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Alternariol alleviates breast carcinoma by inhibiting cellular proliferation correlated with increased apoptotic events in rats 链格孢醇通过抑制与细胞凋亡事件增加相关的细胞增殖来减轻大鼠乳腺癌
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221139485
Jian Xin, Y. Shang
The breast cancer is most frequently diagnosed cancer in the women worldwide. Our study investigated the anticancer effect of alternariol, a secondary metabolite originated from endophytic fungi, against DMBA induced breast carcinoma on Wistar rats. The toxicity study investigated the LD50 and the subsequent doses of alternariol for the carcinogenic study. The breast cancer was developed in rats via induction of DMBA (5 mg/kg, i.v.) and the carcinogenic study was continued for 24 weeks. The induction of breast cancer and the chemotherapeutic effect of alternariol were assessed through histopathological analysis of rat mammary tissue, followed by immunohistochemical analysis, cell proliferation assay and apoptosis assay by TUNEL method. The result showed that alternariol therapy decreased the hyperplastic lesions of mammary tissue and restored the normal histopathological characteristics of breast tissue. Furthermore, alternariol treatment downregulated the expression of carcinogenic markers such as PI3K and Akt increased the expression of apoptotic markers including p53, caspase-3 and Bax. Alternariol therapy also decreased the cellular proliferation and enhanced the apoptotic events. In conclusion, the breast cancer progression was significantly reduced via induction of apoptotic events and inhibition of cell propagation which allowed constructing of suitable mechanism for alternariol mediated chemotherapeutic approach.
癌症是全世界女性中最常见的癌症。本研究探讨了内生真菌次生代谢产物交链孢醇对DMBA诱导的Wistar大鼠乳腺癌的抗癌作用。毒性研究调查了致癌研究中的LD50和随后剂量的交链孢醇。通过诱导DMBA(5mg/kg,静脉注射)在大鼠中发展癌症,致癌研究持续24周。通过大鼠乳腺组织的组织病理学分析、免疫组化分析、TUNEL法细胞增殖和凋亡检测,评价了癌症的诱导作用和交链孢醇的化疗效果。结果表明,交链孢醇治疗减少了乳腺组织的增生性病变,恢复了乳腺组织正常的组织病理学特征。此外,交链孢醇处理下调了致癌标志物如PI3K的表达,Akt增加了凋亡标志物如p53、胱天蛋白酶-3和Bax的表达。链格孢醇治疗还降低了细胞增殖并增强了细胞凋亡事件。总之,通过诱导细胞凋亡事件和抑制细胞增殖,癌症的进展显著减少,这使得能够构建适合的机制来进行交链霉素介导的化疗方法。
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引用次数: 2
A novel cuproptosis-related lncRNA prognostic risk score model for gastric cancer based on bioinformatics 基于生物信息学的癌症亚铜相关lncRNA预后风险评分模型
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221128266
Xue Du, Yu Xiao, Chunbao Chen, Lu Yang, Yu Cui, Tingting Wu, B. Tan
Objective To establish an effective cuproptosis-related long non-coding ribonucleic acid (lncRNA) (CRL) prognostic risk score (RS) model (CRLPRSM) for the prediction of the outcomes of patients with gastric cancer (GC). Introduction Cuproptosis is an up-to-date mode of cell death, and its action mechanism is different from all other known mechanisms that regulate cell death. LncRNAs are RNA species that are over 200 nt long and do not encode proteins. They have prominent actions in tumor onset and development, and their involvement in a variety of intracellular regulatory processes is vital for cell proliferation and differentiation, so they may serve as prognostic biomarkers in tumor patients. Methods We retrieved cuproptosis-associated clinical and lncRNA expression data of GC cases from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD). Then a CRLPRSM was built based on univariate and multivariate Cox regression (UCR and MCR) analyses. As per the RS, the patients fell into high- and low-risk group. Later, the predictive efficacy of the CRLPRSM was confirmed with the aid of Kaplan-Meier (KM) analysis and receiver operating characteristic (ROC) curve analysis. Next, combining independent prognostic factors in clinical characteristics, we plotted a prognosis-related nomogram to predict one-year, three-year and five-year overall survival (OS) in GC patients. Finally, we implemented Gene Ontology enrichment analysis (GOEA) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis (KEGGEA) for clarifying the possible biological actions and molecular mechanisms. Results The constructed CRLPRSM consisted of 3 CRLs, namely, AC092574.1, MAGI2-AS3, AC090204.1. It was found that the hazard ratio (HR) was 1.911 (1.337–2.731) (p < 0.001) in UCR analysis and 1.852 (1.286–1.668) (p < 0.001) in MCR analysis, and the AUC of the CRLPRSM was 0.649. Moreover, the KM analysis showed a pronounced intergroup difference in survival, and the nomogram illustrated some clinical benefits of CRLPRSM. Furthermore, GO terms and KEGG pathways were unveiled to be significantly enriched. Conclusion The constructed CRLPRSM has a significant predicted value for GC patient prognosis, and CRLs may become novel hallmarks for clinical treatment of GC.
目的建立一种有效的与铜相关的长非编码核糖核酸(lncRNA)(CRL)预后风险评分(RS)模型(CRLPRSM),用于预测癌症(GC)患者的预后。引言杯状细胞病是一种最新的细胞死亡模式,其作用机制不同于所有其他已知的调节细胞死亡的机制。lncRNA是长度超过200纳米的RNA,不编码蛋白质。它们在肿瘤的发生和发展中具有突出的作用,并且它们参与各种细胞内调节过程对细胞增殖和分化至关重要,因此它们可以作为肿瘤患者的预后生物标志物。方法检索癌症基因组图谱-胃腺癌(TCGA-STAD)中GC病例的铜蛋白相关临床和lncRNA表达数据。然后基于单变量和多变量Cox回归(UCR和MCR)分析建立CRLPRSM。根据RS,患者分为高危组和低危组。随后,借助Kaplan-Meier(KM)分析和受试者工作特性(ROC)曲线分析,证实了CRLPRSM的预测功效。接下来,结合临床特征中的独立预后因素,我们绘制了预后相关列线图,以预测GC患者的一年、三年和五年总生存期(OS)。最后,我们实现了基因本体论富集分析(GOEA)和京都基因和基因组百科全书富集分析(KEGGEA),以阐明可能的生物学作用和分子机制。结果构建的CRLPRSM由3个CRLs组成,分别为AC092574.1、MAGI2-AS3、AC090204.1。研究发现,在UCR分析中,危险比(HR)为1.911(1.337–2.731)(p<0.001),在MCR分析中为1.852(1.286–1.668)(p>0.001),CRLPRSM的AUC为0.649。此外,KM分析显示组间生存率存在显著差异,列线图显示了CRLPRSM的一些临床益处。此外,GO术语和KEGG途径被揭示为显著富集。结论构建的CRLPRSM对胃癌患者的预后具有重要的预测价值,CRLs可能成为胃癌临床治疗的新标志。
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引用次数: 0
Association of serum biochemical indexes and thyroid nodule with disease activity in patients with chronic spontaneous urticaria 慢性自发性荨麻疹患者血清生化指标及甲状腺结节与疾病活动度的关系
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221141789
Yuandong Su, Wei Cui
Objectives: This study aimed to evaluate the correlation of serum biochemical indexes with disease activity and pruritus in patients with chronic spontaneous urticaria (CSU). Methods: Fifty CSU patients were enrolled and 50 health screen examinees were recruited as the control group. Peripheral blood samples were collected, and thyroid colour Doppler ultrasounds were recorded. Body mass index (BMI) was calculated for both groups. The urticaria activity score over 7 days (UAS-7) was used to evaluate the disease activity and degree of pruritus. Results: There was no significant difference in BMI between CSU patients and control (p > .05). The serum WBC, NEU, CRP (all p = .000) and ALT levels (p = .013) in the CSU patients were significantly higher than those in the healthy control group, and the UAS-7 score was positively correlated with WBC and NEU in the CSU patient group. The TG level of the CSU group was higher than healthy controls, albeit no statistical significance (p = .522). The levels of T3 and TSH were significantly lower in the CSU group (p = .000). The incidence rate of thyroid nodules in the CSU patients was significantly higher (p = .045), and four CSU patients showed papillary carcinoma by pathology examination. The average UAS-7 score of patients with complications was significantly higher than that of patients without complications. Conclusion: Patients experiencing CSU generally exhibit abnormal serum biochemical indexes and thyroid function. Their incidence rates of thyroid nodule and thyroid papillary carcinoma are significantly higher than that of healthy subjects, which should be considered in clinical practice.
目的:探讨慢性自发性荨麻疹(CSU)患者血清生化指标与疾病活动性和瘙痒的相关性。方法:选取50例CSU患者和50名健康体检者作为对照组。采集外周血,记录甲状腺彩色多普勒超声。计算两组的体重指数(BMI)。采用7天荨麻疹活动度评分(UAS-7)评价疾病活动度和瘙痒程度。结果:CSU患者BMI与对照组比较差异无统计学意义(p < 0.05)。CSU患者血清WBC、NEU、CRP (p = 0.000)、ALT水平(p = 0.013)均显著高于健康对照组,且CSU患者组UAS-7评分与WBC、NEU呈正相关。CSU组TG水平高于健康对照组,但差异无统计学意义(p = .522)。CSU组T3和TSH水平明显降低(p = 0.000)。CSU患者甲状腺结节的发生率明显高于CSU患者(p = 0.045), 4例CSU患者病理检查表现为乳头状癌。有并发症患者的平均UAS-7评分明显高于无并发症患者。结论:CSU患者普遍表现为血清生化指标及甲状腺功能异常。他们的甲状腺结节和甲状腺乳头状癌的发病率明显高于健康人,在临床实践中应予以考虑。
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引用次数: 0
Astaxanthin suppresses End MT by LOX-1 pathway in ox-LDL-induced HUVECs 虾青素通过ox- ldl诱导HUVECs的LOX-1途径抑制末端MT
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221105131
Zhongsheng Zhu, Jinyu Li, R. Tong, Xiaorong Zhang, Bo Yu
Introduction Astaxanthin (ASX) is carotenoid with the highest antioxidant activity in various cell types and reverse atherosclerosis. However, the roles and detailed mechanisms of ASX in atherosclerosis associated endothelial injury remains unclear. Methods In vitro atherosclerosis model was established in HUVECs by incubation with oxidized low-density lipoprotein (ox-LDL). Cell viability and oxidative stress were measured. The mRNA and protein expressions of lectin-like ox-LDL receptor (LOX-1) and other related genes were determined. Results ox-LDL reduced cell viability of HUVECs, and induced oxidative stress, as evidenced by elevated cellular malondialdehyde (MDA) and decreased superoxide dismutase (SOD). Pretreatment with ASX (50, 100, 200, and 400 μM) markedly reversed the reduction in cell viability and an increase in migration of HUVECs induced by ox-LDL (50 μg/mL). ASX attenuated the increase in the endothelial-to-mesenchymal transition (EndMT) process, as evidenced by increased CD31 and decreased α-SMA and vimentin proteins by ASX treatment in HUVECs. Furthermore, ASX attenuated the increase in MDA and decrease in SOD induced by ox-LDL, increased supernatant NO production, attenuated the increase in iNOS and decrease in eNOS in HUVECs with ox-LDL. ASX enhanced mRNA and protein expressions of the lectin-like ox-LDL receptor (LOX-1), which was dependent on ASX’s antioxidant activity. The inhibitory effect of ASX on EndMT could be abolished by overexpression of LOX-1 in HUVECs induced by ox-LDL. Conclusions Our data speculate that ASX prevents ox-LDL-induced endothelial cell injury and EndMT by inducing antioxidant property (SOD and NO) and decreasing LOX-1 expression.
简介虾青素(ASX)是一种类胡萝卜素,在各种细胞类型中具有最高的抗氧化活性,可逆转动脉粥样硬化。然而,ASX在动脉粥样硬化相关内皮损伤中的作用和详细机制尚不清楚。方法采用氧化低密度脂蛋白(ox-LDL)培养HUVECs,建立体外动脉粥样硬化模型。测量细胞活力和氧化应激。测定凝集素样ox-LDL受体(LOX-1)及其他相关基因的mRNA和蛋白表达。结果ox-LDL降低HUVECs的细胞活力,并诱导氧化应激,表现为细胞丙二醛(MDA)升高和超氧化物歧化酶(SOD)降低。ASX(50、100、200和400μM)预处理显著逆转了ox-LDL(50μg/mL)诱导的HUVECs的细胞活力降低和迁移增加。ASX减弱了内皮-间充质转化(EndMT)过程的增加,如HUVECs中ASX处理增加的CD31和减少的α-SMA和波形蛋白所证明的。此外,ASX减弱了ox-LDL诱导的HUVECs中MDA的增加和SOD的降低,增加了上清液中NO的产生,减弱了iNOS的增加和eNOS的降低。ASX增强了凝集素样ox-LDL受体(LOX-1)的mRNA和蛋白质表达,LOX-1依赖于ASX的抗氧化活性。ASX对EndMT的抑制作用可以通过ox-LDL诱导的HUVECs中LOX-1的过表达来消除。结论ASX通过诱导抗氧化性(SOD和NO)和降低LOX-1的表达来预防ox-LDL诱导的内皮细胞损伤和EndMT。
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引用次数: 0
Hepatitis C virus: Its prevalence, risk factors and genotype distribution in Pakistan 丙型肝炎病毒:在巴基斯坦的流行、危险因素和基因型分布
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221144391
U. Saleem, N. Aslam, R. Siddique, S. Iqbal, M. Manan
Hepatitis C is a dangerous liver disease transmitted by Hepatitis C virus (HCV). HCV constitutes an important health issue in Pakistan. In Pakistani setting HCV is found frequently and is recognized as an alarming health problem. In this cross sectional study we reviewed published data regarding the seroprevalence of hepatitis C in general community, blood donors and pregnant females and risk factors linked with its occurrence in Pakistan. Data retrieved from163 studies published from 2001 to 2022 was utilized and weighted mean was calculated. Data of 1,875,232 individuals was collected and arranged into three groups, depending upon the population type such as (1) general population, (2) pregnant women, (3) blood donors. General population (765,426) and blood donors (973,260) formed the most of population. Mean Hepatitis C virus prevalence in general public and blood donors was 16.47% and 8.2% respectively. In pregnant females (136,546) the mean frequency was 9.3%. This study exhibits that the frequency of Hepatitis C in general population, pregnant females and blood donors groups was 11.32%. The data suggested that risks factors for transmitting HCV infection in Pakistan include unsterilized needle use, blood transfusions, shaving by barbers, lack of trained staff, needle stick injuries, injection drug users, household contacts/spousal transmission, unsterilized dental and surgical Instruments, improper disposal of hospital waste, poor infra-structure and others. The frequency of HCV infection is distressing in Pakistan. Health education and awareness programs are needed for decreasing Hepatitis C infection in Pakistan. The data necessitate the implementation of preventive and remedial approaches to decrease the disease load and mortality in Pakistan.
丙型肝炎是一种由丙型肝炎病毒(HCV)传播的危险肝脏疾病。丙型肝炎病毒是巴基斯坦的一个重要健康问题。在巴基斯坦,丙型肝炎病毒经常被发现,并被认为是一个令人担忧的健康问题。在这项横断面研究中,我们回顾了已发表的关于巴基斯坦普通社区、献血者和孕妇丙型肝炎血清患病率以及与丙型肝炎发生相关的危险因素的数据。采用2001年至2022年发表的163项研究的数据,计算加权平均值。收集了1,875,232人的数据,并根据人群类型分为三组,如:(1)一般人群,(2)孕妇,(3)献血者。一般人口(765,426人)和献血者(973,260人)构成了人口的大部分。普通公众和献血者的平均丙型肝炎病毒感染率分别为16.47%和8.2%。在孕妇中(136,546),平均频率为9.3%。本研究显示,一般人群、孕妇和献血者的丙型肝炎发病率为11.32%。数据表明,在巴基斯坦传播丙型肝炎病毒感染的风险因素包括未经消毒的针头使用、输血、理发师剃须、缺乏训练有素的工作人员、针头刺伤、注射吸毒者、家庭接触者/配偶传播、未经消毒的牙科和外科器械、医院废物处置不当、基础设施差等。在巴基斯坦,丙型肝炎病毒感染的频率令人痛心。巴基斯坦需要开展健康教育和宣传项目,以减少丙型肝炎感染。这些数据要求采取预防和补救措施,以减少巴基斯坦的疾病负担和死亡率。
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引用次数: 1
Immune response and cytokine storm in SARS-CoV-2 infection: Risk factors, ways of control and treatment SARS-CoV-2感染的免疫反应和细胞因子风暴:危险因素、控制和治疗方法
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221098970
Hamid Chegni, H. Babaii, Z. Hassan, M. Pourshaban
In 2020, a deadly pandemic caused by the SARS-COV-2 virus spread worldwide and killed many people. In some viral infections, in addition to the pathogenic role of the virus, impaired immune function leads to inflammation and further damage in internal tissues. For example, coronavirus in some patients prevents the stimulation of the acquired immune system. Therefore, innate immunity is over-stimulated to compensate, followed by the overproduction of inflammatory cytokines and cytokine storm. Various underlying factors such as age, gender, blood pressure, diabetes, and obesity affect cytokine storm. It seems that cytokine storm is one of the leading causes of death among COVID-19 patients, and providing that this storm is detected and controlled in time, it can reduce the mortality of COVID-19 patients. This article aims to investigate the immune system response to COVID-19, various factors associated with cytokine storm, and its treatment. In the current situation, in parallel with the progress made in the field of vaccination, it is necessary to carefully examine the various dimensions of the immune system in response to the COVID-19 virus to seek a suitable treatment strategy to save the lives of patients in intensive care units
2020年,由严重急性呼吸系统综合征冠状病毒2型引起的致命流行病在全球范围内传播,造成许多人死亡。在一些病毒感染中,除了病毒的致病作用外,免疫功能受损还会导致炎症和内部组织的进一步损伤。例如,一些患者的冠状病毒会阻止对获得性免疫系统的刺激。因此,先天免疫被过度刺激以进行补偿,随之而来的是炎性细胞因子和细胞因子风暴的过度产生。年龄、性别、血压、糖尿病和肥胖等多种潜在因素会影响细胞因子风暴。细胞因子风暴似乎是新冠肺炎患者死亡的主要原因之一,如果及时发现并控制这场风暴,它可以降低新冠肺炎患者的死亡率。本文旨在研究免疫系统对新冠肺炎的反应、与细胞因子风暴相关的各种因素及其治疗。在目前的情况下,在疫苗接种领域取得进展的同时,有必要仔细检查免疫系统应对新冠肺炎病毒的各个方面,以寻求合适的治疗策略来挽救重症监护室患者的生命
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引用次数: 2
Hematological features and risk factors of hospitalized COVID-19 patients: A retrospective analysis 新冠肺炎住院患者血液学特征及危险因素的回顾性分析
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221092909
Chaoyang Hua, Jia Li, Yanfang Yang, Zhan-Yun Liu
Background: Coronavirus disease 2019 (COVID-19) became pandemic in 2020 and recently, mutated coronaviruses have emerged in many countries. The aim of this study was to identify the clinical characteristics and risk factors for critical illness in hospitalized COVID-19 patients in Zhengzhou for clinical prevention and management. Materials and methods: A total of 70 patients hospitalized with COVID-19 were enrolled between 21 January and 29 February 2020, in Zhengzhou, China. Clinical characteristics, hematological findings, neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and inflammatory index on admission were obtained from medical records, COVID-19 patients with different outcomes were compared. Results: The median age was 55 years. Forty-three (61.0%) patients were classified as having severe or critical cases. Eighteen (25.7%) patients died in hospital and the remaining 52 were discharged. Patients who died tend to be old with expectoration and chronic obstructive pulmonary disease. Compared to survivor, non-survivor had significantly higher numbers of leucocytes and neutrophils, NLR, aspartate aminotransferase (AST), γ-glutamyl transpeptidase, total bilirubin, direct bilirubin, lactate dehydrogenase (LDH), prothrombin time, D-dimer, C-reactive protein, and decreased platelets, lymphocytes, uric acid, and albumin (ALB). Logistic regression analysis identified leucocytes, platelets, PLR, NLR, AST, and ALB as independent predictive factors for poor outcomes. The area under curve of the combination of leucocytes, PLR, NLR, and AST was 0.87, with a sensitivity of 0.83 and specificity of 0.81. Conclusion: Our results identified risk factors among COVID-19 patients for in-hospital mortality. Leucocytes, PLR, NLR, and AST could have important reference value for predicting prognosis, especially in low-resource countries.
背景:2019冠状病毒病(新冠肺炎)于2020年成为大流行性疾病,最近,许多国家出现了变异冠状病毒。本研究旨在确定郑州市新冠肺炎住院患者危重症的临床特征和危险因素,以供临床预防和管理。材料和方法:2020年1月21日至2月29日,共有70名新冠肺炎住院患者在中国郑州登记。从病历中获取入院时的临床特征、血液学表现、中性粒细胞淋巴细胞比率(NLR)、血小板淋巴细胞比率(PLR)和炎症指数,比较不同结局的新冠肺炎患者。结果:中位年龄55岁。43名(61.0%)患者被归类为重症或危重病例。18名(25.7%)患者在医院死亡,其余52人出院。死亡的患者往往是老年人,伴有咳痰和慢性阻塞性肺病。与幸存者相比,非幸存者的白细胞和中性粒细胞数量、NLR、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶、总胆红素、直接胆红素、乳酸脱氢酶(LDH)、凝血酶原时间、D-二聚体、C反应蛋白显著增加,血小板、淋巴细胞、尿酸和白蛋白(ALB)减少。Logistic回归分析确定白细胞、血小板、PLR、NLR、AST和ALB是不良预后的独立预测因素。白细胞、PLR、NLR和AST组合的曲线下面积为0.87,敏感性为0.83,特异性为0.81。结论:我们的研究结果确定了新冠肺炎患者住院死亡率的危险因素。白细胞、PLR、NLR和AST对预测预后具有重要的参考价值,尤其是在低资源国家。
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引用次数: 0
Autoantigen spermatid nuclear transition protein 1 enhances pro-inflammatory cytokine production stimulated by anti-DNA autoantibodies in macrophages 自身抗原精子核转移蛋白1促进巨噬细胞抗dna自身抗体刺激的促炎细胞因子产生
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221131792
Laxmi Prasad Uprety, Y. Park, Y. Jang
Introduction Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE), is associated with high fatality rate in patients. The pathogenesis of lupus nephritis is complex and has not been fully elucidated. Kidney inflammation, renal cell damage, and accumulation of immune complexes in the glomerular basement membrane often occur in patients with lupus nephritis. Spermatid nuclear transition protein 1 (TNP1) might be a potentially interesting autoantigen in exploring the pathogenesis and therapy of lupus nephritis. Objective This study aimed to explore the effect of TNP1 and its complexes with anti-double-stranded DNA antibodies on the levels of interleukin-6 (IL-6) and interferon-α (IFN-α) in vitro. Methods We studied the effect of the synthetic peptide of the autoantigen on the pathogenic characteristics of the G2-6 and G5-8 antibodies in mouse macrophages, using enzyme-linked immunosorbent assay, quantitative RT-PCR, western blotting, and flow cytometry. Results The antibodies exhibited cross-reactivity to spermatid TNP1 in direct-binding and competitive enzyme-linked immunosorbent assay. Results of quantitative RT-PCR and western blotting revealed that the antibodies alone enhanced the levels of IL-6 and IFN-α transcripts and proteins, respectively. Flow cytometry revealed that treatment with the autoantigen enhanced the cell-penetrating activities of G2-6 and G5-8 and remarkably increased the cytokine levels. Conclusion TNP1 enhanced the cell-penetrating activities of anti-dsDNA auto-Abs, G2-6 and G5-8, and remarkably increased the levels of IL-6 and IFN-α in macrophages, suggesting that TNP1 and cell-penetrating pathogenic anti-dsDNA auto-Abs is potential targets for future therapeutic approaches to treat LN/SLE.
狼疮肾炎(LN)是系统性红斑狼疮(SLE)的一种严重表现,患者病死率高。狼疮性肾炎的发病机制复杂,尚未完全阐明。狼疮性肾炎患者常出现肾脏炎症、肾细胞损伤和肾小球基底膜免疫复合物的积累。精子核转移蛋白1 (TNP1)可能是探索狼疮性肾炎发病机制和治疗的潜在有趣的自身抗原。目的探讨TNP1及其复合物与抗双链DNA抗体在体外对白细胞介素-6 (IL-6)和干扰素-α (IFN-α)水平的影响。方法采用酶联免疫吸附法、定量RT-PCR、western blotting和流式细胞术研究自身抗原合成肽对小鼠巨噬细胞中G2-6和G5-8抗体致病特性的影响。结果在直接结合和竞争性酶联免疫吸附实验中,抗体对精子TNP1表现出交叉反应性。定量RT-PCR和western blotting结果显示,单抗分别提高了IL-6和IFN-α转录本和蛋白的水平。流式细胞术显示,自体抗原处理可增强G2-6和G5-8的细胞穿透活性,显著提高细胞因子水平。结论TNP1可增强抗dsdna auto-Abs、G2-6和G5-8的细胞穿透活性,并显著提高巨噬细胞中IL-6和IFN-α的水平,提示TNP1和抗dsdna穿透致病性auto-Abs是未来治疗LN/SLE的潜在靶点。
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引用次数: 1
Mechanisms of reactive oxygen species in oral lichen planus: A literature review 口腔扁平苔藓中活性氧的作用机制:文献综述
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221104389
Xin Li, Zhiqiang Wang
Oral lichen planus is a chronic non-infectious mucosal inflammatory disease caused by an imbalance between reactive oxygen species homeostasis and antioxidant defense systems. Notably, excessive oxidative stress products result in related autoimmune reactions. Further, it activates signaling pathways related to the development of oral lichen planus, as evidenced by the detection of damage to deoxyribonucleic acid, protein, and lipid. Thus, the mechanisms of reactive oxygen species-mediated oxidative stress in the pathogenesis of oral lichen planus are numerous and complex. In this review, we first introduce oxidative stress and oxidative products. Then, we summarize the role and possible mechanisms of reactive oxygen species-mediated oxidative stress in the pathogenesis of oral lichen planus and present a clinical correlation between oxidative stress and oral lichen planus. Finally, we discuss the current challenges and future perspectives.
口腔扁平苔藓是一种慢性非感染性粘膜炎症性疾病,由活性氧稳态与抗氧化防御系统失衡引起。值得注意的是,过量的氧化应激产物会导致相关的自身免疫反应。此外,通过检测对脱氧核糖核酸、蛋白质和脂质的损伤,它可以激活与口腔扁平苔藓发育相关的信号通路。因此,活性氧介导的氧化应激在口腔扁平苔藓发病中的作用机制是众多而复杂的。本文首先介绍了氧化应激和氧化产物。然后,我们总结了活性氧介导的氧化应激在口腔扁平苔藓发病中的作用和可能的机制,并提出了氧化应激与口腔扁平苔藓的临床相关性。最后,我们讨论了当前的挑战和未来的展望。
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引用次数: 1
Advance of T regulatory cells in tumor microenvironment remodeling and immunotherapy in pancreatic cancer T调节细胞在胰腺癌肿瘤微环境重塑及免疫治疗中的研究进展
IF 0.7 4区 医学 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/1721727X221092900
Zetian Gao, Qiu-bo Zhang, Xie Zhang, Yufei Song
Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive, deadly, and is rarely diagnosed early. Regulatory T cells (Treg) are a multifunctional class of immunosuppressive T cells that help maintain immunologic homeostasis and participate in autoimmune diseases, transplants, and tumors. This cell type mediates immune homeostasis, tolerance, and surveillance and is associated with poor outcomes in PDAC. Tregs remodel the tumor immune microenvironment, mediate tumor immune escape, and promote tumor invasion and metastasis. A promising area of research involves regulating Tregs to reduce their infiltration into tumor tissues. However, the complexity of the immune microenvironment has limited the efficacy of immunotherapy in PDAC. Treg modulation combined with other treatments is emerging. This review summarizes the mechanisms of Tregs activity in tumor immune microenvironments in PDAC and the latest developments in immunotherapy and clinical trials.
胰腺导管腺癌(PDAC)是一种侵袭性强、致死率高的疾病,很少在早期被诊断出来。调节性T细胞(Treg)是一类多功能的免疫抑制T细胞,有助于维持免疫稳态并参与自身免疫性疾病、移植和肿瘤。这种细胞类型介导免疫稳态、耐受性和监视,并与PDAC的不良预后相关。Tregs重塑肿瘤免疫微环境,介导肿瘤免疫逃逸,促进肿瘤侵袭转移。一个很有前景的研究领域涉及调节treg以减少它们对肿瘤组织的浸润。然而,免疫微环境的复杂性限制了免疫治疗在PDAC中的疗效。Treg调节联合其他治疗方法正在出现。本文综述了Tregs活性在PDAC肿瘤免疫微环境中的作用机制以及免疫治疗和临床试验的最新进展。
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引用次数: 2
期刊
European Journal of Inflammation
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