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Neurobiological Mechanisms of Ketamine Use, its Addiction, and Withdrawal: A Mini Review.
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2025-03-03 DOI: 10.2174/0127724328362434250224105609
Sin Hui Ng, Yu Zhao Lee, Ming Ye Hong, Audrey Siew Foong Kow, Annette d'Arqom, Chau Ling Tham, Yu-Cheng Ho, MIng Tatt Lee

Ketamine, a substance used for anesthesia and known for inducing dissociation, can lead to addiction and the development of severe withdrawal symptoms. Ketamine alters brain networks before affecting somesthetic sensation. Ketamine abuse was especially prevalent in East and Southeast Asia, and its popularity has continued to expand globally in recent decades. Ketamine is gaining popularity in the public and private sectors as a cheaper off-label depression treatment. Unfortunately, ketamine may cause side effects, such as heart and blood vessel instability, respiratory depression, liver injury, hallucinations, etc. The pain-relieving and mental effects of ketamine might induce reliance; thus, it should be used cautiously. This review highlights the neurobiological processes underpinnings of ketamine's addictive potential, withdrawal, and its effects on brain networks like the prefrontal cortex, hippocampus, and mesolimbic pathway, which play vital roles in decision-making, memory, and reward processing. In addition, the involvement of neurotransmitter systems, specifically glutamate and dopamine, in mediating the addictive properties of ketamine and the neuroadaptive changes that occurred during withdrawal are also discussed. It also explains that low-dose ketamine can alter the secretion of stress hormone cortisol and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, possibly attributed to the current repurposing study of ketamine as a fast-acting antidepressant. Understanding these pathways is essential for developing effective ketamine addiction treatments, managing withdrawal symptoms, and possibly reversing brain changes for the betterment of human health and psychological well- being.

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引用次数: 0
The Gut Connection: A Narrative Review on the In-depth Analysis of Gut Microbiota and Metabolites in Depression.
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-31 DOI: 10.2174/0127724328332998250118182255
Ayesha Sultana, Md Sadique Hussain, Mudasir Maqbool, Mohit Agrawal, Ajay Singh Bisht, Navneet Khurrana, Gurvinder Singh, Rajesh Kumar

Depression is a prevalent mood disorder with significant public health implications. Despite extensive research, its precise causes remain inadequately understood. Recently, interest has surged in the role of the gut microbiome and its metabolites in the pathophysiology of depression. This review aims to provide a comprehensive overview of the relationship between gut microbiota, its metabolites, and depression while exploring potential mechanisms influencing the efficacy of antidepressant medications. A narrative review methodology was employed, synthesizing recent studies utilizing a multi-omics approach. We examined alterations in gut microbiome composition and metabolite production in individuals diagnosed with depression, discussing the technical tools and methods commonly applied in this research area. The findings indicate that individuals with depression show significant alterations in gut microbiome composition, notably an imbalance in Firmicutes, Bacteroidetes, and Actinobacteria. Changes in metabolite production, including short-chain fatty acids, tryptophan, and bile acids, were also observed. Moreover, the review highlights that antidepressant medications may exert their therapeutic effects by modulating gut microbiota and its metabolites. This review emphasizes the intricate interplay between gut microbiota, its metabolites, and depression, revealing critical insights into the mechanisms underlying antidepressant efficacy. We recommend that future research focus on elucidating these interactions to develop innovative therapeutic strategies, potentially transforming the management of depression through microbiota-targeted approaches.

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引用次数: 0
Breaking the Mold: Advances and Hurdles in Antifungal Resistance Management for Dermatophytes.
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-30 DOI: 10.2174/0127724328328331241217194034
Zaid Ra'ed Alnsour, Mouiad Ra'ed Alnsour, Ayham Ra'ed Alnsour, Majd Majed Massadeh, Karem Hassan Alzoubi, Majed Mohammad Masadeh

Examining antifungal resistance in dermatophytes is crucial in infectious diseases, dermatology, and clinical microbiology. The increasing occurrence of resistant infections and their influence on the effectiveness of therapy seem overwhelming. This study examines the present condition of antifungal resistance in dermatophytes, highlighting the need for ongoing and up-to-date research. Fungal diseases constantly change, and fungi have developed new resistance mechanisms. Here, we analyze the historical context of research on antifungal resistance, examining the variables that contribute to the development of resistance, such as the growing use of antifungals in clinical and agricultural contexts. We also explore the consequences of resistance to antifungal agents in clinical practice and public health. The review emphasizes the significance of new diagnostic technologies, like next-generation sequencing, in comprehending resistance mechanisms. It also underscores the crucial role of international collaboration in tackling this worldwide health concern. In conclusion, the paper emphasizes the need for continuous research to adjust to the evolving epidemiology of dermatophyte infections, create efficient treatment approaches, and guide public health interventions. This will ensure that the management of antifungal resistance is grounded in the most up-to-date scientific knowledge and optimal methods.

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引用次数: 0
Targeting SIRT1 by Scopoletin to Inhibit XBB.1.5 COVID-19 Life Cycle. 通过 Scopoletin 靶向 SIRT1 抑制 XBB.1.5 COVID-19 生命周期。
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.2174/0127724328281178240225082456
Mohammadjavad Sotoudeheian, Seyed-Mohamad-Sadegh Mirahmadi, Mohammad Pirhayati, Navid Farahmandian, Reza Azarbad, Hamidreza Pazoki Toroudi

Natural products have historically driven pharmaceutical discovery, but their reliance has diminished with synthetic drugs. Approximately 35% of medicines originate from natural products. Scopoletin, a natural coumarin compound found in herbs, exhibits antioxidant, hepatoprotective, antiviral, and antimicrobial properties through diverse intracellular signaling mechanisms. Furthermore, it also enhances the activity of antioxidants. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes viral pneumonia through cytokine storms and systemic inflammation. Cellular autophagy pathways play a role in coronavirus replication and inflammation. The Silent Information Regulator 1 (SIRT1) pathway, linked to autophagy, protects cells via FOXO3, inhibits apoptosis, and modulates SIRT1 in type-II epithelial cells. SIRT1 activation by adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) enhances the autophagy cascade. This pathway holds therapeutic potential for alveolar and pulmonary diseases and is crucial in lung inflammation. Angiotensin-converting enzyme 2 (ACE-2) activation, inhibited by reduced expression, prevents COVID-19 virus entry into type-II epithelial cells. The coronavirus disease 2019 (COVID-19) virus binds ACE-2 to enter into the host cells, and XBB.1.5 COVID-19 displays high ACE-2-binding affinity. ACE-2 expression in pneumocytes is regulated by signal transducers and activators of transcription-3 (STAT3), which can increase COVID-19 virus replication. SIRT1 regulates STAT3, and the SIRT1/STAT3 pathway is involved in lung diseases. Therapeutic regulation of SIRT1 protects the lungs from inflammation caused by viral-mediated oxidative stress. Scopoletin, as a modulator of the SIRT1 cascade, can regulate autophagy and inhibit the entry and life cycle of XBB.1.5 COVID-19 in host cells.

天然产品在历史上一直推动着药物的发现,但随着合成药物的出现,对天然产品的依赖程度有所降低。大约 35% 的药物源自天然产品。Scopoletin 是一种存在于草药中的天然香豆素化合物,它通过多种细胞内信号传导机制表现出抗氧化、保肝、抗病毒和抗菌特性。此外,它还能增强抗氧化剂的活性。严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)通过细胞因子风暴和全身炎症引起病毒性肺炎。细胞自噬途径在冠状病毒复制和炎症中发挥了作用。与自噬有关的沉默信息调节器 1(SIRT1)通路通过 FOXO3 保护细胞,抑制细胞凋亡,并调节 II 型上皮细胞中的 SIRT1。单磷酸腺苷激活蛋白激酶(AMPK)和哺乳动物雷帕霉素靶蛋白激酶(mTOR)对 SIRT1 的激活增强了自噬级联。这一途径具有治疗肺泡和肺部疾病的潜力,在肺部炎症中至关重要。血管紧张素转换酶 2(ACE-2)的活化,通过减少表达受到抑制,可防止 COVID-19 病毒进入 II 型上皮细胞。冠状病毒病2019(COVID-19)病毒与ACE-2结合进入宿主细胞,XBB.1.5 COVID-19显示出很高的ACE-2结合亲和力。ACE-2在肺细胞中的表达受信号转导和激活转录-3(STAT3)的调控,而STAT3可增加COVID-19病毒的复制。SIRT1 可调节 STAT3,而 SIRT1/STAT3 通路与肺部疾病有关。治疗性调节 SIRT1 可保护肺部免受病毒介导的氧化应激引起的炎症。Scopoletin 作为 SIRT1 级联的调节剂,可以调节自噬,抑制 XBB.1.5 COVID-19 在宿主细胞中的进入和生命周期。
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引用次数: 0
Translational Approach using Advanced Therapy Medicinal Products for Huntington's Disease. 利用先进疗法药物产品治疗亨廷顿氏症的转化方法。
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.2174/0127724328300166240510071548
Maryam Alsadat Mousavi, Maliheh Rezaei, Mahsa Pourhamzeh, Mehri Salari, Nikoo Hossein-Khannazer, Anastasia Shpichka, Seyed Massood Nabavi, Peter Timashev, Massoud Vosough

Current therapeutic approaches for Huntington's disease (HD) focus on symptomatic treatment. Therefore, the unavailability of efficient disease-modifying medicines is a significant challenge. Regarding the molecular etiology, targeting the mutant gene or advanced translational steps could be considered promising strategies. The evidence in gene therapy suggests various molecular techniques, including knocking down mHTT expression using antisense oligonucleotides and small interfering RNAs and gene editing with zinc finger proteins and CRISPR-Cas9-based techniques. Several post-transcriptional and post-translational modifications have also been proposed. However, the efficacy and long-term side effects of these modalities have yet to be verified. Currently, cell therapy can be employed in combination with conventional treatment and could be used for HD in which the structural and functional restoration of degenerated neurons can occur. Several animal models have been established recently to develop cell-based therapies using renewable cell sources such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stromal cells, and neural stem cells. These models face numerous challenges in translation into clinics. Nevertheless, investigations in Advanced Therapy Medicinal Products (ATMPs) open a promising window for HD research and their clinical application. In this study, the ATMPs entry pathway in HD management was highlighted, and their advantages and disadvantages were discussed.

目前治疗亨廷顿氏病(HD)的方法主要集中在对症治疗上。因此,无法获得有效的疾病改变药物是一项重大挑战。关于分子病因学,靶向突变基因或先进的转化步骤被认为是有前景的策略。基因治疗方面的证据表明存在多种分子技术,包括利用反义寡核苷酸和小干扰 RNA 敲低 mHTT 的表达,以及利用锌指蛋白和 CRISPR-Cas9 技术进行基因编辑。此外,还提出了一些转录后和翻译后修饰方法。然而,这些方法的疗效和长期副作用还有待验证。目前,细胞疗法可与常规治疗相结合,并可用于 HD,使退化的神经元在结构上和功能上得到恢复。最近建立了几种动物模型,利用胚胎干细胞、诱导多能干细胞、间充质基质细胞和神经干细胞等可再生细胞来源开发细胞疗法。这些模型在应用于临床时面临着诸多挑战。然而,先进治疗药物产品(ATMP)的研究为人类免疫缺陷病毒研究及其临床应用打开了一扇前景广阔的窗口。本研究强调了高级治疗药物在 HD 治疗中的应用途径,并讨论了它们的优缺点。
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引用次数: 0
Spinal Analgesia: Initial Preclinical and Clinical Studies. 脊髓镇痛:初步临床前和临床研究。
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.2174/0127724328310926240704101041
Igor Kissin
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引用次数: 0
Efficacy and Safety of Glycopyrrolate in the Management of Organophosphate and Carbamate Poisoning: A Systematic Review. 甘草酸苷治疗有机磷和氨基甲酸酯中毒的有效性和安全性:系统综述。
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.2174/0127724328290595240509051331
Muhammed Rashid, Pooja Gopal Poojari, Viji Pulikkel Chandran, Rashmi Shetty, Harsimran Kaur, Sreedharan Nair, Girish Thunga

Objective: There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and safety of glycopyrrolate in the management of OPC poisoning.

Methodology: Databases such as PubMed, Scopus, Embase, and Cochrane Library were extensively searched from inception to November 2022 and updated till October 2023. Interventional, observational, and descriptive studies assessing the efficacy and safety of glycopyrrolate administered in any dose, route, and duration for the management of OPC poisoning published in the English language were considered for this review. The treatment with any other regimen that did not include glycopyrrolate was regarded as the comparator. The survival, intensive care unit (ICU) and ventilatory outcomes were considered efficacy outcomes, and adverse effects were considered safety outcomes. Suitable quality assessment tools were used to assess the risk of bias in the included studies. Two independent reviewers were involved in the study selection, data extraction, and quality assessment and any discrepancies were resolved through mutual discussion or consultation with a third reviewer.

Results: A total of 9 studies (2 RCTs, 4 cohorts, 1 case series, and 2 case reports) out of 591 nonduplicate records were considered for this review. Overall, the RCTs were observed to have a moderate quality, and observational studies and descriptive studies were found to have good quality. All the included studies used atropine administration as a standard treatment option along with glycopyrrolate. The OPC patients treated with glycopyrrolate had a fewer hospitalization days with comparable recovery and ventilatory outcomes than those that had not been treated with glycopyrrolate. The occurrence of adverse events and complications was lower in the glycopyrrolate group than in the control group.

Conclusion: Currently, there is a lack of comparative studies to recommend the use of glycopyrrolate in OPC poisoning, and further interventional studies are required to make an evidencebased recommendation on this topic.

目的:在处理有机磷和氨基甲酸酯(OPC)中毒方面,缺乏有关解毒剂有效性的证据。我们旨在回顾甘草酸苷治疗 OPC 中毒的有效性和安全性:对 PubMed、Scopus、Embase 和 Cochrane Library 等数据库进行了广泛检索,检索时间从开始至 2022 年 11 月,更新至 2023 年 10 月。本综述考虑了以英语发表的、评估甘草酸苷以任何剂量、途径和持续时间治疗 OPC 中毒的有效性和安全性的干预性、观察性和描述性研究。使用不包括甘草酸苷的任何其他方案进行治疗均被视为参照组。存活率、重症监护室(ICU)天数和通气结果被视为疗效结果,不良反应被视为安全性结果。我们使用了合适的质量评估工具来评估纳入研究的偏倚风险。两名独立审稿人参与了研究的筛选、数据提取和质量评估,如有任何分歧,将通过相互讨论或咨询第三名审稿人来解决:在 591 条非重复记录中,共有 9 项研究(2 项研究性临床试验、4 项队列研究、1 项病例系列研究和 2 项病例报告)被纳入本综述。总体而言,研究性试验的质量中等,观察性研究和描述性研究的质量良好。所有纳入的研究都将阿托品和甘珀酸作为标准治疗方案。与未使用甘草酸苷治疗的患者相比,使用甘草酸苷治疗的 OPC 患者住院天数较少,恢复和通气效果相当。甘草酸苷组的不良事件和并发症发生率低于对照组:结论:目前,尚缺乏建议在 OPC 中毒中使用甘草酸苷的比较研究,因此需要进一步的干预研究才能就此提出循证建议。
{"title":"Efficacy and Safety of Glycopyrrolate in the Management of Organophosphate and Carbamate Poisoning: A Systematic Review.","authors":"Muhammed Rashid, Pooja Gopal Poojari, Viji Pulikkel Chandran, Rashmi Shetty, Harsimran Kaur, Sreedharan Nair, Girish Thunga","doi":"10.2174/0127724328290595240509051331","DOIUrl":"10.2174/0127724328290595240509051331","url":null,"abstract":"<p><strong>Objective: </strong>There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and safety of glycopyrrolate in the management of OPC poisoning.</p><p><strong>Methodology: </strong>Databases such as PubMed, Scopus, Embase, and Cochrane Library were extensively searched from inception to November 2022 and updated till October 2023. Interventional, observational, and descriptive studies assessing the efficacy and safety of glycopyrrolate administered in any dose, route, and duration for the management of OPC poisoning published in the English language were considered for this review. The treatment with any other regimen that did not include glycopyrrolate was regarded as the comparator. The survival, intensive care unit (ICU) and ventilatory outcomes were considered efficacy outcomes, and adverse effects were considered safety outcomes. Suitable quality assessment tools were used to assess the risk of bias in the included studies. Two independent reviewers were involved in the study selection, data extraction, and quality assessment and any discrepancies were resolved through mutual discussion or consultation with a third reviewer.</p><p><strong>Results: </strong>A total of 9 studies (2 RCTs, 4 cohorts, 1 case series, and 2 case reports) out of 591 nonduplicate records were considered for this review. Overall, the RCTs were observed to have a moderate quality, and observational studies and descriptive studies were found to have good quality. All the included studies used atropine administration as a standard treatment option along with glycopyrrolate. The OPC patients treated with glycopyrrolate had a fewer hospitalization days with comparable recovery and ventilatory outcomes than those that had not been treated with glycopyrrolate. The occurrence of adverse events and complications was lower in the glycopyrrolate group than in the control group.</p><p><strong>Conclusion: </strong>Currently, there is a lack of comparative studies to recommend the use of glycopyrrolate in OPC poisoning, and further interventional studies are required to make an evidencebased recommendation on this topic.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"38-48"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anatomy, Etiology, Management, and Medico-Legal Implications of Botulinum-induced Blepharoptosis.
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.2174/0127724328310459240809073519
Giulio Nittari, Demetris Savva, Filippo Gibelli, Diana Vulcanescu, Domenico De Leo, Giovanna Ricci

Botulinum toxin injections, a popular aesthetic treatment, have over 7.4 million beneficiaries in the U.S. Despite their safety record, these injections pose potential complications. It is essential for aesthetic practitioners to manage these complications with the least impact on the patient. Upper eyelid ptosis, though rare, is a significant side effect of botulinum toxin injections. Through our study, we have identified the etiology, anatomy, and therapeutic management of botulinum- induced blepharoptosis. Hence, the goal of this study was to identify the basic aetiology of blepharoptosis and manage this complication, as well as discuss the basis of medico-legal implications involving this popular drug. The complex medico-legal implications of botulinum toxin-induced blepharoptosis call for continuous discourse, education, and clarity on drug-use legal standards. With evolving global and Italian legislation, practitioners must ensure they meet care standards, weighing treatment benefits against potential legal and ethical outcomes. Blepharoptosis is a rare but significant complication of botulinum-type injections. Etiology and thorough anatomy are crucial for avoiding this complication and handling it with the least impact on the patient. Medico-legal implications are currently not fully established, but the basis of aesthetic treatment standards, as well as continuing medical education, will ensure correct medico-legal coverage of such complications.

肉毒杆菌毒素注射是一种流行的美容疗法,在美国有 740 多万受益者。尽管有安全记录,但这些注射仍有潜在的并发症。对于美容从业者来说,在控制这些并发症的同时将其对患者的影响降至最低至关重要。上眼睑下垂虽然罕见,但却是肉毒杆菌毒素注射的一个重要副作用。通过研究,我们确定了肉毒杆菌引起的眼睑下垂的病因、解剖和治疗方法。因此,本研究的目标是确定眼睑外翻的基本病因,处理这种并发症,并讨论涉及这种流行药物的医学法律影响的基础。肉毒杆菌毒素诱发的眼睑外翻具有复杂的医学法律意义,需要持续开展讨论、教育,并明确药物使用的法律标准。随着全球和意大利立法的不断发展,从业人员必须确保他们符合护理标准,权衡治疗效果与潜在的法律和道德后果。眼睑外翻是肉毒杆菌注射的一种罕见但严重的并发症。病因学和透彻的解剖学是避免这种并发症并将其对患者的影响降至最低的关键。医学法律影响目前尚未完全确定,但美容治疗标准的基础以及持续医学教育将确保对此类并发症的正确医学法律处理。
{"title":"Anatomy, Etiology, Management, and Medico-Legal Implications of Botulinum-induced Blepharoptosis.","authors":"Giulio Nittari, Demetris Savva, Filippo Gibelli, Diana Vulcanescu, Domenico De Leo, Giovanna Ricci","doi":"10.2174/0127724328310459240809073519","DOIUrl":"10.2174/0127724328310459240809073519","url":null,"abstract":"<p><p>Botulinum toxin injections, a popular aesthetic treatment, have over 7.4 million beneficiaries in the U.S. Despite their safety record, these injections pose potential complications. It is essential for aesthetic practitioners to manage these complications with the least impact on the patient. Upper eyelid ptosis, though rare, is a significant side effect of botulinum toxin injections. Through our study, we have identified the etiology, anatomy, and therapeutic management of botulinum- induced blepharoptosis. Hence, the goal of this study was to identify the basic aetiology of blepharoptosis and manage this complication, as well as discuss the basis of medico-legal implications involving this popular drug. The complex medico-legal implications of botulinum toxin-induced blepharoptosis call for continuous discourse, education, and clarity on drug-use legal standards. With evolving global and Italian legislation, practitioners must ensure they meet care standards, weighing treatment benefits against potential legal and ethical outcomes. Blepharoptosis is a rare but significant complication of botulinum-type injections. Etiology and thorough anatomy are crucial for avoiding this complication and handling it with the least impact on the patient. Medico-legal implications are currently not fully established, but the basis of aesthetic treatment standards, as well as continuing medical education, will ensure correct medico-legal coverage of such complications.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":"20 1","pages":"32-37"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Frontiers in Pulmonary Hypertension: A Comprehensive Insight of Etiological Advances. 肺动脉高压的前沿:病因学进展的全面洞察。
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-30 DOI: 10.2174/0127724328325178241210174545
Mudasir Maqbool Bhat, Md Sadique Hussain, Ajay Singh Bisht, Mohit Agrawal, Ayesha Sultana, Navneet Khurrana, Rajesh Kumar

Pulmonary hypertension (PH) is a severe, progressive disorder characterized by elevated pulmonary arterial pressure, leading to right ventricular failure and increased mortality. Despite advancements in management, the median survival for PH patients remains 5-7 years, with an inhospital mortality rate of approximately 6%. The core pathological feature of PH is pulmonary vascular remodeling (PVR), a multifactorial process involving endothelial dysfunction, inflammation, and aberrant immune responses. While current therapies target endothelial dysfunction, they fall short of preventing PVR or halting disease progression. Emerging research highlights the potential of immune-inflammatory pathways, oxygen-sensing mechanisms, and gut microbiota modulation as therapeutic targets. Integrating nutritional strategies, probiotics, and fecal microbiota transplantation (FMT) as adjunctive therapies also shows promise. These factors may collectively influence PVR, offering novel insights into therapeutic avenues for PH management in the future.

肺动脉高压(PH)是一种以肺动脉压升高为特征的严重进行性疾病,可导致右心室衰竭和死亡率增加。尽管在治疗方面取得了进步,但PH患者的中位生存期仍为5-7年,住院死亡率约为6%。PH的核心病理特征是肺血管重构(PVR),这是一个涉及内皮功能障碍、炎症和异常免疫反应的多因素过程。虽然目前的治疗针对内皮功能障碍,但它们无法预防PVR或阻止疾病进展。新兴研究强调了免疫炎症途径、氧感应机制和肠道微生物群调节作为治疗靶点的潜力。整合营养策略、益生菌和粪便微生物群移植(FMT)作为辅助治疗也显示出希望。这些因素可能共同影响PVR,为未来PH管理的治疗途径提供新的见解。
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引用次数: 0
Pharmacogenetic Variations in Arab Populations: Clinical Implications for Personalized Drug Therapy. 阿拉伯人群的药物遗传变异:个体化药物治疗的临床意义。
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-23 DOI: 10.2174/0127724328335492241206075509
Laith Naser Al-Eitan, Iliya Yacoub Khair, Saif Zuhair Alahmad, Doaa Rababa'h, Hana Abu Kharmah, Lamice Shurafa

Previous genetic studies on the genetic makeup of Arab populations highlight the diversity resulting from the distribution of specific genetic markers among various Arab descendant populations. Different genetic variants classified as clinically significant have been identified, impacting the response to administered drugs. Absorption, distribution, and excretion of drugs throughout the human body are managed through the actions of drug transporters and receptor proteins, which are expressed on the cellular membrane. Drug metabolism involves activating or inactivating various compounds, transforming them into therapeutically active or toxic metabolites. With the rapid advancement of pharmacogenetic testing techniques and increased genetic studies involving Arab populations, insights into genetic polymorphisms have emerged, leading to a better understanding of the diverse phenotypes of drug response associated with genotype variation. Variations in transporters and receptor genes have significantly contributed to generating variant phenotypes that affect individuals' responses to treatments and substrates. This necessitates administering individualized drug doses based on the patient's haplotype, which can be determined through advanced genetic diagnosis. This review summarizes the findings of recent pharmacogenetic studies in the Arab world, emphasizing the benefits of pharmacogenetic research and applications to enhance therapeutic aspects of healthcare and treatment among patients in Arab countries.

先前对阿拉伯人口遗传组成的遗传研究强调了在不同阿拉伯后裔人口中特定遗传标记分布的多样性。已经确定了不同的遗传变异,这些变异被归类为具有临床意义,影响对所给药物的反应。药物在整个人体的吸收、分布和排泄是通过药物转运蛋白和受体蛋白的作用来控制的,它们在细胞膜上表达。药物代谢包括激活或灭活各种化合物,将其转化为具有治疗活性或毒性的代谢物。随着药物遗传学检测技术的快速发展和涉及阿拉伯人群的遗传学研究的增加,对遗传多态性的见解已经出现,从而更好地理解与基因型变异相关的药物反应的不同表型。转运体和受体基因的变异对产生影响个体对处理和底物反应的变异表型有重要贡献。这就需要根据患者的单倍型来给药,单倍型可以通过先进的基因诊断来确定。本综述总结了阿拉伯世界最近药物遗传学研究的发现,强调药物遗传学研究和应用在阿拉伯国家患者保健和治疗方面的益处。
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引用次数: 0
期刊
Current Reviews in Clinical and Experimental Pharmacology
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