European journal of pharmacology最新文献_第9页

Thrombolytic efficacy and safety of recombinant scu-PA in a rabbit retinal vein occlusion model

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology

Pub Date : 2025-01-23 DOI: 10.1016/j.ejphar.2025.177293

Dawei Yu , Hua Rong , Dongjun Xing , Liying Hu , Yinping Wen , Xiangyang Wang , Weiran Zhang , Hao Fan , Yi Zhao , Xue Gong , Lu Chen , Xiaohui Ma , Zhiqing Li

Retinal vein occlusion (RVO) has become the second most common retinal vascular disease after diabetic retinopathy. Existing therapeutic approaches, including intravitreal injection of antivascular endothelial growth factors (anti-VEGFs) and/or glucocorticoids and laser therapy, primarily address secondary macular edema and neovascularisation. However, these strategies do not address the underlying cause of the disease and may have harmful side effects. There is an urgent need for therapies that have a better prognosis and include the administration of thrombolytics at an early stage. Therefore, in the present study, we investigated the thrombolytic effect of treatment with recombinant human Single-chain urokinase-type plasminogen activators (scu-PA)and the differences in its efficacy at different doses in a rabbit RVO model. In addition, through a series of ophthalmological examinations, such as optical coherence tomography (OCT) and electrophysiology, conducted to ascertain the effects of treatment with scu-PA on the ocular fibrinolytic system, we noted a definitive safety window for the vitreous administration of scu-PA. Therefore, this study is the first to confirm that an intravenous or vitreous cavity injection of scu-PA has definitive potential for treating RVO; however, additional clinical studies are needed for further validation.

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引用次数: 0

Exploring Serotonin-1A receptor function in the effects of buspirone on cognition by molecular receptor expression and EEG analytical studies

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology

Pub Date : 2025-01-22 DOI: 10.1016/j.ejphar.2025.177275

Nazish Mustafa, Rushda Afroz, Zehra Batool, Tabinda Salman, Shazia Nawaz, Darakhshan Jabeen Haleem

Buspirone, a commonly prescribed medication for generalized anxiety disorder (GAD), is gaining attention for its narrow window of side effects such as lack of physical dependence, non-sedative properties as compared to other anxiolytic drugs. Its dose-specific therapeutic effects beyond anxiety highlights its clinical significance. Pharmacologically, buspirone activates serotonin-1A pre-synaptic autoreceptors and post-synaptic heteroreceptors which modulate serotonergic neurotransmission induced behavioral changes such as anxiolytic and nootropic effects. This study explored change in neural activity associated serotonin-1A receptors, induced by repeated administration of buspirone at specific doses (0.1 mg/kg and 3 mg/kg). Buspirone induced behavioral changes were assessed by Morris Water Maze (MWM) for cognitive functions, Elevated Plus Maze (EPM) for anxiety, RT-PCR (Reverse transcriptase-polymerase chain reaction) for 5-HT_1A receptor expression levels, and EEG (electroencephalography) analysis of neuronal electrical activity in the frontal cortex. Our findings revealed that a low dose of buspirone (0.1 mg/kg) significantly enhanced spatial learning and memory compared to high dose (3 mg/kg). Low-dose treatment elevated mRNA expression levels of serotonin-1A receptors in hippocampus and decreased in midbrain raphe nuclei, with the opposite patterns observed in the high dose. In addition, EEG spectral analysis have revealed dose specific cross coupling frequency of theta-gamma and delta-beta brain waves. At low dose (0.1 mg/kg) positive correlation of theta-gamma coupling effect and negative correlation of delta beta as decoupling effect were observed. Conversely, at high dose (3 mg/kg), results showed opposite pattern with weak correlation of theta gamma coupling effect and positive correlation of delta-beta as coupling effect. These results suggest that buspirone enhances learning and memory with differential activation of pre and postsynaptic serotonin-1A receptors, altering its expression levels which influence neural activity associated with theta-gamma and delta-beta coupling effects. It provides valuable molecular insights on clinical significance of buspirone in mitigating neuropathological disorders such as behavioral disorders and neurocognitive decline associated with disrupted regulation of serotonin-1A neurotransmission at specific doses. Our findings provide molecular insights of dose dependent therapeutic potential of buspirone against neuropathological symptoms of behavioral disorders, neurocognitive decline associated with dysregulated serotonin-1A neurotransmission.

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引用次数: 0

Corrigendum to “Isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate protects lipopolysaccharide-induced acute lung injury in mice by attenuating pyroptosis” [Eur. J. Pharmacol. 5 (2023) 175545]

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology

Pub Date : 2025-01-22 DOI: 10.1016/j.ejphar.2025.177287

Mei-Ling Zhang , Meng Wang , Jian Chen , Yan-Jie Liu , Ya-Jie Yu , Li-Min Liu , Xiao-Hui Zheng , Ying-Chou Xiao , Jun-Ming Zhang , Meng-Xue Zhu , Xian Yue , Ye Zhao , Wen Niu , Zhi-Chao Li

引用次数: 0

Memantine and amantadine KLVFF peptide conjugates: Synthesis, structure determination, amyloid-β interaction and effects on recognition memory in mice

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology

Pub Date : 2025-01-21 DOI: 10.1016/j.ejphar.2025.177274

Eleonora Bocchieri , Stefania Zimbone , Maria Laura Giuffrida , Giuseppe Di Natale , Giuseppina Sabatino , Graziella Vecchio , Giuseppe Pappalardo , Santina Chiechio

Background

Adamantane derivatives, such as memantine (Mem) and amantadine (Ada), have distinct mechanisms and therapeutic applications. Ada is primarily utilized as an antiviral and anti-Parkinson drug without significant pro-cognitive effects, Mem is effective in various clinical conditions characterized by cognitive deficits, including Alzheimer's disease. Recent evidence highlights a neuroprotective role for Aβ monomers, suggesting that preventing their aggregation into toxic oligomers could be a promising therapeutic strategy. Based on the observation that the Lys-Leu-Val-Phe-Phe (KLVFF) peptide, can block the transition of randomly coiled Aβ monomers into toxic β-sheet aggregates, two KLVFF conjugates, the Mem-Succ-KLVFF and Ada-Succ-KLVFF were investigated.

Methods

Peptides were synthesized by Microwave-Assisted Solid Phase Peptide Synthesis (MW-SPPS). Circular Dichroism (CD), Th-T fluorescence and Gel-Electrophoresis techniques were used to assess the inhibitory effect on Aβ₄₂ fibrillogenesis. The formation of inclusion complexes with β-Cyclodextrin (β-CyD) was demonstrated by NMR Spectroscopy. The Novel Object Recognition (NOR) test, followed by double-blind analysis, was applied for in vivo response to compounds administration. In vitro effects on neurons were studied by MTT assay and WB analysis, whereas HR ESI-MS allowed the molecular detection on brain homogenates.

Results

These compounds differently affect Aβ₄₂ aggregation. Mem-Succ-KLVFF, and Succ-KLVFF affect pCREB levels in differentiated SH-SY5Y, a signaling pathway involved in memory processes. In the NOR test, both Mem and KLVFF exhibited pro-cognitive effects individually and synergistically when co-administered.

Conclusion

Structure-activity relationships are discussed, integrating in vivo results, memory-related cellular pathways, and HR-ESI-MS analyses. These findings support the therapeutic potential of these compounds in preserving cognitive function.

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引用次数: 0

Platelet FcRγ inhibits tumor metastasis by preventing the colonization of circulating tumor cells

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology

Pub Date : 2025-01-21 DOI: 10.1016/j.ejphar.2025.177286

Yun Wang , Wei Tian , Rui Li , Dewang Zhou , Kaiqiang Ding , Shuang Feng , Yao Ge , Yan Luo , Zhen Chen , Hui Hou

Fc receptor γ subunit (FcRγ) activation plays a crucial role in cancer carcinogenesis. Here, we aimed to uncover the impact of FcRγ on circulating tumor cells (CTC) colonization and the underlying mechanism. FcRγ deficient (FcRγ^−/−) mice were used to investigate the functional effects of FcRγ in cancer metastasis, and the results demonstrated that FcRγ deficiency significantly promotes metastasis. The tumor metastasis effect, antiplatelet, platelet or neutrophil infusion experiments were conducted with FcRγ deficient (FcRγ^−/−) mice and wild type mice (WT), bearing B16F10 or LCC tumor cells. Blood routine test, flow cytometry, immunofluorescent staining and in vivo image were applied for analysis. Platelet adhesion and neutrophil chemotaxis were analyzed by flow cytometry and ELISA in vitro. Platelet adoptive model was used for mimicing early colonization stage. Our results indicated FcRγ deficiency significantly promoted tumor metastasis accompanied with increased number of platelet and neutrophil in the lung. Further investigation showed that FcRγ^−/− platelet infusion, rather than FcRγ^−/− neutrophils, promoted CTC colonization. While platelet inhibitor Aspirin abrogated the platelet-mediated infiltration of neutrophil in the lung. Mechanistically, platelet FcRγ deficiency facilitated the adhesion of platelets and cancer cells and increased secretion of CXCL5 and CXCL7 which triggered the platelet-induced neutrophil recruitment. In sum, our study indicates that FcRγ is a restrainer in controlling cancer metastasis through regulating the adhesion of platelets and cancer cells and recruiting more neutrophils, which provides a potential target for anti-metastatic therapies. The level of FcRγ expression in platelets could act as a novel biomarker for cancer metastasis.

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引用次数: 0

Vitamin K2 protects against D-galactose induced ageing in mice 维生素K2可以防止d -半乳糖引起的小鼠衰老。

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology

Pub Date : 2025-01-19 DOI: 10.1016/j.ejphar.2025.177277

Kaberi Chatterjee , Papiya Mitra Mazumder , Sugato Banerjee

Background

Ageing is a complex process characterized by the gradual deterioration of physiological functions, often leading to a diminished quality of life. Dementia is among the prominent indicators of ageing characterized by cognitive impairment. Animal studies employing D-galactose have provided insights into the mechanisms underlying cognitive decline and neuronal degeneration, resembling features of human brain ageing while Vitamin K2, known for its diverse physiological functions, also have neuroprotective potential. Here we study the effect of Vitamin K2 in D-galactose induced ageing in mice.

Methods

Ageing was induced in adult Swiss albino mice using D-galactose via subcutaneous (SC) route for 45 days while one group of animals received Vitamin K2 (MK-7) via oral gavage during last 21 days. Then different behavioral studies, including the elevated plus maze, Morris water maze, passive avoidance and novel object recognition test were performed to measure cognitive changes, followed by measuring AChE, corticosterone (plasma), oxidative stress parameters (SOD, GSH, MDA) and pro-inflammatory markers (TNFα, IL1β) in hippocampal homogenates. Histopathology of the hippocampal sections were performed to measure neuronal density.

Results

Vitamin K2, treatment reversed D-galactose associated memory changes. In the biochemical studies, plasma corticosterone was reduced while hippocampal AChE, MDA and pro-inflammatory cytokines were reduced after Vitamin K2 treatment. The antioxidants like SOD and GSH were improved in Vitamin K2 treated animal brain. The hippocampal neuronal density increased in treatment group compared to D-galactose induced aged animals.

Conclusion

Treatment with Vitamin K2 (MK-7) partially reversed cognitive decline associated with ageing, highlighting its potential as a therapeutic intervention for age associated cognitive decline.

背景：衰老是一个复杂的过程，其特征是生理功能逐渐退化，往往导致生活质量下降。痴呆症是以认知障碍为特征的衰老的突出指标之一。利用d -半乳糖进行的动物研究为认知能力下降和神经元退化的潜在机制提供了见解，类似于人类大脑衰老的特征，而维生素K2因其多种生理功能而闻名，也具有神经保护潜力。本文研究了维生素K2对d -半乳糖诱导小鼠衰老的影响。方法：采用d -半乳糖皮下诱导成年瑞士白化小鼠衰老45 d，另一组小鼠在最后21 d内口服维生素K2 （MK-7）。然后通过不同的行为实验，包括升高+迷宫、Morris水迷宫、被动回避和新物体识别测试来测量认知变化，随后测量海马均质液中AChE、血浆皮质酮、氧化应激参数（SOD、GSH、MDA）和促炎标志物（TNFα、il - 1β）。海马切片进行组织病理学检查，测定神经元密度。结果：维生素K2治疗逆转了d -半乳糖相关的记忆变化。在生化研究中，维生素K2治疗后血浆皮质酮降低，海马AChE、MDA和促炎细胞因子降低。在维生素K2处理的动物大脑中，SOD和GSH等抗氧化剂得到改善。与d -半乳糖诱导的老龄动物相比，治疗组海马神经元密度增加。结论：维生素K2 （MK-7）治疗部分逆转了与衰老相关的认知能力下降，突出了其作为年龄相关认知能力下降的治疗干预的潜力。

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引用次数: 0

Genistein: A promising ally in combating neurodegenerative disorders 染料木素：对抗神经退行性疾病的有希望的盟友。

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology

Pub Date : 2025-01-17 DOI: 10.1016/j.ejphar.2025.177273

Diksha Sharma , Varinder Singh , Amit Kumar , Thakur Gurjeet Singh

Neurodegenerative disorders arise when nerve cells in the brain or peripheral nervous system gradually lose functions and eventually die. Although certain therapies may alleviate some of the physical and mental symptoms associated with neurodegenerative disorders, hence slowing their progression, but no sure-shot treatment is currently available. It was shown that the rise in life expectancy and the number of elderly people in the community led to an increasing trend in the incidence and prevalence of neurodegenerative disease. Phytomolecules are demonstrating their effectiveness in combating, regression, and delaying various diseases. Genistein is one of soy isoflavone with antioxidant, anti-inflammatory, and estrogenic effects. Researchers demonstrated that Genistein treatment significantly reduced hyperglycemia, improved cognitive performance by modulating acetylcholinesterase activity and oxidative stress, and alleviated neuroinflammatory conditions in mice. This paper evaluates (in vivo and in vitro) various molecular targets of isoflavones and their ability to effectively counter several neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases and amyotrophic lateral sclerosis. In this review, we aim to provide an overview of the role that genistein plays in delaying the development of neurodegenerative disorders.

当大脑或周围神经系统中的神经细胞逐渐失去功能并最终死亡时，神经退行性疾病就会出现。虽然某些治疗方法可以减轻与神经退行性疾病相关的一些身体和精神症状，从而减缓其进展，但目前尚无可靠的治疗方法。结果表明，预期寿命的延长和社区老年人数量的增加导致神经退行性疾病的发病率和流行率呈上升趋势。植物分子在对抗、恢复和延缓各种疾病方面显示出其有效性。染料木素是大豆异黄酮中的一种，具有抗氧化、抗炎和雌激素的作用。研究人员证明染料木素治疗可显著降低高血糖，通过调节乙酰胆碱酯酶活性和氧化应激改善认知能力，并减轻小鼠的神经炎症状况。本文评估了（体内和体外）异黄酮的各种分子靶点及其有效对抗几种神经退行性疾病（如帕金森病、阿尔茨海默病、亨廷顿病和肌萎缩侧索硬化症）的能力。在这篇综述中，我们旨在概述染料木素在延缓神经退行性疾病发展中的作用。

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引用次数: 0

Actichinone, a new ursane triterpenoid from Actinidia chinensis roots, ameliorates NAFLD via the AMPK and NF-κB pathways Actichinone是一种从猕猴桃根中提取的新型三萜，可通过AMPK和NF-κB途径改善NAFLD。

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology

Pub Date : 2025-01-17 DOI: 10.1016/j.ejphar.2025.177276

Xinhua Li , Yuanlong Zhang , Leiqing Chen , Xiao Xu , Xiaohong Ma , Shuying Lou , Ziqiang Zou , Chenjing Wang , Bing Jiang , Yunrui Cai , Yu Qi , Yiyuan Xi , Min Zhao , Pengcheng Yan

A new ursane triterpenoid, actichinone (3-oxo-2α,24-dihydroxyurs-12-en-28-oic acid, 1), was isolated from the roots of a kiwi plant Actinidia chinensis Planch, together with 18 known triterpenoids (2–19). The structure of actichinone (1) was established by extensive spectroscopic analysis. Actichinone (1) showed the most potent lipid-lowering activity in the oleic acid (OA)-induced primary mouse hepatocytes and the structure-activity relationships (SARs) were analyzed. Chemical semi-synthesis of actichinone (1) was achieved by selective oxidation of the major compound 2. Actichinone (1) exhibited significant alleviation of non-alcoholic fatty liver disease (NAFLD) in a high-fat with methionine and choline deficiency diet (HFMCD)-fed mice model, by regulating lipid accumulation and inflammatory response probably via the AMPK/SREBP-1c/PPAR-α and IKK/IκB/NF-κB signaling pathways. This study provides a promising lead compound and a new insight into the development of novel anti-NAFLD agents based on the pentacyclic triterpenoid family, and is expected to promote the high value-added comprehensive application of the A. chinensis plants.

从猕猴桃植物猕猴桃（Actinidia chinensis Planch）的根部分离到一个新的熊类三萜actichinone (3-oxo-2α,24- dihydroxyours -12-en-28-oic acid, 1)，并分离到18个已知的三萜（2-19）。通过广泛的光谱分析确定了actichinone(1)的结构。Actichinone(1)在油酸（OA）诱导的小鼠原代肝细胞中表现出最强的降脂活性，并对其构效关系（SARs）进行了分析。通过选择性氧化主要化合物2，实现了actichinone(1)的化学半合成。Actichinone(1)可能通过AMPK/SREBP-1c/PPAR-α和IKK/ i -κB /NF-κB信号通路调节脂质积累和炎症反应，在高脂肪蛋氨酸和胆碱缺乏饮食（HFMCD）喂养的小鼠模型中显示出非酒精性脂肪性肝病（NAFLD）的显著缓解。本研究为基于五环三萜家族的新型抗nafld药物的开发提供了有前景的先导化合物和新思路，有望促进金合藤植物的高附加值综合应用。

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引用次数: 0

VDAC1-NF-κB/p65-mediated S100A16 contributes to myocardial ischemia/reperfusion injury by regulating oxidative stress and inflammatory response via calmodulin/CaMKK2/AMPK pathway VDAC1-NF-κB/p65介导的S100A16通过Calmodulin/CaMKK2/AMPK通路调节氧化应激和炎症反应，参与心肌缺血/再灌注损伤。

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology

Pub Date : 2025-01-15 DOI: 10.1016/j.ejphar.2024.177158

Congna Zi , Xian Ma , Maodong Zheng , Ying Zhu

Myocardial injury triggers intense inflammatory reactions and oxidative stress responses. S100 calcium-binding protein A16 (S100A16), a multi-functional calcium (Ca²⁺)-binding protein, participates in inflammatory responses and contributes to ischemia/reperfusion (I/R) injury. Nevertheless, the precise mechanism by which S100A16 operates in myocardial I/R injury remains uncertain. Cardiac I/R injury was produced by ligation/release of the left anterior descending artery, and mouse cardiac cells were subjected to hypoxia/reoxygenation (H/R) to determine the biological effects in vitro. We demonstrated that S100A16 was upregulated in the ischemic hearts and cardiac cells after I/R and H/R injury. Adenovirus-mediated S100A16 inhibition led to a considerable improvement in cardiac function with a reduced infarct size, accompanied by a reduction in cardiomyocyte apoptosis. Similar effects of S100A16 inhibition on inflammation and reactive oxygen species (ROS) production were observed in cultured cardiomyocytes. Importantly, we showed that I/R and H/R treatment upregulated the expression of voltage-dependent anion channel 1 (VDAC1), which subsequently activated NF-κB/p65 to facilitate the binding of NF-κB/p65 to the S100A16 promoter, thereby activating the transcription and expression of S100A16. Mechanically, S100A16 responded to increasing Ca²⁺ and interacted with calmodulin (CaM) to regulate the activation of calcium/calmodulin-dependent protein kinase 2 (CAMKK2)/AMPK pathway. In conclusion, VDAC1 sustained the NF-κB p65 pathway activation to elicit increased S100A16 expression, contributing to myocardial damage and heart failure post-I/R via the CaM/CaMKK2/AMPK pathway. This study revealed a crucial role of the VDAC1-S100A16 axis in the process of myocardial I/R injury, providing novel molecular targets for the treatment of cardiac conditions associated with I/R injury.

心肌损伤引发强烈的炎症反应和氧化应激反应。S100钙结合蛋白A16 （S100A16）是一种多功能钙（Ca2+）结合蛋白，参与炎症反应，参与缺血/再灌注（I/R）损伤。然而，S100A16在心肌I/R损伤中的确切作用机制尚不清楚。通过结扎/释放左前降支造成心脏I/R损伤，并对小鼠心肌细胞进行缺氧/再氧化（H/R），以确定体外生物学效应。我们发现，缺血心脏和心肌细胞在I/R和H/R损伤后，S100A16表达上调。腺病毒介导的S100A16抑制导致心肌功能的显著改善，梗死面积减少，同时心肌细胞凋亡减少。在培养的心肌细胞中，S100A16对炎症和活性氧（ROS）产生的抑制作用也类似。重要的是，我们发现I/R和H/R处理上调了电压依赖性阴离子通道1 （VDAC1）的表达，VDAC1随后激活NF-κB/p65，促进NF-κB/p65与S100A16启动子的结合，从而激活S100A16的转录和表达。机械上，S100A16响应Ca2+的增加，并与钙调素（CaM）相互作用，调节钙/钙调素依赖性蛋白激酶2 (CAMKK2)/AMPK途径的激活。综上所述，VDAC1维持NF-κB p65通路激活，引发S100A16表达增加，通过CaM/CaMKK2/AMPK通路参与i /R后心肌损伤和心力衰竭。本研究揭示了VDAC1-S100A16轴在心肌I/R损伤过程中的重要作用，为I/R损伤相关心脏疾病的治疗提供了新的分子靶点。

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引用次数: 0

Type I interferon-stimulated genes predict clinical response to belimumab in systemic lupus erythematosus I型干扰素刺激基因可预测系统性红斑狼疮患者对贝利木单抗的临床反应。

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology

Pub Date : 2025-01-15 DOI: 10.1016/j.ejphar.2024.177204

Hanchao Li, Bomiao Ju, Jing Luo, Li Zhu, Jing Zhang, Nan Hu, Lingfei Mo, Yanhua Wang, Juan Tian, Qian Li, Xinru Du, Xinyi Liu, Lan He

The type I interferon (IFN-I) response is crucial in systemic lupus erythematosus (SLE). The mRNA level of interferon-stimulated genes (ISGs) is widely used for evaluating the activity of IFN in SLE. However, the character of ISGs in belimumab-treated SLE patients has not be reported. In this study, we enrolled 53 SLE patients undergoing belimumab treatment and assessed their clinical responses at 3, 6, and 12 months. The expression levels of 25 ISGs in Peripheral blood mononuclear cells (PBMCs) were quantified at baseline and at 3 months using quantitative real-time PCR. Using Least absolute shrinkage and selection operator (LASSO)-logistic regression, five genes (CXCL10, EPSTI1, HECR6, IFI27, IFIH1) were identified to predict belimumab efficacy. The IFN signature score, a multivariate logistic regression model based on the change rates of these genes, positively predicted the SLE responder index (SRI) at 12 months, with an area under curve of 0.940 in receiver operating characteristic and favorable outcomes in decision curve analysis. Patients with an IFN signature score ≥0 had higher SRI response rates, better clinical markers (including SLE disease activity index 2000 scores, anti-dsDNA, IgG levels, daily doses of prednisone, and higher complement C3 and C4 levels), and faster B cell decline than those with scores <0. In conclusion, after 3 months of belimumab treatment, the expression levels of IFN-I-inducible genes varied, and the IFN signature score reliably forecasted the SRI response at 6 and 12 months.

I型干扰素（IFN-I）应答在系统性红斑狼疮（SLE）中至关重要。干扰素刺激基因（ISGs）的mRNA水平被广泛用于评估SLE中IFN的活性。然而，在贝莫单抗治疗的SLE患者中，isg的特征尚未报道。在这项研究中，我们招募了53名接受贝利单抗治疗的SLE患者，并在3个月、6个月和12个月时评估他们的临床反应。在基线和3个月时，用实时荧光定量PCR方法定量25种ISGs在外周血单个核细胞（PBMCs）中的表达水平。使用最小绝对收缩和选择算子(LASSO)-逻辑回归，确定了五个基因（CXCL10, EPSTI1, HECR6, IFI27, IFIH1）来预测贝利单抗的疗效。基于这些基因变化率的多变量logistic回归模型IFN特征评分正预测SLE 12个月的应答指数（SRI），受者工作特征曲线下面积为0.940，决策曲线分析结果良好。IFN特征评分≥0的患者SRI反应率更高，临床指标更好（包括SLE疾病活动性指数2000评分、抗dsdna、IgG水平、泼尼松日剂量、补体C3和C4水平较高），B细胞下降速度快于评分< 0的患者。综上所述，在贝利单抗治疗3个月后，IFN- i诱导基因的表达水平发生了变化，IFN特征评分可靠地预测了6个月和12个月时的SRI反应。

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引用次数: 0