International Journal of Nanomedicine
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2021
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IF 6.4
Manman Sun,Ke Huang,Xueshi Luo,Hong Li
Purpose Bone metastasis is one of the common causes of death relative to breast cancer. However, the evolvement of bone niche in cancer progression remains poorly understood. A three-dimensional (3D) engineered bone matrix was developed as an effective biomimetic model to explore the mechanism relative to bone cancer metastasis. Methods In the study, a 3D engineered bone matrix was developed via cell biomineralization templated by a biomimetic collagen template. The process of bone metastasis relative to breast cancer was investigated by co-culturing breast cancer MDA-MB-231-GFP cells with pre-osteogenic MC3T3-E1 cells on the 3D bone matrix. Results A typical bone matrix was obtained, where mineralized collagen fibers were packed into the bundle to form a 3D engineered bone matrix. As the cancer cells were invading along the way vertical to the alignment of mineralized collagen fiber, the bone matrix gradually became thinner, accompanied with the erosion of Col I and the loss of calcium and phosphorus. As a result, the disassembled structure of mineralized collagen fiber was observed, which may be attributed to osteolytic bone metastasis. Conclusion An engineered 3D bone-like matrix was successfully prepared via cell mineralization, which can act as a model for bone metastasis process. The study revealed mineralized collagen fiber disassembled at nanoscale relative to breast cancer cells.
研究领域:
癌症生物学
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生物医学工程
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2022
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IF 4.571
Yuan Jiang,Lin Qin,Anjing Lu,Juan Chen,Jianmei Wang,Qianru Zhang,Yanliu Lu,Qihai Gong,Jianmei Gao,Hong Ma,Daopeng Tan,Yuqi He
Strychnine is one of the main bioactive and toxic constituents of Semen Strychni. In the present study, the neurotoxic effects of strychnine, and the role of individual differences in metabolism on susceptibility to neurotoxicity of strychnine were investigated. The acute toxicity was observed by a single dose of strychnine (2.92 mg/kg, i.g.) in rats, the epileptic stages of rats were scored according to Racine’s scale. The neurotoxicity of strychnine was evaluated by the levels of ROS , MDA , SOD and GSH in hippocampus, striatum, and cortex tissues measurements and histopathological analysis. The concentrations of strychnine in the plasma, hippocampus, striatum, and cortex tissues were determined using high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). The expressions of the cytochrome P450 , which is the most critical protein family involved in drugs metabolism, were detected by proteomics . The mechanism of susceptibility to neurotoxicity of strychnine was elucidated by correlation analysis among above indicators. The results indicated that striatum and cortex were the main toxic targets of strychnine, and the CYP3A1 might be a susceptible biomarker to neurotoxicity of strychnine. These results provide valuable insights into the neurotoxic susceptibility of strychnine that will aid in the rational clinical use of strychnine (possibly including Semen Strychni).
研究领域:
药理学
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毒理学
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神经科学
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蛋白质组学
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DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 18
·4375
·
IF 4.2
Ran Luo,Haoyi Zhao,Siqi Deng,Jiale Wu,Haijun Wang,Xiaoshan Guo,Cuicui Han,Wenkang Ren,Yinglong Han,Jianwen Zhou,Yu Lin,Ming Bu
In this study, novel ergosterol peroxide (EP) derivatives were synthesized and evaluated to assess their antiproliferative activity against four human cancer cell lines (A549, HepG2, MCF-7, and MDA-MB-231). Compound3gexhibited the most potent antiproliferative activity, with an IC50value of 3.20 µM against MDA-MB-231. This value was 5.4-fold higher than that of the parental EP. Bioassay optimization further identified3gas a novel glutaminase 1 (GLS1) inhibitor (IC50= 3.77 µM). In MDA-MB-231 cells,3greduced the cellular glutamate levels by blocking the glutamine hydrolysis pathway, which triggered reactive oxygen species production and induced caspase-dependent apoptosis. Molecular docking indicated that3ginteracts with the reaction site of the variable binding pocket by forming multiple interactions with GLS1. In a mouse model of breast cancer,3gshowed remarkable therapeutic effects at a dose of 50 mg/kg, with no apparent toxicity. Based on these results,3gcould be further evaluated as a novel GLS1 inhibitor for triple-negative breast cancer (TNBC) therapy.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
INFLAMMOPHARMACOLOGY
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2024
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IF 4.6
Iqbal Urooj,Malik Abdul,Sial Nabeela Tabassum,Mehmood Malik Hassan,Nawaz Shoaib,Papadakis Marios,Fouad Dalia,Ateyya Hayam,Welson Nermeen N.,Alexiou Athanasios,Batiha Gaber El-Saber
Background The current study aimed to evaluate the anti-inflammatory, anti-oxidant, and pronounced gastro-protective activities of β- Citronellol using in vitro , in vivo assays and in silico approaches. Methods In vitro assays, denaturation of bovine serum albumin, egg protein, and human Red Blood Cells (RBCs) membrane stabilization were performed, using Piroxicam as standard. For in vivo assessment, Histamine (0.1 ml from 1% w/v) and Formaldehyde (0.1 ml from 2% v/v) were used to mediate inflammation. In silico molecular docking and network pharmacology were employed to probe the possible target genes mediating gastroprotective effect of β-Citronellol at 25, 50, and 100 mg/kg, using indomethacin-induced (25 mg/kg i.p) gastric ulcer in rats. Moreover, Gastric tissues were evaluated for morphological, histopathological, and bio-chemical analysis of PGE 2, COX-I, COX-II, 5-LOX, eNOS, ICAM-1, oxygen-free radical scavengers (SOD, CAT), and oxidative stress marker (MDA). Results β - Citronellol prevented denaturation of proteins and RBCs membrane stabilization with maximum effect observed at 6,400 µg/mL. Citronellol decreased rat’s paw edema. Network pharmacology and docking studies revealed gastro-protective potential of Citronellol possibly mediated through arachidonic acid pathways by targeting COX-I, COX-II, PGE 2 , and 5-LOX. Citronellol reduced the ulcer indices, and histopathological changes. Further, β - Citronellol (50 and 100 mg/kg) increased gastric PGE 2, COX-1, and eNOS; while suppressing COX-2, 5-LOX and ICAM-1. Citronellol markedly enhanced the oxidative balance in isolated rat stomach tissues. Conclusions The anti-inflammatory, anti-oxidant, and gastro-protective effects of β - Citronellol against indomethacin-induced gastric ulcer model in rats through mediating COX-I, COX-II, PGE 2, 5-LOX, eNOS, and ICAM-1 inflammatory markers. Graphical abstract
研究领域:
药理学
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炎症
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胃肠病学
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
FEBS Open Bio
·
2024
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IF 2.8
Linqian Chen,Meifeng Chen,Yan Xie,Yuyan Zhang,Shutian Mo,Yongfei He,Tianyi Liang,Yuan Liao,Renbin Huang,Guodong Huang,Chuangye Han,Thi Thai Hoa Pham
Several studies have suggested a potential antitumor effect of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD). To further understand the mechanism of action of this compound, we investigated its effect on the phosphatidylinositol-3-kinase (PI3K)/serine–threonine kinase (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. We show that DMDD application significantly inhibited the proliferation of breast cancer cell lines MDA-MB-231 and ER-α positive MCF-7. Furthermore, DMDD application resulted in increased intracellular reactive oxygen species (ROS) levels, apoptosis and autophagy, whereas it downregulated the expression of PI3K, Akt and mTOR mRNA and proteins, and increased the expression of LC3II/I and p62 proteins. In a mouse breast cancer xenograft model, DMDD inhibited tumor growth. Expression analyses suggest that ROS levels were higher in DMDD treated tumor tissues, whereas immunohistochemical analyses suggest that apoptotic cells were more prevalent in the DMDD treated group compared to the control group. Taken together, our results suggest that the molecular mechanism of action of DMDD may involve the enhancement of breast cancer autophagy through the PI3K/Akt/mTOR signaling pathway by mediating ROS expression.
研究领域:
肿瘤学
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细胞生物学
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药理学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2019
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IF 3.743
Xiaohong Xu,Vinothakumar Rajamanicham,Sujing Xu,Zhoudi Liu,Tao Yan,Guang Liang,Guilong Guo,Huiping Zhou,Yi Wang
Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking prognostic and effective therapeutic targets currently. In this study, we evaluated the toxic potential of schisandrin A (SchA), a bioactive phytochemical found in Schisandra chinensis in TNBC. The anti-cancer effect and underlying mechanism of SchA on MDA-MB-231 and BT-549 cells were determined in vitro and in xenograft mouse model. Our data show that SchA markedly inhibited the growth of TNBC cells via induction of cell cycle arrest and cell apoptosis. Moreover, over activation of Wnt signaling was observed in TNBC cells, which was significantly suppressed by the treatment of SchA. Also, SchA treatment activated ER stress in TNBC cells. Finally, we verified these inhibitory effects of SchA in the MDA-MB-231 xenograft mouse model. In conclusion, SchA effectively inhibited TNBC in preclinical models by inducing cell cycle arrest and apoptosis via regulating Wnt/ER stress signaling pathway. All of these data indicate that SchA could be a potential candidate for the treatment of TNBC.
研究领域:
肿瘤学
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药理学
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细胞生物学
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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 Materials Chemistry B
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2019
·Vol. 8
·期 6
·1223-1234
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IF 5.047
Huiru Li,Xinyue Zhang,Xilin Lin,Shuqiang Zhuang,Yan Wu,Zhong Liu,Jianhua Rong,Jianhao Zhao
Based on the concept of starving tumor therapy, in this study we put forward a new idea that the pH-sensitive Ca2+ delivery of calcium carbonate nanoparticles (CaCO3 NPs) induced blood coagulation of tumor vessels, and first explored the effect of CaCO3 NPs on the in vitro and in vivo blood coagulation by acid stimulus. CaCO3 NPs with a size of about 100 nm and a porous structure of several nanometers were synthesized in an emulsion system, which showed a high loading capacity (49%) of doxorubicin hydrochloride (DOX) with an encapsulation efficiency of 98% and a pH-sensitive drug delivery. The hemolysis test showed that CaCO3 NPs were blood compatible. The in vitro Ca2+ delivery and blood clotting tests indicated that CaCO3 NPs pH-sensitively released Ca2+, and caused rapid blood coagulation at pH 5.0 but no thrombus at pH 7.4. Confocal laser scanning microscopy showed that after uptake by MCF-7 or MDA-MB-231 breast cancer cells, CaCO3 NPs mainly distributed in endosomes/lysosomes within the initial 2 h and then decomposed by acid stimulus, leading to the intracellular delivery of Ca2+ that subsequently migrated outside the cells. CaCO3 NPs were nontoxic to NIH3T3 mouse fibroblasts, but highly toxic to both MCF-7 and MDA-MB-231 cells after loading DOX. After topical administration into the breast tumors of mice, CaCO3 NPs evoked significant thrombosis and hemorrhage of tumor vasculature by hematoxylin–eosin and Masson's trichrome staining. These results indicated that CaCO3 NPs could induce blood coagulation via acid stimulus, showing potential applications in blocking tumor vessels for starving tumor therapy.
研究领域:
纳米技术
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癌症治疗
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药学科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
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2022
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IF 4.336
Hong-shuang Liu,Man-yu Zhou,Xi Zhang,Ya-lan Li,Jing-wei Kong,Xin Gao,Dong-yu Ge,Jia-jing Liu,Pei-guang Ma,Gui-ying Peng,Yan Liao
The hepatic protective role of Sagittaria sagittifolia polysaccharide (SSP) and its possible mechanism were discussed in mice and L02 hepatocytes injured by heavy metals mixture of Cd + Cr (VI) + Pb + Mn + Zn + Cu. After 30-day intervention, blood and liver samples were collected for the relevant assessments. Methyl thiazolyl tetrazolium (MTT) assay showed 24 h was the best protecting point and the SSP protection at 1 mg/mL was strongest in L02 hepatocytes. SSP can alleviated hepatic injury, as evidenced by significantly decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the malondialdehyde (MDA) content, also increased the superoxide dismutase (SOD) activity and glutathione (GSH), total sulphydryl (T-SH) contents. SSP effectively reduced pathological damage of mice and accumulation of heavy metals in liver, as well as decreased the level of reactive oxygen species (ROS) in L02 hepatocytes. After SSP treatment, the protein expressions or gene transcription of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD( P )H dehydrogenase, quinone 1 (NQO1) and heme oxygenase1 (HO-1) decreased in L02. The protein expression of Nrf2 and NQO1 were increased while HO-1 was decreased in liver. Besides, SSP can attenuates apoptosis through reducing the protein expression of Bcl-2-associated X protein (Bax) and caspase-3, and increasing B-cell lymphoma gene 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl). SSP protects against six-heavy-metal-induced hepatic injury in mice and L02 hepatocytes. Supported by Nrf2 gene silencing, the mechanisms may correlate with activating Nrf2 pathway to mitigate oxidative stress and apoptosis.
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Analytical Chemistry
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2022
·
IF 1.698
Lijing Li,Kaixuan Zhou,Qiulu Zhao,Yuejie Wang,Jia Liu,Huiwei Bao
Buyang Huanwu Decoction (BHD) has lipid-lowering and antioxidant effects. In this study, HPLC was used to establish the fingerprint of extracts from different polar parts of BHD. Through the L02 cell lipid deposition model induced by oleic acid, extracts from different polar parts of BHD were administered for treatment. Oil red O staining, TG detection, and MDA detection were used to determine lipid deposition and antioxidant activity. The component-effect relationship is established by using grey relational analysis and PLSR analysis. The results showed that the extracts from different polar parts of BHD could reduce the levels of TG and MDA. The grey relational analysis showed that the peaks that contributed greatly to the reduction of TG and MDA were peaks 3, 16, 14, 10, 1, 15, 2, and 11, respectively. Peaks 1, 4, 9, 10, 14, 16, and 17 could reduce TG and MDA through PLSR analysis. According to the results of grey relational analysis and PLSR analysis, peaks 1, 10, 14, and 16 may have good lipid-lowering and antioxidant effects. This study provides a certain preliminary basis for follow-up research on lipid-lowering drugs.
研究领域:
药理学
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生物化学
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中医药
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产品关联
DOI
PubMed
高影响因子
CELL STRESS & CHAPERONES
·
2023
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IF 3.8
He Xin,Wang Juan,Sun Lei,Ma Wenqi,Li Miao,Yu Shanshan,Zhou Qi,Jiang Jue
Mastitis is a disease involved in inflammation of breast which affects human and animals. Wogonin is one bioactive compound from many Chinese herbal medicines, which have multiple properties, including anti-inflammatory activity. However, the roles of wogonin in mastitis progression are largely undefined. Mastitis models were established using LPS-treated mice and mammary epithelial cells (MECs). Infiltration of inflammatory cells was analyzed by hematoxylin-eosin staining and myeloperoxidase (MPO) activity. Inflammatory cytokine (TNF-α and IL-1β) levels were detected via ELISA. The phosphorylation and total of Akt and NF-κB levels and content of Nrf2 and HO-1 were measured via western blot. Cell viability was examined by CCK-8 assay. Oxidative stress was assessed by ROS generation and levels of MDA, GSH, and SOD. Wogonin attenuated LPS-induced infiltration of inflammatory cells, increase of MPO activity and levels of TNF-α and IL-1β, and activation of the Akt/NF-κB pathway in murine mammary gland tissues, and promoted activation of Nrf2/HO-1 signaling. Wogonin did not affect MEC viability, but mitigated LPS-induced inflammation in MECs by reducing TNF-α and IL-1β levels. Wogonin relieved LPS-induced oxidative stress in MECs through decreasing ROS generation and MDA level and increasing GSH and SOD levels. Wogonin repressed LPS-induced activation of the Akt/NF-κB pathway in MECs and increased Nrf2/HO-1 signaling activation. Activated Akt/NF-κB signaling or Nrf2/HO-1 signaling inactivation reversed the suppressive effects of wogonin on LPS-induced inflammation and oxidative stress in MECs. Wogonin mitigates LPS-induced inflammation and oxidative stress of MECs via suppressing activation of the Akt/NF-κB signaling and activating Nrf2/HO-1 pathway, indicating the therapeutic potential of wogonin in mastitis.
研究领域:
药理学
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免疫学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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
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纳米技术
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呼吸医学
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分子生物学
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药理学
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病理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
·
IF 4.932
Xiaoqi Sun,Xiaotian Wang,Qianqian He,Muqing Zhang,Li Chu,Yang Zhao,Yongchao Wu,Jianping Zhang,Xue Han,Xi Chu,Zhonglin Wu,Shengjiang Guan
Baicalin (BA), a kind of flavonoids compound, comes from Scutellaria baicalensis Georgi (a kind of perennial herb) and has beneficial effects on the cardiovascular system through anti-oxidant, anti-inflammation, and anti-apoptosis actions. However, the therapeutic effects and latent mechanisms of BA on arsenic trioxide (ATO)-induced cardiac toxicity has not been reported. The present research was performed to explore the effects and mechanisms of BA on ATO-induced heart toxicity. Male Kunming mice were treated with ATO (7.5 mg/kg) to induce cardiac toxicity. After the mice received ATO, BA (50 and 100 mg/kg) was administered for estimating its cardioprotective effects. Statistical data demonstrated that BA treatment alleviated electrocardiogram abnormalities and pathological injury caused by ATO. BA could also lead to recovery of CK and LDH activities to normal range and cause a decrease in MDA levels and ROS generation, augmentation of SOD, CAT, and GSH activities. We also found that BA caused a reduction in the expression of proinflammatory cytokines, such as TNF-α and IL-6. Moreover, BA attenuated ATO-induced apoptosis by promoting the expression of Bcl-2 and suppressing the expression of Bax and caspase-3. TUNEL test result demonstrated BA caused impediment of ATO-induced apoptosis. Furthermore, BA treatment suppressed the high expression of TLR4 , NF-κB and P-NF-κB caused by ATO. In conclusion, these results indicate that BA may alleviate ATO-induced cardiac toxicity by restraining oxidative stress, apoptosis, and inflammation, and its mechanism would be associated with the inhibition of the TLR4/NF-κB signaling pathway.
研究领域:
药理学
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毒理学
·
心脏病学
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产品关联
DOI
PubMed
高影响因子
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