Robust senescence evaluation by transcriptome-based hUSI to facilitate characterizing cellular senescence under various conditions

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 13, 2024

Abstract Despite the manifestation and contribution of cellular senescence to tissue aging aging-related disease, identification in vivo senescent cells recognition senescence-specific communication still remain challenging. Current evaluation methods rely greatly on expression level well-known markers, enrichment gene sets or weighted sum curated genes. However, focusing limited aspects, these could not adequately capture comprehensive features. To evaluate a more general unbiased way from most common easily accessible transcriptome data, we developed human universal index (hUSI) quantify based series genes learned representative RNA-seq profiles using machine learning algorithm. hUSI demonstrated its superior performance distinguishing samples under various conditions robustness handling batch effects sparse profiles. uncover accumulation cell types complex pathological conditions, reflected increasing burden patients provided potential senotherapeutic targets. Furthermore, combined with gaussian mixture model, successfully inferred tumor melanoma identified key target signaling pathways that are beneficial for patient prognosis. Overall, provides valuable choice improve our ability characterizing illustrating promising implications studies clinical situations.

Language: Английский

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A Machine Learning Model for the Prediction of COVID-19 Severity Using RNA-Seq, Clinical, and Co-Morbidity Data

Diagnostics, Journal Year: 2024, Volume and Issue: 14(12), P. 1284 - 1284

Published: June 18, 2024

The premise for this study emanated from the need to understand SARS-CoV-2 infections at molecular level and develop predictive tools managing COVID-19 severity. With varied clinical outcomes observed among infected individuals, creating a reliable machine learning (ML) model predicting severity of became paramount. Despite availability large-scale genomic data, previous studies have not effectively utilized multi-modality data disease prediction using data-driven approaches. Our primary goal is predict machine-learning trained on combination patients’ gene expression, features, co-morbidity data. Employing various ML algorithms, including Logistic Regression (LR), XGBoost (XG), Naïve Bayes (NB), Support Vector Machine (SVM), alongside feature selection methods, we sought identify best-performing prediction. results highlighted XG as superior classifier, with 95% accuracy 0.99 AUC (Area Under Curve), distinguishing groups. Additionally, SHAP analysis revealed vital features contributing prediction, several genes such COX14, LAMB2, DOLK, SDCBP2, RHBDL1, IER3-AS1. Notably, two absolute neutrophil count Viremia Categories, emerged top contributors. Integrating multiple modalities has significantly improved compared any single modality. identified could serve biomarkers prognosis patient care, allowing clinicians optimize treatment strategies refine decision-making processes enhanced outcomes.

Language: Английский

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Interactions of SARS-CoV-2 with Human Target Cells—A Metabolic View

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9977 - 9977

Published: Sept. 16, 2024

Viruses are obligate intracellular parasites, and they exploit the cellular pathways resources of their respective host cells to survive successfully multiply. The strategies viruses concerning how take advantage metabolic capabilities for own replication can vary considerably. most common alterations triggered by affect central carbon metabolism infected cells, in particular glycolysis, pentose phosphate pathway, tricarboxylic acid cycle. upregulation these processes is aimed increase supply nucleotides, amino acids, lipids since products crucial efficient viral proliferation. In detail, however, this manipulation may multiple sites regulatory mechanisms host-cell metabolism, depending not only on specific but also type cells. review, we report situations reprogramming different human tissues, organs that favorable acute persistent SARS-CoV-2 infection. This knowledge be fundamental development host-directed therapies.

Language: Английский

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Subchronic Toxicity of Mineral Oil Saturated Hydrocarbons (MOSH) in Relation to Its Carbon Number Range and Gender of Fischer F344 Rats

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

In this work, the paraffin oil was first molecularly distilled into two mineral saturated hydrocarbons (MOSH) subfractions with their main carbon number range of C

Language: Английский

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Integrated multi-omics characterization across clinically relevant subgroups of long COVID

National Science Review, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 15, 2024

Abstract With SARS-CoV-2 became regional epidemics, substantial amount of patients suffers from post-acute sequelae COVID-19 (PASC, aka long COVID). Exploring the pathogenesis and especially heterogenicity features COVID subgroups is paramount importance for etiology understandings. In this study, through integrative multi-omics analyses encompassing transcriptomics, proteomics, metabolomics, exhibited overall elevated MAPK pathway activation, while recovered showed down-regulation response. Long described by distinct signatures each subgroup. Multisystemic (MULTI) symptoms subgroup characterized enhanced glycerophospholipid ether lipid metabolism, Neurological (NEU) augmented glycoprotein synthesis Cardio cerebral (CACRB) increased pyruvate metabolism suppressed macrophage polarization, Musculoskeletal + Systemic (MSK SYST) Cardiopulmonary (CAPM) inhibited NF-κB signaling pathways. ABHD17A, CSNK1D, PSME4 SYVN1 were general combination biomarkers, CRH (MULTI), FPGT (NEU), CBX6 RBBP4 selected as serum-specific proteins. Our study provides commonly shared pathophysiology explanation underpinning PASC, paving way future diagnosis therapeutic interventions.

Language: Английский

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Uncovering strain- and age-dependent differences in innate immune response to SARS-CoV-2 infection in nasal epithelia using 10X single-cell sequencing

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 6, 2023

Summary Assessing the impact of SARS-CoV-2 variants on host is crucial with continuous emergence new variants. We employed single-cell sequencing to investigate transcriptomic response ancestral and Alpha-strain infections within air-liquid-interface human nasal epithelial cells from adults adolescents. Strong innate immune responses were observed across lowly-infected bystander cell-types, heightened in Alpha-infection. Contrastingly, highly-infected was like mock-control cells. Alpha showed increased expression protein refolding genes compared ancestral-strain-infected adolescent Oxidative phosphorylation- translation-related down-regulated versus infected cells, suggesting that down-regulation protective up-regulation supports viral activity. Infected adult revealed these pathways adolescents, implying enhanced pro-viral states adults. Overall, this highlights complexity cell-type-, age- viral-strain-dependent value cultures.

Language: Английский

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High abundance of butyrate-producing bacteria in the naso-oropharynx of SARS-CoV-2-infected persons in an African population: implications for low disease severity

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 4, 2023

Abstract Background : Microbiome dysbiosis is associated with various diseases, including COVID-19. The association of the oral microbiome SARS-CoV-2 infections and disease progression has been documented in European, Asian, American populations but not Africa. Methods We conducted a study Ghana to evaluate compare naso-oropharyngeal SARS-CoV-2-infected noninfected persons before after vaccination. 16S rDNA was sequenced analysed from DNA extracted swabs consenting participants. Results Alpha diversity high among pre-vaccinated virus-positive individuals (Shannon: p < 0.0001) reduced vaccinated persons. Contrary other reports, differences viral loads did significantly affect alpha diversity. Pre-vaccinated SARS-CoV-2-positive -negative had little yet significant microbial compositional dissimilarity (PERMANOVA: R 2 =0.14, = 0.001) when some were =0.013, 0.49). Consistent studies, Prevotella Atopobium abundant (adjusted value <0.05). Butyrate-producing microbes, members Lachnospiraceae Fusobacterium sp., relatively abundances infected individuals. As biomarkers infection (log 10 LDA> 4.0), they suggest probable protective pathophysiological processes that would prevent severe outcomes this population. Anaerovoracaceae increased persons, further implicating Firmicutes immunity against Conclusion Our results necessitate studies confirm integral role immune responses progression. also recommend expansion microbiome–disease across Africa identify possible bacterial-mediated therapeutics for emerging infections.

Language: Английский

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The effect of myo–inositol supplementation on feed physicochemical structure and viral load of dry cat food contaminated with SARS–CoV–2 by simulating sneezing

Revista Científica de la Facultad de Ciencias Veterinarias, Journal Year: 2023, Volume and Issue: XXXIII(2), P. 1 - 8

Published: Oct. 13, 2023

The study was carried to investigate the effect of myo–inositol supplementation on feed physicochemical structure and viral load dry cat food contaminated with inactive SARS–CoV–2 by simulating sneezing. most natural infection severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) in animals is related close contact their owners COVID–19 which handling, taking care feeding them. can survive food, fomites surfaces for extended periods environmental conditions. Many additives supplements have been a candidate recent antiviral treatment strategies against COVID–19. In this study, permitted animal nutrition used at different concentrations (0, 12.5, 25 50 mg·100 g-1 food) conditions (22°C room temperature 4°C refrigerator) its effects For interactions between myo–inositol, load, matter, moisture, water absorption index (WAI), solubility (WSI), pH virus gene copy (GC) RT–qPCR were measured. As only storage affected both WAI WSI as expected, myo–inostol dose–dependently decreased (IC50:366.4–581.5 22°C temperature. Virus GC did not correlate moisture content, after 30 min time (except WSI). conclusion, additive might potential control serious infections such human–animal One–Health context.

Language: Английский

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SARS-CoV-2 Nsp6 causes cardiac defects through MGA/MAX complex-mediated increased glycolysis

Research Square (Research Square), Journal Year: 2022, Volume and Issue: unknown

Published: June 6, 2022

Abstract SARS-CoV-2 infection causes COVID-19, a severe acute respiratory disease associated with cardiovascular complications including long-term outcomes. The presence of virus in cardiac tissue patients COVID-19 suggests this is direct, rather than secondary, effect infection. By expressing individual proteins the Drosophila heart we demonstrated interaction Nsp6 host MGA/MAX complex (MGA, PCGF6 and TFDP1). Complementing transcriptomic data from fly revealed that blocks antagonistic complex, which shifts balance towards MYC/MAX activates glycolysis—with similar findings mouse cardiomyocytes. Further, Nsp6-induced glycolysis disrupted mitochondrial function, known to increase reactive oxygen species (ROS) failure; could explain COVID-19-associated pathology. Furthermore, inhibiting pathway by 2-deoxy-D-glucose (2DG) treatment attenuated phenotype mice; thus, suggesting as potential pharmacological target for treating failure.

Language: Английский

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