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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 -
Frontiers in Cellular Neuroscience 2022Adolescence is a late developmental period marked by pronounced reorganization of brain networks in which epigenetic mechanisms play a fundamental role. This brain...
Adolescence is a late developmental period marked by pronounced reorganization of brain networks in which epigenetic mechanisms play a fundamental role. This brain remodeling is associated with a peculiar behavior characterized by novelty seeking and risky activities such as alcohol and drug abuse, which is associated with increased susceptibility to stress. Hence, adolescence is a vulnerable postnatal period since short- and long-term deleterious effects of alcohol drinking and drug abuse are a serious worldwide public health concern. Among several other consequences, it has been proposed that exposure to stress, alcohol, or other drugs disrupts epigenetic mechanisms mediated by small non-coding microRNAs (miRNAs). During adolescence, this modifies the expression of a variety of genes involved in neurodevelopmental processes such as proliferation, differentiation, synaptogenesis, neural plasticity, and apoptosis. Hence, the effect of miRNAs dysregulation during adolescence might contribute to a long-term impact on brain function. This systematic review focuses on the miRNA expression patterns in the adolescent rodent brain with special interest in the impact of stress and drugs such as amphetamine, cocaine, nicotine, cannabis, and ketamine. The results point to a relevant and complex role of miRNAs in the regulation of the molecular processes involved in adolescent brain development as part of a dynamic epigenetic network sensitive to environmental events with distinctive changes across adolescence. Several miRNAs have been assessed evidencing changing expression profiles during the adolescent transition which are altered by exposure to stress and drug abuse. Since this is an emerging rapidly growing field, updating the present knowledge will contribute to improving our understanding of the epigenetic regulation mechanisms involved in the neurodevelopmental changes responsible for adolescent behavior. It can be expected that increased knowledge of the molecular mechanisms mediating the effect of environmental threats during the adolescent critical developmental period will improve understanding of psychiatric and addictive disorders emerging at this stage.
PubMed: 35936504
DOI: 10.3389/fncel.2022.956609 -
Clinical Epigenetics Jun 2024Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a... (Review)
Review
BACKGROUND
Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a pivotal role in immune surveillance, orchestrating the recognition and elimination of tumor cells by the immune system. However, the intricate regulation of MHC gene expression is susceptible to dynamic epigenetic modification, which can influence functionality and pathological outcomes.
MAIN BODY
By understanding the epigenetic alterations that drive MHC downregulation, insights are gained into the molecular mechanisms underlying immune escape, tumor progression, and immunotherapy resistance. This systematic review examines the current literature on epigenetic mechanisms that contribute to MHC deregulation in esophageal, gastric, pancreatic, hepatic and colorectal malignancies. Potential clinical implications are discussed of targeting aberrant epigenetic modifications to restore MHC expression and 0 the effectiveness of immunotherapeutic interventions.
CONCLUSION
The integration of epigenetic-targeted therapies with immunotherapies holds great potential for improving clinical outcomes in patients with gastrointestinal malignancies and represents a compelling avenue for future research and therapeutic development.
Topics: Humans; Gastrointestinal Neoplasms; Epigenesis, Genetic; Major Histocompatibility Complex; Gene Expression Regulation, Neoplastic; Immunotherapy; DNA Methylation; Tumor Escape
PubMed: 38915093
DOI: 10.1186/s13148-024-01698-8 -
European Journal of Nuclear Medicine... May 2023Pharmacokinetic modelling with arterial sampling is the gold standard for analysing dynamic PET data of the brain. However, the invasive character of arterial sampling...
Pharmacokinetic modelling with arterial sampling is the gold standard for analysing dynamic PET data of the brain. However, the invasive character of arterial sampling prevents its widespread clinical application. Several methods have been developed to avoid arterial sampling, in particular reference region methods. Unfortunately, for some tracers or diseases, no suitable reference region can be defined. For these cases, other potentially non-invasive approaches have been proposed: (1) a population based input function (PBIF), (2) an image derived input function (IDIF), or (3) simultaneous estimation of the input function (SIME). This systematic review aims to assess the correspondence of these non-invasive methods with the gold standard. Studies comparing non-invasive pharmacokinetic modelling methods with the current gold standard methods using an input function derived from arterial blood samples were retrieved from PubMed/MEDLINE (until December 2021). Correlation measurements were extracted from the studies. The search yielded 30 studies that correlated outcome parameters (V, DVR, or BP for reversible tracers; K or CMR for irreversible tracers) from a potentially non-invasive method with those obtained from modelling using an arterial input function. Some studies provided similar results for PBIF, IDIF, and SIME-based methods as for modelling with an arterial input function (R = 0.59-1.00, R = 0.71-1.00, R = 0.56-0.96, respectively), if the non-invasive input curve was calibrated with arterial blood samples. Even when the non-invasive input curve was calibrated with venous blood samples or when no calibration was applied, moderate to good correlations were reported, especially for the IDIF and SIME (R = 0.71-1.00 and R = 0.36-0.96, respectively). Overall, this systematic review illustrates that non-invasive methods to generate an input function are still in their infancy. Yet, IDIF and SIME performed well, not only with arterial blood calibration, but also with venous or no blood calibration, especially for some tracers without plasma metabolites, which would potentially make these methods better suited for clinical application. However, these methods should still be properly validated for each individual tracer and application before implementation.
Topics: Humans; Arteries; Brain; Kinetics; Positron-Emission Tomography; Veins
PubMed: 36651951
DOI: 10.1007/s00259-022-06057-4 -
World Journal of Stem Cells May 2024Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors,...
BACKGROUND
Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors, contribute to resistance, tumor heterogeneity, and plasticity. Recent studies reveal GSCs' role in therapeutic resistance, driven by DNA repair mechanisms and dynamic transitions between cellular states. Resistance mechanisms can involve different cellular pathways, most of which have been recently reported in the literature. Despite progress, targeted therapeutic approaches lack consensus due to GSCs' high plasticity.
AIM
To analyze targeted therapies against GSC-mediated resistance to radio- and chemotherapy in gliomas, focusing on underlying mechanisms.
METHODS
A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to September 30, 2023. The search strategy utilized relevant Medical Subject Heading terms and keywords related to including "glioma stem cells", "radiotherapy", "chemotherapy", "resistance", and "targeted therapies". Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated resistance to radiotherapy resistance (RTR).
RESULTS
In a comprehensive review of 66 studies on stem cell therapies for SCI, 452 papers were initially identified, with 203 chosen for full-text analysis. Among them, 201 were deemed eligible after excluding 168 for various reasons. The temporal breakdown of studies illustrates this trend: 2005-2010 (33.3%), 2011-2015 (36.4%), and 2016-2022 (30.3%). Key GSC models, particularly U87 (33.3%), U251 (15.2%), and T98G (15.2%), emerge as significant in research, reflecting their representativeness of glioma characteristics. Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) (27.3%) and Notch (12.1%) pathways, suggesting their crucial roles in resistance development. Targeted molecules with mTOR (18.2%), CHK1/2 (15.2%), and ATP binding cassette G2 (12.1%) as frequent targets underscore their importance in overcoming GSC-mediated resistance. Various therapeutic agents, notably RNA inhibitor/short hairpin RNA (27.3%), inhibitors ( LY294002, NVP-BEZ235) (24.2%), and monoclonal antibodies ( cetuximab) (9.1%), demonstrate versatility in targeted therapies. among 20 studies (60.6%), the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance (51.5%), followed by reductions in carmustine resistance (9.1%) and doxorubicin resistance (3.0%), while resistance to RTR is reduced in 42.4% of studies.
CONCLUSION
GSCs play a complex role in mediating radioresistance and chemoresistance, emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.
PubMed: 38817336
DOI: 10.4252/wjsc.v16.i5.604 -
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 Immunology 2020The landscape for medical treatment of lung cancer has irreversibly changed since the development of immuno-oncology (IO). Yet, while immune checkpoint blockade (ICB)...
The landscape for medical treatment of lung cancer has irreversibly changed since the development of immuno-oncology (IO). Yet, while immune checkpoint blockade (ICB) revealed that T lymphocytes play a major role in lung cancer, the precise dynamic of innate and adaptive immune cells induced by anticancer treatments including chemotherapy, targeted therapy, and/or ICB is poorly understood. In lung cancer, studies evaluating specific immune cell populations as predictors of response to medical treatment are scarce, and knowledge is fragmented. Here, we review the different techniques allowing the detection of immune cells in the tumor and blood (multiplex immunohistochemistry and immunofluorescence, RNA-seq, DNA methylation pattern, mass cytometry, functional tests). In addition, we present data that consider different baseline immune cell populations as predictors of response to medical treatments of lung cancer. We also review the potential for assessing dynamic changes in cell populations during treatment as a biomarker. As powerful tools for immune cell detection and data analysis are available, clinicians and researchers could increase understanding of mechanisms of efficacy and resistance in addition to identifying new targets for IO by developing translational studies that decipher the role of different immune cell populations during lung cancer treatments.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Lung Neoplasms; Molecular Targeted Therapy; Monitoring, Immunologic; Treatment Outcome
PubMed: 32670271
DOI: 10.3389/fimmu.2020.01036 -
Frontiers in Immunology 2024This meta-analysis was performed to assess the prevalence and circulating strains of rotavirus (RV) among Chinese children under 5 years of age after the implantation of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis was performed to assess the prevalence and circulating strains of rotavirus (RV) among Chinese children under 5 years of age after the implantation of the RV vaccine.
MATERIAL AND METHODS
Studies published between 2019 and 2023, focused on RV-based diarrhea among children less than 5 years were systematically reviewed using PubMed, Embase, Web of Science, CNKI, Wanfang and SinoMed Data. We synthesized their findings to examine prevalence and genetic diversity of RV after the RV vaccine implementation using a fixed-effects or random-effects model.
RESULTS
Seventeen studies met the inclusion criteria for this meta-analysis. The overall prevalence of RV was found to be 19.00%. The highest infection rate was noted in children aged 12-23months (25.79%), followed by those aged 24-35 months (23.91%), and 6-11 months (22.08%). The serotype G9 emerged as the most predominant RV genotype, accounting for 85.48% of infections, followed by G2 (7.70%), G8 (5.74%), G1 (4.86%), and G3 (3.21%). The most common P type was P[8], representing 64.02% of RV cases. Among G-P combinations, G9P[8] was the most frequent, responsible for 78.46% of RV infections, succeeded by G8P[8] (31.22%) and G3P[8] (8.11%).
CONCLUSION
Despite the variation of serotypes observed in China, the G1, G2, G3, G8 and G9 serotypes accounted for most RV strains. The genetic diversity analysis highlights the dynamic nature of RV genotypes, necessitating ongoing surveillance to monitor changes in strain distribution and inform future vaccine strategies.
Topics: Humans; Rotavirus Infections; Rotavirus; China; Genetic Variation; Prevalence; Infant; Child, Preschool; Genotype; Rotavirus Vaccines; Male
PubMed: 38690265
DOI: 10.3389/fimmu.2024.1364429 -
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