PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Lin Niu,Yu-jie Lu,Xing-wang Zu,Wen Yang,Fu-kui Shen,Yan-yan Xu,Min Jiang,Yang Xie,Su-yun Li,Jie Gao,Gang Bai
Transient receptor potential vanilloid 4 (TRPV4) plays a role in regulating pulmonary fibrosis (PF). While several TRPV4 antagonists including magnolol (MAG), have been discovered, the mechanism of action is not fully understood. This study aimed to investigate the effect of MAG on alleviating fibrosis in chronic obstructive pulmonary disease (COPD) based on TRPV4, and to further analyze its mechanism of action on TRPV4. COPD was induced using cigarette smoke and LPS. The therapeutic effect of MAG on COPD-induced fibrosis was evaluated. TRPV4 was identified as the main target protein of MAG using target protein capture with MAG probe and drug affinity response target stability assay. The binding sites of MAG at TRPV4 were analyzed using molecular docking and small molecule interaction with TRPV4-ankyrin repeat domain (ARD). The effects of MAG on TRPV4 membrane distribution and channel activity were analyzed by co-immunoprecipitation, fluorescence co-localization, and living cell assay of calcium levels. By targeting TRPV4-ARD, MAG disrupted the binding between phosphatidylinositol 3 kinase γ and TRPV4, leading to hampered membrane distribution on fibroblasts. Additionally, MAG competitively impaired ATP binding to TRPV4-ARD, inhibiting TRPV4 channel opening activity. MAG effectively blocked the fibrotic process caused by mechanical or inflammatory signals, thus alleviating PF in COPD. Targeting TRPV4-ARD presents a novel treatment strategy for PF in COPD.
研究领域:
药理学
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肺科学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2023
·
IF 4.9
Dongli Qi,Bei Jia,Hui Peng,Jiachen He,Jiaxin Pi,Pan Guo,Ying Zhang,Xiuping Deng,Jiawei Li,Zhidong Liu
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal lung disease caused by multiple factors. Currently, safe, and effective drugs for the treatment of IPF have been extremely scarce. Baicalin (BA) is used to treat pulmonary fibrosis, IPF, chronic obstructive pulmonary disease, and other lung diseases. Ambroxol hydrochloride (AH), a respiratory tract lubricant and expectorant, is often used to treat chronic respiratory diseases, such as bronchial asthma, emphysema, tuberculosis, and cough. The combination of BA and AH can relieve cough and phlegm, improve lung function, and potentially treat IPF and its symptoms. However, given the extremely low solubility of BA, its bioavailability for oral absorptions is also low. AH, on the other hand, has been associated with certain side effects, such as gastrointestinal tract and acute allergic reactions, which limit its applicability. Therefore, an efficient drug delivery system is urgently needed to address the mentioned problems. This study combined BA and AH as model drugs with L-leucine (L-leu) as the excipient to prepare BA/AH dry powder inhalations (BA/AH DPIs) using the co-spray drying method. We the performed modern pharmaceutical evaluation, which includes particle size, differential scanning calorimetry analysis, X-ray diffraction, scanning electron microscope, hygroscopicity, in vitro aerodynamic analysis, pharmacokinetics, and pharmacodynamics. Notably, BA/AH DPIs were found to be advantageous over BA and AH in treating IPF and had better efficacy in improving lung function than did the positive drug pirfenidone. The BA/AH DPI is a promising preparation for the treatment of IPF given its lung targeting, rapid efficacy, and high lung bioavailability.
研究领域:
药剂学
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肺病学
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药物递送系统
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药理学
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产品关联
DOI
PubMed
高影响因子
Communications Biology
·
2025
·Vol. 8
·期 1
·1-15
·
IF 5.1
Wu Lin,Zhang Fangyuan,Chen Huanhuan,Zhao Gang
Like-Smith protein 12 (LSM12), an RNA-binding protein, is highly expressed in tumor tissues of patients with lung squamous cell carcinoma (LUSC). However, the role of LSM12 in LUSC is unclear. In this study, overexpression of LSM12 promotes the proliferation, migration, and invasion and prevents the apoptosis of LUSC cells. In vivo, LSM12 accelerates the tumor growth and metastasis of LUSC cells using male BALB/c nude mice. Furthermore, we find that the Sterile alpha motif domain containing 4A (SAMD4A) is directly bound to the mRNA of LSM12 and accelerates the mRNA degradation. High-throughput omics analysis is performed to identify the potential target genes of LSM12 in LUSC cells. LSM12 regulates alternative splicing events and increases exon 13 skipped splicing of ARRB1 and mRNA expression. Our findings may provide fundamental research for the investigation of the development of LUSC and the potential role of LSM12 in LUSC cells.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Science Advances
·
2023
·Vol. 9
·期 42
·
IF 13.6
Qingle Ma,Chenlu Yao,Yi Wu,Heng Wang,Qin Fan,Qianyu Yang,Jialu Xu,Huaxing Dai,Yue Zhang,Fang Xu,Ting Lu,Jennifer K. Dowling,Chao Wang
Neurological disorders are a common feature in patients who recover from severe acute pneumonia. However, the underlying mechanisms remain poorly understood. Here, we show that the neurological syndromes after severe acute pneumonia are partly attributed to the translocation of endogenous bacteria from the lung to the brain during pneumonia. Using principal components analysis, similarities were found between the brain’s flora species and those of the lungs, indicating that the bacteria detected in the brain may originate from the lungs. We also observed impairment of both the lung-blood and brain-blood barriers, allowing endogenous lung bacteria to invade the brain during pneumonia. An elevated microglia and astrocyte activation signature via bacterial infection–related pathways was observed, indicating a bacterial-induced disruption of brain homeostasis. Collectively, we identify endogenous lung bacteria that play a role in altering brain homeostasis, which provides insight into the mechanism of neurological syndromes after severe pneumonia.
研究领域:
神经科学
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传染病学
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微生物学
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免疫学
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DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2025
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IF 14.6
Xinxing Li,Wenxin Ding,Yan Lu,Haiyan Zhu,Weilian Bao,Yang Liu,Jiaren Lyu,Lishuang Zhou,Hong Li,Jiyang Li,Daofeng Chen
The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD 50 ) and methicillin-resistant Staphylococcus aureus (MRSA, 10 7 CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut–lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut–lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral–bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.
研究领域:
免疫学
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微生物学
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药理学
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呼吸医学
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DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2024
·
IF 4
Wei Liu,Sufei Zhou,Ke Yang,Di Liu,Yuxing Yan,Fangzhen Tian,Tianyi Cui,Wei Wang,Lewei Bi,Lan Li,Hao Wang,Xiao-Dong Zhang
Currently, pulmonary complications such as lung infections during the perioperative period are still the main cause of prolonged hospitalization and death in patients with lung injury due to the lack of effective drugs. Clusterzyme, a kind of artificial enzyme with a high enzyme-like activity and safety profile, exhibits good effects on reducing oxidative stress and immunomodulation. Here, we present the functionalized patches that is administered on the lung airways and rescues the injured organ via clusterzymes. The long-term antioxidant capacity of the patches significantly ameliorated lipopolysaccharide-induced lung function impairment with a significant reduction in lung goblet cell metaplasia and oxidative stress. The inflammatory factors such as cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α levels decreased by 50%, while the mtDNA copy number increased by 50% and ATP production increased by 100%. Mice lung function was significantly improved, suggesting that the patches can rescue lung injury by modulating oxidative stress and immune responses as well as protecting the mitochondria, providing an avenue for effective intervention of lung injury.
研究领域:
药理学
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免疫学
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呼吸医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Biomedical Engineering Online
·
2021
·Vol. 20
·期 1
·1-13
·
IF 2.819
Ge Jinlin,Yang Huanhuan,Zeng Yufeng,Liu Yunjie
Background Wogonin (5, 7-dihydroxy-8-methoxyflavone) is a natural di-hydroxyl flavonoid extracted from the root of Scutellaria baicalensis Georgi. This paper was intended to investigate the mechanism of action of wogonin in alleviating the inflammation and apoptosis in acute lung injury (ALI).Materials and methodsLipopolysaccharide (LPS) was used to establish the in vitro model of ALI. After wogonin treatment, the cell viability and apoptosis of LPS-induced A549 cells were, respectively, measured by CCK-8, TUNEL assays and acridine orange/ethidium bromide dual staining, while the contents of inflammatory cytokines and oxidative stress markers were estimated by RT-qPCR, ELISA assay, western blot analysis and commercial kits. Western blot was also conducted to assess the expression of proteins involved. Subsequently, the effect of wogonin on the sirtuin 1 (SIRT1)-mediated high-mobility group box 1 protein (HMGB1) deacetylation was investigated. SIRT1 inhibitor EX527 was used to evaluate the regulatory effects of wogonin on SIRT1-mediated HMGB1 deacetylation in A549 cells under LPS stimulation.Results LPS induced inflammation, oxidative stress and apoptosis of A549 cells, which was abolished by wogonin. It was also found that wogonin promoted the HMGB1 deacetylation, accompanied by upregulated SIRT1 expression. However, SIRT1 inhibitor EX527 partially reversed the protective effects of wogonin on the inflammation and apoptosis of LPS-induced A549 cells.Conclusion Wogonin alleviated the inflammation and apoptosis in LPS-induced A549 cells by SIRT1-mediated HMGB1 deacetylation, which might represent the identification of a novel mechanism by which wogonin exerts protective effects on ALI and provide ideas for the application of wogonin to ALI treatment.
研究领域:
药理学
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免疫学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2022
·Vol. 45
·期 6
·1162-1169
·
IF 3.614
Aijin Shen,Weijia Zhou,Lele Xiong,Hongli Jin,Long Yu,Huimin Wu,Wenyi Yu,Dongping Yu,Zhimou Guo,Yanfang Liu,Xinmiao Liang
Qingfei Paidu Decoction is a Chinese medicine formula that has been proved effective in the treatment of coronavirus disease 2019. However, the comprehensive separation and characterization of Qingfei Paidu Decoction are of a great challenge due to the diversity of chemical components in a wide range of polarity. In this study, a triplex off-line two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry is developed for the analysis of Qingfei Paidu Decoction. One reversed-phase liquid chromatography×hydrophilic interaction liquid chromatography system and two reversed-phase liquid chromatography×reversed phase liquid chromatography systems were constructed to separate polar components and weak-polar components in Qingfei Paidu Decoction, respectively. Benefiting from the good orthogonality of two-dimensional liquid chromatography and high sensitivity of quadrupole time-of-flight MS, chemical components with different polarities and content were discovered. A total of 749 peaks were detected in positive and negative ionization mode and presented as a four-dimensional data plot. Meanwhile, 498 compounds belonging to 14 categories were tentatively identified. These results provide good supplementary to elucidate the material basis of Qingfei Paidu Decoction. The triplex off-line two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry strategy can be a powerful and efficient tool for the separation and characterization of chemical substances in traditional Chinese medicine formulas.
研究领域:
药学化学
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分析化学
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中医药
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Wenhua Wang,Wenhao Wang,Shiwei Jin,Fangqin Fu,Zhengwei Huang,Ying Huang,Chuanbin Wu,Xin Pan
Cisplatin (DDP)-based ferroptosis-apoptosis synergetic therapy is a novel strategy of lung cancer treatment based on the targeted induction of high oxidative stress levels in tumor cells. Nevertheless, the strong antioxidant system in tumor cells and low accumulation at the lesion site result in its low sensitivity as well as systemic side effects. To circumvent the strong antioxidant system, the combination of Reactive Oxygen Species (ROS) generator DDP and a glutathione (GSH) scavenger β-Phenethyl isothiocyanate (PEITC) was a potential strategy. Besides, pulmonary delivery equipped with lung tumor targeting nanoformulations was expected to promote tumor lesions accumulation. Herein, an inhalable core–shell nanocomposite, PEITC-loaded solid lipid nanocores coated with DDP-encapsulated hyaluronic acid (HA) shell (PNDH) based on the strategy of “open pocket and tighten holes” was developed. The nicotinamide adenine dinucleotide phosphate oxidases 4 (NOX4) was upregulated by DDP to “open pocket for ROS” while the PEITC could deplete the GSH to “tighten holes”, preventing ROS consumption. Upon nebulization, improved lung drug accumulation with about 6.7 times higher than intravenous injection and excellent lung retention was exhibited. Equipped with tumor membrane CD44 targeted HA, the tumor recognizing efficiency was elevated about two times. The remarkably enhanced tumor inhibition effect was revealed both in vitro and in vivo, and the PNDH-driven cell damage process was described as a result of mitochondrial dysfunction and osmotic pressure mediated cell membrane broken. Taken together, the rationally designed PNDH enhanced the effectiveness of ferroptosis-apoptosis synergetic therapy by the “open pocket and tighten holes” strategy.
研究领域:
肿瘤学
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药学
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纳米技术
·
治疗学
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产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Wenyu Chen,Yuanyuan Gao,Yuanqi Liu,Yujia Luo,Xinrui Xue,Chujie Xiao,Kun Wei
Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by chronic, progressive scarring of the lung parenchyma, leading to an irreversible decline in lung function. Apart from supportive care, there is currently no specific treatment available to reverse the disease. Based on the fact that tanshinone IIA (TAN) had an effect on protecting against TGF-β1-induced fibrosis through the inhibition of Smad and non-Smad signal pathways to avoid myofibroblasts activation, this study reported the development of the inhalable tanshinone IIA-loaded chitosan-oligosaccharides-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CPN@TAN) for enhancing the pulmonary delivery of tanshinone IIA to treat pulmonary fibrosis. The CPN@TAN with a size of 206.5 nm exhibited excellent in vitro aerosol delivery characteristics, featuring a mass median aerodynamic diameter (MMAD) of 3.967 ± 0.025 μm and a fine particle fraction (FPF) of 70.516 ± 0.929%. Moreover, the nanoparticles showed good stability during atomization and enhanced the mucosal penetration capabilities. The results of confocal spectroscopy confirmed the potential of the nanoparticles as carriers that facilitated the uptake of drugs by NIH3T3, A549, and MH-S cells. Additionally, the nanoparticles demonstrated good in vitro biocompatibility. In a mouse model of bleomycin-induced pulmonary fibrosis, noninvasive inhalation of aerosol CPN@TAN greatly suppressed collagen formation and facilitated re-epithelialization of the destroyed alveolar epithelium without causing systemic toxicity compared with intravenous administration. Consequently, our noninvasive inhalation drug delivery technology based on polymers may represent a promising paradigm and open the door to overcoming the difficulties associated with managing pulmonary fibrosis.
研究领域:
药理学
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纳米技术
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呼吸医学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Xidong Tian,Hriday Bera,Xiong Guo,Ruizhao Xu,Jin Sun,Zhonggui He,Dongmei Cun,Mingshi Yang
Chemotherapeutics often failed to elicit optimal antitumor responses against lung cancer due to their limited exposure and accumulation in tumors. To achieve an effective therapeutic outcome of paclitaxel (PTX) against metastatic lung cancer with attenuated systemic and local toxicities, pulmonary delivery of redox-responsive PTX dimeric nanoparticles (NPs) was introduced. PTX dimers conjugated through variable lengths of diacid linkers containing disulfide bonds (−SS−) (i.e., α–PTX–SS–PTX, β–PTX–SS–PTX, and γ–PTX–SS–PTX) were initially synthesized and were subsequently self-assembled into uniform nanosized particles in the presence of vitamin E TPGS with high drug loading capacity (DE > 97%). Among various redox-sensitive scaffolds, β–PTX–SS–PTX NPs exhibited an optimal reactive oxygen species/glutathione-responsive drug release behavior, causing a lower local toxicity profile of PTX in the lungs. The scaffolds also demonstrated excellent colloidal stability, cellular uptake efficiency, and discriminating cytotoxicity between cancer and healthy cells. Further, they depicted an improved lung retention as compared to the control nanovesicles (β–PTX–CC–PTX) devoid of the redox-sensitive disulfide motif. In the B16F10 melanoma metastatic lung cancer mouse model, intratracheally delivered β–PTX–SS–PTX NPs exhibited a stronger anticancer potential with reduced systemic toxicity as compared to Taxol intravenous injection containing an equivalent PTX dose. The PTX dimeric NPs could also dramatically reduce the local toxicity relative to Taxol following their pulmonary delivery. Thus, this study presents redox-responsive PTX dimeric NPs as a promising nanomedicine for improved therapeutic efficacy against metastatic lung cancer.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Natural Product Communications
·
2024
·
IF 1.5
Chunyang Mao,Yan Du,Kun Niu,Fan Yang,Changcai Bai,Bo Zhou,Yang Niu
Objective: The Traditional Chinese Medicine Qingzao Jiufei Tang decoction (QZJFD) is effective for the treatment of idiopathic pulmonary fibrosis (IPF). In this study, we explored the anti-pulmonary fibrosis effect of QZJFD and the underlying mechanism. Methods: The effects of QZJFD at low, medium, and high doses were investigated in a rat model of lung fibrosis induced by tracheal injection of bleomycin; pirfenidone was included as a positive control. Serum levels of interleukin-6 (IL-6), tumor necrosis factors (TNF-α), and IL-1β in rats were detected by enzyme-linked immunosorbent assay (ELISA). Expression of α-smooth muscle actin (α-SMA), TGF-β1, p-Jun N-terminal kinase (p-JNK), JNK, p-P38 mitogen-activated protein kinase (MAPK), P38 MAPK, collagen I, and fibronectin-1 (FN1) in lung tissues was detected by immunofluorescence labeling and western blot analysis. Results: QZJFD contained 209 main components and 575 corresponding targets. In total, 3875 disease action targets were related to IPF, with 308 common targets shared by drugs and diseases. The key targets included albumin (ALB), recombinant protein, TNF, IL-6, and tumor protein p53. In total, 3061 items were identified in the gene ontology enrichment analysis (P < .05) and 197 signaling pathways in the Kyoto encyclopedia of genes and genomes (P < .05), including MAPK, calcium, advanced glycosylation end products - receptors, TNF, and IL-17. Molecular docking simulation showed that the 2 predominant compounds of QZJFD, naringenin, and kaempferol, bound with high affinity to ALB. Serum levels of IL-6, TNF-α, and IL-1β and the expression levels of α-SMA, TGF-β1, p-JNK, p-P38 MAPK, collagen I, and FN1 in lung tissues were significantly increased in the model rats (P < .001). After treatment with pirfenidone and QZJFD at the medium and high doses, serum levels of IL-6, TNF-α, and IL-1β and expression levels of α-SMA, p-JNK, p-P38 MAPK, collagen I, and FN1 in lung tissues of rats were significantly lower than those in the model group (P < .05). Conclusions: QZJFD may exert antifibrotic and anti-inflammatory effects that improve the status of IPF by regulating the MAPK signaling pathway.
研究领域:
中医
·
药理学
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呼吸病学
·
分子生物学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）