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Overview of the role of purinergic signaling and insights into its role in cancer therapy 概述嘌呤能信号传导的作用及其在癌症治疗中的作用。
IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-05 DOI: 10.1016/j.pharmthera.2024.108700
Francesco Di Virgilio, Valentina Vultaggio-Poma, Mario Tarantini, Anna Lisa Giuliani

Innovation of cancer therapy has received a dramatic acceleration over the last fifteen years thanks to the introduction of the novel immune checkpoint inhibitors (ICI). On the other hand, the conspicuous scientific knowledge accumulated in purinergic signaling since the early seventies is finally being transferred to the clinic. Several Phase I/II clinical trials are currently underway to investigate the effect of drugs interfering with purinergic signaling as stand-alone or combination therapy in cancer. This is supporting the novel concept of “purinergic immune checkpoint” (PIC) in cancer therapy.

In the present review we will address a) the basic pharmacology and cell biology of the purinergic system; b) principles of its pathophysiology in human diseases; c) implications for cell death, cell proliferation and cancer; d) novel molecular tools to investigate nucleotide homeostasis in the extracellular environment; e) recent developments in the pharmacology of P1, P2 receptors and related ecto-enzymes; f) P1 and P2 ligands as novel diagnostic tools; g) current issues in PIC-based anti-cancer therapy.

This review will provide an appraisal of the current status of purinergic signaling in cancer and will help identify future avenues of development.

由于新型免疫检查点抑制剂(ICI)的问世,癌症疗法的创新在过去十五年中得到了极大的加速。另一方面,自七十年代初以来在嘌呤能信号转导方面积累的显著科学知识终于被应用于临床。目前正在进行几项 I/II 期临床试验,研究干扰嘌呤能信号转导的药物作为独立疗法或联合疗法对癌症的影响。这支持了癌症治疗中 "嘌呤能免疫检查点"(PIC)的新概念。在本综述中,我们将讨论 a) 嘌呤能系统的基础药理学和细胞生物学;b) 嘌呤能系统在人类疾病中的病理生理学原理;c) 嘌呤能系统对细胞死亡、细胞增殖和癌症的影响;d) 研究细胞外环境中核苷酸平衡的新型分子工具;e) P1、P2 受体和相关外酶的药理学最新发展;f) 作为新型诊断工具的 P1 和 P2 配体;g) 基于嘌呤能免疫检查点的抗癌疗法的当前问题。本综述将对癌症中嘌呤能信号转导的现状进行评估,并将有助于确定未来的发展方向。
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引用次数: 0
Tissue-specific activation of insulin signaling as a potential target for obesity-related metabolic disorders 胰岛素信号的组织特异性激活是肥胖相关代谢紊乱的潜在靶点。
IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-05 DOI: 10.1016/j.pharmthera.2024.108699
Hideyuki Okuma, Kyoichiro Tsuchiya

The incidence of obesity is rapidly increasing worldwide. Obesity-associated insulin resistance has long been established as a significant risk factor for obesity-related disorders such as type 2 diabetes and atherosclerosis. Insulin plays a key role in systemic glucose metabolism, with the liver, skeletal muscle, and adipose tissue as the major acting tissues. Insulin receptors and the downstream insulin signaling-related molecules are expressed in various tissues, including vascular endothelial cells, vascular smooth muscle cells, and monocytes/macrophages. In obesity, decreased insulin action is considered a driver for associated disorders. However, whether insulin action has a positive or negative effect on obesity-related disorders depends on the tissue in which it acts. While an enhancement of insulin signaling in the liver increases hepatic fat accumulation and exacerbates dyslipidemia, enhancement of insulin signaling in adipose tissue protects against obesity-related dysfunction of various organs by increasing the capacity for fat accumulation in the adipose tissue and inhibiting ectopic fat accumulation. Thus, this “healthy adipose tissue expansion” by enhancing insulin sensitivity in adipose tissue, but not in the liver, may be an effective therapeutic strategy for obesity-related disorders. To effectively address obesity-related metabolic disorders, the mechanisms of insulin resistance in various tissues of obese patients must be understood and drugs that enhance insulin action must be developed. In this article, we review the potential of interventions that enhance insulin signaling as a therapeutic strategy for obesity-related disorders, focusing on the molecular mechanisms of insulin action in each tissue.

肥胖症的发病率在全球范围内迅速上升。肥胖相关的胰岛素抵抗早已被证实是导致 2 型糖尿病和动脉粥样硬化等肥胖相关疾病的重要风险因素。胰岛素在全身葡萄糖代谢中起着关键作用,肝脏、骨骼肌和脂肪组织是其主要作用组织。胰岛素受体和下游的胰岛素信号相关分子在多种组织中表达,包括血管内皮细胞、血管平滑肌细胞和单核细胞/巨噬细胞。在肥胖症中,胰岛素作用减弱被认为是相关疾病的驱动因素。然而,胰岛素作用对肥胖相关疾病的影响是积极的还是消极的,取决于胰岛素作用的组织。肝脏中的胰岛素信号增强会增加肝脏脂肪堆积,加剧血脂异常,而脂肪组织中的胰岛素信号增强则会增加脂肪组织的脂肪堆积能力,抑制异位脂肪堆积,从而防止各器官出现与肥胖相关的功能障碍。因此,这种通过增强脂肪组织(而非肝脏)的胰岛素敏感性来实现 "健康脂肪组织扩张 "的方法,可能是治疗肥胖相关疾病的一种有效策略。要有效解决与肥胖相关的代谢紊乱问题,就必须了解肥胖患者各种组织的胰岛素抵抗机制,并开发能增强胰岛素作用的药物。在本文中,我们回顾了增强胰岛素信号传导的干预措施作为肥胖相关疾病治疗策略的潜力,重点探讨了胰岛素在各组织中的作用分子机制。
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引用次数: 0
Entering the TiME machine: How age-related changes in the tumor immune microenvironment impact melanoma progression and therapy response 进入 TiME 机器:肿瘤免疫微环境中与年龄相关的变化如何影响黑色素瘤的进展和治疗反应?
IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-03 DOI: 10.1016/j.pharmthera.2024.108698
Alexis E. Carey , Ashani T. Weeraratna

Melanoma is the deadliest form of skin cancer in the United States, with its incidence rates rising in older populations. As the immune system undergoes age-related changes, these alterations can significantly influence tumor progression and the effectiveness of cancer treatments. Recent advancements in understanding immune checkpoint molecules have paved the way for the development of innovative immunotherapies targeting solid tumors. However, the aging tumor microenvironment can play a crucial role in modulating the response to these immunotherapeutic approaches. This review seeks to examine the intricate relationship between age-related changes in the immune system and their impact on the efficacy of immunotherapies, particularly in the context of melanoma. By exploring this complex interplay, we hope to elucidate potential strategies to optimize treatment outcomes for older patients with melanoma, and draw parallels to other cancers.

黑色素瘤是美国最致命的皮肤癌,其发病率在老年人群中不断上升。随着免疫系统发生与年龄相关的变化,这些变化会极大地影响肿瘤的发展和癌症治疗的效果。最近在了解免疫检查点分子方面取得的进展为开发针对实体瘤的创新免疫疗法铺平了道路。然而,老化的肿瘤微环境在调节对这些免疫治疗方法的反应方面起着至关重要的作用。本综述旨在探讨免疫系统中与年龄有关的变化及其对免疫疗法疗效的影响之间错综复杂的关系,尤其是在黑色素瘤的情况下。我们希望通过探讨这种复杂的相互作用,阐明优化老年黑色素瘤患者治疗效果的潜在策略,并将其与其他癌症进行比较。
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引用次数: 0
Overcoming cancer drug-resistance calls for novel strategies targeting abnormal alternative splicing 克服癌症抗药性需要针对异常剪接的新策略。
IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-23 DOI: 10.1016/j.pharmthera.2024.108697
Ji Zhang , Xinyu Xu , Hongwei Deng , Li Liu , Yuancai Xiang , Jianguo Feng

Abnormal gene alternative splicing (AS) events are strongly associated with cancer progression. Here, we summarize AS events that contribute to the development of drug resistance and classify them into three categories: alternative cis-splicing (ACS), alternative trans-splicing (ATS), and alternative back-splicing (ABS). The regulatory mechanisms underlying AS processes through cis-acting regulatory elements and trans-acting factors are comprehensively described, and the distinct functions of spliced variants, including linear spliced variants derived from ACS, chimeric spliced variants arising from ATS, and circRNAs generated through ABS, are discussed. The identification of dysregulated spliced variants, which contribute to drug resistance and hinder effective cancer treatment, suggests that abnormal AS processes may together serve as a precise regulatory mechanism enabling drug-resistant cancer cell survival or, alternatively, represent an evolutionary pathway for cancer cells to adapt to changes in the external environment. Moreover, this review summarizes recent advancements in treatment approaches targeting AS-associated drug resistance, focusing on cis-acting regulatory elements, trans-acting factors, and specific spliced variants. Collectively, gaining an in-depth understanding of the mechanisms underlying aberrant alternative splicing events and developing strategies to target this process hold great promise for overcoming cancer drug resistance.

异常基因替代剪接(AS)事件与癌症进展密切相关。在此,我们总结了导致耐药性发生的基因替代剪接事件,并将其分为三类:替代顺式剪接(ACS)、替代反式剪接(ATS)和替代逆式剪接(ABS)。研究全面阐述了通过顺式作用调控元件和反式作用因子实现的AS过程的调控机制,并讨论了剪接变体的不同功能,包括ACS产生的线性剪接变体、ATS产生的嵌合剪接变体和ABS产生的circRNA。剪接变体的失调会导致耐药性并阻碍癌症的有效治疗,其鉴定结果表明,异常的AS过程可能是使耐药癌细胞存活的一种精确调控机制,或者是癌细胞适应外部环境变化的一种进化途径。此外,本综述还总结了针对AS相关耐药性的治疗方法的最新进展,重点关注顺式作用元件、反式作用因子和特定剪接变体。总之,深入了解异常替代剪接事件的内在机制并开发针对这一过程的策略,将为克服癌症耐药性带来巨大希望。
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引用次数: 0
Current state and novel outlook on prevention and treatment of rising antibiotic resistance in urinary tract infections 预防和治疗尿路感染中抗生素耐药性上升的现状和新展望。
IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-06 DOI: 10.1016/j.pharmthera.2024.108688

Antibiotic-resistant bacteria are currently an important public health concern posing a serious threat due to their resistance to the current arsenal of antibiotics. Uropathogens Escherichia coli (UPEC), Proteus mirabilis, Klebsiella pneumoniae and Enterococcus faecalis, antibiotic-resistant gram-negative bacteria, cause serious cases of prolonged UTIs, increasing healthcare costs and potentially even leading to the death of an affected patient. This review discusses current knowledge about the increasing resistance to currently recommended antibiotics for UTI therapy, as well as novel therapeutic options. Traditional antibiotics are still a part of the therapy guidelines for UTIs, although they are often not effective and have serious side effects. Hence, novel drugs are being developed, such as combinations of β-lactam antibiotics with cephalosporins and carbapenems. Siderophoric cephalosporins, such as cefiderocol, have shown potential in the treatment of individuals with significant gram-negative bacterial infections, as well as aminoglycosides, fluoroquinolones and tetracyclines that are also undergoing clinical trials. The use of cranberry and probiotics is another potential curative and preventive method that has shown antimicrobial and anti-inflammatory effects. However, further studies are needed to assess the efficacy and safety of probiotics containing cranberry extract for UTI prevention and treatment. An emerging novel approach for UTI treatment is the use of immuno-prophylactic vaccines, as well as different nanotechnology solutions such as nanoparticles (NP). NP have the potential to be used as delivery systems for drugs to specific targets. Furthermore, nanotechnology could enable the development of nano antibiotics with improved features by the application of different NPs in their structure, such as gold and copper NPs. However, further high-quality research is required for the synthesis and testing of these novel molecules, such as safety evaluation and pharmacovigilance.

抗生素耐药细菌是当前公共卫生的一个重要问题,由于它们对现有抗生素库产生耐药性,因此构成了严重威胁。尿路病原菌大肠埃希菌(UPEC)、奇异变形杆菌、肺炎克雷伯菌和粪肠球菌是耐抗生素革兰氏阴性菌,它们会导致严重的长期UTI病例,增加医疗成本,甚至可能导致患者死亡。这篇综述讨论了有关目前推荐用于治疗尿毒症的抗生素耐药性不断增加的现有知识,以及新的治疗方案。传统抗生素仍然是尿毒症治疗指南的一部分,尽管它们往往效果不佳且有严重的副作用。因此,人们正在开发新型药物,如β-内酰胺类抗生素与头孢菌素和碳青霉烯类的复方制剂。嗜苷头孢菌素(如头孢克洛)已显示出治疗严重革兰氏阴性菌感染患者的潜力,氨基糖苷类、氟喹诺酮类和四环素类药物也正在进行临床试验。使用蔓越莓和益生菌是另一种潜在的治疗和预防方法,已显示出抗菌和消炎作用。然而,还需要进一步的研究来评估含有蔓越莓提取物的益生菌在预防和治疗 UTI 方面的有效性和安全性。一种新出现的治疗尿毒症的新方法是使用免疫预防疫苗以及不同的纳米技术解决方案,如纳米颗粒(Nanoparticles)。纳米颗粒有可能被用作向特定靶点输送药物的系统。此外,通过在纳米抗生素的结构中应用不同的纳米粒子(如金和铜纳米粒子),纳米技术还能开发出功能更强的纳米抗生素。不过,这些新型分子的合成和测试,如安全性评估和药物警戒,还需要进一步的高质量研究。
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引用次数: 0
Pharmacological interventions for intraplaque neovascularization in atherosclerosis 针对动脉粥样硬化斑块内新生血管的药物干预。
IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-06 DOI: 10.1016/j.pharmthera.2024.108685
Azizah Ugusman , Nur Syahidah Nor Hisam , Nur Syakirah Othman , Nur Najmi Mohamad Anuar , Adila A. Hamid , Jaya Kumar , Maisarah Md Razmi , Amilia Aminuddin

Advanced atherosclerosis is linked to plaque instability, which can result in rupture and the onset of a heart attack. Evidence gathered from human atheroma plaques indicates that intraplaque neovascularization poses a risk to plaque stability and may lead to plaque hemorrhage. Hence, targeting the neovascularization within the atheroma plaque has the potential to mitigate the plaque's vulnerability. While neovascularization has been extensively explored in the context of cancer, research on pharmacological inhibition of this phenomenon in atherosclerosis remains limited. This systematic review aimed to comprehensively assess current and emerging pharmacological interventions for inhibiting intraplaque neovascularization in preclinical settings. Electronic databases (Web of Science, PubMed, Scopus, and Ovid) were searched from January 2013 until February 1, 2024. Preclinical studies reporting the effect of any pharmacological interventions targeting intraplaque neovascularization were included. A total of 10 articles involving in vivo animal studies were eligible for inclusion, with five of them incorporating in vitro experiments to complement their in vivo findings. The pharmacological interventions studied were axitinib, ghrelin, K5, rosuvastatin, atorvastatin, 3PO, everolimus, melatonin, Si-Miao-Yong-A, and protocatechuic aldehyde. All the interventions showed a positive impact in inhibiting intraplaque neovascularization in various atherosclerotic animal models through various signaling pathways. This review provides valuable insights into pharmacological approaches to attenuate intraplaque neovascularization that could serve as a promising therapeutic avenue to enhance plaque stability.

晚期动脉粥样硬化与斑块不稳定有关,斑块不稳定可导致破裂和心脏病发作。从人类动脉粥样斑块中收集的证据表明,斑块内新生血管对斑块的稳定性构成风险,并可能导致斑块出血。因此,针对动脉粥样斑块内的新生血管有可能减轻斑块的脆弱性。虽然在癌症方面对新生血管进行了广泛的探讨,但在动脉粥样硬化中对这一现象进行药理抑制的研究仍然有限。本系统综述旨在全面评估在临床前环境中抑制斑块内新生血管的现有和新兴药理学干预措施。检索了从 2013 年 1 月至 2024 年 2 月 1 日的电子数据库(Web of Science、PubMed、Scopus 和 Ovid)。纳入了报告任何针对斑块内新生血管的药物干预效果的临床前研究。共有10篇涉及体内动物研究的文章符合纳入条件,其中5篇结合了体外实验以补充体内研究结果。研究的药物干预措施包括阿昔替尼、胃泌素、K5、罗苏伐他汀、阿托伐他汀、3PO、依维莫司、褪黑素、Si-Miao-Yong-A 和原儿茶醛。所有干预措施都通过不同的信号传导途径,对抑制各种动脉粥样硬化动物模型斑块内新生血管的形成产生了积极影响。这篇综述为减轻斑块内新生血管的药理学方法提供了有价值的见解,可作为增强斑块稳定性的一种有前途的治疗途径。
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引用次数: 0
Vitamins and fatty acids against chemotherapy-induced intestinal mucositis 维生素和脂肪酸可预防化疗引起的肠粘膜炎。
IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-05 DOI: 10.1016/j.pharmthera.2024.108689

Chemotherapy has allowed an increase in cancer survivorship, but it causes important adverse effects. Mucositis affecting the gastrointestinal tract is one of the main problems acutely caused by many antineoplastic drugs, such as 5-fluorouracil or methotrexate. Mucositis may cause pain, diarrhea, anorexia, weight loss, systemic infections and even death. This narrative review focuses on intestinal mucositis and the role that some nutraceuticals, namely vitamins (both lipid- and water-soluble) as well as fatty acids (FAs) and lipid-based products, can have in it. In preclinical (cell cultures, animal models) and/or human studies, vitamins A, D, E, B2, B9 and C, omega-3 long-chain FAs (eicosapentaenoic, docosahexaenoic, conjugated linoleic acid), short-chain FAs (mainly butyrate), medium-chain FAs (capric acid), and different lipid-based products (emu oil, extra-virgin olive oil, lipid replacement therapy), enriched in beneficial FAs and natural antioxidants, were shown to exert beneficial effects (both preventative and palliative) against chemotherapy-induced intestinal mucositis. Although the exact mechanisms of action involved in these effects are not yet well known, our review highlights the interest of investigating on diet and nutrition to implement scientifically robust strategies to improve protection of cancer patients against chemotherapy-induced adverse effects.

化疗提高了癌症患者的生存率,但也带来了一些重要的不良反应。影响胃肠道的黏膜炎是许多抗肿瘤药物(如 5-氟尿嘧啶或甲氨蝶呤)引起的主要急性问题之一。粘膜炎可能导致疼痛、腹泻、厌食、体重减轻、全身感染甚至死亡。这篇叙述性综述的重点是肠粘膜炎以及一些营养保健品,即维生素(脂溶性和水溶性)、脂肪酸(FAs)和脂基产品在肠粘膜炎中的作用。在临床前(细胞培养、动物模型)和/或人体研究中,维生素 A、D、E、B2、B9 和 C、ω-3 长链脂肪酸(二十碳五烯酸、二十二碳六烯酸、共轭亚油酸)、短链脂肪酸(主要是丁酸)、中链脂肪酸(癸酸)、研究表明,富含有益脂肪酸和天然抗氧化剂的不同脂质产品(鸸鹋油、特级初榨橄榄油、脂质替代疗法)对化疗引起的肠道粘膜炎具有有益作用(预防和缓解)。虽然这些效果的确切作用机制尚不清楚,但我们的综述强调了对饮食和营养进行研究,以实施科学可靠的策略来提高癌症患者对化疗引起的不良反应的保护的兴趣。
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引用次数: 0
Early life adversities, psychopathologies and novel pharmacological strategies 早年的生活逆境、精神病理学和新型药理学策略。
IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-03 DOI: 10.1016/j.pharmthera.2024.108686
Annamaria Cattaneo , Veronica Begni , Valentina Zonca , Marco A. Riva

Exposure to adversities during early life stages (early life adversities - ELA), ranging from pregnancy to adolescence, represents a major risk factor for the vulnerability to mental disorders. Hence, it is important to understand the molecular and functional underpinning of such relationship, in order to develop strategies aimed at reducing the psychopathologic burden associated with ELA, which may eventually lead to a significant improvement in clinical practice. In this review, we will initially recapitulate clinical and preclinical evidence supporting the link between ELA and psychopathology and we will primarily discuss the main biological mechanisms that have been described as potential mediators of the effects of ELA on the psychopathologic risk, including the role for genetic factors as well as sex differences. The knowledge emerging from these studies may be instrumental for the development of novel therapeutic strategies aimed not only at correcting the deficits that emerge from ELA exposure, but also in preventing the manifestation of a full-blown psychopathologic condition. With this respect, we will specifically focus on adolescence as a key time frame for disease onset as well as for early therapeutic intervention. We believe that incorporating clinical and preclinical research data in the context of early life adversities can be instrumental to elucidate the mechanisms contributing to the risk for psychopathology or that may promote resilience. This will ultimately allow the identification of ‘at risk’ individuals who may benefit from specific forms of interventions that, by interfering with disease trajectories, could result in more benign clinical outcomes.

从怀孕到青春期的生命早期阶段(生命早期逆境--ELA)所遭遇的逆境是易患精神疾病的主要风险因素。因此,了解这种关系的分子和功能基础非常重要,这样才能制定出旨在减轻与 ELA 相关的精神病理负担的策略,从而最终显著改善临床实践。在本综述中,我们将首先回顾支持 ELA 与精神病理学之间联系的临床和临床前证据,并将主要讨论作为 ELA 对精神病理学风险影响的潜在介导因素的主要生物机制,包括遗传因素和性别差异的作用。从这些研究中获得的知识可能有助于开发新的治疗策略,其目的不仅在于纠正因暴露于 ELA 而出现的缺陷,而且还在于防止出现全面的精神病理状况。在这方面,我们将特别关注青少年时期,将其视为发病和早期治疗干预的关键时期。我们相信,将临床和临床前研究数据与早期生活逆境相结合,有助于阐明导致精神病理学风险或可能促进复原力的机制。这最终将有助于识别 "高危 "人群,他们可能会从特定形式的干预措施中获益,而这些干预措施通过干预疾病轨迹,可能会产生更加良性的临床结果。
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引用次数: 0
Spotlight on plasticity-related genes: Current insights in health and disease 聚焦可塑性相关基因:当前对健康和疾病的见解。
IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-03 DOI: 10.1016/j.pharmthera.2024.108687
Nicola Brandt , Franziska Köper , Jens Hausmann , Anja U. Bräuer

The development of the central nervous system is highly complex, involving numerous developmental processes that must take place with high spatial and temporal precision. This requires a series of complex and well-coordinated molecular processes that are tighly controlled and regulated by, for example, a variety of proteins and lipids. Deregulations in these processes, including genetic mutations, can lead to the most severe maldevelopments. The present review provides an overview of the protein family Plasticity-related genes (PRG1–5), including their role during neuronal differentiation, their molecular interactions, and their participation in various diseases. As these proteins can modulate the function of bioactive lipids, they are able to influence various cellular processes. Furthermore, they are dynamically regulated during development, thus playing an important role in the development and function of synapses. First studies, conducted not only in mouse experiments but also in humans, revealed that mutations or dysregulations of these proteins lead to changes in lipid metabolism, resulting in severe neurological deficits. In recent years, as more and more studies have shown their involvement in a broad range of diseases, the complexity and broad spectrum of known and as yet unknown interactions between PRGs, lipids, and proteins make them a promising and interesting group of potential novel therapeutic targets.

中枢神经系统的发育非常复杂,涉及众多发育过程,这些过程必须在空间和时间上高度精确。这需要一系列复杂而协调的分子过程,这些过程受到各种蛋白质和脂质等的严格控制和调节。这些过程的失调,包括基因突变,可导致最严重的发育不良。本综述概述了可塑性相关基因(PRG1-5)蛋白家族,包括它们在神经元分化过程中的作用、分子相互作用以及在各种疾病中的参与。由于这些蛋白可以调节生物活性脂质的功能,因此它们能够影响各种细胞过程。此外,它们在发育过程中受到动态调节,因此在突触的发育和功能中发挥着重要作用。不仅在小鼠实验中,而且在人类身上进行的首次研究显示,这些蛋白质的突变或失调会导致脂质代谢的变化,从而导致严重的神经功能缺陷。近年来,越来越多的研究表明,PRGs 参与了多种疾病的治疗,PRGs、脂质和蛋白质之间已知和未知相互作用的复杂性和广泛性使它们成为一组有希望的、有趣的潜在新型治疗靶点。
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引用次数: 0
HDL-based therapeutics: A promising frontier in combating viral and bacterial infections 基于高密度脂蛋白的疗法:抗击病毒和细菌感染的前景广阔。
IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-02 DOI: 10.1016/j.pharmthera.2024.108684
Alankrita Rani , Julia T. Stadler , Gunther Marsche

Low levels of high-density lipoprotein (HDL) and impaired HDL functionality have been consistently associated with increased susceptibility to infection and its serious consequences. This has been attributed to the critical role of HDL in maintaining cellular lipid homeostasis, which is essential for the proper functioning of immune and structural cells. HDL, a multifunctional particle, exerts pleiotropic effects in host defense against pathogens. It functions as a natural nanoparticle, capable of sequestering and neutralizing potentially harmful substances like bacterial lipopolysaccharides. HDL possesses antiviral activity, preventing viruses from entering or fusing with host cells, thereby halting their replication cycle. Understanding the complex relationship between HDL and the immune system may reveal innovative targets for developing new treatments to combat infectious diseases and improve patient outcomes. This review aims to emphasize the role of HDL in influencing the course of bacterial and viral infections and its and its therapeutic potential.

高密度脂蛋白(HDL)水平低和功能受损一直与感染及其严重后果的易感性增加有关。这归因于高密度脂蛋白在维持细胞脂质平衡方面的关键作用,而细胞脂质平衡对免疫细胞和结构细胞的正常运作至关重要。高密度脂蛋白是一种多功能微粒,在宿主抵御病原体的过程中发挥多种效应。它具有天然纳米颗粒的功能,能够封存和中和潜在的有害物质,如细菌脂多糖。高密度脂蛋白具有抗病毒活性,能阻止病毒进入宿主细胞或与宿主细胞融合,从而停止病毒的复制周期。了解高密度脂蛋白与免疫系统之间的复杂关系可为开发抗击传染病和改善患者预后的新疗法提供创新目标。本综述旨在强调高密度脂蛋白在影响细菌和病毒感染过程中的作用及其治疗潜力。
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引用次数: 0
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Pharmacology & Therapeutics
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