Bilateral diffuse alveolar damage contributes to the fatal toxicity of pre-existing interstitial lung disease mice after partial thoracic irradiation DOI Creative Commons

Jiamei Fu,

Xinglong Liu, Yuchuan Zhou

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Abstract Background Lung cancer patients with comorbid interstitial lung disease (LC-ILD) have an increased risk of developing severe or even fatal radiation pneumonitis after thoracic radiotherapy. However, the underlying mechanisms its pathogenesis are still inconclusive. No approved biomarker medicine is available to prevent pulmonary toxicities in LC-ILD patients. Appropriate management for them remains a challenge clinicians due treatment-related complications. Methods To elucidate histopathological characteristics and molecular responsible this toxicity in vivo, C57BL/6J mice were used develop different injury models, including radiation-induced (RILI), bleomycin-induced fibrosis (BIPF), radiation-related (sRRLI) murine model. Biopsy examination was performed on hematoxylin eosin (H&E), Masson’s trichrome, immunohistochemistry-stained tissue sections. Changes function measured. RNA extracted from mouse tissues sequenced Illumina Novaseq platform. Results A model irradiation built based pre-existing ILD induced by BLM administration. Enhanced observed sRRLI model, higher mortality loss within six months compared mono-treatment groups. Autopsy revealed that bilateral diffuse alveolar damage (DAD) overlap exudative, proliferative, fibrosing patterns usually presented The histological phenotypes manifested exudative DAD phase early proliferating pattern predominated late phase. Bioinformatic analysis showed signaling pathways relevant immune cell migration, epithelial development, extracellular structure organization commonly activated models. Furthermore, involvement cells infiltration macrophages CD4 + lymphocytes validated during extensive remodeling group. They also participated triggering remarkable abscopal responses non-IR contralateral lungs. Conclusions study provides preclinical better understand mice. progressive inflammation lungs contributed complications partial irradiation. More studies needed investigate potential strategies rescue

Language: Английский

Triptolide Alleviates Acute Lung Injury by Reducing Mitochondrial Dysfunction Mediated Ferroptosis Through the STAT3/p53 Pathway DOI

Jia Zhou,

Sanzhong Li,

Yuting Yang

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

2
Pulmonary drug delivery devices and nanosystems as potential treatment strategies for acute respiratory distress syndrome (ARDS) DOI Creative Commons
Clarence T. Dhege, Pradeep Kumar, Yahya E. Choonara

et al.

International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: 657, P. 124182 - 124182

Published: April 30, 2024

Language: Английский

Citations

7
Synthesis, evaluation and mechanism study of novel pyrazole enamides to alleviate lung injury DOI
Guoping Zhang, Mengjie Li,

Yanghui Ou

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 282, P. 117068 - 117068

Published: Nov. 15, 2024

Language: Английский

Citations

4
Development of delayed pulmonary toxicities and transcriptional changes in pre-existing interstitial lung disease mice after partial thoracic irradiation DOI Creative Commons

Jiamei Fu,

Xinglong Liu, Yuchuan Zhou

et al.

Radiation Oncology, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 7, 2025

Lung cancer patients with comorbid interstitial lung disease (LC-ILD) have an increased risk of developing severe or even fatal radiation pneumonitis after thoracic radiotherapy. However, the underlying mechanisms its pathogenesis are still inconclusive. No approved biomarker medicine is available to prevent pulmonary toxicities in LC-ILD patients. Appropriate management for them remains a challenge clinicians due treatment-related complications. To elucidate histopathological characteristics and molecular responsible this toxicity vivo, C57BL/6J mice were used develop different injury models, including radiation-induced (RILI), bleomycin-induced fibrosis (BIPF), radiation-related (sRRLI) murine model. Biopsy examination was performed on hematoxylin eosin (H&E), Masson's trichrome, immunohistochemistry-stained tissue sections. Changes function measured. RNA extracted from mouse tissues sequenced Illumina Novaseq platform. A model irradiation built based pre-existing ILD induced by BLM administration. Enhanced observed sRRLI model, higher mortality loss within six months compared mono-treatment groups. Autopsy revealed that bilateral diffuse alveolar damage (DAD) overlap exudative, proliferative, fibrosing patterns usually presented The histological phenotypes manifested exudative predominated DAD phase early proliferating pattern late phase. Bioinformatic analysis showed signaling pathways relevant immune cell migration, epithelial development, extracellular structure organization commonly activated models. Furthermore, involvement cells infiltration macrophages CD4 + lymphocytes validated during extensive remodeling group. Delayed effects significantly declined high progressive inflammation lungs contributed complications partial irradiation. hyperactivation inflammatory responses clarified long-term toxicities. More studies needed investigate potential strategies rescue

Language: Английский

Citations

0
Kirenol ameliorates endotoxin-induced acute lung injury by inhibiting the ERK and JNK phosphorylation–mediated NFκB pathway in mice DOI
Frank Cheau‐Feng Lin, Shih‐Pin Chen, Sheng‐Di Lin

et al.

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Language: Английский

Citations

0
Rutin ameliorates LPS-induced acute lung injury in mice by inhibiting the cGAS-STING-NLRP3 signaling pathway DOI Creative Commons
Xin Zhou, Zhibin Wang,

Yuting Wang

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: May 8, 2025

Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), represent critical failures with high mortality rates limited treatment options. While the flavonoid rutin exhibits documented anti-inflammatory antioxidant properties, therapeutic mechanisms in ALI/ARDS remain unclear. This study investigated rutin's efficacy against lipopolysaccharide (LPS)-induced ALI mice, a mechanistic focus on cGAS-STING pathway NLRP3 inflammasome activation. Male C57BL/6 mice were divided into Vehicle control, LPS induction, + co-treatment, Rutin monotherapy groups. was induced by intratracheal challenge, administered via gavage. Proteomics analysis, histological evaluation, immunohistochemistry, TUNEL staining, immunofluorescence, RT-qPCR, western blot, ELISA, oxidative stress assays performed to assess effects of ARDS. The proteomic profiling tissues from LPS-challenged identified significant dysregulation proteins integral cascade pyroptotic processes. Gene ontology KEGG analyses underscored pivotal role immune inflammatory responses ALI, particularly cytosolic DNA-sensing NOD-like receptor signaling pathways. administration significantly alleviated LPS-induced injury, reducing stress, apoptosis, proinflammatory cytokine levels (IL-6, IL-1β, TNF-α). Mechanistically, demonstrated dual suppression: 1) inhibiting activation through decreased expression cGAS, STING, phosphorylation TBK1/IRF3 (P<0.05), 2) attenuating NLRP3-mediated pyroptosis downregulation NLRP3-ASC-caspase1-GSDMD (P<0.05). Pharmacological STING inhibition (C-176) validated cGAS-STING-NLRP3 regulatory hierarchy pathogenesis. These findings elucidate novel mechanism coordinated suppression axis, positioning it as promising candidate for intervention.

Language: Английский

Citations

0
Resolvin D4 mitigates lipopolysaccharide-induced lung injury in mice DOI Creative Commons

R. Inomata,

Hironobu Tsubouchi, Toshifumi Takao

et al.

Prostaglandins Leukotrienes and Essential Fatty Acids, Journal Year: 2024, Volume and Issue: 203, P. 102652 - 102652

Published: April 1, 2024

Language: Английский

Citations

2
Macrophage‑driven pathogenesis in acute lung injury/acute respiratory disease syndrome: Harnessing natural products for therapeutic interventions (Review) DOI Creative Commons

Jincun Li,

Wenyu Ma,

Zilei Tang

et al.

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 31(1)

Published: Nov. 4, 2024

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a common disease characterized by hypoxemia and distress. It associated with high morbidity mortality. Due to the complex pathogenesis of ALI, clinical management patients ALI/ARDS challenging, resulting in numerous post‑treatment sequelae compromising quality life patients. Macrophages, as class innate immune cells, play an important role ALI/ARDS. In recent years, functions phenotypes macrophages have been better understood due development flow cytometry, immunofluorescence, single‑cell sequencing spatial genomics. However, no macrophage‑targeted drugs for treatment currently exist practice. Natural products are drug development, it has shown that natural compounds from herbal medicine can alleviate caused various factors modulating macrophage abnormalities. present review, modulate abnormalities treat introduced, their mechanisms action, discovered previous five years (2019‑2024), presented. This will provide novel ideas directions further research, develop new

Language: Английский

Citations

1
Application of Nanobiomedicine in Acute Lung Injury DOI

Doudou Lei,

B Wang,

Mingjing Yin

et al.

Journal of Biomaterials and Tissue Engineering, Journal Year: 2024, Volume and Issue: 14(3), P. 115 - 129

Published: March 1, 2024

The respiratory system plays a crucial role in human life activities, and acute lung injury (ALI) is highly fatal disease caused by variety of reasons. At present, although several preclinical studies have demonstrated the efficacy pharmacological interventions, supportive care mechanical ventilation still remain primary modalities for managing ALI, there are no safe effective treatments ALI. With rapid development nanotechnology, nanobiomedicines with different structures functional moieties been well-designed based on their targeting ability pathophysiology In this review, it summarizes challenges faced ALI therapy, introduces including liposomes, polymers, inorganic materials, others to bring therapeutic effects discusses research progress recent years nanobiomedicine applied injury. Finally, provides summary prospect application

Language: Английский

Citations

0
Bilateral diffuse alveolar damage contributes to the fatal toxicity of pre-existing interstitial lung disease mice after partial thoracic irradiation DOI Creative Commons

Jiamei Fu,

Xinglong Liu, Yuchuan Zhou

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Abstract Background Lung cancer patients with comorbid interstitial lung disease (LC-ILD) have an increased risk of developing severe or even fatal radiation pneumonitis after thoracic radiotherapy. However, the underlying mechanisms its pathogenesis are still inconclusive. No approved biomarker medicine is available to prevent pulmonary toxicities in LC-ILD patients. Appropriate management for them remains a challenge clinicians due treatment-related complications. Methods To elucidate histopathological characteristics and molecular responsible this toxicity in vivo, C57BL/6J mice were used develop different injury models, including radiation-induced (RILI), bleomycin-induced fibrosis (BIPF), radiation-related (sRRLI) murine model. Biopsy examination was performed on hematoxylin eosin (H&E), Masson’s trichrome, immunohistochemistry-stained tissue sections. Changes function measured. RNA extracted from mouse tissues sequenced Illumina Novaseq platform. Results A model irradiation built based pre-existing ILD induced by BLM administration. Enhanced observed sRRLI model, higher mortality loss within six months compared mono-treatment groups. Autopsy revealed that bilateral diffuse alveolar damage (DAD) overlap exudative, proliferative, fibrosing patterns usually presented The histological phenotypes manifested exudative DAD phase early proliferating pattern predominated late phase. Bioinformatic analysis showed signaling pathways relevant immune cell migration, epithelial development, extracellular structure organization commonly activated models. Furthermore, involvement cells infiltration macrophages CD4 + lymphocytes validated during extensive remodeling group. They also participated triggering remarkable abscopal responses non-IR contralateral lungs. Conclusions study provides preclinical better understand mice. progressive inflammation lungs contributed complications partial irradiation. More studies needed investigate potential strategies rescue

Language: Английский

Citations

0