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Correction: Oral Magnesium reduces levels of pathogenic autoantibodies and skin disease in murine lupus. 更正:口服镁可降低小鼠狼疮的致病性自身抗体水平和皮肤疾病。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-10 DOI: 10.1186/s12865-024-00658-4
Alberto Verlato, Teresina Laragione, Sofia Bin, Randie H Kim, Fadi Salem, Percio S Gulko, Paolo Cravedi
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引用次数: 0
The diagnostic value and validation of IL-22 combimed with sCD40L in tuberculosis pleural effusion. IL-22 与 sCD40L 联用对结核性胸腔积液的诊断价值和验证。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-09 DOI: 10.1186/s12865-024-00652-w
Yuzhen Xu, Jing Wu, Qiuju Yao, Qianqian Liu, Huaxin Chen, Bingyan Zhang, Yuanyuan Liu, Sen Wang, Lingyun Shao, Wenhong Zhang, Qinfang Ou, Yan Gao

Background: There is substantial evidence indicating that cytokines play a role in the immune defense against tuberculosis. This study aims to evaluate the levels of various cytokines in pleural effusion to ditinguish between tuberculosis pleurisy and malignant pleurisy.

Methods: A total of 82 participants with pleural effusion were included in the training cohort, and 76 participants were included in the validation cohort. The individuals were divided into tuberculosis and malignant pleurisy groups. The concentrations of interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, interferon-γ (IFN-γ), soluble CD40 ligand (sCD40L) and tumor necrosis factor-α (TNF-α) in pleural effusion were measured using a multiplex cytokine assay. The threshold values were calculated according to the receiver operating characteristic (ROC) curve analysis to aid in diagnosing tuberculosis pleurisy. Furthermore, the combined measure was validated in the validation cohort.

Results: The levels of all 14 cytokines in pleural effusion were significantly higher in participants with tuberculosis compared to those with malignant pleurisy (all P < 0.05). The area under the curve (AUC) was ≥ 0.920 for the IL-22, sCD40L, IFN-γ, TNF-α and IL-31, which were significantly increased in tuberculous pleural effusion (TPE) compared to MPE in the training cohort. Threshold values of 95.80 pg/mL for IFN-γ, 41.80 pg/mL for IL-31, and 18.87 pg/mL for IL-22 provided ≥ 90% sensitivity and specificity in distinguishing between tuberculosis pleurisy and malignant pleurisy in the training cohort. Among these, IL-22 combined with sCD40L showed the best sensitivity and specificity (94.0% and 96.9%) for diagnosing tuberculosis pleurisy, and this finding was validated in the validation cohort.

Conclusion: We demonstrated that the levels of IL-1β, IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, IFN-γ, sCD40L and TNF-α in pleural effusion had significant difference between tuberculosis pleurisy and malignant pleurisy. Specifically, IL-22 ≥ 18.87 pg/mL and sCD40L ≥ 53.08 pg/mL can be clinically utilized as an efficient diagnostic strategy for distinguishing tuberculosis pleurisy from malignant pleurisy.

背景:大量证据表明,细胞因子在结核病的免疫防御中发挥作用。本研究旨在评估胸腔积液中各种细胞因子的水平,以区分结核性胸膜炎和恶性胸膜炎:方法:共有 82 名胸腔积液患者被纳入训练队列,76 名患者被纳入验证队列。这些人被分为结核性胸膜炎组和恶性胸膜炎组。胸腔积液中白细胞介素-1β(IL-1β)、IL-4、IL-6、IL-10、IL-17 A、IL-17 F、IL-21、IL-22、IL-25、IL-31、IL-33、干扰素-γ(IFN-γ)、可溶性 CD40 配体(sCD40L)和肿瘤坏死因子-α(TNF-α)的浓度采用多重细胞因子检测法进行测定。根据接收者操作特征曲线(ROC)分析计算出阈值,以帮助诊断结核性胸膜炎。此外,还在验证组群中对综合测量方法进行了验证:结果:与恶性胸膜炎患者相比,结核病患者胸腔积液中所有 14 种细胞因子的水平都明显升高(均为 P 结论:结核病患者胸腔积液中的细胞因子水平明显高于恶性胸膜炎患者:我们发现胸腔积液中的 IL-1β、IL-4、IL-6、IL-10、IL-17 A、IL-17 F、IL-21、IL-22、IL-25、IL-31、IL-33、IFN-γ、sCD40L 和 TNF-α 在结核性胸膜炎和恶性胸膜炎之间存在显著差异。具体来说,IL-22≥18.87 pg/mL和sCD40L≥53.08 pg/mL可作为临床上区分结核性胸膜炎和恶性胸膜炎的有效诊断策略。
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引用次数: 0
Predictors of change in CD4 cell count over time for HIV/AIDS patients on ART follow-up in northern Ethiopia: a retrospective longitudinal study. 埃塞俄比亚北部接受抗逆转录病毒疗法随访的艾滋病毒/艾滋病患者 CD4 细胞计数随时间变化的预测因素:一项回顾性纵向研究。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-04 DOI: 10.1186/s12865-024-00659-3
Gebru Gebremeskel Gebrerufael, Zeytu Gashaw Asfaw

Background: HIV has an effect on lowering CD4 cell count, which lowers the ability to resist contamination. For patients on ART in areas with limited resources, the CD4 cell count assessment is crucial for determining treatment responses and therapeutic decisions. The volatility of CD4 counts following the introduction of ART over time is still largely uncharacterized, and there are few fresh datasets on CD4 cell count progressions. The goal of this study was to identify the key factors that change over time in CD4 cells for HIV/AIDS patients receiving ART follow-up in northern Ethiopia.

Methods: A total of 216 HIV/AIDS patients who initiated ART in the Mekelle General Hospital between 2013 and 2016 were involved using systematic random selection techniques. An examination of exploratory data was used to describe the individual profiles of HIV patients. A multivariable random intercept and slope linear mixed regression analysis regarded predictor variables to be statistically significant if their p-value was less than 0.05.

Results: The random intercept and slope linear mixed model result indicated that there were statistically significant predictors of baseline CD4 cell count (β = 0.0125, P-value = 0.001*) and bedridden functional status (β = -2.459, p = 0.02*) on the change of CD4 cell count over time in HIV/AIDS patients at the 5% significance level.

Conclusions: Changes in CD4 counts were influenced by the baseline CD4 cell count and the functional status of being bedridden. Because their CD4 cell counts were lower at baseline and they had a functional status of bedridden, the majority of HIV/AIDS patients on ART had substantial predictors on the change of CD4 cell count over time. So, public health service providers should give exceptional guidance and attention is also necessary for those patients who have lower baseline CD4 cell count and bedridden functional status.

背景:艾滋病毒会降低 CD4 细胞计数,从而降低抗感染能力。对于资源有限地区接受抗逆转录病毒疗法的患者来说,CD4 细胞计数评估对于确定治疗反应和治疗决策至关重要。在采用抗逆转录病毒疗法后,CD4 细胞计数随时间推移而波动的情况在很大程度上仍未得到描述,而且有关 CD4 细胞计数进展的新鲜数据集也很少。本研究旨在确定埃塞俄比亚北部接受抗逆转录病毒疗法随访的艾滋病患者 CD4 细胞随时间变化的关键因素:采用系统随机选择技术,对 2013 年至 2016 年期间在默克莱综合医院开始接受抗逆转录病毒疗法的 216 名艾滋病患者进行了研究。通过对探索性数据的检查来描述艾滋病患者的个体特征。多变量随机截距和斜率线性混合回归分析认为,如果预测变量的 p 值小于 0.05,则其具有统计学意义:随机截距和斜率线性混合模型结果表明,基线 CD4 细胞计数(β = 0.0125,P 值 = 0.001*)和卧床功能状态(β = -2.459,P = 0.02*)对艾滋病患者 CD4 细胞计数随时间的变化有统计学意义,显著性水平为 5%:CD4细胞计数的变化受基线CD4细胞计数和卧床不起的功能状态的影响。由于大多数接受抗逆转录病毒疗法的艾滋病患者的 CD4 细胞计数在基线时较低,而且他们的功能状态是卧床不起,因此他们的 CD4 细胞计数随时间的变化有很大的预测因素。因此,公共卫生服务提供者应给予那些基线 CD4 细胞计数较低且功能状态为卧床不起的患者特别的指导和关注。
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引用次数: 0
Correction: Helminth-derived proteins as immune system regulators: a systematic review of their promise in alleviating colitis. 更正:作为免疫系统调节剂的螺旋藻衍生蛋白:对其缓解结肠炎前景的系统综述。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-04 DOI: 10.1186/s12865-024-00661-9
Maimonah Alghanmi, Faisal Minshawi, Tarfa A Altorki, Ayat Zawawi, Isra Alsaady, Abdallah Y Naser, Hassan Alwafi, Soa'ad M Alsulami, Ala A Azhari, Anwar M Hashem, Rowa Alhabbab
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引用次数: 0
Inhibition of CEACAM1 expression in cytokine-activated neutrophils using JAK inhibitors. 使用 JAK 抑制剂抑制细胞因子激活的中性粒细胞中 CEACAM1 的表达。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-01 DOI: 10.1186/s12865-024-00656-6
Haruki Matsumoto, Ryota Sudo, Yuya Fujita, Michio Onizawa, Kenji Saito, Yuya Sumichika, Shuhei Yoshida, Jumpei Temmoku, Naoki Matsuoka, Tomoyuki Asano, Shuzo Sato, Eiji Suzuki, Takeshi Machida, Kiyoshi Migita

Objectives: Carcinoembryonic-antigen-related cell-adhesion molecule 1 (CEACAM1) is an adhesion molecule that acts as a coinhibitory receptor in the immune system. We previously demonstrated that CEACAM1 is predominantly expressed on peripheral blood neutrophils in patients with RA. The aim of the present study was to investigate the effects of Janus kinase inhibitors (JAKi) on cytokine-activated human neutrophils and CEACAM1 expression.

Methods: Peripheral blood neutrophils were obtained from healthy subjects. Isolated neutrophils were stimulated with tumor necrosis factor-alpha (TNF-α) or granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence or absence of JAKi. The expression of CEACAM1 in peripheral blood neutrophils was analyzed by flow cytometry. Protein phosphorylation of signal transducer and activator of transcription (STAT)1, STAT3, and STAT5 was assessed by western blot using phospho-specific antibodies.

Results: We found that TNF-α-induced CEACAM1 expression was marginally suppressed after pretreatment with pan-JAK inhibitor, tofacitinib. Moreover, TNF-α induced STAT1 and STAT3 phosphorylation at the late stimulation phase (4 to 16 h). The expressions of CEACAM1 on neutrophils were markedly up-regulated by GM-CSF not by interleukin (IL)-6 stimulation. All JAKi inhibited GM-CSF-induced CEACAM1 expressions on neutrophils, however, the inhibitory effects of baricitinib were larger compared to those of tofacitinib or filgotinib. Moreover, CEACAM1 was marginally upregulated in interferon (IFN)-γ stimulated neutrophils. Similarly, JAKi inhibited IFN-γ-induced CEACAM1 expressions on neutrophils.

Conclusions: We demonstrated that JAKi prevent GM-CSF-induced CEACAM1 expression in neutrophils, and JAKi-induced inhibition depends on their selectivity against JAK isoforms. These findings suggest that JAKi can modulate the expression of CEACAM1 in cytokine-activated neutrophils, thereby limiting their activation.

研究目的癌胚抗原相关细胞粘附分子 1(CEACAM1)是一种粘附分子,在免疫系统中充当共抑制受体。我们曾证实 CEACAM1 主要表达于 RA 患者的外周血中性粒细胞。本研究旨在探讨Janus激酶抑制剂(JAKi)对细胞因子激活的人中性粒细胞和CEACAM1表达的影响:方法:从健康受试者处获取外周血中性粒细胞。在有或没有 JAKi 的情况下,用肿瘤坏死因子-α(TNF-α)或粒细胞-巨噬细胞集落刺激因子(GM-CSF)刺激分离的中性粒细胞。流式细胞术分析了外周血中性粒细胞中 CEACAM1 的表达。使用磷酸化特异性抗体通过 Western 印迹评估信号转导和转录激活因子(STAT)1、STAT3 和 STAT5 的蛋白磷酸化:结果:我们发现,TNF-α诱导的CEACAM1表达在使用泛JAK抑制剂托法替尼预处理后略有抑制。此外,TNF-α在刺激后期(4-16 h)诱导STAT1和STAT3磷酸化。中性粒细胞上的 CEACAM1 的表达在 GM-CSF 而非白细胞介素(IL)-6 的刺激下明显上调。所有JAKi都能抑制GM-CSF诱导的CEACAM1在中性粒细胞上的表达,但巴利昔替尼的抑制作用大于托法替尼和非格替尼。此外,CEACAM1在干扰素(IFN)-γ刺激的中性粒细胞中略有上调。同样,JAKi抑制了IFN-γ诱导的中性粒细胞上CEACAM1的表达:我们证实,JAKi能阻止GM-CSF诱导的CEACAM1在中性粒细胞中的表达,而JAKi诱导的抑制作用取决于其对JAK同工酶的选择性。这些发现表明,JAKi 可调节细胞因子激活的中性粒细胞中 CEACAM1 的表达,从而限制其活化。
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引用次数: 0
Autoimmunity's enigmatic role: exploring the connection with myalgic encephalomyelitis/chronic fatigue syndrome. 自身免疫的神秘作用:探索与肌痛性脑脊髓炎/慢性疲劳综合征的联系。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-01 DOI: 10.1186/s12865-024-00657-5
Jacob Batham, Jessica Dwyer, Natalie Eaton-Fitch, Sonya Marshall-Gradisnik

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complicated, heterogeneous condition distinguished by post-exertional neuroimmune exhaustion and multisystem symptoms. Its complexity poses challenges for physicians, researchers and those inflicted by its presence. Due to conflicting evidence and limiting consensus, the association and contribution autoimmunity serves in the pathophysiology or aetiology of ME/CFS is yet to be confirmed. This systematic review synthesises the currently available data to clarify the role autoimmunity has in the pathogenesis of ME/CFS and explore the therapeutic limitations.

Methods: This systematic review was conducted in accordance with the PRISMA and Cochrane guidelines. Full-text articles containing the primary key terms "Autoimmunity/Autoimmune" and "ME/CFS" were included provided their suitability to the inclusion and exclusion criteria.

Results: Ten publications investigating the role of autoimmunity in ME/CFS were examined. One investigated the role of cytokine signalling; Three investigated the genetic nature of autoimmunity in ME/CFS patients; One examined the immune lineage of ME/CFS patients; Six investigated the presence and role of autoantibodies in ME/CFS patients.

Conclusion: The findings generated from this systematic review highlight inconsistent and insufficient evidence to classify ME/CFS as an autoimmune disease. Additionally, it further emphasises the complexity of ME/CFS and highlights the challenges in distinguishing autoreactivity from deregulatory processes. Future research is urgently needed to advance the development of diagnostic and treatment strategies.

Prospero registration code: CRD42024533447.

背景:肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)是一种复杂的异质性疾病,以运动后神经免疫衰竭和多系统症状为特征。它的复杂性给医生、研究人员和患者带来了挑战。由于证据相互矛盾、共识有限,自身免疫在 ME/CFS 病理生理学或病因学中的关联和作用仍有待证实。本系统性综述综合了目前可用的数据,以阐明自身免疫在 ME/CFS 发病机制中的作用,并探讨其治疗局限性:本系统综述根据 PRISMA 和 Cochrane 指南进行。只要符合纳入和排除标准,就会纳入包含主要关键词 "自身免疫/自身免疫 "和 "ME/CFS "的全文文章:结果:研究了10篇调查自身免疫在ME/CFS中作用的文章。其中一篇研究了细胞因子信号的作用;三篇研究了ME/CFS患者自身免疫的遗传性质;一篇研究了ME/CFS患者的免疫系统;六篇研究了ME/CFS患者自身抗体的存在和作用:本系统综述的研究结果表明,将ME/CFS归类为自身免疫性疾病的证据并不一致,也不充分。此外,它还进一步强调了ME/CFS的复杂性,并突出了区分自身反应和失调过程所面临的挑战。未来迫切需要开展研究,以推动诊断和治疗策略的发展:CRD42024533447。
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引用次数: 0
Convergence of endothelial dysfunction, inflammation and glucocorticoid resistance in depression-related cardiovascular diseases. 抑郁症相关心血管疾病中内皮功能障碍、炎症和糖皮质激素抵抗的汇合。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-27 DOI: 10.1186/s12865-024-00653-9
Zachary Hage, Miguel M Madeira, Dimitris Koliatsis, Stella E Tsirka

Major Depressive Disorder, or depression, has been extensively linked to dysregulated HPA axis function, chronic inflammation and cardiovascular diseases. While the former two have been studied in depth, the mechanistic connection between depression and cardiovascular disease is unclear. As major mediators of vascular homeostasis, vascular pathology and immune activity, endothelial cells represent an important player connecting the diseases. Exaggerated inflammation and glucocorticoid function are important topics to explore in the endothelial response to MDD. Glucocorticoid resistance in several cell types strongly promotes inflammatory signaling and results in worsened severity in many diseases. However, endothelial health and inflammation in chronic stress and depression are rarely considered from the perspective of glucocorticoid signaling and resistance. In this review, we aim to discuss (1) endothelial dysfunction in depression, (2) inflammation in depression, (3) general glucocorticoid resistance in depression and (4) endothelial glucocorticoid resistance in depression co-morbid inflammatory diseases. We will first describe vascular pathology, inflammation and glucocorticoid resistance separately in depression and then describe their potential interactions with one another in depression-relevant diseases. Lastly, we will hypothesize potential mechanisms by which glucocorticoid resistance in endothelial cells may contribute to vascular disease states in depressed people. Overall, endothelial-glucocorticoid signaling may play an important role in connecting depression and vascular pathology and warrants further study.

重度抑郁症(抑郁症)与 HPA 轴功能失调、慢性炎症和心血管疾病有着广泛的联系。虽然对前两者进行了深入研究,但抑郁症与心血管疾病之间的机理联系尚不清楚。作为血管稳态、血管病理和免疫活动的主要介质,内皮细胞是连接这些疾病的重要角色。炎症加剧和糖皮质激素功能是探讨内皮细胞对多发性硬化症反应的重要课题。几种细胞类型的糖皮质激素抗性会强烈促进炎症信号转导,导致许多疾病的严重程度恶化。然而,人们很少从糖皮质激素信号传导和抵抗的角度来考虑慢性应激和抑郁症中的内皮健康和炎症问题。在这篇综述中,我们旨在讨论:(1) 抑郁症的内皮功能障碍;(2) 抑郁症的炎症;(3) 抑郁症的一般糖皮质激素抵抗;(4) 抑郁症合并炎症性疾病的内皮糖皮质激素抵抗。我们将首先分别描述抑郁症中的血管病理学、炎症和糖皮质激素抵抗,然后描述它们在抑郁症相关疾病中的潜在相互作用。最后,我们将假设内皮细胞的糖皮质激素抵抗可能导致抑郁症患者血管疾病状态的潜在机制。总之,内皮细胞-糖皮质激素信号传导可能在连接抑郁症和血管病理学方面发挥重要作用,值得进一步研究。
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引用次数: 0
β-glucan combined with Envafolimab and Endostar as immune rechallenge for metastatic non-small cell lung cancer β-葡聚糖与恩伐利单抗和 Endostar 联合作为转移性非小细胞肺癌的免疫再挑战疗法
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-14 DOI: 10.1186/s12865-024-00651-x
Qian Geng, Yingying Lu, Dongqing Li, Lanqun Qin, Chunjian Qi, Xiaolin Pu, Yi Zhuang, Yajun Zhu, Quanbin Zha, Ge Wang, Hua Jiang
Immune checkpoint inhibitor rechallenge has emerged as a prominent study area in non-small cell lung cancer (NSCLC). β-glucan was reported to reverse resistance to anti-PD-1/PD-L1 inhibitors by regulating the tumor microenvironment. In this self-initiated clinical trial (ChiCTR2100054796), NSCLC participants who have previously failed anti-PD-1 therapy received β-glucan (500 mg, bid, d1-21), Envafolimab (300 mg, d1) and Endostar (210 mg, civ72h) every 3 weeks until disease progression or unacceptable toxicity. The clinical efficacy and adverse events were observed, while serum samples were collected for proteomic analysis. Twenty Three patients were enrolled from January 2022 to March 2023 (median age, 65 years; male, n = 18 [78.3%]; squamous NSCLC, n = 9 [39.1%]; mutant type, n = 13 [56.5%]). The overall response rate (ORR) was 21.7% and disease control rate (DCR) was 73.9%. Median progression-free survival (mPFS) and median overall survival (mOS) was 4.3 months [95% CI: 2.0–6.6] and 9.8 months [95% CI: 7.2–12.4], respectively. The mPFS between PD-L1 positive and negative subgroup has significant difference (6.3 months vs. 2.3 months, p = 0.002). Treatment-related adverse events (TRAEs) occurred in 52.2% of patients. The most common TRAEs were hypothyroidism (26.1%) and fatigue (26.1%). 2 (8.7%) grade 3 adverse events were reported. No adverse reaction related deaths have been observed. Proteomic analysis revealed that the levels of CASP-8, ARG1, MMP12, CD28 and CXCL5 correlated with resistance to the treatment while the levels of CD40-L and EGF related to the favorable response. β-glucan combined with Envafolimab and Endostar has considerable efficacy and safety for immune rechallenge in metastatic NSCLC patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients.
免疫检查点抑制剂再挑战已成为非小细胞肺癌(NSCLC)的一个重要研究领域。据报道,β-葡聚糖可通过调节肿瘤微环境来逆转抗PD-1/PD-L1抑制剂的耐药性。在这项自发的临床试验(ChiCTR2100054796)中,既往抗PD-1治疗失败的NSCLC参与者每3周接受一次β-葡聚糖(500毫克,bid,d1-21)、恩华利单抗(300毫克,d1)和Endostar(210毫克,civ72h)治疗,直至疾病进展或出现不可接受的毒性。观察临床疗效和不良反应,同时收集血清样本进行蛋白质组分析。从 2022 年 1 月到 2023 年 3 月,共招募了 23 名患者(中位年龄 65 岁;男性,n = 18 [78.3%];鳞状 NSCLC,n = 9 [39.1%];突变型,n = 13 [56.5%])。总反应率(ORR)为21.7%,疾病控制率(DCR)为73.9%。中位无进展生存期(mPFS)和中位总生存期(mOS)分别为4.3个月[95% CI:2.0-6.6]和9.8个月[95% CI:7.2-12.4]。PD-L1阳性亚组和阴性亚组的mPFS差异显著(6.3个月 vs. 2.3个月,P = 0.002)。52.2%的患者发生了治疗相关不良事件(TRAEs)。最常见的不良反应是甲状腺功能减退(26.1%)和疲劳(26.1%)。报告了 2 例(8.7%)3 级不良反应。未发现与不良反应相关的死亡病例。蛋白质组分析显示,CASP-8、ARG1、MMP12、CD28和CXCL5的水平与治疗耐药性相关,而CD40-L和EGF的水平与良好反应相关。β-葡聚糖与恩伐利单抗和恩度斯达联合治疗既往抗PD-1治疗失败的转移性NSCLC患者,尤其是PD-L1阳性患者的免疫再挑战具有相当高的疗效和安全性。
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引用次数: 0
From bioinformatics to clinical applications: a novel prognostic model of cuproptosis-related genes based on single-cell RNA sequencing data in hepatocellular carcinoma 从生物信息学到临床应用:基于肝细胞癌单细胞 RNA 测序数据的杯突症相关基因的新型预后模型
IF 3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-09 DOI: 10.1186/s12865-024-00649-5
Yong Wang, Fenglin Zang, Bing Shao, Yanan Gao, Haicui Yang, Yuhong Guo, Tingting Ding, Baocun Sun
To ascertain the connection between cuproptosis-related genes (CRGs) and the prognosis of hepatocellular carcinoma (HCC) via single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) data, relevant data were downloaded from the GEO and TCGA databases. The differentially expressed CRGs (DE-CRGs) were filtered by the overlaps in differentially expressed genes (DEGs) between HCC patients and normal controls (NCs) in the scRNA-seq database, DE-CRGs between high- and low-CRG-activity cells, and DEGs between HCC patients and NCs in the TCGA database. Thirty-three DE-CRGs in HCC were identified. A prognostic model (PM) was created employing six survival-related genes (SRGs) (NDRG2, CYB5A, SOX4, MYC, TM4SF1, and IFI27) via univariate Cox regression analysis and LASSO. The predictive ability of the model was validated via a nomogram and receiver operating characteristic curves. Research has employed tumor immune dysfunction and exclusion as a means to examine the influence of PM on immunological heterogeneity. Macrophage M0 levels were significantly different between the high-risk group (HRG) and the low-risk group (LRG), and a greater macrophage level was linked to a more unfavorable prognosis. The drug sensitivity data indicated a substantial difference in the half-maximal drug-suppressive concentrations of idarubicin and rapamycin between the HRG and the LRG. The model was verified by employing public datasets and our cohort at both the protein and mRNA levels. A PM using 6 SRGs (NDRG2, CYB5A, SOX4, MYC, TM4SF1, and IFI27) was developed via bioinformatics research. This model might provide a fresh perspective for assessing and managing HCC.
为了通过单细胞RNA测序(scRNA-seq)和RNA测序(RNA-seq)数据确定杯突相关基因(CRGs)与肝细胞癌(HCC)预后之间的联系,研究人员从GEO和TCGA数据库下载了相关数据。根据scRNA-seq数据库中HCC患者与正常对照组(NCs)之间差异表达基因(DEGs)的重叠、高CRG活性细胞与低CRG活性细胞之间的DE-CRGs以及TCGA数据库中HCC患者与NCs之间的DEGs,筛选出差异表达的CRGs(DE-CRGs)。结果发现了 HCC 中的 33 个 DE-CRG。通过单变量 Cox 回归分析和 LASSO,利用六个生存相关基因(SRGs)(NDRG2、CYB5A、SOX4、MYC、TM4SF1 和 IFI27)创建了一个预后模型(PM)。该模型的预测能力通过提名图和接收者操作特征曲线得到了验证。有研究利用肿瘤免疫功能障碍和排斥作为研究 PM 对免疫异质性影响的一种手段。巨噬细胞M0水平在高危组(HRG)和低危组(LRG)之间存在显著差异,巨噬细胞水平越高,预后越差。药物敏感性数据显示,伊达比星和雷帕霉素的半最大药物抑制浓度在高危组和低危组之间存在很大差异。该模型通过使用公共数据集和我们的队列在蛋白质和 mRNA 水平上进行了验证。通过生物信息学研究,利用 6 个 SRG(NDRG2、CYB5A、SOX4、MYC、TM4SF1 和 IFI27)建立了一个 PM。该模型可为评估和管理 HCC 提供新的视角。
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引用次数: 0
Revised version with tracked changes oral Magnesium reduces levels of pathogenic autoantibodies and skin disease in murine lupus. 修订版口服镁可降低小鼠狼疮的致病性自身抗体水平和皮肤病。
IF 2.9 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-06 DOI: 10.1186/s12865-024-00650-y
Alberto Verlato, Teresina Laragione, Sofia Bin, Randie H Kim, Fadi Salem, Percio S Gulko, Paolo Cravedi

Background: Systemic Lupus Erythematosus (SLE) has a strong genetic susceptibility, but little is known about the impact of diet on disease severity. The Western diet is typically deficient in magnesium (Mg), and given the immunomodulatory effects of Mg, we hypothesized that the low Mg intake increases disease risk and that increasing Mg intake would reduce severity of murine lupus. Here, we placed 12-week old MRL/lpr female lupus mice on a normal (Mg500) or a high (Mg2800) Mg diet for 9 weeks. Urine and blood were collected during the study for quantification of urinary albumin, BUN, anti-dsDNA antibodies, and immune phenotyping.

Results: MRL/lpr lupus mice on high Mg2800 diet had significantly fewer skin lesions and less severe skin histology score, and reduced levels of pathogenic anti-dsDNA antibodies, compared with the Mg500 group (143.8±75.0 vs. 47.4±36.2 × 106U/ml; P < 0.05). The high Mg2800 group had a nearly two-fold increase in the percentage of CD4+FOXP3+ Treg cells compared to controls (19.9±5.4 vs. 11.4±5.5%; P < 0.05). Treg percentages inversely correlated with the concentration of anti-dsDNA. None of the mice developed arthritis during the observation period and there were no significant differences in weight, proteinuria, BUN or kidney histology.

Conclusion: In conclusion, oral supplementation of Mg has a protective effect in a murine lupus model and may represent an inexpensive and safe adjuvant in the treatment of SLsE.

背景:系统性红斑狼疮(SLE)有很强的遗传易感性,但人们对饮食对疾病严重程度的影响知之甚少。西方饮食中通常缺乏镁(Mg),鉴于镁具有免疫调节作用,我们假设镁摄入量低会增加患病风险,而增加镁摄入量会降低小鼠狼疮的严重程度。在这里,我们将 12 周大的 MRL/lpr 雌性狼疮小鼠置于正常(Mg500)或高(Mg2800)镁饮食中 9 周。研究期间收集尿液和血液,以定量检测尿白蛋白、BUN、抗dsDNA抗体和免疫表型:结果:与 Mg500 组(143.8±75.0 vs. 47.4±36.2 × 106U/ml;P +FOXP3+ Treg 细胞与对照组相比(19.9±5.4 vs. 11.4±5.5%;P)相比,MRL/lpr 狼疮小鼠摄入高 Mg2800 食物后,皮肤病变显著减少,皮肤组织学评分较轻,致病性抗dsDNA 抗体水平降低:总之,口服补充镁对小鼠狼疮模型有保护作用,可能是治疗 SLsE 的一种廉价、安全的辅助疗法。
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BMC Immunology
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