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Glucose Transporter and Sensor Mechanisms in Fungal Pathogens as Potential Drug Targets. 作为潜在药物靶点的真菌病原体中的葡萄糖转运蛋白和传感器机制。
IF 1.1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0127724328263050230923154326
Archana Mohit Navale

Fungal infections are emerging as major health challenges in recent years. The development of resistance against existing antifungal agents needs urgent attention and action. The limited classes of antifungal drugs available, their tendency to cause adverse effects, lack of effectiveness, etc., are the major limitations of current therapy. Thus, there is a pressing demand for new antifungal drug classes to cope with the present circumstances. Glucose is the key source of energy for all organisms, including fungi. Glucose plays a crucial role as a source of carbon and energy for processes like virulence, growth, invasion, biofilm formation, and resistance development. The glucose transport and sensing mechanisms are well developed in these organisms as an important strategy to sustain survival. Modulating these transport or sensor mechanisms may serve as an important strategy to inhibit fungal growth. Moreover, the structural difference between human and fungal glucose transporters makes them more appealing as drug targets. Limited literature is available for fungal glucose entry mechanisms. This review provides a comprehensive account of sugar transport mechanisms in common fungal pathogens.

近年来,真菌感染正在成为主要的健康挑战。对现有抗真菌药物耐药性的发展急需关注和采取行动。现有的抗真菌药物种类有限,容易引起不良反应,缺乏有效性等,是目前治疗的主要局限性。因此,迫切需要新的抗真菌药物类别来应对当前的情况。葡萄糖是包括真菌在内的所有生物体的主要能量来源。葡萄糖在毒力、生长、入侵、生物膜形成和抗性发展等过程中作为碳和能量来源发挥着至关重要的作用。葡萄糖转运和传感机制在这些生物体中得到了很好的发展,是维持生存的重要策略。调节这些转运或传感器机制可能是抑制真菌生长的重要策略。此外,人类和真菌葡萄糖转运蛋白之间的结构差异使它们作为药物靶点更具吸引力。关于真菌葡萄糖进入机制的文献有限。这篇综述全面介绍了常见真菌病原体的糖转运机制。
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引用次数: 0
Recent Progress in the Understanding and Management of Acute Mountain Sickness: A Narrative Review. 理解和管理急性山病的最新进展:叙事综述。
IF 1.1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0127724328237059230919093818
Divyanshi Gupta, Pranay Wal, Mudita Mishra, Ankita Wal, Shruti Rathore, Shiv Shanker Pandey, Nikita Saraswat, Bhagawati Saxena

Background: Individuals at higher altitudes may experience a decrease in blood oxygen levels, which can result in a variety of clinical illnesses, such as high-altitude pulmonary edema, high-altitude cerebral edema, and milder but more common acute mountain sickness (AMS).

Objective: This study aims to review the current state of knowledge related to motion sickness, the risk of AMS, and pharmacological and non-pharmacological treatments for AMS.

Methods: Several databases, including PubMed, Bentham Science, Elsevier, Springer, and Research Gate, were used to compile the data for the article following a thorough analysis of the various research findings connected to acute mountain sickness and motion sickness, along with treatments and prevention.

Results: This article covers the research on mountain sickness as well as every imaginable form of conventional and alternative medicine. It contains ten medicinal plants that are useful in treating mountain sickness and various other remedies. Additionally, case studies are provided.

Conclusion: Therefore, the information in the paper will help travel medicine specialists better personalize their appropriate care for patients who travel to high-altitude locations. Additionally, all available antiemetic medications, serotonin agonists, nonsteroidal anti-inflammatory drugs, and herbal treatments for motion sickness were discussed. The prevention and consequences of acute mountain sickness are also covered in this study.

背景:高海拔地区的个体可能会经历血氧水平下降,这可能导致各种临床疾病,如高海拔肺水肿、高海拔脑水肿和较轻但更常见的急性山地病(AMS)。目的:本研究旨在综述与晕动病、AMS风险以及AMS的药物和非药物治疗相关的知识现状。方法:在对与急性山地病和晕动病有关的各种研究结果以及治疗和预防进行彻底分析后,使用PubMed、Bentham Science、Elsevier、Springer和Research Gate等多个数据库为文章汇编数据。结果:本文涵盖了山病的研究,以及各种可以想象的常规和替代药物。它含有十种药用植物,可用于治疗山病和各种其他疗法。此外,还提供了案例研究。结论:因此,本文中的信息将有助于旅行医学专家更好地为前往高海拔地区的患者提供个性化的适当护理。此外,还讨论了所有可用的止吐药物、血清素激动剂、非甾体抗炎药和晕动病的草药治疗方法。本研究还涵盖了急性山病的预防和后果。
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引用次数: 0
Metronidazole Induced Cutaneous Adverse Drug Reaction- A Systematic Review of Descriptive Studies. 甲硝唑诱发的皮肤药物不良反应--描述性研究的系统回顾。
IF 1.1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/2772432819666230601155545
Shifa Taj, Mohammed Zuber, Vidhyashree Ballagere Hanumanthaiah, Rajesh Venkataraman, Sathish Kumar Puttegowda, Syed Afrid, Sai Kiran

Background: A substantial number of research studies on metronidazole-related cutaneous symptoms have recently been published. Our objective was to identify and evaluate descriptive studies that described metronidazole-related skin manifestations, therapeutic interventions, and consequences.

Methods: A comprehensive literature search was carried out in the PubMed, Scopus, and grey literature databases from inception to April 2022 without any constraints, as well as a snowball search in Google and a search in Google Scholar. Descriptive articles describing metronidazole-related cutaneous manifestations were considered for the review. Two distinct reviewers carried out the research selection, data extraction, and quality assessment; any discrepancies were resolved by consensus with the third reviewer.

Results: About 24 out of 4648 descriptive studies, including 26 patients (20 Female patients and 6 male patients), were included in this review. The included studies comprised a range of ages from 16 to 78 years old. Metronidazole was indicated for the treatment of bacterial vaginosis, trichomoniasis, sepsis, anti-infection therapy, perforated appendicitis, rosacea, vaginal discharge, dysentery, acne rosacea, trichomonal vaginitis, lichen planus, liver abscess, facial rosacea, intestinal amoebiasis, and gingivitis. Fixed drug eruption was the most common skin manifestation which was reported in 7 cases included in this review. Cutaneous manifestations were ameliorated by cessation of the offending drug and by apportioning antihistamines, topical steroids, parenteral corticosteroids, emollients, and topical moisturizers.

Conclusion: Clinicians and healthcare professionals should be cognizant of the potential cutaneous adverse drug reactions (CADRs) induced by metronidazole to mitigate fatal circumstances. The management of the CADRs appears to respond effectively with immediate drug discontinuation and supportive therapy.

背景:最近发表了大量关于甲硝唑相关皮肤症状的研究。我们的目的是识别和评估描述甲硝唑相关皮肤表现、治疗干预和后果的描述性研究:方法:我们在 PubMed、Scopus 和灰色文献数据库中进行了一次全面的文献检索,检索时间为 PubMed、Scopus 和灰色文献数据库的起始时间至 2022 年 4 月,没有任何限制,同时还在 Google 和 Google Scholar 中进行了滚雪球式检索。综述考虑了描述甲硝唑相关皮肤表现的描述性文章。两位不同的审稿人分别进行了研究选择、数据提取和质量评估,如有任何分歧,则与第三位审稿人达成共识后解决:在 4648 项描述性研究中,约有 24 项纳入了本综述,其中包括 26 名患者(20 名女性患者和 6 名男性患者)。纳入研究的患者年龄从 16 岁到 78 岁不等。甲硝唑适用于治疗细菌性阴道病、滴虫病、败血症、抗感染治疗、阑尾炎穿孔、酒渣鼻、阴道分泌物、痢疾、痤疮酒渣鼻、滴虫性阴道炎、扁平苔藓、肝脓肿、面部酒渣鼻、肠阿米巴病和牙龈炎。固定性药物疹是最常见的皮肤表现,本综述共收录了 7 例。停用违禁药物并适当使用抗组胺药、局部类固醇、肠外皮质类固醇、润肤剂和局部保湿剂后,皮肤表现会有所缓解:临床医生和医护人员应认识到甲硝唑可能诱发皮肤药物不良反应(CADRs),以减少致命情况的发生。立即停药并给予支持性治疗似乎能有效控制皮肤药物不良反应。
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引用次数: 0
Mechanistic Insight into the Role of Peptides Secreted from Bacillus clausii and Future Opportunities. 从机理上洞察克氏芽孢杆菌分泌的肽的作用和未来机遇。
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0127724328273252240201071756
Jyoti Guleria, Minhaj Ahmad Khan

Bacillus clausii is a commercial spore probiotic known to treat multiple diseases. An increased interest in exploring the nutraceutical and probiotic properties of various microorganisms has made researchers explore more about these bacteria. The current trends in the healthcare industry are majorly focused on devising new therapies to avoid drug and pathogen resistance in patients. Antimicrobial peptides have been considered a source of antibiotics for a long time. Still, getting new therapies into the market is a big challenge. Members of the genus Bacillus have been reported to have a broad spectrum of antimicrobial peptides. One of the least explored species under this genus is Bacillus clausii, concerning peptide drug therapy. The applications of Bacillus clausii in treating or preventing gut dysbiosis and respiratory infections have been largely supported in the past two decades. Yet research is lacking in explaining the pathways at molecular levels in targeting pathogens. In this mini-review, we are going to summarise the research that has been reported so far about peptide extraction from Bacillus clausii, their mode of action and advantages to mankind, and the challenges lying in the isolation of peptides.

克劳斯芽孢杆菌是一种商业孢子益生菌,已知可治疗多种疾病。随着人们对各种微生物的营养保健和益生菌特性的兴趣日益浓厚,研究人员对这些细菌进行了更多的探索。目前,医疗保健行业的发展趋势主要集中在设计新疗法,以避免患者产生耐药性和病原体抗药性。长期以来,抗菌肽一直被认为是抗生素的一种来源。然而,将新疗法推向市场仍是一个巨大的挑战。据报道,芽孢杆菌属的成员具有广谱的抗菌肽。在肽类药物疗法方面,枯草芽孢杆菌(Bacillus clausii)是该属中探索最少的物种之一。在过去二十年中,枯草芽孢杆菌在治疗或预防肠道菌群失调和呼吸道感染方面的应用得到了广泛支持。然而,在解释针对病原体的分子水平途径方面还缺乏研究。在这篇小型综述中,我们将总结迄今为止有关从枯草芽孢杆菌中提取多肽的研究、其作用模式和对人类的益处,以及在分离多肽过程中面临的挑战。
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引用次数: 0
The Association between Statins Intake and Risk of Post Stroke Pneumonia: A Systematic Review and Meta-Analysis. 他汀类药物摄入与卒中后肺炎风险的关系:系统综述和荟萃分析。
IF 1.1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0127724328258172230926070748
Mohammad Darvishi, Mehdi Mohammadian Amiri, Saeid Heidari-Soureshjani, Catherine M T Sherwin, Hossein Mardani-Nafchi

Aim: This research aimed to examine the relationship between the intake of statins and the risk of post-stroke pneumonia in a systematic review and meta-analysis study.

Methods: An extensive search of published articles on March 21st, 2023, was done in several databases, like Web of Science (ISI), PubMed, Cochrane Library, Embase, Scopus, and Google Scholar. The Newcastle Ottawa Scale (NOS) checklist was employed to evaluate the quality of observational studies. Statistical tests (Chi-square test and I2) and graphical techniques (Forest plot) were used to determine whether heterogeneity existed in the meta-analysis studies. Funnel plots and Begg and Egger's tests were used to assess the publication bias.

Results: Seven studies (5 cohort and 2 case-control studies) were retrieved to examine the association between statins and post-stroke pneumonia. The sample size of the studies compiled in the meta- analysis was obtained to be 68,966 participants. Meta-analysis demonstrated that the overall odds of post-stroke pneumonia in the statin group was equal to 0.87 (95% CI: 0.67 - 1.13; p-value 0.458). Subgroup analysis indicated that the odds of post-stroke pneumonia in the statin group was equal to 0.93 (95% CI: 0.73-1.18; p-value = 0.558) in the cohort studies, and equal to 0.92 (95% CI: 0.37-2.26; p-value = 0.857) in the case-control studies. The examination of the association between the intake of statins and post-stroke pneumonia showed no evidence of publication bias (Begg's test, p-value = 0.368; Eggers test, p-value = 0.282).

Conclusion: In this study, no relationship has been observed between receiving statins and the risk of post-stroke pneumonia.

目的:本研究旨在通过系统综述和荟萃分析研究来检验他汀类药物的摄入与卒中后肺炎风险之间的关系。方法:在多个数据库中广泛搜索2023年3月21日发表的文章,如Web of Science(ISI)、PubMed、Cochrane Library、Embase、Scopus和Google Scholar。纽卡斯尔-渥太华量表(NOS)用于评估观察性研究的质量。统计检验(卡方检验和I2)和图形技术(森林图)用于确定荟萃分析研究中是否存在异质性。漏斗图和Begg和Egger检验用于评估发表偏倚。结果:检索了7项研究(5项队列研究和2项病例对照研究),以检查他汀类药物与脑卒中后肺炎之间的关系。荟萃分析中汇编的研究样本量为68966名参与者。荟萃分析表明,他汀类药物组发生脑卒中后肺炎的总几率为0.87(95%CI:0.67-1.13;p值0.458)。亚组分析表明,在队列研究中,他汀类化合物组发生脑缺血后肺炎的几率为0.93(95%CI:0.73-1.18;p值=0.558),在病例对照研究中为0.92(95%CI:0.37-2.26;p值0.857)。对他汀类药物摄入与卒中后肺炎之间关系的检查没有显示出发表偏倚的证据(Begg’s检验,p值=0.368;Eggers检验,p值=0.822)。结论:在本研究中,未观察到接受他汀类药物与卒中后肺炎风险之间的关系。
{"title":"The Association between Statins Intake and Risk of Post Stroke Pneumonia: A Systematic Review and Meta-Analysis.","authors":"Mohammad Darvishi, Mehdi Mohammadian Amiri, Saeid Heidari-Soureshjani, Catherine M T Sherwin, Hossein Mardani-Nafchi","doi":"10.2174/0127724328258172230926070748","DOIUrl":"10.2174/0127724328258172230926070748","url":null,"abstract":"<p><strong>Aim: </strong>This research aimed to examine the relationship between the intake of statins and the risk of post-stroke pneumonia in a systematic review and meta-analysis study.</p><p><strong>Methods: </strong>An extensive search of published articles on March 2<sup>1st</sup>, 2023, was done in several databases, like Web of Science (ISI), PubMed, Cochrane Library, Embase, Scopus, and Google Scholar. The Newcastle Ottawa Scale (NOS) checklist was employed to evaluate the quality of observational studies. Statistical tests (Chi-square test and I<sup>2</sup>) and graphical techniques (Forest plot) were used to determine whether heterogeneity existed in the meta-analysis studies. Funnel plots and Begg and Egger's tests were used to assess the publication bias.</p><p><strong>Results: </strong>Seven studies (5 cohort and 2 case-control studies) were retrieved to examine the association between statins and post-stroke pneumonia. The sample size of the studies compiled in the meta- analysis was obtained to be 68,966 participants. Meta-analysis demonstrated that the overall odds of post-stroke pneumonia in the statin group was equal to 0.87 (95% CI: 0.67 - 1.13; p-value 0.458). Subgroup analysis indicated that the odds of post-stroke pneumonia in the statin group was equal to 0.93 (95% CI: 0.73-1.18; p-value = 0.558) in the cohort studies, and equal to 0.92 (95% CI: 0.37-2.26; p-value = 0.857) in the case-control studies. The examination of the association between the intake of statins and post-stroke pneumonia showed no evidence of publication bias (Begg's test, p-value = 0.368; Eggers test, p-value = 0.282).</p><p><strong>Conclusion: </strong>In this study, no relationship has been observed between receiving statins and the risk of post-stroke pneumonia.</p>","PeriodicalId":29871,"journal":{"name":"Current Reviews in Clinical and Experimental Pharmacology","volume":" ","pages":"285-293"},"PeriodicalIF":1.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41214660","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
Advanced Therapeutic Medicinal Products in Bone and Cartilage Defects. 骨和软骨缺陷的高级治疗药物。
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0127724328274436231207062008
Dylana Diaz-Solano, Bahareh Sadri, Maria Peshkova, Anastasia Shpichka, Olga Smirnova, Roshanak Shams, Peter Timashev, Massoud Vosough

The number of patients with functional loss of bone and cartilage tissue has shown an increasing trend. Insufficient or inappropriate conventional treatments applied for trauma, orthopedic diseases, or other bone and cartilage-related disorders can lead to bone and cartilage damage. This represents a worldwide public health issue and a significant economic burden. Advanced therapeutic medicinal products (ATMPs) proposed promising alternative therapeutic modalities by application of cell-based and tissue engineering approaches. Recently, several ATMPs have been developed to promote bone and cartilage tissue regeneration. Fifteen ATMPs, two related to bone and 13 related to cartilage, have received regulatory approval and marketing authorization. However, four ATMPs were withdrawn from the market for various reasons. However, ATMPs that are still on the market have demonstrated positive results, their broad application faced limitations. The development and standardization of methodologies will be a major challenge in the coming decades. Currently, the number of ATMPs in clinical trials using mesenchymal stromal cells or chondrocytes indicates a growing recognition that current ATMPs can be improved. Research on bone and cartilage tissue regeneration continues to expand. Cell-based therapies are likely to be clinically supported by the new ATMPs, innovative fabrication processes, and enhanced surgical approaches. In this study, we highlighted the available ATMPs that have been used in bone and cartilage defects and discussed their advantages and disadvantages in clinical applications.

骨和软骨组织功能丧失的患者人数呈上升趋势。对创伤、骨科疾病或其他与骨和软骨有关的疾病所采用的传统治疗方法不足或不当,都会导致骨和软骨损伤。这是一个全球性的公共卫生问题,也是一个重大的经济负担。先进治疗药物产品(ATMPs)通过应用基于细胞和组织工程的方法,提出了前景广阔的替代治疗模式。最近,已开发出几种促进骨和软骨组织再生的 ATMP。已有 15 种 ATMP 获得了监管部门的批准和上市许可,其中 2 种与骨有关,13 种与软骨有关。然而,有 4 种 ATMP 因各种原因退出了市场。不过,仍在市场上销售的 ATMP 虽然取得了积极成果,但其广泛应用也面临着局限性。未来几十年,方法的开发和标准化将是一项重大挑战。目前,使用间充质基质细胞或软骨细胞的 ATMP 已进入临床试验阶段,这表明越来越多的人认识到目前的 ATMP 还可以改进。有关骨和软骨组织再生的研究仍在继续扩展。基于细胞的疗法很可能会得到新型 ATMP、创新制造工艺和改进手术方法的临床支持。在本研究中,我们重点介绍了已用于骨和软骨缺损的现有 ATMP,并讨论了它们在临床应用中的优缺点。
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引用次数: 0
The Application of Kinesin Inhibitors in Medical Issues. 驱动蛋白抑制剂在医学领域的应用
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0127724328277623231204064614
Mojgan Nejabat, Farzin Hadizadeh, Amirhossein Sahebkar

Kinesins are a group of motor proteins in charge of several crucial functions in the cell. These proteins often bind to microtubules and perform their functions using the energy produced by ATP hydrolysis. One function of mitotic kinesin, a subclass of kinesin that is expressed during cell division at the mitotic phase, is to create the mitotic spindle. Uncontrolled cell growth is one trait of cancerous cells. Traditional anticancer medications still used in clinics include taxanes (paclitaxel) and vinca alkaloids (vincristine, vinblastine), which interfere with microtubule dynamics. However, because non-dividing cells like post-mitotic neurons contain microtubules, unwanted side effects like peripheral neuropathy are frequently found in patients taking these medications. More than ten members of the mitotic kinesin family play distinct or complementary roles during mitosis. The mitotic kinesin family's KSP, or Eg5, is regarded as its most dramatic target protein. The current work systematically reviews the use of kinesin inhibitors in the medical field. The challenges of KSP and the practical solutions are also examined, and the outcomes of the previous works are reported. The significant gaps and shortcomings of the related works are also highlighted, which can be an onset topic for future works.

驱动蛋白是一组运动蛋白,在细胞中发挥着多种重要功能。这些蛋白通常与微管结合,并利用 ATP 水解产生的能量来实现其功能。有丝分裂驱动蛋白是驱动蛋白的一个亚类,在有丝分裂阶段的细胞分裂过程中表达,其功能之一是建立有丝分裂纺锤体。不受控制的细胞生长是癌细胞的特征之一。目前仍在临床上使用的传统抗癌药物包括紫杉醇类(taxanes)和长春碱类(vinca alkaloids)(长春新碱、长春碱),它们都会干扰微管的动力学。然而,由于像有丝分裂后神经元这样的非分裂细胞含有微管,服用这些药物的患者经常会出现外周神经病变等不必要的副作用。有丝分裂驱动蛋白家族的十多个成员在有丝分裂过程中发挥着不同或互补的作用。有丝分裂驱动蛋白家族的 KSP 或 Eg5 被认为是其最引人注目的靶蛋白。目前的研究系统地回顾了驱动蛋白抑制剂在医学领域的应用。研究还探讨了 KSP 所面临的挑战和切实可行的解决方案,并报告了前人的研究成果。同时还强调了相关工作中的重大差距和不足,这些都可以成为未来工作的启动主题。
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引用次数: 0
Novel Information Regarding the Treatment of Helicobacter pylori Infection: A Systematic Review and Meta-analysis of Randomized Clinical Trials. 治疗幽门螺旋杆菌感染的新信息:随机临床试验的系统回顾和元分析》。
IF 1.1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/2772432818666230120111237
Faezeh Kiani, Sara Khademolhosseini, Jasem Mohammadi, Arian Tavasol, Ramtin Hajibeygi, Mobina Fathi, Majid Dousti

Objective: Helicobacter pylori infects at least 50% of the world's human population. The current study aimed to assess and compare the efficacy of triple versus quadruple therapy.

Methods: Randomized clinical trials (RCTs) consisting of triple and quadruple therapy were identified through electronic and manual searches in the national and international online databases (IsI, Magiran, Embase, PubMed, and Scopus). The random-effects model was applied to pool analysis. Funnel plots and the Egger test were used to examine publication bias.

Results: After a detailed review of the selected articles, 80 RCTs were included in the meta-analysis; it was based on using triple and quadruple therapy as the first and second-line treatment. The results showed that quadruple therapy in the first-line treatment had a higher eradication rate than triple therapy. Overall, the eradication rate with triple therapy was 74% (95% CI, 71%-77%) for intention-totreat (ITT) analysis and 80% (95% CI, 77%-82%) for per-protocol (PP) analysis. Generally, the eradication rate with quadruple therapy was 82% (95% CI, 78.0%-86.0%) for ITT analysis and 85% (95% CI, 82.0%-89.0%) for PP analysis. The analysis also revealed that quadruple therapy was more effective for 7 or 10 days.

Conclusion: The current study results demonstrated that quadruple therapy has better effectiveness than triple therapy as the first-line treatment; however, in the second-line treatment, the effectiveness of quadruple and triple regimens is almost similar. The effectiveness of quadruple therapy in the Asian population was found to be slightly higher than that of triple therapy, while this difference was considerably higher in the European population.

目的:全球至少有 50%的人感染幽门螺杆菌。本研究旨在评估和比较三联疗法与四联疗法的疗效:通过在国内和国际在线数据库(IsI、Magiran、Embase、PubMed 和 Scopus)中进行电子和人工检索,确定了由三联疗法和四联疗法组成的随机临床试验(RCT)。采用随机效应模型进行汇总分析。使用漏斗图和 Egger 检验来检查发表偏倚:对所选文章进行详细审查后,80 项研究纳入了荟萃分析;荟萃分析以三联疗法和四联疗法作为一线和二线疗法。结果显示,一线治疗中四联疗法的根除率高于三联疗法。总体而言,在意向治疗(ITT)分析中,三联疗法的根除率为74%(95% CI,71%-77%),在每方案(PP)分析中为80%(95% CI,77%-82%)。一般来说,四联疗法的根除率在 ITT 分析中为 82%(95% CI,78.0%-86.0%),在 PP 分析中为 85%(95% CI,82.0%-89.0%)。分析还显示,7 天或 10 天的四联疗法更有效:目前的研究结果表明,在一线治疗中,四联疗法的疗效优于三联疗法;但在二线治疗中,四联疗法和三联疗法的疗效基本相似。研究发现,在亚洲人群中,四联疗法的疗效略高于三联疗法,而在欧洲人群中,这一差异要大得多。
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引用次数: 0
Zebrafish Experimental Animal Models for AD: A Comprehensive Review. 斑马鱼AD实验动物模型:全面回顾
IF 1.3 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0127724328279684240104094257
Ruksar Sande, Angel Godad, Gaurav Doshi

AD disease (AD) is a multifaceted and intricate neurodegenerative disorder characterized by intracellular neurofibrillary tangle (NFT) formation and the excessive production and deposition of Aβ senile plaques. While transgenic AD models have been found instrumental in unravelling AD pathogenesis, they involve cost and time constraints during the preclinical phase. Zebrafish, owing to their simplicity, well-defined behavioural patterns, and relevance to neurodegenerative research, have emerged as a promising complementary model. Zebrafish possess glutaminergic and cholinergic pathways implicated in learning and memory, actively contributing to our understanding of neural transmission processes. This review sheds light on the molecular mechanisms by which various neurotoxic agents, including okadaic acid (OKA), cigarette smoke extract, metals, and transgenic zebrafish models with genetic similarities to AD patients, induce cognitive impairments and neuronal degeneration in mammalian systems. These insights may facilitate the identification of effective neurotoxic agents for replicating AD pathogenesis in the zebrafish brain. In this comprehensive review, the pivotal role of zebrafish models in advancing our comprehension of AD is emphasized. These models hold immense potential for shaping future research directions and clinical interventions, ultimately contributing to the development of novel AD therapies.

注意力缺失症(AD)是一种多方面、错综复杂的神经退行性疾病,其特征是细胞内神经纤维缠结(NFT)的形成以及 Aβ 老年斑的过度产生和沉积。虽然转基因多发性硬化症模型被认为有助于揭示多发性硬化症的发病机制,但在临床前阶段,这些模型受到成本和时间的限制。斑马鱼因其结构简单、行为模式明确以及与神经退行性病变研究相关,已成为一种前景广阔的补充模型。斑马鱼拥有与学习和记忆有关的谷氨酸能和胆碱能通路,有助于我们了解神经传导过程。这篇综述揭示了各种神经毒剂(包括 okadaic 酸(OKA)、香烟烟雾提取物、金属以及与 AD 患者基因相似的转基因斑马鱼模型)在哺乳动物系统中诱导认知障碍和神经元变性的分子机制。这些见解可能有助于确定有效的神经毒剂,以便在斑马鱼大脑中复制注意力缺失症的发病机制。在这篇综述中,我们强调了斑马鱼模型在促进我们理解注意力缺失症方面的关键作用。这些模型在塑造未来的研究方向和临床干预措施方面具有巨大的潜力,最终有助于开发新型的注意力缺失症疗法。
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引用次数: 0
The Neuroanatomical Basis of the 5-HT Syndrome and Harmalineinduced Tremor. 5-HT 综合征和哈马林诱发震颤的神经解剖学基础》(The Neuroanatomical Basis of the 5-HT Syndrome and Harmalineinduced Tremor)。
IF 1.1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/2772432819666230703095203
Robert Lalonde, Catherine Strazielle

The 5-HT syndrome in rats is composed of head weaving, body shaking, forepaw treading, flat body posture, hindlimb abduction, and Straub tail. The importance of the brainstem and spinal cord for the syndrome is underlined by findings of 5,7-dihydroxytryptamine (5,7-DHT)-induced denervation supersensitivity in response to 5-HT-stimulant drugs. For head weaving and Straub tail, supersensitivity occurred when the neurotoxin was injected into the cisterna magna or spinal cord, for forepaw treading in cisterna magna, and for hindlimb abduction in the spinal cord. Although 5,7- DHT-related body shaking increased in the spinal cord, the sign decreased when injected into the striatum, indicating the modulatory influence of the basal ganglia. Further details on body shaking are provided by its reduced response to harmaline after 5-HT depletion caused by intraventricular 5,7-DHT, electrolytic lesions of the medial or dorsal raphe, and lesions of the inferior olive caused by systemic injection of 3-acetylpyridine along with those found in Agtpbp1pcd or nr cerebellar mouse mutants. Yet the influence of the climbing fiber pathway on other signs of the 5-HT syndrome remains to be determined.

大鼠的 5-HT 综合征包括摆头、身体摇晃、前爪蹬地、身体姿势扁平、后肢外展和 Straub 尾。5,7-二羟色胺(5,7-DHT)诱导的神经支配超敏感性对 5-HT 兴奋剂药物的反应,强调了脑干和脊髓对该综合征的重要性。在织头和斯特劳布尾中,当神经毒素被注射到蝶窦或脊髓中时,对前爪在蝶窦中的踩踏以及后肢在脊髓中的外展都会出现超敏感性。虽然脊髓中与 5,7- DHT 相关的身体抖动会增加,但注射到纹状体后,抖动会减少,这表明基底神经节具有调节作用。通过脑室内 5,7-DHT、内侧或背侧剑突的电解损伤以及全身注射 3-acetylpyridine 引起的下橄榄损伤,以及 Agtpbp1pcd 或 nr 小鼠小脑突变体中发现的损伤,在 5-HT 耗尽后身体抖动对哈玛灵的反应减弱,这提供了有关身体抖动的更多细节。然而,攀缘纤维通路对 5-HT 综合征其他症状的影响仍有待确定。
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Current Reviews in Clinical and Experimental Pharmacology
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