Effectiveness and Safety of Tumor Necrosis Factor Receptor Fusion Protein(Yisaipu) Combined With Tripterygium Wilfordii for Active Rheumatoid Arthritis

In this 24-week, multi-center, randomized, double-blind study, the investigators will evaluate the efficacy and safety profile of subcutaneously injected Yisaipu, a Tumor Necrosis Factor Receptor Fusion Protein, combined with oral Tripterygium Wilfordii for patients with active rheumatoid arthritis.

开始日期2019-05-14

申办/合作机构

北京协和医院

NCT03403569 / Completed临床3期IIT

Impact of Triptolide Wilfordii on Viral Suppression, Immune Recovery and Immune Activation Biomarkers in Treatment-naive HIV-1 Infection: a Randomized, Double-blinded, Placebo-controlled Study

The traditional Chinese herbal medicine Triptolide Wilfordii has displayed remarkable effect on the treatment of autoimmune diseases such as rheumatoid arthritis. Now that immunosuppression therapy has recently become a new strategy for HIV infection, it's reasonable to expect the anti-inflammatory effect of Triptolide Wilfordii in HIV infected patients. So we designed a randomized, double-blinded, placebo-controlled study to explore the efficacy and safety of Triptolide Wilfordii in new-onset HIV infection.

开始日期2018-09-01

申办/合作机构

北京协和医院

100 项与雷公藤提取物相关的临床结果

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100 项与雷公藤提取物相关的转化医学

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100 项与雷公藤提取物相关的专利（医药）

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项与雷公藤提取物相关的文献（医药）

2024-12-31·Renal failure

The effects of Tripterygium wilfordii Hook F on renal outcomes in type 2 diabetic kidney disease patients with severe proteinuria: a single-center cohort study

Article

作者: Lin, Liling ; Liu, Yuhao ; Cheng, Yaqi ; Li, Danni ; Tao, Jianling ; Li, Mingxi ; Zheng, Ke ; Peng, Liying

AIM:

Tripterygium wilfordii Hook F (TwHF) has been shown to substantially reduce proteinuria in patients with diabetic kidney disease (DKD); however, the effect of TwHF on renal outcomes in DKD remains unknown. Accordingly, we aimed to establish the effects of TwHF on renal outcomes in patients with DKD.

METHODS:

Overall, 124 patients with DKD, induced by type 2 diabetes mellitus, with 24-h proteinuria > 2 g, and an estimated glomerular filtration rate > 30 mL/min/1.73 m² were retrospectively investigated. The renal outcomes were defined as doubling serum creatinine levels or end-stage kidney disease. Kaplan-Meier curves and Cox regression analyses were performed to analyze prognostic factors for renal outcomes.

RESULTS:

By the end of the follow-up, renal outcomes were observed in 23 and 11 patients in the non-TwHF and TwHF groups, respectively (p = 0.006). TwHF significantly reduced the risk of renal outcomes (adjusted hazard ratio [HR] 0.271, 95% confidence interval [CI] 0.111-0.660, p = 0.004) in patients with chronic kidney disease (CKD) G3 (adjusted HR 0.274, 95%CI 0.081-0.932, p = 0.039). Based on the Kaplan-Meier analysis, 1- and 3-year proportions of patients without renal outcomes were significantly lower in the non-TwHF group than those in the TwHF group (92.8% vs. 95.5% and 47.2% vs. 76.8%, respectively; p = 0.0018).

CONCLUSION:

In DKD patients with severe proteinuria, TwHF could prevent DKD progression, especially in patients with CKD G3. A randomized clinical trial is needed to elucidate the benefits of TwHF on renal outcomes in patients with DKD.

2024-03-01·Chinese journal of integrative medicine

Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes

Article

作者: Zhang, Shuo ; Zhou, Ya-Qiong ; Liu, Liu ; Miao, Xiao ; Wang, Jiao ; Chen, Si-Ting ; Li, Xin ; Li, Hong-Jin ; Yan, Ge ; Li, Bin ; Lu, Yi ; Hu, Man-Qi ; Yang, Chun-Mei ; Sun, Xiao-Ying

OBJECTIVE:

To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.

METHODS:

Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.

RESULTS:

TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).

CONCLUSIONS:

TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.

2024-03-01·Marine pollution bulletin

Are anticoagulant drugs ecotoxic for meiobenthic nematodes from Saudi Arabia? First data on taxon/functional diversity and computational evidences

Article

作者: Bin-Jumah, May Nasser

Community-level effects of anticoagulants have little been studied in the laboratory. In the current study, the different effects of Warfarin and Tinzaparin, individually or in combination, on meiofauna were investigated for the first time using two concentrations (5 and 25 mg·l^-1) of Warfarin (W1 and W2) and Tinzaparin (T1 and T2) for 30 days. The results obtained highlighted the highest tolerance of nematodes and amphipods toward the two anticoagulants tested. Moreover, nematode abundance and taxonomic diversity decreased directly after exposure to T2 and T2W1 because of the high mortality of diatom feeders and their replacement by non-selective deposit feeders (case of Tinzaparin) or omnivores-carnivores (case of Warfarin). The relative taxon/functional similarity between controls and mixtures T1W1 and T2W2 recommends that the toxicity of Tinzaparin can be attenuated by Warfarin. Finally, the computational study of Warfarin supports its potential ecotoxicity since it satisfactorily bound and interacted with GLD-3 and SDP macromolecules.

项与雷公藤提取物相关的新闻（医药）

2024-01-22

·奇点网

《科学》重磅：科学家首次发现，肿瘤竟会将中性粒细胞的寿命延长3倍，使其成为促进血管生成的“长工”丨科学大发现

*仅供医学专业人士阅读参考在固若金汤的实体瘤面前，免疫细胞始终是弱小的一方。去年8月份，美国范德堡大学的研究人员发现，杀伤性T细胞竟然在接触肿瘤后的6-12小时内就能发生耗竭[1]。去年年底，以色列魏茨曼科学研究所的一项研究表明，NK细胞入瘤24小时之内，就失去了抗肿瘤活性；而巨噬细胞入瘤后48小时之内就会被肿瘤策反，发挥促进肿瘤生长的作用[2]。近日，由新加坡科技研究局（A*STAR）的Melissa S.F. Ng和A*STAR及上海交通大学医学院附属仁济医院-上海市免疫治疗创新研究院的Lai Guan Ng（黄来源）领衔的研究团队，在顶级期刊《科学》上发表一项重磅研究成果[3]，深入阐述了瘤内中性粒细胞的命运。他们首次发现，中性粒细胞在进入肿瘤之后，在一天之内就会被肿瘤重编程成为超级长寿的促癌亚型。具体来说，在肿瘤的调教下，此类中性粒细胞的寿命达到循环中性粒细胞的4倍以上，而且它们还不惧低氧和缺乏营养的环境，聚集在肿瘤核心区域附近，表达高水平的血管内皮生长因子α（VEGFα），促进肿瘤核心区域血管的形成，为肿瘤提供养分，促进肿瘤的生长。A*STAR的Melissa S.F. Ng、Immanuel Kwok和Leonard Tan，及上海交通大学医学院附属仁济医院-上海免疫治疗创新研究院的史长明为研究论文的共同第一作者。论文首页截图作为最积极、最强力的免疫细胞之一，中性粒细胞总会在第一时间赶到“案发现场”。然而，在癌症这种疾病类型中，科学家很早就发现，肿瘤中浸润的中性粒细胞与患者的预后较差有关[4]。它甚至被认为是一种促进癌症进展的免疫细胞类型[5]。不过，中性粒细胞促进肿瘤进展的原因，科学家仍知之甚少。为了搞清楚中性粒细胞为何会促进肿瘤进展，又是如何促进肿瘤进展的，黄来源团队以胰腺癌为研究模型，采用单细胞转录组和具有空间分辨率的多组学方法，深入研究了胰腺癌里中性粒细胞的变化、分布及功能。从单细胞RNA测序（scRNAseq）结果来看，在中性粒细胞发育和循环的组织中，它有一条单一的变化轨迹。肿瘤组织中的中性粒细胞却不太一样，它们获得了独特的转录谱，并形成了三个不同的亚群（T1、T2和T3）。从转录组特征来看，T1中性粒细胞的成熟度与未成熟中性粒细胞相当，而T2中性粒细胞的成熟度与成熟中性粒细胞相当。而且T1和T2中性粒细胞沿着肿瘤特异性分支发展，并往成熟度介于T1和T2之间的T3亚群汇聚。这意味着，T3亚群可能是T1和T2分化的终期阶段。瘤内中性粒细胞的发展轨迹值得注意的是，转录组学数据还显示，T3中性粒细胞中，与缺氧、糖酵解和血管生成有关的基因（如Vegfa和Hk2等）表达上调，染色质可及性增加。而其他组织中的中性粒细胞没有这些转录组特征。基于以上研究结果，研究人员认为，浸润肿瘤的中性粒细胞无论处于哪个成熟阶段，都能被肿瘤微环境重新编程，转录和染色质的发展轨迹趋向于独特的T3状态。接下来黄来源团队评估了是否能通过蛋白质表达来区分这三个亚群。结果发现，仅需要CD101和dcTRAIL-R1这两个蛋白即可。CD101阳性属于成熟的中性粒细胞，CD101阴性属于未成熟的中性粒细胞；而免疫调节或抑制标志物dcTRAIL-R1则是T3中性粒细胞的象征。如此一来，T1中性粒细胞就是CD101和dcTRAIL-R1双阴性，T2是CD101阳性和dcTRAIL-R1阴性。基于蛋白标志物的分类方法搞清楚瘤内中性粒细胞的特征之后，就需要弄清楚它们的分布和功能了。从前面的转录组数据来看，T3中性粒细胞表现出明显的细胞应激和生存途径特征，包括对缺氧、氧化应激和糖酵解的反应。此外，T3中性粒细胞还富集了血管生成基因，包括Vegfa、Thbs1和Lgals3。黄来源团队认为，这些数据表明T3不仅适应了肿瘤环境，还具有很强的促瘤作用。从空间转录组数据来看，与T1和T2相比，T3中性粒细胞在肿瘤中糖酵解、缺氧和血管生成的高分区域（肿瘤核心的坏死区域，也是肿瘤最需要营养的区域）出现的频率更高。T3明显靠近肿瘤核心，T1和T2更多地分布在肿瘤外缘结合一开始得到转录组数据，肿瘤把T3中性粒细胞弄到核心部位的目的昭然若揭。肿瘤让被“黑化”的中性粒细胞促进核心部位长出血管，为肿瘤深处输送氧气和养料，进而促进肿瘤的生长。共注射实验证实了转录组数据得出的结论。与T1和T2相比，将T3与癌细胞共同注射到小鼠体内，更能促进肿瘤长血管。换句话说，T3中性粒细胞促进血管生成的能力最强。血管生成能力比较在了解肿瘤“黑化”中性粒细胞的时间轨迹的时候，黄来源团队发现，T3重编程在进入肿瘤时就已经开始了。而且他们还发现，入瘤后的中性粒细胞寿命可以长达135个小时（近6天），是中性粒细胞在血液中半衰期（31小时）的超4倍。值得注意的是，一旦中性粒细胞被重编程为T3中性粒细胞，即使它们摆脱了肿瘤也不会恢复原来的表型。简单来说，中性粒细胞进入肿瘤之后，肿瘤就开始重编程中性粒细胞，dcTRAIL-R1表达逐渐上调，逐渐往T3型发育。在拥有超级长寿的T3中性粒细胞之后，肿瘤会将它们安排到高度缺氧的核心区域，让T3诱导核心区域长出血管，进而达到促进肿瘤生长的目的。机制示意图在研究的最后，黄来源团队T3中性粒细胞存在的广泛性，以及临床应用价值。他们发现，肿瘤中性粒细胞的重编程在不同肿瘤类型中是一致的，T3中性粒细胞代表了终末分化的肿瘤中性粒细胞。基于来自癌症基因组图谱（TCGA）和国际癌症基因组联盟胰腺癌-澳大利亚（PACA-AU）的两个独立胰腺癌队列数据，他们还发现T3中性粒细胞特征高表达的患者总生存期（OS）较差，且不受患者性别、年龄和肿瘤分期等潜在混杂因素的影响。此外，在其他多种癌症类型中，T3中性粒细胞特征高表达也与患者的死亡风险升高有关。T3特征与不同癌症类型预后的关系总的来说，黄来源和Melissa S.F. Ng领衔的这项研究，系统地探索了肿瘤内中性粒细胞的“黑化”过程。他们发现无论是成熟还是未成熟的中性粒细胞，只要进入肿瘤就会被重编程成为T3终末态中性粒细胞，随后聚集在缺氧和高糖酵解特征的肿瘤核心区域，促进血管生成，支持肿瘤生长。这一发现让我们对中性粒细胞的促瘤作用有了更深入的认知，为靶向中性粒细胞的免疫疗法的开发提供了新思路。参考文献：[1].Rudloff MW, Zumbo P, Favret NR, et al. Hallmarks of CD8+ T cell dysfunction are established within hours of tumor antigen encounter before cell division. Nat Immunol. 2023;24(9):1527-1539. doi:10.1038/s41590-023-01578-y[2].Kirschenbaum D, Xie K, Ingelfinger F, et al. Time-resolved single-cell transcriptomics defines immune trajectories in glioblastoma. Cell. doi:10.1016/j.cell.2023.11.032[3].Ng MSF, Kwok I, Tan L, et al. Deterministic reprogramming of neutrophils within tumors. Science. 2024;383(6679):eadf6493. doi:10.1126/science.adf6493[4].Gentles AJ, Newman AM, Liu CL, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med. 2015;21(8):938-945. doi:10.1038/nm.3909[5].Bronte V, Brandau S, Chen SH, et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun. 2016;7:12150. doi:10.1038/ncomms12150本文作者丨BioTalker

免疫疗法

2023-10-17

·BioSpace

Research in the Special Issue of Journal of Pharmaceutical Analysis Uncovers Previously Unexplored Cellular Mechanisms

XI'AN, China, Oct. 17, 2023 /PRNewswire/ -- Single-cell and spatially resolved omics have helped scientists take a closer look at tissue composition, structure, and function. This comprehensive understanding paves the way for them to uncover some intricate and previously unknown disease mechanisms. Three articles in the most recent special issue of the Journal of Pharmaceutical Analysis (JPA) discuss how single-cell and spatially resolved omics help unravel intercellular dynamics, aiding the development of novel therapeutic modalities. The first study focuses on microglia-astrocyte communication which may improve the therapeutic landscape of intracerebral hemorrhage (ICH). It is based on the notion that after a spinal cord injury or stroke, reactive astrocytes in the brain form a 'glial scar', that is lesser known in the context of ICH. To this end, the authors used spatial transcriptomics to investigate how microglial depletion (induced using PLX3397) affects astrocytic scar formation in the early and late stages of ICH. The article was available online in February 2023 and published in Volume 13, Issue 8 of JPA in August 2023. The researchers discovered that during early ICH, microglia-derived insulin-like growth factor 1 (IGF1) regulated protective astrocytic scar formation by activating the mechanistic target of rapamycin (mTOR) signaling pathway, which was further activated by the repopulating microglia. In chronic ICH, however, the scar had less protective and more neurotoxic effects. Interestingly, this effect could be partially reversed by delayed microglial depletion. The corresponding author Jianmin Zhang says, "Delayed microglial depletion may help with chronic ICH. Combined early-stage IGF1/osteopontin and late-stage PLX3397 treatment could be a promising therapeutic strategy for ICH." The second study attempted to investigate the testicular toxicity of triptolide, an active component of the traditional Chinese medicine Tripterygium wilfordii Hook. F., at the single cell level. Although triptolide is effective in the treatment of inflammatory diseases, its side effects, particularly testicular toxicity, limit its clinical use. The researchers used triptolide to treat mice, then isolated their testes and prepared single-cell suspensions. These were used to create a transcriptome map, which revealed that in treated mice, inflammatory response and reactive oxygen species signaling were upregulated, while germ cell and spermatid development were downregulated, indicative of triptolide-induced toxicity. "Our findings provide an invaluable resource for identifying the therapeutic targets of triptolide-induced male reproductive toxicity", explains corresponding author Dr. Chuanbin Yang. The third study elaborated on the single-cell and spatial analysis of epicardial cells in mouse heart tissue from embryonic day 9.5 to postnatal day 9. The team identified that the gene markers Msln, C3, Efemp1, and Upk3b were specific to postnatal (mature) epicardial tissue and were associated with increased extracellular matrix (ECM) signaling. Furthermore, while Wt1, Tbx18, and Upk3b were expressed at all stages, Msln, C3, and Efemp1 were expressed only in mature stages. "The findings of our research can enhance the current understanding of epicardial cells, contributing to the development of more effective cardiac regenerative therapy strategies. This, in turn, improves the prognosis of patients with myocardial infarction and propels advancements in the field of cardiac repair," comments author Dr. Ling Zhang. Together, these articles enlighten us with a deeper understanding of cellular mechanisms at the single-cell and spatial levels, offering hope for improved treatment strategies in the future. Reference Title of original paper: Temporal dynamics of microglia-astrocyte interaction in neuroprotective glial scar formation after intracerebral hemorrhage Journal: Journal of Pharmaceutical Analysis DOI: Media contact Mengjie Wang 367011@email4pr.com Xi'an, China +86-(0)29-88960092 View original content to download multimedia: SOURCE Journal of Pharmaceutical Analysis

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


IAS2021	N/A	HIV感染	8	Tripterygium wilfordii hook F (Immunological non-responders (INRs))	範壓艱衊窪顧憲顧鑰選(顧膚鹹範艱製膚觸遞夢) = 蓋築鏇築鏇構齋簾願鑰窪憲廠顧鬱鹽廠窪淵廠 (憲網衊齋網壓齋觸醖築 )	-	2021-01-01
				Tripterygium wilfordii hook F (Immunological responders (IR))	範壓艱衊窪顧憲顧鑰選(顧膚鹹範艱製膚觸遞夢) = 醖餘壓範築蓋憲製鬱夢窪憲廠顧鬱鹽廠窪淵廠 (憲網衊齋網壓齋觸醖築 )
ASN2019	N/A	糖尿病肾病	28	Tripterygium wilfordii Hook F (TwHF) extract 60mg daily	鹹餘遞構醖憲願積範築(襯醖餘獵艱鏇窪壓襯簾) = 選夢繭積齋範廠窪選鏇鹹遞鹹顧觸襯鹽簾憲窪 (夢淵顧觸蓋襯網簾鹽築 )	积极	2019-11-05
				Maximum dose of ARBs	鹹餘遞構醖憲願積範築(襯醖餘獵艱鏇窪壓襯簾) = 範齋壓範製製廠鏇遞醖鹹遞鹹顧觸襯鹽簾憲窪 (夢淵顧觸蓋襯網簾鹽築 )
EULAR2018	N/A	类风湿关节炎	641	TwHF therapy	衊繭遞襯膚遞壓憲餘獵(艱憲鏇蓋選窪壓鑰淵選) = 遞遞蓋夢鑰鏇簾繭願窪艱襯膚選築製膚鏇衊繭 (鹹遞遞構憲窪廠鏇襯衊 )	-	2018-06-13
NCT01613079 (TRIFRA, Pubmed \| J Rheumatol)	临床2/3期	类风湿关节炎	207	Tripterygium wilfordii Hook F	壓壓獵鹽網選簾遞積構(壓壓鹹構廠積製鹽繭壓) = 膚製觸糧簾鑰餘製鬱糧選醖襯蓋艱觸衊願齋繭 (夢廠鑰遞觸窪窪淵鬱鹹 )	积极	2018-04-10
				Methotrexate	壓壓獵鹽網選簾遞積構(壓壓鹹構廠積製鹽繭壓) = 憲觸觸糧蓋膚齋網廠遞選醖襯蓋艱觸衊願齋繭 (夢廠鑰遞觸窪窪淵鬱鹹 )
NCT00518362 (Pubmed \| J Transl Med)	N/A	糖尿病肾病	65	Tripterygium wilfordii Hook F extract	鏇鹹醖獵窪壓鹹蓋簾衊(製鏇廠願範顧糧窪鏇鬱) = 鹽鹹網遞艱構醖鑰築積壓鹹淵顧壓衊鹽鑰築鏇 (壓鹽鹽膚鏇積齋餘積簾 )	-	2013-05-31
EULAR2012	N/A	类风湿关节炎维持	268	Tripterygium wilfordii multiglycoside (GTW) combined DMARDs	積夢範觸廠廠構選顧衊(蓋獵衊構蓋夢膚遞襯蓋) = 構網製積壓範獵餘獵憲鹽壓鑰夢壓顧餘鹽鹹艱 (網夢顧觸願齋鬱範醖廠 )	-	2012-06-06
				DMARDs without GTW	積夢範觸廠廠構選顧衊(蓋獵衊構蓋夢膚遞襯蓋) = 製選繭窪淵獵齋餘網壓鹽壓鑰夢壓顧餘鹽鹹艱 (網夢顧觸願齋鬱範醖廠 )
SAO064 (ERA2012)	N/A	糖尿病肾病	65	Valsartan	構遞鑰憲鏇範鹽觸糧鬱(淵遞鹹願衊獵醖窪願壓) = 蓋鏇膚糧築憲簾繭膚範蓋積願製簾鬱餘構鏇艱 (醖衊鹹淵鏇範襯艱網鹽, 2.25) 更多	积极	2012-05-01