mechanisms

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  • 文章类型: Journal Article
    目前对酒精使用障碍(AUD)的治疗具有有限的功效。最近,大麻二酚(CBD)已经在许多临床环境中进行了检查。临床前和临床结果表明,CBD可能特别适合治疗AUD,并可能减少酒精提示和压力引起的渴望和寻求酒精。这项研究旨在研究这种新的药物疗法,特别关注渴望的神经生物学和生理指标。方法:在这种双盲中,在主题内,随机化,安慰剂对照,交叉研究,非治疗寻求者将被随机分配到三天的四个200毫克CBD凝胶胶囊(800毫克/天)或安慰剂,有18天的冲洗期。Cognitive,临床,神经影像学评估将在这三天内完成。将比较CBD和安慰剂评估。主要结果是i)BOLD信号作为提示反应性和使用功能磁共振成像(fMRI)测量的恐惧反应任务期间区域活动的代理,ii)心率变异性和皮肤电导水平作为对酒精刺激的心理生理反应的代理。次要结果是:i)神经代谢物水平(γ-氨基丁酸,乙醇,谷胱甘肽,和谷氨酸+谷氨酰胺(组合信号))使用磁共振波谱(MRS);ii)使用静息状态fMRI(rsfMRI)的功能连接;iii)执行功能任务结果;iv)临床结果,例如渴望,焦虑,和睡眠。讨论:这项研究将提高对CBD作用机制的理解,并提供有关CBD在治疗酒精使用障碍中的治疗潜力的早期功效信号。ClinicalTrials.gov标识符:NCT05387148。
    Current treatments for alcohol use disorders (AUD) have limited efficacy. Recently, Cannabidiol (CBD) has been examined in a multitude of clinical settings. Preclinical and clinical results suggest that CBD might be particularly well suited for the treatment of AUD and may reduce alcohol cue and stress-induced craving and alcohol seeking. This study aims to investigate this new pharmacotherapy with a particular focus on neurobiological and physiological indicators of craving. Methods: In this double-blind, within-subject, randomised, placebo-controlled, cross-over study, non-treatment seekers will be randomly allocated to three days of four 200 mg CBD gel capsules (800 mg/day) or placebo, with an 18-day washout period. Cognitive, clinical, and neuroimaging assessments will be completed during these three days. The CBD and placebo assessments will be compared. The primary outcomes are i) BOLD signal as a proxy for regional activity during a cue reactivity and a fear response task measured with functional magnetic resonance imaging (fMRI), ii) heart rate variability and skin conductance levels as a proxy for psychophysiological responses to alcohol stimuli. The secondary outcomes are: i) neurometabolite levels (γ-Aminobutyric acid, ethanol, glutathione, and glutamate + glutamine (combined signal)) using magnetic resonance spectroscopy (MRS); ii) functional connectivity using resting state fMRI (rsfMRI); iii) executive functioning task results; iv) clinical outcomes such as craving, anxiety, and sleep. Discussion: This study will improve the understanding of the mechanisms of action of CBD and provide early signals of efficacy regarding the therapeutic potential of CBD in the treatment of alcohol use disorder. ClinicalTrials.gov Identifier: NCT05387148.
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  • 文章类型: Case Reports
    背景:室管膜瘤是一种神经胶质肿瘤,通常发生在心室中或附近,靠近室管膜.它很少仅在脑实质中发生,而与心室无关。
    方法:这里,我们报告了一例罕见的小脑室管膜瘤完全位于脑实质内。我们医院收治了一名先前健康的32岁女性,有1个月的头晕病史。住院期间,大脑的磁共振成像显示,右侧小脑半球和小脑下部的占位病变为57mm×41mm×51mm。患者接受了右小脑肿块的手术切除。术后病理检查显示室管膜瘤。随访1年,患者情况良好,无复发.
    结论:我们进行了文献综述,并总结了关于仅位于脑实质的室管膜瘤的三种理论,这是诊断脑实质内小脑室管膜瘤的关键。手术和术后放疗是室管膜瘤的主要治疗选择。
    BACKGROUND: An ependymoma is a glial tumor that usually occurs in or near the ventricle, close to the ependyma. It rarely occurs exclusively in the brain parenchyma without being associated with the ventricle.
    METHODS: Here, we report a rare case of a cerebellar ependymoma completely located in the brain parenchyma. A previously healthy 32-year-old female with a 1-month history of dizziness was admitted to our hospital. During hospitalization, magnetic resonance imaging of the brain revealed a space-occupying lesion measuring 57 mm × 41 mm × 51 mm in the right cerebellar hemisphere and inferior cerebellar vermis. The patient underwent surgical resection for the right cerebellar mass. Postoperative pathological examination revealed an ependymoma. At 1 year follow-up, the patient was doing well and showed no recurrence.
    CONCLUSIONS: We conducted a literature review and summarized three theories regarding ependymomas located exclusively in the brain parenchyma, which are key to the diagnosis of intraparenchymal cerebellar ependymomas. Surgery and postoperative radiotherapy are the primary treatment options for ependymomas.
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  • 文章类型: Journal Article
    慢性硬膜下血肿(CSDH)是神经外科的常见并发症。颅脑外伤是可能的原因。没有关于CSDH与肾病综合征的报道。其发病机制非常罕见,以前没有关于这种疾病治疗的报道。我们报告了一例可能由肾病综合征引起的慢性硬膜下血肿,并回顾了有关该主题的文献。
    我们报告了一例罕见的慢性硬膜下血肿,可能由肾病综合征引起。病人入院后,进行了相关的实验室测试,在病人的尿液中检测到大量的蛋白质,表明低蛋白血症和高脂血症。患者被诊断为肾病综合征。排除相关手术禁忌症后,患者接受了慢性硬膜下血肿的钻孔引流术。手术后提供口服阿托伐他汀的后续治疗。如果患者的神经系统状况改善,则将其转移到肾脏病科进行肾病综合征的进一步治疗。术后3个月随访未发现神经系统后遗症。
    慢性硬膜下血肿很少由肾病综合征引起。对于影像学证实有充分的血肿液化并且可以耐受开颅手术的患者,可以考虑进行钻孔和引流。术后应补充阿托伐他汀作为预防性治疗。肾病综合征应在患者神经状况稳定后立即治疗。
    UNASSIGNED: Chronic subdural hematoma (CSDH) is a common complication of neurosurgery. Craniocerebral trauma is the likely cause. There are no reports relating CSDH with nephrotic syndrome. Its pathogenesis is very rare, and there are no previous reports on treatments for this disease. We report a case of chronic subdural hematoma that may be caused by nephrotic syndrome and review the previous literature on this subject.
    UNASSIGNED: We report a rare case of chronic subdural hematoma that may be caused by nephrotic syndrome. After the patient was admitted to the hospital, relevant laboratory tests were conducted, and a large amount of protein was detected in the patient\'s urine, indicating hypoproteinaemia and hyperlipidemia. The patient was diagnosed with nephrotic syndrome. After the exclusion of related surgical contraindications, the patient underwent trepanation and drainage of the chronic subdural hematoma. Subsequent treatment with oral atorvastatin was provided after surgery. The patient was transferred to the nephrology department for further treatment of nephrotic syndrome if his neurological condition improved. No neurological sequelae were detected at the follow-up visit 3 months after the operation.
    UNASSIGNED: Chronic subdural hematomas are rarely caused by nephrotic syndrome. Trepanation and drainage may be considered for patients confirmed to have adequate hematoma liquefaction on imaging and who can tolerate craniotomy. Atorvastatin should be supplemented as prophylactic treatment after the operation. Nephrotic syndrome should be treated as soon as the patient\'s neurological condition is stable.
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  • 文章类型: Journal Article
    背景:关于复杂的基于社区的计划如何成功实现长期影响,仍然未知。需要更多的洞察力来了解这些方案运作的关键机制。因此,我们在五个实施健康青年的社区进行了深入研究,健康未来(JOGG)方法,荷兰基于社区的肥胖预防计划。我们旨在确定当地利益相关者之间的感知结果和长期影响,并探索潜在的因果途径和工作机制。
    方法:我们使用了波纹效应映射(REM),一种定性的参与式方法来绘制结果图并确定因果路径,在五个社区。我们涉及26个利益相关者,与当地JOGG方法相关的专业人士和政策制定者,分布在八个REM会议上,并与另外24个利益相关者进行了单独访谈。为了揭示工作机制,我们比较了不同社区的结果和因果途径.
    结果:实施了5-9年,参与者认为JOGG改善了对当地利益相关者的所有权,卫生政策,促进健康生活方式的部门间合作和社会规范。因果途径包括微小的初始结果,这些结果创造了实现长期影响的先决条件。尽管社区之间确切的JOGG行动差异很大,我们确定了五种共同的工作机制,通过这些机制,JOGG方法有助于因果途径:(1)用JOGG创造积极的内涵,(2)动员利益相关者参与JOGG方法,(3)促进项目,以提高利益相关者的知识和意识,同时创造促进健康生活方式的成功经验,(4)连接利益相关者,从而促进部门间合作和(5)分享利益相关者的成功,促进健康的生活方式,逐渐形成了参与的社会规范。
    结论:JOGG方法似乎通过激活最初的利益相关者参与和加强所有权过程来发挥作用,政策变化,和部门间合作,以促进健康的生活方式。关键的工作机制可以为JOGG的进一步发展以及其他复杂的基于社区的预防计划提供信息。
    BACKGROUND: Much remains unknown about how complex community-based programmes can successfully achieve long-term impact. More insight is needed to understand the key mechanisms through which these programmes work. Therefore, we conducted an in-depth study in five communities that implemented the Healthy Youth, Healthy Future (JOGG) approach, a Dutch community-based obesity prevention programme. We aimed to identify perceived outcomes and long-term impacts among local stakeholders and explore potential causal pathways and working mechanisms.
    METHODS: We used ripple effects mapping (REM), a qualitative participatory method to map outcomes and identify causal pathways, in five communities. We involved 26 stakeholders, professionals and policy-makers affiliated with the local JOGG approach, spread over eight REM sessions and conducted individual interviews with 24 additional stakeholders. To uncover working mechanisms, we compared outcomes and causal pathways across communities.
    RESULTS: Over 5-9 years of implementation, participants perceived that JOGG had improved ownership of local stakeholders, health policies, intersectoral collaboration and social norms towards promoting healthy lifestyles. Causal pathways comprised small initial outcomes that created the preconditions to enable the achievement of long-term impact. Although exact JOGG actions varied widely between communities, we identified five common working mechanisms through which the JOGG approach contributed to causal pathways: (1) creating a positive connotation with JOGG, (2) mobilizing stakeholders to participate in the JOGG approach, (3) facilitating projects to promote knowledge and awareness among stakeholders while creating successful experiences with promoting healthy lifestyles, (4) connecting stakeholders, thereby stimulating intersectoral collaboration and (5) sharing stakeholder successes that promote healthy lifestyles, which gradually created a social norm of participation.
    CONCLUSIONS: The JOGG approach seems to work through activating initial stakeholder participation and bolstering the process towards ownership, policy change, and intersectoral collaboration to promote healthy lifestyles. Key working mechanisms can inform further development of JOGG as well as other complex community-based prevention programmes.
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  • 文章类型: Published Erratum
    [这更正了文章DOI:10.3389/fhar.202.1078090。].
    [This corrects the article DOI: 10.3389/fphar.2022.1078090.].
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  • 文章类型: Journal Article
    多酚,作为植物的从属代谢产物,已经证明了显著的抗菌作用,抗炎,和科学学习中的抗氧化作用。这些化合物通过各种机制发挥作用,含有对微生物细胞结构的干扰,宿主免疫反应的规则,和自由基的中和。这种多方面的活性使多酚成为维持人类健康和治疗相关疾病的有希望的候选物。值得注意的是,在抗生素耐药性不断升级的背景下,多酚的抗菌性能为开发新的治疗剂提供了创新的途径。此外,它们的抗炎和抗氧化作用对于治疗炎症性疾病和减轻衰老过程具有巨大的潜力。本文旨在总结多酚生物活性的最新发现,强调其在健康和疾病管理中的作用机制和潜在应用。此外,优化多酚提取方法符合可持续和绿色加工的目标,减少环境影响,同时提高食品安全和延长保质期。采用先进的分析技术,如光谱学和色谱法,能保证准确评价多酚含量和功效。这些努力共同促进了食品加工实践和产品质量的持续改进,促进食品行业更健康、更可持续的未来。
    Polyphenols, as subordinate metabolites of plants, have demonstrated significant antibacterial, anti-inflammatory, and antioxidant action in scientific learn. These compounds exert their effects through various mechanisms, containing interference with microbial cell structures, rule of host immune responses, and neutralization of free radicals. This multifaceted activity positions polyphenols as promising candidates for maintaining human health and treating related diseases. Notably, in the context of escalating antibiotic resistance, the antibacterial properties of polyphenols offer innovative avenues for the development of new therapeutic agents. Additionally, their anti-inflammatory and antioxidant effects hold substantial potential for treating inflammatory diseases and mitigating the aging process. This review aims to summarize the latest findings on the biological activities of polyphenols, highlighting their mechanisms of action and potential applications in health and disease management. Furthermore, optimizing polyphenol extraction methods aligns with the goals of sustainable and green processing, reducing environmental impact while enhancing food safety and extending shelf life. Employing advanced analytical techniques, such as spectroscopy and chromatography, can ensure the accurate evaluation of polyphenol content and efficacy. These efforts collectively contribute to the ongoing improvement of food processing practices and product quality, promoting a healthier and more sustainable future in the food industry.
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  • 文章类型: Journal Article
    背景:正念技能训练是辩证行为疗法的核心组成部分,旨在改善边缘性人格障碍(BPD)患者的情绪失调(ED)。然而,变化的潜在机制还没有完全理解。
    方法:共有75名BPD门诊患者参加了为期10周的正念技能训练。进行了具有时滞方法的多级模型,以检查所提出的机制与ED之间的时间动态。渐减,不判断,将身体意识和注意力意识作为假定机制,将ED作为结果进行逐次评估.
    结果:更大的非判断力和身体意识显示了人内效应;在给定的一周内,报告对内部经验和身体意识的非判断力高于其个人平均水平的参与者在接下来的一周内表现出ED的改善。值得注意的是,偏心调节了这些协会,因此,非判断力和身体意识的增加更强烈地预测了那些具有高分中心能力的参与者的ED改善。最后,发现机制与ED之间存在双向关系;当参与者情绪失调比平时状态更严重时,在接下来的一周,他们在机制方面的收益较少。
    结论:了解正念训练的工作原理与优化治疗相关。当目标是改善BPD的情绪调节困难时,临床医生可能会使用策略来增加这些机制。
    BACKGROUND: Mindfulness skills training is a core component of Dialectical Behavior Therapy and aims to improve emotion dysregulation (ED) in people with Borderline Personality Disorder (BPD). However, the underlying mechanisms of change are not fully understood.
    METHODS: A total of 75 BPD outpatients participated in a 10-week mindfulness skills training. Multilevel models with a time-lagged approach were conducted to examine the temporal dynamics between the proposed mechanisms and ED. Decentering, nonjudgment, body awareness and attention awareness as putative mechanisms and ED as outcome were assessed on a session-by-session basis.
    RESULTS: Greater nonjudgment and body awareness showed within-person effects; participants who reported higher nonjudgement of inner experience and body awareness than their own personal average at a given week showed improvement in ED at the following week. Notably, decentering moderated these associations, such that increased nonjudgment and body awareness predicted improvements in ED more strongly in those participants with high decentering ability. Lastly, a bidirectional relationship between the mechanisms and ED was found; when participants were more emotionally dysregulated than their usual state, they showed less gain in the mechanisms at the following week.
    CONCLUSIONS: Knowing how mindfulness training works is relevant to optimize treatments. Clinicians may use strategies to increase these mechanisms when the goal is to improve emotion regulation difficulties in BPD.
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  • 文章类型: Journal Article
    乳腺癌(BC)与全球女性恶性肿瘤有关,发病率和死亡率一直很高。包括手术在内的传统疗法,化疗,放疗和靶向治疗对BC患者有一定的治疗效果,但获得性耐药可导致肿瘤复发和转移。这仍然是治疗期间难以解决的临床挑战。因此,需要继续研究以确定有效的目标和治疗方法,最终实施个性化治疗策略。一些研究表明,长链非编码RNALINC00511与这种情况的发生密切相关,BC的发展和耐药性。在这里,我们将回顾lncRNALINC00511在各种癌症中的结构和作用机制,然后探讨其在BC中的表达及其相关调控机制。此外,我们将讨论LINC00511在BC的生物学功能和潜在的临床应用。
    Breast cancer (BC) is associated with malignant tumors in women worldwide with persistently high incidence and mortality rates. The traditional therapies including surgery, chemotherapy, radiotherapy and targeted therapy have certain therapeutic effects on BC patients, but acquired drug resistance can lead to tumor recurrence and metastasis. This remains a clinical challenge that is difficult to solve during treatment. Therefore, continued research is needed to identify effective targets and treatment methods, to ultimately implement personalized treatment strategies. Several studies have implicated that the long non-coding RNA LINC00511 is closely linked to the occurrence, development and drug resistance of BC. Here we will review the structure and the mechanisms of action of lnc RNA LINC00511 in various cancers, and then explore its expression and its related regulatory mechanisms during BC. In addition, we will discuss the biological functions and the potential clinical applications of LINC00511 in BC.
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  • 文章类型: Journal Article
    核桃(JuglansregiaL.)在改善炎症性肠病(IBD)方面显示出有希望的效果,归因于它们丰富的生物活性化合物。这篇综述全面阐述了核桃在IBD管理中的治疗潜力的关键机制。包括肠粘膜通透性的调节,炎症途径的调节(如NF-kB,COX/COX2,MAPCK/MAPK,和iNOS/NOS),缓解氧化应激,和肠道微生物群的调节。此外,我们强调核桃衍生的抗炎化合物,如多不饱和脂肪酸(PUFA;例如,ω-3PUFA),生育酚,植物甾醇,鞘脂,磷脂,酚类化合物,黄酮类化合物,还有单宁.我们还讨论了独特的抗炎化合物,如肽和多糖,包括它们的提取和制备方法。我们的综述为IBD管理中膳食补充核桃提供了理论基础,并为学术界和工业界提供了指导。在未来,研究应集中于核桃抗炎化合物的目标分离和纯化或优化提取方法以提高其产量,从而帮助食品工业开发针对IBD患者定制的膳食补充剂或核桃衍生的功能性食品。
    Walnuts (Juglans regia L.) have shown promising effects in terms of ameliorating inflammatory bowel disease (IBD), attributed to their abundant bioactive compounds. This review comprehensively illustrates the key mechanisms underlying the therapeutic potential of walnuts in IBD management, including the modulation of intestinal mucosa permeability, the regulation of inflammatory pathways (such as NF-kB, COX/COX2, MAPCK/MAPK, and iNOS/NOS), relieving oxidative stress, and the modulation of gut microbiota. Furthermore, we highlight walnut-derived anti-inflammatory compounds, such as polyunsaturated fatty acids (PUFA; e.g., ω-3 PUFA), tocopherols, phytosterols, sphingolipids, phospholipids, phenolic compounds, flavonoids, and tannins. We also discuss unique anti-inflammatory compounds such as peptides and polysaccharides, including their extraction and preparation methods. Our review provides a theoretical foundation for dietary walnut supplementation in IBD management and provides guidance for academia and industry. In future, research should focus on the targeted isolation and purification of walnut-derived anti-inflammatory compounds or optimizing extraction methods to enhance their yields, thereby helping the food industry to develop dietary supplements or walnut-derived functional foods tailored for IBD patients.
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  • 文章类型: Journal Article
    肝病的全球影响正在稳步增加,发病率和死亡率持续上升。慢性肝病(CLDs)是指肝功能进行性恶化超过6个月,其中包括异常的凝血因子,排毒失败,和肝胆汁淤积.CLDs最常见的病因主要是慢性病毒性肝炎,MAFLD/MASH,酒精性肝病,和遗传因素,引起炎症和对肝脏的伤害,最终导致肝硬化,CLD不可逆转的最后阶段。最新研究表明,三方基序家族蛋白(TRIMs)作为E3连接酶,通过翻译后修饰调节基因和蛋白质表达水平参与CLDs的发展。在这次审查中,我们的目标是阐明CLDs中TRIMs的分子机制和潜在治疗靶点,并为治疗指南和未来研究提供见解.
    The worldwide impact of liver diseases is increasing steadily, with a consistent upswing evidenced in incidence and mortality rates. Chronic liver diseases (CLDs) refer to the liver function\'s progressive deterioration exceeding six months, which includes abnormal clotting factors, detoxification failure, and hepatic cholestasis. The most common etiologies of CLDs are mainly composed of chronic viral hepatitis, MAFLD/MASH, alcoholic liver disease, and genetic factors, which induce inflammation and harm to the liver, ultimately resulting in cirrhosis, the irreversible final stage of CLDs. The latest research has shown that tripartite motif family proteins (TRIMs) function as E3 ligases, which participate in the progression of CLDs by regulating gene and protein expression levels through post-translational modification. In this review, our objective is to clarify the molecular mechanisms and potential therapeutic targets of TRIMs in CLDs and provide insights for therapy guidelines and future research.
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