物。
{"title":"Analysis of TRIM27 prognosis value and immune infiltrates in hepatocellular carcinoma.","authors":"Haichuan Wang, Yu Zhang, Li Yan, Qiang Lv, Jie Lu, Bei Yun","doi":"10.1177/03946320221132986","DOIUrl":"10.1177/03946320221132986","url":null,"abstract":"<p><p>Up-regulation of tripartite motif-containing 27 (TRIM27) in varieties of tumors found that TRIM27 advanced tumor metastasis and invasion. Nevertheless, the relation of TRIM27 and immune infiltration in hepatocellular carcinoma (HCC) and the prognostic value of TRIM27 expression is unknown. We assessed TRIM27 association with immune infiltrates and the prognostic value of TRIM27 in HCC. From the Cancer Genome Atlas, we obtained TRIM27 transcriptional expression profiles of HCC and normal tissues. Using the Human Protein Atlas to evaluate the expression TRIM27, protein-protein interaction (PPI) networks were produced using the STRING database. Functional enrichment analysis was performed by using the clusterProfiler package. The tumor immune estimation resource was used to determine the relation of TRIM27 expression and immune infiltrates. We found that the expression of TRIM27 was up-regulated in HCC tissues compared with adjacent normal tissues. High TRIM27 expression correlated with high pathologic stage and high TNM stage. The receiver operating characteristic curve of TRIM27 area was 0.946. Kaplan-Meier analyses showed poor prognosis in HCC patients with high expression of TRIM27. Correlation analysis suggested that the expression of TRIM27 was related to immune infiltrates and tumor purity. This study indicated in HCC up-regulated the expression of TRIM27 is correlated to poor survival and immune infiltration. TRIM27 is an underlying target of immune therapy and is an underlying biomarker for poor prognosis in HCC.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ba/69/10.1177_03946320221132986.PMC9558858.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33498705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enriched CD45RA-CD62L+ central memory T and decreased CD3+CD56+ natural killer T lymphocyte subsets in the rectum of ulcerative colitis patients. 增强溃疡性结肠炎患者直肠CD45RA-CD62L+中枢记忆T,降低CD3+CD56+自然杀伤T淋巴细胞亚群。
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-01-01 DOI: 10.1177/20587384211051982
Masaya Iwamuro, Takahide Takahashi, Natsuki Watanabe, Takehiro Tanaka, Toshihiro Inokuchi, Sakiko Hiraoka, Fumio Otsuka, Hiroyuki Okada

Objectives: To investigate the distinctive features of lymphocytes promoting inflammation in ulcerative colitis.

Methods: We performed flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and colorectal mucosa lymphocytes in ulcerative colitis patients (n = 13) and control patients (n = 5).

Results: CD62L+/CD3+CD4+ (35.7 ± 14.0% vs. 19.9 ± 6.4%) and CD62L+/CD3+CD4- cells (17.1 ± 17.4% vs. 2.4 ± 3.9%) were higher in the rectum of ulcerative colitis patients than in control patients. Subpopulation analysis revealed that CD45RA-CD62L+/CD3+CD4+, that is, central memory T cell fraction in CD4+ T cells, was significantly increased in the rectum of ulcerative colitis, compared to that in control patients (23.3 ± 10.5% vs. 8.2 ± 4.0%). Comparison of rectum and colon samples in ulcerative colitis patients indicated that CD56+/CD3+ was decreased in the rectum compared to that in the colon (11.3 ± 12.5% vs. 21.3 ± 16.5%). The ratio of CD56+/CD3+ was also decreased in the rectum of active ulcerative colitis patients compared to that in ulcerative colitis patients at the endoscopic remission stages (2.8 ± 1.7% vs. 18.5 ± 13.3%).

Conclusion: We demonstrated that CD62L+ T lymphocytes, particularly the CD45RA-CD62L+ T cell subset that represents central memory T cells, were increased in the rectum of patients with ulcerative colitis. In addition, the CD56+/CD3+ subset (natural killer T cells) was decreased in the rectum compared to that of less inflamed colonic mucosa. These results suggest that the enrichment of central memory T lymphocytes and the reduction of natural killer T cells in the gut mucosa are involved in the pathogenesis of ulcerative colitis.

目的:探讨溃疡性结肠炎中淋巴细胞促炎的特点。方法:对13例溃疡性结肠炎患者(n = 13)和5例对照组(n = 5)的外周血单核细胞(PBMCs)和结直肠粘膜淋巴细胞进行流式细胞术分析。结果:溃疡性结肠炎患者直肠CD62L+/CD3+CD4+(35.7±14.0%比19.9±6.4%)和CD62L+/CD3+CD4-(17.1±17.4%比2.4±3.9%)高于对照组。亚群分析显示,溃疡性结肠炎患者直肠中CD45RA-CD62L+/CD3+CD4+,即CD4+ T细胞中的中枢记忆T细胞分数显著高于对照组(23.3±10.5% vs. 8.2±4.0%)。溃疡性结肠炎患者直肠和结肠样本比较显示,直肠CD56+/CD3+较结肠CD56+/CD3+降低(11.3±12.5%比21.3±16.5%)。与内镜缓解期溃疡性结肠炎患者相比,活动性溃疡性结肠炎患者直肠中CD56+/CD3+的比值也有所降低(2.8±1.7%比18.5±13.3%)。结论:我们证明了CD62L+ T淋巴细胞,特别是CD45RA-CD62L+ T细胞亚群(代表中枢记忆T细胞)在溃疡性结肠炎患者的直肠中增加。此外,与炎症较少的结肠粘膜相比,直肠中的CD56+/CD3+亚群(自然杀伤T细胞)减少。这些结果提示,肠道黏膜中央记忆T淋巴细胞的富集和自然杀伤T细胞的减少参与了溃疡性结肠炎的发病机制。
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引用次数: 4
Rapamycin as a potent and selective inhibitor of vascular endothelial growth factor receptor in breast carcinoma. 雷帕霉素是乳腺癌血管内皮生长因子受体的强效选择性抑制剂。
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-01-01 DOI: 10.1177/20587384211059673
Muhammad Shahidan Muhammad Sakri, Tengku Ahmad Damitri Al-Astani Tengku Din, Hasnan Jaafar, Vinod Gopalan, Wan Faiziah Wan Abdul Rahman

Angiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1 and Flt-4, have been found to play an essential role in regulating angiogenesis. Rapamycin is a macrolide compound with anti-proliferative properties, while platelet factor-4 (PF-4) is an antiangiogenic ELR-negative chemokine. Rapamycin inhibits mTOR ligands activation, thus suppressing cell proliferation, while PF-4 inhibits cell proliferation through several mechanisms. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4 and rapamycin+platelet factor-4. The tumours were subsequently subjected to immunohistochemical protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semiquantitative scoring method, while the mRNA expression levels were analysed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4-treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent antiangiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.

血管生成是新血管形成的过程,它源于各种因素。为抑制癌细胞生长,针对血管生成的治疗方法之一。研究发现,血管内皮生长因子家族受体,包括 Flt-1、Flk-1 和 Flt-4,在调节血管生成方面发挥着重要作用。雷帕霉素是一种具有抗增殖特性的大环内酯化合物,而血小板因子-4(PF-4)是一种抗血管生成的 ELR 阴性趋化因子。雷帕霉素可抑制 mTOR 配体的活化,从而抑制细胞增殖,而血小板因子-4 则通过多种机制抑制细胞增殖。在本研究中,我们从蛋白质组和基因组水平评估了雷帕霉素和血小板因子-4对乳腺癌的影响。我们用雷帕霉素、血小板因子-4和雷帕霉素+血小板因子-4处理了60个N-甲基-N-亚硝基脲诱导的大鼠乳腺癌。随后对肿瘤进行免疫组化蛋白质分析和聚合酶链反应基因分析。蛋白质分析采用半定量评分法,而 mRNA 表达水平则根据相对表达比进行分析。所选标记物的蛋白质和 mRNA 表达水平存在明显差异。在雷帕霉素+血小板因子-4处理组中,Flt-4标记物下调,而其他标记物(如Flt-1和Flk-1)的表达水平没有差异。另一方面,血小板因子-4在本研究中并没有表现出卓越的血管生成抑制能力。雷帕霉素是一种有效的抗血管生成药物,但血小板因子-4对大鼠乳腺癌模型的抗血管生成效果较差。
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引用次数: 0
A novel 8-genome instability-associated lncRNAs signature predicting prognosis and drug sensitivity in gastric cancer 一种新的8基因组不稳定性相关lncRNAs特征预测胃癌预后和药物敏感性
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-01-01 DOI: 10.1177/03946320221103195
C. Yi, Xiulan Zhang, Xia Chen, Birun Huang, Jing Song, Minghui Ma, Xiaolu Yuan, Chaohao Zhang
Background Genome instability lncRNA (GILnc) is prevalently related with gastric cancer (GC) pathophysiology. However, the study on the relationship GILnc and prognosis and drug sensitivity of GC remains scarce. Method We extracted expression data of 375 GC patients from TCGA cohort and 205 GC patients from GSE26942 cohort. Then, lncRNA was separated from expression data, and systematically characterized the 8 marker lncRNAs using the LASSO method. Next, we constructed a GILnc model (GILnc score) to quantify the GILnc index of each GC patient. Finally, we analyzed the relationship between GILnc score and clinical traits including survival outcomes, TP53, and drug sensitivity of GC. Results Based on a computational frame, 205 GILncs in GC has been identified. Then, a 8 GILncs was successfully established to predict overall survival in GC patients based on LASSO analysis, divided GC samples into high GILnc score and low GILnc score groups with significantly different outcome and was validated in multiple independent patient cohorts. Furthermore, GILnc model is better than the prediction performance of two recently published lncRNA signatures, and the high GILnc score group was more sensitive to mitomycin. Besides, the GILnc score has greater prognostic significance than TP53 mutation status alone and is capable of identifying intermediate subtype group existing with partial TP53 functionality in TP53 wild-type patients. Finally, GILnc signature as verified in GSE26942. Conclusion We applied bioinformatics approaches to suggest that a 8 GILnc signature could serve as prognostic biomarkers, and provide a novel direction to explore the pathogenesis of GC.
背景基因组不稳定性lncRNA(GILnc)与癌症(GC)病理生理学普遍相关。然而,关于GILnc与GC的预后和药物敏感性的关系的研究仍然很少。方法我们从TCGA队列中提取375例GC患者和GSE26942队列中提取205例GC患者的表达数据。然后,从表达数据中分离出lncRNA,并使用LASSO方法对8个标志物lncRNA进行系统表征。接下来,我们构建了一个GILnc模型(GILnc评分)来量化每个GC患者的GILnc指数。最后,我们分析了GILnc评分与临床特征之间的关系,包括生存结果、TP53和GC的药物敏感性。结果基于一个计算框架,已识别出205个GC中的GILncs。然后,基于LASSO分析,成功建立了8个GILnc来预测GC患者的总生存率,将GC样本分为结果显著不同的高GILnc评分组和低GILnc分数组,并在多个独立患者队列中进行了验证。此外,GILnc模型的预测性能优于最近发表的两个lncRNA特征的预测性能,并且高GILnc评分组对丝裂霉素更敏感。此外,GILnc评分比单独的TP53突变状态具有更大的预后意义,并且能够识别TP53野生型患者中存在部分TP53功能的中间亚型组。最后,在GSE26942中验证了GILnc签名。结论我们应用生物信息学方法表明,8 GILnc信号可以作为预后的生物标志物,并为探索GC的发病机制提供了新的方向。
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引用次数: 1
Identification of potential biomarkers and immune infiltration characteristics in severe asthma. 重症哮喘潜在生物标志物和免疫浸润特征的鉴定。
IF 3.5 3区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-01-01 DOI: 10.1177/03946320221114194
Yuanyuan Jiang, Shuanglinzi Deng, Xinyue Hu, Lisha Luo, Yingyu Zhang, Daimo Zhang, Xiaozhao Li, Juntao Feng

Objectives: We hope to identify key molecules that can be used as markers of asthma severity and investigate their correlation with immune cell infiltration in severe asthma.

Methods: An asthma dataset was downloaded from the Gene Expression Omnibus database and then processed by R software to obtain differentially expressed genes (DEGs). First, multiple enrichment platforms were applied to analyze crucial biological processes and pathways and protein-protein interaction networks related to the DEGs. We next combined least absolute shrinkage and selection operator logistic regression and the support vector machine-recursive feature elimination algorithms to screen diagnostic markers of severe asthma. Then, a local cohort consisting of 40 asthmatic subjects (24 with moderate asthma and 16 with severe asthma) was used for biomarker validation. Finally, infiltration of immune cells in asthma bronchoalveolar lavage fluid and their correlation with the screened markers was evaluated by CIBERSORT.

Results: A total of 97 DEGs were identified in this study. Most of these genes are enriched in T cell activation and immune response in the asthma biological process. CC-chemokine receptor 7 (CCR7) and natural killer cell protein 7(NKG7) were identified as markers of severe asthma. The highest area under the ROC curve (AUC) was from a new indicator combining CCR7 and NKG7 (AUC = 0.851, adj. p < 0.05). Resting and activated memory CD4 T cells, activated NK cells, and CD8 T cells were found to be significantly higher in the severe asthma group (adj. p < 0.01). CCR7 and NKG7 were significantly correlated with these infiltrated cells that showed differences between the two groups. In addition, CCR7 was found to be significantly positively correlated with eosinophils (r = 0.38, adj. p < 0.05) infiltrated in bronchoalveolar lavage fluid.

Conclusion: CCR7 and NKG7 might be used as potential markers for asthma severity, and their expression may be associated with differences in immune cell infiltration in the moderate and severe asthma groups.

目的:我们希望找到可以作为哮喘严重程度标志物的关键分子,并研究它们与严重哮喘免疫细胞浸润的相关性。方法:从Gene Expression Omnibus数据库下载哮喘数据集,用R软件进行处理,获得差异表达基因(differential Expression genes, DEGs)。首先,应用多个富集平台分析与deg相关的关键生物过程和途径以及蛋白质-蛋白质相互作用网络。接下来,我们结合最小绝对收缩和选择算子逻辑回归以及支持向量机递归特征消除算法来筛选严重哮喘的诊断标记。然后,一个由40名哮喘患者组成的本地队列(24名中度哮喘患者和16名重度哮喘患者)被用于生物标志物验证。最后用CIBERSORT评价哮喘支气管肺泡灌洗液中免疫细胞的浸润情况及其与筛选标志物的相关性。结果:本研究共鉴定出97个deg。这些基因大多富集于哮喘生物学过程中的T细胞活化和免疫应答中。cc趋化因子受体7(CCR7)和自然杀伤细胞蛋白7(NKG7)被确定为重度哮喘的标志物。合并CCR7和NKG7的新指标的ROC曲线下面积(AUC)最高(AUC = 0.851, p < 0.05)。重度哮喘组静息期和活化记忆期CD4 T细胞、活化NK细胞、CD8 T细胞明显增高(p < 0.01)。CCR7和NKG7与这些浸润细胞显著相关,两组间存在差异。CCR7与支气管肺泡灌洗液中嗜酸性粒细胞浸润呈显著正相关(r = 0.38, p < 0.05)。结论:CCR7和NKG7可能作为哮喘严重程度的潜在标志物,其表达可能与哮喘中重度组免疫细胞浸润的差异有关。
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引用次数: 3
期刊
International Journal of Immunopathology and Pharmacology
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