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Journal of Vector Borne Diseases 2022Dengue virus (DENV) is an RNA virus that infects approximately 2.5 billion people around the world. The incidence of dengue fever has rapidly increased at an alarming... (Review)
Review
BACKGROUND & OBJECTIVES
Dengue virus (DENV) is an RNA virus that infects approximately 2.5 billion people around the world. The incidence of dengue fever has rapidly increased at an alarming rate in the last few years and has affected thousands of people in Pakistan. This review explores the prevalence, serotypes and pathogenesis of dengue virus circulating in Pakistan.
METHODS
A systematic review of observational studies published between 1994 and December 2019 was performed. All records of the confirmed outbreak of dengue fever in Pakistan were reviewed and articles containing no primary data were excluded.
RESULTS
Four identified serotypes of dengue virus (DENV 1-4) circulate in different regions of the world causing epidemics. The most prevalent serotype, which is still epidemic and dominant in Pakistan, is DENV-2. Many factors like over-population, rapid urbanization, travelling, lack of vector control in dengue endemic areas and inadequate health-care are responsible of dynamic and huge raise of dengue in Pakistan.
INTERPRETATION & CONCLUSION
Currently there is no specific treatment for prevention of dengue virus. Recently some antiviral compounds were being tested to eradicate this disease. There is a need to develop an efficient and safe vaccine for all four serotypes to combat dengue viral infection globally and particularly in Pakistan.
Topics: Antiviral Agents; Dengue; Dengue Virus; Humans; Pakistan; Serogroup
PubMed: 36124476
DOI: 10.4103/0972-9062.331412 -
Medicina Oral, Patologia Oral Y Cirugia... Sep 2019Despite decades of research, our knowledge of several important aspects of periodontal pathogenesis remains incomplete. Epigenetics allows to perform dynamic analysis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite decades of research, our knowledge of several important aspects of periodontal pathogenesis remains incomplete. Epigenetics allows to perform dynamic analysis of different variations in gene expression, providing this great advantage to the static measurement provided by genetic markers. The aim of this systematic review is to analyze the possible relationships between different epigenetic mechanisms and periodontal diseases, and to assess their potential use as biomarkers of periodontitis.
MATERIAL AND METHODS
A systematic search was conducted in six databases using MeSH and non-MeSH terms. The review fulfilled PRISMA criteria (Preferred Reporting Items for Systematic reviews and Meta-analysis).
RESULTS
36 studies met the inclusion criteria. Due to the heterogeneity of the articles, it was not possible to conduct quantitative analysis. Regarding qualitative synthesis, however, it was found that epigenetic mechanisms may be used as biological markers of periodontal disease, as their dynamism and molecular stability makes them a valuable diagnostic tool.
CONCLUSIONS
Epigenetic markers alter gene expression, producing either silencing or over-expression of molecular transcription that respond to the demands of the cellular surroundings. Gingival crevicular fluid collection is a non-invasive and simple procedure, which makes it an ideal diagnostic medium for detection of both oral and systemic issues. Although further research is needed, this seems to be a promising field of research in the years to come.
Topics: Epigenesis, Genetic; Gingival Crevicular Fluid; Humans; Periodontal Diseases; Periodontics; Periodontitis
PubMed: 31433392
DOI: 10.4317/medoral.23008 -
Journal of Nuclear Cardiology :... Aug 2022With the appearance of cadmium-zinc-telluride (CZT) cameras, dynamic myocardial perfusion imaging (MPI) has been introduced, but comparable data to other MPI modalities,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With the appearance of cadmium-zinc-telluride (CZT) cameras, dynamic myocardial perfusion imaging (MPI) has been introduced, but comparable data to other MPI modalities, such as quantitative coronary angiography (CAG) with fractional flow reserve (FFR) and positron emission tomography (PET), are lacking. This study aimed to evaluate the diagnostic accuracy of dynamic CZT single-photon emission tomography (SPECT) in coronary artery disease compared to quantitative CAG, FFR, and PET as reference.
MATERIALS AND METHODS
Different databases were screened for eligible citations performing dynamic CZT-SPECT against CAG, FFR, or PET. PubMed, OvidSP (Medline), Web of Science, the Cochrane Library, and EMBASE were searched on the 5th of July 2020. Studies had to meet the following pre-established inclusion criteria: randomized controlled trials, retrospective trails or observational studies relevant for the diagnosis of coronary artery disease, and performing CZT-SPECT and within half a year the methodological references. Studies which considered coronary stenosis between 50% and 70% as significant based only on CAG were excluded. Data extracted were sensitivity, specificity, likelihood ratios, and diagnostic odds ratios. Quality was assessed with QUADAS-2 and statistical analysis was performed using a bivariate model.
RESULTS
Based on our criteria, a total of 9 studies containing 421 patients were included. For the assessment of CZT-SPECT, the diagnostic value pooled analysis with a bivariate model was calculated and yielded a sensitivity of 0.79 (% CI 0.73 to 0.85) and a specificity of 0.85 (95% CI 0.74 to 0.92). Diagnostic odds ratio (DOR) was 17.82 (95% CI 8.80 to 36.08, P < 0.001). Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 3.86 (95% CI 2.76 to 5.38, P < 0.001) and 0.21 (95% CI 0.13 to 0.33, P < 0.001), respectively.
CONCLUSION
Based on the results of the current systematic review and meta-analysis, dynamic CZT-SPECT MPI demonstrated a good sensitivity and specificity to diagnose CAD as compared to the gold standards. However, due to the heterogeneity of the methodologies between the CZT-SPECT MPI studies and the relatively small number of included studies, it warrants further well-defined study protocols.
Topics: Cadmium; Coronary Angiography; Coronary Artery Disease; Fractional Flow Reserve, Myocardial; Humans; Myocardial Perfusion Imaging; Retrospective Studies; Tellurium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Zinc
PubMed: 34350553
DOI: 10.1007/s12350-021-02721-8 -
Frontiers in Medicine 2023Traditional Chinese medicine (TCM) is widely used in the clinical treatment of hepatolenticular degeneration (HLD) and liver fibrosis (LF). In the present study, the...
Treatment of liver fibrosis in hepatolenticular degeneration with traditional Chinese medicine: systematic review of meta-analysis, network pharmacology and molecular dynamics simulation.
BACKGROUND
Traditional Chinese medicine (TCM) is widely used in the clinical treatment of hepatolenticular degeneration (HLD) and liver fibrosis (LF). In the present study, the curative effect was assessed using meta-analysis. The possible mechanism of TCM against LF in HLD was investigated using network pharmacology and molecular dynamics simulation.
METHODS
For literature collection, we searched several databases, including PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals (VIP) and Wan Fang database until February 2023, and the Review Manager 5.3 was used to analyze the data. Network pharmacology and molecular dynamics simulation were used to explore the mechanism of TCM in treating LF in HLD.
RESULTS
The results of the meta-analysis revealed that the addition of Chinese herbal medicine (CHM) in treating HLD resulted in a higher total clinical effective rate than western medicine alone [RR 1.25, 95% CI (1.09, 1.44), = 0.002]. It not only has a better effect on liver protection [Alanine aminotransferase: SMD = -1.20, 95% CI (-1.70, -0.70), < 0.00001; Aspartate aminotransferase: SMD = -1.41, 95% CI (-2.34, -0.49), = 0.003; Total bilirubin: SMD = -1.70, 95% CI (-3.36, -0.03), = 0.05] but also had an excellent therapeutic effect on LF through four indexes [Hyaluronic acid: SMD = -1.15, 95% CI (-1.76, -0.53), = 0.0003; Procollagen peptide III: SMD = -0.72, 95% CI (-1.29, -0.15), = 0.01; Collagen IV: SMD = -0.69, 95% CI (-1.21, -0.18), = 0.008; Laminin: SMD = -0.47, 95% CI (-0.95, 0.01), = 0.06]. Concurrently, the liver stiffness measurement decreased significantly [SMD = -1.06, 95% CI (-1.77, -0.36), = 0.003]. The results of network pharmacological experiments and molecular dynamics simulation indicate that the three high-frequency TCMs (Rhei Radix Et Rhizoma-Coptidis Rhizoma-Curcumae Longae Rhizoma, DH-HL-JH) primarily act on the core targets (AKT1, SRC, and JUN) via the core components (rhein, quercetin, stigmasterol, and curcumin), regulate the signal pathway (PI3K-Akt, MAPK, EGFR, and VEGF signaling pathways), and play a role of anti-LF.
CONCLUSION
Meta-analysis indicates that TCM is beneficial in treating HLD patients and improving LF. The present study successfully predicts the effective components and potential targets and pathways involved in treating LF for the three high-frequency CHMs of DH-HL-JH. The findings of the present study are hoped to provide some evidence support for clinical treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022302374.
PubMed: 37250630
DOI: 10.3389/fmed.2023.1193132 -
Frontiers in Immunology 2021Although proteomics has been employed in the study of several models of liver injury, proteomic methods have only recently been applied not only to biomarker discovery...
BACKGROUND
Although proteomics has been employed in the study of several models of liver injury, proteomic methods have only recently been applied not only to biomarker discovery and validation but also to improve understanding of the molecular mechanisms involved in transplantation.
METHODS
The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and the guidelines for performing systematic literature reviews in bioinformatics (BiSLR). The PubMed, ScienceDirect, and Scopus databases were searched for publications through April 2020. Proteomics studies designed to understand liver transplant outcomes, including ischemia-reperfusion injury (IRI), rejection, or operational tolerance in human or rat samples that applied methodologies for differential expression analysis were considered.
RESULTS
The analysis included 22 studies after application of the inclusion and exclusion criteria. Among the 497 proteins annotated, 68 were shared between species and 10 were shared between sample sources. Among the types of studies analyzed, IRI and rejection shared a higher number of proteins. The most enriched pathway for liver biopsy samples, IRI, and rejection was metabolism, compared to cytokine-cytokine receptor interactions for tolerance.
CONCLUSIONS
Proteomics is a promising technique to detect large numbers of proteins. However, our study shows that several technical issues such as the identification of proteoforms or the dynamic range of protein concentration in clinical samples hinder the successful identification of biomarkers in liver transplantation. In addition, there is a need to minimize the experimental variability between studies, increase the sample size and remove high-abundance plasma proteins.
Topics: Animals; Biomarkers; Computational Biology; Humans; Liver Transplantation; Proteomics
PubMed: 34381445
DOI: 10.3389/fimmu.2021.672829 -
Current Neuropharmacology 2023Traditional medicine and biomedical sciences are reaching a turning point because of the constantly growing impact and volume of Big Data. Machine Learning (ML)...
Traditional medicine and biomedical sciences are reaching a turning point because of the constantly growing impact and volume of Big Data. Machine Learning (ML) techniques and related algorithms play a central role as diagnostic, prognostic, and decision-making tools in this field. Another promising area becoming part of everyday clinical practice is personalized therapy and pharmacogenomics. Applying ML to pharmacogenomics opens new frontiers to tailored therapeutical strategies to help clinicians choose drugs with the best response and fewer side effects, operating with genetic information and combining it with the clinical profile. This systematic review aims to draw up the state-of-the-art ML applied to pharmacogenomics in psychiatry. Our research yielded fourteen papers; most were published in the last three years. The sample comprises 9,180 patients diagnosed with mood disorders, psychoses, or autism spectrum disorders. Prediction of drug response and prediction of side effects are the most frequently considered domains with the supervised ML technique, which first requires training and then testing. The random forest is the most used algorithm; it comprises several decision trees, reduces the training set's overfitting, and makes precise predictions. ML proved effective and reliable, especially when genetic and biodemographic information were integrated into the algorithm. Even though ML and pharmacogenomics are not part of everyday clinical practice yet, they will gain a unique role in the next future in improving personalized treatments in psychiatry.
Topics: Humans; Pharmacogenetics; Precision Medicine; Machine Learning; Mental Disorders; Psychiatry
PubMed: 37559539
DOI: 10.2174/1570159X21666230808170123 -
International Journal of Molecular... Mar 2023Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor...
Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor growth. Molecular rearrangements occur in neoplasms before any macroscopic morphological changes become visible, and the former are the underlying cause of disease behavior. Tumor microenvironment (TME) encompasses cellular and non-cellular elements interacting together, resulting in a complex and dynamic key of tumorigenesis, drug response, and treatment outcome. The aim of this systematic, narrative review was to assess the level of knowledge on TME implicated in the biology, behavior, and prognosis of sporadic VSs. A search (updated to November 2022) was run in Scopus, PubMed, and Web of Science electronic databases according to the PRISMA guidelines, retrieving 624 titles. After full-text evaluation and application of inclusion/exclusion criteria, 37 articles were included. VS microenvironment is determined by the interplay of a dynamic ecosystem of stromal and immune cells which produce and remodel extracellular matrix, vascular networks, and promote tumor growth. However, evidence is still conflicting. Further studies will enhance our understanding of VS biology by investigating TME-related biomarkers able to predict tumor growth and recognize immunological and molecular factors that could be potential therapeutic targets for medical treatment.
Topics: Humans; Ecosystem; Neuroma, Acoustic; Treatment Outcome; Tumor Burden; Tumor Microenvironment
PubMed: 37047498
DOI: 10.3390/ijms24076522 -
Cancers Apr 2023Liquid biopsy (LB) analysis using (ctDNA)/cell-free DNA (cfDNA) is an emerging alternative to tissue profiling in (NSCLC). LB is used to guide treatment decisions,... (Review)
Review
BACKGROUND
Liquid biopsy (LB) analysis using (ctDNA)/cell-free DNA (cfDNA) is an emerging alternative to tissue profiling in (NSCLC). LB is used to guide treatment decisions, detect resistance mechanisms, and predicts responses, and, therefore, outcomes. This systematic review and meta-analysis evaluated the impact of LB quantification on clinical outcomes in molecularly altered advanced NSCLC undergoing targeted therapies.
METHODS
We searched Embase, MEDLINE, PubMed, and Cochrane Database, between 1 January 2020 and 31 August 2022. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), objective response rate (ORR), sensitivity, and specificity. Age stratification was performed based on the mean age of the individual study population. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS).
RESULTS
A total of 27 studies (3419 patients) were included in the analysis. Association of baseline ctDNA with PFS was reported in 11 studies (1359 patients), while that of dynamic changes with PFS was reported in 16 studies (1659 patients). Baseline ctDNA-negative patients had a trend towards improved PFS (pooled hazard ratio [pHR] = 1.35; 95%CI: 0.83-1.87; < 0.001; I = 96%) than ctDNA-positive patients. Early reduction/clearance of ctDNA levels after treatment was related to improved PFS (pHR = 2.71; 95%CI: 1.85-3.65; I = 89.4%) compared to those with no reduction/persistence in ctDNA levels. The sensitivity analysis based on study quality (NOS) demonstrated improved PFS only for good [pHR = 1.95; 95%CI: 1.52-2.38] and fair [pHR = 1.99; 95%CI: 1.09-2.89] quality studies, but not for poor quality studies. There was, however, a high level of heterogeneity (I = 89.4%) along with significant publication bias in our analysis.
CONCLUSIONS
This large systematic review, despite heterogeneity, found that baseline negative ctDNA levels and early reduction in ctDNA following treatment could be strong prognostic markers for PFS and OS in patients undergoing targeted therapies for advanced NSCLC. Future randomised clinical trials should incorporate serial ctDNA monitoring to further establish the clinical utility in advanced NSCLC management.
PubMed: 37173891
DOI: 10.3390/cancers15092425 -
Diagnostics (Basel, Switzerland) Feb 2022Fetal malformations occur in 2-3% of pregnancies. They require invasive procedures for cytogenetics and molecular testing. "Structural anomalies" include non-transient... (Review)
Review
Fetal malformations occur in 2-3% of pregnancies. They require invasive procedures for cytogenetics and molecular testing. "Structural anomalies" include non-transient anatomic alterations. "Soft markers" are often transient minor ultrasound findings. Anomalies not fitting these definitions are categorized as "dynamic". This meta-analysis aims to evaluate the diagnostic yield and the rates of variants of uncertain significance (VUSs) in fetuses undergoing molecular testing (chromosomal microarray (CMA), exome sequencing (ES), genome sequencing (WGS)) due to ultrasound findings. The CMA diagnostic yield was 2.15% in single soft markers (vs. 0.79% baseline risk), 3.44% in multiple soft markers, 3.66% in single structural anomalies and 8.57% in multiple structural anomalies. Rates for specific subcategories vary significantly. ES showed a diagnostic rate of 19.47%, reaching 27.47% in multiple structural anomalies. WGS data did not allow meta-analysis. In fetal structural anomalies, CMA is a first-tier test, but should be integrated with karyotype and parental segregations. In this class of fetuses, ES presents a very high incremental yield, with a significant VUSs burden, so we encourage its use in selected cases. Soft markers present heterogeneous CMA results from each other, some of them with risks comparable to structural anomalies, and would benefit from molecular analysis. The diagnostic rate of multiple soft markers poses a solid indication to CMA.
PubMed: 35328129
DOI: 10.3390/diagnostics12030575 -
Advances in Pharmacological and... 2023The coronavirus disease 2019 (COVID-19) is a severe worldwide pandemic. Due to the emergence of various SARS-CoV-2 variants and the presence of only one Food and Drug... (Review)
Review
The coronavirus disease 2019 (COVID-19) is a severe worldwide pandemic. Due to the emergence of various SARS-CoV-2 variants and the presence of only one Food and Drug Administration (FDA) approved anti-COVID-19 drug (remdesivir), the disease remains a mindboggling global public health problem. Developing anti-COVID-19 drug candidates that are effective against SARS-CoV-2 and its various variants is a pressing need that should be satisfied. This systematic review assesses the existing literature that used in silico models during the discovery procedure of anti-COVID-19 drugs. Cochrane Library, Science Direct, Google Scholar, and PubMed were used to conduct a literature search to find the relevant articles utilizing the search terms "In silico model," "COVID-19," "Anti-COVID-19 drug," "Drug discovery," "Computational drug designing," and "Computer-aided drug design." Studies published in English between 2019 and December 2022 were included in the systematic review. From the 1120 articles retrieved from the databases and reference lists, only 33 were included in the review after the removal of duplicates, screening, and eligibility assessment. Most of the articles are studies that use SARS-CoV-2 proteins as drug targets. Both ligand-based and structure-based methods were utilized to obtain lead anti-COVID-19 drug candidates. Sixteen articles also assessed absorption, distribution, metabolism, excretion, toxicity (ADMET), and drug-likeness properties. Confirmation of the inhibitory ability of the candidate leads by or assays was reported in only five articles. Virtual screening, molecular docking (MD), and molecular dynamics simulation (MDS) emerged as the most commonly utilized in silico models for anti-COVID-19 drug discovery.
PubMed: 37362912
DOI: 10.1155/2023/4562974