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Extended-Spectrum β-Lactamase-Producing Escherichia coli and Virulence Genes in Pediatric Patients with Health-Care Urinary Tract Infections. 保健尿路感染患儿产β-内酰胺酶大肠杆菌及其毒力基因
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.2174/1871526523666221104150123
Mohamed Anies Rizk, Maysaa El Sayed Zaki, Hanan Abdelfattah Abdelmohsen Mohamed, Dina Mohammed Abdelhady Mahmood, Karim Monatasser

Introduction: Healthcare-associated urinary tract infection (UTI) represents a significant health problem, especially in infants and young children. The most common pathogen associated with this infection is Escherichia coli (E. coli).

Objective: The present study aimed to detect the frequency of virulence genes among clinical isolates of E. coli isolated from healthcare-associated urinary tract infections in children and the correlation between these virulence genes and the presence of the blaCTX gene.

Methods: The study included one hundred clinical isolates of E. coli isolated from healthcareassociated urinary tract infections in children in intensive care units. The isolates were subjected to antibiotics sensitivity by disc diffusion method and detection of extended-spectrum beta-lactamase by double disc diffusion method. In addition, multiplex polymerase chain reaction (PCR) was used to detect some virulence genes, and PCR was used to detect the blaCTX-M gene.

Results: E. coli producing ESBL by double discs method was identified in 74 isolates. blaCTX-M gene detection by PCR was identified among 38 isolates representing 51.4% of ESBL-producing E. coli. There was a significant association between ESBL and blaCTX-M Gene, P = 0.0001. The frequency of the studied virulence genes by multiplex PCR in the isolated E. coli was 66% for the Fim gene, 75% for the Aer gene, 68% for the FliC gene, 53% for each of IucD gene and Usp gene, 40% for pap gene, 35% for each of AFA and ironN genes and 17% for sfa gene. None of the isolated E. coli had the Cdt gene. There was a significant association between the presence of the FimH gene (P = 0.0001), Pap gene (P = 0.05), sfa (P = 0.026), Afa gene (P = 0.018), and aer gene (P = 0.035) and the presence of the blaCTX-M gene in the isolated E. coli.

Conclusion: The present study highlights the presence of virulence genes and blaCTX-M gene in uropathogenic E. coli isolated from pediatric patients with healthcare-associated urinary tract infections. There was an association between the blaCTX-M gene and virulence genes FimH, pap, sfa, Afa, and aer. Various distributions of the studied genes with a high frequency of fimbria are flic genes. Moreover, the ESBL had high frequency in E. coli with the presence of blaCTX-M in about one-third of the isolates.

导读:医疗保健相关的尿路感染(UTI)是一个重要的健康问题,特别是在婴幼儿中。与这种感染相关的最常见病原体是大肠杆菌。目的:本研究旨在检测儿童卫生保健相关尿路感染大肠杆菌临床分离株中毒力基因的频率,以及这些毒力基因与blaCTX基因存在的相关性。方法:本研究纳入了从重症监护病房中卫生保健相关尿路感染的儿童中分离出的100株大肠杆菌。采用圆盘扩散法对分离菌株进行药敏试验,采用双圆盘扩散法检测扩展谱β -内酰胺酶。此外,采用多重聚合酶链反应(PCR)检测部分毒力基因,并采用PCR检测blaCTX-M基因。结果:在74株分离株中鉴定出双片法产ESBL的大肠杆菌。在38株产esbl的大肠杆菌中检测到blaCTX-M基因,占51.4%。ESBL与blaCTX-M基因有显著相关性,P = 0.0001。在分离的大肠杆菌中,多重PCR所研究的毒力基因频率分别为:薄膜基因66%、Aer基因75%、FliC基因68%、IucD基因和Usp基因各53%、pap基因40%、AFA基因和铁蛋白基因各35%、sfa基因17%。分离的大肠杆菌中没有Cdt基因。分离的大肠杆菌中FimH基因(P = 0.0001)、Pap基因(P = 0.05)、sfa基因(P = 0.026)、Afa基因(P = 0.018)和aer基因(P = 0.035)的存在与blaCTX-M基因存在显著相关。结论:本研究强调了从儿童卫生保健相关尿路感染患者分离的尿路致病性大肠杆菌中存在毒力基因和blaCTX-M基因。blaCTX-M基因与毒力基因FimH、pap、sfa、Afa和aer存在相关性。所研究基因的各种分布与高频率的被毛是flic基因。此外,ESBL在大肠杆菌中频率较高,约三分之一的分离株中存在blaCTX-M。
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引用次数: 0
The Impact of COVID-19 Pandemic on the Levels of Physical Activity: A Systematic Review. COVID-19大流行对身体活动水平的影响:一项系统综述。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.2174/1871526523666230120143118
Esmaeil Mehraeen, Amirali Karimi, Seyed Peyman Mirghaderi, Pegah Mirzapour, Zahra Pashaei, Kowsar Qaderi, Amir Masoud Afsahi, Alireza Barzegary, Parsa Mohammadi, Alireza Shojaei, Solmaz Saeidi, Fatemeh Afroughi, Mehrzad MohsseniPour, Nazanin Janfaza, Omid Dadras, Ava Amiri, Kimia Azad, SeyedAhmad SeyedAlinaghi, Marcarious M Tantuoyir, Fabricio Voltarelli

Introduction: Earlier studies demonstrated a decreased level of physical activity (PA) during the COVID-19 pandemic. Therefore, we aimed to systematically review the relevant studies among various age groups and explore the impact on physical and mental health.

Methods: We searched and retrieved all relevant articles using the keywords on the online databases of PubMed, Scopus, and Cochrane from the start of the pandemic until May 3rd, 2021. A two-phase screening process of identified records was carried out to shortlist the most relevant studies. First, the studies were evaluated based on their title/abstract, and then the full-text of included studies was thoroughly read. The eligible studies based on the eligibility criteria were included in this review.

Results: A total of 57 studies were included based on the eligibility criteria. Lockdowns and infection with SARS-CoV-2 have led to a decreased level of PA in the general population compared to the prepandemic era. Men had significantly less PA compared to women in some studies, probably due to higher pre-pandemic PA. The level of PA among those with chronic diseases also significantly diminished, putting them at a higher risk of cardiovascular incidents. Sedentary lifestyles have dominated people's life, including adolescents and university students. The increased levels of mental health issues, such as depression, anxiety, and occupational stress, have been suggested to contribute to the decreased PA. On the other hand, the decreased PA appeared to lead to more mental health issues. Fortunately, the decreasing trend of PA seemed to taper towards the end of the quarantines.

Conclusion: Overall, the COVID-19 pandemic and subsequent quarantines reduced PA among all age groups and both sexes and had detrimental effects on people's physical and mental health. We suggest countries implement strategies to alleviate restrictions and encourage people to exercise in safe environments and prepare healthy routines for themselves.

早期的研究表明,在COVID-19大流行期间,身体活动水平(PA)下降。因此,我们旨在系统回顾不同年龄组的相关研究,探讨其对身心健康的影响。方法:使用关键词检索PubMed、Scopus和Cochrane在线数据库中自疫情开始至2021年5月3日的所有相关文章。对已确定的记录进行了两阶段筛选,以选出最相关的研究。首先,根据研究的标题/摘要对研究进行评估,然后全面阅读纳入研究的全文。本综述纳入了符合入选标准的研究。结果:根据入选标准,共纳入57项研究。与大流行前时代相比,封锁和SARS-CoV-2感染导致普通人群中PA水平下降。在一些研究中,男性的PA明显低于女性,这可能是由于大流行前的PA较高。慢性疾病患者的PA水平也显著降低,使他们患心血管疾病的风险更高。久坐不动的生活方式已经主导了人们的生活,包括青少年和大学生。心理健康问题水平的增加,如抑郁、焦虑和职业压力,被认为是导致PA下降的原因。另一方面,PA的下降似乎会导致更多的心理健康问题。幸运的是,PA的下降趋势似乎在隔离结束时逐渐减弱。结论:总体而言,COVID-19大流行和随后的隔离措施降低了所有年龄组和性别的PA,并对人们的身心健康产生了不利影响。我们建议各国实施战略,减轻限制,鼓励人们在安全的环境中锻炼,并为自己制定健康的日常活动。
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引用次数: 3
Fatal Clostridium sporogenes Soft Tissue Polymicrobial Infections in Two Immunocompetent Cases: Case Report. 致死性芽孢梭菌软组织多微生物感染两例免疫功能正常病例报告。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.2174/1871526523666230112161134
Preeti Chaudhary, Neelam Gulati, Varsha Gupta, Gazal Dhanda, Mani Bhushan Kumar, Swati Sharma, Anku Goel, Ashok Kumar Attri

Background: Clostridium sporogenes is reported rarely in literature. Reports from the skin and soft tissue infections are even less, more so in immunocompetent patients.

Case presentation: Two skin and soft tissue infections with C. sporogenes in immunocompetent patients have been presented in this study. One of the cases was following an electrical burn wound, and the other was following a bedsore. Both patients expired despite antibacterial treatment and debridement.

Discussion and conclusion: C. sporogenes had usually been reported after trauma particularly after penetrating and deep wound infection. More attention should be given to these patients so that the infection can be treated and diagnosed early in suspected anaerobic infections like Clostridium species.

背景:产孢梭菌文献报道较少。皮肤和软组织感染的报告甚至更少,在免疫能力强的患者中更是如此。病例介绍:两个皮肤和软组织感染的芽孢杆菌免疫正常的病人已经提出了这项研究。其中一例是电烧伤,另一例是褥疮。尽管进行了抗菌治疗和清创,但两名患者均死亡。讨论与结论:孢子囊菌通常在创伤后,特别是在穿透性和深度伤口感染后报道。应给予这些患者更多的关注,以便在疑似厌氧菌感染(如梭状芽胞杆菌)时及早治疗和诊断感染。
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引用次数: 1
Human ACE-2, MCP1 and micro-RNA 146 as Novel Markers for COVID- 19 Affection and Severity. 人ACE-2、MCP1和微rna 146作为COVID- 19影响和严重程度的新标志物
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.2174/1871526522666220829153042
Amal Ahmed Mohamed, Sherief Abd-Elsalam, Ahmed Abdelghani, Mohamed Badr Hassan, Doaa Ghaith, Omnia Ezzat, Dalia Ali El-Damasy, Norhan Nagdi Madbouli, Mohmoud Hamada, Mohamed Abdel Khalik Hepatology Gastroenterology And Infectious Diseases, Shaimaa M Al-Tabbakh, Kareman Ahmed Ebrahim Eshra, Nivin Baiomy

Background & aims: Coronavirus disease - 2019 (COVID-19) is a major pandemic that causes high morbidity and mortality rates.

Aim of this study: to detect the relations between many risk factors, ACE-2, MCP-1, Micro RNA 146 gene expression, and COVID-19 infection and disease severity.

Methods: This study was carried out on 165 cases of COVID-19 and 138 controls. ACE2 and MCP1 levels were measured in COVID-19 cases and control by ELISA and micro-RNA-146 expression by PCR.

Results: We found an increased blood level of ACE2 and MCP1 in COVID- 19 patients than in healthy persons and a significant down-regulation of micro-RNA 146 gene expression in cases than in controls. There was a significant correlation between increased blood level of ACE2, regulation of micro-RNA 146 gene expression and severity of lung affection, a significant correlation was found between increased blood level of MCP1 and thrombosis in COVID-19 patients. Neurological complications were significantly correlated with more viral load, more ACE2 blood level, and down regulation of micro RNA146 expression.

Conclusion: High viral load, increased blood level of ACE2, and down-regulation of micro-RNA 146 expression are associated with more severe lung injury and the presence of neurologic complications like convulsions and coma in COVID-19 Egyptian patients.

背景与目的:冠状病毒病- 2019 (COVID-19)是一种导致高发病率和死亡率的重大流行病。本研究目的:检测多种危险因素、ACE-2、MCP-1、Micro RNA 146基因表达与COVID-19感染及病情严重程度的关系。方法:选取新冠肺炎病例165例,对照组138例。采用ELISA法检测COVID-19病例和对照组的ACE2和MCP1水平,采用PCR法检测micro-RNA-146的表达。结果:我们发现COVID- 19患者血液中ACE2和MCP1水平高于健康人,微rna 146基因表达明显低于对照组。新冠肺炎患者血中ACE2水平升高、微rna 146基因表达调控与肺损伤严重程度有显著相关性,MCP1水平升高与血栓形成有显著相关性。神经系统并发症与病毒载量升高、ACE2血药浓度升高、微RNA146表达下调显著相关。结论:埃及新冠肺炎患者高病毒载量、血中ACE2水平升高、微rna 146表达下调与更严重的肺损伤及惊厥、昏迷等神经系统并发症相关。
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引用次数: 0
Anti-COVID-19 Vaccination, COVID-19, and Female Contraception: The Exacerbated Risks (Thromboembolism) of the Estrogen-progestin Pill. 抗COVID-19疫苗接种,COVID-19和女性避孕:雌激素-黄体酮丸的风险增加(血栓栓塞)。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.2174/1871526523666230224094439
Ziad Fajloun, Ziad Abi Khattar, Hervé Kovacic, Christian Legros, Jean-Marc Sabatier
{"title":"Anti-COVID-19 Vaccination, COVID-19, and Female Contraception: The Exacerbated Risks (Thromboembolism) of the Estrogen-progestin Pill.","authors":"Ziad Fajloun,&nbsp;Ziad Abi Khattar,&nbsp;Hervé Kovacic,&nbsp;Christian Legros,&nbsp;Jean-Marc Sabatier","doi":"10.2174/1871526523666230224094439","DOIUrl":"https://doi.org/10.2174/1871526523666230224094439","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":13678,"journal":{"name":"Infectious disorders drug targets","volume":"23 4","pages":"e240223214000"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10574639","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
Bacterial Persister Cells: Mechanisms of Formation, Control, and Eradication. 细菌持久性细胞:形成、控制和根除的机制。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.2174/1871526523666230511142054
Ebrahim Kouhsari, Vahab Hassan Kaviar, Arezoo Asadi, Alireza Ahmadi, Mohammad Sholeh, Ali Mirbalouchzehi, Sajad Yaghoubi, Milad Abdi
Bacterial persister cells are quiescent, slow-growing or growth-arrested phenotypic variants of normal bacterial cells that are transiently tolerant to antibiotics. It seems that persister cells are the main cause of the recurrence of various chronic infections. Stress response (RpoS-mediated), toxin-antitoxin (TA) systems, inhibition of ATP production, reactive oxygen species (ROS), efflux pumps, bacterial SOS response, cell-to-cell communication and stringent response (ppGpp- mediated) are the primary potential mechanisms for persistence cell formation. However, eradicating persistent cells is challenging as the specific molecular mechanisms that initiate their formation remain fuzzy and unknown. Here we reviewed and summarized the current understanding of how bacterial persister cells are formed, controlled, and destroyed.
细菌持久性细胞(BPCs)是正常细菌细胞的静止、生长缓慢或生长受阻的表型变异,对抗生素具有短暂的耐受性。持久性细胞似乎是各种慢性感染复发的主要原因。应激反应(rpos -介导)、毒素-抗毒素(TA)系统、ATP生成抑制、活性氧(ROS)、外排泵、细菌SOS反应、细胞间通讯和严格反应(ppGpp-介导)是持久性细胞形成的主要潜在机制。然而,根除持久性细胞是具有挑战性的,因为启动它们形成的具体分子机制仍然模糊和未知。在这里,我们回顾和总结了目前对细菌持久性细胞如何形成、控制和破坏的理解。
{"title":"Bacterial Persister Cells: Mechanisms of Formation, Control, and Eradication.","authors":"Ebrahim Kouhsari,&nbsp;Vahab Hassan Kaviar,&nbsp;Arezoo Asadi,&nbsp;Alireza Ahmadi,&nbsp;Mohammad Sholeh,&nbsp;Ali Mirbalouchzehi,&nbsp;Sajad Yaghoubi,&nbsp;Milad Abdi","doi":"10.2174/1871526523666230511142054","DOIUrl":"https://doi.org/10.2174/1871526523666230511142054","url":null,"abstract":"Bacterial persister cells are quiescent, slow-growing or growth-arrested phenotypic variants of normal bacterial cells that are transiently tolerant to antibiotics. It seems that persister cells are the main cause of the recurrence of various chronic infections. Stress response (RpoS-mediated), toxin-antitoxin (TA) systems, inhibition of ATP production, reactive oxygen species (ROS), efflux pumps, bacterial SOS response, cell-to-cell communication and stringent response (ppGpp- mediated) are the primary potential mechanisms for persistence cell formation. However, eradicating persistent cells is challenging as the specific molecular mechanisms that initiate their formation remain fuzzy and unknown. Here we reviewed and summarized the current understanding of how bacterial persister cells are formed, controlled, and destroyed.","PeriodicalId":13678,"journal":{"name":"Infectious disorders drug targets","volume":"23 7","pages":"17-28"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10118885","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
Hemofiltration as an Alternative for IL-6 Inhibitors in COVID-19 Cytokines Storm Associated with Underlaying Bacterial Infections: A Review Article. 血液滤过作为IL-6抑制剂在COVID-19细胞因子风暴相关的潜在细菌感染中的替代方案:综述文章
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.2174/1871526523666230502143507
Samy Zaky, Mohamed El Badry, Hoda A Makhlouf, Sherief M Abd-Elsalam, Tarik S Sarhan, Noha H Eltaweel, Heba Aly, Akram Abdelbary, Ahmed Said, Mohammed Hamdy Farouk, Amin Abdelbaki, Hanaa Fathelbab, Reham Hammad, Fathiya El-Raey

SARS-CoV-2 causes mostly mild cases. However, a considerable number of patients develop fatal acute respiratory distress syndrome due to the cytokine storm and imbalanced immune response. Several therapies depending on immunomodulation have been used, including glucocorticoids and IL-6 blockers. However, their efficacy is not perfect with all patients and patients with concomitant bacterial infections and sepsis. Accordingly, studies on different immunomodulators, including extracorporeal techniques, are crucial to save this category of patients. In this review, we overviewed the different immunomodulation techniques shortly, with a brief review of extracorporeal methods.

SARS-CoV-2引起的大多是轻微病例。然而,由于细胞因子风暴和不平衡的免疫反应,相当多的患者发生致命的急性呼吸窘迫综合征。几种依赖免疫调节的治疗方法已经被使用,包括糖皮质激素和IL-6阻滞剂。然而,对于所有患者以及合并细菌感染和败血症的患者,其疗效并不完美。因此,研究不同的免疫调节剂,包括体外技术,对于拯救这类患者至关重要。在这篇综述中,我们简要概述了不同的免疫调节技术,并简要回顾了体外方法。
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引用次数: 0
Extensive Multifocal Emphysematous Osteomyelitis of Spine: A Rare Case and a Review of Literature. 脊柱广泛多灶性肺气肿性骨髓炎:一例罕见病例及文献复习。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.2174/1871526522666220614163310
Bhawna Sharma, Vikas Lakhanpal, Abeer Goyal, Ritu Shree, Shashank Raj, Priya Sreenivasan, Manisha Biswal, Pallab Ray, Archana Angrup

Background: Emphysematous osteomyelitis (EO) is an extremely rare form of osteomyelitis which is complicated mainly by infection with gas-forming organisms. The common causative agents of this disease are mainly members of Enterobacteriaceae family, the most common are Escherichia coli and Klebsiella pneumoniae along with anaerobes. A total of 48 cases of EO have been reported in the literature till now globally and none have documented the isolation of Corynebacterium amycolatum.

Case presentation: We report a rare case of emphysematous osteomyelitis of the spine and pelvis due to Escherichia coli along with the isolation of Corynebacterium amycolatum from the same pus samples on two consecutive occasions in a 50-year-old female with uncontrolled diabetes mellitus, who was successively treated with antibiotics and drainage of pus. We also did a brief review of the literature of all cases reported till now.

Conclusion: The role of Corynebacterium amycolatum in the etiology of emphysematous osteomyelitis needs to be evaluated further in future studies as we cannot completely ignore its isolation in two consecutive samples as a mere contaminant.

背景:肺气肿性骨髓炎(EO)是一种极为罕见的骨髓炎,主要并发有气体形成的微生物感染。本病的常见病原体主要是肠杆菌科的成员,最常见的是大肠杆菌和肺炎克雷伯菌以及厌氧菌。迄今为止,在全球范围内共报道了48例EO病例,尚未报道分离出淀粉状棒状杆菌。病例介绍:我们报告一例罕见的脊柱和骨盆肺气肿性骨髓炎,由大肠杆菌引起,并连续两次从相同的脓液样本中分离出amycolatum棒状杆菌,患者是一名50岁的女性,患有未控制的糖尿病,她先后接受了抗生素治疗和脓液引流。我们也对迄今为止报道的所有病例的文献做了简要的回顾。结论:淀粉状棒状杆菌在肺气肿性骨髓炎的病因学中的作用有待于在今后的研究中进一步评估,因为我们不能完全忽视它在连续两个样本中作为单纯污染物的分离。
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引用次数: 2
Identification of a Chemical Inhibitor with a Novel Scaffold Targeting Decaprenylphosphoryl-β-D-Ribose Oxidase (DprE1). 靶向十戊烯基磷酸基-β- d -核糖氧化酶(DprE1)的新型支架化学抑制剂的鉴定
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.2174/1871526523666230309110705
Tatsuki Matsunaga, Kohei Monobe, Shunsuke Aoki

Background: Tuberculosis is the second leading cause of death from infectious diseases worldwide. Multidrug-resistant Mycobacterium tuberculosis is spreading throughout the world, creating a crisis. Hence, there is a need to develop anti-tuberculosis drugs with novel structures and versatile mechanisms of action.

Objective: In this study, we identified antimicrobial compounds with a novel skeleton that inhibits mycobacterium decaprenylphosphoryl-β-D-ribose oxidase (DprE1).

Methods: A multi-step, in silico, structure-based drug screening identified potential DprE1 inhibitors from a library of 154,118 compounds. We experimentally verified the growth inhibitory effects of the eight selected candidate compounds against Mycobacterium smegmatis. Molecular dynamics simulations were performed to understand the mechanism of molecular interactions between DprE1 and ompound 4.

Results: Eight compounds were selected through in silico screening. Compound 4 showed strong growth inhibition against M. smegmatis. Molecular dynamics simulation (50 ns) predicted direct and stable binding of Compound 4 to the active site of DprE1.

Conclusion: The structural analysis of the novel scaffold in Compound 4 can pave way for antituberculosis drug development and discovery.

背景:结核病是全球第二大传染病致死原因。耐多药结核分枝杆菌正在全世界蔓延,造成了一场危机。因此,有必要开发具有新型结构和多种作用机制的抗结核药物。目的:在本研究中,我们鉴定了具有抑制分枝杆菌十烯丙基磷酸基-β- d -核糖氧化酶(DprE1)的新型骨架的抗菌化合物。方法:通过多步骤、基于计算机结构的药物筛选,从一个包含154,118个化合物的文库中鉴定出潜在的DprE1抑制剂。实验验证了8种候选化合物对耻垢分枝杆菌的生长抑制作用。通过分子动力学模拟了解DprE1与化合物4分子相互作用的机理。结果:通过硅筛选筛选出8个化合物。化合物4对耻垢分枝杆菌有较强的生长抑制作用。分子动力学模拟(50 ns)预测了化合物4与DprE1活性位点的直接稳定结合。结论:化合物4中新型支架的结构分析可为抗结核药物的开发和发现铺平道路。
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引用次数: 0
Human Monkeypox Virus: Current State of Knowledge and Implications for the Imminent Days. 人类猴痘病毒:人类对猴痘病毒的认识现状及其对未来的影响。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.2174/1871526523666230427144755
Suman Kumar Ray, Sukhes Mukherjee
Monkeypox, a zoonotic orthopoxvirus, unintentionally infects humans and causes a condition resembling smallpox with noticeably reduced fatality. Despite the name monkeypox, the virus did not originate in monkeys. The virus has been linked to several rodents and small mammals, but the real source of monkeypox is still unknown. It was first noticed in macaque monkeys; hence it is named monkeypox. Although monkeypox transmission from person to person is extremely uncommon, it is frequently linked to respiratory droplets or close contact with mucocutaneous lesions of an infected person. This virus is indigenous to western and central Africa, with outbreaks in the Western Hemisphere linked to the exotic pet trade and international travel, making it clinically significant. The immunization against vaccinia virus provided coincidental immunity to monkeypox, but the eradication of smallpox and the consequent lack of vaccination campaigns allowed monkeypox to become clinically relevant. Even though the smallpox vaccine offers protection against the monkeypox virus, the incidence is increasing because of newly non-immunized generations. There is currently no designated treatment for infected individuals; however, supportive treatments are used to relieve symptoms. In extremely severe cases, medications such as tecovirimat may be effective and are used in Europe. Because there are no precise recommendations for symptom alleviation, many treatments are on trial. Smallpox immunizations like JYNNEOS and ACAM2000 are also used as prophylactic measures in the case of the monkeypox virus. This article describes the assessment and treatment of monkeypox infections in humans and emphasizes the need for a multidisciplinary team to treat patients with this condition and prevent disease outbreaks.
猴痘是一种人畜共患的正痘病毒,会无意中感染人类,导致类似天花的病症,但死亡率明显降低。尽管名为猴痘,但这种病毒并非起源于猴子。这种病毒与几种啮齿类动物和小型哺乳动物有关,但猴痘的真正来源至今不明。猴痘最早出现在猕猴身上,因此被命名为猴痘。尽管猴痘在人与人之间的传播极为罕见,但它经常与呼吸道飞沫或密切接触感染者的皮肤黏膜病变有关。这种病毒原产于非洲西部和中部,在西半球的爆发与外来宠物交易和国际旅行有关,因此具有重要的临床意义。接种天花病毒疫苗可偶然获得对猴痘的免疫力,但天花的根除和随之而来的疫苗接种运动的缺乏使猴痘变得与临床相关。尽管天花疫苗提供了对猴痘病毒的保护,但由于新生代未接种疫苗,猴痘的发病率仍在上升。目前还没有针对受感染者的指定治疗方法,但可通过辅助治疗缓解症状。在极其严重的病例中,特考韦利马特(tecovirimat)等药物可能有效,在欧洲也有使用。由于没有关于缓解症状的确切建议,许多治疗方法都在试用中。对于猴痘病毒,JYNNEOS 和 ACAM2000 等天花免疫接种也被用作预防措施。本文介绍了人类猴痘感染的评估和治疗方法,并强调了多学科团队治疗猴痘患者和预防疾病爆发的必要性。
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引用次数: 0
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