NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2023
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IF 3.6
Zhu Xiaona,Bai Bin,Ge Xiangting,Zheng Bin,Xiao Zhongxiang,Tang Yue,Fang Letong,Tang Yelin,Dai Yuanrong,Zhang Bing,Zhang Yali
Inflammation is an important pathological process of many acute and chronic diseases, such as sepsis, arthritis, and cancer. Many factors can lead to an inflammatory state of the body, among which bacterial infection plays an important role. Bacterial infection often leads to sepsis, acute lung injury (ALI), or its more serious form of acute respiratory distress syndrome, which are the main fatal diseases in intensive care units. Costunolide has been reported to possess excellent anti-inflammatory activity; however, whether it can affect inflammation induced by gram-negative bacterial is still unclear. Lipopolysaccharide (LPS) stimulated mouse peritoneal macrophages (MPMs) to release proinflammatory cytokines was used as the cell model. The mouse model of sepsis and ALI was built through injecting intravenously and intratracheally of LPS. In the present study, costunolide inhibited LPS-induced inflammatory response through IKK/NF-κB signaling pathway in macrophages. In vivo, costunolide attenuated LPS-induced septic death in mice. Meanwhile, costunolide treatment alleviated LPS-induced lung injury and inflammation via inhibiting the infiltration of inflammatory cells and the expression of inflammatory cytokines. Taken together, these results demonstrated that costunolide could attenuate gram-negative bacterial induced inflammation and diseases and might be a potential candidate for the treatment of inflammatory diseases.
研究领域:
免疫学
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药理学
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炎症研究
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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 NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-20
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IF 10.6
Ye Lusha,Gao Yanan,Mok Simon Wing Fai,Liao Wucan,Wang Yazhou,Chen Changjiang,Yang Lijun,Zhang Junfeng,Shi Liyun
Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted macrophages and hence lung disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles have gained significant attention because of their therapeutic potential, but the targeting cells and the underlying mechanism remain elusive. We herein prepared the nanovesicles from Artemisia annua, a well-known medicinal plant with multiple attributes involving anti-inflammatory, anti-infection, and metabolism-regulating properties. By applying three mice models of acute lung injury caused by bacterial endotoxin, influenza A virus (IAV) and SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived nanovesicles (ADNVs) substantially alleviated lung immunopathology and raised the survival rate of challenged mice. Macrophage depletion and adoptive transfer studies confirmed the requirement of AMs for ADNVs effects. We identified that gamma-aminobutyric acid (GABA) enclosed in the vesicles is a major molecular effector mediating the regulatory roles of ADNVs. Specifically, GABA acts on macrophages through GABA receptors, promoting mitochondrial gene programming and bioenergy generation, reducing oxidative stress and inflammatory signals, thereby enhancing the adaptability of AMs to inflammation resolution. Collectively, this study identifies a promising nanotherapeutics for alleviating lung pathology, and elucidates a mechanism whereby the canonical neurotransmitter modifies AMs and mitochondria to resume tissue homeostasis, which may have broader implications for treating critical pulmonary diseases such as COVID-19.
研究领域:
药理学
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免疫学
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肺科学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Mingxing Li,Xuwei Shang,Haiya Lou,Zixu Wang,Shanshan Xiang,Yihe Qiu,Fuqiang Hu,Fangying Yu,Hong Yuan
Recently, nanotechnology-based drug delivery platforms in treating pulmonary arterial hypertension (PAH) have gradually emerged. However, large mechanical stress and shear stress in blood vessels greatly affect the retention of nanopreparative materials at lesion sites, severely limiting nanotechnology-based drug delivery. Herein, a stimuli-responsive nanocraft is rationally designed by actively anchoring E-selectin overexpressed on pulmonary arterial endothelial cells (PAECs), under hypoxic conditions, allowing effective accumulation and retention of the drug at the lesion site. Briefly, a nitrobenzene group is incorporated into the framework of a nanocarrier, and then it is simultaneously linked with chitosan. Additionally, the surface of the nanocarrier with sialic acid (SA) and encapsulated the clinically used drug ambrisentan (Am), which enables the anchoring of E-selectin and subsequent drug delivery is modifed. This system facilitates intercellular transport to pulmonary artery smooth muscle cells (PASMCs) when targeting PAECs and specifically responds to a reductive hypoxic microenvironment with elevated nitroreductase in PASMCs. Moreover, compared with free Am, nanoencapsulation and SA-PEG 2000 -NH 2 prolong the blood circulation time, achieving better therapeutic outcomes in preventing vascular remodeling and reversing systolic dysfunction. The originality and contribution of this work reveal the promising value of this pulmonary arterial anchoring stimuli-responsive nanocraft as a novel therapeutic strategy for satisfactory PAH treatment.
研究领域:
纳米技术
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药学
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心血管医学
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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
CARBOHYDRATE POLYMERS
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2024
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IF 10.7
Ke Zhang,Hui Huang,Yilin Zhao,Qinghao Zhen,Dongjian Shi,Jinghua Chen,Xi Chen
To address the main challenges for thoracoscopic lung cancer surgery, including persistent pulmonary air leaks and cancer recurrence, this study developed an in-situ adhesive that can effectively adhere to the lung and release the anticancer drug in response to pH. The adhesive was formulated using hydrophobically modified cold-water fish skin gelatin (hm-CFG) and cross-linking agent pullulan dialdehyde (PDA), in which succinic dihydrazide-modified doxorubicin (SDH-DOX) can be incorporated. Utilizing PDA could improve both cohesion and interfacial adhesion, while also offering drug-loading sites through the aldehyde groups that were not involved in cross-linking. The optimal adhesive formulation was 9C10-CFG/PDA (30 w/v% 9 mol% decanal modified CFG/20 w/v% PDA). The 9C10-CFG/PDA adhesive exhibited suitable cohesive strength, good mechanical flexibility (tensile strain over 170 %), and strong interface adhesion. The burst strength of 9C10-CFG/PDA adhesive (131.5 ± 22.2 mm Hg) was almost 6-fold higher than that of commercial fibrin sealant. In a rat pneumothorax model, 9C10-CFG/PDA adhesive displayed favorable wound-sealing properties, as evidenced by CT imaging and restored rat behavior. When combined with the anticancer drug, SDH-DOX@Adhesive could release the drug in response to pH more gradually than DOX@Adhesive. This dual-action adhesive is anticipated to mitigate post-surgical occurrences of lung air leaks and cancer recurrence.
研究领域:
生物医学工程
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药学
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材料科学
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外科手术
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产品关联
DOI
PubMed
高影响因子
Theranostics
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2016
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IF 8.854
Caixia Yue,Yuming Yang,Chunlei Zhang,Gabriel Alfranca,Shangli Cheng,Lijun Ma,Yanlei Liu,Xiao Zhi,Jian Ni,Weihua Jiang,Jie Song,Jesús M. de la Fuente,Daxiang Cui
Mitochondria in cancer cells maintain a more negative membrane potential than normal cells. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Thus, the strategy of targeting mitochondria can maximize the photodynamic therapeutic efficiency for cancer. Here we report, for the first time, synthesis of a new mitochondria-targeting drug delivery system, ZnPc/CPT-TPPNPs. To synthesize this novel compound, polyethylene glycol was functionalized with thioketal linker-modified camptothecin (TL-CPT) and triphenylphosphonium to form the block copolymer, TL-CPT-PEG 1K -TPP. The ZnPc/CPT-TPPNPs was constructed for delivery of the photosensitizer Zinc phthalocyanine (ZnPc) by blending the block copolymer TL-CPT-PEG 1K -TPP with 1, 2-distearoyl- sn -glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)] (DSPE-PEG).Triphenylphosphine can accumulate selectively several hundred-fold within mitochondria. The thioketal linker is ROS-responsive and CPT can be released upon ROS cleavage. We also show that the ZnPc loaded in ZnPc/CPT-TPPNPs absorbed the 633 nm laser to produce ROS, which could be utilized both in photodynamic therapy and to cleave the thioketal linker thereby releasing camptothecin for chemotherapy. Thus, the mitochondria-targeting nanoparticles could elevate photodynamic therapeutic efficacy. Our results showed that surface modification of the nanoparticles with triphenylphosphine cations facilitated efficient subcellular delivery of the photosensitizer to mitochondria. The nanoparticles had a good ROS-responsive effect to release CPT, which could transfer to the nucleus and interfere with DNA replication as a topoisomeraseⅠinhibitor. Thus, the blended nanoparticles provide a new promising approach as a mitochondria-targeting ROS-activated chemo- and photodynamic therapy with a single light source for lung cancer.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Ping Li,Changchang Wang,Gun Chen,Yixiao Han,Hanyu Lu,Nan Li,Yangbin Lv,Chu Chu,Xin Peng
Ethnopharmacological relevance Tetrastigma hemsleyanum （ T. hemsleyanum ）, valued in traditional medicine for its potential to boost immunity and combat tumors, contains uncharacterized active compounds and mechanisms. This represents a significant gap in our understanding of its ethnopharmacological relevance. Aim of the study To involve the mechanism of anti-lung cancer effect of T. hemsleyanum by means of experiment and bioinformatics analysis. Materials and methods The anticancer mechanism of T. hemsleyanum against lung squamous carcinoma (LUSC) in zebrafish was investigated. The LUSC model was established by injecting NCI–H2170 cells in the zebrafish and evaluating its anti-tumor efficacy. Next, component targets and key genes were obtained by molecular complex detection (MCODE) analysis and protein-protein interaction (PPI) network analysis. Component analysis of T. hemsleyanum was performed by UPLC-Q-TOF-MS. Molecular docking was used to simulate the binding activities of key potential active components to core targets were simulated using. Prognostic and pan-cancer analyses were then performed to validate the signaling pathways involved in the prognostic genes using gene set enrichment analysis (GSEA). Subsequently, Molecular dynamics simulations were then performed for key active components and core targets. Finally, cellular experiments were used to verify the expression of glutamate metabotropic receptor 3 (GRM3) and glutamate metabotropic receptor 7 (GRM7) in the anticancer effect exerted of T. hemsleyanum . Results We experimentally confirmed the inhibitory effect of T. hemsleyanum on LUSC by transplantation of NCI–H2170 cells into zebrafish. There are 20 main compounds in T. hemsleyanum , such as procyanidin B1, catechin , quercetin , and kaempferol , etc. A total of 186 component targets of T. hemsleyanum and sixteen hub genes were screened by PPI network and MCODE analyses. Molecular docking and molecular dynamics simulation results showed that Gingerglycolipid B and Rutin had higher affinity with GRM3 and GRM7 , respectively. Prognostic analysis, Pan-cancer analysis and verification experiment also confirmed that GRM3 and GRM7 were targets for T. hemsleyanum to exert anti-tumor effects and to participate in immune and mutation processes. In vitro experiments suggested that the inhibitory effect of T. hemsleyanum on cancer cells was correlated with GRM3 and GRM7. Conclusion In vivo, in vitro and in silico results confirmed the potential anticancer effects against LUSC of T. hemsleyanum , which further consolidated the claim of its traditional uses.
研究领域:
药理学
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生物信息学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2025
·
IF 4
Rui Ge,Qikai Su,Jian Liang,Lu Zheng,Qing-shan Li,Li Tang
The identification of natural compounds with therapeutic efficacy for acute lung injury has consistently represented a critical area of research. Dulcitol, a natural product isolated from plants, is extensively used in the food and medical industries as a sweetener. Herein, we investigated whether dulcitol exerts an anti-inflammatory effect on LPS-induced acute lung injury (ALI) in mice. In our study, ICR mice were pretreated with dulcitol at dose of 6, 12 and 24 mg/kg for seven consecutive days, followed by intratracheally instilled with LPS (10 mg/kg) to induce acute lung injury. In vitro, RAW264.7 and A549 cells were incubated with LPS in the presence of dulcitol to investigate the anti-inflammatory activity and mechanism. The results demonstrated that dulcitol effectively inhibited the infiltration of inflammatory cells and reduced the excessive production of pro-inflammatory cytokines triggered by LPS to ameliorates acute lung injury in mice. Additionally, in vitro experiments indicated that dulcitol suppressed the release of NO, IL-6 and TNF-α while reducing mRNA expression levels of IL-1β, IL-6, COX-2, iNOS and TNF-α in RAW264.7 and A549 cells in a dose-dependent manner. Furthermore, dulcitol significantly decreased TLR4, MyD88, and TRIF levels and inhibited the translocation of NF-κB from the cytoplasm to the nucleus. Our finding suggested that dulcitol could serve as a protective agent against LPS-induced acute lung injury by inhibiting the TLR-4/NF-κB signaling pathway.
研究领域:
免疫学
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药理学
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分子生物学
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产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Yixu Wang,Jin Zhang,Sihan Xu,Junjie Li,Wenjuan Liu,Min Jiang,Gang Bai
Background Acute lung injury (ALI) is a critical pathophysiological response in various respiratory diseases characterized by alveolar damage and excessive inflammation. It can progress to acute respiratory distress syndrome, with current treatments showing limited efficacy and considerable side effects. Psoralen (Pso), derived from Psoralea corylifolia L., has anti-inflammatory properties, but its role in ALI remains fully elucidated. Purpose This study aimed to investigate the therapeutic effects of Pso on ALI, and to explore its therapeutic targets and mechanisms. Methods The therapeutic potential of Pso was assessed using a model of ALI induced by lipopolysaccharide (LPS). The direct target was investigated using alkynyl-Psoralen (A-Pso) for chemical proteomic analysis, and a series of molecular biology methods were used to explore the underlying mechanism. Results Pso treatment significantly alleviated LPS-induced lung injury in mice, targeted macrophages, and inhibited the LPS-induced activation of macrophages. Target-fishing experiments identified high-mobility group box-1 (HMGB1) as a direct target of Pso in macrophages. FTS and CETSA confirmed Pso binding to HMGB1, and LC-MS/MS analysis indicated a covalent interaction between Pso and Cys106 of HMGB1. Furthermore, Pso covalently targeted Cys106, affecting HMGB1 binding to TLR4 and downregulating the phosphorylation of NF-κB, indicating the inhibition of the TLR4/NF-κB signaling pathway both in macrophages and in lung tissues of ALI mice. These findings suggest that Pso exerts its therapeutic effects by covalently targeting HMGB1 in macrophages and modulating the TLR4/NF-κB signaling pathway. Conclusion This study not only found that Pso improves LPS-induced ALI inflammation by targeting macrophages, but also verified that this mechanism of action is mainly caused by Pso covalently targeting Cys106 of HMGB1, inhibiting the HMGB1-TLR4 interaction, and thereby suppressing cytokine storm generation. As the first naturally derived HMGB1 covalent inhibitor with a clear binding site, Pso plays an important role in HMGB1 induced inflammatory diseases and is an active precursor for the development of new HMGB1 covalent inhibitors.
研究领域:
药理学
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免疫学
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呼吸病学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Quanwei Sun,Huiyu Lu,Wenshuo Yang,Zhengwei Song,Chen Chen,Xu Ruan,Min Luo,Yunlong Li,Huihui Li,Zexin Yang,Kang Liu,Wencui Shang,Yujing Xu,Qinghua Wu,Wei Shen,Ye Yang,Dengke Yin
Humoral immunity-cancer crosstalk has gained attention recently owing to its impact on tumor immune responses and therapy responsiveness. Here, it is shown that epithelial breast cancer cells can directly bind with non-antigen-specific IgA, dependent on polymeric immunoglobulin receptor (PIGR)-mediated transcytosis function, modulating tumoral inflammatory genes and sensitizing antitumor response. To harness this biology, a hybrid tumor vaccine is designed by covering the adjuvant-loaded cancer cell vesicles with a calcium phosphate shell, which retains the antigen information of the original tumor cells and exhibits robust mucosal adhesion in nasal tissues. Following intranasal vaccination, such a hybrid vaccine preferentially activates germinal center responses in nasal-associated lymphoid tissues and drives the production of tumoral antigen-specific IgA-dominated humoral immunity in both serum and lung through the property of “common mucosal immune system”, thus coordinating cellular immune responses to prevent lung colonization of IgA-opsonized breast cancer. In the inoperable and postoperative breast cancer model, intranasal vaccination with the hybrid vaccine also enables the amplification of the therapeutic benefits of local/systemic therapies. In summary, this work presents insights into the antitumor biology of IgA in epithelial breast cancer and explores a highly effective vaccine strategy focused on governing IgA-dominated humoral immunity to combat breast cancer, especially lung metastasis.
研究领域:
肿瘤学
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免疫学
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微生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Zong-hui Xu,Man Li,Lin Liu,Shu-jing Wu,Ruo-an Wei,Mpofu Uphakeme Inobubele Sitholumusa,Xiao-ping Zhao,Jun-qiu Liu,Guo-yin Kai
Astragaloside IV (AS-IV), derived from Astragalus membranaceus , exhibits significant anti-inflammatory properties in a variety of diseases. However, the specific anti-inflammatory mechanism of AS-IV depends on the different organs and doses. Its protective effect is still unknown in acute lung injury (ALI). This study aims to investigate the potential anti-inflammatory mechanism of AS-IV in ALI. Lipopolysaccharide (LPS) and adenosine triphosphate (ATP) were utilized to form pyroptosis models in MH-S and RAW264.7 cells. Mouse model of ALI was induced by intranasal LPS administration. In addition, the anti-pyroptosis effect of AS-IV was evaluated by using the C5aR1 agonists BM-213, the C5aR1 overexpression plasmids and C5aR1 siRNA. AS-IV significantly reduced pulmonary edema, improved histopathological injury, and decreased inflammatory factors. Meanwhile, AS-IV reduced ROS level and the amount of NLRP3 and GSDMD-N in vitro and in vivo . Inhibiting C5aR1 can effectively and significantly alleviate the pyroptosis of alveolar macrophages. Further studies found that BM-213 and C5aR1 overexpression plasmids partially reversed the anti-pyroptosis effect of AS-IV. The anti-pyroptosis effect of AS-IV was significantly inhibited when C5aR1 was knocked down. Our study demonstrate that AS-IV has anti-inflammatory protective effects on LPS-induced ALI, indicating that AS-IV may be a potential therapeutic agent for the treatment of ALI. This effect may be achieved by reducing the content of C5a, lowering the expression of C5aR1, and inhibiting cell pyroptosis.
研究领域:
药理学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR IMMUNOLOGY
·
2025
·
IF 2.9
Yiqi Wang,Xiuhua Zhang,Jiannan Zhang,Mingbo Zhao,Yang Chong,Quankuan Gu,Xianglin Meng,Mingyan Zhao
Acute lung injury (ALI) is a respiratory disease induced by uncontrolled inflammatory responses in the lungs. The pathological features of ALI include alveolar structural damage and pulmonary edema, which ultimately leads to pulmonary dysfunction. ANAPC5 (Anaphase-promoting complex subunit 5) is an E3 ubiquitin ligase known for its anti-inflammatory properties. This study aims to investigate the effects of ANAPC5 on ALI and its underlying molecular mechanism. In the lung tissue of an ALI mouse model induced by lipopolysaccharide (LPS) administration, we observed downregulation of ANAPC5. Through both in vivo and in vitro experiments, we assessed the effect of ANAPC5 on lung injury by conducting pathological analysis and molecular biological detection. ANAPC5 overexpression alleviated inflammatory cell infiltration, reduced alveolar wall thickening, suppressed pulmonary inflammation, and decreased the levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung tissue of the ALI model. Moreover, ANAPC5 inhibited M1 polarization and promoted M2 polarization of macrophages both in vitro and in vivo . We also found that ANAPC5 significantly suppressed the activation and expression of the epidermal growth factor receptor (EGFR) through inducing its ubiquitination in macrophages. In LPS-induced M1 macrophages, the presence of EGFR significantly decreased CD24 expression, followed by reversing the inhibitory effects of ANAPC5 on inflammatory responses and macrophage polarization. Collectively, our findings suggest that ANAPC5 serves as a therapeutic molecular target that mitigates ALI through regulating macrophage M1/M2 polarization via the EGFR/CD24 axis.
研究领域:
免疫学
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呼吸病学
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分子生物学
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炎症反应调控
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转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
OncoTargets and Therapy
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2019
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IF 3.046
Qiao Zhang,Juan Zhang,Jian Zhang,Patiguli Aerxiding,Amina Quhai,Cuncun Chen,Li Shan
Purpose This study aims to elucidate the biological behavior of Neuritin abnormal expression in pulmonary vascular endothelial cells (VECs) of non-small cell lung cancer (NSCLC), and explore its possible underlying mechanisms. Patients and methods Primary NSCLC-VECs were isolated from 10 cancer tissues from NSCLC patients, purified and identified by CD34 and Factor VIII staining. Real-time PCR and Western-blot were adopted for detecting the expression levels of Neuritin, Notch1, and VEGFR in NSCLC-VECs and HPMECs. Neuritin-overexpression, Neuritin-knockdown NSCLC-VECs and HPMECs were constructed by transfection of pcDNA3, 1-Neuritin vector, and pBS/U6-Neuritin siRNA. Changes in cell proliferation, migration, cell cycle, and apoptosis were determined by using the MTT assay, scratch assay, transwell migration assay, and flow cytometry, respectively. Post-transfection changes in cell morphology were examined by scanning electron microscopy. Results The expression of Neuritin in NSCLC-VECs was significantly higher compared to that in HPMECs (p<0.01). Overexpression of Neuritin increased the expression of VEGFR while it reduced the expression of Notch1 (p<0.01); it also promoted cell proliferation, scratch healing, and in vitro migration (p<0.05) in HPMECs and NSCLC-VECs cells. Additionally, overexpression of Neuritin stimulated cell cycle progression and inhibited apoptosis in HPMECs and NSCLC-VECs (p<0.001). Under electron microscope, the pseudopodium of cell surface was obvious, indicating that the intercellular adhesion was upregulated. However, knockdown of Neuritin in HPMECs and NSCLC-VECs played exactly the opposite roles. Conclusion Neuritin was key in the progression of NSCLC through its biological activities, including anti-apoptosis, promoting VEC proliferation, migration, and cell cycle progression. Neuritin may affect its biological activity by positively regulating VEGFR expression and negatively regulating Notch1 signaling. Neuritin may serve as a potential biomarker for NSCLC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
✓ 已验证
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）