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Journal of Cardiovascular Development... Apr 2022Myocardial damage in acute myocardial infarctions (AMI) is primarily the result of ischemia−reperfusion injury (IRI). Recognizing the timing of transcriptional events... (Review)
Review
Myocardial damage in acute myocardial infarctions (AMI) is primarily the result of ischemia−reperfusion injury (IRI). Recognizing the timing of transcriptional events and their modulation by cardioprotective strategies is critical to address the pathophysiology of myocardial IRI. Despite the relevance of pigs for translational studies of AMI, only a few have identified how transcriptomic changes shape cellular signaling pathways in response to injury. We systematically reviewed transcriptomic studies of myocardial IRI and cardioprotection in Sus scrofa. Gene expression datasets were analyzed for significantly enriched terms using the Enrichr analysis tool, and statistically significant results (adjusted p-values of <0.05) for Signaling Pathways, Transcription Factors, Molecular Functions, and Biological Processes were compared between eligible studies to describe how these dynamic changes transform the myocardium from an injured and inflamed tissue into a scar. Then, we address how cardioprotective interventions distinctly modulate the myocardial transcriptome and discuss the implications of uncovering gene regulatory networks for cardiovascular pathologies and translational applications.
PubMed: 35621843
DOI: 10.3390/jcdd9050132 -
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 -
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 -
Gene Apr 2022The limited regenerative capacity in mammals has serious implications for cardiac tissue damage. Meanwhile, zebrafish has a high regenerative capacity, but the...
The limited regenerative capacity in mammals has serious implications for cardiac tissue damage. Meanwhile, zebrafish has a high regenerative capacity, but the regulation of the heart healing process has yet to be elucidated. The dynamic nature of cardiac regeneration requires consideration of the inherent temporal dimension of this process. Here, we conducted a systematic review to find genes that define the regenerative cell state of the zebrafish heart. We then performed an in silico temporal gene regulatory network analysis using transcriptomic data from the zebrafish heart regenerative process obtained from databases. In this analysis, the genes found in the systematic review were used to represent the final cell state of the transition process from a non-regenerative cell state to a regenerative state. We found 135 transcription factors driving the cellular state transition process during zebrafish cardiac regeneration, including Hand2, Nkx2.5, Tbx20, Fosl1, Fosb, Junb, Vdr, Wt1, and Tcf21 previously reported for playing a key role in tissue regeneration. Furthermore, we demonstrate that most regulators are activated in the first days post-injury, indicating that the transition from a non-regenerative to a regenerative state occurs promptly.
Topics: Animals; Gene Regulatory Networks; Heart; Regeneration; Transcription Factors; Transcriptome; Zebrafish; Zebrafish Proteins
PubMed: 35114280
DOI: 10.1016/j.gene.2022.146242 -
Sleep Medicine Reviews Feb 2022Current theories of the glymphatic system (GS) hypothesize that it relies on cerebrospinal fluid (CSF) circulation to disseminate growth factors and remove metabolic... (Review)
Review
Current theories of the glymphatic system (GS) hypothesize that it relies on cerebrospinal fluid (CSF) circulation to disseminate growth factors and remove metabolic waste from the brain with increased CSF production and circulation during sleep; thereby, linking sleep disturbance with elements of CSF circulation and GS exchange. However, our growing knowledge of the relations between sleep, CSF, and the GS are plagued by variability in sleep and CSF measures across a wide array of pathologies. Hence, this review aims to summarize the dynamic relationships between sleep, CSF-, and GS-related features in samples of typically developing individuals and those with autoimmune/inflammatory, neurodegenerative, neurodevelopmental, sleep-related, neurotraumatic, neuropsychiatric, and skull atypicalities. One hundred and ninety articles (total n = 19,129 participants) were identified and reviewed for pathology, CSF circulation and related metrics, GS function, and sleep. Numerous associations were documented between sleep problems and CSF metabolite concentrations (e.g., amyloid-beta, orexin, tau proteins) and increased CSF volumes or pressure. However, these relations were not universal, with marked differences across pathologies. It is clear that elements of CSF circulation/composition and GS exchange represent pathways influenced by sleep; however, carefully designed studies and advances in GS measurement are needed to delineate the nuanced relationships.
Topics: Amyloid beta-Peptides; Brain; Glymphatic System; Humans; Sleep; Sleep Wake Disorders
PubMed: 34902819
DOI: 10.1016/j.smrv.2021.101572 -
International Journal of Molecular... Oct 2021The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide...
The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide variety of animal species. Despite their differences, they share a high homology in the pore region in which the ion discrimination takes place. Although ion selectivity has been studied for decades, the mechanisms underlying this selectivity for trimeric channels, and particularly for the ENaC/DEG family, are still poorly understood. This systematic review follows PRISMA guidelines and aims to determine the main components that govern ion selectivity in the ENaC/DEG family. In total, 27 papers from three online databases were included according to specific exclusion and inclusion criteria. It was found that the G/SxS selectivity filter (glycine/serine, non-conserved residue, serine) and other well conserved residues play a crucial role in ion selectivity. Depending on the ion type, residues with different properties are involved in ion permeability. For lithium against sodium, aromatic residues upstream of the selectivity filter seem to be important, whereas for sodium against potassium, negatively charged residues downstream of the selectivity filter seem to be important. This review provides new perspectives for further studies to unravel the mechanisms of ion selectivity.
Topics: Amiloride; Animals; Epithelial Sodium Channels; Humans; Ion Transport; Lithium; Molecular Dynamics Simulation; Mutagenesis, Site-Directed; Protein Structure, Quaternary; Sodium
PubMed: 34681656
DOI: 10.3390/ijms222010998 -
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 -
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 -
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 -
Drugs Sep 2021Clinical metagenomics (CMg) is the process of sequencing nucleic acid of clinical samples to obtain clinically relevant information such as the identification of...
Clinical metagenomics (CMg) is the process of sequencing nucleic acid of clinical samples to obtain clinically relevant information such as the identification of microorganisms and their susceptibility to antimicrobials. Over the last decades, sequencing and bioinformatic solutions supporting CMg have much evolved and an increasing number of case reports and series covering various infectious diseases have been published. Metagenomics is a new approach to infectious disease diagnosis that is currently being developed and is certainly one of the most promising for the coming years. However, most CMg studies are retrospective, and few address the potential impact CMg could have on patient management, including initiation, adaptation, or cessation of antimicrobials. In this narrative review, we have discussed the potential role of CMg in bacteriology, virology, mycology, and parasitology. Several reports and case-series confirm that CMg is an innovative tool with which one can (i) identify more microorganisms than with conventional methods in a single test, (ii) obtain results within hours, and (iii) tailor the antimicrobial regimen of patients. However, the cost-efficiency of CMg and its real impact on patient management are still to be determined.
Topics: Anti-Infective Agents; Communicable Diseases; Computational Biology; Humans; Metagenomics; Nucleic Acid Amplification Techniques
PubMed: 34328626
DOI: 10.1007/s40265-021-01572-4