COPD-Journal of Chronic Obstructive Pulmonary Disease
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2023
·
IF 2.2
Chuanxin Yang,Libing Deng,Fang Bao,Hui Jiang,Long Zhang
Chronic obstructive pulmonary disease (COPD) is a difficult-to-cure disease that mainly affects the respiratory system. Inhaled anesthetic drug such as sevoflurane plays a controversial role in COPD by different concentration, but the underlying epigenetic mechanism remains unclear. Here, we prepared lipopolysaccharide (LPS)-induced COPD rat model, and isolated Alveolar type II (ATII) cells. We mainly focused DNA methylation on the promoter of COPD-related genes including Sftpa1, Napsa, Ca2, Sfta2, Lamp3, Wif1, Pgc, and Etv5. We observed COPD rat treated by sevoflurane with low (0.5%) and high (2%) concentrations displayed an opposite DNA methylation pattern. These six genes' promoter were all hypomethylated by 0.5% sevoflurane whereas hypermethylated by 2% sevoflurane, accompanied with the opposite transcriptional activity. We further verified that the DNMT1 binding ability contributed to DNA methylation these six genes' promoter. Moreover, we also captured DNMT1 and identified REC8 meiotic recombination protein (REC8) as the specific binding protein only existed in ATII cells treated with 0.5% sevoflurane rather than 2% and control. The binding ability of REC8 on these target genes' promoter showed highly positive correlation with DNMT1. In summary, we uncovered a potential epigenetic role of sevoflurane with low concentration in ATII cells of COPD that may help us deeply understand the pathogenesis and treatment mechanism of inhaled anesthesia drugs in COPD via a dose-dependent manner.
研究领域:
肺病学
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分子生物学
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表观遗传学
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药理学
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DOI
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 8
·e70566
·
IF 4.2
Ying‐jie Ren,Tian‐qi Sun,Yu Lu,Dan‐Li Liu,Rui Gao,Ting Li,Min Guo,Qing‐hua Liu,Hai‐long Wang,Min Pang
Chronic obstructive pulmonary disease (COPD) is a widespread lung disease marked by alveolar wall damage, leading to inflammation and fibrosis. Key risk factors include age, smoking, sex, and education, with smoking being the most crucial. These factors are globally consistent and linked with aging. Club cell secretory protein 16 (CC16), primarily secreted by non‐ciliated bronchial epithelial cells, is crucial for pulmonary health, offering anti‐inflammatory and antioxidant benefits. CC16 levels are notably reduced in COPD, suggesting its enhancement as a potential treatment. In this study, cellular senescence of BEAS‐2B cells was stimulated using cigarette smoke extract (CSE) and the function of recombinant human CC16 protein (rhCC16) in cellular senescence was assessed by detecting the levels of β‐galactosidase, p16, p21, ROS and the underlined mechanism was revealed by measuring mitochondrial biogenesis and metabolism. Additionally, COPD mice were prepared, and rhCC16's role on the cellular senescence of lung tissues was examined. Our findings showed that rhCC16 ameliorated cellular senescence in BEAS‐2B cells and lung tissues of COPD mice accompanied by lower levels of β‐galactosidase, p16, p21 and ROS. Mechanically, rhCC16 mitigated senescence via triggering PGC‐1α expression through the AMPK/SIRT1 pathway and fostering mitochondrial biogenesis and metabolism to reduce the levels of ROS. Furthermore, the results also indicated that rhCC16 exerted its effect via both integrin α4β1 and clathrin‐mediated endocytosis. Collectively, rhCC16 suppresses cellular senescence and ameliorates COPD‐like symptoms by activating the AMPK/Sirt1‐PGC‐1‐α‐TFAM pathway to foster mitochondrial function.
研究领域:
医学
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生物学
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呼吸系统疾病
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR MEDICINE-JMM
·
2024
·
IF 4.8
Wang Pengtao,Tao Wei,Li Qiujie,Ma Wanting,Jia Wei,Kang Yuting
Indole-3-aldehyde (I3A) is an intestinal microbial metabolite that regulates inflammation in various inflammatory diseases; however, its role in chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to investigate the anti-inflammatory effects and molecular mechanisms of I3A in COPD. We constructed in vivo models using cigarette smoke (CS)-stimulated mice and in vitro models using cigarette smoke extract (CSE)-stimulated MH-S cells. The results demonstrated that I3A significantly alleviated bronchial obstruction in mice with COPD and reduced the expression of inflammatory factors such as TNF-α, IL-1β, and IL-6. Additionally, I3A decreased the levels of matrix metalloproteinases MMP2, MMP12, and inhibited the NF-κB p65/NLRP3 pathways. Further investigation revealed that I3A inhibited NF-κB activity by suppressing p65 phosphorylation and nuclear translocation in CSE-stimulated MH-S cells. The activation of the NF-κB and NLRP3 signaling pathways is mediated by histone deacetylase 5 (HDAC5) and HDAC6, both of which are inhibited by I3A. Subsequent experiments indicated that aryl hydrocarbon receptor (AHR) knockdown attenuated the inhibitory effect of I3A on pro-inflammatory cytokines and the HDACs/NF-κB/NLRP3 signaling pathways, highlighting the dependence of I3A's anti-inflammatory effects on the AHR receptor. Key messages
I3A effectively reduced lung inflammation in COPD mice by inhibiting the NF-κB pathway.
In CSE-stimulated MH-S cells, I3A suppressed p65 phosphorylation and nuclear translocation, thereby inhibiting NF-κB activity.
The activation of the NF-κB/NLRP3 pathways by HDAC5 and HDAC6 was diminished by I3A.
Through the activation of the AHR receptor, I3A suppressed the activities of HDAC5/6, leading to a decrease in inflammatory factor levels.
Graphical abstract
研究领域:
呼吸病学
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免疫学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Bei Jia,Jiachen He,Ying Zhang,Wenli Dang,Bin Xing,Mengru Yang,Haonan Xie,Jiawei Li,Zhidong Liu
Chronic obstructive pulmonary disease (COPD) is a prevalent lung condition characterized by airflow obstruction, disability, and high mortality rates. Magnolol (MA), known for its anti-inflammatory and antioxidant properties, holds the potential for alleviating COPD symptoms. However, MA faces challenges like poor aqueous solubility and low bioavailability. Herein MA-loaded nanostructured lipid carriers (MA-NLC) were prepared using emulsification and solvent evaporation. These carriers exhibited a particle size of (19.67 ± 0.36) nm, a polydispersity index of (0.21 ± 0.01), and a zeta potential of (−5.18 ± 0.69) mV. The fine particle fraction of MA-NLC was (68.90 ± 0.07)%, indicating minimal lung irritation and enhanced safety. Pulmonary delivery of MA-NLC via nebulizer actively targeted the diseased lung tissues, facilitated slow release, and overcame the challenges of low oral absorption and bioavailability associated with MA. This formulation prolonged the residence time of MA and optimized its therapeutic effect in pulmonary tissues. Upon pulmonary administration, MA-NLC effectively regulated inflammatory and oxidative stress markers in COPD models, demonstrating its potential as a promising therapeutic platform for COPD management.
研究领域:
药学
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肺科学
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纳米技术
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药物递送系统
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DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2024
·Vol. 30
·期 1
·1-16
·
IF 6
Xie Bin,Chen Qiong,Dai Ziyu,Jiang Chen,Chen Xi
Background Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with high morbidity and mortality worldwide. Oxidative injury and mitochondrial dysfunction in the airway epithelium are major events in COPD progression.Methods and resultsThe therapeutic effects of Progesterone (P4) were investigated in vivo and in vitro in this study. In vivo, in a cigarette smoke (CS) exposure-induced COPD mouse model, P4 treatment significantly ameliorated CS exposure-induced physiological and pathological characteristics, including inflammatory cell infiltration and oxidative injury, in a dose-dependent manner. The c-MYC/SIRT1/PGC-1α pathway is involved in the protective function of P4 against CS-induced COPD. In vitro, P4 co-treatment significantly ameliorated H2O2-induced oxidative injury and mitochondrial dysfunctions by promoting cell proliferation, increasing mitochondrial membrane potential, decreasing ROS levels and apoptosis, and increasing ATP content. Moreover, P4 co-treatment partially attenuated H2O2-caused inhibition in Nrf1, Tfam, Mfn1, PGR-B, c-MYC, SIRT1, and PGC-1α levels. In BEAS-2B and ASM cells, the c-MYC/SIRT1 axis regulated P4’s protective effects against H2O2-induced oxidative injury and mitochondrial dysfunctions.Conclusion P4 activates the c-MYC/SIRT1 axis, ameliorating CS-induced COPD and protecting both airway epithelial cells and smooth muscle cells against H2O2-induced oxidative damage. PGC-1α and downstream mitochondrial signaling pathways might be involved.
研究领域:
呼吸病学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Changfeng Yin,Yushan Tian,An Yan,Hongjuan Wang,Fengjun Lu,Xianmei Li,Xiao Li,Shulei Han,Ruijuan Miao,Huan Chen,Di Li,Hongwei Hou,Qingyuan Hu
Introduction Chronic obstructive pulmonary disease (COPD) is a disease with severe therapeutic obstacles and high worldwide death rate. COPD progresses predominantly through inflammatory response followed by fibrotic destruction. Quercetin (Que), recognized for its anti-inflammatory effects, presents significant promise as a therapeutic candidate for COPD therapy. However, poor water solubility and low bioavailability of Que hinder its further clinical application. Liposomes are renowned for their unique structure and function, which provided an efficient approach for the delivery of Que in various drug delivery systems. This study was aim to prepare a novel Que liposome (Que-lipo) and administrated via intratracheal (i.t.) with cigarette smoke induced COPD mice. The underlying therapeutic mechanisms against lung damage of Que-lipo were explored. Methods Que-lipo were prepared based on thin film dispersion method and administrated via intratracheal administration. The cigarette smoke induced COPD mice were established and a comprehensive approach was employed to explore the inflammation, pulmonary function and histopathology of lung after i.t. administration of Que-lipo, including enzyme-linked immunosorbent assay, histopathology and immunohistochemistry, reverse transcription-quantitative polymerase chain reaction. Results and discussion Que-lipo not only improved the solubility and biocompatibility of Que but also demonstrated effective cellular uptake in vitro . The inflammation, pulmonary function and pathological condition of lung were improved after i.t. administration of Que-lipo. Que-lipo also regulated the expression of key apoptosis-associated proteins such as Bcl-2 and caspase-3/7, leading to significant inhibition of apoptotic activity in COPD. Furthermore, Que-lipo markedly enhanced its ability to alleviate lung inflammation and fibrosis symptoms by modulating inflammation-related factors and fibrosis signaling molecules. The potential mechanisms of Que-lipo in treating COPD were elucidated, including the suppression of the NLRP3/IL-1β inflammasome pathway and the TGF-β1-related fibrosis signaling pathway.
研究领域:
药理学
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呼吸病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Yuezhu Wang,Xianqiang Yu,Ruikai Qi,Cheng Fan,Mengxiao Zhong,Zhengjie Chen,Xiaofeng Lu
Electrocatalytic nitrate reduction reaction (NO 3 RR) to ammonia (NH 3 ) provides a promising, environmentally benign, and energy-efficient strategy to eliminate nitrate (NO 3 − ) pollution within the nitrogen cycle while simultaneously producing a valuable chemical feedstock. Herein, we report the synthesis of bimetallic CoPd alloy nanoparticles embedded within carbon nanofibers (CNFs) via a two-step electrospinning and carbonization approach, designed specifically for high-performance NO 3 RR. The interconnected CNFs provide robust structural support, ensuring excellent catalyst stability and cycling performance. Remarkably, the optimized Co 2 Pd 1 -CNF catalyst delivers exceptional NO 3 RR activity, achieving a high NH 3 yield rate of 43.6 ± 0.7 mg h −1 cm −2 at −0.7 V vs. RHE, alongside outstanding long-term stability exceeding 100 h of continuous operation, greatly surpassing not only the single-metallic Co-CNF and Pd-CNF but also most recently reported NO 3 RR electrocatalysts. Moreover, the integration of Co 2 Pd 1 -CNFs as the cathode into an aqueous Zn-NO 3 − battery demonstrates its practical utility, yielding an impressive power density of 9.28 mW cm −2 . This work highlights CoPd-CNFs as a highly efficient and durable catalyst for sustainable NO 3 − removal, simultaneously enabling valuable ammonia synthesis and demonstrating promising applicability in next-generation energy storage devices.
研究领域:
电催化
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环境化学
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能量存储
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纳米材料
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可持续化学
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产品关联
DOI
PubMed
高影响因子
RESPIRATORY RESEARCH
·
2026
·Vol. 27
·期 1
·103
·
IF 5.7
Ge Shaobo,Li Rui,Li Yuer,Liu Jin,Yao Shiyuan,Zhang Rui,Sun Yuanliang,Zhang Tao,Zhang Jie,Zhang Ming
Background Oxidative stress contributes to airway mucus hypersecretion in the pathogenesis of chronic obstructive pulmonary disease (COPD). Although reactive oxygen species modulator 1 (ROMO1) is involved in mitochondrial oxidative stress, its role in airway mucus hypersecretion in COPD remains unclear. Methods The protein expression of ROMO1 and mucin5AC (MUC5AC) in human airway epithelium was determined by immunohistochemistry. The effects of ROMO1 on mitochondrial injury and MUC5AC expression in cigarette smoke extract (CSE)-treated airway epithelial cells were evaluated by a series of experimental techniques, including real-time PCR, western-blot and immunofluorescent staining. Results Protein expression of ROMO1 and MUC5AC was significantly elevated in the airway epithelium of COPD patients compared with the controls. The mRNA and protein expression of ROMO1 and MUC5AC were significantly increased in concentration- and time-dependent manners when airway epithelial cells were treated with CSE. ROMO1 silencing significantly suppressed 7.5% CSE-induced mitochondrial structure damage, mitochondrial membrane potential loss, intracellular ATP depletion, mitochondrial reactive oxygen species production, signal transducer and activator of transcription 6 (STAT6) phosphorylation, and MUC5AC expression in airway epithelial cells. Moreover, pretreatment with either a mitochondrial-targeted antioxidant or STAT6 inhibitor significantly inhibited the up-regulated expression of p-STAT6/STAT6 and MUC5AC in airway epithelial cells stimulated with 7.5% CSE. Conclusion Our findings suggest that ROMO1 contributes to airway mucus hypersecretion in COPD by mediating MUC5AC expression in airway epithelial cells via the mitochondrial ROS-STAT6 pathway, thereby highlighting its potential clinical value as a therapeutic target.
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DOI
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2018
·Vol. 22
·期 7
·3514-3525
·
IF 4.302
Wenhui Cui,Zhihui Zhang,Panpan Zhang,Jiao Qu,Cheng Zheng,Xiaoting Mo,Wencheng Zhou,Liang Xu,Hongwei Yao,Jian Gao
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and abnormal inflammatory response. Wnt/β-catenin and AMP-activated protein kinase (AMPK) have been shown to modulate lung inflammatory responses and injury. However, it remains elusive whether Wnt/β-catenin and AMPK modulate nuclear factor erythroid-2 related factor-2 (Nrf2)-mediated protective responses during the development of emphysema. Here we showed that treatment with a Wnt pathway activator (LiCl) reduced elastase-induced airspace enlargement and cigarette smoke extract (CSE)-induced lung inflammatory responses in WT mice, which was associated with increased activation of Nrf2 pathway. Interestingly, these effects of LiCl were not observed in Nrf2 −/− mice exposed to elastase. In normal human bronchial epithelial (NHBE) cells, Wnt3a overexpression up-regulated, whereas Wnt3a knockdown further down-regulated the levels of Nrf2 and its target proteins heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) by CSE treatment. In contrast, Nrf2 deficiency did not have any effects on Wnt/β-catenin pathway in mouse lungs and NHBE cells. Both elastase and CSE exposures reduced AMPK phosphorylation. A specific AMPK activator metformin increased Wnt3a, β-catenin, Nrf2 phosphorylation and activation but reduced the levels of IL-6 and IL-8 in NHBE cells and mouse lungs exposed to CSE. Furthermore, Nrf2 deficiency abolished the protection of metformin against CSE-induced increase in IL-6 and IL-8 in NHBE cells. In conclusion, Nrf2 mediates the protective effects of both Wnt3a/β-catenin and AMPK on lung inflammatory responses during the development of COPD/emphysema. These findings provide potential therapeutic targets for the intervention of COPD/emphysema.
研究领域:
医学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
International Journal of Chronic Obstructive Pulmonary Disease
·
2024
·
IF 2.7
Liguo Lu,Chengdong Zhu,Jian Xu,Yulan Hu,Juxiang Dai,Sheng Wang,Tao Wei
Introduction The Lifei Decoction (LD) is a commonly utilized Chinese medicine for the treatment of sepsis and bronchial inflammation. However, its therapeutic potential in chronic obstructive pulmonary disease (COPD) remains unknown. Therefore, the objective of this study was to investigate the therapeutic efficacy and underlying mechanism of LD in a mouse model of COPD induced by cigarette smoke (CS) combined with lipopolysaccharide (LPS).Methods Hematoxylin-eosin (H&E) staining was employed to observe the pathological alterations in lung tissue, while ELISA was utilized for the detection of levels of inflammatory factors in both lung tissue and bronchoalveolar lavage fluid (BALF). Additionally, Western blot analysis was conducted to assess the expression of p-NF-κB, GDF11, ZO-1, and Occludin-1 proteins. The changes in intestinal flora were evaluated using the viable bacteria count method.Results The administration of LD demonstrates significant efficacy in mitigating pulmonary tissue damage in a murine model, while concurrently inhibiting the activation of the inflammatory pathway NF-κB to attenuate the levels of pro-inflammatory factors. Moreover, LD exhibits the capacity to enhance the expression of intestinal functional proteins ZO-1 and Occludin-1, thereby rectifying dysbiosis within the gut microbiota.Conclusion The LD shows great promise as a potential treatment for COPD.
研究领域:
药理学
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呼吸病学
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免疫学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Letters in Drug Design & Discovery
·
2026
·
IF 1.6
Liqun Liu,Minhong Peng,Yuanfeng Lai,Weibin Chen,Yiwen Du,Xingyu Chen,Tian Zhang
CMR ameliorates lung histopathological injury, oxidative stress, and inflammatory response in COPD rats. • CMR suppresses EMT and ERS in a rat model of COPD. • CMR suppresses TGF-β1-induced fibroblast migration and invasion through the inhibition of ERS. • CMR alleviates TGF-β1-induced oxidative stress, inflammation, and fibrosis in fibroblasts via ERS inhibition. • CMR inhibits TGF-β1-induced fibroblast activation by suppressing the ERS pathway. Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition defined by persistent airway inflammation. While traditional Chinese medicine offers distinct advantages in its management, the pharmacological effects and mechanisms of cortex mori radices (CMR) in COPD remain largely unexplored. Methods A cigarette smoke-induced COPD rat model and a transforming growth factor‑β1 (TGF‑β1)‑stimulated MRC‑5 fibroblast model were established. To evaluate the therapeutic effects, multiple endpoint indicators were assessed, including histopathology by hematoxylin‑eosin (HE) staining; oxidative stress markers including malondialdehyde (MDA), glutathione peroxidase (GSH‑Px), and superoxide dismutase (SOD); inflammatory cytokines including tumor necrosis factor‑α (TNF‑α), interleukin‑6 (IL‑6), interleukin‑1β (IL‑1β), and monocyte chemoattractant protein‑1 (MCP‑1); and fibrosis and fibroblast activation by Transwell assay, wound healing assay, quantitative real‑time PCR (qRT‑PCR), and Western blot. Results Animal experiments confirmed that CMR alleviated lung injury in COPD rats, inhibited oxidative stress (reduced MDA levels and increased GSH-Px and SOD activities) and inflammatory factor levels (TNF-α, IL-6, IL-1β, MCP-1) ( P < 0.001), upregulated E-cadherin expression, and downregulated N-cadherin, COL-1, ATF6, GRP78, and XBP1 ( P < 0.05, P < 0.01, P < 0.001). Furthermore, in vitro rescue experiments using tunicamycin (TM) confirmed that endoplasmic reticulum stress (ERS) was successfully reactivated. Upon ERS activation, the CMR‑mediated inhibitory effects on TGF‑β1‑induced fibroblast activation, migration, invasion, oxidative stress, and inflammation were significantly reversed ( P < 0.05, P < 0.01, P < 0.001). Conclusion This study elucidates the mechanism by which CMR inhibits fibroblast inflammation and enhances lung function in COPD, highlighting its clinical potential as a promising candidate drug for combating COPD. Download: Download high-res image (205KB) Download: Download full-size image
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DOI
高影响因子
METHODS
·
2025
·
IF 4.3
Wensi Li,Zhichao Tang,Xiang Zhu,Beijuan Wang,Xiuqin Zhang,Ze Ji,Suhang Cheng
In this work, an electrochemiluminescence (ECL) biosensor integrating T7 RNA polymerase amplification and CRISPR/Cas13a-mediated signal enhancement was developed for the ultrasensitive detection of matrix metalloproteinase-2 (MMP-2), a key biomarker associated with chronic inflammatory diseases such as COPD. A peptide nucleic acid (PNA) probe was designed to respond specifically to MMP-2 cleavage, enabling the release of DNA templates for subsequent T7 RNA polymerase-driven transcription amplification. The generated RNA triggers the collateral cleavage activity of CRISPR/Cas13a, resulting in a significant amplification of the ECL signal. The biosensor’s surface was constructed using a AuNPs/Ti 3 C 2 Tx/Ru(II)-PEI nanocomposite, which enhanced signal transduction and stability. Under optimized conditions, the proposed biosensor achieved a detection limit as low as 62.05 fM, demonstrating superior sensitivity compared to conventional methods, as summarized in Table 1 . The platform also exhibited excellent specificity and anti-interference capability, ensuring reliable detection of MMP-2 in complex biological samples. This study provides a simple yet highly efficient strategy for enzymatic biomarker detection, offering great potential for clinical applications in early disease diagnosis and monitoring.
研究领域:
生物传感器
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分子诊断
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CRISPR技术
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纳米技术
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慢性阻塞性肺疾病
·
酶检测
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）