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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
Infectious disorders drug targets 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
{"title":"Extended-Spectrum β-Lactamase-Producing <i>Escherichia coli</i> and Virulence Genes in Pediatric Patients with Health-Care Urinary Tract Infections.","authors":"Mohamed Anies Rizk,&nbsp;Maysaa El Sayed Zaki,&nbsp;Hanan Abdelfattah Abdelmohsen Mohamed,&nbsp;Dina Mohammed Abdelhady Mahmood,&nbsp;Karim Monatasser","doi":"10.2174/1871526523666221104150123","DOIUrl":"https://doi.org/10.2174/1871526523666221104150123","url":null,"abstract":"<p><strong>Introduction: </strong>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).</p><p><strong>Objective: </strong>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 bla<sub>CTX</sub> gene.</p><p><strong>Methods: </strong>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 bla<sub>CTX-M</sub> gene.</p><p><strong>Results: </strong>E. coli producing ESBL by double discs method was identified in 74 isolates. bla<sub>CTX-M</sub> 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 bla<sub>CTX-M</sub> 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 bla<sub>CTX-M</sub> gene in the isolated E. coli.</p><p><strong>Conclusion: </strong>The present study highlights the presence of virulence genes and bla<sub>CTX-M</sub> gene in uropathogenic E. coli isolated from pediatric patients with healthcare-associated urinary tract infections. There was an association between the bla<sub>CTX-M</sub> 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 bla<sub>CTX-M</sub> in about one-third of the isolates.</p>","PeriodicalId":13678,"journal":{"name":"Infectious disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10133364","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
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。
Infectious disorders drug targets 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
{"title":"The Impact of COVID-19 Pandemic on the Levels of Physical Activity: A Systematic Review.","authors":"Esmaeil Mehraeen,&nbsp;Amirali Karimi,&nbsp;Seyed Peyman Mirghaderi,&nbsp;Pegah Mirzapour,&nbsp;Zahra Pashaei,&nbsp;Kowsar Qaderi,&nbsp;Amir Masoud Afsahi,&nbsp;Alireza Barzegary,&nbsp;Parsa Mohammadi,&nbsp;Alireza Shojaei,&nbsp;Solmaz Saeidi,&nbsp;Fatemeh Afroughi,&nbsp;Mehrzad MohsseniPour,&nbsp;Nazanin Janfaza,&nbsp;Omid Dadras,&nbsp;Ava Amiri,&nbsp;Kimia Azad,&nbsp;SeyedAhmad SeyedAlinaghi,&nbsp;Marcarious M Tantuoyir,&nbsp;Fabricio Voltarelli","doi":"10.2174/1871526523666230120143118","DOIUrl":"https://doi.org/10.2174/1871526523666230120143118","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13678,"journal":{"name":"Infectious disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10145353","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: 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。
Infectious disorders drug targets 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
{"title":"Fatal <i>Clostridium sporogenes</i> Soft Tissue Polymicrobial Infections in Two Immunocompetent Cases: Case Report.","authors":"Preeti Chaudhary,&nbsp;Neelam Gulati,&nbsp;Varsha Gupta,&nbsp;Gazal Dhanda,&nbsp;Mani Bhushan Kumar,&nbsp;Swati Sharma,&nbsp;Anku Goel,&nbsp;Ashok Kumar Attri","doi":"10.2174/1871526523666230112161134","DOIUrl":"https://doi.org/10.2174/1871526523666230112161134","url":null,"abstract":"<p><strong>Background: </strong>Clostridium sporogenes is reported rarely in literature. Reports from the skin and soft tissue infections are even less, more so in immunocompetent patients.</p><p><strong>Case presentation: </strong>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.</p><p><strong>Discussion and conclusion: </strong>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.</p>","PeriodicalId":13678,"journal":{"name":"Infectious disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9777879","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: 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
Infectious disorders drug targets 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
{"title":"Human ACE-2, MCP1 and micro-RNA 146 as Novel Markers for COVID- 19 Affection and Severity.","authors":"Amal Ahmed Mohamed,&nbsp;Sherief Abd-Elsalam,&nbsp;Ahmed Abdelghani,&nbsp;Mohamed Badr Hassan,&nbsp;Doaa Ghaith,&nbsp;Omnia Ezzat,&nbsp;Dalia Ali El-Damasy,&nbsp;Norhan Nagdi Madbouli,&nbsp;Mohmoud Hamada,&nbsp;Mohamed Abdel Khalik Hepatology Gastroenterology And Infectious Diseases,&nbsp;Shaimaa M Al-Tabbakh,&nbsp;Kareman Ahmed Ebrahim Eshra,&nbsp;Nivin Baiomy","doi":"10.2174/1871526522666220829153042","DOIUrl":"https://doi.org/10.2174/1871526522666220829153042","url":null,"abstract":"<p><strong>Background & aims: </strong>Coronavirus disease - 2019 (COVID-19) is a major pandemic that causes high morbidity and mortality rates.</p><p><strong>Aim of this study: </strong>to detect the relations between many risk factors, ACE-2, MCP-1, Micro RNA 146 gene expression, and COVID-19 infection and disease severity.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13678,"journal":{"name":"Infectious disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10666209","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
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)。
Infectious disorders drug targets 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":null,"pages":null},"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。
Infectious disorders drug targets 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
{"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":null,"pages":null},"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
Infectious disorders drug targets 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
{"title":"Hemofiltration as an Alternative for IL-6 Inhibitors in COVID-19 Cytokines Storm Associated with Underlaying Bacterial Infections: A Review Article.","authors":"Samy Zaky,&nbsp;Mohamed El Badry,&nbsp;Hoda A Makhlouf,&nbsp;Sherief M Abd-Elsalam,&nbsp;Tarik S Sarhan,&nbsp;Noha H Eltaweel,&nbsp;Heba Aly,&nbsp;Akram Abdelbary,&nbsp;Ahmed Said,&nbsp;Mohammed Hamdy Farouk,&nbsp;Amin Abdelbaki,&nbsp;Hanaa Fathelbab,&nbsp;Reham Hammad,&nbsp;Fathiya El-Raey","doi":"10.2174/1871526523666230502143507","DOIUrl":"https://doi.org/10.2174/1871526523666230502143507","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13678,"journal":{"name":"Infectious disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10045575","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
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。
Infectious disorders drug targets 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
{"title":"Extensive Multifocal Emphysematous Osteomyelitis of Spine: A Rare Case and a Review of Literature.","authors":"Bhawna Sharma,&nbsp;Vikas Lakhanpal,&nbsp;Abeer Goyal,&nbsp;Ritu Shree,&nbsp;Shashank Raj,&nbsp;Priya Sreenivasan,&nbsp;Manisha Biswal,&nbsp;Pallab Ray,&nbsp;Archana Angrup","doi":"10.2174/1871526522666220614163310","DOIUrl":"https://doi.org/10.2174/1871526522666220614163310","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Case presentation: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13678,"journal":{"name":"Infectious disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10665171","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: 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
Infectious disorders drug targets Pub Date : 2023-01-01 DOI: 10.2174/1871526523666230309110705
Tatsuki Matsunaga, Kohei Monobe, Shunsuke Aoki
{"title":"Identification of a Chemical Inhibitor with a Novel Scaffold Targeting Decaprenylphosphoryl-β-D-Ribose Oxidase (DprE1).","authors":"Tatsuki Matsunaga,&nbsp;Kohei Monobe,&nbsp;Shunsuke Aoki","doi":"10.2174/1871526523666230309110705","DOIUrl":"https://doi.org/10.2174/1871526523666230309110705","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>In this study, we identified antimicrobial compounds with a novel skeleton that inhibits mycobacterium decaprenylphosphoryl-β-D-ribose oxidase (DprE1).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>The structural analysis of the novel scaffold in Compound 4 can pave way for antituberculosis drug development and discovery.</p>","PeriodicalId":13678,"journal":{"name":"Infectious disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9831522","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
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。
Infectious disorders drug targets Pub Date : 2023-01-01 DOI: 10.2174/1871526523666230427144755
Suman Kumar Ray, Sukhes Mukherjee
{"title":"Human Monkeypox Virus: Current State of Knowledge and Implications for the Imminent Days.","authors":"Suman Kumar Ray, Sukhes Mukherjee","doi":"10.2174/1871526523666230427144755","DOIUrl":"10.2174/1871526523666230427144755","url":null,"abstract":"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.","PeriodicalId":13678,"journal":{"name":"Infectious disorders drug targets","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10043495","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
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