JOURNAL OF VIROLOGY
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2021
·Vol. 95
·期 3
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IF 5.103
Ning Ma,Xingjie Li,Hongyu Jiang,Yulong Dai,Guofeng Xu,Zongde Zhang
Influenza A viruses cause severe respiratory illnesses in humans and animals. Overreaction of the innate immune response to influenza virus infection results in hypercytokinemia, which is responsible for mortality and morbidity. However, the mechanism by which influenza induces hypercytokinemia is not fully understood. In this study, we established a mouse-adapted H9N2 virus, MA01, to evaluate the innate immune response to influenza in the lung. MA01 infection caused high levels of cytokine release, enhanced pulmonary injury in mice, and upregulated CD83 protein in dendritic cells and macrophages in the lung. Influenza virus neuraminidase (NA) unmasked CD83 protein and contributed to high cytokine levels. Furthermore, we provide evidence that CD83 is a sialylated glycoprotein. Neuraminidase treatment enhanced lipopolysaccharide (LPS)-stimulated NF-κB activation in RAW264.7 cells. Anti-CD83 treatment alleviated influenza virus-induced lung injury in mice. Our study indicates that influenza virus neuraminidase modulates CD83 status and contributes to the “cytokine storm,” which may suggest a new approach to curb this immune injury.IMPORTANCE The massive release of circulating mediators of inflammation is responsible for lung injury during influenza A virus infection. This phenomenon is referred to as the “cytokine storm.” However, the mechanism by which influenza induces the cytokine storm is not fully understood. In this study, we have shown that neuraminidase unmasked CD83 protein in the lung and contributed to high cytokine levels. Anti-CD83 treatment could diminish immune damage to lung tissue. The NA-CD83 axis may represent a target for an interruption of influenza-induced lung damage.
研究领域:
免疫学
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病毒学
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医学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Hend Mohamed Anwar,Gad Elsayed Mohamed Salem,Hanan M. Abd El-Latief,Amany Abd Elhameid Osman,Sahar K. Ghanem,Haroon Khan,Suchana Chavanich,Alshaymaa Darwish
The COVID-19 pandemic has drawn attention to acute lung injury and respiratory distress syndrome as major causes of death, underscoring the urgent need for effective treatments. Protease enzymes possess a wide range of beneficial effects, including antioxidant, anti-inflammatory, antifibrotic, and fibrinolytic effects. This study aimed to evaluate the potential therapeutic effects of bacterial protease and chymotrypsin in rats in mitigating acute lung injury induced by lipopolysaccharide . Molecular docking was employed to investigate the inhibitory effect of bacterial protease and chymotrypsin on TLR-4, the receptor for lipopolysaccharide. Bacterial protease restored TLR-4, Nrf2 , p38 MAPK , NF-kB, and IKK-β levels to normal levels, while chymotrypsin normalized TLR-4, IKK-β, IL-6, and IL-17 levels. The expression of TGF-β, caspase-3, and VEGF in the bacterial protease- and chymotrypsin-treated groups was markedly reduced. Our results suggest that both therapies ameliorate LPS-induced acute lung injury and modulate the TLR4/Nrf2/NF-k signaling pathway. Each protease exhibited distinct mechanisms, with bacterial protease showing a better response to oxidative stress, edema, and fibrosis , whereas chymotrypsin provided a better response in the acute phase and innate immunity. These findings highlight the potential of each protease as a promising therapeutic option for acute lung injury and respiratory distress syndrome.
研究领域:
医学
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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
Heliyon
·
2023
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IF 4
Xiao-Ping Zhao,Xiao-Li Zheng,Min Huang,Ya-Jia Xie,Xiao-Wen Nie,Ali Adnan Nasim,Xiao-Jun Yao,Xing-Xing Fan
Although some important advances have been achieved in clinical and diagnosis in the past few years, the management of non-small cell lung cancer (NSCLC) is ultimately dissatisfactory due to the low overall cure and survival rates. Epidermal growth factor (EGFR) has been recognized as a carcinogenic driver and is a crucial pharmacological target for NSCLC. DMU-212, an analog of resveratrol, has been reported to have significant inhibitory effects on several types of cancer. However, the effect of DMU-212 on lung cancer remains unclear. Therefore, this study aims to determine the effects and underlying mechanism of DMU-212 on EGFR-mutant NSCLC cells. The data found that the cytotoxicity of DMU-212 on three EGFR-mutant NSCLC cell lines was significantly higher than that of normal lung epithelial cell. Further study showed that DMU-212 can regulate the expression of cell cycle-related proteins including p21 and cyclin B1 to induce G2/M phase arrest in both H1975 and PC9 cells. Moreover, treatment with DMU-212 significantly promoted the activation of AMPK and simultaneously down-regulated the expression of EGFR and the phosphorylation of PI3K, Akt and ERK. In conclusion, our study suggested that DMU-212 inhibited the growth of NSCLCs via targeting of AMPK and EGFR.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
高影响因子
BIOMATERIALS
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2014
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IF 8.312
Yang Wang,Tao Liu,Erlong Zhang,Shenglin Luo,Xu Tan,Chunmeng Shi
Personalized oncology significantly relies on the development of theranostic agents to integrate cancer therapeutics and diagnostics. Current strategy for development of such multifunctional agents requires multistep chemical conjugation with cancer specific ligands, contrast agents and therapeutic drugs. In this study, we reported a near infrared (NIR) heptamethine indocyanine dye, IR-780, which selectively accumulated in the mitochondria of drug-resistant human lung cancer cells (A549/DR) and significantly inhibited cell growth, self-renewal and migration without the need of any chemical conjugation. IR-780 was also able to induce A549/DR cell apoptosis by disrupting the mitochondrial function. Furthermore, IR-780 dye exhibited remarkable tumoricidal activity and inhibited tumor recurrence in mouse syngeneic Lewis lung carcinoma xenograft model. With the unique properties of targeting, near infrared imaging and inhibitive effect to the drug-resistant cancer cells both in vitro and in vivo, IR-780 may represent a potential theranostic agent for tumor recurrence.
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
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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
Scientific Reports
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2025
·Vol. 15
·期 1
·1-15
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IF 3.9
Xia Hong,Tai Xue-jiao,Cheng Wang,Wu Yi,He Dan,Wang Li-feng,Liu Hao,Zhang Shen-yi,Sun Yu-ting,Liu Hang-zhi,Liu Dan-dan,Zhao Hu-zi,Ji Fu-yun,Li Xi-hua
Small cell lung cancer (SCLC) is a therapeutically challenging disease. Metformin, an effective agent for the treatment of type 2 diabetes, has been shown to have antitumour effects on many cancers, including non-small cell lung cancer (NSCLC) and breast cancer. Currently, the antitumour effects of metformin on SCLC and the underlying molecular mechanisms remain unclear. CCK-8, EdU, colony formation, flow cytometry, immunofluorescence, molecular docking, western blotting, nude mouse transplanted tumour model, and immunohistochemistry experiments were conducted to analyse gene functions and the underlying mechanism involved. In vitro experiments demonstrated that metformin inhibited the growth of SCLC cells (H446, H526, H446/DDP and H526/DDP), which was confirmed in xenograft mouse models in vivo. Additionally, metformin induced cell cycle arrest, apoptosis, and autophagy in these SCLC cells. The molecular docking results indicated that metformin has a certain binding affinity for EGFR. The western blotting results revealed that metformin decreased the expression of EGFR, p-EGFR, AKT, and p-AKT, which could be reversed by EGF and SC79. Moreover, metformin activated AMPK and inactivated mTOR, and compound C and SC79 increased the levels of p-mTOR. Metformin can not only enhance the antitumour effect of cisplatin but also alleviate the toxic effects of cisplatin on the organs of xenograft model animals. In summary, the current study revealed that metformin inhibits the growth of SCLC by inducing autophagy and apoptosis via suppression of the EGFR/AKT/AMPK/mTOR pathway. Metformin might be a promising candidate drug for combination therapy of SCLC.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Laser & Photonics Reviews
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2024
·
IF 9.8
Min Fan,Jingbo Chen,Xiaomeng Zheng,Luyun Xu,Jianqin Ye,Xueliang Lin,Kien Voon Kong,Duo Lin,Yudong Lu,Shangyuan Feng
The emergence of “precision medicine” marks a notable shift in cancer treatment, moving from a tumor type–oriented approach to a more targeted, gene-oriented approach. Detecting low-abundance mutant genes in blood is challenging but crucial for personalized treatment plans. Herein, a novel platform combining catalytic hairpin self-assembly (CHA)-mediated self-calibrating surface-enhanced Raman spectroscopy (SERS) with a high-throughput Raman system (CCSPS) was designed. This platform enables ultrasensitive and rapid genotype analysis of gene mutations. The development of CCSPS specifically targets EGFR mutations, which serve as crucial therapeutic targets for precision therapy in lung cancer. This system shows excellent sensitivity and selectivity, capable of detecting multiple EGFR mutations ( Del-19 , L858R , and T790M ) with a detection limit as low as attomolar levels. Additionally, precise genotyping analysis was successfully conducted on 42 clinical samples using the CCSPS, yielding results consistent with those obtained through next-generation sequencing. These results underscore the efficacy of the CCSPS in noninvasively identifying circulating tumor DNA (ctDNA) mutations, facilitating immediate therapeutic decision making at the bedside. In summary, the CCSPS is a fast, accurate, versatile, and compact testing system capable of precisely screening individuals who stand to benefit from targeted therapy, thus promoting personalized and precise healthcare.
研究领域:
医学
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分子生物学
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产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
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2024
·
IF 6.7
Dechan Lu,Zufang Huang,Jingbo Chen,Yudong Lu
Surface-enhanced Raman spectroscopy (SERS) provides a rapid and nondestructive method for biological plasma analysis, offering unparalleled sensitivity and specificity. However, most current studies predominantly employ the drop-cast method, where liquid samples are dried on the SERS substrate for spectral recording. While effective, this method is both time-consuming and inconsistent. Additionally, the Raman spectral signal of uric acid in plasma often dominates, overshadowing other crucial biomarkers necessary for disease differentiation. In this study, we present the application of label-free SERS detection for distinguishing early stage lung cancer (LC) from healthy controls (HC) using plasma samples. Plasma was diluted, adjusted to a weakly acidic pH, and combined with silver nanoparticles (Ag NPs) for SERS analysis. To maintain the plasma in a liquid state and prevent evaporation, liquid paraffin was employed. Our findings indicate that a 10-fold dilution of plasma under weakly acidic conditions significantly enhanced diagnostic performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.975. This method is featured by its simplicity and high efficiency, presenting a promising strategy for the minimally invasive diagnosis of early stage LC using SERS technology.
研究领域:
医学诊断
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生物分析化学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
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2025
·Vol. 26
·期 5
·1-14
·
IF 4
Liu Hongting,Sun Yao,Cai Shihao,Zhao Conglu,xu Xiang,Xu Aiguo,Zhou Honggang,Yang Cheng,Gu Xiaoting,Ai Xiaoyu
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown cause, with few effective therapies available and high mortality rates. Our preceding research indicated that formononetin (FMN) could improve the symptoms of the bleomycin-induced pulmonary fibrosis and be a promising drug against IPF. In this study, an inhalable formononetin-loaded poly(lactic-co-glycolic) acid (PLGA) large porous microspheres (FMN-PLGA-MSs) was prepared by the method of emulsion solvent evaporation. SEM showed that FMN-PLGA-MSs were loose particles existing many pores on the surfaces, and the measured mean geometric diameter was more than 10 µm. The encapsulation efficiency (EE) and drug loading efficiency (DL) were 87.72 ± 6.34% and 4.18 ± 0.30%. FMN in FMN-PLGA-MSs could be rapidly released within 2 h and sustainably released for 21 d. Cell tests and q-RT-PCR tests showed that FMN could inhibit the activation of fibroblasts and the deposition of extracellular matrix (ECM) by acting on the TGF-β1/Smad3 signaling pathway. FMN-PLGA-MSs showed higher antifibrotic effects than free FMN oral administration in the pulmonary fibrosis models of mice, remarkably improving pulmonary function, decreasing hydroxyproline levels, and attenuating lung injuries. By formulating formononetin into microsphere preparations, its solubility can be significantly enhanced, enabling effective pulmonary drug delivery. This approach not only improves lung targeting but also reduces systemic toxicity. Additionally, it facilitates superior lung deposition and extends the retention time of the formononetin within the lungs. Taken together, FMN-PLGA-MSs may be a promising inhaled medication for the treatment of IPF. Graphical Formononetin (FMN) can improve the symptoms of idiopathic pulmonary fibrosis (IPF). Large porous microparticle can improve lung retention and lung targeting. FMN is loaded in poly(lactic-co-glycolic)acid (PLGA) to get microspheres (FMN-PLGA-MSs) for intratracheal instillation treatment of IPF. FMN-PLGA-MSs remarkably improved pulmonary function, decreased hydroxyproline, and attenuated lung injuries. FMN-PLGA-MSs are promising intratracheal instillation medication for the treatment of IPF.
研究领域:
药学
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呼吸病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Jiawang Huang,Jianing Shi,Jingmin Fu,Zhuolin Liu,Zhiying Feng,Kangyu Wang,Chunjing Chen,Yi Ning,Fangguo Lu,Ling Li
Ethnopharmacology relevance Maxing Shigan Decoction (MXSGD), derived from the traditional Chinese medicine (TCM) classic Shang Han Lun , is recognized as an effective TCM herbal formula for treating respiratory diseases, although its precise molecular mechanisms against influenza A virus (IAV) have not yet been fully elucidated. Aim of the study This study aimed to clarify the pharmacological effects of MXSGD on IAV-infected pneumonia mouse models, with a particular focus on its regulatory mechanism through miR-1260. Materials and methods The chemical composition of MXSGD was analyzed using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). After establishing IAV-infected mouse models, the pathological changes in lung tissues were observed by hematoxylin-eosin (HE) staining; the pulmonary epithelial cells and macrophages in lung tissues were examined through immunological assays; and the expression levels of miR-1260 and its target genes in lung tissues were evaluated by RT-qPCR and Western blot analysis. A co-culture system of MLE-12 and RAW246.7 cells was constructed as the research model. Then, the intracellular miR-1260 expression was detected by RT-qPCR, and the Sema3A expression was examined by immunofluorescence. The macrophages were further transfected with miR-1260 mimic, inhibitor, and Sema3A siRNA to determine whether MXSGD exerts its therapeutic effects through the miR-1260-targeted Sema3A-mediated PI3K/AKT/mTOR signaling pathway. Subsequently, alveolar macrophage-depleted mouse models were established using CL2MBP, and were infected with IAV. To clarify the role of macrophages in the therapeutic mechanism of MXSGD against IAV, the body weight and organ indices of mice were monitored and recorded; the total protein content and levels of inflammatory factors in the bronchoalveolar lavage fluid (BALF) were measured; the histopathological changes were observed by HE staining; the pulmonary epithelial cells and macrophages in lung tissues were examined through immunological assays; and the expressions of miR-1260 and its target genes in lung tissues were evaluated by RT-qPCR and Western blot analysis. Results MXSGD was found to alleviate IAV-induced pathological injury and suppress macrophage recruitment in mouse lung tissues, while downregulating the viral load and levels of inflammatory factors. The attenuation of macrophage recruitment was closely associated with pulmonary epithelial cells, potentially mediated through the miR-1260-targeted Sema3A-regulated PI3K/AKT/mTOR signaling pathway. In cellular experiments, both cell types in the co-culture system were restored following MXSGD treatment, accompanied by lowered intracellular viral load and levels of inflammatory factors. Additionally, macrophage apoptosis and miR-1260 expression were significantly reduced, whereas the Sema3A fluorescence intensity in macrophages was markedly increased. By transfecting miR-1260 mimic, inhibitor, and Sema3A siRNA into co-cultured macrophages, the therapeutic effects of MXSGD were further confirmed to be associated with the miR-1260/Sema3A-mediated PI3K/AKT/mTOR pathway. In IAV-infected models established after pulmonary macrophage depletion, the therapeutic efficacy of MXSGD was partially weakened following elimination of alveolar macrophages. In general, above in vivo findings are consistent with the cellular experimental results, collectively supporting the involvement of the miR-1260-targeted Sema3A-mediated PI3K/AKT/mTOR signaling pathway in the therapeutic mechanism of MXSGD. Conclusions MXSGD was demonstrated to regulate the PI3K/AKT/mTOR pathway through the macrophage miR-1260/Sema3A axis, through which excessive inflammatory responses in IAV-induced pneumonia were effectively suppressed. The findings provide a novel therapeutic target for antiviral treatment in TCM.
研究领域:
免疫学
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病毒学
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分子生物学
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呼吸病学
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中药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 13
·e70688
·
IF 4.2
Li‐Ping Kang,Cong Xu,Pan Xu,Dong‐Hui Huang,Ze‐Bo Jiang
Non‐small cell lung cancer (NSCLC) stands as a predominant cause of cancer‐related mortality worldwide. Brazilin, an active isoflavonoid compound derived from Chinese herbs, has displayed anti‐cancer properties across various cancer cell lines. However, the precise anti‐tumour mechanism of Brazilin in NSCLC remains incompletely understood. In this paper, we demonstrated that Brazilin treatment significantly reduced the proliferation of NSCLC cells and induced apoptosis. Additionally, Brazilin caused G2 cell cycle arrest in NSCLC cells, characterised by decreased expression of Cyclin B1 and increased expression of P21. Brazilin also induced mitochondrial dysfunction and ROS production in NSCLC cells. Mechanistically, Brazilin treatment significantly activated the STING pathway and upregulated the expression of CXCL10, CXCL9, and CCL5 in NSCLC cell lines. Notably, the inhibition of the STING pathway with H‐151 enhances cell viability, suggesting STING is involved in Brazilin‐induced apoptosis. These findings underscore Brazilin as a promising anti‐cancer agent for NSCLC.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancer Medicine
·
2024
·Vol. 13
·期 17
·e70197
·
IF 2.9
Yidan Ma,Yifei Wang,Lei He,Jun Du,Lin Li,Zhixin Bie,Yuanming Li,Xiaomao Xu,Wei Zhou,Xiaonan Wu,Li Yang,Jing Di,Chenyang Li,Xiaoguang Li,Dongge Liu,Zheng Wang
Backgroud Supernatants from various cytological samples, including body cavity effusion, sputum, bronchoalveolar lavage fluid (BALF), and needle aspiration, have been validated for detecting genetic alterations using cell-free DNA (cfDNA) in patients with non-small cell lung cancer (NSCLC). However, the sensitivity of fusion variations detection remains challenging. The protection of cell-free RNA (cfRNA) is critical for resolving the issue. Methods A protective solution (PS) was applied for preserving cfRNA in cytological supernatant (CS), and the quality of protected cfRNA was assessed by cycle threshold (CT) values from reverse transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, we collected an additional set of malignant cytological and matched tumor samples from 84 NSCLC patients, cfDNA & cfRNA extraction and double detection for driver gene mutations was validated using the multi-gene mutations detection by RT-qPCR. Results Under the optimal protection system, 91.0% (101/111) of cfRNA were protected effectively. Among the 84 NSCLC patient samples, seven cytological samples failed the tests. In comparison with tumor samples, the overall sensitivity and specificity of detecting driver genes of supernatant cfDNA and cfRNA were 93.8% (74/77) and 100% (77/77), respectively. Notably, when focusing exclusively on patients with fusion gene changes, both sensitivity and specificity reached 100% (11/11) for EML4-ALK, ROS1, RET fusions, and MET ex14 skipping. Conclusion These findings suggest that cfDNA & cfRNA extraction and double detection strategy recommended in this study improve the accuracy of driver genes mutations test, especially for RNA-based assay.
研究领域:
医学
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分子生物学
✓ 已验证
DOI
高影响因子
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