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Evidence-based Complementary and Alternative Medicine · 2022 · IF 2.65

Electroacupuncture Preconditioning Alleviates Lipopolysaccharides-Induced Acute Lung Injury by Downregulating LC3‐II/I and Beclin 1 Expression

Guanghua Sun,Yahua Zeng,Fu Luo,Lixian Zhang,Jinqu Tan,Jie Tong,Lu Yang,Danni Liu,Liu Liu,Jun Zhou

Our study aimed to investigate the effect of electroacupuncture pretreatment on the inflammatory response and expression levels of LC3-II/I and Beclin 1 using a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Eighteen male Sprague-Dawley (SD) rats were randomly divided into three groups: normal control group (NC, n = 6), LSP modeling group (LM, n = 6), and electroacupuncture group (EA, n = 6). Rats in the EA group received electroacupuncture pretreatment at bilateral Zusanli (ST36) and Chize (LU5) points for five days (30 min each time daily, frequency; 3 Hz/15 Hz, intensity; 1 mA). Rats in the EA and LM groups were then injected with 5 mg/kg LPS (Beijing, Solarbio Company, concentration; 5 mg/mL) through the tail vein, while those in the NC group were injected with 5 mg/kg saline. The animals were sacrificed six hours after LPS or saline injection through cervical vertebrae by dislocation under deep anesthesia. Orbital blood was collected for the analysis of serum inflammatory factors including interleukin-1β (IL-1β) and transforming growth factor-β (TGF-β). The lower left lung was excised, stained with hematoxylin-eosin (HE), and subjected to histopathological analysis. The mRNA and protein expression of Beclin 1 and LC3 II/I in the lower right lung tissues were detected via RT-qPCR and Western blot analyses, respectively. The results showed that lung injury score was significantly higher in the LM group than that of the NC group () and EA group (). The IL-1β contents were significantly decreased in the EA group () than in the LM group. In contrast, the GF-β contents were increased in the EA group significantly when compared with the LM group (). RT-qPCR and Western blot detection showed that the relative gene expression of LC3‐II/I and Beclin 1 was significantly lower in the EA group than in the LM group (). However, the relative protein expression level of LC3‐II/I and Beclin 1 was slightly lower in the EA group than the in LM group (). These results show that electroacupuncture pretreatment reduces the inflammatory response in ALI and can protect lung tissue by inhibiting the gene and protein expression levels of LC3‐II/I and Beclin 1.

CAS / MDL: 110-18-9
研究领域: 药理学 · 免疫学 · 肺病学 · 中医
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD AND CHEMICAL TOXICOLOGY · 2019 · IF 3.775

Cyanidin chloride modestly protects Caco-2 cells from ZnO nanoparticle exposure probably through the induction of autophagy

Leying Jiang,Zhen Li,Yixi Xie,Liangliang Liu,Yi Cao

Recent studies suggest that phytochemicals , as part of the food matrix, might alter the toxicity of nanoparticles (NPs); however, relatively few studies have investigated the impact of anthocyanidins on the toxicity of NPs to cells lining the gastrointestinal tract. Therefore, this study used cyanidin chloride (CC) as the model for anthocyanidins and investigated the effects of CC on the toxicity of ZnO or Ag NPs to Caco-2 cells. Exposure to ZnO but not Ag NPs significantly induced cytotoxicity. The presence of CC, but not its analog quercetin (Qu), modestly protected Caco-2 cells from ZnO NP exposure. However, the intracellular superoxide, Zn ions , or release of interleukin-8 after ZnO NP exposure were not significantly affected by the presence of CC. Rather, CC promoted the expression of autophagic genes ATG5 , ATG7 , and BECN1 as well as the ratio of LC3-II/I after exposure to ZnO NPs. Meanwhile, the presence of autophagic inhibitors (chloroquine, NH 4 Cl, bafilomycin A1) significantly promoted the cytotoxicity of ZnO NPs and inhibited the cytoprotective effects of CC. In conclusion, these data suggest that CC could modestly protect Caco-2 cells from ZnO NP exposure, probably through the induction of autophagy.

CAS / MDL: 12125-02-9
研究领域: 毒理学 · 细胞生物学 · 药理学 · 纳米技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Molecular Medicine Reports · 2023 ·Vol. 28 ·期 4 ·1-13 · IF 3.4

Iron oxide nanoparticles induce ferroptosis via the autophagic pathway by synergistic bundling with paclitaxel

Qi Nie,Wenqing Chen,Tianmei Zhang,Shangrong Ye,Zhongyu Ren,Peng Zhang,Jian Wen

In recent years, inhibiting tumor cell activity by triggering cell ferroptosis has become a research hotspot. The development of generic targeted nanotherapeutics might bring new ideas for non‑invasive applications. Currently, the potential mechanism underlying the universal application of paclitaxel (PTX)‑loaded iron oxide nanoparticles (IONP@PTX) to different types of tumors is unclear. The present study aimed to prepare IONP@PTX for targeted cancer therapy and further explore the potential mechanisms underlying the inhibitory effects of this material on the NCI‑H446 human small cell lung cancer and brain M059K malignant glioblastoma cell lines. First, a CCK‑8 assay was performed to determine cell viability, and then the combination index for evaluating drug combination interaction effect was evaluated. Intracellular reactive oxygen species (ROS) and lipid peroxidation levels were monitored using a DCFH‑DA fluorescent probe and a C11‑BODIPY™ fluorescent probe, respectively. Furthermore, western blotting assay was performed to determine the expression of autophagy‑ and iron death‑related proteins. The experimental results showed that, compared with either IONP monotherapy, PTX monotherapy, or IONP + PTX, IONP@PTX exerted a synergistic effect on the viability of both cell types, with significantly increased total iron ion concentration, ROS levels and lipid peroxidation levels. IONP@PTX significantly increased the expression of autophagy‑related proteins Beclin 1 and histone deacetylase 6 (HDAC6) in both cell lines (P<0.05), increased the expression of light chain 3 (LC3)‑II/I in NCI‑H446 cells (P<0.05) and decreased that of sequestosome1 (p62) in M059K cells (P<0.05). Moreover, the addition of rapamycin enhanced the IONP@PTX‑induced the upregulation of Beclin 1, LC3‑II/I and HDAC6 and the downregulation of mTORC1 protein in both cell lines (P<0.05). Moreover, rapamycin enhanced the IONP@PTX‑induced downregulation of p62 protein in NCI‑H446 cells (P<0.05), suggesting that IONP@PTX induces ferroptosis, most likely through autophagy. Collectively, the present findings show that IONP works synergistically with PTX to induce ferroptosis via the autophagic pathway.

研究领域: 纳米技术 · 癌症治疗 · 细胞生物学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Jove-Journal of Visualized Experiments · 2023 · IF 1.2

Therapeutic Effects of Huazhuojiedu Decoction on Precancerous Lesions of Gastric Cancer by Regulating Mitophagy

Tianxiao Yang,Pingping Zhou,Ziwei Zhang,Xinyu Hao,Shaowei Liu,Haoyu Chen,Yuhua Wang,Yangang Wang

This research aims to explore the therapeutic effect and potential mechanisms of Huazhuojiedu decoction (HZJD) for alleviating precancerous lesions of gastric cancer (PLGC) both in vivo and in vitro. HZJD is a traditional Chinese herbal formula consisting of 11 herbs. Sprague-Dawley (SD) rats were randomly divided into four subgroups: control group, model group, positive drug group, and HZJD group. Hematoxylin-eosin (H&E) staining, high iron diamine-alcian blue (HID-AB) staining, alcian blue-periodic acid Schiff (AB-PAS) staining, immunohistochemistry, immunofluorescence, RT-qPCR, and Western blot assays were performed after 10 weeks of HZJD treatment. In vitro, the cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation. RT-qPCR and Western blot assays were performed to evaluate mitophagy levels. The results indicated that HZJD could retard the pathological progression in PLGC rats and reduce PLGC cell proliferation. Treatment with HZJD significantly increased the mRNA and protein expression levels of Sirt3, Foxo3a, Parkin, and LC3 II/I, while decreasing the mRNA and protein expression levels of p62 and Tomm20. HZJD was found to have the ability to reverse the decline in mitophagy activity both in vivo and in vitro. In conclusion, the study assessed the impact of HZJD and provided evidence regarding its potential molecular mechanism.

CAS / MDL: 54-21-7
研究领域: 中医药 · 肿瘤学 · 分子生物学 · 病理学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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