Inhalable Carbonyl Sulfide Donor-Hybridized Selective Phosphodiesterase 10A Inhibitor for Treating Idiopathic Pulmonary Fibrosis by Inhibiting Tumor Growth Factor-β Signaling and Activating the cAMP/Protein Kinase A/cAMP Response Element-Binding Protein (CREB)/p53 Axis DOI Creative Commons

Quan Wang,

Xinyue Liu,

Yuan Han

и другие.

ACS Pharmacology & Translational Science, Год журнала: 2024, Номер 8(1), С. 256 - 269

Опубликована: Дек. 28, 2024

Idiopathic pulmonary fibrosis (IPF) is a debilitating, incurable, and life-threatening disease that lacks effective therapy. The overexpression of phosphodiesterase 10A (PDE10A) plays vital role in (PF). However, the impact selective PDE10A inhibitors on tumor growth factor-β (TGF-β)/small mother against decapentaplegic (Smad) signaling pathway remains unclear. Herein, we have exploited novel carbonyl sulfide (COS)/hydrogen (H2S)-donor hybrid inhibitor called COS-2080 with well-defined mechanism H2S-releasing action. It exhibited highly potent inhibitory activity excellent PDE subfamily selectivity. Moreover, demonstrated significant antifibrotic effects by inhibiting cell proliferation mitigating fibroblast-to-myofibroblast transition (FMT). A dry powder inhalation formulation COS-2080-DPI has been developed using ultrasonic spray freeze drying (USFD) technique, demonstrating efficacy mice bleomycin-induced PF at dosage approximately 600 times lower than pirfenidone. This remarkable TGF-β1-induced FMT could be primarily attributed to its inhibition Smad2/Smad3 phosphorylation. effectively attenuated MRC-5 cells activating cAMP/protein kinase (PKA)/CREB potentially increasing levels p53 protein. Our findings suggest confers protective effect impeding TGF-β cAMP/PKA/CREB/p53 axis.

Язык: Английский

Pathophysiologie der Fibrose – entzündlich vs. nichtentzündlich DOI

Elena Neumann,

Philipp Klemm

Deleted Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Fibrosis is characterized by an excessive accumulation of extracellular matrix components produced connective tissue cells. It a pathophysiological feature many chronic inflammatory diseases. Nearly every the body can be affected fibrosis. Its progression lead to dysfunction and organs potentially death. Early fibrotic mechanisms include activation immune responses leading cells misdirected wound healing responses, finally scarring Different pathways factors contribute pathophysiology fibrosis are summarized in this review.

Язык: Английский

Процитировано

0
3,4-Dimethoxycinnamic acid from coffee silverskin biowaste ameliorates bleomycin-induced pulmonary fibrosis via modulating caveolin-1-dependent activation of NF-κB, TGF-β1/Smad3, and ERK1/2 signaling pathways DOI
Mahmoud Elshal, Abdelrahman Hamdi,

Iya Khalil

и другие.

Toxicology and Applied Pharmacology, Год журнала: 2025, Номер 501, С. 117414 - 117414

Опубликована: Май 25, 2025

Язык: Английский

Процитировано

0
Synthesis, anticancer evaluation, and electrochemical investigation of new chiral pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides DOI Creative Commons
Mateusz Kciuk,

Gabriela Machura,

Somdutt Mujwar

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Май 28, 2025

Язык: Английский

Процитировано

0
Respiratory Pathophysiology Through the Lens of Mitochondria DOI Open Access
Masafumi Noguchi, Keiko Iwata, Norihito Shintani

и другие.

Clinical bioenergetics, Год журнала: 2025, Номер 1(1), С. 4 - 4

Опубликована: Июнь 5, 2025

Mitochondrial integrity is indispensable for pulmonary cellular homeostasis, with its dysfunction increasingly being implicated as a central mechanism in the etiology of respiratory disorders. We present comprehensive overview integral role played by mitochondrial dynamics, such fusion, fission, mitophagy, intracellular trafficking, and biogenesis, maintaining homeostasis. This study further explores how perturbations these processes contribute to pathogenesis diverse lung disorders, including chronic obstructive disease (COPD), bronchopulmonary dysplasia (BPD), arterial hypertension (PAH), idiopathic fibrosis (IPF), drug-induced disease. It disorders—for example, (COPD; responsible roughly 55% cases), (BPD; affecting up 45% infants born before 29 weeks gestation), (PAH; rare condition causing about 22,000 deaths worldwide 2021), (IPF; 0.33–4.51 cases per 10,000 persons), Evidence demonstrates that mitochondria-triggered apoptosis, metabolic shifts, subsequent inflammatory signaling act together drive airway tissue remodeling fibrotic progression across diseases. Furthermore, this review evaluates therapeutic potential mitochondrial-targeted drugs, MitoQ SS31, metformin, which have shown promise basic preclinical studies. Preclinical early clinical evaluations include an ongoing trial antioxidant (NCT02966665, phase 1) COPD, 4-month open-label DCA PAH patients, studies determining efficacy SS-31 metformin IPF models. Ultimately, integrating biomarkers into practice holds not only facilitate detection but also enable development precision therapies, thereby offering renewed hope patients afflicted

Язык: Английский

Процитировано

0
Erythropoietin Reduces Inflammation, Oxidative Stress, and Apoptosis in a Rat Model of Bleomycin-Induced Idiopathic Pulmonary Fibrosis DOI Open Access
Drosos Tsavlis, Kalliopi Domvri, Κonstantinos Porpodis

и другие.

Journal of Personalized Medicine, Год журнала: 2024, Номер 14(9), С. 972 - 972

Опубликована: Сен. 13, 2024

Background: Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial disease with unknown etiology and no effective cure, posing great health burden to society. Erythropoietin (EPO) has been demonstrated have protective roles in various tissues such as brain, spinal cord, heart, kidney lung tissues. In this study, we investigate the specific anti-inflammatory, antioxidant antiapoptotic effects of erythropoietin on tissue bleomycin-induced rat model idiopathic fibrosis. Methods: Recombinant human EPO or saline was injected, animals were monitored for 14 days after bleomycin instillation. Their hematocrit serum levels determined. Histological immunohistochemical analyses performed. Results: The extent injury, determined through morphometric analysis, significantly decreased size treated erythropoietin. An analysis expression cyclooxygenase-2 (COX-2), inducible synthase nitric oxide (i-NOS), metalloproteinase-9 (MMP-9), receptor (EPO-R), cytochrome-C (cyt-C) found these enzymes be statistically significant manner when compared non-treated group. Conclusions: reduced COX-2, i-NOS, MMP-9, EPO-R, i-NOS indicates action erythropoietin, suggesting its potential therapeutic role

Язык: Английский

Процитировано

0
Effect of ethyl acetate extract of the whole plant Clerodendrum phlomidis on improving bleomycin (BLM)-induced idiopathic pulmonary fibrosis (IPF) in Rats: In vitro and in vivo research DOI
Rajendra Sangaraju, Sukesh Narayan Sinha, Sathish Kumar Mungamuri

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 145, С. 113688 - 113688

Опубликована: Дек. 6, 2024

Язык: Английский

Процитировано

0
Inhalable Carbonyl Sulfide Donor-Hybridized Selective Phosphodiesterase 10A Inhibitor for Treating Idiopathic Pulmonary Fibrosis by Inhibiting Tumor Growth Factor-β Signaling and Activating the cAMP/Protein Kinase A/cAMP Response Element-Binding Protein (CREB)/p53 Axis DOI Creative Commons

Quan Wang,

Xinyue Liu,

Yuan Han

и другие.

ACS Pharmacology & Translational Science, Год журнала: 2024, Номер 8(1), С. 256 - 269

Опубликована: Дек. 28, 2024

Idiopathic pulmonary fibrosis (IPF) is a debilitating, incurable, and life-threatening disease that lacks effective therapy. The overexpression of phosphodiesterase 10A (PDE10A) plays vital role in (PF). However, the impact selective PDE10A inhibitors on tumor growth factor-β (TGF-β)/small mother against decapentaplegic (Smad) signaling pathway remains unclear. Herein, we have exploited novel carbonyl sulfide (COS)/hydrogen (H2S)-donor hybrid inhibitor called COS-2080 with well-defined mechanism H2S-releasing action. It exhibited highly potent inhibitory activity excellent PDE subfamily selectivity. Moreover, demonstrated significant antifibrotic effects by inhibiting cell proliferation mitigating fibroblast-to-myofibroblast transition (FMT). A dry powder inhalation formulation COS-2080-DPI has been developed using ultrasonic spray freeze drying (USFD) technique, demonstrating efficacy mice bleomycin-induced PF at dosage approximately 600 times lower than pirfenidone. This remarkable TGF-β1-induced FMT could be primarily attributed to its inhibition Smad2/Smad3 phosphorylation. effectively attenuated MRC-5 cells activating cAMP/protein kinase (PKA)/CREB potentially increasing levels p53 protein. Our findings suggest confers protective effect impeding TGF-β cAMP/PKA/CREB/p53 axis.

Язык: Английский

Процитировано

0