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Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases 用迷幻药预防痴呆症?迷幻药在改变重度抑郁症和神经退行性疾病相关机制方面的潜在作用
IF 13.5 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-06 DOI: 10.1016/j.pharmthera.2024.108641
Zarah R. Haniff , Mariia Bocharova , Tim Mantingh , James J. Rucker , Latha Velayudhan , David M. Taylor , Allan H. Young , Dag Aarsland , Anthony C. Vernon , Sandrine Thuret

Major depression is an established risk factor for subsequent dementia, and depression in late life may also represent a prodromal state of dementia. Considering current challenges in the clinical development of disease modifying therapies for dementia, the focus of research is shifting towards prevention and modification of risk factors to alter the neurodegenerative disease trajectory. Understanding mechanistic commonalities underlying affective symptoms and cognitive decline may reveal biomarkers to aid early identification of those at risk of progressing to dementia during the preclinical phase of disease, thus allowing for timely intervention. Adult hippocampal neurogenesis (AHN) is a phenomenon that describes the birth of new neurons in the dentate gyrus throughout life and it is associated with spatial learning, memory and mood regulation. Microglia are innate immune system macrophages in the central nervous system that carefully regulate AHN via multiple mechanisms. Disruption in AHN is associated with both dementia and major depression and microgliosis is a hallmark of several neurodegenerative diseases.

Emerging evidence suggests that psychedelics promote neuroplasticity, including neurogenesis, and may also be immunomodulatory. In this context, psilocybin, a serotonergic agonist with rapid-acting antidepressant properties has the potential to ameliorate intersecting pathophysiological processes relevant for both major depression and neurodegenerative diseases. In this narrative review, we focus on the evidence base for the effects of psilocybin on adult hippocampal neurogenesis and microglial form and function; which may suggest that psilocybin has the potential to modulate multiple mechanisms of action, and may have implications in altering the progression from major depression to dementia in those at risk.

重度抑郁是继发痴呆症的既定风险因素,晚年抑郁也可能是痴呆症的前兆状态。考虑到目前临床开发痴呆症疾病调节疗法所面临的挑战,研究重点正转向预防和改变风险因素,以改变神经退行性疾病的发展轨迹。了解情感症状和认知能力下降的机理共性可能会发现一些生物标志物,有助于在疾病的临床前阶段及早识别那些有可能发展成痴呆症的人,从而进行及时干预。成人海马神经发生(AHN)是一种描述齿状回终生诞生新神经元的现象,它与空间学习、记忆和情绪调节有关。小胶质细胞是中枢神经系统中的先天性免疫系统巨噬细胞,它通过多种机制仔细调节 AHN。AHN 的破坏与痴呆症和重度抑郁症有关,而小胶质细胞病变则是多种神经退行性疾病的标志。在这种情况下,迷幻药作为一种具有速效抗抑郁特性的血清素能激动剂,有可能改善与重度抑郁症和神经退行性疾病相关的交叉病理生理过程。在这篇叙述性综述中,我们将重点关注迷幻药对成人海马神经发生和小胶质细胞形态与功能影响的证据基础;这可能表明迷幻药具有调节多种作用机制的潜力,并可能对改变高危人群从重度抑郁症发展为痴呆症的过程产生影响。
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引用次数: 0
Therapeutic targeting of DNA methylation alterations in cancer 针对癌症 DNA 甲基化改变的治疗方法
IF 13.5 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-01 DOI: 10.1016/j.pharmthera.2024.108640
Abigail V. Lee , Kevin A. Nestler , Katherine B. Chiappinelli

DNA methylation is a critical component of gene regulation and plays an important role in the development of cancer. Hypermethylation of tumor suppressor genes and silencing of DNA repair pathways facilitate uncontrolled cell growth and synergize with oncogenic mutations to perpetuate cancer phenotypes. Additionally, aberrant DNA methylation hinders immune responses crucial for antitumor immunity. Thus, inhibiting dysregulated DNA methylation is a promising cancer therapy. Pharmacologic inhibition of DNA methylation reactivates silenced tumor suppressors and bolster immune responses through induction of viral mimicry. Now, with the advent of immunotherapies and discovery of the immune-modulatory effects of DNA methylation inhibitors, there is great interest in understanding how targeting DNA methylation in combination with other therapies can enhance antitumor immunity. Here, we describe the role of aberrant DNA methylation in cancer and mechanisms by which it promotes tumorigenesis and modulates immune responses. Finally, we review the initial discoveries and ongoing efforts to target DNA methylation as a cancer therapeutic.

DNA 甲基化是基因调控的重要组成部分,在癌症的发展中扮演着重要角色。肿瘤抑制基因的过度甲基化和DNA修复途径的沉默会促进细胞的失控生长,并与致癌突变协同作用,使癌症表型永久化。此外,DNA 甲基化异常还会阻碍对抗肿瘤免疫至关重要的免疫反应。因此,抑制失调的 DNA 甲基化是一种很有前景的癌症疗法。对 DNA 甲基化的药物抑制可重新激活沉默的肿瘤抑制因子,并通过诱导病毒模拟来增强免疫反应。现在,随着免疫疗法的出现和 DNA 甲基化抑制剂免疫调节作用的发现,人们对了解 DNA 甲基化靶向与其他疗法的结合如何增强抗肿瘤免疫产生了浓厚的兴趣。在此,我们将介绍 DNA 甲基化异常在癌症中的作用,以及促进肿瘤发生和调节免疫反应的机制。最后,我们回顾了针对 DNA 甲基化作为癌症疗法的初步发现和正在进行的努力。
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引用次数: 0
SIRT3: A potential therapeutic target for liver fibrosis SIRT3:肝纤维化的潜在治疗靶点
IF 13.5 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-30 DOI: 10.1016/j.pharmthera.2024.108639
Yan Ning , Xinyue Dou , Zhichao Wang , Kao Shi , Zeping Wang , Chuan Ding , Xianan Sang , Xiang Zhong , Meiyu Shao , Xin Han , Gang Cao

Sirtuin3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase located in the mitochondria, which mainly regulates the acetylation of mitochondrial proteins. In addition, SIRT3 is involved in critical biological processes, including oxidative stress, inflammation, DNA damage, and apoptosis, all of which are closely related to the progression of liver disease. Liver fibrosis characterized by the deposition of extracellular matrix is a result of long termed or repeated liver damage, frequently accompanied by damaged hepatocytes, the recruitment of inflammatory cells, and the activation of hepatic stellate cells. Based on the functions and pharmacology of SIRT3, we will review its roles in liver fibrosis from three aspects: First, the main functions and pharmacological effects of SIRT3 were investigated based on its structure. Second, the roles of SIRT3 in major cells in the liver were summarized to reveal its mechanism in developing liver fibrosis. Last, drugs that regulate SIRT3 to prevent and treat liver fibrosis were discussed. In conclusion, exploring the pharmacological effects of SIRT3, especially in the liver, may be a potential strategy for treating liver fibrosis.

Sirtuin3(SIRT3)是一种烟酰胺腺嘌呤二核苷酸(NAD+)依赖性蛋白去乙酰化酶,位于线粒体中,主要调节线粒体蛋白的乙酰化。此外,SIRT3 还参与重要的生物过程,包括氧化应激、炎症、DNA 损伤和细胞凋亡,所有这些过程都与肝病的进展密切相关。以细胞外基质沉积为特征的肝纤维化是肝脏长期或反复受损的结果,经常伴随着肝细胞受损、炎症细胞招募和肝星状细胞活化。基于 SIRT3 的功能和药理,我们将从三个方面回顾其在肝纤维化中的作用:首先,根据SIRT3的结构研究其主要功能和药理作用。其次,总结 SIRT3 在肝脏主要细胞中的作用,揭示其在肝纤维化中的作用机制。最后,讨论了调节 SIRT3 以预防和治疗肝纤维化的药物。总之,探索SIRT3的药理作用,尤其是在肝脏中的作用,可能是治疗肝纤维化的一种潜在策略。
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引用次数: 0
Epigenetic determinants and non-myocardial signaling pathways contributing to heart growth and regeneration 促进心脏生长和再生的表观遗传决定因素和非心肌信号通路
IF 13.5 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-26 DOI: 10.1016/j.pharmthera.2024.108638
Jihyun Jang , Federica Accornero , Deqiang Li

Congenital heart disease is the most common birth defect worldwide. Defective cardiac myogenesis is either a major presentation or associated with many types of congenital heart disease. Non-myocardial tissues, including endocardium and epicardium, function as a supporting hub for myocardial growth and maturation during heart development. Recent research findings suggest an emerging role of epigenetics in nonmyocytes supporting myocardial development. Understanding how growth signaling pathways in non-myocardial tissues are regulated by epigenetic factors will likely identify new disease mechanisms for congenital heart diseases and shed lights for novel therapeutic strategies for heart regeneration.

先天性心脏病是全球最常见的出生缺陷。心肌发育缺陷是多种先天性心脏病的主要表现或相关因素。在心脏发育过程中,包括心内膜和心外膜在内的非心肌组织是心肌生长和成熟的支持枢纽。最近的研究结果表明,表观遗传学在非心肌细胞支持心肌发育方面发挥着新的作用。了解表观遗传因素如何调控非心肌组织的生长信号通路,将有可能发现先天性心脏病的新发病机制,并为心脏再生的新型治疗策略提供启示。
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引用次数: 0
Characteristics of anticancer activity of CBP/p300 inhibitors – Features of their classes, intracellular targets and future perspectives of their application in cancer treatment CBP/p300 抑制剂的抗癌活性特征--其类别特征、细胞内靶点及其在癌症治疗中的应用前景。
IF 13.5 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-22 DOI: 10.1016/j.pharmthera.2024.108636
Magdalena Strachowska , Agnieszka Robaszkiewicz

Due to the contribution of highly homologous acetyltransferases CBP and p300 to transcription elevation of oncogenes and other cancer promoting factors, these enzymes emerge as possible epigenetic targets of anticancer therapy. Extensive efforts in search for small molecule inhibitors led to development of compounds targeting histone acetyltransferase catalytic domain or chromatin-interacting bromodomain of CBP/p300, as well as dual BET and CBP/p300 inhibitors. The promising anticancer efficacy in in vitro and mice models led CCS1477 and NEO2734 to clinical trials. However, none of the described inhibitors is perfectly specific to CBP/p300 since they share similarity of a key functional domains with other enzymes, which are critically associated with cancer progression and their antagonists demonstrate remarkable clinical efficacy in cancer therapy. Therefore, we revise the possible and clinically relevant off-targets of CBP/p300 inhibitors that can be blocked simultaneously with CBP/p300 thereby improving the anticancer potential of CBP/p300 inhibitors and pharmacokinetic predicting data such as absorption, distribution, metabolism, excretion (ADME) and toxicity.

由于高度同源的乙酰转移酶 CBP 和 p300 对癌基因和其他促癌因子的转录升高有促进作用,因此这些酶可能成为抗癌治疗的表观遗传学靶标。在寻找小分子抑制剂的广泛努力下,开发出了以组蛋白乙酰转移酶催化结构域或 CBP/p300 的染色质相互作用溴结构域为靶点的化合物,以及 BET 和 CBP/p300 双重抑制剂。CCS1477 和 NEO2734 在体外和小鼠模型中具有良好的抗癌效果,因此已进入临床试验阶段。然而,由于 CBP/p300 与其他酶的关键功能域具有相似性,而这些酶与癌症进展密切相关,且其拮抗剂在癌症治疗中表现出显著的临床疗效,因此所描述的抑制剂中没有一种对 CBP/p300 具有完全特异性。因此,我们对 CBP/p300 抑制剂可能存在的与临床相关的非靶点进行了修订,这些非靶点可与 CBP/p300 同时阻断,从而提高 CBP/p300 抑制剂的抗癌潜力以及药代动力学预测数据,如吸收、分布、代谢、排泄(ADME)和毒性。
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引用次数: 0
CYP2J2-mediated metabolism of arachidonic acid in heart: A review of its kinetics, inhibition and role in heart rhythm control CYP2J2 介导的花生四烯酸在心脏中的代谢:花生四烯酸在心脏中的代谢:关于其动力学、抑制作用和在心律控制中的作用的综述。
IF 13.5 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-22 DOI: 10.1016/j.pharmthera.2024.108637
Jacqueline Wen Hui Leow, Eric Chun Yong Chan

Cytochrome P450 2 J2 (CYP2J2) is primarily expressed extrahepatically and is the predominant epoxygenase in human cardiac tissues. This highlights its key role in the metabolism of endogenous substrates. Significant scientific interest lies in cardiac CYP2J2 metabolism of arachidonic acid (AA), an omega-6 polyunsaturated fatty acid, to regioisomeric bioactive epoxyeicosatrienoic acid (EET) metabolites that show cardioprotective effects including regulation of cardiac electrophysiology. From an in vitro perspective, the accurate characterization of the kinetics of CYP2J2 metabolism of AA including its inhibition and inactivation by drugs could be useful in facilitating in vitro-in vivo extrapolations to predict drug-AA interactions in drug discovery and development. In this review, background information on the structure, regulation and expression of CYP2J2 in human heart is presented alongside AA and EETs as its endogenous substrate and metabolites. The in vitro and in vivo implications of the kinetics of this endogenous metabolic pathway as well as its perturbation via inhibition and inactivation by drugs are elaborated. Additionally, the role of CYP2J2-mediated metabolism of AA to EETs in cardiac electrophysiology will be expounded.

细胞色素 P450 2 J2(CYP2J2)主要在肝外表达,是人体心脏组织中最主要的环氧化酶。这凸显了它在内源性底物代谢中的关键作用。科学界对 CYP2J2 在心脏中将花生四烯酸(AA)(一种欧米伽-6 多不饱和脂肪酸)代谢为具有生物活性的环氧二十碳三烯酸(EET)代谢物的过程非常感兴趣,这种代谢物具有保护心脏的作用,包括调节心脏电生理。从体外角度来看,准确描述 AA 的 CYP2J2 代谢动力学(包括药物对其的抑制和灭活)有助于促进体外-体内推断,从而预测药物发现和开发过程中药物-AA 之间的相互作用。本综述介绍了 CYP2J2 在人体心脏中的结构、调节和表达的背景信息,以及 AA 和 EETs 作为其内源性底物和代谢物的情况。详细阐述了这一内源性代谢途径的体外和体内动力学影响,以及药物对其抑制和灭活的干扰作用。此外,还将阐述 CYP2J2 介导的 AA 向 EETs 的代谢在心脏电生理学中的作用。
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引用次数: 0
Musculoskeletal crosstalk in chronic obstructive pulmonary disease and comorbidities: Emerging roles and therapeutic potentials 慢性阻塞性肺病和合并症中的肌肉骨骼串扰:新的作用和治疗潜力。
IF 13.5 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-18 DOI: 10.1016/j.pharmthera.2024.108635
Kevin Mou, Stanley M.H. Chan, Ross Vlahos

Chronic Obstructive Pulmonary Disease (COPD) is a multifaceted respiratory disorder characterized by progressive airflow limitation and systemic implications. It has become increasingly apparent that COPD exerts its influence far beyond the respiratory system, extending its impact to various organ systems. Among these, the musculoskeletal system emerges as a central player in both the pathogenesis and management of COPD and its associated comorbidities. Muscle dysfunction and osteoporosis are prevalent musculoskeletal disorders in COPD patients, leading to a substantial decline in exercise capacity and overall health. These manifestations are influenced by systemic inflammation, oxidative stress, and hormonal imbalances, all hallmarks of COPD. Recent research has uncovered an intricate interplay between COPD and musculoskeletal comorbidities, suggesting that muscle and bone tissues may cross-communicate through the release of signalling molecules, known as “myokines” and “osteokines”. We explored this dynamic relationship, with a particular focus on the role of the immune system in mediating the cross-communication between muscle and bone in COPD. Moreover, we delved into existing and emerging therapeutic strategies for managing musculoskeletal disorders in COPD. It underscores the development of personalized treatment approaches that target both the respiratory and musculoskeletal aspects of COPD, offering the promise of improved well-being and quality of life for individuals grappling with this complex condition. This comprehensive review underscores the significance of recognizing the profound impact of COPD on the musculoskeletal system and its comorbidities. By unravelling the intricate connections between these systems and exploring innovative treatment avenues, we can aspire to enhance the overall care and outcomes for COPD patients, ultimately offering hope for improved health and well-being.

慢性阻塞性肺病(COPD)是一种多发性呼吸系统疾病,其特点是进行性气流受限和全身性影响。越来越明显的是,慢性阻塞性肺病对呼吸系统的影响远远超出了呼吸系统,而是扩展到了多个器官系统。其中,肌肉骨骼系统在慢性阻塞性肺病及其相关并发症的发病机制和治疗中发挥着核心作用。肌肉功能障碍和骨质疏松症是慢性阻塞性肺病患者常见的肌肉骨骼疾病,会导致运动能力和整体健康水平大幅下降。这些表现受到全身炎症、氧化应激和激素失衡的影响,而这些都是慢性阻塞性肺病的特征。最近的研究发现,慢性阻塞性肺病和肌肉骨骼合并症之间存在着错综复杂的相互作用,这表明肌肉和骨骼组织可能会通过释放信号分子(即 "肌动素 "和 "骨动素")进行交叉交流。我们探讨了这种动态关系,尤其关注免疫系统在慢性阻塞性肺病患者肌肉和骨骼之间的交叉交流中的作用。此外,我们还深入研究了治疗慢性阻塞性肺病肌肉骨骼疾病的现有和新兴治疗策略。它强调了针对慢性阻塞性肺病的呼吸和肌肉骨骼两方面的个性化治疗方法的发展,为与这种复杂病症作斗争的患者带来了改善生活质量的希望。本综述强调了认识慢性阻塞性肺病对肌肉骨骼系统及其并发症的深远影响的重要性。通过揭示这些系统之间错综复杂的联系并探索创新的治疗途径,我们可望提高慢性阻塞性肺病患者的整体护理水平和治疗效果,最终为改善患者的健康和福祉带来希望。
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引用次数: 0
Efficacy and safety of transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor in the treatment of advanced hepatocellular carcinoma: A meta-analysis 经动脉化疗栓塞联合来伐替尼和PD-1抑制剂治疗晚期肝细胞癌的有效性和安全性:一项荟萃分析。
IF 13.5 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-16 DOI: 10.1016/j.pharmthera.2024.108634
Lei Wang , Li Lin , Wei Zhou

The study aims to evaluate the benefits and potential adverse effects of transarterial chemoembolization (TACE) combined with lenvatinib and programmed cell death 1 (PD-1) protein inhibitors in the treatment of advanced hepatocellular carcinoma (HCC). A systematic literature search of several databases for relevant studies, published from inception up to May 2023, was performed. Clinical trials investigating TACE combined with lenvatinib and PD-1 inhibitors compared with other treatment regimens for advanced HCC were included. Data were pooled using fixed- or random-effects models and expressed as hazard ratios (HRs) or risk ratios (RRs) with corresponding 95% confidence interval (CI). Trial sequential analysis was used to determine whether the study results were sufficiently conclusive. Totally thirteen cohort studies comprising 1279 patients were included. The combined use of TACE, lenvatinib, and PD-1 inhibitors significantly improved overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) compared with other treatment regimens. The incidences of all-grade or grade ≥ 3 adverse events were comparable and did not differ significantly between the two groups. Prognostic factor analysis identified treatment options, portal vein tumor thrombus, extrahepatic metastasis, and Barcelona Clinic Liver Cancer (BCLC) stage as independent prognostic factors for OS. Extrahepatic metastasis, Child–Pugh score, and hepatic vein invasion emerged as independent prognostic factors for PFS. TSA suggested that the available data were adequate for drawing numerical conclusions regarding ORR and DCR. An approach combining TACE, lenvatinib, and PD-1 inhibitors appeared to offer significant improvements in OS, PFS, ORR, and DCR in patients with advanced HCC without significantly increasing the risk for all-grade adverse events.

本研究旨在评估经动脉化疗栓塞术(TACE)联合来伐替尼和程序性细胞死亡1(PD-1)蛋白抑制剂治疗晚期肝细胞癌(HCC)的益处和潜在不良反应。我们在多个数据库中系统检索了从开始到2023年5月发表的相关研究文献。纳入了研究TACE联合来伐替尼和PD-1抑制剂与其他晚期HCC治疗方案比较的临床试验。采用固定效应或随机效应模型对数据进行汇总,并以危险比(HRs)或风险比(RRs)及相应的95%置信区间(CI)表示。试验序列分析用于确定研究结果是否具有足够的结论性。共纳入了 13 项队列研究,包括 1279 名患者。与其他治疗方案相比,联合使用TACE、来伐替尼和PD-1抑制剂可显著提高总生存期(OS)、无进展生存期(PFS)、客观反应率(ORR)和疾病控制率(DCR)。所有级别或≥3级不良事件的发生率相当,两组之间无明显差异。预后因素分析表明,治疗方案、门静脉瘤栓、肝外转移和巴塞罗那临床肝癌(BCLC)分期是影响OS的独立预后因素。肝外转移、Child-Pugh评分和肝静脉侵犯则是影响PFS的独立预后因素。TSA认为,现有数据足以得出ORR和DCR的数字结论。结合TACE、来伐替尼和PD-1抑制剂的方法似乎能显著改善晚期HCC患者的OS、PFS、ORR和DCR,而不会明显增加所有级别不良事件的风险。
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引用次数: 0
Orthotopic and metastatic tumour models in preclinical cancer research 临床前癌症研究中的正位和转移性肿瘤模型。
IF 13.5 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-11 DOI: 10.1016/j.pharmthera.2024.108631
Stephen M. Stribbling , Callum Beach , Anderson J. Ryan

Mouse models of disease play a pivotal role at all stages of cancer drug development. Cell-line derived subcutaneous tumour models are predominant in early drug discovery, but there is growing recognition of the importance of the more complex orthotopic and metastatic tumour models for understanding both target biology in the correct tissue context, and the impact of the tumour microenvironment and the immune system in responses to treatment. The aim of this review is to highlight the value that orthotopic and metastatic models bring to the study of tumour biology and drug development while pointing out those models that are most likely to be encountered in the literature. Important developments in orthotopic models, such as the increasing use of early passage patient material (PDXs, organoids) and humanised mouse models are discussed, as these approaches have the potential to increase the predictive value of preclinical studies, and ultimately improve the success rate of anticancer drugs in clinical trials.

小鼠疾病模型在癌症药物开发的各个阶段都起着举足轻重的作用。细胞系衍生的皮下肿瘤模型在早期药物发现中占主导地位,但越来越多的人认识到更复杂的原位和转移肿瘤模型对于了解正确组织背景下的靶点生物学以及肿瘤微环境和免疫系统对治疗反应的影响的重要性。本综述旨在强调原位和转移瘤模型对肿瘤生物学研究和药物开发的价值,同时指出文献中最有可能出现的模型。本文讨论了正位模型的重要发展,如越来越多地使用早期病人材料(PDXs、organoids)和人源化小鼠模型,因为这些方法有可能提高临床前研究的预测价值,并最终提高抗癌药物在临床试验中的成功率。
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引用次数: 0
Immunotherapy for depression: Recent insights and future targets 抑郁症的免疫疗法:最新见解和未来目标
IF 13.5 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-03 DOI: 10.1016/j.pharmthera.2024.108624
Ying Bai , Yang Cai , Di Chang , Daxing Li , Xinchen Huo , Tianhao Zhu

Depression stands as a prominent contributor to global disability, entailing an elevated risk of suicide. Substantial evidence supports the notion that immune dysregulation may play a role in the development of depression and impede responses to antidepressant treatments. Immune dysregulation may cause depression in susceptible individuals through raising inflammatory responses. Differences in immune cell types and the release of pro-inflammatory mediators are observed in the blood and cerebrospinal fluid of patients with major depressive disorder, which is associated with neuroimmune dysfunction. Therefore, the interaction of peripheral and central immune targets in depression needs to be understood. Urgent attention is required for the development of innovative therapeutics directed at modulating immune responses for the treatment of depression. This review delineates the immune mechanisms involved in the pathogenesis of depression, assesses the therapeutic potential of immune system targeting for depression treatment, and deliberates on the merits and constraints of employing immunotherapy in the management of depression.

抑郁症是导致全球残疾的一个重要因素,同时也增加了自杀的风险。大量证据表明,免疫失调可能在抑郁症的发病过程中起作用,并阻碍对抗抑郁治疗的反应。免疫失调可能会通过提高炎症反应导致易感人群患上抑郁症。在重度抑郁症患者的血液和脑脊液中可以观察到免疫细胞类型的差异和促炎介质的释放,这与神经免疫功能紊乱有关。因此,需要了解抑郁症中外周和中枢免疫靶点的相互作用。开发旨在调节免疫反应的创新疗法以治疗抑郁症刻不容缓。本综述阐述了抑郁症发病机制中涉及的免疫机制,评估了以免疫系统为靶点治疗抑郁症的潜力,并探讨了在抑郁症治疗中采用免疫疗法的优点和限制因素。
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引用次数: 0
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Pharmacology & Therapeutics
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