TRPV Cation Channels

TRPV 阳离子通道
  • 文章类型: Journal Article
    伤口愈合涉及身体,化学和免疫过程。瞬时受体电位(TRP)和其他离子通道与表皮再上皮化有关。跨离子通道的离子运动可以诱导跨膜电位,从而导致跨上皮电位(TEP)变化。TEP存在于病变周围的表皮中,减少并诱导内源性直流电产生上皮电场(EF),这可能与伤口上皮再形成有关。TRP通道主要在伤口愈合的炎症阶段参与免疫细胞的激活。该研究的目的是在小鼠体内实验中回顾离子通道参与伤口愈合的机制(小鼠,大鼠)以及如何影响这一过程。这篇评论使用了过去一年和今年迄今为止(2023年1月1日至12月31日3000)在科学期刊上发表的最新结果,以包括新闻中的文章。某些类型的TRP频道,如TRPV1、TRPV3和TRPA1,在免疫细胞中表达,并可被炎症介质激活。使用TRPV1,TRPV4和TRPA1通道的激动剂或通过用拮抗剂抑制,反义寡核苷酸或敲低TRPV3和TRPM8通道。
    Wound healing involves physical, chemical and immunological processes. Transient receptor potential (TRP) and other ion channels are implicated in epidermal re-epithelization. Ion movement across ion channels can induce transmembrane potential that leads to transepithelial potential (TEP) changes. TEP is present in epidermis surrounding the lesion decreases and induces an endogenous direct current generating an epithelial electric field (EF) that could be implicated in wound re-epithelialization. TRP channels are involved in the activation of immune cells during mainly the inflammatory phase of wound healing. The aim of the study was to review the mechanisms of ion channel involvement in wound healing in in vivo experiments in murine (mice, rats) and how can this process be influenced. This review used the latest results published in scientific journals over the last year and this year to date (1 January 2023-31 December 3000) in order to include the in-press articles. Some types of TRP channels, such as TRPV1, TRPV3 and TRPA1, are expressed in immune cells and can be activated by inflammatory mediators. The most beneficial effects in wound healing are produced using agonists of TRPV1, TRPV4 and TRPA1 channels or by inhibiting with antagonists, antisense oligonucleotides or knocking down TRPV3 and TRPM8 channels.
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  • 文章类型: Journal Article
    本研究探讨了辣椒素对癌症产生有利影响的基本化学机制,专门研究其对癌症转移中的炎症等多种生物过程的影响,凋亡,血管生成,和细胞增殖。该实体与其他信号通路的连接,包括PI3K/AKT,NF-B,和TRPV通道,与肿瘤生长有关,在这项工作中被彻底检查。本研究对辣椒素治疗多种癌症的临床前研究和临床试验进行了全面分析。如乳房,前列腺,结直肠,胰腺,和其他人。通过在活生物体和实验室环境中进行的测试,已经确定辣椒素具有抑制肿瘤生长和诱导癌细胞凋亡的能力。(体外和体内)。研究人员还研究了传统治疗中辣椒素与化疗药物联合使用的结果。辣椒素作为一种可行的药物的功效和生物利用度正在研究中,以及提高其临床价值的方法。本调查仔细评估了最大限度地提高辣椒素治疗效果的挑战和潜在选择。包括定制的药物输送和个性化的治疗策略。在定稿中,这项全面的调查汇集了目前可获得的关于辣椒素抗癌特性的证据,强调其作为对抗癌症的自主治疗选择的潜力。辣椒素是与癌症治疗领域的持续研究和临床探索具有显著相关性的化合物,由于其不同的作用机制和促进流行的治疗方法的能力。
    This study examines the fundamental chemical mechanisms responsible for capsaicin\'s advantageous impact on cancer, specifically investigating its influence on several biological processes such as inflammation in cancer metastasis, apoptosis, angiogenesis, and cellular proliferation. This entity\'s connections with other signaling pathways, including PI3K/AKT, NF-B, and TRPV channels, which have been linked to tumor growth, are thoroughly examined in this work. This study presents a thorough analysis of preclinical studies and clinical trials investigating the efficacy of capsaicin in treating many forms of cancer, such as breast, prostate, colorectal, pancreatic, and others. Through tests conducted in both live organisms and laboratory settings, it has been determined that capsaicin has the ability to inhibit tumor growth and induce apoptosis in cancer cells. (in vitro and in vivo). Researchers have also looked at the results of combining capsaicin with chemotherapy medications in traditional treatment. The efficacy and bioavailability of capsaicin as a viable medicinal drug are being studied, along with ways to improve its clinical value. The present investigation carefully assesses the challenges and potential options for maximizing the therapeutic benefits of capsaicin, including customized drug delivery and personalized therapeutic strategies. In finalization, this comprehensive investigation brings together the evidence currently obtainable on the anticancer properties of capsaicin, underscoring its potential as an autonomous treatment option in the struggle against cancer. Capsaicin is a compound of significant relevance for continuing research and clinical exploration in the field of cancer treatment due to its diverse mechanisms of action and ability for boosting prevailing therapy approaches.
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  • 文章类型: Journal Article
    骨关节炎(OA)是一种使人衰弱的关节疾病,影响全球数百万人。尽管流行,我们对潜在机制的理解仍然不完整。近年来,瞬时受体电位香草素(TRPV)通道已成为OA发病机制的关键参与者。本文对TRPV通路在OA中的作用进行了深入的探讨,包括它参与疼痛感知,炎症,和机械转换。此外,我们讨论最新的研究成果,潜在的治疗策略,以及该领域的未来方向,揭示OA中TRPV通道的多面性。
    Osteoarthritis (OA) is a debilitating joint disorder that affects millions of people worldwide. Despite its prevalence, our understanding of the underlying mechanisms remains incomplete. In recent years, transient receptor potential vanilloid (TRPV) channels have emerged as key players in OA pathogenesis. This review provides an in-depth exploration of the role of the TRPV pathway in OA, encompassing its involvement in pain perception, inflammation, and mechanotransduction. Furthermore, we discuss the latest research findings, potential therapeutic strategies, and future directions in the field, shedding light on the multifaceted nature of TRPV channels in OA.
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  • 文章类型: Journal Article
    几十年的研究支持瞬时受体电位(TRP)通道参与伤害感受。尽管早期的TRPV1拮抗剂计划令人失望,TRP家族仍然是疼痛障碍的有希望的治疗靶点.高剂量辣椒素贴剂已经在临床上用于缓解神经性疼痛。目前,在骨关节炎和骨癌疼痛患者中,局部注射侧向TRPV1激动剂辣椒素和树脂毒素正在进行临床试验.TRPA1、TRPM3和TRPC5通道也非常感兴趣。这篇综述讨论了TRP通道在人类疼痛状况中的作用。
    Several decades of research support the involvement of transient receptor potential (TRP) channels in nociception. Despite the disappointments of early TRPV1 antagonist programs, the TRP family remains a promising therapeutic target in pain disorders. High-dose capsaicin patches are already in clinical use to relieve neuropathic pain. At present, localized injections of the side-directed TRPV1 agonist capsaicin and resiniferatoxin are undergoing clinical trials in patients with osteoarthritis and bone cancer pain. TRPA1, TRPM3, and TRPC5 channels are also of significant interest. This review discusses the role of TRP channels in human pain conditions.
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  • 文章类型: Journal Article
    慢性非过敏性鼻炎综合征包括各种疾病,其中血管运动性鼻炎是最常见的形式,代表大约80%的患者,也称为非过敏性鼻病(NAR),鼻腔高反应性,神经性鼻炎,或者特发性鼻炎.专家小组建议替换血管运动性鼻炎术语,因为它更多地描述了这种情况,其特征是由化学刺激物和天气变化通过化学传感器触发的症状,机械传感器,温度传感器,和/或通过不同的瞬时受体电位钙离子通道激活的渗透传感器。阐明辣椒素引发的瞬时受体电位香草酸1的特定作用,在更好地理解NAR的病理生理学方面取得了重要进展,因为现在已经表明,几种治疗性化合物对瞬时受体电位香草素1受体的下调可以缓解这种情况。NAR的分类因其与变应性鼻炎(称为混合鼻炎)的关联而进一步复杂化。涉及免疫球蛋白E介导的和神经源性的机制途径。与NAR相关的合并症,包括鼻窦炎,头痛,哮喘,慢性咳嗽,和睡眠障碍,强调全面管理的必要性。NAR的治疗方案包括环境干预,药物治疗,在难治性病例中,手术选择,强调需要为每个患者量身定制的方法。因此,准确诊断NAR极为重要,因为不适当的治疗会导致不良的临床结局,并给这些患者带来不必要的医疗保健和经济负担.这篇综述提供了NAR亚型的全面概述,注重分类,诊断,和NAR的治疗方法。
    Chronic nonallergic rhinitis syndromes encompass various conditions, of which vasomotor rhinitis is the most common form, representing approximately 80% of patients, also referred to as nonallergic rhinopathy (NAR), nasal hyperreactivity, neurogenic rhinitis, or idiopathic rhinitis. Expert panels have recommended replacing vasomotor rhinitis terminology because it is more descriptive of this condition that is characterized by symptoms triggered by chemical irritants and weather changes through chemosensors, mechanosensors, thermosensors, and/or osmosensors activated through different transient receptor potential calcium ion channels. Elucidating the specific role of transient receptor potential vanilloid 1, triggered by capsaicin, has been an important advancement in better understanding the pathophysiology of NAR because it has now been shown that downregulation of transient receptor potential vanilloid 1 receptors by several therapeutic compounds provides symptomatic relief for this condition. The classification of NAR is further complicated by its association with allergic rhinitis referred to as mixed rhinitis, which involves both immunoglobulin E-mediated and neurogenic mechanistic pathways. Comorbidities associated with NAR, including rhinosinusitis, headaches, asthma, chronic cough, and sleep disturbances, underscore the need for comprehensive management. Treatment options for NAR include environmental interventions, pharmacotherapy, and in refractory cases, surgical options, emphasizing the need for a tailored approach for each patient. Thus, it is extremely important to accurately diagnose NAR because inappropriate therapies lead to poor clinical outcomes and unnecessary health care and economic burdens for these patients. This review provides a comprehensive overview of NAR subtypes, focusing on classification, diagnosis, and treatment approaches for NAR.
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  • 文章类型: Review
    辣椒素,辣椒中含有丰富的辣椒,发挥抗氧化作用,抗肿瘤,抗溃疡和镇痛作用,它已经证明了作为心血管治疗的潜力,胃肠,肿瘤和皮肤病学条件。在天然刺激物中独一无二,辣椒素最初会激发神经元,但随后会使它们变得持久无反应。辣椒素还可以促进减肥,使其有可能用于治疗肥胖症。已经提出了几种机制来解释辣椒素的治疗作用,包括抗氧化,镇痛和促进细胞凋亡。一些机制被认为是由辣椒素受体(瞬时受体电位阳离子通道亚家族V成员1)介导的,但有些被认为是独立于该受体的。辣椒素的临床用途受到其半衰期短的限制。本综述概述了有关辣椒素的治疗作用及其机制的已知知识,并提到了某些反对其临床应用的研究。
    Capsaicin, which is abundant in chili peppers, exerts antioxidative, antitumor, antiulcer and analgesic effects and it has demonstrated potential as a treatment for cardiovascular, gastrointestinal, oncological and dermatological conditions. Unique among natural irritants, capsaicin initially excites neurons but then \'calms\' them into long‑lasting non‑responsiveness. Capsaicin can also promote weight loss, making it potentially useful for treating obesity. Several mechanisms have been proposed to explain the therapeutic effects of capsaicin, including antioxidation, analgesia and promotion of apoptosis. Some of the mechanisms are proposed to be mediated by the capsaicin receptor (transient receptor potential cation channel subfamily V member 1), but some are proposed to be independent of that receptor. The clinical usefulness of capsaicin is limited by its short half‑life. The present review provided an overview of what is known about the therapeutic effects of capsaicin and the mechanisms involved and certain studies arguing against its clinical use were mentioned.
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  • 文章类型: Systematic Review
    辣椒素和辣椒素是主要存在于辣椒中的生物活性化合物。尽管临床前研究已经报道,由于瞬时受体电位香草素亚型1(TRPV1)介导的产热,这些化合物可以改善运动表现,交感神经调制,释放钙,目前还不清楚它们如何影响人类的运动表现。根据2020年系统评价和荟萃分析报告指南的首选报告项目进行,该系统评价研究了辣椒素和辣椒素对健康成年人运动能力的影响。共有19项随机安慰剂对照试验纳入研究。通过搜索五个数据库(PubMed,Scopus,SPORTDiscus,WebofScience,和Cochrane图书馆)。使用Cochrane偏差风险评估工具评估研究质量。根据研究结果,10项研究检查了辣椒素和辣椒素补充剂对运动表现的影响,报告了积极的影响。此外,辣椒素和辣椒素对运动表现的影响在阻力训练中更为明显。这种差异,根据运动类型的不同,可能是由于辣椒素瞬时受体电位香草素亚型1和胰岛素样生长因子-1之间的相关性。
    Capsaicinoids and capsinoids are bioactive compounds mostly found in peppers. Although preclinical studies have reported that these compounds can improve exercise performance due to transient receptor potential vanilloid subtype 1 (TRPV1)-mediated thermogenesis, sympathetic modulation, and releasing calcium, it is still unclear how they affect exercise performance in humans as ergogenic supplements. Conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guide 2020, this systematic review examined the ergogenic effect of capsaicinoids and capsinoids on exercise performance in healthy adults. A total of 19 randomized placebo-controlled trials were included in the study. Studies were accessed by searching five databases (PubMed, Scopus, SPORTDiscus, Web of Science, and Cochrane Library). The quality of the studies was evaluated using the Cochrane risk-of-bias assessment tool. According to the study results, 10 studies examining the effect of capsaicinoid and capsinoid supplements on exercise performance reported positive effects. Also, the effect of capsaicinoids and capsinoids on exercise performance is more pronounced in resistance training. This difference, which varies according to the type of exercise, may be due to the correlation between capsaicin transient receptor potential vanilloid subtype 1 and insulin-like growth factor-1.
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  • 文章类型: Review
    背景:Charcot-Marie-Tooth病2C(CMT2C)和肩腓骨脊髓性肌萎缩(SPSMA)是TRPV4突变的不同临床表型。据报道,p.R316C的突变分别引起CMT2C和SPSMA。
    方法:这里,我们报道了一个中国家庭拥有相同的p.R316C变体,但有重叠综合征和不同的临床表现。一名58岁的男子出现严重的肩胛骨肌肉萎缩,导致倾斜的肩膀。他的四肢还表现出明显的肌肉萎缩,尤其是下肢。腓肠神经活检显示有髓神经纤维严重丧失,并有分散的再生簇和假洋葱鳞茎。神经传导研究显示运动神经和感觉神经轴突损伤。不能在双侧腓肠或腓浅神经中诱发感觉神经动作电位。他被诊断出患有Charcot-Marie-Tooth病2C型和肩腓骨肌萎缩重叠综合征,而他27岁的儿子出生时患有马蹄内翻足和斜牙。肌电图检查提示慢性神经源性改变和前角细胞受累。虽然没有明显的虚弱或感觉症状,他可以考虑早期的SPSMA。
    结论:对具有TRPV4突变的CMT2C和SPSMA患者的临床特征的文献综述表明,由于重叠综合征和表型变异,我们的病例是明显的。总之,该病例扩大了表型谱,并提供了TRPV4相关神经病的神经活检病理细节.
    BACKGROUND: Charcot-Marie-Tooth disease 2C (CMT2C) and scapuloperoneal spinal muscular atrophy (SPSMA) are different clinical phenotypes of TRPV4 mutation. The mutation of p.R316C has been reported to cause CMT2C and SPSMA separately.
    METHODS: Here, we reported a Chinese family harboring the same p.R316C variant, but with an overlap syndrome and different clinical manifestations. A 58-year-old man presented with severe scapula muscle atrophy, resulting in sloping shoulders. He also exhibited distinct muscle atrophy in his four limbs, particularly in the lower limbs. The sural nerve biopsy revealed severe loss of myelinated nerve fibers with scattered regenerating clusters and pseudo-onion bulbs. Nerve conduction study showed axon damage in both motor and sensory nerves. Sensory nerve action potentials could not be evoked in bilateral sural or superficial peroneal nerves. He was diagnosed with Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome, whereas his 27-year-old son was born with clubfoot and clinodactyly. Electromyogram examination indicated chronic neurogenic changes and anterior horn cells involvement. Although there was no obvious weakness or sensory symptoms, early SPSMA could be considered for him.
    CONCLUSIONS: A literature review of the clinical characteristics in CMT2C and SPSMA patients with TRPV4 mutation suggested that our case was distinct due to the overlap syndrome and phenotype variation. Altogether, this case broadened the phenotype spectrum and provided the nerve biopsy pathological details of TRPV4-related neuropathies.
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  • 文章类型: Journal Article
    近年来,由于钙选择性通道TRPV6在人类健康和疾病中可能发挥的多种作用,因此越来越受到关注。然而,可能的医学含义与以下事实有关:该基因的非洲祖先变体似乎比衍生的欧亚变体多25%的钙滞留性在遗传文献中继续被忽略。TRPV6基因主要在肠道中表达,结肠,胎盘,乳腺和前列腺.出于这个原因,跨学科线索已经开始将其mRNA在表达TRPV6的癌症中的不受控制的增殖与祖先变体的非裔美国人携带者中这些恶性肿瘤的异常高风险联系起来。医学基因组学社区需要变得更加关注不同人群的相关历史和生态细节,现在的情况比以往任何时候都更多,因为全基因组关联研究正在努力赶上越来越多的致病基因变异,这些变异被证明是特定于人群的。
    In recent years, growing attention has become focused on the calcium selective channel TRPV6 because of the multiplicity of roles it may play in human health and disease. However, possible medical implications related to the fact that the African ancestral variant of this gene appears to be 25% more calcium-retentive than the derived Eurasian variant continue to be discounted in the genetic literature. The TRPV6 gene is expressed primarily in the intestines, the colon, the placenta, mammary and prostate glands. For this reason, transdisciplinary clues have begun to link the uncontrolled proliferation of its mRNA in TRPV6-expressing cancers to the unusually high risk of these malignancies in African-American carriers of the ancestral variant. The medical genomics community needs to become more attentive to diverse populations\' relevant historical and ecological details. This is the case now more than ever as Genome Wide Association Studies wrestle to catch up with the growing number of disease causative gene variants that are turning out to be population-specific.
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  • 背景:瞬时受体电位(TRP)通道是非选择性的Ca2+渗透通道,广泛而动态地参与口腔环境刺激的感知,在口腔组织病理学和口腔疾病中起关键作用。牙髓炎和牙周炎期间分泌的几种因素,例如促炎细胞因子,前列腺素,谷氨酸,胞外ATP,和缓激肽,可以触发TRP,直接或间接,降低感觉神经元的阈值,调节免疫细胞功能。
    目的:研究TRP通道在口腔病理中的多种功能和分子机制,并探讨其临床意义和治疗靶向潜力。
    方法:相关关键词用于科学数据库中的研究(泵送,Scopus,和科学直接)。只包括英文文章,筛选,并批判性地分析。这些研究的关键发现包括在内,以及它们的临床重要性。
    结果:某些TRP通道被检测为口腔病理学的关键介质。发现TRPV1在髓核疼痛传导中起重要作用,诱导炎症,并参与牙周炎期间的骨吸收。TRPM2激活可能会减少头颈部放射后腺泡唾液细胞的唾液分泌和口干症,而TRPV1和TRPA1通道介导三叉神经疼痛。已证明几种TRP激动剂和拮抗剂与某些化合物如辣椒素一起阻断口腔疾病的病理途径。卡沙西平,硝苯地平,丁香酚,thapsigargin和特定的靶向技术,如UHF-USP和Er:YAG激光器。目前的TRP靶向方法已被证明在成骨细胞和成纤维细胞增殖中发挥有益作用。癌细胞凋亡,唾液分泌,和伤害性。
    结论:TRP在疼痛传导中起核心作用,口腔组织的炎症反应,和口腔粘膜的病理状况,包括口腔鳞状细胞癌和溃疡性粘膜炎。
    BACKGROUND: Transient Receptor Potential (TRP) channels are non-selective Ca2+ permeable channels with a wide and dynamic involvement in the perception of environmental stimuli in the oral cavity and a pivotal role in oral tissues\' pathology and oral diseases. Several factors secreted during pulpitis and periodontitis, such as pro-inflammatory cytokines, prostaglandins, glutamate, extracellular ATP, and bradykinin, can trigger TRPs, either directly or indirectly, lowering the threshold of sensory neurons and regulate immune cell function.
    OBJECTIVE: To investigate the diverse functions and molecular mechanisms of TRP channels in oral pathology and critically discuss their clinical significance and therapeutic targeting potential.
    METHODS: Relevant keywords were used for research in scientific databases (Pumped, Scopus, and Science Direct). Only articles in English were included, screened, and critically analyzed. The key findings of these studies were included, along with their clinical importance.
    RESULTS: Certain TRP channels were detected as key mediators of oral pathology. TRPV1 was revealed to play an important role in pain transduction in pulpits, induce inflammation, and be involved in bone resorption during periodontitis. TRPM2 activation may reduce saliva secretion in acinar salivary cells and xerostomia after head and neck radiation, while TRPV1 and TRPA1 channels mediate trigeminal nerve pain. Several TRP agonists and antagonists have been demonstrated to block pathological pathways in oral diseases along with certain compounds such as capsaicin, capsazepine, nifedipine, eugenol, thapsigargin and specific targeting techniques such as UHF-USP and Er: YAG lasers. Current TRP targeting approaches have been shown to exert beneficial effects in osteoblasts and fibroblasts proliferation, carcinoma cells\' apoptosis, saliva secretion, and nociception.
    CONCLUSIONS: TRPs play a central role in pain transduction, inflammatory responses in oral tissues, and pathological conditions of the oral mucosa, including oral squamous cell carcinoma and ulcerative mucositis.
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