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Journal of Infection and Public Health Nov 2022The first infection case of new coronavirus was reported at the end of 2019 and after then, the cases are reported in all nations across the world in a very short... (Review)
Review
An understanding of coronavirus and exploring the molecular dynamics simulations to find promising candidates against the Mpro of nCoV to combat the COVID-19: A systematic review.
The first infection case of new coronavirus was reported at the end of 2019 and after then, the cases are reported in all nations across the world in a very short period. Further, the regular news of mutations in the virus has made life restricted with appropriate behavior. To date, a new strain (Omicron and its new subvariant Omicron XE) has brought fear amongst us due to a higher trajectory of increase in the number of cases. The researchers thus started giving attention to this viral infection and discovering drug-like candidates to cure the infections. Finding a drug for any viral infection is not an easy task and takes plenty of time. Therefore, computational chemistry/bioinformatics is followed to get promising molecules against viral infection. Molecular dynamics (MD) simulations are being explored to get drug candidates in a short period. The molecules are screened via molecular docking, which provides preliminary information which can be further verified by molecular dynamics (MD) simulations. To understand the change in structure, MD simulations generated several trajectories such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, and radius of gyration for the main protease (Mpro) of the new coronavirus (nCoV) in the presence of small molecules. Additionally, change in free energy for the formation of complex of Mpro of nCoV with the small molecule can be determined by applying molecular mechanics with generalized born and surface area solvation (MM-GBSA). Thus, the promising molecules can be further explored for clinical trials to combat coronavirus disease-19 (COVID-19).
Topics: Humans; Computational Biology; Coronavirus 3C Proteases; COVID-19; COVID-19 Drug Treatment; Drug Discovery; Molecular Docking Simulation; Molecular Dynamics Simulation
PubMed: 36288640
DOI: 10.1016/j.jiph.2022.10.013 -
International Journal of Surgery... Jun 2024Computer-aided drug design (CADD) is a drug design technique for computing ligand-receptor interactions and is involved in various stages of drug development. To better...
AIM
Computer-aided drug design (CADD) is a drug design technique for computing ligand-receptor interactions and is involved in various stages of drug development. To better grasp the frontiers and hotspots of CADD, we conducted a review analysis through bibliometrics.
METHODS
A systematic review of studies published between 2000 and 20 July 2023 was conducted following the PRISMA guidelines. Literature on CADD was selected from the Web of Science Core Collection. General information, publications, output trends, countries/regions, institutions, journals, keywords, and influential authors were visually analyzed using software such as Excel, VOSviewer, RStudio, and CiteSpace.
RESULTS
A total of 2031 publications were included. These publications primarily originated from 99 countries or regions led by the U.S. and China. Among the contributors, MacKerell AD had the highest number of articles and the greatest influence. The Journal of Medicinal Chemistry was the most cited journal, whereas the Journal of Chemical Information and Modeling had the highest number of publications.
CONCLUSIONS
Influential authors in the field were identified. Current research shows active collaboration between countries, institutions, and companies. CADD technologies such as homology modeling, pharmacophore modeling, quantitative conformational relationships, molecular docking, molecular dynamics simulation, binding free energy prediction, and high-throughput virtual screening can effectively improve the efficiency of new drug discovery. Artificial intelligence-assisted drug design and screening based on CADD represent key topics that will influence future development. Furthermore, this paper will be helpful in better understanding the frontiers and hotspots of CADD.
Topics: Bibliometrics; Humans; Computer-Aided Design; Drug Design; Molecular Docking Simulation
PubMed: 38502850
DOI: 10.1097/JS9.0000000000001289 -
Biomedicines Feb 2022Despite current therapeutic strategies for immunomodulation and relief of symptoms in multiple sclerosis (MS), remyelination falls short due to dynamic neuropathologic... (Review)
Review
Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination.
Despite current therapeutic strategies for immunomodulation and relief of symptoms in multiple sclerosis (MS), remyelination falls short due to dynamic neuropathologic deterioration and relapses, leading to accrual of disability and associated patient dissatisfaction. The potential of cannabinoids includes add-on immunosuppressive, analgesic, neuroprotective, and remyelinative effects. This study evaluates the efficacy of medical marijuana in MS and its experimental animal models. A systematic review was conducted by a literature search through PubMed, ProQuest, and EBSCO electronic databases for studies reported since 2007 on the use of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in MS and in experimental autoimmune encephalomyelitis (EAE), Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and toxin-induced demyelination models. Study selection and data extraction were performed by 3 reviewers, and 28 studies were selected for inclusion. The certainty of evidence was appraised using the Cochrane GRADE approach. In clinical studies, there was low- and moderate-quality evidence that treatment with ~1:1 CBD/THC mixtures as a nabiximols (Sativex) oromucosal spray reduced numerical rating scale (NRS) scores for spasticity, pain, and sleep disturbance, diminished bladder overactivity, and decreased proinflammatory cytokine and transcription factor expression levels. Preclinical studies demonstrated decreases in disease severity, hindlimb stiffness, motor function, neuroinflammation, and demyelination. Other experimental systems showed the capacity of cannabinoids to promote remyelination in vitro and by electron microscopy. Modest short-term benefits were realized in MS responders to adjunctive therapy with CBD/THC mixtures. Future studies are recommended to investigate the cellular and molecular mechanisms of cannabinoid effects on MS lesions and to evaluate whether medical marijuana can accelerate remyelination and retard the accrual of disability over the long term.
PubMed: 35327341
DOI: 10.3390/biomedicines10030539 -
International Journal of Molecular... Apr 2024In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic... (Review)
Review
In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research question "What therapeutic targets have been used in in silico analysis for the treatment of obesity?" and structured based on the acronym PECo (P, problem; E, exposure; Co, context). The systematic review protocol was formulated and registered in PROSPERO (CRD42022353808) in accordance with the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the PRISMA was followed for the systematic review. The studies were selected according to the eligibility criteria, aligned with PECo, in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, BVS, and EMBASE. The search strategy yielded 1142 articles, from which, based on the evaluation criteria, 12 were included in the systematic review. Only seven these articles allowed the identification of both in silico and in vivo reassessed therapeutic targets. Among these targets, five were exclusively experimental, one was exclusively theoretical, and one of the targets presented an experimental portion and a portion obtained by modeling. The predominant methodology used was molecular docking and the most studied target was Human Pancreatic Lipase (HPL) (n = 4). The lack of methodological details resulted in more than 50% of the papers being categorized with an "unclear risk of bias" across eight out of the eleven evaluated criteria. From the current systematic review, it seems evident that integrating in silico methodologies into studies of potential drug targets for the exploration of new therapeutic agents provides an important tool, given the ongoing challenges in controlling obesity.
Topics: Humans; Obesity; Animals; Computer Simulation; Molecular Docking Simulation; Anti-Obesity Agents; Lipase; Molecular Targeted Therapy
PubMed: 38731918
DOI: 10.3390/ijms25094699 -
Toxics Dec 2023A growing body of literature has attempted to characterize how traffic-related air pollution (TRAP) affects molecular and subclinical biological processes in ways that... (Review)
Review
Methylomic, Proteomic, and Metabolomic Correlates of Traffic-Related Air Pollution in the Context of Cardiorespiratory Health: A Systematic Review, Pathway Analysis, and Network Analysis.
A growing body of literature has attempted to characterize how traffic-related air pollution (TRAP) affects molecular and subclinical biological processes in ways that could lead to cardiorespiratory disease. To provide a streamlined synthesis of what is known about the multiple mechanisms through which TRAP could lead to cardiorespiratory pathology, we conducted a systematic review of the epidemiological literature relating TRAP exposure to methylomic, proteomic, and metabolomic biomarkers in adult populations. Using the 139 papers that met our inclusion criteria, we identified the omic biomarkers significantly associated with short- or long-term TRAP and used these biomarkers to conduct pathway and network analyses. We considered the evidence for TRAP-related associations with biological pathways involving lipid metabolism, cellular energy production, amino acid metabolism, inflammation and immunity, coagulation, endothelial function, and oxidative stress. Our analysis suggests that an integrated multi-omics approach may provide critical new insights into the ways TRAP could lead to adverse clinical outcomes. We advocate for efforts to build a more unified approach for characterizing the dynamic and complex biological processes linking TRAP exposure and subclinical and clinical disease and highlight contemporary challenges and opportunities associated with such efforts.
PubMed: 38133415
DOI: 10.3390/toxics11121014 -
International Journal of Molecular... Nov 2022Aldehydes, particularly acetaldehyde, are carcinogenic molecules and their concentrations in foodstuffs should be controlled to avoid upper aerodigestive tract (UADT)... (Review)
Review
Aldehydes, particularly acetaldehyde, are carcinogenic molecules and their concentrations in foodstuffs should be controlled to avoid upper aerodigestive tract (UADT) and liver cancers. Highly reactive, acetaldehyde forms DNA and protein adducts, impairing physiological functions and leading to the development of pathological conditions. The consumption of aged beer, outside of the ethanol metabolism, exposes habitual drinkers to this carcinogen, whose concentrations can be over-increased due to post-brewing chemical and biochemical reactions. Storage-related changes are a challenge faced by the brewing industry, impacting volatile compound formation and triggering flavor instability. Aldehydes are among the volatile compounds formed during beer aging, recognized as off-flavor compounds. To track and understand aldehyde formation through multiple pathways during beer storage, consequent changes in flavor but particularly quality losses and harmful compound formation, this systematic review reunited data on volatile compound profiles through gas chromatography analyses from 2011 to 2021. Conditions to avoid flavor instability and successful methods for reducing beer staling, and consequent acetaldehyde accumulation, were raised by exploring the dynamic conversion between free and bound-state aldehydes. Future research should focus on implementing sensory analyses to investigate whether adding aldehyde-binding agents, e.g., cysteine and bisulfite, would contribute to consumer acceptance, restore beer flavor, and minimize acetaldehyde-related health damage.
Topics: Humans; Aged; Acetaldehyde; Aldehydes; Beer; Carcinogens; Carcinogenesis
PubMed: 36430619
DOI: 10.3390/ijms232214147 -
Journal of Clinical Medicine Jun 2020Mesenteric fibrosis (MF) constitutes an underrecognized sequela in patients with small intestinal neuroendocrine neoplasms (SI-NENs), often complicating the disease... (Review)
Review
Mesenteric fibrosis (MF) constitutes an underrecognized sequela in patients with small intestinal neuroendocrine neoplasms (SI-NENs), often complicating the disease clinical course. The aim of the present systematic review, carried out by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, is to provide an update in evolving aspects of MF pathogenesis and its clinical management in SI-NENs. Complex and dynamic interactions are present in the microenvironment of tumor deposits in the mesentery. Serotonin, as well as the signaling pathways of certain growth factors play a pivotal, yet not fully elucidated role in the pathogenesis of MF. Clinically, MF often results in significant morbidity by causing either acute complications, such as intestinal obstruction and/or acute ischemia or more chronic conditions involving abdominal pain, venous stasis, malabsorption and malnutrition. Surgical resection in patients with locoregional disease only or symptomatic distant stage disease, as well as palliative minimally invasive interventions in advanced inoperable cases seem clinically meaningful, whereas currently available systemic and/or targeted treatments do not unequivocally affect the development of MF in SI-NENs. Increased awareness and improved understanding of the molecular pathogenesis of MF in SI-NENs may provide better diagnostic and predictive tools for its timely recognition and intervention and also facilitates the development of agents targeting MF.
PubMed: 32521677
DOI: 10.3390/jcm9061777 -
Frontiers in Genetics 2021Approximately 50% of cataracts are associated with genetic factors. Genetic etiology and molecular mechanisms based on gene research increase the understanding of...
Approximately 50% of cataracts are associated with genetic factors. Genetic etiology and molecular mechanisms based on gene research increase the understanding of cataracts and provide direction for diagnosis and intervention. In the present study, SCIE papers related to the modeling of cataract gene research from 2010-2019 were evaluated and qualitative and quantitative analyses with modeling performed. The SCIE database was searched on July 6, 2021 for cataract gene publications and relevant papers published since 2010 were considered for review. Subsequently, 1,904 SCIE papers associated with cataract genes from 2010-2019 were analyzed using a bibliometric method. The publication, country, institution, journal, references, knowledgebase, keywords, and research hotspots of the papers were analyzed using an online analysis platform of literature metrology, bibliographic item co-occurrence matrix builder (BICOMB), CiteSpace V, and VOS viewer analysis tool. 78 countries published the related articles, and the United States ranks of America had the most publications. Two thousand seven hundred and eighty three institutions contributed to the related publications. Fudan University had the most publications. The reference clusters of SCI papers were clustered into six categories, namely, causing congenital cataract-microcornea syndrome, functional snp, cataractous lenses, a1 mutation, foxe3 mutation, cell adhesion gene pvrl3, nid1 gene. The key words representing the research frontiers were cerebrotendinous xanthomatosis (2017-2019), oxidative stress (2017-2019). This study provided a systematic, objective and comprehensive analysis of the literature related to gene research of cataract. Moreover, this study demonstrated the current hotspots and the future trends in the field of gene research of cataract. This review will help ophthalmologist to discern the dynamic evolution of cataract gene research, as well as highlight areas for future research.
PubMed: 34434212
DOI: 10.3389/fgene.2021.610728 -
MedRxiv : the Preprint Server For... Oct 2023A growing body of literature has attempted to characterize how traffic-related air pollution (TRAP) affects molecular and subclinical biological processes in ways that...
Methylomic, proteomic, and metabolomic correlates of traffic-related air pollution: A systematic review, pathway analysis, and network analysis relating traffic-related air pollution to subclinical and clinical cardiorespiratory outcomes.
A growing body of literature has attempted to characterize how traffic-related air pollution (TRAP) affects molecular and subclinical biological processes in ways that could lead to cardiorespiratory disease. To provide a streamlined synthesis of what is known about the multiple mechanisms through which TRAP could lead cardiorespiratory pathology, we conducted a systematic review of the epidemiological literature relating TRAP exposure to methylomic, proteomic, and metabolomic biomarkers in adult populations. Using the 139 papers that met our inclusion criteria, we identified the omic biomarkers significantly associated with short- or long-term TRAP and used these biomarkers to conduct pathway and network analyses. We considered the evidence for TRAP-related associations with biological pathways involving lipid metabolism, cellular energy production, amino acid metabolism, inflammation and immunity, coagulation, endothelial function, and oxidative stress. Our analysis suggests that an integrated multi-omics approach may provide critical new insights into the ways TRAP could lead to adverse clinical outcomes. We advocate for efforts to build a more unified approach for characterizing the dynamic and complex biological processes linking TRAP exposure and subclinical and clinical disease, and highlight contemporary challenges and opportunities associated with such efforts.
PubMed: 37873294
DOI: 10.1101/2023.09.30.23296386 -
Frontiers in Immunology 2021Dynamic D-dimer level is a key biomarker for the severity and mortality of COVID-19 (coronavirus disease 2019). How aberrant fibrinolysis influences the clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dynamic D-dimer level is a key biomarker for the severity and mortality of COVID-19 (coronavirus disease 2019). How aberrant fibrinolysis influences the clinical progression of COVID-19 presents a clinicopathological dilemma challenging intensivists.
METHODS
We performed meta-analysis and meta regression to analyze the associations of plasma D-dimer with 106 clinical variables to identify a panoramic view of the derangements of fibrinolysis in 14,862 patients of 42 studies. There were no limitations of age, gender, race, and country. Raw data of each group were extracted separately by two investigators. Individual data of case series, median and interquartile range, and ranges of median or mean were converted to SDM (standard deviation of mean).
FINDINGS
The weighted mean difference of D-dimer was 0.97 µg/mL (95% CI 0.65, 1.29) between mild and severe groups, as shown by meta-analysis. Publication bias was significant. Meta-regression identified 58 of 106 clinical variables were associated with plasma D-dimer levels. Of these, 11 readouts were negatively related to the level of plasma D-dimer. Further, age and gender were confounding factors. There were 22 variables independently correlated with the D-dimer level, including respiratory rate, dyspnea plasma K, glucose, SpO2, BUN (blood urea nitrogen), bilirubin, ALT (alanine aminotransferase), AST (aspartate aminotransferase), systolic blood pressure, and CK (creatine kinase).
INTERPRETATION
These findings support elevated D-dimer as an independent predictor for both mortality and complications. The identified D-dimer-associated clinical variables draw a landscape integrating the aggregate effects of systemically suppressive and pulmonary hyperactive derangements of fibrinolysis, and the D-dimer-associated clinical biomarkers, and conceptually parameters could be combined for risk stratification, potentially for tracking thrombolytic therapy or alternative interventions.
Topics: Biomarkers; COVID-19; Diagnostic Tests, Routine; Disease Progression; Fibrin Fibrinogen Degradation Products; Humans; Patient Admission; SARS-CoV-2; Severity of Illness Index
PubMed: 34025688
DOI: 10.3389/fimmu.2021.691249