α-Bisabolol alleviates diesel exhaust particle-induced lung injury and mitochondrial dysfunction by regulating inflammatory, oxidative stress, and apoptotic biomarkers through the c-Jun N-terminal kinase signaling pathway

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 3, 2025

Exposure to particulate matter ≤2.5 μm in diameter (PM2.5) is associated with adverse respiratory outcomes, including alterations lung morphology and function. These associations were reported even at concentrations lower than the current annual limit of PM2.5. Inhalation PM2.5, which diesel exhaust particles (DEPs) a major component, induces inflammation oxidative stress. α-Bisabolol (BIS) bioactive dietary phytochemical various pharmacological properties, anti-inflammatory antioxidant actions. Here, we evaluated possible protective effects BIS on DEP-induced injury. Mice exposed DEPs (20 µg/mouse) or saline (control) by intratracheal instillation. was administered orally two doses (25 50 mg/kg) approximately 1 h before DEP exposure. Twenty-four hours after administration, multiple endpoints evaluated. administration observed prevent airway hyperreactivity methacholine; influx macrophages, neutrophils, lymphocytes bronchoalveolar lavage fluid; increases epithelial endothelial permeabilities. exposure caused levels myeloperoxidase, proinflammatory cytokines, stress markers tissue homogenates, all these abated treatment. The activities mitochondrial complexes I, II, III, IV markedly increased lungs mice DEPs, significantly reduced BIS-treated group. Intratracheal instillation induced DNA damage increase apoptotic marker cleaved caspase-3. latter prevented treated DEPs. Moreover, mitigated expression phospho-c-Jun N-terminal kinase (JNK) dose-dependent manner. alleviated injury regulating inflammatory, stress, biomarkers through JNK signaling pathway. Following additional studies, may be considered as plausible agent against inhaled-particle-induced pulmonary effects.

Язык: Английский

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Mitochondrial Dysfunction in Chronic Obstructive Pulmonary Disease: Unraveling the Molecular Nexus

Biomedicines, Год журнала: 2024, Номер 12(4), С. 814 - 814

Опубликована: Апрель 7, 2024

Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory disorder characterized by persistent airflow limitation chronic inflammation. In recent years, the role of mitochondrial dysfunction in COPD pathogenesis has emerged as focal point investigation. This review endeavors to unravel molecular nexus between COPD, delving into intricate interplay oxidative stress, bioenergetic impairment, genetics, downstream cellular consequences. Oxidative consequence dysfunction, explored driving force behind inflammation, exacerbating cascade events leading progression. Bioenergetic impairment sheds light on systemic consequences impacting functions contributing overall energy imbalance observed patients. navigates through genetic landscape, elucidating DNA mutations, variations, haplogroups susceptibility severity. Cellular consequences, including apoptosis, autophagy, senescence, are examined, providing insights mechanisms which influences pathology. Therapeutic implications, spanning antioxidant strategies, mitochondria-targeted compounds, lifestyle modifications, discussed context translational research. Important future directions include identifying novel biomarkers, advancing therapies, embracing patient-centric approaches redefine management. abstract provides comprehensive overview our review, offering roadmap for understanding addressing with potential implications precision medicine improved patient outcomes.

Язык: Английский

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An integrated investigation of mitochondrial genes in COPD reveals the causal effect of NDUFS2 by regulating pulmonary macrophages

Biology Direct, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 9, 2025

Despite the increasing body of evidence that mitochondrial activities implicate in chronic obstructive pulmonary disease (COPD), we are still far from a causal-logical and mechanistic understanding malfunctions COPD pathogenesis. Differential expression genes (DEGs) six publicly available bulk human lung tissue transcriptomic datasets patients were intersected with known mitochondria-related MitoCarta3.0 to obtain DEGs associated (MitoDEGs). The 32 hub MitoDEGs identified protein-protein interaction (PPI) networks demonstrated superior overall diagnostic efficacy non-hub MitoDEGs. Random forest (RF) analysis, least absolute shrinkage selection operator (LASSO) regression, Mendelian Randomization (MR) analysis further nominated NDUFS2, CAT, MRPL2 as causal for COPD, whose predominate expressions macrophages revealed by an independent single-cell dataset lungs. Finally, NDUFS2 was evaluated top-ranked contributor nomogram model its downregulation could result pro-inflammatory secretion, enhanced intercellular communications, whereas depressed phagocytosis gene set variation (GSVA) cell-cell (CCI) lungs, which later confirmed mouse macrophage cell lines. Our study established linkage between providing potential therapeutic avenue alleviate inflammation accounting targeting genes. canonical component electron respiratory chain, highlighted instrumental susceptibility risk-exposed individuals COPD.

Язык: Английский

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Mitochondrial fusion protein: a new therapeutic target for lung injury diseases

Frontiers in Physiology, Год журнала: 2025, Номер 16

Опубликована: Март 19, 2025

Mitochondria are essential organelles responsible for cellular energy supply. The maintenance of mitochondrial structure and function relies heavily on quality control systems, including biogenesis, fission, fusion. Mitochondrial fusion refers to the interconnection two similar mitochondria, facilitating exchange DNA, metabolic substrates, proteins, other components. This process is crucial rescuing damaged mitochondria maintaining their normal function. In mammals, involves sequential steps: outer membrane fusion, regulated by mitofusin 1 2 (MFN1/2), inner mediated optic atrophy (OPA1). Dysfunction in has been implicated development various acute chronic lung injuries. Regulating dynamics, improving effective strategies mitigating tissue damage. study reviews expression regulatory mechanisms proteins injuries different etiologies, explores relationship with injury diseases, offers a theoretical foundation developing novel therapeutic approaches targeting injury.

Язык: Английский

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A potential therapeutic approach for ulcerative colitis: targeted regulation of mitochondrial dynamics and mitophagy through phytochemicals

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 7, 2025

Mitochondria are important organelles that regulate cellular energy and biosynthesis, as well maintain the body's response to environmental stress. Their dynamics autophagy influence occurrence of function, particularly under stressful conditions. They can generate reactive oxygen species (ROS) which is a major contributor inflammatory diseases such ulcerative colitis (UC). In this review, we discuss key effects mitochondrial mitophagy on pathogenesis UC, with particular focus metabolism, oxidative stress, apoptosis, immunoinflammatory activities. The therapeutic efficacy existing drugs phytochemicals targeting pathway discussed reveal insights for developing strategies treating UC. addition, new molecular checkpoints potential identified. We show integration biology clinical aspects UC may ideas enhancing management

Язык: Английский

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Drp1–associated genes implicated in sepsis survival

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 8, 2025

Sepsis is a severe and life-threatening medical syndrome that can lead to organ failure death. Despite advances in treatment, current therapies are often inadequate, with high septic mortality rates. Therefore, there critical need for reliable prognostic markers be used clinical settings improve the management outcomes of patients sepsis. Recent studies have suggested mitochondrial dynamics, including processes fission fusion, closely related severity sepsis status inflammation. By monitoring transcriptomic signals new biomarkers engineered more accurately predict survival risk. Such would invaluable settings, aiding healthcare providers early identification high-risk improving treatment strategies. To achieve this goal, we utilized major regulatory protein dynamin-related 1 (Drp1, gene code DNM1L) identified Drp1-associated genes enriched genes. A 12-gene signature (GS) was established as differentially expressed (DEG)-based GS. Next, compared proteins interact Drp1 7 common genes, establishing GS term protein-protein interaction (PPI)-based evaluate if these GSs survival, publicly available human blood datasets from patients. We confirmed both successfully discovery validation cohorts sensitivity specificity, PPI-based showing enhanced performance. Together, study engineers validated blood-borne biomarker (PPI-based 7-gene GS) risk prediction. This holds potential optimizing personalized strategies reduce mortality.

Язык: Английский

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Update of Aging Hallmarks in Idiopathic Pulmonary Fibrosis

Cells, Год журнала: 2025, Номер 14(3), С. 222 - 222

Опубликована: Фев. 5, 2025

Idiopathic Pulmonary Fibrosis (IPF) is an epithelial-driven interstitial lung disease of unknown etiology characterized by the excessive proliferation fibroblast populations that synthesize large amounts extracellular matrix. In this devastating disorder, all aging hallmarks appear prematurely or are altered. This review highlights key findings about IPF characteristics recently recognized as aging, including mechanical alterations, inflammaging, dysbiosis, alternative splicing, and disabled macroautophagy. It also revisits classic which encompass stem cell exhaustion, cellular senescence, altered intercellular communication. Enhancing our understanding fundamental processes underlie in may facilitate development innovative experimental strategies to improve therapeutic outcomes.

Язык: Английский

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Lithospermic acid etched ZIF-8 nanoparticles delays osteoarthritis progression by inhibiting inflammatory signaling pathways and rescuing mitochondrial damage

Materials Today Bio, Год журнала: 2025, Номер 31, С. 101589 - 101589

Опубликована: Фев. 21, 2025

Osteoarthritis (OA) is the most common chronic inflammatory joint disease. Improving microenvironment expected to promote early intervention and delay progression of OA. However, effective strategies for inhibiting OA-related inflammation are still lacking. Lithospermic acid (LA), a polycyclic phenol carboxylic extracted from salvia miltiorrhiza, has strong anti-inflammatory antioxidant effects. its role in treatment OA underlying mechanisms unclear. To improve bioavailability LA, an LA synergistic protects etched zeolitic imidazolate framework (ZIF)-8 nanoparticles (LA@ZIF-8) was designed developed targeted delivery modulate This study confirmed that LA@ZIF-8 inhibits pro-inflammatory phenotype RAW264.7 macrophages through NF-ĸB signaling pathway, effectively alleviates mitochondrial dysfunction, delays articular cartilage degeneration caused by mediated synoval macrophages. In summary, synovial macrophage-mediated responses, highlighting clinical application potential.

Язык: Английский

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Aerosolized nicotine-free e-liquid base constituents exacerbates mitochondrial dysfunction and endothelial glycocalyx shedding via the AKT/GSK3β-mPTP pathway in lung injury models

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

Опубликована: Март 1, 2025

Smoking has been recognized as a risk factor of cancer, heart disease, stroke, diabetes, and lung diseases such chronic obstructive pulmonary nicotine appears to be the responsible component tobacco smoke that affects development. While nicotine-free electronic cigarettes (e-cigarettes) are often promoted safer alternative traditional smoking, recent evidence suggests they might pose significant health risks. This study investigates effects e-cigarette vapor (ECV) on tissue endothelial function. A mouse model ECV-induced injury human microvascular cells (HPMVECs) were utilized evaluate impact ECV exposure mitochondrial function, cell viability, glycocalyx shedding. significantly damages tissue, characterized by alveolar enlargement, inflammation, vascular remodeling, indicative emphysematous changes. In vitro, HPMVECs exposed extract (ECE) demonstrated dose-dependent increases in reactive oxygen species (ROS), membrane depolarization, mPTP opening, reduced ATP production, leading enhanced permeability degradation. The inhibition opening with Cyclosporin (CsA) was found mitigate dysfunction damage induced ECE, indicating protective role preserving integrity. AKT/GSK3β signaling pathway identified key regulator these processes, ECE downregulating p-AKT p-GSK3β, thereby promoting opening. Activation AKT partially reversed effects, highlighting potential targeting AKT/GSK3β-mPTP axis adverse These findings underscore risks associated e-cigarettes suggest novel therapeutic targets for preventing progression.

Язык: Английский

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Nicotinamide mononucleotide combined with PJ-34 protects microglial cells from lipopolysaccharide-induced mitochondrial impairment through NMNAT3-PARP1 axis

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 6, 2025

Lipopolysaccharide (LPS) is known to induce cell injury and mitochondrial dysfunction, which are pivotal in neuroinflammation related disorders. Recent studies have demonstrated the potential of nicotinamide mononucleotide (NMN) poly(ADP-ribose) polymerase-1 (PARP1) inhibitors enhance function. However, underlying mechanisms not been fully elucidated. This study investigates impact NMN conjunction with PJ-34, a PARP1 inhibitor, on LPS-induced damage, focusing adenylyl transferase 3 (NMNAT3) -PARP1 axis. The results showed that LPS treatment led down-regulation NMNAT3 (decreased 58.72% at 1 µM), up-regulation (enhanced 22.78% thereby impairing mitophagy negative effects can be mitigated through supplementation PJ-34. Specifically, compared group, expression increased by 63.29% decreased 27.94% concentration 400 µM NMN. Additionally, when was combined 5 21.99%. Mechanistic reveal PJ-34 counteracted detrimental promoting binding FoxO1 PINK1 promoter activate PINK1/Parkin mediated pathway. Further experimental demonstrate inhibit initiation autophagic processes. Consequently, targeting NMNAT3-PARP1 signaling pathway holds promise for development novel therapeutic strategies alleviate damage-related

Язык: Английский

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