JAK2 inhibitor protects the septic heart through enhancing mitophagy in cardiomyocytes

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117279 - 117279

Published: Aug. 8, 2024

Sepsis-induced myocardial dysfunction (SIMD) is a severe complication in sepsis, manifested as systolic dysfunction, which associated with poor prognosis and higher mortality. Mitophagy, self-protective mechanism maintaining cellular homeostasis, plays an indispensable role cardioprotection. This study aimed to unveil the cardioprotective effects of Baricitinib on LPS-induced its effect mitophagy. Herein, we demonstrated that LPS induced initiated mitophagy septic mice hearts. Despite initiation mitophagy, significant number apoptotic cells damaged mitochondria persisted myocardium, energy metabolism remained impaired, indicating limited was insufficient mitigate damage. The JAK2-AKT-mTOR signaling pathway activated cardiomyocytes hearts mice. administration remarkably improved cardiac function, suppressed systemic inflammatory response, attenuated histopathological changes, inhibited cell apoptosis alleviated damage Furthermore, treatment significantly enhanced PINK1-Parkin-mediated increased autophagosomes, decreased impaired mitochondria, restored metabolism. Mechanically, myocardium p-ULK1 (Ser757), regulated by p-mTOR. reduced (Ser757) inhibiting pathway. Inhibition Mdivi-1 reversed protective anti-inflammatory These findings suggest attenuates SIMD enhancing via pathway, providing novel mechanistic therapeutic insight into SIMD.

Language: Английский

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Single-cell transcriptomics reveals CD8+ T cell structure and developmental trajectories in idiopathic pulmonary fibrosis

Molecular Immunology, Journal Year: 2024, Volume and Issue: 172, P. 85 - 95

Published: June 26, 2024

Immune cells in the human lung are associated with idiopathic pulmonary fibrosis. However, contribution of different immune cell subpopulations to pathogenesis fibrosis remains unclear. We used single-cell RNA sequencing data investigate transcriptional profiles lungs 5 IPF patients and 3 subjects non-fibrotic lungs. In an identifiable population cells, we found increased percentage CD8+ T subpopulation IPF. Monocle analyzed dynamic status transformation as well cytotoxicity exhausted at stages. Among differences metabolic pathways Ctrl, including lipid, amino acid carbohydrate metabolic. By analyzing metabolites that populations have unique characteristics, but they also multiple identical up-regulated or down-regulated metabolites. IPF, signaling were enriched suggesting may important Finally, interactions between other cells. Together, these studies highlight key features help develop effective therapeutic targets.

Language: Английский

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Qingfei Tongluo Mixture Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis through mTOR-Dependent Autophagy in Rats

Mediators of Inflammation, Journal Year: 2024, Volume and Issue: 2024, P. 1 - 11

Published: Feb. 8, 2024

As an interstitial fibrosis disease characterized by diffuse alveolitis and structural alveolar disorders, idiopathic pulmonary (IPF) has high lethality but lacks limited therapeutic drugs. A hospital preparation used for the treatment of viral pneumonia, Qingfei Tongluo mixture (QFTL), is rumored to have protective effects against inflammatory respiratory disease. This study aims confirm whether it a effect on bleomycin-induced IPF in rats elucidate its mechanism action. Male SD were randomly divided into following groups: control, model, CQ + QFTL (84 mg/kg chloroquine (CQ) 3.64 g/kg QFTL), QFTL-L, M, H (3.64, 7.28, 14.56 g/kg, respectively) pirfenidone (PFD 420 mg/kg). After induction modeling drug intervention, blood samples lung tissue collected further detection. Body weight coefficient examined, combined with hematoxylin eosin (H&E) Masson staining observe lesions. The enzyme-linked immunosorbent assay (ELISA) hydroxyproline (HYP) kit detect changes proinflammatory factors (transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)) HYP. Immunohistochemistry Western blotting performed proteins related (α-smooth muscle actin (α-SMA) matrix metalloproteinase 12 (MMP12)) autophagy (P62 mechanistic target rapamycin (mTOR)). Treatment significantly improved adverse bleomycin body weight, coefficient, pathological changes. Then, reduced increases mediators expression marker are attenuated QFTL. Furthermore, inhibitor reversed downward trend HYP levels α-SMA protein expression, which BLM-induced rats. In conclusion, could effectively attenuate inflammation through mTOR-dependent Therefore, potential be alternative clinical practice.

Language: Английский

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Understanding the molecular regulatory mechanisms of autophagy in lung disease pathogenesis

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 31, 2024

Lung disease development involves multiple cellular processes, including inflammation, cell death, and proliferation. Research increasingly indicates that autophagy its regulatory proteins can influence programmed proliferation, innate immune responses. Autophagy plays a vital role in the maintenance of homeostasis adaptation eukaryotic cells to stress by enabling chelation, transport, degradation subcellular components, organelles. This process is essential for sustaining balance ensuring health mitochondrial population. Recent studies have begun explore connection between different lung diseases. article reviews latest findings on molecular mechanisms diseases, with an emphasis potential targeted therapies autophagy.

Language: Английский

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Construction of the pulmonary bio-adhesive delivery system of nintedanib nanocrystalline for effective treatment of pulmonary fibrosis

International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: 660, P. 124302 - 124302

Published: June 5, 2024

Language: Английский

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