INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Wen-Jing Zhong,Chen-Yu Zhang,Jia-Xi Duan,Meng-Rui Chen,Ping-Deng,Bo-Liang Zhang,Nan-Shi-Yu Yang,Han-Xi Sha,Jun Zhang,Jian-Bing Xiong,Cha-Xiang Guan,Yong Zhou
Pulmonary fibrosis (PF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia, occurring primarily in older adults with poor prognosis. Alveolar epithelial cell (AEC) senescence is the critical pathological mechanism of PF. However, the molecular mechanisms regulating AEC senescence in PF are incompletely understood. Herein, we provided evidence to support the function of Krüppel-like factor 14 (KLF14), a novel Krüppel-like transcription factor, in the regulation of AEC senescence during PF. We confirmed that the expression of KLF14 was up-regulated in PF patients and mice treated with bleomycin (BLM). KLF14 knockdown resulted in more pronounced structural disruption of the lung tissue and swelling of the alveolar septum, which led to significantly increased mortality in BLM-induced PF mice. Mechanistically, RNA-seq analysis indicated that KLF14 decreased the senescence of AECs by inhibiting endoplasmic reticulum (ER) stress. Furthermore, the pharmacological activation of KLF14 conferred protection against PF in mice. In conclusion, our findings reveal a protective role for KLF14 in preventing AECs from senescence and shed light on the development of KLF14-targeted therapeutics for PF.
研究领域:
肺病学
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分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
·
2019
·
IF 4.067
Jingjing Liu,Jie Meng,Liming Cao,Yuanyuan Li,Pengbo Deng,Pinhua Pan,Chengping Hu,Huaping Yang
Treatment of chronic lung infection becomes a great challenge due to the drug resistant bacteria. In this scenario, evolving a new drug based on lipid metal conjugation loaded with potential antibiotic provides better drug delivery. In this study, ciprofloxacin loaded selenium-lipid nanoparticle (CxLSENPs) is produced in a novel route and its antimicrobial properties were tested against clinically important Gram-negative P. aeruginosa . The synthesized CxLSENPs was characterized by biophysical techniques (UV, Fluorescence spectroscopy , Raman spectroscopy , FTIR , FESEM , HRTEM and Zeta potential). Raman spectra coupled with FTIR spectra confirmed the possible interaction of lipid components in the NPs. HRTEM analysis confirmed the spherical shape of NPs. CxLSENPs recorded greater antibacterial effects on P. aeruginosa . A drastic reduction in the count of P. aeruginosa was observed after treatment with CxLSENPs. In order to further confirm the antibacterial efficiency, the live/dead cell assay was carried out. Live/dead analysis helps us to investigate the viability of bacterial cells . The number of dead bacterial cells was significantly higher in CxLSENPs treated groups when compare to the control. Furthermore, CxLSENPs increased the antioxidant enzyme activities (SOD, GPx, CAT and LPO) in mouse and protected the liver damage from bacterial infection. This study concludes that the developed CxLSENPs might be employed as strong antimicrobial and antioxidant agents for treating lung infection or interstitial lung diseases .
研究领域:
药剂学
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微生物学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2022
·
IF 7.31
Xinye Wang,Ran Huo,Zhongjie Liang,Congcong Xu,Tingting Chen,Jingjing Lin,Luyao Li,Wei Lin,Bingting Pan,Xiaoqin Fu,Shangqin Chen
Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly found in premature infants. Excessive inflammation and oxidative stress contribute to BPD occurrence and development. Simvastatin, as an inhibitor of HMG-CoA reductase, has been reported to have antioxidative and anti-inflammatory effects. However, its effect and possible mechanisms in hyperoxia-induced lung injury are rarely reported. In this study, in vivo and in vitro experiments were conducted to investigate whether simvastatin could ameliorate hyperoxia-induced lung injury and explore its potential mechanism. For the in vivo study, simvastatin could improve alveolar development after hyperoxic lung injury and reduce hyperoxic stress and inflammation. The in vitro study revealed that simvastatin can reduce inflammation in A549 cells after high-oxygen exposure. Simvastatin suppressed NLRP3 inflammasome activation and played anti-inflammatory and antioxidant roles by increasing KLF2 (Krüppel-like factor 2) expression. In vitro experiments also revealed that these effects of simvastatin were partially reversed by KLF2 shRNA, indicating that KLF2 was involved in simvastatin effects. In summary, our findings indicate that simvastatin could downregulate NLRP3 inflammasome activation and attenuate lung injury in hyperoxia-induced bronchopulmonary dysplasia via KLF2-mediated mechanism.
研究领域:
儿科
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肺科学
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药理学
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炎症
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氧化应激
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Zimin Cai,Qin Wang,Jinzhuan Xu,Jia Zhou,Zhaohui Jiang,Di Pan,Yanyan Zhang,Ling Tao,Jianqing Peng,Yi Chen,Xiangchun Shen
Emphysema is a type of chronic obstructive pulmonary disease (COPD) usually leading to difficulty breathing. It is highly in need of effective interventions to prevent airspace damage and stretch. Herein, we studied the protective effect of 1,8-cineole (CIN) on porcine pancreatic elastase (PPE)-induced emphysema in mice via quantitative pulmonary administration. To overcome the volatility, instability and poor water solubility of CIN that limits its pharmacological activities in vivo , a hyaluronic acid (HA)-coated liposome was prepared to encapsulate CIN (Lipo/ [email protected] ), which facilitated the delivery of CIN to lung tissue and improved its therapeutic effect for emphysema. A Microsprayer Ⓡ aerosolizer was used to deliver free CIN and its liposomal preparations every other day for four weeks and evaluate the therapeutic effects on emphysema in mice. The results clearly showed that CIN significantly reduced the level of inflammation and oxidative stress, resulting in less lung cell apoptosis. Compared with the free CIN and Lipo/CIN, Lipo/ [email protected] exhibited superior protective effects on mice to prevent the PPE-induced emphysema. Furthermore, the therapeutic mechanisms were verified to be mainly mediated by Nrf2/NQO1 and NF-κB/IκBα pathways. In conclusion, quantitative pulmonary administration of CIN could alleviate the progression of emphysema and the therapeutic effects were further improved by the HA-coated liposome carrier.
研究领域:
药理学
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肺病学
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药物递送系统
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分子生物学
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产品关联
DOI
高影响因子
Frontiers in Medicine
·
2025
·
IF 3
Jianing Sun,Di Zhang,Panpan Wang,Junhan Shi,Tan Xue,Panpan Zhang,Qi Wang,Xinjing Gui,Suyun Li,Jiansheng Li,Xuelin Li,Ruixin Liu
Purpose: This study aims to identify the transdermal penetration components of Shufeitie ointment (SFTOT) and investigate the potential active components and mechanisms through which SFTOT exerts its effects on Chronic Obstructive Pulmonary Disease (COPD).Methods: An in vitro permeation test (IVPT) of SFTOT was conducted using a modified Franz diffusion cell method. Ultra-high-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap/MS) was employed to analyze data from the transdermal receiving solution, enabling comprehensive identification of the components that permeate through the skin. To predict the potential mechanisms by which SFTOT may treat COPD, network pharmacology was used to construct a component-target-collaterals network. Additionally, molecular docking was applied to verify the interactions between the potential transdermal active components of SFTOT and the core targets.Results: Using UHPLC-Q-Orbitrap/MS, we identified 129 transdermal permeation components in SFTOT. Network pharmacology analysis revealed 222 common targets between SFTOT and COPD. The primary active components were predicted to be luteolin, kaempferol, quercetin, 7-O-methylluteolin, apigenin, ferulic acid, palmitic acid, inapinic acid, 6-shogaol, and myristic acid. These components were primarily enriched in the AGE-RAGE, TNF, PI3K-Akt, and MAPK signaling pathways. Protein–protein interaction (PPI) analysis identified TNF, ALB, AKT1, EGFR, and CASP3 as core targets. Molecular docking results showed that 72% of component-target interactions had a binding energy of < −5.0 kcal/mol, indicating strong binding activity. Among these, apigenin exhibited the lowest binding energy with EGFR and consistently lower binding energies with other core targets compared to the other components. This suggests that apigenin may play a key role in treatment.Conclusion: High-resolution liquid chromatography-mass spectrometry effectively identified the transdermal penetration components of SFTOT, providing a foundation for further screening of key active compounds. Our findings suggest that SFTOT may alleviate COPD by downregulating TNF, ALB, AKT1, EGFR, and CASP3 while inhibiting inflammatory mediator release through the AGE-RAGE, TNF, PI3K-Akt, and MAPK signaling pathways. These effects may help reduce COPD-related symptom clusters. Notably, apigenin appears to be a crucial bioactive component in the prevention and treatment of COPD.
研究领域:
药理学
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呼吸系统疾病
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药物分析
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Animal Diseases
·
2021
·Vol. 1
·期 1
·1-13
·
IF 0
Yang Xiaoqi,Fu Yang,Wu Lianfeng,Li Antong,Ji Luyao,Li Hao,Peng Yuxuan,Zhang Jiabin,Zhou Donghai,Zhou Huiping
The major cause of pulmonary vascular remodeling in broilers is abnormal proliferation of vascular smooth muscle cells (VSMCs), and one of the main causes of pulmonary hypertension syndrome (PHS) in broilers is pulmonary artery vascular remodeling. Forty Arbor Acres (AA) broilers were randomly divided into four groups ( n = 10): a control group (deionized water, 0 g/L NaCl), a freshwater group (FW, deionized water + 1 g/L NaCl), highly salinized freshwater group 1 (H-SFW-1, deionized water + 2.5 g/L NaCl) and highly salinized freshwater group 2 (H-SFW-2, deionized water + 5 g/L NaCl). The results of in vivo experiments showed that vascular smooth muscle of the broilers could be significantly proliferated by intake of high-salinity fresh water (H-SFW-1 & H-SFW-2), which significantly increased the content of angiotensin II (Ang II) and the expression of angiotensin II type 1 (AT1) receptor protein. Meanwhile, it significantly decreased the expression of dopamine receptor D4 (DRD4) protein. The results of in vitro experiments showed that exogenous Ang II induced the proliferation of primary VSMCs in broilers, which could be significantly inhibited by DRD4 agonists (D4A, HY-101384A) and enhanced by DRD4 inhibitors (D4I, HY-B0965). In addition, the results of immunoblotting and fluorescence quantitative PCR showed that AT1 receptors could be negatively regulated by DRD4 in VSMCs of broilers, either at the transcriptional or translational level. At the same time, the expression of AT1 receptor could be increased by DRD4 inhibition by D4I and decreased by DRD4 activation by D4A. The negative regulatory effect of DRD4 on AT1 receptor occurred in a dose-dependent manner. These results indicate that long-term intake of highly salinized fresh water can cause PHS in broilers, accompanied by varying degrees of proliferation of pulmonary artery smooth muscle. This mechanism may involve response of its receptor being induced by increased Ang II, while DRD4 can negatively regulate it.
研究领域:
兽医学
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生理学
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分子生物学
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药理学
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DOI
FEBS Journal
·
2019
·Vol. 287
·期 8
·1666-1680
·
IF 4.739
Chen-Yu Zhang,Jia-Xi Duan,Hui-Hui Yang,Chen-Chen Sun,Wen-Jing Zhong,Jia-Hao Tao,Xin-Xin Guan,Hui-Ling Jiang,Bruce D. Hammock,Sung Hee Hwang,Yong Zhou,Cha-Xiang Guan
Pulmonary fibrosis (PF) is a senescence-associated disease with poor prognosis. Currently, there is no effective therapeutic strategy for preventing and treating the disease process. Mounting evidence suggests that arachidonic acid (ARA) metabolites are involved in the pathogenesis of various fibrosis. However, the relationship between the metabolism of ARA and PF is still elusive. In this study, we observed a disorder in the cyclooxygenase-2/cytochrome P450 (COX-2/CYP) metabolism of ARA in the lungs of PF mice induced by bleomycin (BLM). Therefore, we aimed to explore the role of COX-2/CYP-derived ARA metabolic disorders in PF. PTUPB, a dual COX-2 and soluble epoxide hydrolase (sEH) inhibitor, was used to restore the balance of COX-2/CYP metabolism. sEH is an enzyme hydrolyzing epoxyeicosatrienoic acids derived from ARA by CYP. We found that PTUPB alleviated the pathological changes in lung tissue and collagen deposition, as well as reduced senescence marker molecules (p16 Ink4a and p53-p21 Waf1/Cip1 ) in the lungs of mice treated by BLM. In vitro , we found that PTUPB pretreatment remarkably reduced the expression of senescence-related molecules in the alveolar epithelial cells (AECs) induced by BLM. In conclusion, our study supports the notion that the COX-2/CYP-derived ARA metabolic disorders may be a potential therapeutic target for PF via inhibiting the cellular senescence in AECs.
研究领域:
药理学
·
肺病学
·
分子生物学
·
治疗学
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DOI
PubMed
高影响因子
PHARMACEUTICAL CHEMISTRY JOURNAL
·
2018
·Vol. 52
·期 2
·95-102
·
IF 0.679
Xu Xiaoya,Chen Yajun,Zhang Min,Wang Dianlei,Wu Jie,Yao Zhaomin,Wu Qingqing,Fang Wei
The therapy of Huatanjiangqi capsule (HTJQ) has been used in the treatment of chronic obstructive pulmonary disease (COPD) clinically, with remarkable benefits. A lower functional activity of MRP1 is related to COPD development. However, the mechanism that contributes to MRP1 up-regulation by HTJQ was unclear. This study aimed to investigate the effects of HTJQ on the expression of Nrf2 and MRP1 in COPD rats. Rats were exposed to cigarette smoke plus lipopolysaccharide tracheal instillation to induce a COPD model. Then, Nrf2, HO-1, and MRP1 mRNA expression and their protein production in lung tissues were examined. The model group showed significant changes in the above assessments as compared to those of the control group ( p < 0.05). The lung function of model group treated with low/high dose of HTJQ was significantly strengthened (both p < 0.05), and the inflammatory cells and goblet cells were decreased in lung tissues. Treatment with low/high dose of HTJQ resulted in obvious increase in Nrf2, HO-1, and MRP1 mRNA and protein expression levels ( p < 0.05). HTJQ could up-regulate Nrf2 and MRP1 expression in lung tissues of COPD model rats. The mechanism by which HTJQ up-regulates MRP1 expression may be associated with Nrf2.
研究领域:
药理学
·
呼吸病学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
·
2022
·Vol. 21
·期 10
·2139-2146
·
IF 0.523
Limei Du,Xinglan Huo,Ying Liu
Purpose: To study the influence of resveratrol on chronic obstruction in Aspergillus fumigatus infection-induced chronic lung disease (COPD) in rats, and the process involved.
Methods: Seventy-five Sprague Dawley SD) rats were assigned to blank control, COPD model, Aspergillus fumigatus-infected COPD model, low (100 mg/kg) and high-dose (200 mg/kg) resveratrol groups, with 15 rats in each group. Enzyme-linked immunosorbent assay (ELISA) was used to assay IL-6, IL-8 and TNF-α in bronchoalveolar lavage fluid (BALF), while lung protein concentrations of AMPK and PGC-1α were assayed by immunoblotting.
Results: In low- and high-dose resveratrol groups, inflammatory factor levels were significantly lower than the corresponding levels in COPD model and Aspergillus fumigatus-infected COPD model (p < 0.05), while lung tissue proteins of AMPK, PGC-1α, and AQP5 of the rats given high-dose resveratrol were significantly raised, relative to corresponding levels in rats given low-dose resveratrol (p < 0.05).
Conclusion: Resveratrol modulates expression levels of secretory factors and surface markers in alveolar macrophages in COPD model rats infected with Aspergillus fumigatus. Resveratrol exerts this effect through the regulation of AMPK/PGC-1α signaling pathway.
研究领域:
药理学
·
免疫学
·
呼吸医学
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产品关联
DOI
高影响因子
Experimental and Therapeutic Medicine
·
2023
·Vol. 25
·期 2
·1-10
·
IF 2.7
Qing Chen,Shaojin Zhu,Nanlin Jiao,Ziyu Zhang,Guangjian Gao,Wenqiang Zheng,Gang Feng,Wenzheng Han
The early diagnosis of lung cancer is closely associated with the decline of mortality. A panel consisting of seven lung cancer‑related autoantibodies (7‑AABs) has been shown to be a reliable and specific indicator for the early detection of lung cancer, with a specificity of ~90% and a positive predictive value of ~85%. However, its low sensitivity and negative predictive value limit its wide application. To improve its diagnostic value, the diagnostic efficiencies of 7‑AABs in combination with non‑specific tumor markers were retrospectively investigated for the detection of early‑stage lung cancer. A total of 217 patients with small lung nodules who presented with ground‑glass opacity or solid nodules as well as 30 healthy controls were studied. The concentrations of 7‑AABs and heat shock protein 90a (HSP90a) were assessed using ELISA. Automated flow fluorescence immune analysis was used for the assessment of CEA, CYFRA21‑1, CA199 and CA125 levels. The results showed that 7‑AABs + HSP90a possessed a remarkably improved diagnostic efficiency for patients with small pulmonary nodules or for patients with lung nodules of different types, which suggested that 7‑AABs in combination with HSP90a could have a high clinical value for the improvement of the diagnostic efficiency of early‑stage lung cancer.
研究领域:
肿瘤学
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医学诊断学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOLOGY AND TOXICOLOGY
·
2025
·Vol. 41
·期 1
·1-17
·
IF 5.9
Mao Shitao,Yu Na,Wang Wei,Mao Yikai,Du Ying,Zhao Qihe,Gu Xiu,Kang Jian
Idiopathic pulmonary fibrosis (IPF), characterized by fibroblast activation and collagen deposition, is a progressive lung disease that lacks effective interventions. Ubiquitin-specific peptidase 10 (USP10) acts as a multifunctional player in inflammatory response and progression of cancers, the effect on pulmonary fibrosis is unknown. Here, we demonstrated downregulated expression of USP10 in fibrotic lung tissues of IPF patients. In the current study, lung tissues were collected at the end of weeks 1, 2, or 3 post bleomycin (BLM)-intratracheal delivery. Consistently, USP10 expression levels were reduced after BLM challenge in a time-dependent manner. Mice treated with lentivirus overexpressing USP10 exhibited mitigative lung injury and reduced collagen deposition. USP10 overexpression enhanced autophagy in BLM-treated mouse lungs. Interestingly, the protective effect of USP10 was attenuated as the pulmonary autophagy flux was blocked by autophagy inhibitor 3-methyladenine (3-MA). Primary human and mouse lung fibroblasts were treated with pro-fibrotic TGF-β1 to verify the role of USP10 in vitro. Mechanically, the deubiquitinating enzyme USP10 interacted with Sirtuin 6 (Sirt6) and inhibited its degradation. Furthermore, USP10 overexpression inhibited the activation of Sirt6-mediated AKT/mTOR pathway in both lung tissues and fibroblasts. Our findings suggest that USP10 might attenuate pulmonary fibrosis through the promotion of Sirt6/AKT/mTOR-mediated autophagy. These data prioritize USP10 as a therapeutic target for treating IPF. Graphical
研究领域:
医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LASER PHYSICS
·
2014
·Vol. 24
·期 11
·115606
·
IF 1.025
L P Zhou,G Y Wu,H J Wei,Z Y Guo,H Q Yang,Y H He,S S Xie,Y Liu
The present study is concerned with the in vitro study of different sized titanium dioxide (TiO2) nanoparticles' (NPs) penetration and accumulation in human normal lung (NL) tissue and lung adenocarcinoma tumor (LAT) tissue by the methods of continuous optical coherence tomography (OCT) monitoring and diffuse reflectance (DR) spectra measurement, and their evaluating the effects of TiO2 NPs in two sizes (60 nm and 100 nm) and their combination with ultrasound (US) on the optical properties of human NL and LAT tissue. Spectral measurements indicate that TiO2 NPs penetrate and accumulate into the tissues and thus induce enhancement of DR. The averaged and normalized OCT signal intensity suggests that light penetration depth is significantly enlarged by ultrasound. The average attenuation coefficient of NL tissue changes from 5.10 ± 0.26 mm−1 to 3.12 ± 0.43 mm−1 and 2.15 ± 0.54 mm−1 at 120 min for 60 nm TiO2 NPs and 60 nm TiO2NPs/US treatment, respectively, and from 5.54 ± 0.46 mm−1 to 3.24 ± 0.73 mm−1 and 2.69 ± 0.34 mm−1 at 150 min for 100 nm TiO2 NPs and 100 nm TiO2NPs/US, respectively. The average attenuation coefficient of LAT tissue changes from 9.12 ± 0.54 mm−1 to 4.54 ± 0.39 mm−1 and 3.61 ± 0.38 mm−1 at 120 min for 60 nm TiO2 NPs and 60 nm TiO2NPs/US treatment, respectively, and from 9.79 ± 0.32 mm−1 to 5.12 ± 0.47 mm−1 and 4.89 ± 0.59 mm−1 at 150 min for 100 nm TiO2 NPs and 100 nm TiO2NPs/US, respectively. The results suggest that the optical properties of NL and LAT tissues are greatly influenced by TiO2 NPs and their combination with ultrasound.
研究领域:
生物医学工程
·
肿瘤学
·
光学成像
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）