Immunity, Inflammation and Disease最新文献_第2页

Associations between single nucleotide polymorphisms of cytokines and hepatitis B virus-related liver cirrhosis: A case-control study 细胞因子单核苷酸多态性与乙型肝炎病毒相关肝硬化的关系：病例对照研究

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-09-24 DOI: 10.1002/iid3.70017

Yijun Li, Haowei Zhou, Weikang Wu, Wenhua Zhang, Yancheng Ye, Wenling Jia, Chunhui Liang, Haitao Tang, Fengmei Wang, Zhongjun Shao, Xiaojie Yuan, Weilu Zhang

Background and Aims

Various inflammatory and immune cytokines play key roles in the progression of hepatitis B virus (HBV)-related liver cirrhosis (LC). This study explored the relationship between single nucleotide polymorphisms (SNPs) in cytokines with the combined effect of polymorphisms and gender-polymorphisms interaction and LC risk.

Methods

In this study, a case–control design was used, samples were selected from 45 patients with hepatitis B-related cirrhosis and 45 age-gender-matched chronic HBV-infected patients without cirrhosis attending the tumor hospital of Wuwei Academy of Medical Sciences. Fifteen SNPs were examined using a real-time polymerase chain reaction allelic discrimination system. Logistic regression was utilized to assess cytokine-associated SNPs and the association between SNPs and LC progression in HBV-infected patients.

Results

The multivariate-adjusted logistic model revealed that the GG/AG dominant model (OR, 16.38; 95% CI, 1.13–236.70) and G allele (OR, 5.93; 95% CI, 0.98–36.01) of rs1800896 were associated with an increased risk of cirrhosis in CHB patients. Instead, rs2227306 CT presented a reduced cirrhosis risk (OR, 0.22; 95% CI, 0.04–1.38). Rs2055979 AA/AC was negatively associated with the risk of cirrhosis, potentially reversed in males (p = 0.021). Rs1799964 CC/CT was positively related to the risk of cirrhosis but reduced the risk of cirrhosis in males (OR, 0.13; 95% CI, 0.022–0.808; p = 0.028). Both rs1799964 TT and rs1799724 CT/TT genotype showed a synergistic effect in reducing the risk of cirrhosis with rs1800896 AA (OR, 0.08; 95% CI, 0.01–1.43 and OR, 0.12; 95% CI, 0.01–2.21).

Conclusion

Polymorphisms rs1800896 and rs2227306 are potentially associated with the risk of cirrhosis. For the first time, the study highlights that the rs2055979 AA/AC and rs1799964 CC/CT polymorphism interact with gender and its potential reversal of cirrhosis risk in males. Furthermore, rs1800896 AA showed a synergistic effect with rs1799964 TT and rs1799724 CT/TT to prevent the progression of HBV infection to cirrhosis.

背景和目的：各种炎症和免疫细胞因子在乙型肝炎病毒（HBV）相关肝硬化（LC）的进展中起着关键作用。本研究探讨了细胞因子中的单核苷酸多态性（SNPs）与多态性和性别-多态性相互作用的综合效应与 LC 风险之间的关系：本研究采用病例对照设计，样本选自武威医学科学院肿瘤医院的45例乙肝相关性肝硬化患者和45例年龄性别匹配的非肝硬化慢性HBV感染者。使用实时聚合酶链反应等位基因鉴别系统检测了 15 个 SNPs。利用逻辑回归评估细胞因子相关的SNPs以及SNPs与HBV感染者LC进展之间的关系：多变量调整逻辑模型显示，rs1800896的GG/AG显性模型（OR，16.38；95% CI，1.13-236.70）和G等位基因（OR，5.93；95% CI，0.98-36.01）与CHB患者肝硬化风险增加有关。相反，rs2227306 CT 降低了肝硬化风险（OR，0.22；95% CI，0.04-1.38）。Rs2055979 AA/AC 与肝硬化风险呈负相关，在男性中可能发生逆转（p = 0.021）。Rs1799964 CC/CT 与肝硬化风险呈正相关，但降低了男性的肝硬化风险（OR，0.13；95% CI，0.022-0.808；p = 0.028）。rs1799964 TT 和 rs1799724 CT/TT 基因型与 rs1800896 AA 在降低肝硬化风险方面具有协同作用（OR，0.08；95% CI，0.01-1.43 和 OR，0.12；95% CI，0.01-2.21）：多态性 rs1800896 和 rs2227306 可能与肝硬化风险有关。该研究首次强调了 rs2055979 AA/AC 和 rs1799964 CC/CT 多态性与性别的相互作用，以及其对男性肝硬化风险的潜在逆转作用。此外，rs1800896 AA 与 rs1799964 TT 和 rs1799724 CT/TT 在预防 HBV 感染进展为肝硬化方面具有协同作用。

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引用次数: 0

Efficacy and mechanism of action of ginsenoside Rg3 on radiation proctitis in rats 人参皂苷 Rg3 对大鼠放射性直肠炎的疗效和作用机制

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-09-24 DOI: 10.1002/iid3.70015

Xuxia Li, Lili Lin, Xiaoyu Duan, Jiuju Dai, Tingting Hu, Hongyi Cai

Objective

Radiation proctitis (RP) refers to rectal injury caused by radiation treatment of pelvic and retroperitoneal malignancies, which has a major impact on the treatment prognosis and quality of life of patients with cancer. The tetracyclic triterpene saponin monomer ginsenoside Rg3 (GRg3), the primary bioactive ingredient in ginseng extracts, has therapeutic effects against RP in rats. Here, we validated its efficacy and elucidated its mechanism of action.

Methods

A rat RP model was established in 48 Wistar rats. Rats were randomly divided into control (untreated), irradiation, irradiation + dexamethasone, and irradiation + GRg3 (low-, medium-, and high-dose) groups. After 2 weeks' treatment, serum IL-4, IL-10, and TNF-α levels were tested by enzyme-linked immunosorbent assays. In rectal tissue, Ikbkb, Ikka, and Casp8 mRNA expression was detected by a reverse transcription-quantitative polymerase chain reaction. IKK-β, IκB-α, p-IκB-α, p50, and caspase-8 protein levels were determined by western blot analysis.

Results

GRg3 significantly improved the general condition and histopathological damage in rats with RP. Moreover, GRg3 decreased the levels of factors that promote inflammation (TNF-α) and increased the levels of factors that reduce inflammation (IL-4 and IL-10). GRg3 markedly reduced the activation of NF-κB and caspase-8 signaling pathways.

Conclusions

Thus, GRg3 may reduce the inflammatory response by blocking the NF-κB signaling pathway and improving the balance of inflammation-related factors. GRg3 may also inhibit intestinal cell apoptosis by suppressing the TNF-α/caspase-8 signaling cascade, thereby reducing radiological rectal injury. Our results verify that GRg3 is a promising therapeutic agent for RP treatment and shed light on its mechanism.

目的：放射性直肠炎（RP）是指盆腔和腹膜后恶性肿瘤放射治疗引起的直肠损伤，对癌症患者的治疗预后和生活质量有很大影响。四环三萜皂苷单体人参皂苷 Rg3（GRg3）是人参提取物中的主要生物活性成分，对大鼠的 RP 有治疗作用。在此，我们验证了其疗效并阐明了其作用机制：方法：在 48 只 Wistar 大鼠中建立大鼠 RP 模型。大鼠被随机分为对照组（未处理）、照射组、照射+地塞米松组和照射+GRg3（低、中、高剂量）组。治疗2周后，用酶联免疫吸附试验检测血清中IL-4、IL-10和TNF-α的水平。通过反转录定量聚合酶链反应检测直肠组织中 Ikbkb、Ikka 和 Casp8 mRNA 的表达。IKK-β、IκB-α、p-IκB-α、p50和Caspase-8蛋白水平通过Western印迹分析进行测定：结果：GRg3能明显改善RP大鼠的一般状况和组织病理学损伤。此外，GRg3 还降低了促进炎症的因子（TNF-α）的水平，提高了减轻炎症的因子（IL-4 和 IL-10）的水平。GRg3明显减少了NF-κB和caspase-8信号通路的激活：因此，GRg3 可通过阻断 NF-κB 信号通路和改善炎症相关因子的平衡来减轻炎症反应。GRg3还可通过抑制TNF-α/caspase-8信号级联抑制肠细胞凋亡，从而减轻放射性直肠损伤。我们的研究结果验证了GRg3是一种很有前景的治疗直肠癌的药物，并揭示了其作用机制。

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引用次数: 0

Correlation between serum vitamin D level and acute invasive enteritis in children 儿童血清维生素 D 水平与急性侵袭性肠炎之间的相关性。

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-09-24 DOI: 10.1002/iid3.70024

Lingrong Yang, Yu Fang, Jinyu Zheng, Qiaoying Zhu, Li Tang, Fu Xiong

Background

Diarrhea is a leading cause of death in young children worldwide. Vitamin D deficiency impairs the body's ability to clear pathogens, reduces tight junction protein expression in intestinal epithelial cells, and enhances Th1-mediated intestinal inflammation. This study aimed to investigate the effects of serum vitamin D levels on acute invasive enteritis in children.

Methods

This prospective cohort study included 82 children aged 1–3 years with clinically diagnosed acute invasive enteritis at Sichuan Maternal and Child Health Hospital from February 2021 to February 2022, alongside a control group of 80 healthy children. Fecal specimens were collected for routine tests and occult blood analysis, while blood samples were taken for routine tests, C-reactive protein, and 25-OHD levels. Comparative analyses were performed between groups, and multifactorial logistic regression was used to identify factors influencing invasive enteritis.

Results

The study group showed significantly lower serum 25-OHD levels (27.95 ± 9.91 ng/mL) compared to controls (32.76 ± 10.23 ng/mL, p < .01). Among the study group, 19.5% (16/82) had levels <20 ng/mL, versus 12.5% (10/80) in controls. Regular vitamin D supplementation was lower in the study group (58.5% vs. 77.5%, p < .05). Outdoor activity duration was also reduced (2.57 ± 0.98 h vs. 3.04 ± 0.88 h, p < .01). Multivariate analysis identified that exclusive breastfeeding, greater outdoor activity time and regular vitamin D supplementation were all associated with reduced risk of invasive enteritis (p < .05).

Conclusion

The findings indicate an association between low serum 25-OHD levels and acute invasive enteritis in children aged 1-3 years, suggesting that consistent vitamin D supplementation and sufficient outdoor activity may protect against this condition.

背景：腹泻是全球幼儿死亡的主要原因。维生素 D 缺乏会损害机体清除病原体的能力，降低肠上皮细胞中紧密连接蛋白的表达，并增强 Th1 介导的肠道炎症。本研究旨在探讨血清维生素 D 水平对儿童急性侵袭性肠炎的影响：这项前瞻性队列研究纳入了2021年2月至2022年2月在四川省妇幼保健院就诊的82名临床诊断为急性侵袭性肠炎的1-3岁儿童，以及由80名健康儿童组成的对照组。研究人员采集粪便标本进行常规检测和隐血分析，同时采集血液标本进行常规检测、C反应蛋白和25-OHD水平检测。各组间进行比较分析，并采用多因素逻辑回归法确定影响侵袭性肠炎的因素：结果：研究组的血清 25-OHD 水平（27.95 ± 9.91 ng/mL）明显低于对照组（32.76 ± 10.23 ng/mL，P 结论：研究结果表明，血清 25-OHD 水平低与侵袭性肠炎有关：研究结果表明，1-3 岁儿童血清 25-OHD 水平低与急性侵袭性肠炎之间存在关联，这表明坚持补充维生素 D 和充足的户外活动可预防这种疾病。

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引用次数: 0

Research of recombinant influenza A virus as a vector for Mycoplasma pneumoniae P1a and P30a 重组甲型流感病毒作为肺炎支原体 P1a 和 P30a 载体的研究

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-09-18 DOI: 10.1002/iid3.70021

Liang Yu, Wang Yongbo, Yang Shengjun, Tan Jia, Xu Ya, Liao Guoyang, Ma Linna

<div> <section> <h3> Background</h3> <p><i>Mycoplasma pneumoniae</i> (<i>MP</i>) is a common respiratory pathogen affecting the longevity of the elderly and the health of children. However, the human vaccine against MP has not been successfully developed till now due to the poor immunogenicity and side effects of <i>MP</i> inactivated or attenuated vaccine. Therefore, it is necessary to develop a <i>MP</i> genetic engineering vaccine with influenza virus strain as vector.</p> </section> <section> <h3> Methods</h3> <p>In this study, the major antigen genes P1a of <i>MP</i> adhesion factor P1(3862-4554 bases) and P30a of P30(49-822 bases) were inserted into the nonstructural protein (NS) gene of Influenza A virus strain A/Puerto Rio/8/34(H1N1), PR8 for short, to construct the recombinant vectors NS-P1a or NS-P30a. The recombinant pHW2000 plasmids containing NS-P1a or NS-P30a were cotransfected with the rest 7 fragments of PR8 into HEK293T cells. After inoculating chicken embryos, the recombinant influenza viruses rFLU-P1a and rFLU-P30a were rescued. RT-PCR and sequencing were used to identify the recombinant viruses. The hemagglutination titers of rFLU-P1a and rFLU-P30a were determined after five successive generations in chicken embryos so as to indicate the genetic stability of the recombinant viruses. The morphology of recombinant influenza viruses was observed under electron microscopy.</p> </section> <section> <h3> Results</h3> <p>P1a or P30a was designed to be inserted into the modified NS gene sequence separately and synthesized successfully. RT-PCR identification of the recombinant viruses rFLU-P1a and rFLU-P30a showed that P1a (693 bp), P30a (774 bp), NS-P1a (1992bp) and NS-P30a (2073 bp) bands were found, and the sequencing results were correct. After five successive generations, each virus generation has a certain hemagglutination titer (from 1:32 to 1:64), and the band of P1a or P30a can be seen in the corresponding positions. The virus particles under the electron microscope appeared as spheres or long strips connected by several particles, revealing a complete viral membrane structure composed of virus lipid bilayer, hemagglutinin, neuraminidase, and matrix proteins.</p> </section> <section> <h3> Conclusion</h3> <p>The recombinant viruses rFLU-P1a and rFLU-P30a which carried the advantaged immune regions of the P1 and P30 genes in MP were successfully constructed and identified. And the genetic stability of rFLU-P1a or rFLU-P30a was relatively high. The typical and complete morphology of influenza virus was observed under the electron m

背景肺炎支原体（MP）是一种常见的呼吸道病原体，影响着老年人的寿命和儿童的健康。然而，由于肺炎支原体灭活疫苗或减毒疫苗的免疫原性差、副作用大，人类尚未成功研制出肺炎支原体疫苗。因此，有必要以流感病毒株为载体，开发一种 MP 基因工程疫苗。方法本研究将 MP 粘附因子 P1 的主要抗原基因 P1a（3862-4554 碱基）和 P30 的主要抗原基因 P30a（49-822 碱基）插入甲型流感病毒株 A/Puerto Rio/8/34（H1N1），简称 PR8 的非结构蛋白（NS）基因中，构建重组载体 NS-P1a 或 NS-P30a。将含有 NS-P1a 或 NS-P30a 的重组 pHW2000 质粒与 PR8 其余 7 个片段共转染 HEK293T 细胞。接种鸡胚后，重组流感病毒 rFLU-P1a 和 rFLU-P30a 得到了挽救。利用 RT-PCR 和测序鉴定重组病毒。在鸡胚中连续繁殖五代后，测定了rFLU-P1a和rFLU-P30a的血凝滴度，以表明重组病毒的遗传稳定性。用电子显微镜观察重组流感病毒的形态。结果 P1a 或 P30a 分别被设计插入到修改过的 NS 基因序列中，并成功合成。对重组病毒rFLU-P1a和rFLU-P30a进行RT-PCR鉴定，发现P1a（693bp）、P30a（774bp）、NS-P1a（1992bp）和NS-P30a（2073bp）条带，测序结果正确。经过连续五代，每一代病毒都有一定的血凝滴度（从 1:32 到 1:64），在相应的位置可以看到 P1a 或 P30a 的条带。电镜下的病毒颗粒呈球状或由多个颗粒连接而成的长条状，显示了由病毒脂质双分子层、血凝素、神经氨酸酶和基质蛋白组成的完整病毒膜结构。结论成功构建并鉴定了携带MP中P1和P30基因优势免疫区的重组病毒rFLU-P1a和rFLU-P30a。rFLU-P1a或rFLU-P30a的遗传稳定性相对较高。电镜下观察到流感病毒典型而完整的形态。我们的研究为进一步开发人用 MP 疫苗奠定了基础。

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引用次数: 0

Association of rs2241766 and rs1501299 polymorphisms in the adiponectin gene with metabolic syndrome 脂肪连蛋白基因中的 rs2241766 和 rs1501299 多态性与代谢综合征的关系

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-09-18 DOI: 10.1002/iid3.70025

Yinghua Tang, Lianli Yin, Faquan Lin

Objective

To investigate the influence of adiponectin (APN) rs2241766 and rs1501299 polymorphisms on adiponectin levels and their association with metabolic syndrome (MetS).

Methods

Analyzed two polymorphisms (rs2241766 and rs1501299) of the adiponectin gene (ADIPOQ) in 210 MetS patients and 102 control patients using the polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing technology.

Results

The genotypes of the rs2241766 T/G and rs1501299 G/T polymorphism were significantly associated with serum APN levels in MetS patients. The ADIPOQ polymorphisms were associated with a risk of MetS when compared with that in healthy controls. TG and GG genotypes of rs2241766 were associated with a significantly elevated risk of MetS as compared with the TT genotype (OR = 1.32 and OR = 2.53). Subjects with the G allele appeared to have higher susceptibility to MetS than those with the T allele (OR = 2.21). In common with the findings for rs2241766, the rs1501299 GT and TT genotypes were associated with a significantly increased risk of MetS as compared with the GG genotype (OR = 1.51 and OR = 2.24). The susceptibility to MetS appeared to be higher in subjects with the T allele than in those with the G allele (OR = 1.88).

Conclusions

The occurrence of MetS may be associated with genetic variations at the rs2241766 and rs1501299 loci, especially in individuals with T to G mutations (rs2241766) and G to T mutations (rs1501299). These mutations may lead to decreased APN levels and a higher risk of developing MetS.

目的探讨脂肪直链素（APN）rs2241766和rs1501299多态性对脂肪直链素水平的影响及其与代谢综合征（MetS）的关系。方法采用聚合酶链式反应-限制性片段长度多态性方法和 DNA 测序技术，分析 210 名 MetS 患者和 102 名对照组患者的脂肪直链素基因（ADIPOQ）的两个多态性（rs2241766 和 rs1501299）。结果 rs2241766 T/G和rs1501299 G/T多态性基因型与MetS患者血清APN水平显著相关。与健康对照组相比，ADIPOQ 多态性与 MetS 风险相关。与 TT 基因型相比，rs2241766 的 TG 和 GG 基因型与 MetS 风险的显著升高有关（OR = 1.32 和 OR = 2.53）。具有 G 等位基因的受试者似乎比具有 T 等位基因的受试者更易患 MetS（OR = 2.21）。与 rs2241766 的研究结果相同，与 GG 基因型相比，rs1501299 GT 和 TT 基因型与 MetS 风险显著增加有关（OR = 1.51 和 OR = 2.24）。T等位基因受试者的 MetS 易感性似乎高于 G 等位基因受试者（OR = 1.88）。结论 MetS 的发生可能与 rs2241766 和 rs1501299 位点的遗传变异有关，尤其是在 T 变 G 突变（rs2241766）和 G 变 T 突变（rs1501299）的个体中。这些突变可能导致 APN 水平下降，并增加患 MetS 的风险。

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引用次数: 0

Clinical analysis of 163 pediatric patients with infectious mononucleosis: a single-center retrospective analysis 163 例传染性单核细胞增多症儿科患者的临床分析：单中心回顾性分析

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-09-16 DOI: 10.1002/iid3.70020

Yan Li, Kun Wang

Objective

This study aims to enhance the management of Epstein-Barr Virus (EBV) infections by analyzing the correlation between laboratory indicators and clinical manifestations in children, thereby proposing more precise diagnostic and treatment strategies.

Methods

In this retrospective study included 163 pediatric patients with EBV infections treated at the Children's Hospital of Soochow University from December 2017 to December 2019. Data collected through retrospective analysis included gender, age, clinical symptoms, signs, liver function tests, T-cell subset distribution, EBV-DNA copy numbers in plasma, and treatment outcomes. Patients were grouped based on EBV-DNA copy numbers in plasma and hospital stay duration to compare clinical indicators across different groups.

Results

The dichotomous results of EBV-DNA copy numbers in plasma showed that the two groups of children were significantly different in the number of days of fever (p = .0022), platelet count (p = .0212), ALT (p = .001), immunoglobulin IgM (p = .0039), IgG (p = .0195), TBiL (p = .025), LDH (p = 0.0001), and length of hospital stay (p < .001) were significantly different, indicating that EBV-DNA copy numbers in plasma may be correlated with these characteristic variables. The dichotomous results of the length of hospital stay showed that the two groups were significantly increased in tonsil enlargement (p = .0024), platelet count (p = .0059), LDH (p = .0394), and ferritin (p = .0106) and EBV-DNA copy numbers in plasma (p = 0.0361) were significantly different, This suggests a potential correlation between EBV-DNA copy numbers in plasma and these clinical indicators.

Conclusion

Variations in platelet counts and lactate dehydrogenase (LDH) levels in children with EBV infections may serve as indicators of clinical outcomes.

摘要] 目的本研究旨在通过分析儿童EB病毒（Epstein-Barr Virus，EBV）感染的实验室指标与临床表现之间的相关性，从而提出更精确的诊断和治疗策略，加强对EBV感染的管理。方法在这项回顾性研究中，纳入了2017年12月至2019年12月在苏州大学附属儿童医院接受治疗的163例EB病毒感染儿科患者。通过回顾性分析收集的数据包括性别、年龄、临床症状、体征、肝功能检查、T细胞亚群分布、血浆中EBV-DNA拷贝数和治疗结果。根据血浆中的 EBV-DNA 拷贝数和住院时间对患者进行分组，以比较不同组别的临床指标。结果血浆中 EBV-DNA 拷贝数的二分法结果显示，两组患儿在发热天数（p = .0022）、血小板计数（p = .0212）、谷丙转氨酶（p = .001）、免疫球蛋白 IgM（p = .0039）、IgG（p = .0195）、TBiL（p = .025）、LDH（p = 0.0001）和住院时间（p <.001）均有显著差异，表明血浆中的 EBV-DNA 拷贝数可能与这些特征变量相关。住院时间的二分法结果显示，两组患者的扁桃体肿大（p = .0024）、血小板计数（p = .0059）、LDH（p = .0394）和铁蛋白（p = .0106）显著增加，而血浆中的 EBV-DNA 拷贝数（p = 0.0361）显著不同，这表明血浆中的 EBV-DNA 拷贝数与这些临床指标之间可能存在相关性。结论 EBV 感染儿童血小板计数和乳酸脱氢酶（LDH）水平的变化可作为临床结果的指标。

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引用次数: 0

B7-H3 promotes nasopharyngeal carcinoma progression by regulating CD8+ T cell exhaustion B7-H3 通过调节 CD8+ T 细胞衰竭促进鼻咽癌进展

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-09-13 DOI: 10.1002/iid3.70005

Zhaoen Ma, Gui Chen, Hao Li, Saixuan Yang, Yali Xu, Bolin Pan, Wuping Lai, Guangui Chen, Wenjing Liao, Xiaowen Zhang

Background

B7-H3 protein is an important regulator of the adaptive immune response in human tumorigenesis. 4-1BB is a co-stimulatory receptor expressed on activated CD8+ T cells, and regulates T cell immunity. Here, we investigated the role of B7-H3 in the growth and invasion of nasopharyngeal carcinoma (NPC) and the effect of its interaction with 4-1BB on tumor immunity.

Methods

Short hairpin (sh) RNA was designed to knock down B7-H3 expression in NPC cells. NPC cells with stable knockdown of B7-H3 were established and injected into nude mice. The effects of B7-H3 on cell proliferation, apoptosis, and epithelial-to-mesenchymal transition (EMT) were detected by the CCK8 assay, flow cytometry, TUNEL assay, and western blot analysis. The migration and invasion abilities were determined using the Transwell assay and scratch assay. Co-immunoprecipitation (Co-IP) assays were performed to study the interaction between B7-H3 and 4-1BB. Anti-4-1BB antibody was used in a co-culture system and xenograft mice to study the effect of 4-1BB on NPC development.

Results

NPC cells transfected with sh-B7-H3 showed a higher rate of apoptosis, slower growth rate, impaired migration, and less EMT in vitro. Xenograft mice with stable knockout of B7-H3 had lower tumor burdens, and the stripped tumors had lower rates of cell proliferation, higher rates of apoptosis, and less EMT in vivo. Additionally, decreased B7-H3 expression was positively correlated with interferon-γ, tumor necrosis factor-α, and 4-1BB+CD8+ tumor-infiltrating lymphocytes. Co-IP studies showed that B7-H3 interacts with 4-1BB. Also, the inhibitory effects of sh-B7-H3 on NPC tumor growth, invasion, and tumor immunity could be alleviated by the anti-4-1BB antibody both in vivo and in vitro.

Conclusion

Our findings suggest that B7-H3 may accelerate tumor growth, tumor cell invasion, and EMT, and interact with 4-1BB to produce CD8+ T cell exhaustion that inhibits tumor immunity. B7-H3 might serve as a novel target for treating NPC.

背景 B7-H3 蛋白是人类肿瘤发生过程中适应性免疫反应的重要调节因子。4-1BB 是表达在活化的 CD8+ T 细胞上的共刺激受体，可调节 T 细胞免疫。在此，我们研究了 B7-H3 在鼻咽癌（NPC）生长和侵袭中的作用，以及它与 4-1BB 相互作用对肿瘤免疫的影响。方法设计短发夹（sh）RNA来敲除鼻咽癌细胞中B7-H3的表达。建立稳定敲除 B7-H3 的鼻咽癌细胞并将其注射到裸鼠体内。B7-H3 对细胞增殖、凋亡和上皮细胞向间质转化（EMT）的影响通过 CCK8 试验、流式细胞术、TUNEL 试验和 Western 印迹分析进行检测。迁移和侵袭能力通过 Transwell 试验和划痕试验进行检测。共免疫沉淀（Co-IP）试验用于研究 B7-H3 和 4-1BB 之间的相互作用。在共培养系统和异种移植小鼠中使用抗 4-1BB 抗体研究 4-1BB 对鼻咽癌发展的影响。结果转染了 sh-B7-H3 的鼻咽癌细胞在体外表现出更高的凋亡率、更慢的生长速度、更差的迁移能力和更少的 EMT。稳定敲除 B7-H3 的异种移植小鼠肿瘤负荷较低，剥离的肿瘤在体内细胞增殖率较低、凋亡率较高且 EMT 较少。此外，B7-H3表达的减少与干扰素-γ、肿瘤坏死因子-α和4-1BB+CD8+肿瘤浸润淋巴细胞呈正相关。Co-IP 研究表明，B7-H3 与 4-1BB 相互作用。此外，sh-B7-H3 在体内和体外对鼻咽癌肿瘤生长、侵袭和肿瘤免疫的抑制作用可通过抗 4-1BB 抗体得到缓解。结论我们的研究结果表明，B7-H3可能会加速肿瘤生长、肿瘤细胞侵袭和EMT，并与4-1BB相互作用产生CD8+ T细胞衰竭，从而抑制肿瘤免疫。B7-H3 可作为治疗鼻咽癌的新靶点。

{"title":"B7-H3 promotes nasopharyngeal carcinoma progression by regulating CD8+ T cell exhaustion","authors":"Zhaoen Ma, Gui Chen, Hao Li, Saixuan Yang, Yali Xu, Bolin Pan, Wuping Lai, Guangui Chen, Wenjing Liao, Xiaowen Zhang","doi":"10.1002/iid3.70005","DOIUrl":"https://doi.org/10.1002/iid3.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>B7-H3 protein is an important regulator of the adaptive immune response in human tumorigenesis. 4-1BB is a co-stimulatory receptor expressed on activated CD8+ T cells, and regulates T cell immunity. Here, we investigated the role of B7-H3 in the growth and invasion of nasopharyngeal carcinoma (NPC) and the effect of its interaction with 4-1BB on tumor immunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Short hairpin (sh) RNA was designed to knock down B7-H3 expression in NPC cells. NPC cells with stable knockdown of B7-H3 were established and injected into nude mice. The effects of B7-H3 on cell proliferation, apoptosis, and epithelial-to-mesenchymal transition (EMT) were detected by the CCK8 assay, flow cytometry, TUNEL assay, and western blot analysis. The migration and invasion abilities were determined using the Transwell assay and scratch assay. Co-immunoprecipitation (Co-IP) assays were performed to study the interaction between B7-H3 and 4-1BB. Anti-4-1BB antibody was used in a co-culture system and xenograft mice to study the effect of 4-1BB on NPC development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NPC cells transfected with sh-B7-H3 showed a higher rate of apoptosis, slower growth rate, impaired migration, and less EMT in vitro. Xenograft mice with stable knockout of B7-H3 had lower tumor burdens, and the stripped tumors had lower rates of cell proliferation, higher rates of apoptosis, and less EMT in vivo. Additionally, decreased B7-H3 expression was positively correlated with interferon-γ, tumor necrosis factor-α, and 4-1BB+CD8+ tumor-infiltrating lymphocytes. Co-IP studies showed that B7-H3 interacts with 4-1BB. Also, the inhibitory effects of sh-B7-H3 on NPC tumor growth, invasion, and tumor immunity could be alleviated by the anti-4-1BB antibody both in vivo and in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that B7-H3 may accelerate tumor growth, tumor cell invasion, and EMT, and interact with 4-1BB to produce CD8+ T cell exhaustion that inhibits tumor immunity. B7-H3 might serve as a novel target for treating NPC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Vitamin D treatment distinctly modulates cytokine production by peripheral blood mononuclear cells among patients with chronic cardiac and indeterminate clinical forms of Chagas disease 维生素 D 治疗可明显调节慢性心源性南美锥虫病和临床症状不确定南美锥虫病患者外周血单核细胞产生的细胞因子

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-09-13 DOI: 10.1002/iid3.1330

Kamila Kássia dos Santos Oliveira, Diego José Lira Torres, Michelle da Silva Barros, Leyllane Rafael Moreira, Claudeir Dias da Silva Junior, Ana Karine de Araújo Soares, Maria da Piedade Costa Reis de Albuquerque, Maria da Glória Aureliano Melo Cavalcante, Wilson Alves de Oliveira Junior, Michelle Christiane da Silva Rabello, Virginia Maria Barros de Lorena

Introduction

Chagas disease is caused by the protozoan Trypanosoma cruzi and is clinically divided into acute and chronic phases. Chronic Chagas cardiomyopathy is the most studied manifestation of the disease. Vitamin D deficiency has been suggested as a risk factor for cardiovascular disease. No studies demonstrate the action of this hormone in the cells of patients with chronic Chagas heart disease.

Objective

To evaluate the in vitro immunomodulatory effect of vitamin D on peripheral blood mononuclear cells of patients with the different chronic clinical forms of Chagas disease. Evaluating vitamin D's in vitro effect on blood cells by producing cytokines.

Methods

Thirteen patients of the undetermined form (IND), 13 of the mild cardiac form (CARD1) and 14 of the severe cardiac form (CARD2) of Chagas disease, and 12 with idiopathic heart disease (CARDid) were included. The cells obtained from peripheral blood were treated in vitro with vitamin D (1 × 10⁻⁷M) for 24 h and cytokines were dosed in the culture supernatant.

Results

Although it was not possible to demonstrate statistically significant differences between the groups studied, our data showed that the cells treated with vitamin D modify (p < .05) the production of interferon-γ (IFN-γ) (decrease in IND), tumor necrosis factor-α (TNF-α) (decreased in CARD1 and CARDid), interleukin (IL)-6 (increased in all groups), and IL-10 (decreased in CARD1, CARD2, and CARDid) when compared to untreated cells.

Conclusion

In vitro treatment with vitamin D distinctly modulated the production of cytokines by mononuclear cells of peripheral blood among patients with chronic and indeterminate cardiac clinical forms of Chagas disease.

导言恰加斯病是由原生动物克鲁斯锥虫引起的，临床上分为急性期和慢性期。慢性恰加斯病心肌病是研究最多的一种疾病表现。维生素 D 缺乏被认为是心血管疾病的一个风险因素。目前还没有研究表明这种激素对慢性恰加斯心脏病患者的细胞有作用。目标评估维生素 D 对不同临床慢性恰加斯病患者外周血单核细胞的体外免疫调节作用。评估维生素 D 通过产生细胞因子对血细胞的体外作用。方法纳入了 13 名南美锥虫病未定型患者（IND）、13 名轻度心脏病患者（CARD1）和 14 名重度心脏病患者（CARD2），以及 12 名特发性心脏病患者（CARDid）。从外周血中获得的细胞在体外用维生素 D（1 × 10-7 M）处理 24 小时，并在培养上清液中加入细胞因子。结果虽然无法证明所研究的各组之间存在统计学意义上的显著差异，但我们的数据显示，与未处理的细胞相比，经维生素 D 处理的细胞改变了干扰素-γ（IFN-γ）（在 IND 中减少）、肿瘤坏死因子-α（TNF-α）（在 CARD1 和 CARDid 中减少）、白细胞介素（IL）-6（在所有组中增加）和 IL-10（在 CARD1、CARD2 和 CARDid 中减少）的产生（p <.05）。结论用维生素 D 进行体外治疗可明显调节南美锥虫病慢性和不确定心脏临床形式患者外周血单核细胞产生的细胞因子。

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引用次数: 0

The balance between helper T 17 and regulatory T cells in osteoimmunology and relevant research progress on bone tissue engineering 骨免疫学中辅助性 T 细胞 17 和调节性 T 细胞之间的平衡以及骨组织工程学的相关研究进展

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-09-12 DOI: 10.1002/iid3.70011

Shuyu Zhu, Jing Zhou, Zhigang Xie

Background

Bone regeneration is a well-regulated dynamic process, of which the prominent role of the immune system on bone homeostasis is more and more revealed by recent research. Before fully activation of the bone remodeling cells, the immune system needs to clean up the microenvironment in facilitating the bone repair initiation. Furthermore, this microenvironment must be maintained properly by various mechanisms over the entire bone regeneration process.

Objective

This review aims to summarize the role of the T-helper 17/Regulatory T cell (Th17/Treg) balance in bone cell remodeling and discuss the relevant progress in bone tissue engineering.

Results

The role of the immune response in the early stages of bone regeneration is crucial, especially the impact of the Th17/Treg balance on osteoclasts, mesenchymal stem cells (MSCs), and osteoblasts activity. By virtue of these knowledge advancements, innovative approaches in bone tissue engineering, such as nano-structures, hydrogel, and exosomes, are designed to influence the Th17/Treg balance and thereby augment bone repair and regeneration.

Conclusion

Targeting the Th17/Treg balance is a promising innovative strategy for developing new treatments to enhance bone regeneration, thus offering potential breakthroughs in bone injury clinics.

背景骨再生是一个调节良好的动态过程，近年来的研究越来越多地揭示了免疫系统在骨平衡中的突出作用。在骨重塑细胞完全激活之前，免疫系统需要清理微环境以促进骨修复的启动。此外，在整个骨再生过程中，这种微环境必须通过各种机制得到适当维持。目的本综述旨在总结 T 辅助细胞 17/调节性 T 细胞（Th17/Treg）平衡在骨细胞重塑中的作用，并讨论骨组织工程中的相关进展。结果免疫反应在骨再生早期阶段的作用至关重要，尤其是 Th17/Treg 平衡对破骨细胞、间充质干细胞（MSCs）和成骨细胞活性的影响。凭借这些知识的进步，纳米结构、水凝胶和外泌体等骨组织工程的创新方法旨在影响 Th17/Treg 平衡，从而促进骨修复和再生。结论以 Th17/Treg 平衡为目标是一种很有前途的创新策略，可用于开发新的治疗方法以促进骨再生，从而为骨损伤临床提供潜在的突破。

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引用次数: 0

The relationship between the tertiary lymphoid structure and immune-infiltrating cells in gastrointestinal cancers: A systematic review and meta-analysis 胃肠道癌症中三级淋巴结构与免疫浸润细胞之间的关系：系统回顾与荟萃分析

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-09-11 DOI: 10.1002/iid3.70003

Aoyang Yu, Zhixiang Fan, Luyao Ma, Juanjuan Tang, Wenlou Liu, Zhengxiang Han, Hongmei Wang

Objectives

This study systematically evaluated the relationship between tertiary lymphoid structures (TLS) and clinical pathological features as well as immune infiltrating cells in gastrointestinal cancers.

Methods

We searched Web of science, Pubmed, Embase, and Cochrane Library for studies that met the requirements as of July 1, 2023, and the odds ratio, the corresponding 95% confidence interval or mean and standard deviation, were included in the analysis.

Findings

We eventually included 20 studies, involving a total of 4856 patients. TLS were found to be significantly associated with T stage, N stage, TNM stage, and tumor size. Moreover, patients with positive TLS showed significantly elevated expression of T-cell related markers, including CD3, CD4, CD8, CD45RO; B-cell related markers, such as CD11c and CD20; and dendritic cell-related marker CD103. On the other hand, positive TLS correlated significantly with low expression of FOXP3 and CD68. Additionally, there was a significant positive association between TLS and overall infiltration of tumor-infiltrating lymphocytes.

Conclusion

The presence of TLS is significantly correlated with the infiltration of various immune cells in gastrointestinal cancers. To determine the ideal balance between the presence of mature TLS and appropriate immune cell infiltration, further high-quality and multicenter clinical studies need to be conducted.

目的本研究系统评估了胃肠道癌症中三级淋巴结构（TLS）与临床病理特征以及免疫浸润细胞之间的关系。方法我们在 Web of science、Pubmed、Embase 和 Cochrane Library 中检索了截至 2023 年 7 月 1 日符合要求的研究，并将几率比、相应的 95% 置信区间或平均值和标准差纳入分析。研究结果我们最终纳入了 20 项研究，共涉及 4856 名患者。研究发现，TLS与T分期、N分期、TNM分期和肿瘤大小明显相关。此外，TLS 阳性患者的 T 细胞相关标记物（包括 CD3、CD4、CD8、CD45RO）、B 细胞相关标记物（如 CD11c 和 CD20）以及树突状细胞相关标记物 CD103 的表达均明显升高。另一方面，TLS 阳性与 FOXP3 和 CD68 的低表达显著相关。此外，TLS 与肿瘤浸润淋巴细胞的总体浸润呈显著正相关。结论 TLS 的存在与胃肠道癌症中各种免疫细胞的浸润密切相关。要确定成熟 TLS 的存在与适当的免疫细胞浸润之间的理想平衡，需要进一步开展高质量的多中心临床研究。

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引用次数: 0