Persisting Gastrointestinal Symptoms in Children with SARS-CoV-2: Temporal Evolution over 18 Months and Possible Role of Lactoferrin

Children, Год журнала: 2024, Номер 11(1), С. 105 - 105

Опубликована: Янв. 15, 2024

Background and aim: Persisting gastrointestinal symptoms are reported to be relatively common in children with long COVID; however, their detailed characterization long-term outcomes have not yet been described. Methods: We performed a retrospective study aiming investigate the temporal evolution of SARS-CoV-2, from acute infection 18-months follow-up. To further possible therapeutic strategies, we evaluated role lactoferrin improving these children, compared those treated. Results: A total 1224 patients (47.7% females) were included. Of participants, 246 (19.8%) vaccinated 143 (11.5%) presented comorbidities. 175 (14.1%) during infection, 54 (4.4%) at three months, 23 (1.9%) six 6 (3.3%) twelve 2 (2.3%) eighteen months At follow-up, who treated 3 oral had less persisting did receive lactoferrin, although this difference was statistically significant (three (25%) group vs. fourteen (33.3%) treated, p = 0.73), probably due low number GI symptoms. Conclusions: SARS-CoV-2 non-negligible proportion for up 12–18 after infection. In addition, found trend even if nonsignificant toward faster improvement COVID lactoferrin. Despite limitations relating present study’s design, given burden COVID, our findings provide basis perform prospective, placebo-controlled study.

Язык: Английский

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Untargeted serum metabolomics analysis of Trichinella spiralis-infected mouse

PLoS neglected tropical diseases, Год журнала: 2023, Номер 17(2), С. e0011119 - e0011119

Опубликована: Фев. 21, 2023

Background Trichinellosis, caused by a parasitic nematode of the genus Trichinella , is zoonosis that affects people worldwide. After ingesting raw meat containing spp. larvae, patients show signs myalgia, headaches, and facial periorbital edema, severe cases may die from myocarditis heart failure. The molecular mechanisms trichinellosis are unclear, sensitivity diagnostic methods used for this disease unsatisfactory. Metabolomics an excellent tool studying progression biomarkers; however, it has never been applied to trichinellosis. We aimed elucidate impacts infection on host body identify potential biomarkers using metabolomics. Methodology/Principal findings Mice were infected with T . spiralis sera collected before 2, 4, 8 weeks after infection. Metabolites in extracted identified untargeted mass spectrometry. Metabolomic data annotated via XCMS online platform analyzed Metaboanalyst version 5.0. A total 10,221 metabolomic features identified, levels 566, 330, 418 significantly changed at 2-, 4-, 8-weeks post-infection, respectively. altered metabolites further pathway analysis biomarker selection. major affected was glycerophospholipid metabolism, glycerophospholipids comprised main metabolite class identified. Receiver operating characteristic revealed 244 molecules power trichinellosis, phosphatidylserines (PS) being primary lipid class. Some molecules, e.g., PS (18:0/19:0)[U] PA (O-16:0/21:0), not present metabolome databases humans mice, thus they have secreted parasites. Conclusions/Significance Our study highlighted metabolism as hence species markers represent initial steps discovery benefit future diagnosis.

Язык: Английский

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Multi-Omics Profiling Reveals Phenotypic and Functional Heterogeneity of Neutrophils in COVID-19

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3841 - 3841

Опубликована: Март 29, 2024

Accumulating evidence has revealed unexpected phenotypic heterogeneity and diverse functions of neutrophils in several diseases. Coronavirus disease (COVID-19) can alter the leukocyte phenotype based on severity, including neutrophil activation severe cases. However, plasticity phenotypes their relative impact COVID-19 pathogenesis not been well addressed. This study aimed to identify validate evaluate each subpopulation. We analyzed public single-cell RNA-seq, bulk proteome data from healthy donors patients with investigate subpopulations response pathogenesis. identified eight subtypes: pro-neutrophil, pre-neutrophil, immature neutrophil, five mature subpopulations. The subtypes exhibited distinct features, signatures multiple enriched pathways. pro-neutrophil subtype was associated fatal disease, while pre-neutrophil particularly abundant mild/moderate disease. One showed consistently large fractions different severity. Bulk RNA-seq dataset analyses using a cellular deconvolution approach validated abundances expansion pro-neutrophils patients. Cell-cell communication analysis representative ligand-receptor interactions among subtypes. Further investigation into transcription factors differential protein abundance regulatory network differences between COVID-19. Overall, we demonstrated complex heterogeneous other blood cell types during Our work great value terms both clinical health as it furthers our understanding functional populations

Язык: Английский

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Drug Repurposing for COVID-19 by Constructing a Comorbidity Network with Central Nervous System Disorders

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 8917 - 8917

Опубликована: Авг. 16, 2024

In the post-COVID-19 era, treatment options for potential SARS-CoV-2 outbreaks remain limited. An increased incidence of central nervous system (CNS) disorders has been observed in long-term COVID-19 patients. Understanding shared molecular mechanisms between these conditions may provide new insights developing effective therapies. This study developed an integrative drug-repurposing framework COVID-19, leveraging comorbidity data with CNS disorders, network-based modular analysis, and dynamic perturbation analysis to identify drug targets candidates against SARS-CoV-2. We constructed a network based on literature collection, including COVID-19-related proteins genes associated Alzheimer’s disease, Parkinson’s multiple sclerosis, autism spectrum disorder. Functional module detection annotation identified primarily involved protein synthesis as key target module, utilizing connectivity map data. Through construction weighted drug–target ubiquitin–carboxy-terminal hydrolase L1 emerged target. Molecular dynamics simulations suggested pregnenolone BRD-K87426499 two COVID-19. introduces dynamic-perturbation-network-based approach by incorporating disorders.

Язык: Английский

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Methylprednisolone therapy induces differential metabolic trajectories in severe COVID-19 patients

mSystems, Год журнала: 2023, Номер 8(6)

Опубликована: Окт. 24, 2023

The SARS-CoV-2 virus infection in humans induces significant inflammatory and systemic reactions complications of which corticosteroids like methylprednisolone have been recommended as treatment. Our understanding the metabolic metabolomic pathway dysregulations while using intravenous COVID-19 is limited. This study will help enlighten underlying high daily doses patients compared to those receiving placebo. information on key metabolites pathways identified this together with crosstalk inflammation biochemistry components may be used, future, leverage use any future pandemics from coronavirus family.

Язык: Английский

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The Impact of Serum/Plasma Proteomics on SARS-CoV-2 Diagnosis and Prognosis

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 8633 - 8633

Опубликована: Авг. 8, 2024

While COVID-19’s urgency has diminished since its emergence in late 2019, it remains a significant public health challenge. Recent research reveals that the molecular intricacies of this virus are far more complex than initially understood, with numerous post-translational modifications leading to diverse proteoforms and viral particle heterogeneity. Mass spectrometry-based proteomics patient serum/plasma emerges as promising complementary approach traditional diagnostic methods, offering insights into SARS-CoV-2 protein dynamics enhancing understanding disease long-term consequences. This article highlights key findings from three years pandemic-era research. It delves biomarker discovery, advancements, drug development efforts aimed at monitoring COVID-19 onset progression exploring treatment options. Additionally, examines global abundance modification profiling elucidate signaling pathway alterations protein-protein interactions during infection. Finally, explores potential emerging multi-omics analytic strategies combatting SARS-CoV-2.

Язык: Английский

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Methylprednisolone Therapy Induces Differential Metabolic Trajectories in Severe COVID-19 Patients

Опубликована: Янв. 1, 2023

Summary: Corticosteroids have become a choice for managing severe COVID-19, but the molecular mechanisms behind response after corticosteroid administration remain incompletely understood. This study assessed temporal metabolic profiles in plasma of methylprednisolone (MP)-treated COVID-19 patients.Background: patients.Methods: Patient was obtained from double blind, randomized, placebo-controlled Phase IIb clinical trial performed on patients Brazilian Amazon. Patients received placebo or 0.5 mg/kg MP intravenously twice daily five days. Plasma samples collected before treatment and longitudinally over 14 days were then analyzed using high-resolution untargeted metabolomics. Network analysis also included blood cell counts, inflammation tissue damage markers, cytokine data.Findings: reduced number metabolites during follow-up associated with different pathways related to steroid hormones eicosanoids. Direct comparison between two groups revealed differences at baseline, which peaked initiation treatment. Metabolic differing time galactose metabolism, glucose gluconeogenesis, N-glycan prostaglandin formation arachidonate. Deoxy-galactose, H2, sphingosine, sphinganine exhibited differential trajectories Survival MP-treated modulation tryptophan metabolism. that is highly alterations reflecting eicosanoid such as arachidonic acid prostaglandins.Interpretation: Treatment modulates activity inflammatory lipids.Funding: work financially supported by Fundação de Amparo à Pesquisa do Estado Amazonas (under Resolutions # 002/2008, 007/2018, 005/2019, 005/2020, 006/2020 005/2022), Conselho Nacional Desenvolvimento Científico e Tecnológico (403253/2020-9) Serrapilheira Institute (to LGG, grant Serra – R-2011-37433).Declaration Interest: VIM, RLAN MGSB report they are recipients doctorate scholarships Coordenação Aperfeiçoamento Pessoal Nível Superior (CAPES). MNY reports be scholarship recipient CNPq. We disclose BGV, MGVL, WMM, AGC, LGG GCM CNPq productivity fellows. All other authors declare no competing interests. Ethical Approval: The Medicina Tropical Doutor Heitor Vieira Dourado Research Ethics Committee approved this (CAAE 46193821.5.0000.0005), sub-study larger (30615920.2.0000.0005).

Язык: Английский

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The exploration of glucocorticoid pathway based on disease severity in COVID-19 patients

Heliyon, Год журнала: 2023, Номер 10(1), С. e23579 - e23579

Опубликована: Дек. 10, 2023

Systemic inflammation is a hallmark of Coronavirus Disease 2019 (COVID-19) and the key to pathophysiology its severe cases with host cytokine involvement. Glucocorticoids can moderate this inflammatory effect due receptor binding (NRC31-the gene encoded), influencing expression effector genes pro-inflammatory cytokines. Another important pathway in processes immune responses nuclear factor-κB (NF-κB) signaling (NFKBIA-the encoded). We aimed explore glucocorticoid mild COVID-19. performed cross-sectional, observational study on COVID-19 cases, assessing RNA white blood cells. The Illumina® platform was used for sequencing, FASTQ data were quality-checked Multiqc. raw analyzed using CLC Genomics Workbench®. Our included 23 patients 21 an average age 49.9 ± 18.2 years old. NR3C1 NFKBIA expressions did not show significantly significant difference between groups (log2 fold change 0.5, p = 0.1; 0.82, 0.09). However, TSC22D3, DUSP-1, JAK-1 MAPK-1 higher 1.3, < 0.001; 2.6, 0.9, 1.48, p-value<0.001; respectively). Furthermore, TNF, IL-1β, IL-6 lower 4.05, 3.33, 6.86, In conclusion, our results showed that although NRC31 statistically groups, TSC22D3 cases. These highlight importance genes, specifically combatting systemic inflammation. recent findings have potential lead identification novel pharmacological targets could prove be vital fight against diseases associated

Язык: Английский

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