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Drugs in R&D Sep 2023At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical efficacy of a combination of various conventional and adjuvant drugs in treating dilated cardiomyopathy via network meta-analysis.
METHODS
The study was reported according to the PRISMA 2020 statement. From inception through 27 June 2022, the PubMed, Embase, Cochrane library, and Web of Science databases were searched for randomized controlled trials on medicines for treating dilated cardiomyopathy. The quality of the included studies was evaluated according to the Cochrane risk of bias assessment. R4.1.3 and Revman5.3 software were used for analysis.
RESULTS
There were 52 randomized controlled trials in this study, with a total of 25 medications and a sample size of 3048 cases. The network meta-analysis found that carvedilol, verapamil, and trimetazidine were the top three medicines for improving left ventricular ejection fraction (LVEF). Ivabradine, bucindolol, and verapamil were the top 3 drugs for improving left ventricular end-diastolic dimension (LVEDD). Ivabradine, L-thyroxine, and atorvastatin were the top 3 drugs for improving left ventricular end-systolic dimension (LVESD). Trimetazidine, pentoxifylline, and bucindolol were the top 3 drugs for improving the New York Heart Association classification (NYHA) cardiac function score. Ivabradine, carvedilol, and bucindolol were the top 3 drugs for reducing heart rate (HR).
CONCLUSION
A combination of different medications and conventional therapy may increase the clinical effectiveness of treating dilated cardiomyopathy. Beta-blockers, especially carvedilol, can improve ventricular remodeling, cardiac function, and clinical efficacy in patients with dilated cardiomyopathy (DCM). Hence, they can be used if patients tolerate them. If LVEF and HR do not meet the standard, ivabradine can also be used in combination with other treatments. However, since the quality and number of studies in our research were limited, large sample size, multi-center, and high-quality randomized controlled trials are required to corroborate our findings.
Topics: Humans; Cardiomyopathy, Dilated; Carvedilol; Ivabradine; Stroke Volume; Trimetazidine; Network Meta-Analysis; Ventricular Function, Left; Verapamil; Randomized Controlled Trials as Topic
PubMed: 37556093
DOI: 10.1007/s40268-023-00435-5 -
Genes Jul 2023On a planet experiencing constant human population growth, it is necessary to explore the anthropogenic effects on the genetic diversity of species, and specifically...
On a planet experiencing constant human population growth, it is necessary to explore the anthropogenic effects on the genetic diversity of species, and specifically invasive species. Using an analysis that integrates comparative phylogeography, urban landscape genetics, macrogenetics and a systematic review, we explore the worldwide genetic diversity of the human commensal and anthropogenic species and . Based on metadata obtained considering 35 selected studies related to observed heterozygosity, measured by nuclear molecular markers (microsatellites, Single Nucleotide Polymorphisms-SNPs-, restrictition site-associated DNA sequencing -RAD-Seq-), socioeconomic and mobility anthropogenic factors were used as predictors of genetic diversity of and , using the Gini index, principal component analysis and Random Forest Regression as analysis methodology. Population density was on average the best predictor of genetic diversity in the species analyzed, indicating that the species respond in a particular way to the characteristics present in urban environments because of a combination of life history characteristics and human-mediated migration and colonization processes. To create better management and control strategies for these rodents and their associated diseases, it is necessary to fill the existing information gap in urban landscape genetics studies with more metadata repositories, with emphasis on tropical and subtropical regions of the world.
Topics: Humans; Rats; Animals; Population Density; Phylogeography; Introduced Species; Microsatellite Repeats; Polymorphism, Single Nucleotide
PubMed: 37510346
DOI: 10.3390/genes14071442 -
Complex Psychiatry 2023Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and... (Review)
Review
INTRODUCTION
Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and transcriptomic modifications may help to dissect the biological factors underlying the gene-environment interplay in PTSD. To date, most human PTSD epigenetics studies have used peripheral tissue, and these findings have complex and poorly understood relationships to brain alterations. Studies examining brain tissue may help characterize the brain-specific transcriptomic and epigenomic profiles of PTSD. In this review, we compiled and integrated brain-specific molecular findings of PTSD from humans and animals.
METHODS
A systematic literature search according to the PRISMA criteria was performed to identify transcriptomic and epigenomic studies of PTSD, focusing on brain tissue from human postmortem samples or animal-stress paradigms.
RESULTS
Gene- and pathway-level convergence analyses revealed PTSD-dysregulated genes and biological pathways across brain regions and species. A total of 243 genes converged across species, with 17 of them significantly enriched for PTSD. Chemical synaptic transmission and signaling by G-protein-coupled receptors were consistently enriched across omics and species.
DISCUSSION
Our findings point out dysregulated genes highly replicated across PTSD studies in humans and animal models and suggest a potential role for the corticotropin-releasing hormone/orexin pathway in PTSD's pathophysiology. Further, we highlight current knowledge gaps and limitations and recommend future directions to address them.
PubMed: 37404872
DOI: 10.1159/000529536 -
Scientific African Sep 2023The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus's worldwide pandemic has highlighted the urgent need for reliable, quick, and affordable...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus's worldwide pandemic has highlighted the urgent need for reliable, quick, and affordable diagnostic tests for comprehending and controlling the epidemic by tracking the world population. Given how crucial it is to monitor and manage the pandemic, researchers have recently concentrated on creating quick detection techniques. Although PCR is still the preferred clinical diagnostic test, there is a pressing need for substitutes that are sufficiently rapid and cost-effective to provide a diagnosis at the time of use. The creation of a quick and simple POC equipment is necessary for home testing. Our review's goal is to provide an overview of the many methods utilized to identify SARS-CoV 2 in various samples utilizing portable devices, as well as any potential applications for smartphones in epidemiological research and detection. The point of care (POC) employs a range of microfluidic biosensors based on smartphones, including molecular sensors, immunological biosensors, hybrid biosensors, and imaging biosensors. For example, a number of tools have been created for the diagnosis of COVID-19, based on various theories. Integrated portable devices can be created using loop-mediated isothermal amplification, which combines isothermal amplification methods with colorimetric detection. Electrochemical approaches have been regarded as a potential substitute for optical sensing techniques that utilize fluorescence for detection and as being more beneficial to the Minimizing and simplicity of the tools used for detection, together with techniques that can amplify DNA or RNA under constant temperature conditions, without the need for repeated heating and cooling cycles. Many research have used smartphones for virus detection and data visualization, making these techniques more user-friendly and broadly distributed throughout nations. Overall, our research provides a review of different novel, non-invasive, affordable, and efficient methods for identifying COVID-19 contagious infected people and halting the disease's transmission.
PubMed: 37351482
DOI: 10.1016/j.sciaf.2023.e01757 -
Frontiers in Genetics 2023In the last years, liquid biopsy gained increasing clinical relevance for detecting and monitoring several cancer types, being minimally invasive, highly informative and... (Review)
Review
In the last years, liquid biopsy gained increasing clinical relevance for detecting and monitoring several cancer types, being minimally invasive, highly informative and replicable over time. This revolutionary approach can be complementary and may, in the future, replace tissue biopsy, which is still considered the gold standard for cancer diagnosis. "Classical" tissue biopsy is invasive, often cannot provide sufficient bioptic material for advanced screening, and can provide isolated information about disease evolution and heterogeneity. Recent literature highlighted how liquid biopsy is informative of proteomic, genomic, epigenetic, and metabolic alterations. These biomarkers can be detected and investigated using single-omic and, recently, in combination through multi-omic approaches. This review will provide an overview of the most suitable techniques to thoroughly characterize tumor biomarkers and their potential clinical applications, highlighting the importance of an integrated multi-omic, multi-analyte approach. Personalized medical investigations will soon allow patients to receive predictable prognostic evaluations, early disease diagnosis, and subsequent treatments.
PubMed: 37077538
DOI: 10.3389/fgene.2023.1152470 -
Cells Mar 2023Epigenetic research has the potential to improve our understanding of the pathogenesis of cancer, specifically non-small-cell lung cancer, and support our efforts to... (Review)
Review
Epigenetic research has the potential to improve our understanding of the pathogenesis of cancer, specifically non-small-cell lung cancer, and support our efforts to personalize the management of the disease. Epigenetic alterations are expected to have relevance for early detection, diagnosis, outcome prediction, and tumor response to therapy. Additionally, epi-drugs as therapeutic modalities may lead to the recovery of genes delaying tumor growth, thus increasing survival rates, and may be effective against tumors without druggable mutations. Epigenetic changes involve DNA methylation, histone modifications, and the activity of non-coding RNAs, causing gene expression changes and their mutual interactions. This systematic review, based on 110 studies, gives a comprehensive overview of new perspectives on diagnostic (28 studies) and prognostic (25 studies) epigenetic biomarkers, as well as epigenetic treatment options (57 studies) for non-small-cell lung cancer. This paper outlines the crosstalk between epigenetic and genetic factors as well as elucidates clinical contexts including epigenetic treatments, such as dietary supplements and food additives, which serve as anti-carcinogenic compounds and regulators of cellular epigenetics and which are used to reduce toxicity. Furthermore, a future-oriented exploration of epigenetic studies in NSCLC is presented. The findings suggest that additional studies are necessary to comprehend the mechanisms of epigenetic changes and investigate biomarkers, response rates, and tailored combinations of treatments. In the future, epigenetics could have the potential to become an integral part of diagnostics, prognostics, and personalized treatment in NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Epigenesis, Genetic; DNA Methylation
PubMed: 36980246
DOI: 10.3390/cells12060905 -
Biomedicines Feb 2023A small subset of people with nephrotic syndrome (NS) have genetically driven disease. However, the disease mechanisms for the remaining majority are unknown. Epigenetic... (Review)
Review
A small subset of people with nephrotic syndrome (NS) have genetically driven disease. However, the disease mechanisms for the remaining majority are unknown. Epigenetic marks are reversible but stable regulators of gene expression with utility as biomarkers and therapeutic targets. We aimed to identify and assess all published human studies of epigenetic mechanisms in NS. PubMed (MEDLINE) and Embase were searched for original research articles examining any epigenetic mechanism in samples collected from people with steroid resistant NS, steroid sensitive NS, focal segmental glomerulosclerosis or minimal change disease. Study quality was assessed by using the Joanna Briggs Institute critical appraisal tools. Forty-nine studies met our inclusion criteria. The majority of these examined micro-RNAs ( = 35, 71%). Study quality was low, with only 23 deemed higher quality, and most of these included fewer than 100 patients and failed to validate findings in a second cohort. However, there were some promising concordant results between the studies; higher levels of serum miR-191 and miR-30c, and urinary miR-23b-3p and miR-30a-5p were observed in NS compared to controls. We have identified that the epigenome, particularly DNA methylation and histone modifications, has been understudied in NS. Large clinical studies, which utilise the latest high-throughput technologies and analytical pipelines, should focus on addressing this critical gap in the literature.
PubMed: 36831050
DOI: 10.3390/biomedicines11020514 -
Sensors (Basel, Switzerland) Jan 2023This systematic review describes and discusses three commercially available integrated systems for forensic DNA analysis, i.e., ParaDNA, RapidHIT, and ANDE. A variety of... (Review)
Review
This systematic review describes and discusses three commercially available integrated systems for forensic DNA analysis, i.e., ParaDNA, RapidHIT, and ANDE. A variety of aspects, such as performance, time-to-result, ease-of-use, portability, and costs (per analysis run) of these three (modified) rapid DNA analysis systems, are considered. Despite their advantages and developmental progress, major steps still have to be made before rapid systems can be broadly applied at crime scenes for full DNA profiling. Aspects in particular that need (further) improvement are portability, performance, the possibility to analyze a (wider) variety of (complex) forensic samples, and (cartridge) costs. Moreover, steps forward regarding ease-of-use and time-to-result will benefit the broader use of commercial rapid DNA systems. In fact, it would be a profit if rapid DNA systems could be used for full DNA profile generation as well as indicative analyses that can give direction to forensic investigators which will speed up investigations.
Topics: Forensic Genetics; Microsatellite Repeats; Polymerase Chain Reaction; DNA Fingerprinting; DNA
PubMed: 36772114
DOI: 10.3390/s23031075 -
Applied and Environmental Microbiology Feb 2023Site-specific recombinases (integrases) can mediate the horizontal transfer of genomic islands. The ability to integrate large DNA sequences into target sites is very...
Site-specific recombinases (integrases) can mediate the horizontal transfer of genomic islands. The ability to integrate large DNA sequences into target sites is very important for genetic engineering in prokaryotic and eukaryotic cells. Here, we characterized an unprecedented catalogue of 530 tyrosine-type integrases by examining genes potentially encoding tyrosine integrases in bacterial genomic islands. The phylogeny of putative tyrosine integrases revealed that these integrases form an evolutionary clade that is distinct from those already known and are affiliated with novel integrase groups. We systematically searched for candidate integrase genes, and their integration activities were validated in a bacterial model. We verified the integration functions of six representative novel integrases by using a two-plasmid integration system consisting of a donor plasmid carrying the integrase gene and site and a recipient plasmid harboring an site in -deficient Escherichia coli. Further quantitative reverse transcription-PCR (qRT-PCR) assays validated that the six selected integrases can be expressed with their native promoters in E. coli. The region reductions showed that the extent of sites of integrases is approximately 200 bp for integration capacity. In addition, mutational analysis showed that the conserved tyrosine at the C terminus is essential for catalysis, confirming that these candidate proteins belong to the tyrosine-type recombinase superfamily, i.e., tyrosine integrases. This study revealed that the novel integrases from bacterial genomic islands have site-specific recombination functions, which is of physiological significance for their genomic islands in bacterial chromosomes. More importantly, our discovery expands the toolbox for genetic engineering, especially for efficient integration activity. Site-specific recombinases or integrases have high specificity for DNA large fragment integration, which is urgently needed for gene editing. However, known integrases are not sufficient for meeting multiple integrations. In this work, we discovered an array of integrases through bioinformatics analysis in bacterial genomes. Phylogeny and functional assays revealed that these new integrases belong to tyrosine-type integrases and have the ability to conduct site-specific recombination. Moreover, region extent and catalysis site analysis were characterized. Our study provides the methodology for discovery of novel integrases and increases the capacity of weapon pool for genetic engineering in bacteria.
Topics: Integrases; Genomic Islands; Escherichia coli; Tyrosine; Plasmids; Bacteriophages; Attachment Sites, Microbiological
PubMed: 36719242
DOI: 10.1128/aem.01738-22 -
Biomedicines Jan 2023Neutrophil extracellular traps (NETs) recently emerged as a newly recognized contributor to venous and arterial thrombosis. These strands of DNA, extruded by activated... (Review)
Review
Neutrophil extracellular traps (NETs) recently emerged as a newly recognized contributor to venous and arterial thrombosis. These strands of DNA, extruded by activated or dying neutrophils, decorated with various protein mediators, become solid-state reactors that can localize at the critical interface of blood with the intimal surface of diseased arteries alongside propagating and amplifying the regional injury. NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thrombosis, oxidative stress, and cardiovascular diseases. In response to disease-relevant stimuli, neutrophils undergo a specialized series of reactions that culminate in NET formation. DNA derived from either nuclei or mitochondria can contribute to NET formation. The DNA liberated from neutrophils forms a reticular mesh that resembles morphologically a net, rendering the acronym NETs particularly appropriate. The DNA backbone of NETs not only presents intrinsic neutrophil proteins (e.g., MPO (myeloperoxidase) and various proteinases) but can congregate other proteins found in blood (e.g., tissue factor procoagulant). This systematic review discusses the current hypothesis of neutrophil biology, focusing on the triggers and mechanisms of NET formation. Furthermore, the contribution of NETs to atherosclerosis and thrombosis is extensively addressed. Again, the use of NET markers in clinical trials was considered. Ultimately, given the vast body of the published literature, we aim to integrate the experimental evidence with the growing body of clinical information relating to NET critically.
PubMed: 36672621
DOI: 10.3390/biomedicines11010113