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  • 文章类型: Journal Article
    动脉粥样硬化(AS)是各种心血管疾病背后的主要病理和全球死亡和残疾的主要原因。最近的研究表明,AS是一种由多种因素引起的慢性血管炎症性疾病。在这种情况下,NLRP3炎性体,作为免疫系统的信号传感器,在AS的发生和进展中起着至关重要的作用。NLRP3炎性体参与内皮损伤,泡沫细胞的形成,AS中的焦亡。因此,靶向NLRP3炎性体为AS提供了一种新的治疗策略.这篇综述强调了对AS发病机制和靶向NLRP3炎性体的药物治疗的最新见解,专注于小分子抑制剂的最佳靶标。这些见解对于合理的药物设计和新的靶向NLRP3炎性体抑制剂治疗AS的药理学评估是有价值的。
    Atherosclerosis (AS) is the primary pathology behind various cardiovascular diseases and the leading cause of death and disability globally. Recent evidence suggests that AS is a chronic vascular inflammatory disease caused by multiple factors. In this context, the NLRP3 inflammasome, acting as a signal transducer of the immune system, plays a critical role in the onset and progression of AS. The NLRP3 inflammasome is involved in endothelial injury, foam cell formation, and pyroptosis in AS. Therefore, targeting the NLRP3 inflammasome offers a new treatment strategy for AS. This review highlights the latest insights into AS pathogenesis and the pharmacological therapies targeting the NLRP3 inflammasome, focusing on optimal targets for small molecule inhibitors. These insights are valuable for rational drug design and the pharmacological assessment of new targeted NLRP3 inflammasome inhibitors in treating AS.
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  • 文章类型: Journal Article
    脑震荡占运动损伤的很大比例。本研究旨在描述诊断为脑震荡的儿科患者的损伤和相关症状的机制(年龄范围,4-17岁)接触运动。
    伤害机制因性别和年龄而异,女性运动员和年龄在4至11岁之间的年轻运动员的脑震荡较少。
    描述性流行病学研究。
    国家电子伤害监测系统被询问向美国急诊部门提交的所有接触性运动脑震荡。分析的运动包括篮球,足球,足球,曲棍球,橄榄球,还有曲棍球.描述性数据,损伤机制,并对每项运动的相关症状进行分析。年和运动持续的脑震荡数量差异,受伤的严重程度,和相关症状使用卡方检验进行比较,并计算了按性别和年龄分层的损伤机制的比例差异。
    在2012年至2021年之间,共有12,602名青年运动员遭受了脑震荡。大多数患者为男性(78.5%),平均年龄13.48岁。足球脑震荡是最常见的,45.32%的脑震荡.损伤的机制主要是运动特异性的,与玩家对玩家接触最常见的整体。年龄较大的男性运动员更有可能因球员与球员的接触而发生脑震荡,而年轻运动员受到头对地机制的影响更大。症状表现不是运动特异性的,头痛和头晕是最常见的表现,分别为41.2%和26.2%,分别。
    受伤的最重要的整体机制是球员之间的接触,尤其是老年男性青年运动员,而年轻运动员更有可能因头对地受伤而脑震荡。
    UNASSIGNED: Concussions make up a significant proportion of sports injuries. This study aimed to describe the mechanisms of injury and associated symptoms of pediatric patients diagnosed with concussions (age range, 4-17 years) from contact sports.
    UNASSIGNED: Mechanisms of injury would differ based on sex and age, with female athletes and younger athletes aged 4 to 11 years sustaining fewer concussions from player-to-player contact.
    UNASSIGNED: Descriptive epidemiology study.
    UNASSIGNED: The National Electronic Injury Surveillance System was queried for all contact sport concussions presented to United States emergency departments. The sports analyzed included basketball, football, soccer, hockey, rugby, and lacrosse. Descriptive data, mechanisms of injury, and associated symptoms were analyzed for each sport. Differences in the number of concussions sustained by year and sport, the severity of the injury, and associated symptoms were compared using chi-square test, and differences in proportion were calculated for mechanisms of injury stratified by sex and age.
    UNASSIGNED: A total of 12,602 youth athletes sustained concussions between 2012 and 2021. Most patients were male (78.5%), with a mean age of 13.48 years. Football concussions were the most common, with 45.32% of the concussions. The mechanism of injury was largely sport-specific, with player-to-player contact the most common overall. Older male athletes were more likely to have concussions from player-to-player contact, whereas younger athletes were more impacted by head-to-ground mechanisms. Symptom presentation was not sport-specific, and headache and dizziness were the most common presentation at 41.2% and 26.2%, respectively.
    UNASSIGNED: The most important overall mechanism of injury was player-to-player contact, especially in older male youth athletes, whereas younger athletes were more likely to be concussed due to head-to-ground injuries.
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  • 文章类型: Journal Article
    高毒力和耐碳青霉烯类肺炎克雷伯菌的进化可分为三种主要模式:KL1/KL2-hvKp菌株进化为CR-hvKp,耐碳青霉烯类肺炎克雷伯菌(CRKp)菌株向hv-CRKp的演变,以及经典肺炎克雷伯菌(cKp)获得携带碳青霉烯抗性和毒力基因的杂交质粒。这些菌株的特点是多药耐药性,高毒力,和高传染性。目前,没有有效的方法来治疗和监测这种病原体。此外,这些细菌在医院抗生素的压力下不断的水平转移和克隆传播导致了更多的耐药菌株的出现。这篇综述讨论了高毒力和耐碳青霉烯类肺炎克雷伯菌的进化和分布特征,碳青霉烯耐药和高毒力的机制,易感性的危险因素,感染综合征,治疗方案,实时监测和预防控制措施。它还概述了用于治疗这种病原体的抗菌药物的耐药机制,为开发新药提供见解,联合疗法,和“一个健康”的方法。缩小监测范围但加大执行力度是可行的解决办法。菌株的监测可以主要集中在医院和城市污水处理厂。
    The evolution of hypervirulent and carbapenem-resistant Klebsiella pneumoniae can be categorized into three main patterns: the evolution of KL1/KL2-hvKp strains into CR-hvKp, the evolution of carbapenem-resistant K. pneumoniae (CRKp) strains into hv-CRKp, and the acquisition of hybrid plasmids carrying carbapenem resistance and virulence genes by classical K. pneumoniae (cKp). These strains are characterized by multi-drug resistance, high virulence, and high infectivity. Currently, there are no effective methods for treating and surveillance this pathogen. In addition, the continuous horizontal transfer and clonal spread of these bacteria under the pressure of hospital antibiotics have led to the emergence of more drug-resistant strains. This review discusses the evolution and distribution characteristics of hypervirulent and carbapenem-resistant K. pneumoniae, the mechanisms of carbapenem resistance and hypervirulence, risk factors for susceptibility, infection syndromes, treatment regimens, real-time surveillance and preventive control measures. It also outlines the resistance mechanisms of antimicrobial drugs used to treat this pathogen, providing insights for developing new drugs, combination therapies, and a \"One Health\" approach. Narrowing the scope of surveillance but intensifying implementation efforts is a viable solution. Monitoring of strains can be focused primarily on hospitals and urban wastewater treatment plants.
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  • 文章类型: Journal Article
    随着消费者对健康和保健意识的提高,对加强食品安全的需求正在迅速增加。在食品材料的热加工过程中产生化学污染物,包括多环芳烃,杂环芳香胺,丙烯酰胺每天都在世界各地的每个厨房里发生。与外来化学污染物不同(例如,杀虫剂,除草剂,和化肥),这些内生化学污染物发生在烹饪过程中,不能在食用前去除。因此,在寻找减少这种热诱导的化学污染物的方法方面已经投入了大量的努力。最近,已发现添加生物活性化合物是有效且有前景的。然而,尚未对该实用科学进行系统的审查。本文旨在总结生物活性化合物在食品热处理过程中控制化学污染物的最新应用。深入讨论了这些化学污染物的潜在生成机制和毒性作用,以揭示如何以及为什么通过添加某些生物活性成分来抑制它们。特定生物活性化合物的例子,如酚类化合物和有机酸,以及他们的应用场景,概述了。最后,在全面总结和反思参考文献的基础上,对未来的发展提出了展望和期望。
    With rising consumer awareness of health and wellness, the demand for enhanced food safety is rapidly increasing. The generation of chemical contaminants during the thermal processing of food materials, including polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, and acrylamide happens every day in every kitchen all around the world. Unlike extraneous chemical contaminants (e.g., pesticides, herbicides, and chemical fertilizers), these endogenic chemical contaminants occur during the cooking process and cannot be removed before consumption. Therefore, much effort has been invested in searching for ways to reduce such thermally induced chemical contaminants. Recently, the addition of bioactive compounds has been found to be effective and promising. However, no systematic review of this practical science has been made yet. This review aims to summarize the latest applications of bioactive compounds for the control of chemical contaminants during food thermal processing. The underlying generation mechanisms and the toxic effects of these chemical contaminants are discussed in depth to reveal how and why they are suppressed by the addition of certain bioactive ingredients. Examples of specific bioactive compounds, such as phenolic compounds and organic acids, as well as their application scenarios, are outlined. In the end, outlooks and expectations for future development are provided based on a comprehensive summary and reflection of references.
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  • 文章类型: Journal Article
    Ferroptosis是细胞死亡的非凋亡形式,在细胞形态方面与众所周知的细胞死亡形式有很大不同。遗传学,和生物化学。细胞铁凋亡的三个主要途径是系统Xc-/谷胱甘肽过氧化物酶4(GPX4),脂质代谢,和铁代谢。自从发现铁性死亡以来,越来越多的证据揭示了它在几种疾病中的关键调节作用,特别是作为癌症治疗的新的潜在靶点,从而在肿瘤生物学和抗肿瘤治疗领域引起越来越多的关注。因此,将铁性凋亡确定为潜在的治疗靶标存在广阔的前景。在这次审查中,我们旨在系统地总结铁死亡的激活和防御机制,突出治疗目标,并讨论了用于铁凋亡调节的纳米药物的设计。此外,我们选择介绍当前铁中毒研究的优缺点,并对相关领域的未来方向提供乐观的看法。总的来说,我们旨在为进一步的铁死亡研究提供新思路,并为疾病诊断和治疗提供新的策略。
    Ferroptosis is a nonapoptotic form of cell death and differs considerably from the well-known forms of cell death in terms of cell morphology, genetics, and biochemistry. The three primary pathways for cell ferroptosis are system Xc-/glutathione peroxidase 4 (GPX4), lipid metabolism, and ferric metabolism. Since the discovery of ferroptosis, mounting evidence has revealed its critical regulatory role in several diseases, especially as a novel potential target for cancer therapy, thereby attracting increasing attention in the fields of tumor biology and anti-tumor therapy. Accordingly, broad prospects exist for identifying ferroptosis as a potential therapeutic target. In this review, we aimed to systematically summarize the activation and defense mechanisms of ferroptosis, highlight the therapeutic targets, and discuss the design of nanomedicines for ferroptosis regulation. In addition, we opted to present the advantages and disadvantages of current ferroptosis research and provide an optimistic vision of future directions in related fields. Overall, we aim to provide new ideas for further ferroptosis research and inspire new strategies for disease diagnosis and treatment.
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  • 文章类型: Journal Article
    心房颤动(AF)已经受到科学家和临床医生的广泛关注,因为它是一种非常常见的临床疾病。由于其特殊的血液动力学变化,AF具有高致残率和死亡率。到目前为止,虽然房颤有一些治疗手段,由于其复杂的危险因素和病理生理机制,它仍然是一种不治之症,这是全球公共卫生的难题。年龄是房颤的重要独立危险因素。房颤的发病率随年龄增长而增加。迄今为止,没有关于衰老相关AF的全面审查.在这次审查中,我们系统地讨论了衰老相关房颤的病理生理证据,特别是探索线粒体功能障碍的病理生理机制,端粒磨耗,细胞衰老,禁用巨自噬,和肠道菌群失调涉及最近的研究与衰老相关的AF。我们希望通过探索与衰老相关的AF的各个维度,我们可以更好地理解年龄和房颤之间的具体关系,这对于创新治疗与衰老相关的房颤可能至关重要。
    Atrial fibrillation (AF) has been receiving a lot of attention from scientists and clinicians because it is an extremely common clinical condition. Due to its special hemodynamic changes, AF has a high rate of disability and mortality. So far, although AF has some therapeutic means, it is still an incurable disease because of its complex risk factors and pathophysiologic mechanisms, which is a difficult problem for global public health. Age is an important independent risk factor for AF, and the incidence of AF increases with age. To date, there is no comprehensive review on aging-associated AF. In this review, we systematically discuss the pathophysiologic evidence for aging-associated AF, and in particular explore the pathophysiologic mechanisms of mitochondrial dysfunction, telomere attrition, cellular senescence, disabled macroautophagy, and gut dysbiosis involved in recent studies with aging-associated AF. We hope that by exploring the various dimensions of aging-associated AF, we can better understand the specific relationship between age and AF, which may be crucial for innovative treatments of aging-associated AF.
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  • 文章类型: Journal Article
    多不饱和脂肪酸(PUFA),特别是omega-3(n-3)和omega-6(n-6),由于其多方面的影响,不仅在管理各种病理状况方面,而且在维持个人整体健康方面也受到了广泛的关注。不成比例的高n-6与n-3比率有助于各种疾病的发展,包括癌症。它是世界范围内死亡的主要原因,具有深刻的社会和经济负担。流行病学研究和临床试验结合动物和细胞培养模型已经证明了n-3PUFA在降低包括乳腺癌在内的各种癌症风险方面的有益作用。前列腺癌和结肠癌.n-3PUFA的抗癌作用主要归因于它们在调节广泛的细胞过程中的作用,包括膜动力学。凋亡,炎症,血管生成,氧化应激,基因表达和信号转导途径。相反,n-6PUFA已被证明具有促肿瘤作用;然而,不一致的发现和有争议的数据强调了进一步调查的必要性。然而,未来最大的挑战之一是优化n-6与n-3的比例,尽管有遗传倾向,年龄,性别和疾病严重程度。此外,需要更好地了解这些PUFA的潜在风险和益处以及基本作用的细胞和分子机制,以探索其在癌症治疗中作为佐剂的作用.所有这些方面都将在本章中进行回顾。
    Polyunsaturated fatty acids (PUFAs), notably omega-3 (n-3) and omega-6 (n-6), have received much attention owing to their multifaceted effects not only in the management of diverse pathological conditions but also in the maintenance of overall health of an individual. A disproportionately high n-6 to n-3 ratio contributes to the development of various disorders including cancer, which ranks as a leading cause of death worldwide with profound social and economic burden. Epidemiological studies and clinical trials combined with the animal and cell culture models have demonstrated the beneficial effects of n-3 PUFAs in reducing the risk of various cancer types including breast, prostate and colon cancer. The anti-cancer actions of n-3 PUFAs are mainly attributed to their role in the modulation of a wide array of cellular processes including membrane dynamics, apoptosis, inflammation, angiogenesis, oxidative stress, gene expression and signal transduction pathways. On the contrary, n-6 PUFAs have been shown to exert pro-tumor actions; however, the inconsistent findings and controversial data emphasize upon the need to further investigation. Nevertheless, one of the biggest challenges in future is to optimize the n-6 to n-3 ratio despite the genetic predisposition, age, gender and disease severity. Moreover, a better understanding of the potential risks and benefits as well as the cellular and molecular mechanisms of the basic actions of these PUFAs is required to explore their role as adjuvants in cancer therapy. All these aspects will be reviewed in this chapter.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    开发具有高核糖核酸(RNA)含量的微生物对于RNA工业至关重要。已经进行了许多研究以通过基因工程增强酵母细胞中的RNA产生,然而精确的机制仍然难以捉摸。以前,TAL1或PGM2的上调和PRS5或DBP8的单独删除可以增加巴氏酵母中的RNA含量。在这项研究中,在这些转基因菌株中,细胞断裂后,细胞内核苷酸水平显着增加。菌株中PRS5和DBP8的缺失促使具有相似功能的基因上调,从而增加了基因通路的流动。此外,在G03-△PRS5菌株中观察到编码细胞周期依赖性蛋白激酶(CDK)的基因上调。TAL1和PGM2对RNA含量的影响归因于戊糖磷酸途径(PPP)。多基因重组菌株的RNA含量,G03-△PRS5+△DBP8和G03-△PRS5+△DBP8+PGM2,表现出最显著的改善,与亲本菌株相比,分别增加了71.8%和80.1%。此外,在这些菌株中,细胞的最大比生长速率增加。这项研究为巴斯德氏链球菌高核酸合成的遗传机制提供了有价值的见解。
    Developing microorganisms with a high ribonucleic acid (RNA) content is crucial for the RNA industry. Numerous studies have been conducted to enhance RNA production in yeast cells through genetic engineering, yet precise mechanisms remain elusive. Previously, upregulation of TAL1 or PGM2 and deleting PRS5 or DBP8 individually could increase the RNA content in Saccharomyces pastorianus. In this study, within these genetically modified strains, the intracellular nucleotide levels notably increased following cell fragmentation. Deletion of PRS5 and DBP8 within the strain prompted the upregulation of genes sharing similar functions, consequently augmenting the flow of the gene pathway. Furthermore, the upregulation of genes encoding cell-cycle-dependent protein kinases (CDK) was observed in the G03-△PRS5 strain. The influence of TAL1 and PGM2 on RNA content was attributed to the pentose phosphate pathway (PPP). The RNA content of polygenic recombinant strains, G03-△PRS5+△DBP8 and G03-△PRS5+△DBP8+PGM2, displayed the most significant improvement, increasing by 71.8 and 80.1% when compared to the parental strain. Additionally, the maximum specific growth rate of cells increased in these strains. This study contributes valuable insights into the genetic mechanisms underlying high nucleic acid synthesis in S. pastorianus.
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  • 文章类型: Journal Article
    细菌抗生素耐药性已被认为是对公共卫生的全球威胁。它挑战了目前在临床实践中使用的抗生素,并导致严重且通常致命的传染病。对抗抗生素抗性细菌(ARB)的斗争变得越来越紧迫。虽然了解抗性的分子机制是先决条件,之前已经提出了几种主要机制,包括细菌外排系统,降低细胞膜通透性,抗生素被酶灭活,目标修改,和目标保护。在这种情况下,这篇综述提出了一组有希望和潜在的策略,以对抗抗生素耐药性/耐药细菌。不同类型的直接作用和间接电阻断路器,如外排泵抑制剂,抗生素佐剂,和氧化处理进行了讨论。此外,重点介绍了用于快速耐药性鉴定的新兴多组学方法和有希望的现有抗生素替代品.总的来说,这篇综述表明,需要继续努力和投资于研究,以开发新的抗生素和现有抗生素的替代品,并将其转化为环境和临床应用。
    Bacterial antibiotic resistance has been recognized as a global threat to public health. It challenges the antibiotics currently used in clinical practice and causes severe and often fatal infectious diseases. Fighting against antibiotic-resistant bacteria (ARB) is growing more urgent. While understanding the molecular mechanisms that underlie resistance is a prerequisite, several major mechanisms have been previously proposed including bacterial efflux systems, reduced cell membrane permeability, antibiotic inactivation by enzymes, target modification, and target protection. In this context, this review presents a panel of promising and potential strategies to combat antibiotic resistance/resistant bacteria. Different types of direct-acting and indirect resistance breakers, such as efflux pump inhibitors, antibiotic adjuvants, and oxidative treatments are discussed. In addition, the emerging multi-omics approaches for rapid resistance identification and promising alternatives to existing antibiotics are highlighted. Overall, this review suggests that continued effort and investment in research are required to develop new antibiotics and alternatives to existing antibiotics and translate them into environmental and clinical applications.
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