Cigarette Smoke-Induced Respiratory Response: Insights into Cellular Processes and Biomarkers

Antioxidants, Год журнала: 2023, Номер 12(6), С. 1210 - 1210

Опубликована: Июнь 3, 2023

Cigarette smoke (CS) poses a significant risk factor for respiratory, vascular, and organ diseases owing to its high content of harmful chemicals reactive oxygen species (ROS). These substances are known induce oxidative stress, inflammation, apoptosis, senescence due their exposure environmental pollutants the presence enzymes. The lung is particularly susceptible stress. Persistent stress caused by chronic CS can lead respiratory such as obstructive pulmonary disease (COPD), fibrosis (PF), cancer. Avoiding pollutants, like cigarette air pollution, help mitigate A comprehensive understanding impact on lungs requires future research. This includes identifying strategies preventing treating well investigating underlying mechanisms behind Thus, this review aims investigate cellular processes induced CS, specifically senescence, associated biomarkers. Furthermore, will delve into alveolar response provoked emphasizing roles potential therapeutic target markers in inflammation

Язык: Английский

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Pathophysiological mechanisms of ARDS: a narrative review from molecular to organ-level perspectives

Respiratory Research, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 13, 2025

Acute respiratory distress syndrome (ARDS) remains a life-threatening pulmonary condition with persistently high mortality rates despite significant advancements in supportive care. Its complex pathophysiology involves an intricate interplay of molecular and cellular processes, including cytokine storms, oxidative stress, programmed cell death, disruption the alveolar-capillary barrier. These mechanisms drive localized lung injury contribute to systemic inflammatory response multiple organ dysfunction syndrome. Unlike prior reviews that primarily focus on isolated mechanisms, this narrative review synthesizes key pathophysiological processes ARDS across molecular, cellular, tissue, levels. By integrating classical theories recent research advancements, we provide comprehensive analysis how mediators, metabolic reprogramming, immune dysregulation synergistically onset progression. Furthermore, critically evaluate current evidence-based therapeutic strategies, such as lung-protective ventilation prone positioning, while exploring innovative therapies, stem therapy, gene immunotherapy. We emphasize significance subtypes their inherent heterogeneity guiding development personalized treatment strategies. This provides fresh perspectives for future research, ultimately enhancing patient outcomes optimizing management approaches ARDS.

Язык: Английский

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Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment

Circulation Research, Год журнала: 2023, Номер 132(10), С. 1320 - 1337

Опубликована: Май 11, 2023

The current epidemic of corona virus disease (COVID-19) has resulted in an immense health burden that became the third leading cause death and potentially contributed to a decline life expectancy United States. severe acute respiratory syndrome-related coronavirus-2 binds surface-bound peptidase angiotensin-converting enzyme 2 (ACE2, EC 3.4.17.23) tissue infection viral replication. ACE2 is important enzymatic component renin-angiotensin system (RAS) expressed lung other organs. regulates levels peptide hormones Ang II Ang-(1–7), which have distinct opposing actions one another, as well cardiovascular peptides. A potential consequence reduced activity by internalization viral-ACE2 complex subsequent activation RAS (higher ratio II:Ang-[1–7]) may exacerbate inflammatory events COVID-19 patients possibly contribute effects long COVID-19. Moreover, present with array autoantibodies various components including II, ACE2, AT 1 Mas receptors. Greater severity also evident male patients, reflect underlying sex differences regulation functional arms RAS. review provides critical evaluation evidence for activated subjects whether this contributes greater males compared females.

Язык: Английский

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Ferroptosis and pyroptosis signatures in critical COVID-19 patients

Cell Death and Differentiation, Год журнала: 2023, Номер 30(9), С. 2066 - 2077

Опубликована: Авг. 15, 2023

Abstract Critical COVID-19 patients admitted to the intensive care unit (ICU) frequently suffer from severe multiple organ dysfunction with underlying widespread cell death. Ferroptosis and pyroptosis are two detrimental forms of regulated death that could constitute new therapeutic targets. We enrolled 120 critical in a two-center prospective cohort study monitor systemic markers ferroptosis, iron dyshomeostasis, pyroptosis, pneumocyte damage on first three consecutive days after ICU admission. Plasma 20 post-operative (PO) 39 healthy controls (HC) without failure served as controls. Subsets displayed increases individual biomarkers compared Unsupervised clustering was used discern latent clusters based biomarker profiles. Pyroptosis-related interleukin-18 accompanied by high independently associated higher odds at mechanical ventilation, while subgroup interleuking-1 beta (but limited death) reduced ventilation lower mortality hazard. Meanwhile, dyshomeostasis tendency towards ferroptosis marker malondialdehyde had no association outcome, except for small subset very catalytic survival. Forty percent did not have clear signature mechanisms studied this cohort. Moreover, repeated moderate levels soluble receptor advanced glycation end products growth differentiation factor 15 during admission adverse clinical outcome sustained levels. Altogether, data point distinct subgroups different signatures or outcomes ICU. The groups may allow ‘personalized’ treatment allocation

Язык: Английский

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Alveolar epithelial cells mitigate neutrophilic inflammation in lung injury through regulating mitochondrial fatty acid oxidation

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 22, 2024

Type 2 alveolar epithelial (AT2) cells of the lung are fundamental in regulating inflammation response to injury. Impaired mitochondrial long-chain fatty acid β-oxidation (mtLCFAO) AT2 is assumed aggravate acute injury (ALI), yet importance mtLCFAO cell function needs be defined. Here we show that expression carnitine palmitoyltransferase 1a (CPT1a), a rate limiting enzyme, significantly decreased respiratory distress syndrome (ARDS). In mice, Cpt1a deletion impairs without reducing ATP production and alters surfactant phospholipid abundance alveoli. Impairing via deleting either or Acadl (acyl-CoA dehydrogenase long chain) restricts ALI by hindering neutrophilic chemokine CXCL2 from cells. This study thus highlights as immunometabolism suggests impaired an anti-inflammatory ARDS. type thought Here, authors enzyme CPT1a syndrome, highlighting role this context.

Язык: Английский

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Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality

Cell Death and Differentiation, Год журнала: 2024, Номер 31(5), С. 544 - 557

Опубликована: Март 21, 2024

Abstract The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized this process might also or contribute to inflammatory disease lung failure following SARS-CoV-2 infection. To test hypothesis, developed a novel mouse-adapted model (MA20) recapitulates key pathological features of COVID-19. Concomitantly with occurrence FasL expression was significantly increased on monocytic macrophages NK cells the lungs MA20-infected mice. Importantly, therapeutic inhibition markedly survival both, young old mice coincident substantially reduced their lungs. Intriguingly, bronchoalveolar lavage fluid critically-ill patients. Together, these results identify as crucial host factor driving immuno-pathology underlies severity lethality, imply patients may benefit from FasL.

Язык: Английский

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Acute lung injury: a view from the perspective of necroptosis

Inflammation Research, Год журнала: 2024, Номер 73(6), С. 997 - 1018

Опубликована: Апрель 14, 2024

Язык: Английский

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Global prevalence of COVID-19-induced acute respiratory distress syndrome: systematic review and meta-analysis

Systematic Reviews, Год журнала: 2023, Номер 12(1)

Опубликована: Ноя. 13, 2023

Abstract Background Acute respiratory distress syndrome (ARDS) is potentially a fatal form of failure among COVID-19 patients. Globally, there are inconsistent findings regarding ARDS Therefore, this study aimed to estimate the pooled prevalence COVID-19-induced patients worldwide. Methods To retrieve relevant studies, authors searched Embase, MEDLINE, PubMed, Web Science, Cochrane Library, Google, and Google Scholar using combination search terms. The was conducted for articles published from December 2019 September 2022. Articles were screened by title (ti), abstract (ab), full-text (ft) two reviewers independently. quality each included article assessed Newcastle–Ottawa Assessment Scale. Data entered into Microsoft Word exported Stata version 14 analysis. Heterogeneity detected Q statistics I -square ( 2 ). Then sources variations identified subgroup meta-regression A random effect meta-analysis model used. publication bias graphic asymmetry test funnel plot and/or Egger’s p value < 0.05). treat potential bias, trim fill analysis computed. protocol has been registered in an international database, Prospective Register Systematic Reviews (PROSPERO) with reference number: CRD42023438277. Results total 794 studies worldwide their eligibility. Of these 11 2845 participants systematic review meta-analysis. overall world found be 32.2% (95%CI = 27.70–41.73%), 97.3%, 0.001). Conclusion high. virus remains global burden because its genetic causes constantly changing or it mutated throughout pandemic emerge new strain infection. interventions such as massive vaccination, early case detection, screening, isolation, treatment cases need implemented tackle severity.

Язык: Английский

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RAGE engagement by SARS-CoV-2 enables monocyte infection and underlies COVID-19 severity

Cell Reports Medicine, Год журнала: 2023, Номер 4(11), С. 101266 - 101266

Опубликована: Ноя. 1, 2023

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has fueled the COVID-19 pandemic with its enduring medical and socioeconomic challenges because subsequent waves long-term consequences great concern. Here, we chart molecular basis pathogenesis by analyzing patients' immune responses at single-cell resolution across disease course severity. This approach confirms cell subpopulation-specific dysregulation in severity identifies a severity-associated activation receptor for advanced glycation endproducts (RAGE) pathway monocytes. In vitro THP1-based experiments indicate that monocytes bind SARS-CoV-2 S1-receptor binding domain (RBD) via RAGE, pointing to RAGE-Spike interaction enabling monocyte infection. Thus, our results demonstrate RAGE is functional contributing

Язык: Английский

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COVID-19 Biogenesis and Intracellular Transport

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(5), С. 4523 - 4523

Опубликована: Фев. 24, 2023

SARS-CoV-2 is responsible for the COVID-19 pandemic. The structure of and most its proteins have been deciphered. enters cells through endocytic pathway perforates endosomes’ membranes, (+) RNA appears in cytosol. Then, starts to use protein machines host their membranes biogenesis. generates a replication organelle reticulo-vesicular network zippered endoplasmic reticulum double membrane vesicles. viral start oligomerize are subjected budding within ER exit sites, virions passed Golgi complex, where glycosylation appear post-Golgi carriers. After fusion with plasma membrane, glycosylated secreted into lumen airways or (seemingly rarely) space between epithelial cells. This review focuses on biology SARS-CoV-2’s interactions transport Our analysis revealed significant number unclear points related intracellular SARS-CoV-2-infected

Язык: Английский

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