Aspects of molecular medicine最新文献_第4页

Human serum albumin binds spike protein and protects cells from SARS-CoV-2 infection by modulating the RAS pathway 人血清白蛋白与尖峰蛋白结合，通过调节 RAS 通路保护细胞免受 SARS-CoV-2 感染

Aspects of molecular medicine Pub Date : 2023-12-14 DOI: 10.1016/j.amolm.2023.100033

Romualdo Varricchio , Giovanna De Simone , Gian Marco Vita , Walter Nocera Cariola , Maurizio Viscardi , Sergio Brandi , Gerardo Picazio , Verena Zerbato , Raffaella Koncan , Ludovica Segat , Stefano Di Bella , Giovanna Fusco , Paolo Ascenzi , Alessandra di Masi

{"title":"Human serum albumin binds spike protein and protects cells from SARS-CoV-2 infection by modulating the RAS pathway","authors":"Romualdo Varricchio , Giovanna De Simone , Gian Marco Vita , Walter Nocera Cariola , Maurizio Viscardi , Sergio Brandi , Gerardo Picazio , Verena Zerbato , Raffaella Koncan , Ludovica Segat , Stefano Di Bella , Giovanna Fusco , Paolo Ascenzi , Alessandra di Masi","doi":"10.1016/j.amolm.2023.100033","DOIUrl":"10.1016/j.amolm.2023.100033","url":null,"abstract":"<div><p>Since the start of the pandemic, scientists have directed their research towards identifying COVID-19 risk factors and predictive elements. Numerous clinical studies have established a strong connection between hypoalbuminemia and an unfavorable prognosis for COVID-19. Here, we aim to explore the impact of human serum albumin (HSA) on SARS-CoV-2 infection. Our findings indicate that HSA plays a role in reducing the replication rate of SARS-CoV-2 in Vero E6 cells. This protective effect is due to HSA ability to bind to the S1 domain of the spike protein, effectively competing with ACE2. Moreover, we show that the protective role of HSA is dependent also on its ability to activate the protective axis within the RAS system pathway, which is responsible for inducing vasodilation and promoting anti-inflammatory, anti-fibrotic, and anti-apoptotic responses. In summary, the data presented in this study support the idea that reduced levels of circulating HSA in hypoalbuminemic patients may heighten their susceptibility to SARS-CoV-2 infection, as the spike protein is unhindered in its ability to bind to ACE2 and penetrate human cells. Besides, hypoalbuminemia exacerbates the imbalance of the RAS pathway towards the classical “detrimental” axis. This could potentially contribute to the increased severity and elevated mortality rate observed in individuals with low levels of circulating albumin.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100033"},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688823000333/pdfft?md5=0c53d54701d04e1e52bec07beb4f8e52&pid=1-s2.0-S2949688823000333-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139013329","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

In silico study of the flavonoid compound of Sauropus androgynus leaves ON RNA-Dependent RNA polymerase (RdRp) SARS-CoV-2 Sauropus androgynus 叶中黄酮类化合物 ON RNA 依赖性 RNA 聚合酶（RdRp）SARS-CoV-2 的硅学研究

Aspects of molecular medicine Pub Date : 2023-12-07 DOI: 10.1016/j.amolm.2023.100032

Aghnia Nabila Ananda , Triawanti Triawanti , Bambang Setiawan , Annisa Camellia Makati , Jasmine Aisyah Putri , Sentot Joko Raharjo

{"title":"In silico study of the flavonoid compound of Sauropus androgynus leaves ON RNA-Dependent RNA polymerase (RdRp) SARS-CoV-2","authors":"Aghnia Nabila Ananda , Triawanti Triawanti , Bambang Setiawan , Annisa Camellia Makati , Jasmine Aisyah Putri , Sentot Joko Raharjo","doi":"10.1016/j.amolm.2023.100032","DOIUrl":"10.1016/j.amolm.2023.100032","url":null,"abstract":"<div><h3>Objective</h3><p>RNA-dependent RNA polymerase (RdRp) is a protein that is essential in the replication and transcription processes of SARS-CoV-2. RdRp inhibitors must be sought, particularly in the identification of active substances in herbal or human dietary sources. The purpose of this study was to investigate the molecular docking of phytochemistry from the leaves of <em>Sauropus androgynus</em> against the RdRp protein.</p></div><div><h3>Methods</h3><p>This in silico study was performed using AutoDock Tools 1.5.7, AutoDock Vina v1.2.3 software, and BIOVIA Discovery Studio Visualizer 4.1.</p></div><div><h3>Results</h3><p>Afzelin, kaempferol, and trifolin were found as phytochemistry in Sauropus androgynus leaves. Among the three flavonoid molecules, afzelin has the lowest negative binding affinity (−7.677 kcal/mol), followed by trifolin (−6.906 kcal/mol) and kaempferol (−6.65 kcal/mol). All three flavonoid compounds have a binding affinity that is more negative than the three conventional drugs (favipiravir, remdesivir, ribavirin).</p></div><div><h3>Conclusions</h3><p>Flavonoid from the leaves of <em>Sauropus androgynus</em> leaves can be utilized as candidate for herbal or complementary medicine as an inhbitor of RdRp for COVID-19 treatment.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688823000321/pdfft?md5=0d7af3c65653d94265a12879357adc18&pid=1-s2.0-S2949688823000321-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138615677","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

Mefenamic acid inhibit transforming growth factor-beta type-1: Repurposing anti-inflammatory drugs in wound healing using in-silico approaches 甲非那明酸抑制转化生长因子-1型:用芯片方法在伤口愈合中重新利用消炎药

Aspects of molecular medicine Pub Date : 2023-12-01 DOI: 10.1016/j.amolm.2023.100031

Miah Roney , Abdul Rashid Issahaku , Normaiza Binti Zamri , Mohd Fadhlizil Fasihi Mohd Aluwi

{"title":"Mefenamic acid inhibit transforming growth factor-beta type-1: Repurposing anti-inflammatory drugs in wound healing using in-silico approaches","authors":"Miah Roney , Abdul Rashid Issahaku , Normaiza Binti Zamri , Mohd Fadhlizil Fasihi Mohd Aluwi","doi":"10.1016/j.amolm.2023.100031","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100031","url":null,"abstract":"<div><p>Due to low cost and time-saving benefits, drug repurposing is a safe and successful method to discover drug. A druggable target for inflammation, transforming growth factor-beta type-1 (TGF-β 1) has been identified to be associated with wound healing. Finding the most effective TGF-β 1 inhibitor among FDA-approved anti-inflammatory medications was the goal of the current investigation. To find the best hits against TGF-β 1, we used structure-based virtual screening on medications that have received FDA approval. We discovered two FDA-approved medications with notable selectivity and affinity for the binding pocket of TGF-β 1. Mefenamic acid, one of these found hits, interacts with key TGF-β 1 residues and favourably attaches to the binding pocket, requiring further study. The kinetics of the binding between mefenamic acid and TGF-β 1 were revealed by all-atom precise molecular dynamics (MD) simulations. Mefenamic acid, which may also be used as a possible lead chemical against TGF-β 1, may be a promising TGF-β 1 inhibitor.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294968882300031X/pdfft?md5=f66163663185f30d3e426aa14a2f9faf&pid=1-s2.0-S294968882300031X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138467100","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

Relationship between genetic ancestry and metabolic syndrome in community-dwelling old adults 社区老年人遗传祖先与代谢综合征的关系

Aspects of molecular medicine Pub Date : 2023-12-01 DOI: 10.1016/j.amolm.2023.100027

Jamille Silva Oliveira , Gabriel Novaes Miranda , Icaro J.S. Ribeiro , Ivna Vidal Freire , Cezar Augusto Casotti , Ana Angélica Leal Barbosa , Rafael Pereira

{"title":"Relationship between genetic ancestry and metabolic syndrome in community-dwelling old adults","authors":"Jamille Silva Oliveira , Gabriel Novaes Miranda , Icaro J.S. Ribeiro , Ivna Vidal Freire , Cezar Augusto Casotti , Ana Angélica Leal Barbosa , Rafael Pereira","doi":"10.1016/j.amolm.2023.100027","DOIUrl":"10.1016/j.amolm.2023.100027","url":null,"abstract":"<div><p>Genetic ancestry may contribute to ethnic differences in the risk of metabolic disorders. Aging leads to a worse ability for homeostasis maintenance, favoring the establishment of metabolic disorders.</p></div><div><h3>Purpose</h3><p>This study aimed to evaluate the relationship between the degree of genetic ancestry (European, African, and Amerindian) with the Metabolic Syndrome (MetS) diagnosis and its diagnostic components separately, in community-dwelling old adults. One hundred and sixty-one community-dwelling old adults volunteered in this study. Sociodemographic data and health history were recorded. Venous blood samples were withdrawal for biochemical analysis and DNA extraction aiming to obtain genetic ancestry estimates (Amerindian [AME], European [EUR], and African [AFR]), which was done from 12 loci. MetS diagnosis followed the NCEP-ATPIII criteria. Additionally, the sample was stratified according to the presence or absence of each criterion used for MetS diagnosis (i.e., Type 2 diabetes mellitus (T2DM), hypertension, hypertriglyceridemia, dyslipidemia [low HDL], and central obesity (elevated waist circumference)). Comparisons of genetic ancestry estimates were performed using the Mann-Whitney test, with the significance level set at p < 0.05. The prevalence of MetS was 40.4%. The degree AME, EUR and AFR genetic ancestry was not different between volunteers with or without MetS (p > 0.05). However, AME ancestry was significantly higher among diabetic volunteers (non-diabetics: 13.7% (6.3–35.8) x Diabetics: 26.1% (10.6–48.5); p < 0.05). Community-dwelling old adults with a higher percentage of Amerindian ancestry seem to be prone to T2DM diagnosis.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100027"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688823000278/pdfft?md5=5622aed5070444ef6d4e6cf7cf3dd1a0&pid=1-s2.0-S2949688823000278-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135669985","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

Academic examination stress: Effects on salivary cortisol, neuropeptide Y and interleukin-1β 学业考试压力对唾液皮质醇、神经肽Y和白细胞介素-1β的影响

Aspects of molecular medicine Pub Date : 2023-11-22 DOI: 10.1016/j.amolm.2023.100030

Rabia Şemsi , Erdal Ergünol , Emre Kanad Er , Aylin Sepici Dinçel

{"title":"Academic examination stress: Effects on salivary cortisol, neuropeptide Y and interleukin-1β","authors":"Rabia Şemsi , Erdal Ergünol , Emre Kanad Er , Aylin Sepici Dinçel","doi":"10.1016/j.amolm.2023.100030","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100030","url":null,"abstract":"<div><p>Saliva is one of the preferred non-invasive body fluids for biomarker studies. This study aimed to investigate the possible alteration of stress biomarkers of the students before and after the examinations via salivary cortisol, neuropeptide Y (NPY), and Interleukin-1β (IL-1β) levels. Forty-four adults were included in the study and divided into groups of pre-examination (Group I) and post-examination (Group II). Salivary samples were collected between 8 and 9 a.m. before and after the exam, which ended at 5 p.m. by SARSTEDT saliva collection tubes. Participants were asked to soak the swab with saliva and take it out after 1 min. Swabs were kept at room temperature for 15–30 min and centrifuged for 10–15 min at 1500 g. Salivary cortisol (ng/mL), NPY (ng/mL), and IL-1β (pg/mL) levels were analyzed by Enzyme-linked immunosorbent assay (ELISA). The salivary cortisol, NPY and IL-1 β levels were significantly increased in Group II compared to Group I (9.65 ± 4.53, 6.37 ± 4.14, p < 0.019; 32.12 ± 4.69, 27.10 ± 4.71 p < 0.001; 11.69 ± 3.61, 7.20 ± 3.49, p < 0.0003 respectively). The IL-1β levels were positively and significantly correlated with salivary cortisol and NPY levels in Group II (r = 0.642, p = 0.03; r = 0.589, p = 0.004, respectively). Also, IL-1β levels were positively and significantly correlated with salivary NPY levels in Group I (r = 0.430, p = 0.04). These data indicated that acute stress can alter the inflammatory response and increase NPY release, which is positively associated with cortisol.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100030"},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688823000308/pdfft?md5=9a681beb8339e4ab09c51cfa49dfdbe4&pid=1-s2.0-S2949688823000308-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138413594","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

Gut microbiome associated dysbiosis: Limited regimens and expanding horizons of phage therapy 肠道微生物相关的生态失调:有限的方案和噬菌体治疗的扩展视野

Aspects of molecular medicine Pub Date : 2023-11-21 DOI: 10.1016/j.amolm.2023.100029

Biplab Singha , Bhupendra Singh Rawat , Ramya Venkataraman , Tripti Nair , Eric H. Rosenn , Vijay Soni

{"title":"Gut microbiome associated dysbiosis: Limited regimens and expanding horizons of phage therapy","authors":"Biplab Singha , Bhupendra Singh Rawat , Ramya Venkataraman , Tripti Nair , Eric H. Rosenn , Vijay Soni","doi":"10.1016/j.amolm.2023.100029","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100029","url":null,"abstract":"<div><p>Human gut microbiota plays an important role in health, broadly influencing metabolism to the immune system and drug resistance to pathogenic colonization. Since antibiotic resistance is on the rise, and wide-spectrum antibiotics are known to have deleterious effects on microbial biodiversity targeted therapeutic interventions must be made. Bacteriophages are viruses that are commonly recognized to have a high level of specificity, targeting only the intended bacterial species without disrupting the overall microbial community. Advancements in genomics, bioinformatics, and synthetic biology led us to the identification and design of phages, capable of precisely targeting specific pathogens. In this review article, we aim to discuss both the challenges and opportunities of integrating phage therapies into clinical practice, discussing the limitations of traditional therapy as it pertains to the manipulation of the gut microbiome.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100029"},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688823000291/pdfft?md5=1315a9379986533a4d8a50b610b53379&pid=1-s2.0-S2949688823000291-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138437682","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

Inhibitory effect of Sinapic acid derivatives targeting structural and non-structural proteins of dengue virus serotype 2: An in-silico assessment 辛酸衍生物对2型登革热病毒结构蛋白和非结构蛋白的抑制作用:计算机模拟评估

Aspects of molecular medicine Pub Date : 2023-11-10 DOI: 10.1016/j.amolm.2023.100028

Miah Roney , Amit Dubey , Normaiza Binti Zamri , Mohd Fadhlizil Fasihi Mohd Aluwi

{"title":"Inhibitory effect of Sinapic acid derivatives targeting structural and non-structural proteins of dengue virus serotype 2: An in-silico assessment","authors":"Miah Roney , Amit Dubey , Normaiza Binti Zamri , Mohd Fadhlizil Fasihi Mohd Aluwi","doi":"10.1016/j.amolm.2023.100028","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100028","url":null,"abstract":"<div><p>DENV infects 50–100 million individuals, and 500,000 of them go on to acquire the more serious dengue hemorrhagic fever, which causes around 20,000 fatalities every year. Despite its widespread nature, there is no medication licenced to treat this condition. The purpose of this work is to identify <em>anti</em>-DENV medicines from sinapic acid (SA) derivatives utilising in-silico evaluation through docking and pharmacokinetics investigations. For the DENV-2 envelop protein, 1-<em>O</em>-β-<span>d</span>-glucopyranosyl sinapate had a significant docking score of −7.7 kcal/mol, while sinapoyl malate had a docking score of −6.7 kcal/mol for the DENV-2 NS2B/NS3 protein. Additionally, according to the PASS server, 1-<em>O</em>-β-<span>d</span>-glucopyranosyl sinapate and sinapoyl malate have a wide range of enzymatic activities since their probability active (Pa) values is > 0.700. These compounds exhibit a numerous pharmacological effect through activating the body's enzymes, according to analyses of their pharmacokinetic qualities. Accordingly, these substances showed acute toxicity rates at LD50 log10 (mmol/g) and LD50 (mg/g) concentrations when administered via various routes, including intraperitoneal, intravenous, oral, and subcutaneous. The result of this research suggests, 1-<em>O</em>-β-<span>d</span>-glucopyranosyl sinapate and sinapoyl malate may function as possible inhibitors to halt the DENV, and more in-vitro and in-vivo research is required to validate their activity and other features.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100028"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294968882300028X/pdfft?md5=3d3d845efe3147fd6769e3d568c51c04&pid=1-s2.0-S294968882300028X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134656524","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

Isogenic hiPSC-derived liver-on-chip platforms: A valuable tool for modeling metabolic liver diseases 等基因hipsc衍生的肝脏芯片平台:代谢性肝脏疾病建模的宝贵工具

Aspects of molecular medicine Pub Date : 2023-10-17 DOI: 10.1016/j.amolm.2023.100025

Kehinde Oluwasegun Aina

{"title":"Isogenic hiPSC-derived liver-on-chip platforms: A valuable tool for modeling metabolic liver diseases","authors":"Kehinde Oluwasegun Aina","doi":"10.1016/j.amolm.2023.100025","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100025","url":null,"abstract":"<div><p>The liver is a complex organ with vital functions in metabolism, detoxification, and immunity. The anatomy, physiology, and cellular composition of the liver are crucial for comprehending its spatial heterogeneity and regulation of homeostasis. Hepatocytes, liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs), and liver macrophages play pivotal roles in liver function and pathology. Liver diseases such as NAFLD, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and Liver fibrosis are prevalent and pose significant health challenges. Studying liver development provides insights into liver model evolution, including differentiation protocols for human hepatocyte-like cells (HLCs), hiPSC -derived endothelial cells, stellate cells and macrophages.</p><p>Currently, the research landscape of liver tissue models encompasses in vivo and in vitro approaches, including 2D and 3D liver cell culture methods, on-chip systems, and patient-derived hiPSC-based liver disease models. The integration of hiPSCs with micro-physiological systems holds promise for recapitulating liver function and disease in vitro. However, challenges remain in achieving the physiological relevance and scalability of liver models. Advances in the research landscape of liver tissue models are discussed, providing insights into identifying individual patient groups, the current status quo, and prospects of liver research at the interface of developmental biology, tissue engineering, and disease modeling which will allow conclusions to be drawn about the molecular mechanisms of liver diseases and ultimately the targeted use of suitable therapeutics.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100025"},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688823000254/pdfft?md5=f43a35de3b4cf35578f3848573646414&pid=1-s2.0-S2949688823000254-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136968401","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

Polypharmacological assessment of Amoxicillin and its analogues against the bacterial DNA gyrase B using molecular docking, DFT and molecular dynamics simulation 利用分子对接、DFT和分子动力学模拟对阿莫西林及其类似物对细菌DNA旋切酶B的多药理作用进行评价

Aspects of molecular medicine Pub Date : 2023-10-03 DOI: 10.1016/j.amolm.2023.100024

Miah Roney , Gagandeep Singh , Amit Dubey , Hemant Soni , Smriti Tandon , Cheemlapati Venkata Narasimhaji , Aisha Tufail , Moyeenul Huq Akm , Mohd Fadhlizil Fasihi Mohd Aluwi

{"title":"Polypharmacological assessment of Amoxicillin and its analogues against the bacterial DNA gyrase B using molecular docking, DFT and molecular dynamics simulation","authors":"Miah Roney , Gagandeep Singh , Amit Dubey , Hemant Soni , Smriti Tandon , Cheemlapati Venkata Narasimhaji , Aisha Tufail , Moyeenul Huq Akm , Mohd Fadhlizil Fasihi Mohd Aluwi","doi":"10.1016/j.amolm.2023.100024","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100024","url":null,"abstract":"<div><p>There has been an increase in the emergence and spread of drug-resistant pathogens, leading to a steep incline in the cases of antimicrobial resistance. Due to this, there is an imperative need for the development and identification of new antimicrobials to combat this menace of antimicrobial resistance. But this need is not being completely fulfilled by conventional drug discovery focused on a one molecule-one target approach. Polypharmacology, i.e., designing a drug in a way that acts on multiple cellular or molecular targets, a new approach for the identification of antimicrobial compounds, has been gaining attention. DNA gyrase B is one of the critical proteins involved in DNA replication and cell division in <em>E. coli</em>. In this study, the polypharmacological effect of amoxicillin and its analogues was studied on the DNA gyrase B and various other proteins of <em>E. coli</em>, using multiple in silico approaches like molecular docking, structural similarity, DFT, and molecular dynamics simulation. Both amoxicillin and its analogue, Cefaclor, tend to disrupt bacterial cell wall synthesis, but this study, based on in silico analysis, suggests a probable additional mode of action involving DNA gyrase B of <em>E. coli</em> which can be further explored to design novel dual-target inhibitors.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100024"},"PeriodicalIF":0.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49708081","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

Biomarkers in acute myeloid leukemia: From state of the art in risk classification to future challenges of RNA editing as disease predictor and therapy target 急性髓性白血病的生物标志物:从风险分类的最新进展到RNA编辑作为疾病预测和治疗靶点的未来挑战

Aspects of molecular medicine Pub Date : 2023-09-13 DOI: 10.1016/j.amolm.2023.100023

Alberto Quattrocchi , Luca Vincenzo Cappelli , Giovanna De Simone , Elisabetta De Marinis , Martina Gentile , Tecla Gasperi , Alessandro Pulsoni , Paolo Ascenzi , Clara Nervi

{"title":"Biomarkers in acute myeloid leukemia: From state of the art in risk classification to future challenges of RNA editing as disease predictor and therapy target","authors":"Alberto Quattrocchi , Luca Vincenzo Cappelli , Giovanna De Simone , Elisabetta De Marinis , Martina Gentile , Tecla Gasperi , Alessandro Pulsoni , Paolo Ascenzi , Clara Nervi","doi":"10.1016/j.amolm.2023.100023","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100023","url":null,"abstract":"<div><p>Acute Myeloid Leukemia (AML) is currently diagnosed based on morphological assessment of myeloid cells’ features, immunophenotypic characterization of specific cell surface and intracellular markers, conventional cytogenetic testing and screening for genetic abnormalities in bone marrow and peripheral blood specimens. In recent years new technologies have shed light on the complexity and heterogeneity of this elusive leukemia and are providing useful biomarkers, predictive of prognosis in AML patients. Hence, technological efforts are being made in order to identify more accurate AML biomarkers also useful to track minimal residual disease at the various follow-up times. This remains an unmet need that, together with the intrinsic tumor features of AML, results in the highest death rate of all leukemias and a 5-year overall survival <50%. This review provides insights into the state-of-the-art of AML-related biomarkers and their role in clinical practice as prognostic indicators, minimal residual disease detection or candidates for targeted therapy. In addition, we report modifications of RNA epitranscriptome during normal hematopoiesis that are de-regulated in AML, recently revealed by new and more sophisticated techniques. We focus on alterations of m<sup>6</sup>A modifications on mRNAs and of enzymes catalyzing them, which have been reported to affect normal hematopoiesis and leukemogenesis and are providing novel promising biomarkers for AML risk assessment and newly druggable targets for treatment.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100023"},"PeriodicalIF":0.0,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49708080","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}

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