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临床试验 1

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Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

《农业科学与工程前沿（英文）》 2017年 第4卷 第3期   页码 260-267 doi: 10.15302/J-FASE-2016116

摘要： The innate immune response is the first line of defense against viral invasion and pro-inflammatory chemokines and cytokines have a critical function in the innate immune responses against virus infections. The ability of a rabies virus (RABV) to induce the expression of chemokines and cytokines can lead to viral clearance from the central nervous system (CNS), whereas the ability to evade such expression and activation contributes to virulence and pathogenicity. In this review, the crucial contribution of chemokines/cytokines to clearing RABV from the CNS is discussed, including recruiting leukocytes into the CNS, enhancement of blood brain barrier permeability and activation of various immune cells that are essential for viral clearance. In addition, recombinant RABV expressing cytokines and chemokines can induce elevated innate and adaptive immune responses which result in clearing an established wild-type RABV infection in the CNS.

关键词： antiviral     blood brain barrier     chemokines and cytokines     innate immunity     rabies virus    

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Cytokines and inflammation in adipogenesis: an updated review

Ning Jiang, Yao Li, Ting Shu, Jing Wang

《医学前沿（英文）》 2019年 第13卷 第3期   页码 314-329 doi: 10.1007/s11684-018-0625-0

摘要： The biological relevance of cytokines is known for more than 20 years. Evidence suggests that adipogenesis is one of the biological events involved in the regulation of cytokines, and pro-inflammatory cytokines (e.g., TNF and IL-1 ) inhibit adipogenesis through various pathways. This inhibitory effect can constrain the hyperplastic expandability of adipose tissues. Meanwhile, chronic low-grade inflammation is commonly observed in obese populations. In some individuals, the impaired ability of adipose tissues to recruit new adipocytes to adipose depots during overnutrition results in adipocyte hypertrophy, ectopic lipid accumulation, and insulin resistance. Intervention studies showed that pro-inflammatory cytokine antagonists improve metabolism in patients with metabolic syndrome. This review focuses on the cytokines currently known to regulate adipogenesis under physiological and pathophysiological circumstances. Recent studies on how inhibited adipogenesis leads to metabolic disorders were summarized. Although the interplay of cytokines and lipid metabolism is yet incompletely understood, cytokines represent a class of potential therapeutic targets in the treatment of metabolic disorders.

关键词： cytokines     inflammation     adipogenesis     type 2 diabetes mellitus     metabolic disorder    

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The relationship between progesterone and Th-related cytokines in plasma during early pregnancy in cows

Lei CHENG,Youdong XIN,Xiaohua LIU,Xiuzhong HU,Min XIANG,Dingfa WANG,Shuhong ZHAO

《农业科学与工程前沿（英文）》 2016年 第3卷 第2期   页码 147-152 doi: 10.15302/J-FASE-2016099

摘要： In cows, progesterone (P4) is essential for the maintenance of pregnancy and successful embryo development is dependent on the maternal immunomodulation of Th-related cytokines. However, investigation of the relationship between P4 and Th immunity in cattle remains incomplete. Therefore, we evaluated plasma P4 concentrations and expressions of three Th-related cytokines, interleukins IL-1β, IL-4 and IL-6, in 15 pregnant and 11 non-pregnant cows 0, 14, 18, 21, and 28 d post artificial insemination. Pregnant cows had significantly higher plasma P4 levels and pregnant cows with higher P4 on 14 d tended to have higher P4 in the subsequent period of pregnancy. There was no difference in IL-4 and IL-6 expression between pregnant cows and non-pregnant cows, whereas plasma IL-1β was temporally upregulated on 21 d. The cytokines measured were not affected in either the high-P4 group (>11.1 ng·mL ) or the low-P4 group (<11.1 ng·mL ) in pregnant cows. A weak negative correlation between IL-1β and IL-6 was observed, but none of the cytokines was associated with a change in plasma P4. In conclusion, there was no clear relationship between P4 and Th immunity in maternal plasma in the pregnant cows, which differs from what occurs in humans and mice during early pregnancy.

关键词： dairy cow     progesterone     pregnancy     cytokine    

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Advances in immunopathogenesis of adult immune thrombocytopenia

null

《医学前沿（英文）》 2013年 第7卷 第4期   页码 418-424 doi: 10.1007/s11684-013-0297-8

摘要：

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immune-mediated accelerated platelet destruction and/or suppressed platelet production. Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP, several abnormalities involving the cellular mechanisms of immune modulation have been identified, and the pathways behind the immune-mediated destruction of platelets have opened new avenues for the design of specific immunotherapies in an attempt to reduce the platelet destruction. This review is primarily focused on the recent literature with respect to immunopathological mechanisms in patients with ITP.

关键词： primary immune thrombocytopenia     B lymphocytes     T lymphocytes     antigen-presenting cells     cytokines    

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Predictive values of plasma TNFα and IL-8 for intracranial hemorrhage in patients with acute promyelocytic leukemia

《医学前沿（英文）》 2022年 第16卷 第6期   页码 909-918 doi: 10.1007/s11684-021-0890-1

摘要： In patients with acute promyelocytic leukemia (APL), intracranial hemorrhage (ICH), if not identified promptly, could be fatal. It is the leading cause of failure of induction and early death. Thus, biomarkers that could promptly predict severe complications are critical. Here, cytokine differences between patients with APL with and without ICH were investigated to develop predictive models for this complication. The initial cytokine profiling using plasma samples from 39 patients and 18 healthy donors found a series of cytokines that were remarkedly different between patients with APL and healthy controls. The APL patients were subsequently divided into high and low white blood cell count groups. Results showed that tumor necrosis factor α and interleukin 8 (IL-8) were vital in distinguishing patients with APL who did or did not develop ICH. In addition, verification in 81 patients with APL demonstrated that the two cytokines were positively correlated with the cumulative incidence of ICH. Finally, in-vitro and in-vivo experimental evidence were provided to show that IL-8 influenced the migration of APL-derived NB4 cells and impaired the blood–brain barrier in PML/RARα positive blast-transplanted FVB/NJ mice. These assessments may facilitate the early warning of ICH and reduce future mortality levels in APL.

关键词： acute promyelocytic leukemia     intracranial hemorrhage     cytokines     biomarker    

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单克隆抗体治疗过敏性疾病的研究现状 Review

陈彦, 王炜, 袁慧慧, 李艳, 吕喆, 崔烨, 刘杰, 孙英

《工程（英文）》 2021年 第7卷 第11期   页码 1552-1556 doi: 10.1016/j.eng.2020.06.029

摘要：

过敏性疾病是常见的慢性疾病之一，由变应原在不同器官上引发变态反应，在临床上以不同器官的疾病为主要表现形式，如哮喘、特应性皮炎、鼻-鼻窦炎等，常累及儿童和成人。由于其在世界范围内的广泛流行和对患者生活质量的影响，采用新型生物疗法治疗过敏性疾病的研究业已成为该领域的热点。已知多种因素可促进或触发Th2 型免疫应答，导致2 型细胞因子和免疫球蛋白E（IgE）的产生并参与过敏性疾病的发生发展，因此，开发针对2 型细胞因子和IgE 的单克隆抗体为治疗过敏性疾病提供了新的策略。此外，一些潜在的靶点，如上皮源性预警素-胸腺基质淋巴细胞生成素（TSLP）和白介素33（IL-33）业已进入临床研究阶段。这些新的和潜在的靶点极大地提高了变应性疾病的治疗机会。本文阐述了目前已开发的针对细胞因子、细胞因子受体和IgE 的单克隆抗体在过敏性疾病治疗中的作用，并对这些抗体的临床效果进行了讨论和分析。

关键词： 过敏性疾病     单克隆抗体     抗免疫球蛋白E     细胞因子     临床试验    

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Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the Toll-like receptor 4 signaling pathway

Na You, Sasa Chu, Binggang Cai, Youfang Gao, Mizhou Hui, Jin Zhu, Maorong Wang

《医学前沿（英文）》 2021年 第15卷 第2期   页码 292-301 doi: 10.1007/s11684-020-0806-5

摘要： The high- and the low-molecular weight hyaluronic acids (HMW-HA and LMW-HA, respectively) showed different biological activities in inflammation. However, the role of LMW-HA in inflammatory response is controversial. In this study, we aimed to investigate the effect of bioactive hyaluronan (B-HA) on lipopolysaccharide (LPS)-induced inflammatory responses in human macrophages and mice. B-HA was produced from HA treated with glycosylated recombinant human hyaluronidase PH20. Human THP-1 cells were induced to differentiate into macrophages. THP-1-derived macrophages were treated with B-HA, LPS, or B-HA+LPS. The mRNA expression and the production of inflammatory cytokines were determined using quantitative real-time PCR and enzyme-linked immunosorbent assay. The phosphorylation levels of proteins in the nuclear factor- B (NF- B), mitogen-activated protein kinase (MAPK), and IRF-3 signaling pathways were measured using Western blot. The efficacy of B-HA was assessed in a mouse model of LPS-induced inflammation. Results showed that B-HA inhibited the expression of TNF-α, IL-6, IL-1, and IFN-β, and enhanced the expression of the anti-inflammatory cytokine IL-10 in LPS-induced inflammatory responses in THP-1-derived macrophages and . B-HA significantly suppressed the phosphorylation of the TLR4 signaling pathway proteins p65, IKKα/β, I Bα, JNK1/2, ERK1/2, p38, and IRF-3. In conclusion, our results demonstrated that the B-HA attenuated the LPS-stimulated inflammatory response by inhibiting the activation of the TLR4 signaling pathway. B-HA could be a potential anti-inflammatory drug in the treatment of inflammatory disease.

关键词： bioactive hyaluronan     lipopolysaccharide     inflammatory cytokines     TLR4     human macrophages    

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The “Traditional Chinese medicine regulating liver regeneration” treatment plan for reducing mortality of patients with hepatitis B-related liver failure based on real-world clinical data

Ling Dai, Xiang Gao, Zhihua Ye, Hanmin Li, Xin Yao, Dingbo Lu, Na Wu

《医学前沿（英文）》 2021年 第15卷 第3期   页码 495-505 doi: 10.1007/s11684-020-0790-9

摘要： On the basis of real-world clinical data, the study aimed to explore the effect and mechanisms of the treatment plan of “traditional Chinese medicine (TCM) regulating liver regeneration.” A total of 457 patients with HBV-related liver failure were retrospectively collected. The patients were divided into three groups: the modern medicine control group (MMC group), patients treated with routine medical treatment; the control group combining traditional Chinese and Western medicine (CTW), patients treated with routine medical treatment plus the common TCM formula; and the treatment group of “TCM regulating liver regeneration” (RLR), patients treated with both routine medical treatment and the special TCM formula of RLR. After 8 weeks of treatment, the mortality of patients in the RLR group (12.31%) was significantly lower than those in the MMC (50%) and CTW (29.11%) groups. Total bilirubin level significantly decreased and albumin increased in the RLR group when compared with the MMC and CTW groups ( <0.05). In addition, there were significant differences in the expression of several cytokines related to liver regeneration in the RLR group compared with the MMC group. RLR treatment can decrease jaundice, improve liver function, and significantly reduce the mortality in patients with HBV-related liver failure. The mechanism may be related to the role of RLR treatment in influencing cytokines related to liver regeneration.

关键词： hepatitis B virus-related liver failure     traditional Chinese medicine     liver regeneration     liver regeneration microenvironment     cytokines    

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新冠病毒肺炎抗体应答、细胞因子的动态变化及其与生存状况的关联 ——一项回顾性队列研究 Article

刘莉, 陈亨贵, 李莹, 李辉军, 李娇元, 王意, 姚霜, 秦川, 童书韬, 袁旭, 罗霞, 缪小平, 潘安, 刘争, 程黎明

《工程（英文）》 2021年 第7卷 第7期   页码 958-965 doi: 10.1016/j.eng.2021.04.015

摘要：

目前，患者感染严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）后，机体免疫状况随时间的纵向变化及其与临床结局的关联尚不明确。因此，我们致力于研究新冠病毒特异性抗体[免疫球蛋白G（IgG）和免疫球蛋白M（IgM）]随时间变化的特征，并分析特异性抗体、炎性细胞因子及其与新冠病毒肺炎（COVID-19，简称新冠肺炎）患者的生存状况之间的关联。研究共招募了1830例实验室确诊的新冠肺炎感染病例。利用局部加权回归散点平滑法（LOWESS）拟合患者自发病以来直至12周的病毒载量、特异性抗体及细胞因子水平随时间的变化谱。通过中介分析，探究细胞因子在抗体应答与生存状况之间的中介效应。在1830例患者中，新冠病毒核酸阳性患者共1435例，新冠病毒特异性IgG和（或）IgM抗体阳性患者为395例。在1435例患者中，2.4%的患者在住院期间既未出现IgG也未出现IgM的血清学转变。特异性IgG和IgM的血清阳性率在发病后的第1周分别为29.6%和48.1%，并在5周内达到峰值。对于痊愈出院患者组，在发病后的12周内，IgM水平缓慢下降，而IgG水平基本维持在188 AU· mL−1左右。反之，对于最终进展为死亡的患者，其IgM水平迅速下降，IgG水平在第12周也下降至87 AU· mL−1。与出院患者组相比，病亡患者组的白细胞介素6（IL-6）、白细胞介素8（IL-8）、白细胞介素10（IL-10）、白细胞介素1β（IL-1β）、白细胞介素2受体（IL-2R）及肿瘤坏死因子-α（TNF-α）水平均较高，IgG水平与死亡风险之间12.5%的关联由上述细胞因子介导。本研究阐明了新冠病毒特异性抗体自发病以来12周内的实时变化特征，并表明了抗体应答对生存结局的积极作用，相关发现对新冠肺炎患者的预后评估可能有所帮助。

关键词： 新冠病毒肺炎     抗体应答     细胞因子     死亡率     病毒载量    

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标题 作者 时间 类型 操作

Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

期刊论文

Cytokines and inflammation in adipogenesis: an updated review

Ning Jiang, Yao Li, Ting Shu, Jing Wang

期刊论文

The relationship between progesterone and Th-related cytokines in plasma during early pregnancy in cows

Lei CHENG,Youdong XIN,Xiaohua LIU,Xiuzhong HU,Min XIANG,Dingfa WANG,Shuhong ZHAO

期刊论文

Advances in immunopathogenesis of adult immune thrombocytopenia

null

期刊论文

Predictive values of plasma TNFα and IL-8 for intracranial hemorrhage in patients with acute promyelocytic leukemia

期刊论文

单克隆抗体治疗过敏性疾病的研究现状

陈彦, 王炜, 袁慧慧, 李艳, 吕喆, 崔烨, 刘杰, 孙英

期刊论文

Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the Toll-like receptor 4 signaling pathway

Na You, Sasa Chu, Binggang Cai, Youfang Gao, Mizhou Hui, Jin Zhu, Maorong Wang

期刊论文

The “Traditional Chinese medicine regulating liver regeneration” treatment plan for reducing mortality of patients with hepatitis B-related liver failure based on real-world clinical data

Ling Dai, Xiang Gao, Zhihua Ye, Hanmin Li, Xin Yao, Dingbo Lu, Na Wu

期刊论文

新冠病毒肺炎抗体应答、细胞因子的动态变化及其与生存状况的关联 ——一项回顾性队列研究

刘莉, 陈亨贵, 李莹, 李辉军, 李娇元, 王意, 姚霜, 秦川, 童书韬, 袁旭, 罗霞, 缪小平, 潘安, 刘争, 程黎明

期刊论文