Preliminary results and a theoretical perspective of co‑treatment using a miR‑93‑5p mimic and aged garlic extract to inhibit the expression of the pro‑inflammatory interleukin‑8 gene

Experimental and Therapeutic Medicine, Journal Year: 2025, Volume and Issue: 29(4), P. 1 - 11

Published: Feb. 25, 2025

The coronavirus disease‑19 (COVID‑19) pandemic has been a very significant health issue in the period between 2020 and 2023, forcing research to characterize severe acute respiratory syndrome 2 (SARS‑CoV‑2) sequences develop novel therapeutic approaches. Interleukin‑6 (IL‑6) IL‑8 are considered targets for COVID‑19 emerging evidence suggested that microRNAs (miRNAs/miRs) serve key role regulating these genes. MiRNAs short, 19‑25 nucleotides length, non‑coding RNAs regulate gene expression at post‑transcriptional level through sequence‑selective recognition of 3'‑untranslated region (3'‑UTR) regulated mRNAs, eventually repressing translation, commonly, via mRNA degradation. For example, among several miRNAs involved regulation 'cytokine storm', miR‑93‑5p can inhibit by directly targeting 3'‑UTR mRNA. In addition, Toll‑like receptor‑4 (TLR4) interleukin‑1 receptor‑associated kinase 4 (IRAK4) expression, thus affecting nuclear factor‑κB (NF‑κB) pathway NF‑κB‑regulated genes, such as IL‑6, IL‑1β other hyper‑expressed genes during storm'. present study, results provided preliminary suggesting miR‑93‑5p‑based miRNA therapeutics could be combined with anti‑inflammatory aged garlic extract (AGE) more effectively expression. human bronchial epithelial IB3‑1 cell line was employed experimental model system. cells were stimulated BNT162b2 vaccine transfected pre‑miR‑93‑5p absence or presence AGE, verify inhibitory effects on BNT162b2‑induced gene. accumulation assessed RT‑qPCR; release protein determined Bio‑Plex assay. possible applications TLR4/NF‑κB agents (such AGE) treating pathologies hyperinflammatory state, COVID‑19, cystic fibrosis diseases, summarized.

Language: Английский

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Neuroinflammation in Post COVID‐19 Sequelae: Neuroinvasion and Neuroimmune Crosstalk

Reviews in Medical Virology, Journal Year: 2024, Volume and Issue: 34(6)

Published: Nov. 1, 2024

Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in December 2019 triggered a swift global spread, leading to devastating pandemic. Alarmingly, approximately one four individuals diagnosed with disease (COVID‐19) experience varying degrees cognitive impairment, raising concerns about potential increase neurological sequelae cases. Neuroinflammation seems be the key pathophysiological hallmark linking mild COVID‐19 fatigue, and patients, highlighting interaction between nervous immune systems following SARS‐CoV‐2 infection. Several hypotheses have been proposed explain how virus disrupts physiological pathways trigger inflammation within CNS, potentially neuronal damage. These include neuroinvasion, systemic inflammation, disruption lung gut‐brain axes, reactivation latent viruses. This review explores origins neuroinflammation underlying neuroimmune cross‐talk, important unanswered questions field. Addressing these fundamental issues could enhance our understanding virus's impact on CNS inform strategies mitigate its detrimental effects.

Language: Английский

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Acute and long-term SARS-CoV-2 infection and neurodegeneration processes—circulus vitiosus

Acta Virologica, Journal Year: 2024, Volume and Issue: 68

Published: Oct. 15, 2024

The global pandemic of COVID-19 caused by SARS-CoV-2 has had a devastating impact. Although many survived the acute effects pandemic, significant number survivors, including those with only mild symptoms, are now experiencing prolonged and debilitating post-viral syndrome known as LC/PASC (long COVID/post-acute sequelae SARS-CoV-2). Typical symptoms include fatigue, breathlessness, chest pain, impaired cognition, difficulty sleeping, fever gastrointestinal symptoms. Anxiety depression can also last for weeks to months range from disabling. association between neuropsychiatric infection raises questions about possible routes entry central nervous system (CNS) long-term virus on CNS, their molecular basis, potential risk neuronal damage associated subsequent development neurodegenerative diseases.

Language: Английский

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Aged Garlic Extract (AGE) and Its Constituent S-Allyl-Cysteine (SAC) Inhibit the Expression of Pro-Inflammatory Genes Induced in Bronchial Epithelial IB3-1 Cells by Exposure to the SARS-CoV-2 Spike Protein and the BNT162b2 Vaccine

Molecules, Journal Year: 2024, Volume and Issue: 29(24), P. 5938 - 5938

Published: Dec. 16, 2024

Garlic (Allium sativum L.) is a species of the onion family (Alliaceae) widely used as food and folk medicine. The objective this study was to determine effects AGE (aged garlic extract) on pro-inflammatory genes relevant COVID-19. To aim, we treated bronchial epithelial IB3-1 cells with SARS-CoV-2 spike protein (S-protein) or COVID-19 BNT162b2 vaccine in absence presence AGE. results obtained demonstrated that potent inhibitor S-protein-induced expression IL-1β, IL-6 IL-8 genes. Bio-Plex analysis reduced release IL-8, which were highly induced by S-protein. No inhibition cells' growth, toxicity pro-apoptotic found AGE-treated cells. one major constituents (S-allyl cysteine, SAC) studied same experimental model systems. SAC able inhibit extracellular confirming S-allyl-cysteine responsible for inhibiting Docking experiments suggest possible mechanism action an interference activity Toll-like receptors (TLRs), particularly TLR4, thereby NF-κB- NF-κB-regulated genes, such These both deserve further efforts verify their SARS-CoV-2-infected

Language: Английский

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Epithelial Antimicrobial Peptide/Protein and Cytokine Expression Profiles Obtained from Nasopharyngeal Swabs of SARS-CoV-2-Infected and Non-Infected Subjects

Viruses, Journal Year: 2024, Volume and Issue: 16(9), P. 1471 - 1471

Published: Sept. 15, 2024

Immune responses of the epithelia upper respiratory tract are likely crucial in early inhibition viral replication and finally clearance SARS-CoV-2. We aimed to compare expression profiles antimicrobial peptides/proteins (AMPs) related cytokines observed nasopharynx SARS-CoV-2-infected patients non-infected controls assess associations between these parameters COVID-19 patients’ outcomes. included 45 subjects who had tested positive for SARS-CoV-2 22 control negative Biomaterial detection, as well gene protein studies, was obtained from all using nasopharyngeal swabs which were performed a maximum 7 days before inclusion study. Univariable multivariable statistics performed. When compared controls, mRNA levels human β-defensin 1 (hBD-1), LL-37, trappin-2 significantly higher specimens patients. Protein hBD-1 also increased group. interferon-ɣ (IFN-ɣ), tumor necrosis factor- ɑ (TNF-ɑ), interleukin-6 (IL-6) measured than those could be confirmed IFN-ɣ IL-6. A significant correlation only analysis revealed that low associated with severe/fatal The occurrence pneumonia lower IL-6 mRNA, TNF-ɑ mRNA. Concerning outcomes, logistic regression model none aforementioned remained model. However, independent predictor absence [odds ratio: 0.35 (95% CI 0.14 0.88, p = 0.024)]. In conclusion, AMPs (hBD-1, trappin-2) (IL-6, IFN-ɣ, TNF-ɑ) is upregulated response infection, indicating play role local host defense against virus. Upregulated during phase infection pneumonia. Hence, high appears protective factor lung complications

Language: Английский

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Interplay of TLR4 and SARS-CoV-2: Possible Involvement of microRNAs [Letter]

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 7963 - 7964

Published: Oct. 31, 2024

Language: Английский

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