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Impact of Chronic Moderate Exercise on Immune Cells and Cytokine Levels in Rats: Focus on the Endocannabinergic Pathway. 慢性适度运动对大鼠免疫细胞和细胞因子水平的影响:内源性大麻素途径的研究
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 Epub Date: 2023-11-14 DOI: 10.1089/jir.2023.0120
Salvador Valencia-Sánchez, Karen Elizabeth Nava-Castro, Claudia Angélica Garay-Canales, Víctor Hugo Del Río-Araiza, Jorge Morales-Montor

Although the modulation of immunity by exercise has been a long-studied paradigm, the molecular pathways connecting the two are still not fully understood. Regular moderate aerobic exercise is associated with improved health and directly impacts the immune system by changing the proportion of cell subpopulations, their function, and interleukin production. The endocannabinoid system has gained importance as an immune modulator, affected by moderate aerobic promoting the production of endocannabinoids, which are ligands of the cannabinoid receptors (CBRs) expressed on the surface of all immune cells. Our group previously reported a reduction of lymphocytic populations in the spleen of chronically exercised rats, accompanied by an increase in CBR expression. Given the complex and compartmentalized nature of the immune system, we decided to study the effects of chronic exercise on the proportion of peripheral blood mononuclear cells, serum interleukins, and the expression of CBRs on these cells. Overall, our results indicate that chronic exercise decreases the proportion of T helper and Tγδ cells but increases the expression of cannabinoids (CBR1) on T helper and natural killer cells, and the production of interleukins, including IL-1β, interferon-gamma, tumor necrosis factor-alpha, IL-10, and IL-4, suggesting higher reactivity and efficiency from the immune system conferred by exercise.

虽然运动对免疫的调节已经被研究了很长时间,但连接两者的分子途径仍然没有完全被理解。定期适度的有氧运动与改善健康有关,并通过改变细胞亚群的比例、功能和白细胞介素的产生直接影响免疫系统。内源性大麻素系统作为一种重要的免疫调节剂,受到适度有氧运动的影响,促进内源性大麻素的产生,内源性大麻素是在所有免疫细胞表面表达的大麻素受体(CBRs)的配体。本研究小组之前报道了长期运动大鼠脾脏淋巴细胞数量减少,并伴有CBR表达增加。鉴于免疫系统的复杂性和区隔性,我们决定研究慢性运动对外周血单个核细胞比例、血清白细胞介素和这些细胞上cbr表达的影响。总体而言,我们的研究结果表明,慢性运动降低了T辅助细胞和Tγδ细胞的比例,但增加了大麻素(CBR1)在T辅助细胞和自然杀伤细胞上的表达,以及白细胞介素(包括IL-1β、干扰素γ、肿瘤坏死因子α、IL-10和IL-4)的产生,表明运动赋予免疫系统更高的反应性和效率。
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引用次数: 0
Acknowledgment of Reviewers 2023. 鸣谢 2023 年审稿人。
IF 2.3 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 Epub Date: 2023-12-21 DOI: 10.1089/jir.2023.29059.ack
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引用次数: 0
Cytokine Profile Response of Human Peripheral Blood Mononuclear Cells Stimulated by Bartonella bacilliformis. 杆菌状巴尔通体刺激人外周血单个核细胞的细胞因子谱反应。
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 Epub Date: 2023-11-15 DOI: 10.1089/jir.2023.0107
Barbara Ymaña, Javier Enciso-Benavides, Gemma Moncunill, Maria J Pons

Carrion's disease is a neglected endemic disease found in remote Andean areas. As an overlooked disease, knowledge of innate immune responses to Bartonella bacilliformis, the etiological agent, is scarce. This study aimed to evaluate the cytokine response to B. bacilliformis using in vitro human peripheral blood mononuclear cells (PBMCs) stimulations. PBMCs from naive adults were isolated by gradient centrifugation and cocultured with heat-inactivated (HI) B. bacilliformis at different incubation times (3, 6, 12, 24, and 36 h). Cytokines, chemokines, and growth factors were determined in culture supernatants by multiplex fluorescent bead-based quantitative suspension array technology. During the first 36 h, a proinflammatory response was observed, including tumor necrosis factor-α, interleukin (IL)-1α, IL-1β, interferon-α2, and IL-6, followed by an anti-inflammatory response mainly related to IL-1RA. Moreover, high expression levels of chemokines IL-8, monocyte chemoattractant protein-1α, and macrophage inflammatory protein (MIP)-1β were detected from 3 h poststimulation and MIP-1α was detected at 24 h. Some growth factors, mainly granulocyte macrophage colony-stimulating factor and granulocyte colony-stimulating factor, and in minor concentrations vascular endothelial growth factor, epidermal growth factor, and eotaxin, were also detected. Innate response to HI B. bacilliformis stimulation consists of a rapid and strong proinflammatory response characterized by a wide range of cytokines and chemokines followed by an anti-inflammatory response and increased specific growth factors.

腐肉病是一种被忽视的地方病,常见于偏远的安第斯地区。作为一种被忽视的疾病,对病原体巴通体杆菌的先天免疫反应的了解很少。本研究旨在通过体外刺激人外周血单个核细胞(PBMCs)来评估细胞因子对芽孢杆菌的反应。通过梯度离心分离初生成人的pbmc,并在不同孵育时间(3,6,12,24和36 h)与热灭活(HI)芽孢杆菌共培养。细胞因子、趋化因子和生长因子通过基于多重荧光珠的定量悬浮阵列技术在培养上清液中进行检测。在前36小时,观察到促炎反应,包括肿瘤坏死因子-α、白细胞介素(IL)-1α、IL-1β、干扰素-α2和IL-6,随后是主要与IL- 1ra相关的抗炎反应。此外,趋化因子IL-8、单核细胞趋化蛋白-1α和巨噬细胞炎症蛋白(MIP)-1β在刺激后3小时高表达,MIP-1α在24小时高表达。部分生长因子,主要是粒细胞巨噬细胞集落刺激因子和粒细胞集落刺激因子,以及少量浓度的血管内皮生长因子、表皮生长因子和eotaxin。对HI芽孢杆菌刺激的先天反应包括快速而强烈的促炎反应,其特征是广泛的细胞因子和趋化因子,随后是抗炎反应和特异性生长因子的增加。
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引用次数: 0
Activation of the Interleukin-18 Signaling Pathway via Direct Receptor Dimerization in the Absence of Interleukin-18. 在不存在白细胞介素-18的情况下通过直接受体二聚激活白细胞介蛋白-18信号通路。
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-01 Epub Date: 2023-11-06 DOI: 10.1089/jir.2023.0129
Yasaman Mortazavi, Robert Herrera, Matthieu Masureel, Timurs Maculins, Isabelle Lehoux, Jonathan Sockolosky, Nathan West, Beyza Bulutoglu, Yue Zhao

Interleukin 18 (IL-18) is a key cytokine involved in the activation of T and NK cells, which are major effector cells in tumor killing. However, recombinant IL-18 showed limited efficacy in clinical trials. A recent study showed the lack of efficacy was largely due to the existence of IL-18BP, a soluble decoy receptor for IL-18. It was shown that engineered IL-18 variants that maintained pathway activation, but avoided IL-18BP binding, could exert potent antitumor effects. In this study, we demonstrated an alternative strategy to activate IL-18 signaling through direct receptor dimerization. These results provide evidences that the IL-18 pathway can be activated by directly bridging the receptors and, therefore, bypassing the IL-18BP-mediated inhibition.

白细胞介素18(IL-18)是一种关键的细胞因子,参与T细胞和NK细胞的活化,这两种细胞是肿瘤杀伤的主要效应细胞。然而,重组IL-18在临床试验中显示出有限的疗效。最近的一项研究表明,缺乏疗效主要是由于IL-18BP的存在,IL-18BP是IL-18的可溶性诱饵受体。研究表明,维持通路激活但避免IL-18BP结合的工程IL-18变体可以发挥强大的抗肿瘤作用。在这项研究中,我们展示了一种通过直接受体二聚化激活IL-18信号传导的替代策略。这些结果提供了证据,证明IL-18通路可以通过直接桥接受体而被激活,从而绕过IL-18BP介导的抑制。
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引用次数: 0
Acknowledgment of Reviewers 2023. 鸣谢 2023 年审稿人。
IF 2.3 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-21 DOI: 10.1089/jir.2023.29059.ack
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引用次数: 0
BioHabana 2022: Preventive and Immunotherapeutic Strategies Against COVID-19 and Cancer in Cuba. 生物哈瓦那2022:古巴针对COVID-19和癌症的预防和免疫治疗战略。
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 Epub Date: 2023-12-04 DOI: 10.1089/jir.2023.0141
Iraldo Bello-Rivero, Tania Crombet-Ramos, Circe Mesa-Pardillo, Yanelys Morera-Díaz, Zaima Mazorra-Herrera, Dagmar Garcia-Rivera, Hugo Nodarse-Cuní, Francisco Hernández-Bernal, Verena Muzio-Gonzalez, Ana Aguilera-Barreto, Dania Vazquez-Blomquist, Maria Del Carmen Domínguez-Horta, Gerardo Guillen-Nieto

The convergence of life sciences with neurosciences, nanotechnology, data management, and engineering has caused a technological diversification of the biotechnology, pharmaceutical, and medical technology industries, including the phenomenon of digital transformation, which has given rise to the so-called Fourth Industrial Revolution (Industry 4.0). Confronting the COVID-19 pandemic revealed the outstanding response capacity of the scientific community and the biopharmaceutical industry, based on a multidisciplinary and interinstitutional approach that has achieved an unprecedented integration in the history of biomedical science. Cuba, a small country, with scarce material resources, has had remarkable success in controlling the disease, which also highlights the impact of social factors. This report presents a summary of the most relevant presentations of selected topics during the scientific meeting, "BioHabana 2022: Cancer Immunotherapy and the COVID-19 Pandemic," which was held in Havana Cuba in April 2022.

生命科学与神经科学、纳米技术、数据管理和工程学的融合,导致了生物技术、制药和医疗技术行业的技术多样化,包括数字化转型现象,从而引发了所谓的第四次工业革命(工业4.0)。面对2019冠状病毒病大流行,科学界和生物制药行业基于多学科和跨机构的方法展现了卓越的应对能力,实现了生物医学科学史上前所未有的一体化。古巴是一个物质资源匮乏的小国,但在控制这一疾病方面取得了显著成功,这也突出了社会因素的影响。本报告概述了2022年4月在古巴哈瓦那举行的“生物哈瓦那2022:癌症免疫治疗和COVID-19大流行”科学会议上选定主题的最相关演讲。
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引用次数: 0
Conversation with Dr. Daniela Novick. 与Daniela Novick博士的对话。
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 Epub Date: 2023-10-25 DOI: 10.1089/jir.2023.29057.int
Daniela Novick
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引用次数: 0
The Association of Serum Midkine Level with Invasion in Placenta Previa: A Case-Control Study from a Tertiary Reference Center. 血清 Midkine 水平与前置胎盘侵犯的关系:一项来自三级参考中心的病例对照研究
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 DOI: 10.1089/jir.2023.0106
Nihat Farisoğullari, Atakan Tanaçan, Bedri Sakcak, Ramazan Denizli, Osman Onur Özkavak, Ezgi Turgut, Özgür Kara, Nuray Yazihan, Dilek Şahin

We aimed to examine the relationship between serum midkine levels and placental invasion in pregnant women with placenta previa. The study group consisted of 43 pregnant women diagnosed with placenta previa, whereas the control group consisted of 60 healthy pregnant women. Serum midkine levels were compared between pregnant women with placenta previa and the control group in this study's first part. Thereafter, the utility of midkine in the prediction of the abnormally invasive placenta (AIP) was investigated and optimal cutoff values were calculated. Significantly higher serum midkine level was observed in placenta previa cases than in the controls (1.16 ng/mL vs. 0.18 ng/mL, P < 0.001). Serum midkine level was also significantly higher in the AIP group among the placenta previa cases (P = 0.004). In the receiver operating characteristic analysis, the cutoff value of the midkine level in predicting AIP was 1.19 ng/mL. This study revealed that the serum midkine level is higher in pregnant women with AIP. Maternal serum midkine level may be used as a complementary biomarker to the radiological and clinical findings for the prediction of the AIP in placenta previa cases.

我们的目的是研究患有前置胎盘的孕妇血清中midkine水平与胎盘侵袭之间的关系。研究组由 43 名确诊为前置胎盘的孕妇组成,对照组由 60 名健康孕妇组成。研究的第一部分比较了前置胎盘孕妇和对照组孕妇的血清 midkine 水平。随后,研究人员对 midkine 在预测异常侵入性胎盘(AIP)中的作用进行了调查,并计算出了最佳临界值。前置胎盘病例的血清 midkine 水平明显高于对照组(1.16 纳克/毫升对 0.18 纳克/毫升,P = 0.004)。在接收器操作特征分析中,预测 AIP 的 midkine 水平的临界值为 1.19 纳克/毫升。这项研究表明,患有 AIP 的孕妇血清中的 midkine 水平较高。母体血清中midkine水平可作为放射学和临床结果的补充生物标志物,用于预测前置胎盘病例中的AIP。
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引用次数: 0
Biology of Interleukin-17 and Novel Therapies for Hidradenitis Suppurativa. 白细胞介素-17的生物学特性及对化脓性痢疾的新疗法。
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 Epub Date: 2023-10-12 DOI: 10.1089/jir.2023.0105
Robert Sabat, Johann Eli Gudjonsson, Nicolo Costantino Brembilla, Kelsey R van Straalen, Kerstin Wolk

Skin disorders affect ∼40% of the human population. One of the most debilitating cutaneous disorders is Hidradenitis suppurativa (HS), a noncommunicable chronic inflammatory disease with an estimated global prevalence of 0.4% to 2.5%. In January 2011, high levels of IL-17 were discovered in skin lesions of HS patients. In the following years, translational and clinical research led to a better understanding of the pathogenesis of HS. In June 2023, more than 12 years after the initial note, secukinumab, an anti-IL-17A monoclonal antibody, was approved for the treatment of moderate to severe HS. This is the next milestone in improving the treatment of these patients after the approval of the anti-TNF-α monoclonal antibody adalimumab in 2015. In this review article, we present the IL-17 pathway in HS and discuss the use of secukinumab as a therapeutic option for this disease. Our review starts with a description of the epidemiology, clinical features, etiology, and pathogenesis of HS. An overview of the IL-17/IL-17 receptor system in general and a detailed description of the known facts about the expression and action of IL-17 in HS follow. Afterward, we consider the results of clinical trials evaluating the safety and efficacy of IL-17 inhibitors in HS. Finally, a comparison is made between secukinumab and adalimumab and the characteristics of the patients that may be particularly suitable for each of these biologics are described.

皮肤病影响了约40%的人口。最令人衰弱的皮肤疾病之一是化脓性Hidradenitis化脓性(HS),这是一种非传染性慢性炎症性疾病,估计全球患病率为0.4%至2.5%。2011年1月,在HS患者的皮肤病变中发现了高水平的IL-17。在接下来的几年里,翻译和临床研究使人们对HS的发病机制有了更好的了解。2023年6月,在首次发布12年多后,抗IL-17A单克隆抗体secukinumab被批准用于治疗中重度HS。这是继2015年批准抗TNF-α单克隆抗体阿达木单抗后,改善这些患者治疗的下一个里程碑。在这篇综述文章中,我们介绍了HS中的IL-17通路,并讨论了使用secukinumab作为该疾病的治疗选择。我们的综述从HS的流行病学、临床特征、病因和发病机制的描述开始。以下是IL-17/IL-17受体系统的概述以及关于IL-17在HS中的表达和作用的已知事实的详细描述。之后,我们考虑了评估IL-17抑制剂在HS中的安全性和有效性的临床试验结果。最后,对secukinumab和阿达木单抗进行了比较,并描述了可能特别适合每种生物制剂的患者特征。
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引用次数: 0
High Anti-Interferon-Alpha Autoantibody Levels in Severe/Critical COVID-19 Patients from Peru. 秘鲁重症/危重新冠肺炎患者的高抗干扰素-α自身抗体水平。
IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 Epub Date: 2023-10-31 DOI: 10.1089/jir.2023.0087
Maria J Pons, Ana Mayanga-Herrera, Luciano A Palomino-Kobayashi, Antonio M Quispe, Manuel F Ugarte-Gil

Innate immune responses through the production of type I interferon-α (anti-IFN-α) play an essential role in the defense against viruses. The autoantibodies (auto-Abs) anti-IFN-α are implicated in COVID-19 pathogenesis with higher levels among patients with worse prognoses. The study aimed to assess the levels of anti-IFN-α auto-Abs in Peruvian patients with severe/critical hospitalized COVID-19 compared to asymptomatic/mild COVID-19 outpatients and healthy controls. We analyzed 101 serum samples, including 56 (55.5%) severe/critical, 13 (12.3%) asymptomatic/mild COVID-19 patients, and 32 (32.2%) healthy controls, which we tested using a commercial ELISA anti-IFN-α-auto-Abs kit. We observed seropositivity of 48.2% (26/54) to anti-IFN-α auto-Abs among the severe/critical COVID-19 group, but 0% (0/13) and 3.1% (1/32) among the asymptomatic/mild COVID-19 and healthy groups (P = 0.021), respectively. Furthermore, we observed a significant association between the log10 of anti-IFN-α auto-Abs and the COVID-19 status, with the log10 of anti-IFN-α auto-Abs levels being significantly higher among the severe/critical COVID-19 group compared to the healthy controls (β = 1.20; confidence interval [95% CI]: 0.72-1.67; P < 0.001). Such association remains significant either when adjusted by age and gender (adjusted β = 1.16; 95% CI: 0.62-1.70; P < 0.001) and when adjusted by the subjects' age, gender, and obesity (adjusted β = 1.16; 95% CI: 0.62-1.70; P < 0.001). Despite not measuring neutralizing activity, this study highlights the high frequency of these auto-Abs in the Peruvian population with a worse prognosis of COVID-19.

通过产生I型干扰素-α(抗干扰素-α)的先天免疫反应在防御病毒中发挥着重要作用。抗IFN-α自身抗体(auto-Abs)与新冠肺炎发病机制有关,在预后较差的患者中其水平较高。该研究旨在评估秘鲁重症/危重住院新冠肺炎患者与无症状/轻度新冠肺炎门诊患者和健康对照者的抗IFN-αauto-Abs水平。我们分析了101份血清样本,包括56名(55.5%)重症/危重症患者、13名(12.3%)无症状/轻度新冠肺炎患者和32名(32.2%)健康对照,我们使用商业ELISA抗IFN-α-auto-Abs试剂盒对其进行了检测。我们观察到,在重症/危重新冠肺炎组中,抗IFN-α自身抗体的血清阳性率为48.2%(26/54),而在无症状/轻度新冠肺炎和健康组中,血清阳性率分别为0%(0/13)和3.1%(1/32)(P = 0.021)。此外,我们观察到抗IFN-αauto-Abs的log10与新冠肺炎状态之间存在显著关联,严重/危重新冠肺炎组的抗IFN-βauto-Abs水平显著高于健康对照组(β = 1.20;置信区间[95%CI]:0.72-1.67;P P P
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引用次数: 0
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Journal of Interferon and Cytokine Research
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