On fine particulate matter and COVID-19 spread and severity: An in vitro toxicological plausible mechanism

Environment International, Год журнала: 2023, Номер 179, С. 108131 - 108131

Опубликована: Авг. 11, 2023

COVID-19 pandemic had a significant impact on global public health. The spread of the disease was related to high transmissibility SARS-CoV-2 virus but incidence and mortality rate suggested possible relationship with environmental factors. Air pollution has been hypothesized play role in transmission resulting severity disease. Here we report plausible vitro toxicological mode action by which fine particulate matter (PM2.5) could promote higher infection PM2.5 promotes 1.5 fold over-expression angiotensin 2 converting enzyme (ACE2) is exploited viral particles enter human lung alveolar cells (1.5 increase RAB5 protein) increases their inflammatory state (IL-8 NF-kB protein expression). Our results provide basis for further exploring synergy between biological threats air pollutants ask deeper understanding how quality influence new pandemics future.

Язык: Английский

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Combination therapy with oral antiviral and anti-inflammatory drugs improves the efficacy of delayed treatment in a COVID-19 hamster model

EBioMedicine, Год журнала: 2023, Номер 99, С. 104950 - 104950

Опубликована: Дек. 30, 2023

Pulmonary infection with SARS-CoV-2 stimulates host immune responses and can also result in the progression of dysregulated critical inflammation. Throughout pandemic, management treatment COVID-19 has been continuously updated a range antiviral drugs immunomodulators. Monotherapy oral antivirals proven to be effective COVID-19. However, should initiated early stages ensure beneficial therapeutic outcomes, there is still room for further consideration on strategies using antivirals.

Язык: Английский

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Effects of diarylbutane lignans from Schisandra chinensis fruit on SARS-CoV-2 3CLpro and PLpro and their in vitro anti-inflammatory properties

Phytomedicine Plus, Год журнала: 2023, Номер 3(2), С. 100432 - 100432

Опубликована: Март 11, 2023

Schisandra chinensis fruit is a well-known traditional Chinese medicine (TCM), whose extract has potent inhibitory effect on the severe acute respiratory syndrome-coronavirus-2 (SARS‑CoV‑2) 3-chymotrypsin-like protease (3CLpro) and papain-like (PLpro).This work aims to find active components from of S. against SARS‑CoV‑2 3CLpro PLpro.The chemical constituents were retrieved based electronic databases, such as Web Science, PubMed, Medline Plus, CNKI. Molecular docking was used screen PLpro. Potential hit compounds further evaluated by enzymatic activity assay. Furthermore, anti-inflammatory activities explored using phorbol-12-myristate-13-acetate (PMA)-induced THP1 cells model.In this work, we 75 fruit, including 62 dibenzocyclooctadiene-type lignans, 3 diarylbutane-type 2 tetrahydrofuran-type 8 nortriterpenoids. Combining molecular study in vitro experiments, found that pregomisin (63), meso‑dihydroguaiaretic acid (64), nordihydroguaiaretic (65) could potently inhibit with IC50 values 3.07 ± 0.38, 4.12 6.06 0.62 μM, respectively, PLpro 5.23 0.33, 4.24 0.46, 16.28 0.54 respectively. Interestingly, 63, 64, 65 also have regulating inflammatory response vitro.Our results suggest may be promising SARS-CoV-2 inhibitors anti-inflammatory.

Язык: Английский

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IRF1 Mediates Growth Arrest and the Induction of a Secretory Phenotype in Alveolar Epithelial Cells in Response to Inflammatory Cytokines IFNγ/TNFα

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3463 - 3463

Опубликована: Март 19, 2024

In COVID-19, cytokine release syndrome can cause severe lung tissue damage leading to acute respiratory distress (ARDS). Here, we address the effects of IFNγ, TNFα, IL-1β and IL-6 on growth arrest alveolar A549 cells, focusing role IFN regulatory factor 1 (IRF1) transcription factor. The efficacy JAK1/2 inhibitor baricitinib has also been tested. WT IRF1 KO cells were exposed cytokines for up 72 h. Cell proliferation death evaluated with resazurin assay, analysis cell cycle cycle-regulator proteins, LDH Annexin-V positivity; induction senescence senescence-associated secretory phenotype (SASP) was through β-galactosidase staining quantitation secreted inflammatory mediators. While IL-1 proved ineffective, IFNγ plus TNFα caused a proliferative in alterations morphology, along acquisition phenotype. These STAT IRF1-dependent since they prevented by much less evident than cells. STATs/IRF1 axis is required cytokine-induced Hence, baricitininb promising therapeutic strategy attenuation inflammation.

Язык: Английский

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Characterizing the diabetes-induced pathological changes of the mouse lung by single-cell RNA sequencing

Life Sciences, Год журнала: 2025, Номер unknown, С. 123408 - 123408

Опубликована: Янв. 1, 2025

Язык: Английский

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