Evidence-based Complementary and Alternative Medicine
·
2022
·
IF 2.65
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.
研究领域:
药理学
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免疫学
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肺病学
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中医
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2017
·Vol. 8
·期 8
·e2988
·
IF 5.965
Yan Siyuan,Liu Ling,Ren Fengxia,Gao Quan,Xu Shanshan,Hou Bolin,Wang Yange,Jiang Xuejun,Che Yongsheng
Deficiency of autophagy has been linked to increase in nuclear instability, but the role of autophagy in regulating the formation and elimination of micronuclei, a diagnostic marker for genomic instability, is limited in mammalian cells. Utilizing immunostaining and subcellular fractionation, we found that either LC3-II or the phosphorylated Ulk1 localized in nuclei, and immunoprecipitation results showed that both LC3 and Unc-51-like kinase 1 (Ulk1) interacted with γ -H2AX, a marker for the DNA double-strand breaks (DSB). Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, was found to enhance the autophagic flux concurring with increase in the frequency of micronuclei accrued upon inhibition of autophagy, and similar results were also obtained in the rasfonin-treated cells. Moreover, the punctate LC3 staining colocalized with micronuclei. Unexpectedly, deprivation of SQSTM1/p62 alone accumulated micronuclei, which was not further increased upon challenge with ST. Rad51 is a protein central to repairing DSB by homologous recombination and treatment with ST or rasfonin decreased its expression. In several cell lines, p62 appeared in the immunoprecipites of Rad51, whereas LC3, Ulk1 and p62 interacted with PARP-1, another protein involved in DNA repair and genomic stability. In addition, knockdown of either Rad51 or PARP-1 completely inhibited the ST-induced autophagic flux. Taken together, the data presented here demonstrated that both LC3-II and the phosphorylated Ulk1 localized in nuclei and interacted with the proteins essential for nuclear stability, thereby revealing a more intimate relationship between autophagy and genomic stability.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2018
·
IF 3.974
Peng Chen,Na Geng,Dong Zhou,Yiran Zhu,Yuliang Xu,Kangping Liu,Yongxia Liu,Jianzhu Liu
Hexavalent chromium (Cr(VI)) is a common environmental pollutant. Exposure of Cr(VI) can lead to cell autophagy, but the preventive measures for diminishing Cr(VI)-induced autophagy need further study. COX-2 can be induced by several heavy metals and can lead to endoplasmic reticulum (ER) stress and autophagy; thus, COX-2, ER stress, and autophagy may be related. This study mainly investigated the role of COX-2 in the eIF2α-ATF4 pathway, which is a major pathway in cell autophagy. In this study, Cr(VI) was used as a xenobiotic to determine changes in the parameters of ER stress, autophagy, and COX-2 levels. At the same time, a clear contrast was obtained by assigning positive and negative controls of ER stress and autophagy. The results showed that during Cr(VI) invasion, the parameters of ER stress and autophagy (such as BiP, PERK, p62, LC3-II, and mTOR) were enhanced, similarly to the positive control of ER stress and/or the autophagy controls. Such enhancement is a protective mechanism for cell survival. Additionally, the COX-2 levels increased. Moreover, when COX-2 was inhibited, the PERK level remained high, whereas the LC3-II level decreased. This finding suggests that COX-2 specifically affects the interaction between ER stress and autophagy. Notably, this study reveals that Cr(VI) can induce ER stress and autophagy in DF-1 cells and that COX-2 plays an essential role in the interaction between ER stress and autophagy.
研究领域:
毒理学
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细胞生物学
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环境科学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2020
·Vol. 25
·期 22
·5302
·
IF 3.267
Lili Qin,Tianfeng Lu,Yao Qin,Yiwei He,Ningxin Cui,Ai Du,Jingyu Sun
Resveratrol (RSV) is a natural flavonoid polyphenol compound extracted from the plants which shows various biological activities. However, the clinical application of RSV is limited by its poor aqueous solubility, rapid metabolism and poor bioavailability. In this study, resveratrol-loaded solid lipid nanoparticles (RSV- SLNs) was design as a nano-antioxidant against the physical fatigue. The resultant RSV-SLNs were characterized by photon correlation spectroscopy (PCS), transmission electron micrographs (TEM), zeta potential, differential scanning calorimetry (DSC) and Raman spectroscopy pattern. Furthermore, the in vivo anti-fatigue effect assays showed that RSV-SLNs prolonged the mice exhausted time and running distance. The biochemical parameters of blood related to fatigue suggested that RSV-SLNs have potential applications to improve the antioxidant defense of the mice after extensive exercise and confer anti-fatigue capability. Furthermore, the molecular mechanisms of antioxidant by RSV-SLNs supplementation was investigated through the analysis of silent information regulator 2 homolog 1 (SIRT1) protein expression, which demonstrated that it could downregulate the expression of SIRT1 and increase autophagy markers, microtubule-associated protein 1 light chain 3-II (LC3-II) and sequestosome-1 (SQSTM1/p62). These results reveal that the RSV-SLNs may have great potential used as a novel anti-fatigue sports nutritional supplement.Keywords:solid lipid nanoparticles (SLNs);resveratrol;drug delivery;anti-fatigue;nutrition supplements
研究领域:
药理学
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纳米技术
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运动科学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2025
·Vol. 39
·期 9
·e70455
·
IF 2.8
Lihan Xie,Weinan Li,Shiqi Fan,Jinsong Jin
Diabetic kidney disease (DKD) is a common complication of diabetes, often characterized by podocyte injury, proteinuria, and eventual renal failure. Sinomenine hydrochloride (SH), an active component derived from traditional Chinese medicine, is clinically effective in treating kidney diseases. This study investigates the protective effects of SH on podocytes under high-glucose conditions and its mechanism of action. Mouse podocytes (MPC-5) were treated with SH at concentrations of 50, 200, and 600 μg/mL under high-glucose conditions (30 mmol/L) for 24 h to establish a DKD model. Cell viability was assessed using CCK-8 assays, and apoptosis rates were measured using flow cytometry. Autophagy levels were evaluated by detecting LC3-II, Beclin-1, and P62 proteins via Western blot analysis, while the involvement of the PI3K/AKT/mTOR pathway was analyzed by examining phosphorylated AKT and mTOR. Transmission electron microscopy was employed to observe autophagosomes. SH improved podocyte viability, reduced apoptosis, and enhanced autophagic activity by increasing LC3-II and Beclin-1 expression while decreasing P62 levels. SH also downregulated p-AKT and p-mTOR, indicating inhibition of the PI3K/AKT/mTOR pathway. Electron microscopy confirmed increased autophagosomes in SH-treated groups. SH protects podocytes in a high-glucose environment by enhancing autophagy through inhibition of the PI3K/AKT/mTOR pathway. These findings provide insights into SH as a potential therapeutic agent for DKD management.
研究领域:
药理学
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细胞生物学
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肾病学
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分子生物学
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中医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2021
·Vol. 25
·期 11
·4962-4973
·
IF 5.31
Mingyu He,Gege Yan,Yang Wang,Rui Gong,Hong Lei,Shuting Yu,Xiaoqi He,Guanghui Li,Weijie Du,Tianshuai Ma,Manqi Gao,Meixi Yu,Shenzhen Liu,Zihang Xu,Elina Idiiatullina,Naufal Zagidullin,Valentin Pavlov,Benzhi Cai,Ye Yuan,Lei Yang
Osteosarcoma (OS) is the most common primary malignant bone tumour in adolescence. Lately, light-emitting diodes (LED)-based therapy has emerged as a new promising approach for several diseases. However, it remains unknown in human OS. Here, we found that the blue LED irradiation significantly suppressed the proliferation, migration and invasion of human OS cells, while we observed blue LED irradiation increased ROS production through increased NADPH oxidase enzymes NOX2 and NOX4, as well as decreased Catalase (CAT) expression levels. Furthermore, we revealed blue LED irradiation-induced autophagy characterized by alterations in autophagy protein markers including Beclin-1, LC3-II/LC3-I and P62. Moreover, we demonstrated an enhanced autophagic flux. The blockage of autophagy displayed a remarkable attenuation of anti-tumour activities of blue LED irradiation. Next, ROS scavenger N-acetyl-L-cysteine (NAC) and NOX inhibitor diphenyleneiodonium (DPI) blocked suppression of OS cell growth, indicating that ROS accumulation might play an essential role in blue LED-induced autophagic OS cell death. Additionally, we observed blue LED irradiation decreased EGFR activation (phosphorylation), which in turn led to Beclin-1 release and subsequent autophagy activation in OS cells. Analysis of EGFR colocalization with Beclin-1 and EGFR-immunoprecipitation (IP) assay further revealed the decreased interaction of EGFR and Beclin-1 upon blue LED irradiation in OS cells. In addition, Beclin-1 down-regulation abolished the effects of blue LED irradiation on OS cells. Collectively, we concluded that blue LED irradiation exhibited anti-tumour effects on OS by triggering ROS and EGFR/Beclin-1-mediated autophagy signalling pathway, representing a potential approach for human OS treatment.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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光生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Tong Yuling,Liu Liping,Wang Ruilin,Yang Tao,Wen Jianxia,Wei Shizhang,Jing Manyi,Zou Wenjun,Zhao Yanling
The purpose of this study was to investigate the therapeutic effect of berberine (BBR) on MNNG-induced chronic atrophic gastritis (CAG) and the possible mechanism of BBR through TGF-β1/PI3K signal pathway. GES-1 were pretreated with MNNG for 2 h before BBR treatment in all procedures. Cell viability was quantified by cell counting kit-8, and GES-1 morphology and proliferation were detected by high content screening (HCS) assay. The rat model of CAG was established by MNNG, and the therapeutic effect of BBR on stomach histopathology and serum supernatant were analyzed in vivo. In addition, the possible mechanism of BBR was further discussed, and the expression of related genes and proteins in TGF-β1/PI3K signal pathway was detected. The results showed that BBR could significantly improve the survival rate and morphological changes of GES-1, improve the gastric tissue injury of CAG rats, and reduce the expression of G-17 and inflammatory factors IL-8, TNF-α, IL-6 and IL-1β. In addition, BBR down-regulated the expression of TGF-β1 axis-related signals such as TGF-β1, PI3K, p-Akt/Akt, p-mTOR/mTOR and P70S6K, and promoted the expression of PTEN, LC3-II and Beclin-1. In Conclusion, BBR can improve CAG which may be closely related to TGF-β1/PI3K signal pathway.
研究领域:
药理学
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胃肠病学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 5
·4193-4201
·
IF 4.171
Xianghe Meng,Chaosheng Xia,Qin Ye,Xiaohua Nie
tert-Butyl-p-benzoquinone (TBBQ), a metabolite of tert-butylhydroquinone from food, has cytotoxicity, the underlying mechanism of which is not clear. In this study, the viability of RAW 264.7 cells exposed to TBBQ at concentrations of 0.5–10 μg mL−1 was assayed by MTT. Results suggest that TBBQ decreased the viability in a dose-dependent manner. Monodansylcadaverine (MDC) staining results indicate the occurrence of autophagy induced by TBBQ, which was manifested by activation of LC3-II concurrent with the increased levels of Beclin1 and reduced levels of p62. Elevated lipid peroxide and decreased SOD activity by TBBQ exposure suggest the overproduction of ROS, which may account for the increase in the genotoxic stress protein p53. Both upregulation of p53 and reduction of Akt levels inhibited mTOR, which activated autophagy. Addition of 3-MA counteracted the impact of TBBQ on ATG proteins and cell viability. All of these results suggest that TBBQ induces autophagy of RAW 264.7 cells principally by inhibition of the Akt/mTOR signaling pathway, and they implicate ROS in this regulation.
研究领域:
药理学
·
细胞生物学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2019
·
IF 3.775
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.
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
ACTA HISTOCHEMICA
·
2021
·
IF 2.479
Hongxi Wu,Guodong Li,Weiwei Chen,Wenbin Luo,Zhongyi Yang,Zhipeng You,Yuling Zou
Diabetic retinopathy (DR) is the leading clinical cause of blindness in diabetic patients. Mitophagy participates in the pathogenesis of DR. Dynamin related protein 1 (Drp1) is associated with mitophagy. Here, we investigated whether Drp1 can regulate mitophagy to affect the progression of DR. We constructed DR rat model by administration of streptozocin . Primary rat retinal endothelial cells (RECs) were treated with high glucose (HG) as a DR cell model. Drp1 was highly expressed in the retinal tissues of DR rats and HG-treated RECs. Drp1 knockdown inhibited HG-mediated increase of reactive oxygen species (ROS) levels and apoptosis in RECs. Moreover, Drp1 silencing inhibited the expression of autophagy-related proteins LC3-II/LC3–1 and Beclin-1 and reduced LC3 puncta in HG-treated RECs. The expression of mitochondrial marker Tom20 was reduced and the levels of mitophagy were increased in the HG-treated RECs, which was rescued by Drp1 silencing. Drp1 knockdown repressed LC3-II expression in HG-treated RECs, indicating that autophagy flux was inhibited. Rapamycin (autophagy activator) enhanced ROS levels and apoptosis in HG-treated RECs by activating autophagy, which was rescued by Drp1 knockdown. In conclusion, these data demonstrated that Drp1 knockdown repressed apoptosis of rat retinal endothelial cells by inhibiting mitophagy. Thus, this work suggests that targeted regulation of Drp1 may become a treatment for DR.
研究领域:
眼科学
·
细胞生物学
·
分子生物学
·
糖尿病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Yanzi Zhao,Yujing Niu,Xuefei Wang,Peng Wan,Zhanfei Ma,Jian Sun,Shoufang Jiang,Ling Xue,Nan Liu
Indium-tin oxide nanoparticles (Nano-ITO) are widely used in various applications as infrared shielding materials, which increase the risk of occupational exposure. According to reports, Nano-ITO can cause indium lung disease in occupational exposed workers, but the specific mechanism of Nano-ITO-induced pulmonary toxicity remains unclear. In this study, 50 8-week-old male Sprague-Dawley rats were divided into five groups (10 rats in each group) as follows: control group (physiological saline), 1.2 mg/kg Nano-ITO group, 6 mg/kg Nano-ITO group, N-Acetyl-L-Cysteine (NAC) control group (200 mg/kg), and NAC + Nano-ITO group (200 mg/kg NAC intraperitoneal injection, after 1.5 h, 6 mg/kg Nano-ITO intratracheal instillation), twice a week for 12 weeks. Pathological and ultrastructural changes in the rat lung tissue, immunofluorescence assays, immunohistochemistry, protein and mRNA levels of apoptosis- and autophagy-related genes were measured. The levels of ROS, MDA, H 2 O 2 , and LDH, and the activities of T-AOC and SOD, were determined using oxidative stress assay kits. The results showed that Nano-ITO caused strong pulmonary inflammation, pulmonary alveolar proteinosis, and pulmonary interstitial fibrosis. In addition, Nano-ITO-induced oxidative stress in rat lungs presented as increased levels of ROS and H 2 O 2 in the lungs, increased LDH and MDA levels, SOD and T-AOC activity in BALF, and activation of the Nrf2/NQO1/HO-1 signaling pathway. Intriguingly, Nano-ITO significantly increased the protein expression of microtubule-associated protein light chain 3 (LC3-II), the protein levels of autophagy-related genes 5 (ATG5), and Beclin-1 (BECN1), and reduced the protein levels of phosphatidylinositol 3-kinase (PI3K) in lung tissues. In addition, transmission electron microscopy (TEM) showed a significant increase in autophagic vesicles in the cytoplasm of lungs treated with Nano-ITO, indicating that Nano-ITO induces autophagy in rat lungs. Moreover, apoptosis also participates in Nano-ITO-induced pulmonary injury in a synchronous manner, as evidenced by the enhancement of TUNEL-positive signals and activation of the apoptosis pathway (Bax and Bcl-2 positive proportions). NAC supplementation restored most of the pathological structural features of rat lung tissue to their physiological range and effectively weakened apoptosis, as demonstrated by the notable reductions in TUNEL, Bax, and Bcl-2 protein expression levels in the lungs. Although autophagy was detected in the lungs of rats in the Nano-ITO and NAC + Nano-ITO groups, we discovered that NAC could rescue the expression of ATG5 and BECN1 induced by Nano-ITO, thus indicating that exposure to Nano-ITO promotes pulmonary apoptosis and autophagy by mediating oxidative stress. These results indicate that Nano-ITO can cause pulmonary injury by inducing oxidative stress, which activates apoptosis and autophagy, ultimately leading to alveolar proteinosis and interstitial fibrosis.
研究领域:
毒理学
·
纳米技术
·
呼吸医学
·
分子生物学
·
药理学
·
病理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yuling Tong,Ruilin Wang,Xia Liu,Miao Tian,Yanling Wang,Yanfei Cui,Wenjun Zou,Yanling Zhao
Ethnopharmacological relevance Zuojin Pill (ZJP) is a classic prescription composed of Coptis chinensis and Tetradium ruticarpum (A.Juss.) T.G.Hartley, which is often used in the treatment of digestive system diseases . Aim of this study The purpose of this study was to explore the therapeutic effect and potential mechanism of ZJP on chronic atrophic gastritis (CAG) induced by MNNG . Materials and methods The GES-1 and rat model of CAG was established by MNNG. Detection of cell viability, morphological changes and proliferation of GES-1 by CCK-8 and high content screening (HCS) assay. G-17, IL-8 and TNF-α in rat serum were detected by ELISA kit. The expression of related mRNA and protein on TGF-β1/PI3K/Akt signal axis were detected by RT-PCR and Western blot . Results The results showed that ZJP could significantly improve the GES-1 damage induced by MNNG and improve the gastric histomorphology of CAG rats. The intervention of ZJP could significantly reduce the content of G-17 and inflammatory factors IL-8, TNF- α, IL-6 and IL-1β, inhibit the expression of TGF-β1, PI3K and their downstream signals p-Akt, p-mTOR, P70S6K, and promote the expression level of PTEN, LC3-II and Beclin-1. Conclusion ZJP has a good therapeutic effect on CAG induced by MNNG, which may be closely related to the inhibition of TGF-β1/PI3K/Akt signal pathway.
研究领域:
药理学
·
民族药理学
·
胃肠病学
·
分子生物学
·
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）