Clinical evaluation of the 3 allergens: Methyldibromoglutharonitrile, Parthenolide and Goldsodiumthiosulphate for "TRUE Test Panel 3" - a phase II, dose-response study.

开始日期2005-01-26

申办/合作机构

Mekos Laboratories AS

100 项与 Parthenolide 相关的临床结果

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100 项与 Parthenolide 相关的转化医学

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100 项与 Parthenolide 相关的专利（医药）

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1,211

项与 Parthenolide 相关的文献（医药）

2026-02-01·NEUROPHARMACOLOGY

Parthenolide attenuates neuroinflammation by targeting NLRP3 inflammasome & mitochondrial dysfunction in experimental diabetic neuropathy

Article

作者: Kumar, Ashutosh ; Pal, Anubroto ; Babu, S.Sarath ; Jain, Rachit ; Sharan, Lokesh ; Banerjee, Sugato

BACKGROUND:

Diabetic Neuropathy (DN) is one of the most common complications of diabetes induced by intricate mechanisms including oxidative stress, mitochondrial dysfunction, and chronic inflammation, primarily driven by NLRP3 inflammasome activation. Current treatments provide mostly symptomatic relief, necessitating the quest for therapies addressing underlying mechanisms of diabetic neuropathy.

OBJECTIVE:

This study evaluated the therapeutic potential of Parthenolide, a sesquiterpene lactone with anti-inflammatory and mitochondrial protective properties, in mitigating diabetic neuropathy.

METHODS:

Molecular docking studies assessed Parthenolide binding with NLRP3, DRP1, and OPA1. High-glucose-exposed SH-SY5Y cells were used to explore Parthenolide effects on oxidative stress, mitochondrial function, and inflammasome activity. In vivo, diabetes in rats induced with Streptozotocin (55 mg/kg) were treated with Parthenolide at 0.25 mg/kg and 0.5 mg/kg for two weeks. Neurobehavioral tests, nerve conduction studies, and analyses of oxidative stress markers, mitochondrial integrity, and inflammation were conducted.

RESULTS:

Parthenolide exhibited strong binding affinities with NLRP3 (-8.3 kcal/mol), DRP1 (-7.4 kcal/mol), and OPA1 (-6.7 kcal/mol). In vitro, Parthenolide reduced ROS levels, restored mitochondrial membrane potential, and enhanced mitochondrial protective proteins (SIRT1, FIS1, OPA1) while suppressing NLRP3 activation. In vivo, Parthenolide significantly improved nerve function (motor nerve conduction velocity and nerve blood flow), and alleviated sensorimotor changes. It enhanced antioxidant defences (GSH, SOD2), upregulated mitochondrial regulators (OPA1, PGC1α, NRF1), and reduced oxidative damage (MDA). Parthenolide also lowered inflammasome markers (NLRP3, ASC, and Caspase-1) and pro-inflammatory cytokines, including TNF-α, IL-6, IL-1β, and IL-18.

CONCLUSION:

Parthenolide showed neuroprotective potential against experimental DN by reducing oxidative stress, mitochondrial dysfunction, and inflammasome activation.

2026-01-01·JOURNAL OF ETHNOPHARMACOLOGY

Pi Ji Pills reshape the pancreatic cancer immune microenvironment and enhance the efficacy of gemcitabine through dual mechanisms of PI3K/AKT pathway blockade and NETs inhibition

Article

作者: Li, Yi ; Liu, Fudong ; Jiang, Xiaochen ; Pang, Bo ; Shen, Qian ; Lin, Hai ; Zhang, Chuanlong

ETHNOPHARMACOLOGICAL RELEVANCE:

Pancreatic cancer presents a significant challenge in clinical treatment. Pi Ji Pills (PJP) is a compound formula made up of seven traditional Chinese medicinal herbs. It has demonstrated positive clinical outcomes in the treatment of pancreatic cancer, and its potential pharmacological mechanisms warrant further investigation.

AIM OF THE STUDY:

This study aimed to identify the possible mechanisms by which PJP inhibits pancreatic cancer, followed by experimental verification and more profound exploration.

MATERIALS AND METHODS:

An in vivo pancreatic cancer xenograft model was established to observe the effect and safety of PJP on tumor growth. The SW1990 cells were cultured to investigate the intervention effects of PJP-containing serum on the malignant biological behavior of pancreatic cancer cells. Subsequently, network pharmacology analysis was employed to explore the potential mechanisms. Furthermore, both in vivo and in vitro experiments were conducted to validate the core pathways and targets. An in-depth exploration was performed, with a focus on the role of neutrophil extracellular traps (NETs) in the inhibition of pancreatic cancer by PJP.

RESULTS:

PJP inhibits tumor growth, and its combination with gemcitabine exhibits enhanced inhibitory effects, partially alleviating immune suppression. PJP-containing serum was found to inhibit the malignant biological behavior of SW1990 cells. naringenin, atractylenolide I, isoalantolactone, curcumenol, parthenolide, and arglabin are the main active components of PJP. PJP inhibits PI3K/AKT pathway, key to its anti-pancreatic cancer effects. Additionally, PJP's treatment inhibited SW1990 cell proliferation indenpence of reducing IL-8 and downregulating NETs-related protein expression in the co-culture system.

CONCLUSIONS:

PJP combats pancreatic cancer and enhances gemcitabine efficacy by remodeling the immunosuppressive tumor microenvironment. This anticancer effect may be attributed to a dual-target mechanism involving suppression of the PI3K/AKT pathway and regulation of NETs formation in the tumor microenvironment.

2026-01-01·BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Exploring shared diagnostic genes and molecular mechanisms in multiple sclerosis and psoriasis through bioinformatics analysis and machine learning

Article

作者: Duan, Zhenfei ; Yang, Fangjie ; Li, Xinmin ; Wang, Ye ; Liu, Feizhou ; Guo, Pengxue ; Zhang, Yasu ; Wang, Jing ; Bi, Mengyao ; Ren, Chunlin ; Kong, Yuting

BACKGROUND:

Multiple sclerosis (MS) and psoriasis are both immune-mediated inflammatory diseases. Previous studies have reported comorbidity between MS and psoriasis, but the underlying mechanisms remain unclear. This study aims to elucidate the shared pathogenesis and core genes underlying MS and psoriasis.

METHODS:

Microarray data for MS and psoriasis were downloaded from the GEO database. Differentially expressed genes (DEGs) were analyzed using "limma" package. Functional enrichment analyses were conducted to elucidate biological functions of common DEGs. PPI analysis and machine learning were used to select core genes, and the diagnostic efficacy was evaluated using nomograms. Single-cell analysis and CeRNA network construction were performed. Immune cell infiltration was assessed by single-sample gene set enrichment. Drug prediction, molecular docking and molecular dynamics (MD) simulations identified potential therapeutic drugs.

RESULTS:

89 DEGs identified in MS and psoriasis datasets were enriched in the NOD-like receptor, NF-κB, and JAK-STAT signaling pathways. IL7R and IRF8 were determined as core genes with good diagnostic performance (AUC >0.7). Immune infiltration analysis showed dysregulation of activated CD4 T cells, activated dendritic cells, and gamma delta T cells in both diseases. Single-cell analysis suggested that IL7R and IRF8 were mainly expressed in immune cells. Molecular docking and MD simulations revealed that parthenolide is a potential therapeutic agent.

CONCLUSION:

This study highlights the critical role of immune dysregulation and chronic inflammation in MS and psoriasis comorbidity. IL7R and IRF8 were identified as core genes and novel intervention targets for both diseases. These findings provide new insights for future research.

项与 Parthenolide 相关的新闻（医药）

2025-12-27

·食品生物技术与食品营养

基于活性的蛋白质分析（ABPP）在抗菌靶点鉴定中的方法学进展与应用范式

01 研究内容本文系统评述了活性蛋白质分析（Activity-Based Protein Profiling, ABPP）技术在抗菌药物靶点发现中的最新研究动态与方法学演进。ABPP作为化学蛋白质组学的关键分支，通过设计功能化小分子探针，实现对活性位点导向的蛋白质标记与鉴定，为目标去卷积与作用机制解析提供了直接证据。 ABPP 探针通常由三部分构成：①反应基团，如共价弹头或光亲和基团；②连接链，用于空间调控与物化性质优化；③报告标签，如生物素或荧光基团，用于后续富集或检测。借助点击化学（如CuAAC），可实现“两步法”标记，显著提高活细胞兼容性。优势：①在体标记能力：维持蛋白质天然构象及细胞内环境；②功能选择性：仅标记处于活性状态的酶或结合蛋白；③高灵敏度：可鉴定低丰度靶点及瞬时相互作用。关键词：活性蛋白质分析；靶点鉴定；抗菌化合物；化学蛋白质组学；点击化学；耐药性研究 02 应用实例解析 01 天然产物靶点发现如parthenolide探针鉴定出Xoo呼吸链复合物 I/II 关键亚基，揭示其通过诱导氧化应激发挥抗菌活性的分子机制。（图1）图1. (A) 探针捕获了Xoo呼吸链中的两个重要亚基（复合体I的NuoF和复合体II的SdhB）并经LCMS/MS鉴定。(B) PTL 对Xoo的作用机制。二氢香豆素可以直接与NuoF和SdhB结合，这会损害呼吸链中复合体I和II的功能，导致ROS积累；同时，PTL会导致Xoo中GSH的消耗，极大地削弱其清除ROS的能力，从而抑制细菌生长。 02 合成化合物靶点去卷积如磺酰类候选药物JHXJZ通过ABPP技术发现其作用于二氢硫辛酰胺琥珀酰转移酶（DLST），首次将抗菌活性与TCA循环调控相关联。（图2）图2. (A)JHXJZ的靶点检测与鉴定以及(B)JHXJZ抑制DLST，即2-酮戊二酸脱氢酶复合物的结构和催化核心。该复合物负责催化2-酮戊二酸氧化脱羧生成琥珀酰辅酶A，并在三羧酸循环（TCA）中的能量产生过程中充当关键的调节酶。 03 耐药菌研究针对 MRSA，OXA 类探针揭示其多靶点抑制模式，包括 FabH、FphC等关键酶，为克服耐药性提供新视角。 03 结语当前ABPP已与多种蛋白质组学策略深度融合，结合SILAC、TMT等同位素标记，实现靶点占有率定量分析；FluoPol-ABPP实现酶活性抑制剂的高通量筛选；isoTOP-ABPP可精确识别半胱氨酸等亲核残基的修饰位点。目前，探针设计仍存在合成难度与活性保持的平衡问题，在细菌系统中的渗透性与选择性需进一步优化，未来可拓展至植物病原菌及肠道微生物等复杂体系，新型点击化学有望提升活体标记效率与生物相容性。 ABPP通过将小分子工具转化为化学探针，实现了在功能层面系统性解析药物－靶点互作，已成为抗菌药物机制研究与靶点发现的关键使能技术。随着化学蛋白质组学方法与生物信息学的持续整合，ABPP有望在耐药性研究与创新药物研发中发挥更重要的作用。原文链接扫描下方二维码即可获得： ☆ END ☆ 免责声明：文章仅供学术交流，如有侵权，请联系删除。

微生物疗法

2025-12-16

·百度百家

以制剂为核心，中新康明助力结直肠癌治疗制剂解决方案

近年来，结直肠癌（ColorectalCancer,CRC）的发病率和死亡率在全球范围内持续攀升，已成为威胁人类健康的重大公共卫生问题。尽管免疫检查点抑制剂等新型疗法在部分患者中取得显著疗效，但多数CRC患者仍面临治疗耐药、T细胞耗竭及肿瘤微环境免疫抑制等挑战。在此背景下，探索能够同时诱导肿瘤细胞死亡并重塑抗肿瘤免疫微环境的创新策略，成为当前研究的重要方向。近期，一项发表于《JournalofNanobiotechnology》的研究揭示了天然化合物小白菊内酯（Parthenolide,PTL）在结直肠癌治疗中的双重作用机制：一方面通过诱导程序性坏死（necroptosis），直接杀伤肿瘤细胞；另一方面通过改善CD8+T细胞耗竭状态，增强抗肿瘤免疫应答。更重要的是，研究团队通过构建靶向脂质体（TCP-1-PTL-LNPs），显著提升了PTL的肿瘤靶向性和治疗效果，为临床转化提供了有力支撑。一、结直肠癌治疗新方向：从细胞死亡到免疫重塑该研究首先通过CCK-8实验证实，PTL可剂量依赖性地抑制多种结直肠癌细胞系（包括SW480、DLD1、HCT116和MC38）的增殖。进一步机制研究表明，PTL诱导的细胞死亡可被程序性坏死抑制剂Nec-1显著逆转，且WesternBlot检测显示RIP3与MLKL蛋白磷酸化水平显著升高——这是程序性坏死通路激活的关键标志。更引人注目的是，在MC38皮下瘤小鼠模型中，高剂量PTL（15mg/kg）不仅显著抑制肿瘤生长，还显著增加了肿瘤组织中CD3+CD8+T细胞的浸润（P<0.01）。流式分析进一步发现，PTL处理后，PD-1hiTIM-3+耗竭型T细胞比例上升，而PD-1loTIM-3−效应型T细胞比例下降，提示PTL可能通过调节T细胞分化状态，延缓或逆转T细胞耗竭进程。在更具临床相关性的原位移植瘤模型中，研究团队开发的TCP-1靶向脂质体包裹PTL（TCP-1-PTL-LNPs）展现出更强的抗肿瘤效果。免疫组化结果显示，高剂量靶向脂质体组肿瘤组织中CD8+T细胞浸润显著高于游离PTL组（P<0.01），充分证明了纳米递送系统在提升药物靶向性与免疫激活能力方面的巨大潜力。二、中新康明：赋能结直肠癌创新疗法的CDMO合作伙伴作为国内领先的mRNA与脂质纳米颗粒（LNP），中新康明始终致力于为全球科研机构与生物制药企业提供从原料合成、制剂开发到分析检测的一站式CDMO服务。针对结直肠癌等实体瘤的靶向治疗需求，我们可提供：高纯度LNP核心脂质原料：包括DOTMA、DOTAP、DSPC、胆固醇及PEG化脂质，严格符合GMP标准；定制化LNP处方开发：支持mRNA、siRNA、小分子药物（如PTL）的包封与靶向修饰（如TCP-1肽段偶联）；全面的理化与生物评价服务：粒径/Zeta电位、包封率、体外释放、细胞摄取、流式细胞术（T细胞表型分析）、免疫组化、WesternBlot、ROS/LDH检测等；动物模型药效学支持：包括皮下瘤、原位瘤、PDX模型构建及免疫微环境分析。三、技术优势：从“精准递送”到“免疫激活” 中新康明依托自主知识产权的微流控混合平台与双乳化工艺优化体系，可实现LNP粒径均一（PDI<0.15）、包封率>90%、批次间高度稳定。同时，我们具备成熟的表面功能化技术，可高效偶联肿瘤靶向配体（如肽、抗体片段），显著提升药物在肿瘤部位的富集。在本研究中所采用的TCP-1-PTL-LNPs，正是基于类似技术路径开发而成。其成功验证了“程序性坏死诱导+免疫微环境重塑+靶向递送”三位一体的治疗策略可行性，也为后续联合免疫检查点抑制剂（如抗PD-1）提供了理论基础。四、成功案例：助力客户发表高水平研究成果中新康明已为多家高校、医院及Biotech公司提供LNP相关CDMO服务，支持其在肿瘤免疫治疗、基因编辑、传染病疫苗等领域的研究。例如，某知名高校团队利用我们提供的DOTMA/PLGA杂化纳米粒成功递送mRNA至树突状细胞（DC2.4），实现高效转染与实时成像。五、综述：中新康明——您值得信赖的LNP CDMO伙伴面对结直肠癌治疗的复杂挑战，单一机制药物往往难以奏效。而像PTL这样兼具直接杀伤与免疫调节功能的天然产物，配合先进纳米递送系统，正代表了未来精准免疫治疗的新范式。中新康明将持续深耕LNP技术平台，以高标准原料、灵活定制能力、全流程质控体系，助力全球科研与产业界加速创新疗法从实验室走向临床。无论是基础机制研究、药效验证，还是IND申报前的CMC开发，我们都愿成为您最坚实的后盾。

免疫疗法信使RNAsiRNA

2025-12-16

·PMLiVE

Researchers at University of Geneva develop test platform for cancer treatments

Researchers at the University of Geneva (UNIGE) have developed in vitro models of the kidneys, liver and heart for the purposes of testing the effects of new cancer treatments on healthy tissue. Acquired resistance, when tumours develop resistance to cancer treatments, represents a major challenge in oncology. While combination therapies have shown great promise in overcoming that resistance, they are often highly toxic to healthy organs and tissues. The UNIGE team’s new laboratory platform allows for the rapid testing of drug effects without the need for animal models. Patrycja Nowak-Sliwinska, associate professor in the School of Pharmaceutical Sciences at the UNIGE Faculty of Science, said: “This platform models the human kidney, heart and liver in vitro, as clusters of cells derived from human tissue. “[It enables us to] study how new drug combinations interact with these organs and then decide whether it is justified to move on to in vivo testing in humans or animals.” The research, published in Biomedicine and Pharmacotherapy, focused on the kidneys, liver and heart – three organs that are particularly sensitive to combination therapies. Scientists from the School of Pharmaceutical Sciences, in collaboration with the UNIGE Faculty of Medicine and Geneva University Hospital (HUG), tested two drug combinations currently in development, C2 (erlotinib HCl, dasatinib, tubacin, tacedinaline) and REMP (erlotinib HCl, parthenolide, metformin HCl, RAPTA-C). In one notable finding, they discovered that C2 demonstrated significant liver toxicity, showing that in vivo testing may not be appropriate for this combination. Another advantage of this new approach is that it takes only two weeks to obtain results, whereas animal models take around ten weeks or more. The researchers noted: “In addition to saving a significant amount of time, this approach is fully in line with the 3R principle, which aims to ‘reduce’, ‘replace’ and ‘refine’ the use of animal models in research.” The next step in the research will be to extend the model to other treatment-sensitive organs. The researchers hope to one day move beyond standard cell lines and instead use patient-derived cells, allowing drug combinations to be tested for toxicity in a personalised context.