Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Viruses, Год журнала: 2023, Номер 15(1), С. 175 - 175

Опубликована: Янв. 7, 2023

The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease death. Understanding the risk factors is relevant both in setting at epidemiological level. Here, we provide an overview host, viral environmental that have been shown or (in some cases) hypothesized be associated with outcomes. considered detail include age frailty, genetic polymorphisms, biological sex (and pregnancy), co- superinfections, non-communicable comorbidities, immunological history, microbiota, lifestyle patient; variation infecting dose; socioeconomic factors; air pollution. For each category, compile (sometimes conflicting) evidence for association factor outcomes (including strength effect) outline possible action mechanisms. We also discuss complex interactions between various factors.

Язык: Английский

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Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer’s Disease Pathogenesis—From Gut Microbiota and Viruses to Brain Biofilms

Microorganisms, Год журнала: 2025, Номер 13(1), С. 90 - 90

Опубликована: Янв. 5, 2025

For decades, Alzheimer's Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as primary driver of disease. However, consistent failure Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores need rethink our approach AD treatment. Emerging evidence points microbial infections environmental factors in pathoetiology. Although a definitive causal link remains unestablished, collective is compelling. This review explores unconventional perspectives and emerging paradigms regarding involvement pathogenesis, emphasizing gut-brain axis, brain biofilms, oral microbiome, viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes Aβ accumulation, signaling pathways. Viral like Herpes Simplex Virus Type 1 (HSV-1) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead by modulating host processes immune system. peptide's antimicrobial function response infection might inadvertently promote AD. We discuss potential microbiome-based promising strategies for managing potentially preventing progression. Fecal transplantation (FMT) restores balance, reduces improves cognition preclinical models. Probiotics prebiotics reduce neuroinflammation plaques, while antiviral targeting HSV-1 vaccines shingles vaccine mitigate pathology. Developing effective treatments requires standardized methods identify measure patients, enabling personalized address individual contributions pathogenesis. Further needed clarify interactions between microbes Aβ, explore bacterial interplay, understand their broader effects translate these insights into clinical interventions.

Язык: Английский

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Transcriptomic analysis reveals sex-specific patterns in the hippocampus in Alzheimer’s disease

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Апрель 16, 2024

Background The hippocampus, vital for memory and learning, is among the first brain regions affected in Alzheimer’s Disease (AD) exhibits adult neurogenesis. Women face twice risk of developing AD compare to men, making it crucial understand sex differences hippocampal function comprehending susceptibility. Methods We conducted a comprehensive analysis bulk mRNA postmortem samples from whole hippocampus (GSE48350, GSE5281) its CA1 CA3 subfields (GSE29378). Our aim was perform comparative molecular signatures analysis, investigating sex-specific similarities AD. This involved comparing gene expression profiles among: (a) male controls (M-controls) vs. female (F-controls), (b) females with (F-AD) F-controls, (c) males (M-AD) M-controls, (d) M-AD F-AD. Furthermore, we identified susceptibility genes interacting key targets menopause hormone replacement drugs, specifically ESR1 ESR2 genes, along GPER1 . Results revealed contrasting patterns between M-controls F-AD as well F-controls. Notably, BACE1 , enzyme linked amyloid-beta production pathology, found be upregulated compared F-controls both subfields. In GABAergic synapse downregulated, Estrogen signaling pathway subfields, unlike Analysis also upregulation While direct comparison F-AD, small subfield males. Conversely, exhibited downregulation Dopaminergic while Calcium showed mixed regulation, being but downregulated CA3, M-controls. M-AD, suggests compensatory response neurodegenerative results potential including MAPK1, IGF1, AKT1, TP53 CD44 Conclusion These findings underscore importance disease mechanisms pathogenesis. Region-specific offers more detailed examination localized changes enabling capture progression.

Язык: Английский

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Molecular signatures of premature aging in Major Depression and Substance Use Disorders

Scientific Data, Год журнала: 2024, Номер 11(1)

Опубликована: Июнь 26, 2024

Abstract Major depressive disorder (MDD) and substance-use disorders (SUDs) often lead to premature aging, increasing vulnerability cognitive decline other forms of dementia. This study utilized advanced systems bioinformatics identify aging “signatures” in MDD SUDs evaluated the potential for known lifespan-extending drugs target reverse these signatures. The results suggest that inhibiting transcriptional activation FOS gene family members holds promise mitigating SUDs. Conversely, antidepressant activating PI3K/Akt/mTOR pathway, a common mechanism rapid-acting antidepressants, may accelerate patients, making them unsuitable those with comorbid aging-related conditions like dementia Alzheimer’s disease. Additionally, this innovative approach identifies anti-aging interventions such as Deferoxamine, Resveratrol, Estradiol valerate, natural compounds zinc acetate, genistein, ascorbic acid, regardless anxiety disorders. These findings illuminate effects offer insights into treatment strategies patients conditions, including

Язык: Английский

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From Viral Infections to Alzheimer's Disease: Unveiling the Mechanistic Links Through Systems Bioinformatics

The Journal of Infectious Diseases, Год журнала: 2024, Номер 230(Supplement_2), С. S128 - S140

Опубликована: Май 9, 2024

Abstract Background Emerging evidence suggests that viral infections may contribute to Alzheimer's disease (AD) onset and/or progression. However, the extent of their involvement and mechanisms through which specific viruses increase AD susceptibility risk remain elusive. Methods We used an integrative systems bioinformatics approach identify viral-mediated pathogenic mechanisms, by Herpes Simplex Virus 1 (HSV-1), Human Cytomegalovirus (HCMV), Epstein-Barr virus (EBV), Kaposi Sarcoma-associated Herpesvirus (KSHV), Hepatitis B (HBV), C (HCV), Influenza A (IAV) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) could facilitate pathogenesis via virus-host protein-protein interactions (PPIs). also explored potential synergistic effects resulting from herpesvirus reactivation (HSV-1, HCMV, EBV) during acute SARS-CoV-2 infection, potentially increasing susceptibility. Results Herpesviridae members EBV, KSHV, HCMV) impact AD-related processes like amyloid-β (Aβ) formation, neuronal death, autophagy. (HBV, HCV) influence crucial for cellular homeostasis dysfunction, they affect microglia activation PPIs. Reactivation HCMV infection foster a lethal interplay neurodegeneration, on response unfolded protein, regulation autophagy, oxidative stress, Aβ formation. Conclusions These findings underscore complex link between development. Viruses shared distinct influencing variations in

Язык: Английский

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Efficacy and Safety of Acupuncture for Post–COVID-19 Insomnia: Protocol for a Systematic Review and Meta-Analysis

JMIR Research Protocols, Год журнала: 2025, Номер 14, С. e69417 - e69417

Опубликована: Март 3, 2025

The COVID-19 pandemic has had a profound global impact, leading to range of persistent sequelae referred as post-COVID-19 condition or "long COVID" that continue affect patients worldwide. Among these sequelae, insomnia (PCI) emerged significant issue. Conventional treatments, including cognitive behavioral therapy and pharmacological interventions, face limitations such variable efficacy, potential side effects, substantial costs. Recently, acupuncture gained traction due its cost-effectiveness, safety profile. This study aims conduct meta-analysis systematic review evaluating the efficacy for treatment PCI delineate optimal modality, intervention frequency, duration achieving most beneficial outcomes, thereby providing comprehensive understanding acupuncture's role in managing PCI, contributing evidence-based clinical practice, informing decision-making. Electronic searches will be performed 12 databases from inception October 2024 without language restrictions. includes both English (PubMed, Cochrane Library, Web Science, Embase, OVID Scopus), well Chinese (China National Knowledge Infrastructure, Wan-Fang Data, Biomedical Literature Database, Scientific Journal Duxiu Database Clinical Trial Registry Center). Randomized controlled trials on included. Primary outcomes include response rate severity; secondary Traditional Medicine Symptom Scale (TCMSS) adverse event rates. Data synthesis use risk ratios dichotomous data mean differences continuous data. Study selection, extraction, quality assessment conducted independently by 2 reviewers. Methodological eligible studies evaluated following Handbook Systematic Reviews Interventions (version 6.3). Meta-analysis with RevMan 5.3. Based rate, severity, TCMSS score, rates, this provide an treatment. present current evidence aiming inform practices decision-making enhance PCI. Furthermore, it identify research gaps suggest areas future investigation. PROSPERO CRD42024499284; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=499284. DERR1-10.2196/69417.

Язык: Английский

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Exploring the active ingredients and potential mechanisms of Pingchan granules in Parkinson’s disease treatment through network pharmacology and transcriptomics

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 6, 2025

Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, poses significant challenges to single-target therapeutic strategies due its complex etiology. This has driven interest in multi-target approaches, particularly those leveraging natural compounds. Pingchan granules (PCG), a traditional Chinese medicine composed of plant- and animal-derived compounds, have shown efficacy alleviating PD symptoms. Here, we identify 96 PCG-associated anti-PD targets, enriched neuronal synaptic signaling G protein-coupled receptor pathways. Through protein-protein interaction network analysis targets random forest modeling substantia nigra transcriptomic data from patients, SLC6A3 SRC emerged as central hub with Mendelian randomization further validating potential target. Molecular docking single-cell sequencing reveal that dauricine, PCG's principal active compound, binds strongly SRC, modulating glucose metabolism pathways dopaminergic neurons. These findings illuminate molecular basis effects, offer foundation for future drug development, underscore dauricine targeted treatment PD.

Язык: Английский

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Deep learning, artificial intelligence, and bioinformatics promises innovations and imminent forecasts in SARS-COVID-19 genome data analysis

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 1 - 24

Опубликована: Янв. 1, 2025

Язык: Английский

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Omics and Network-based Approaches in Understanding HD Pathogenesis

IntechOpen eBooks, Год журнала: 2024, Номер unknown

Опубликована: Фев. 29, 2024

Huntington’s Disease (HD) is a rare, progressive neurodegenerative disease caused by CAG repeat expansion in the Huntingtin gene. HD an incurable disease; therefore, there growing need for effective therapeutic treatments and candidate biomarkers prognosis diagnosis of HD. Technological advancements over past couple years, have led to high-throughput experiments omics data. The use System Bioinformatics (SB) approaches, allows integration information across different -omics, this can clarify synergistic relationships biological molecules, resulting complex networks. SB network-based are able shed light on potential interactions genes, proteins, metabolites pathways participating pathogenesis how dysregulation these entities, affect age onset, severity progression. Moreover, −omics data analysis approaches provide better understanding molecules interact with each other provides drug targets that be used treat or delay symptom onset; opening door towards precision medicine. aim following chapter, discuss most popular -omics related research, popularity single cell analysis, repositories software available bulk analysis. In addition, regarding will also mentioned.

Язык: Английский

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One Path, Two Solutions: Network-Based Analysis Identifies Targetable Pathways for the Treatment of Comorbid Type II Diabetes and Neuropsychiatric Disorders

Computational and Structural Biotechnology Journal, Год журнала: 2024, Номер 23, С. 3610 - 3624

Опубликована: Окт. 10, 2024

Язык: Английский

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