American Journal of Translational Research
·
2024
·Vol. 16
·期 12
·8008
·
IF 1.7
Yalan Zuo,Peidan Yang,Ruixia Yang,Juan Hou,Rui Feng,Ping Liang,Jiang Liu
Objectives: The aim of this study was to establish an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the detection of osimertinib in rat plasma, lung and brain tissues. Methods: Forty-eight rats were randomly divided into an experimental group (receiving osimertinib at doses of 5, 8, and 10 mg/kg) and a control group. After continuous intragastric administration for 15 days, samples of blood, lung, and brain tissue were collected. Chromatographic separation was achieved using a BEH C18 column with gradient elution, employing a mobile phase of water (containing 0.1% (v/v) formic acid) and acetonitrile. The concentration of osimertinib in the samples was determined using an AB SCIEX 5500 triple quadrupole mass spectrometer operated in positive electrospray ionization (ESI+) and multiple reaction monitoring (MRM) mode. Results: A UPLC-MS/MS analytical method for determining osimertinib concentrations was successfully established and validated. A linear relationship was observed for osimertinib concentrations in plasma within the range of 1-300 ng/mL, and in lung and brain tissues within the range of 0.5-50 ng/mL. The selectivity, accuracy, precision, matrix effect, extraction recovery, and stability all meet the requirements of methodological validation criteria. Conclusions: A rapid and sensitive UPLC-MS/MS method was developed and validated for quantifying osimertinib concentrations in rat plasma, lung, and brain tissues, providing a valuable tool for pharmacokinetic and tissue distribution studies.
研究领域:
药理学
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分析化学
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药物代谢动力学
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DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMISTRY
·
2018
·Vol. 164
·期 6
·427-435
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IF 2.35
Xu Tanye,Zhou Lin,Shi Yingying,Liu Liwei,Zuo Lihua,Jia Qingquan,Du Shuzhang,Kang Jian,Zhang Xiaojian,Sun Zhi
Sepsis is the dysregulated host response to an infection which leads to life-threatening organ dysfunction. Metabolomic profiling in bio-fluid or tissue is vital for elucidating the pathogenesis of sepsis and evaluating therapeutic effects of medication. In this study, an untargeted metabolomics approach was applied to study the metabolic changes in lung tissue of septic rats induced by cecal ligation and puncture (CLP) and investigate the treatment effects of Xubijing injection (XBJ). Metabolomics analyses were performed on ultra-high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap-HRMS) together with multivariate statistical analysis. A total of 26 differential metabolites between CLP and sham-operated group were identified. The altered metabolic pathways included energy metabolism, amino metabolism, lipid metabolism, fatty acid metabolism and hormone metabolism. Among the 26-varied metabolites, 15 were significantly regulated after XBJ treatment. The metabolic pathway network of sepsis was drawn to interpret the pathological feature of lung damage caused by sepsis and the underlying regulating mechanism of XBJ on the molecular levels. Our findings display that LC-MS-based metabolomics is a useful tool for uncovering the underlying molecular mechanism of sepsis, and XBJ may exert therapeutic effect by regulating multiple metabolic pathways.
研究领域:
医学
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药理学
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生物化学
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DOI
PubMed
高影响因子
Journal of Traditional Chinese Medicine
·
2025
·Vol. 45
·期 5
·1040
·
IF 2.2
Yuanmei ZHANG,Heqing LIU,Shaowen WANG,Lele WANG,Yawen GAO,Rui SUN,Jihui TANG
OBJECTIVE: To investigate whether Jiegeng ( Radix Platycodi , RP) has a Yin - Jing potentiating effect on Jingjie ( Herba Schizonepetae Tenuifoliae, ST). We investigated the pharmacokinetics and tissue distribution of pulegone, the active ingredient in ST volatile oil, in rats to verify the scientific validity of the Yin - Jing doctrine, the basic theory of Traditional Chinese Medicine (TCM). METHODS: The volatile oil and aqueous extract of ST were extracted by hydrodistillation. RP's aqueous extract underwent aqueous extraction. After individual and co-administration, we conducted pharmacokinetic and tissue distribution studies on Sprague-Dawley male rats. RESULTS: Peak concentration (Cmax), mean retention time from 0 to ∞ (MRT0→∞), and area under the curve (AUC0→10), (AUC0→∞) were 1.51, 1.14, 2.34, and 3.86 times higher in the co-administration group than in the individual administration group, respectively ( P < 0.05). In addition, half-life (T1/2) was significantly prolonged in the co-administration group ( P < 0.05). Meanwhile, the clearance and elimination rate constant (Ke) in the co-administration group were significantly lower than those in the individual administration group, just 50% of those in the individual administration group ( P < 0.05). After co-administration of the drug, the pulegone content in all tissues of the rats was elevated to varying degrees, especially a significant increase in the drug content in lung tissues ( P < 0.05). CONCLUSION: After co-administration, the retention of pulegone in the body was prolonged, the elimination of pulegone from the body was delayed, and the accumulation of pulegone in the lungs was facilitated. Therefore, using RP as a Yin - Jing drug concoction has a significant cumulative effect of inducing upward mobilization and targeting lung tissues.
研究领域:
中药药理学
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药物代谢
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药代动力学
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传统中医药理论
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组织分布
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天然药物化学
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药物相互作用
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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
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肿瘤学
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光学成像
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DOI
高影响因子
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
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2024
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IF 2.1
Lingyu Zhang,Lina Cai,Yashi Cai,Weiyi Ke,Linqian Zhou,Yuhua Yang,Weixu Huang,Jianming Zou,Huifeng Chen
Purpose To investigate the role of moderate doses of ionizing radiation-induced cellular senescence in mouse lung tissue and whole-body inflammation levels.Material and methods Forty-two C57BL/6J mice were randomly divided into the control group, the 1, 3, and 7 days after 2 Gy irradiation group, and the 1, 3, and 7 days after 4 Gy irradiation group, with six mice in each group. The histopathology, cellular senescence, oxidative-antioxidant, DNA damage repair, and inflammation-related indicators of irradiated mice were examined.Results Compared with the control group, the histopathological scores, the positive area of senescence-associated-β-galactosidase (SA-β-Gal) staining, and the mRNA levels of senescence-related genes in the lung tissues in all dose groups increased on 1, 3, and 7 days after irradiation. In peripheral blood, erythrocytes, leukocytes, platelets, hemoglobin, 8-hydroxydeoxyguanosine (8-OHdG), C-reactive protein, and other indicators showed a different trend in all dose groups. The levels of malondialdehyde(MDA), superoxide dismutase (SOD), glutathione (GSH), and 8-OHdG in the lung tissue showed different trends after 2 Gy and 4 Gy irradiation. The 8-Oxoguanine DNA glycosylase 1 (hOGG1) and O-6-methylguanine-DNA methyltransferase (MGMT) mRNA levels showed a trend of increasing and then decreasing. The levels of whole-body inflammation were significantly correlated with the levels of indicators related to cellular senescence and damage repair in the lung tissue of mice.Conclusions The moderate doses of ionizing radiation induce oxidative stress, and DNA damage and increase DNA repair gene expression in mouse lung tissue. The lung tissue cellular senescence correlates with the level of whole-body inflammation.
研究领域:
放射生物学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2025
·
IF 3.5
Zhiqiang Ji,Zekang Su,Changmao Long,Shiyi Hong,Yali Zhang,Xiaoli Wang,Guiping Hu,Guang Jia
Hexavalent chromium [Cr(VI)] is a known human carcinogen that is associated with environmental pollution and health risks. However, the relationship between its immunotoxicity and inflammation is still poorly understood. In this study, researchers used a mouse dynamic inhalation exposure system to simulate Cr(VI) occupational environments and conducted multi-organ immunological assessment along with lung tissue inflammatory profiling. It was observed that Cr(VI) inhalation exposure induced selective, time-dependent variations in lymphocyte subsets across specific organs, accompanied by significant upregulation of immune-related cytokines. The exposure triggered neutrophil extracellular traps (NETs) formation in lung tissue with concurrent elevation in NETs-associated gene expression and inflammasome-related gene activation. Immune dysregulation demonstrated close correlation with inflammation characterized by NETs formation and inflammasome activation. Furthermore, a two-week recovery period resulted in significant amelioration of these Cr(VI)-induced immunological disturbances and inflammatory manifestations. These findings provide critical insights into the crosstalk between immune dysfunction and inflammatory activation in occupational Cr(VI) exposure.
研究领域:
免疫毒理学
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环境卫生
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职业医学
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肺部生物学
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分子毒理学
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DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2023
·
IF 7.4
Daohui Gong,Xueping Liu,Pengfei Wu,Yue Chen,Yuhang Xu,Zhan Gao,Hang Qian,Guansong Wang,Binfeng He
Macrophage dysfunction is a significant contributor to more than 70 % of sepsis-related deaths, specifically secondary bacterial infections, during the immunosuppression stage of sepsis. Nevertheless, the role of Rab26 in this context remains unclear. In this study, we observed a substantial decrease in Rab26 expression in macrophages during the immunosuppressive phase of sepsis, which was also found to be suppressed by high extracellular levels of HMGB1 . During the progression of sepsis, Rab26 deficiency promotes a polarization shift from the M1 to the M2-like phenotype in macrophages, rendering them susceptible to ferroptosis . Subsequent experimentation has revealed that Rab26 deficiency facilitates the degradation of GPX4, thereby aggravating macrophage ferroptosis through the upregulation of levels of lipid ROS , MDA , and ferrous iron induced by RSL3, a ferroptosis inducer. Additionally, Rab26-deficient mice in the immunosuppressed phase of sepsis exhibit heightened susceptibility to secondary infections, leading to exacerbated lung tissue damage and increased mortality rate. Overall, these findings indicate that Rab26 plays a crucial role in sepsis-induced macrophage immunosuppression by regulating macrophage ferroptosis and polarization. Hence, it represents a potential novel target for sepsis therapy.
研究领域:
免疫学
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细胞生物学
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传染病学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
·
IF 12.2
Zhe Du,Qingping Liu,Mengruo Wang,Yifu Gao,Qi Li,Yizhe Yang,Tianyu Lu,Lei Bao,Yaxian Pang,Haijun Wang,Yujie Niu,Rong Zhang
Accumulating evidence indicates that maternal exposure to carbon black nanoparticles (CBNPs) during gestation can induce multiple system abnormalities in offspring, whereas its potential mechanism in respiratory disease is still largely unknown. In order to explore the effect of maternal exposure to CBNPs on offspring’s lung and latent pathogenesis, we respectively established in vivo model of pregnant rats exposed to CBNPs and ex vivo model of lung epithelial cells treated with pups’ serum of pregnant rats exposed to CBNPs. After maternal exposure to CBNPs, epithelial-mesenchymal transition (EMT) and fibrosis levels increased as a result of DDRGK1-mediated reticulophagy upregulated in offspring’s lung. DDRGK1 as FAM134B’s cargo bound with FAM134B to mediate reticulophagy. Transcription factor “SP1” positively regulated DDRGK1 gene expression by binding to its promoter. Furthermore, the upregulation of NSUN2 elevated m 5 C methylation of SP1 mRNA and the protein level of SP1 subsequently increased through Ybx1 recognizing and stabilizing m 5 C-methylated SP1 mRNA, followed by the increased levels of reticulophagy and fibrosis in lung epithelial cells treated with offspring’s serum of matrix exposed to CBNPs during gestation. In conclusion, NSUN2/Ybx1/m 5 C-SP1 axis promoted DDRGK1-mediated reticulophagy, which played an important role in EMT-induced fibrosis in offspring’s lung tissue after maternal exposure to CBNPs during gestation.
研究领域:
呼吸系统疾病
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纳米毒理学
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分子生物学
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表观遗传学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Yingying Xu,Liu Yang,Ting Zhao,Zhouyu Liao,Yijing Zheng,Haohua Deng,Chenghai Zhang,Wei Dang,Junjin Lin,Cailin Yan,Quanquan Zhuang,Wei Chen
Pulmonary delivery of monoclonal antibodies has revolutionized the treatment of various types of lung diseases, such as severe asthma. However, the inconsistent antibody drug concentrations in the lungs and serum highlight the importance of monitoring the actual antibody distribution change in the lungs. In this study, we developed a novel antibody-functionalized gold nanocluster with high spatiotemporal resolution for fluorescence/CT dual-modal imaging based on an antibody targeting an allergic-airway-inflammation-related free cytokine in lungs. Specifically, the antiasthmatic effects of an IL-5-specific antibody (reslizumab) were first confirmed following pulmonary administration in mice, and reslizumab-functionalized gold nanoclusters successfully achieved the real-time and in situ monitoring of the therapeutic antibody’s change in lung tissues and differentiated the discrepancy between asthmatic and normal mice under fluorescence or CT imaging systems at an early stage after administration. As a proof of concept, it is the first report that an antibody-functionalized gold nanocluster could be used to provide comprehensive pharmacokinetic and pharmacodynamic insight into the quick lung tissue distribution change of a monoclonal antibody drug in mice, which will facilitate the development of both inhaled antibody drugs and other tissue-specific therapeutic antibodies that target different disease-related factors that are pathologically overexpressed in a specific tissue or organ.
研究领域:
纳米技术
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生物医学成像
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呼吸病学
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药理学
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免疫学
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药物递送
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产品关联
DOI
PubMed
高影响因子
Annals of Medicine and Surgery
·
2023
·Vol. 85
·期 11
·5469
·
IF 1.7
Ren Yuzhe,Li Xing,Zhang Yuanjie,Yan Zilong
Xiaoqinglong decoction (XQLD) is widely used clinically in the treatment of childhood cough variant asthma (CVA). However, its potential mechanism is still unknown. In the present study, the authors investigate the biological network and signalling pathway of XQLD in treatment of childhood CVA using network pharmacology-based analysis and experimental validation. By using the Bioinformatics Analysis Tool Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, the authors confirmed the correlation between XQLD and asthma, and the authors screened 1338 potential target genes of Mahuang and Guizhi, the most active herbs in XQLD. By overlapping “Childhood asthma-related genes” of DisGeNET database, the authors identified 58 intersecting genes of Childhood asthma and 1338 target genes of Mahuang and Guizhi. The intersecting genes were used to construct the protein-to-protein interaction and performed Gene Ontology (GO) functional and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Gene Ontology enrichment analysis demonstrated 359 Biological Process terms, 16 Cellular Component terms, and 26 Molecular Function terms. Meantime, 75 terms of Kyoto Encyclopedia of Genes and Genomes signalling pathway were involved in enrichment analysis. These candidates showed a significant correlation with inflammatory response and positive regulation of tyrosine phosphorylation of STAT protein. In addition, XQLD treatment significantly upregulated serum interferon-γ expression, and downregulated serum interlukin-6 expression of CVA mice. XQLD treatment significantly inhibited phosphorylation of STAT3 in bronchial-lung tissues. Our data suggest that XQLD effectively alleviated bronchial-lung tissue damage in CVA mice and inhibited the body inflammatory response by regulating interlukin-6/STAT3 signalling pathway.
研究领域:
药理学
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免疫学
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分子生物学
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中医
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DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2022
·
IF 4.631
Renhui Huang,Qi Shi,Shutian Zhang,Hong Lin,Chengzhi Han,Xinyi Qian,Yijun Huang,Xiaorong Ren,Jiayuan Sun,Nana Feng,Chunmei Xia,Meng Shi
Purpose: Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis of lung ischemia/reperfusion (I/R) injury. Cyclic GMP-AMP synthase (cGAS) is a cytosol dsDNA sensor, coupling with downstream stimulator of interferon genes (STING) located in the ER, which involves innate immune responses. The aim of our present study was to investigate the effects of cGAS on lung I/R injury via regulating ERS.Methods: We used Sprague-Dawley rats to make the lung I/R model by performing left hilum occlusion-reperfusion surgery. cGAS-specific inhibitor RU.521, STING agonist SR-717, and 4-phenylbutyric acid (4-PBA), the ERS inhibitor, were intraperitoneally administered in rats. Double immunofluorescent staining was applied to detect the colocalization of cGAS or BiP, an ERS protein, with alveolar epithelial type II cells (AECIIs) marker. We used transmission electron microscopy to examine the ultrastructure of ER and mitochondria. Apoptosis and oxidative stress in the lungs were assessed, respectively. The profiles of pulmonary edema and lung tissue injury were evaluated. And the pulmonary ventilation function was measured using a spirometer system.Results: In lung I/R rats, the cGAS-STING pathway was upregulated, which implied they were activated. After cGAS-STING pathway was inhibited or activated in lung I/R rats, the ERS was alleviated after cGAS was inhibited, while when STING was activated after lung I/R, ERS was aggravated in the AECIIs, these results suggested that cGAS-STING pathway might trigger ERS responses. Furthermore, activation of cGAS-STING pathway induced increased apoptosis, inflammation, and oxidative stress via regulating ERS and therefore resulted in pulmonary edema and pathological injury in the lungs of I/R rats. Inhibition of cGAS-STING pathway attenuated ERS, therefore attenuated lung injury and promoted pulmonary ventilation function in I/R rats.Conclusion: Inhibition of the cGAS-STING pathway attenuates lung ischemia/reperfusion injury via alleviating endoplasmic reticulum stress in alveolar epithelial type II cells of rats.
研究领域:
免疫学
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病理生理学
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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
Acta Pharmaceutica Sinica B
·
2021
·
IF 11.614
Ting Chen,Bo Zhuang,Yueqi Huang,Yan Liu,Bochuan Yuan,Wanmei Wang,Tianyu Yuan,Lina Du,Yiguang Jin
Radiation therapy is an effective method to kill cancer cells and shrink tumors using high-energy X-ray or γ -ray. Radiation pneumonitis (RP) is one of the most serious complications of radiation therapy for thoracic cancers, commonly leading to serious respiratory distress and poor prognosis. Here, we prepared curcumin-loaded mesoporous polydopamine nanoparticles (CMPN) for prevention and treatment of RP by pulmonary delivery. Mesoporous polydopamine nanoparticles (MPDA) were successfully synthesized with an emulsion-induced interface polymerization method and curcumin was loaded in MPDA via π‒π stacking and hydrogen bonding interaction. MPDA owned the uniform spherical morphology with numerous mesopores that disappeared after loading curcumin. More than 80% curcumin released from CMPN in 6 h and mesopores recovered. CMPN remarkably protected BEAS-2B cells from γ -ray radiation injury by inhibiting apoptosis. RP rat models were established after a single dose of 15 Gy 60 Co γ -ray radiation was performed on the chest area. Effective therapy of RP was achieved by intratracheal administration of CMPN due to free radical scavenging and anti-oxidation ability, and reduced proinflammatory cytokines, high superoxide dismutase, decreased malondialdehyde, and alleviated lung tissue damages were observed. Inhaled CMPN paves a new avenue for the treatment of RP.
研究领域:
放射肿瘤学
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纳米技术
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药剂学
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肺科学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）