ENVIRONMENTAL TOXICOLOGY
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2020
·Vol. 35
·期 9
·982-990
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IF 3.118
Liyang Yao,Yizhou Tang,Bolu Chen,Wuding Hong,Xinyue Xu,Yang Liu,Zoraida P. Aguilar,Hengyi Xu
In this work, we aimed to evaluate the adverse effects and the mechanism of intestinal barrier caused by titanium dioxide nanoparticles (TiO 2 NPs). Here, the effects of two different dosages (300 and 1200 mg/kg) of TiO 2 NPs on female mice (n = 5) were investigated. After 28-day oral exposure, the results of Ti content were significantly increased in the ileum in comparison with the control. The histopathological structure index of the ileum was significantly changed after TiO 2 NPs exposure; villi height and crypt depth were decreased and increased, respectively. Meanwhile, TiO 2 NPs treatment also significantly altered the transcription levels of genes. First, the GATA-3 and STAT-4 were upregulation and downregulation, respectively. Second, gene expressions of the Zonula Occludens-1, claudin ( CLDN ) -12 , occludin, and myosin light chain kinase were significantly upregulated, while the CLDN-3 was decreased. Finally, the caspase-3 , caspase-9 , and caspase-12 were upregulated. The results of TUNEL staining indicated apoptosis in the ileum. In general, TiO 2 NPs treatment significantly changed the intestine physical barrier in a dose-dependent manner. The toxicity of TiO 2 NPs could be through the imbalance in the Th1/Th2.
研究领域:
毒理学
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免疫学
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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
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2020
·
IF 3.69
Pengfei Li,Jingkang Wang,Chunguo Wang,Long Cheng,Quantao Ma,Yaqi Li,Yongcheng An,Hongyu Dai,Yuhui Duan,Tieshan Wang,Xuan Ma,Minghui Zhang,Ting Wang,Baosheng Zhao
Ethnopharmacological relevance Hanchuan Zupa Granule (HCZP), a traditional Chinese ethnodrug, has the functions of supressing a cough, resolving phlegm, warming the lungs, and relieving asthma. In clinical practice employing traditional Chinese medicine (TCM), HCZP is commonly used to treat acute colds, cough and abnormal mucous asthma caused by a cold, or “Nai-Zi-Lai” in the Uygur language. Studies have confirmed the use of HCZP to treat cough variant asthma (CVA) and other respiratory diseases . However, the pharmacological mechanisms of HCZP remain unrevealed. Aim of the study To investigate the anti-tussive and anti-asthmatic effects and the possible pharmacological mechanisms of HCZP in the treatment of CVA. Materials and methods A guinea pig CVA animal model was established by intraperitoneal injection of ovalbumin (OVA) combined with intraperitoneal injection of aluminium hydroxide adjuvant and atomized OVA. Meanwhile, guinea pigs with CVA received oral HCZP (at dosages of 0.571, 0.285 and 0.143 g/kg bodyweight). The number of coughs induced by aerosol capsaicin was recorded, and the airway hyperresponsiveness (AHR) of CVA guinea pigs was detected with the FinePointe series RC system. H&E staining of lung tissues was performed to observe pathological changes. ELISA was used to detect inflammatory cytokines. qRT-PCR and western blotting analyses were used to detect the expression of Th1-specific transcription factor (T-bet), Th2-specific transcription factor (GATA3), and Toll-like receptor 4 (TLR4) signal transduction elements. These methods were performed to assess the protective effects and the potential mechanisms of HCZP on CVA. Results Great changes were found in the CVA guinea pig model after HCZP treatment. The number of coughs induced by capsaicin in guinea pigs decreased, the body weights of guinea pigs increased, and inflammation of the eosinophilic airway and AHR were reduced simultaneously. These results indicate that HCZP has a significant protective effect on CVA. A pharmacological study of HCZP showed that the levels of interleukin-4 (IL-4) and IL-5 and tumour necrosis factor-α (TNF-α) in serum decreased. The amount of interferon-γ (IFN-γ) increased, mRNA and protein expression of TLR4 and GATA3 weakened, and mRNA and protein expression of T-bet increased. Conclusions HCZP ameliorated the symptoms of guinea pigs with CVA induced by OVA by regulating the Th1/Th2 imbalance and TLR4 receptors.
研究领域:
药理学
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传统中药
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呼吸系统疾病
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免疫学
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产品关联
DOI
PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2021
·
IF 2.73
Jinhui Dong,Ou Xu,Jianxing Wang,Chunguang Shan,Xiumin Ren
Objective Luteolin has an anti-allergic effect but its mechanism is not clear. This study attempted to determine the mechanisms of luteolin in rhinitis.Methods Allergic rhinitis rat model was established by ovalbumin (OVA) stimulation. Then, the rats were treated with normal saline, luteolin, or lipopolysaccharide (LPS) for 14 days. Nasal symptoms were scored; the histopathological changes of nasal mucosa were detected by hematoxylin–eosin staining. Serum levels of Th1 type cytokines (IFN-γ, IL-2), Th2 type cytokines (IL-4, IL-5, IL-13), and OVA-specific IgE (sIgE) were determined by ELISA. The expressions of Toll-like receptor 4 (TLR4) and p65 in nasal mucosa were detected by Western blot or immunohistochemistry.Results Luteolin decreased symptom scores, specifically, the scores in control group, model group, model + 0.1 mg/kg luteolin, model + 1 mg/kg luteolin, and model + 10 mg/kg luteolin groups were 0.63 ± 0.52, 7.88 ± 0.83, 1.38 ± 0.52, 2.75 ± 0.46, and 5.00 ± 0.53, respectively. Luteolin ameliorated nasal mucosa inflammation by promoting the down-regulated levels of Th1 type cytokines, and suppressing the up-regulated levels of Th2 type cytokines, OVE-sIgE, TLR4, and p65. LPS further increased symptom scores, aggravated nasal mucosa inflammation, improved the unbalance of Th1/Th2 type cytokines, and lowered the expressions of OVE-sIgE, TLR4, and p65. Moreover, LPS reversed the effect of luteolin on allergic rhinitis rats.Conclusion Luteolin ameliorated inflammation and Th1/Th2 imbalance via regulating the TLR4/NF-κB pathway in allergic rhinitis rats. This study provided novel evidence that luteolin could be used as a candidate drug in allergic rhinitis treatment.
研究领域:
免疫学
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药理学
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过敏
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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
·
2024
·
IF 10
Wei Liu,Di Liu,Tianyi Cui,Yili Wang,Sufei Zhou,Fangzhen Tian,Ke Yang,Wei Wang,Lewei Bi,Kelong Fan,Lan Li,Hao Wang,Xiao-Dong Zhang
Pneumonia involves complex immunological and pathological processes leading to pulmonary dysfunction, which can be life-threatening yet lacks effective specialized medications. Natural enzymes can be used as biological agents for the treatment of oxidative stress-related diseases, but limiting to catalytic and environmental stability as well as high cost. Herein, an artificial enzyme, gold nanoclusters (Au NCs) with excellent stability, bioactivity, and renal clearance can be used as the next-generation biological agents for acute lung injury (ALI) and allergic lung disease (ALD). The Au 25 clusters can mimic catalase (CAT) and glutathione peroxidase (GPx), and the K m of Au 24 Er 1 with H 2 O 2 reaches 1.28 mM, about 22 times higher than natural CAT (≈28.8 mM). The clusters inhibit the oxidative stress in the mitochondria and promote the synthesis of adenosine triphosphate (ATP). The molecular mechanism shows that the TLR4/MyD88/NF-κB pathway and M1 macrophage-mediated inflammatory response are suppressed in ALI and the Th1/Th2 imbalance in ovalbumin (OVA)-induced ALD is rescued. Further, the clusters can notably improve lung function in both ALI and ALD models which paves the way for immunomodulation and intervention for lung injury and can be used as a substitute for natural enzymes and potential biopharmaceuticals in the treatment of various types of pneumonia.
研究领域:
纳米技术
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免疫学
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药理学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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