Metallomics
·
2019
·Vol. 12
·期 2
·173-182
·
IF 3.571
Lv Xiaoguang,Zheng Qiaoqiao,Li Ming,Huang Zhiwei,Peng Min,Sun Jing,Shi Ping
Clioquinol is recently considered to be the most promising drug for treating cancer and neurodegenerative diseases. However, its mode of action varies from different disease models. In this study, we found that clioquinol inhibited cell growth in human neurotypic SHSY-5Y cells, which was attributed to both S-phase cell-cycle arrest and autophagic cell death. Clioquinol increased the intracellular contents of iron and zinc as well as calcium as measured by ICP-AES. Staining of Fluo-3 confirmed an increase in the level of calcium. Analysis of the metal-binding ability of clioquinol showed that it was not a chelating agent of calcium ions and the elevation of intracellular calcium content is not achieved by clioquinol as an ionophore. CaCl2 could simulate or even aggravate the cytotoxicity of clioquinol and it increased S-phase cell cycle arrest induced by clioquinol in a concentration dependent manner. Staining of acridine orange demonstrated that autophagy induced by clioquinol was not affected by addition of calcium ions. In contrast, the intracellular calcium ion chelator BAPTA-am abolished the clioquinol-induced S phase arrest and reduced the cell death caused by clioquinol. The WB assay of cell cycle-related proteins (CDK2, p21 and p27) further confirmed that S phase arrest is positively correlated with intracellular calcium elevation, which was due to the alterations of the mRNA and protein levels of calcium pumps (SERCA and SPCA). Taken together, these data indicate that clioquinol regulates the level of intracellular calcium ions to induce S-phase cell cycle arrest in human SH-SY5Y cells. Our results demonstrate for the first time that an increase of intracellular calcium content is one of the mechanisms of clioquinol in the inhibition of human neurotypic SHSY-5Y cells.
研究领域:
肿瘤学
·
神经科学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Jiaxin Dong,Qi Wang,Tingting Gu,Guanxiong Liu,Yuri V. Petrov,Vladimir E. Baulin,Aslan Yu Tsivadze,Dechang Jia,Yu Zhou,Huiping Yuan,Baoqiang Li
Suppression of vascular cell senescence is of great significance in preventing cardiovascular diseases such as hypertension and atherosclerosis. The oxidative stress damage caused by reactive oxygen species (ROS) can lead to cellular senescence. Rapamycin (Rapa) is well known to suppress cell senescence via mammalian target of rapamycin (mTOR) pathway. However, poor water solubility and lack of ROS scavenging ability limit the further development of Rapa. To improve the solubility of Rapa and endow with ROS scavenging ability, Rapa functionalized carbon dots (Rapa-CDs) are target-oriented synthesized via free radical polymerization combination with hydrothermal carbonization. Rapa-CDs improve the solubility of Rapa and show ROS scavenging abilities. The solubility of Rapa-CDs with 9.41 g is improved 3.6 × 10 4 times higher than that of Rapa (2.6 × 10 -4 g). The half maximal inhibitory concentration (IC 50 ) of Rapa-CDs toward hydroxyl radical ( • OH) and 2,2-Diphenyl-1-picrylhydrazyl free radical (DPPH•) are 0.18 and 0.17 mg/mL, respectively. Rapa-CDs show anti-oxidative stress effect in HEVECs (Human Umbilical Vein Endothelial Cells) via reducing ROS levels by 87 %. Rapa-CDs alleviate HUVECs senescence by suppressing mTOR overactivation, attenuate the expression of P53, P 21 and P16. The study demonstrates the target-oriented synthesis of drugs functionalized CDs with anti-senescence via dual-pathway of anti-oxidative stress and mTOR.
研究领域:
药理学
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纳米技术
·
心血管疾病
·
细胞生物学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SOLID STATE SCIENCES
·
2023
·
IF 3.5
Ningxia Li,Qi Luo,Meiyan Cui,Zhiying Zhao,Zhangzhen He
New fluorophosphate compounds H A 5 M 6 (OH) 4 F 4 (HPO 4 ) 8 ( A = K, Rb; M = Fe, Ga) were synthesized by a fluorine-rich hydrothermal method . These compounds crystallize in the monoclinic system with a P2 1 /n space group, exhibiting an open framework structure built by [PO 3 (OH)] groups, [MO 4 (OH)F], and [MO 4 F 2 ] octahedra, where ten-membered-ring channels, eight-membered-ring channels, six-membered-ring channels, and the linear M 3+ trimers are seen. The characterizations were carried out by powder XRD , EDS , FT-IR spectra, and magnetic measurements. The results confirmed that H A 5 Fe 6 (OH) 4 F 4 (HPO 4 ) 8 ( A = K, Rb) show a quite similar magnetic behavior, possessing an antiferromagnetic ordering at 14.7 K and 15.6 K, respectively. The changes of the magnetic entropy for such antiferromagnetic orderings can be estimated as ∼10.7 J mol −1 K −1 and ∼13.4 J mol −1 K −1 .
研究领域:
无机化学
·
材料科学
·
固体化学
✓ 已验证
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Yu-Jia Kuang,Qian-Qian Chen,Jin-hua Hao,Yang Lin,Ping-Ting Xiao,E-Hu Liu
Ethnopharmacological relevance Atherosclerosis is a pathological condition characterized by the accumulation of lipid-rich lesions within the endothelial layer, and it remains a significant contributor to global morbidity and mortality. Typhae Pollen (TP) has been extensively used in the treatment of blood stasis. However, the potential protective effects and underlying mechanisms of TP in atherosclerosis remain poorly understood. Aim of the study To explore the protective effects and mechanisms of Typhae Pollen extract (TPEX) on atherosclerosis. Materials and methods We established atherosclerosis models in ApoE -/- mice using high-fat diet (HFD), with continuous oral administration of TPEX at specified doses and intervals in vivo . To explore the underlying mechanisms of TPEX, we employed integrated network pharmacology and transcriptome analysis. In vitro , palmitic acid and H 2 O 2 induced primary hepatic cells lipid accumulation and endothelial cells dysfunction model were employed to investigate the potential mechanisms of TPEX using western blot, immunofluorescence, nuclear/cytoplasmic proteins isolation techniques. Results TPEX improved aortic lipid deposition and arterial injury, alleviated hyperlipidemia, and reduced liver damage in HFD-induced ApoE -/- mice. Mechanistically, TPEX mitigated endothelial cell senescence through the p53/p21 signaling pathway, suppressed inflammation by inhibiting the translocation of p65 into the nucleus, and alleviated oxidative stress by preventing the nuclear translocation of NRF2 and modulating the NRF2/HO-1 pathway. Furthermore, TPEX reduced inflammation and regulated lipid metabolism via the NOD signaling pathway and the SREBPs signaling pathway in the liver. Conclusion TPEX alleviates atherosclerosis by regulating endothelial dysfunction, hepatic lipid metabolism, and inflammatory processes. These findings provide new insights into the protective role of TPEX in atherosclerosis, especially regarding endothelial dysfunction and hepatic lipid metabolism.
研究领域:
药理学
·
心血管医学
·
分子生物学
·
民族药理学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2024
·
IF 3.2
Jianping Chen,Xuehua Chen,Anqi Tang,Zhuo Wang,Kit-Leong Cheong,Xiaofei Liu,Saiyi Zhong
This study aimed to evaluate the anti-cervical cancer activity of chondroitin sulfate–functionalized selenium nanoparticles (SeCS) and to elucidate their action mechanism. Cytotoxic effect of SeCS on HeLa cells was assessed by MTT assay. Further molecular mechanism of SeCS was analyzed by flow cytometric assay and western blotting. The results showed that treatment with SeCS resulted in a dose- and time-dependent inhibition in the proliferation of HeLa cells. The data obtained from flow cytometry demonstrated that SeCS inhibited HeLa cell growth via the induction of S-phase arrest and cell apoptosis. Further mechanism analysis found that SeCS down-regulated expression levels of cyclin A and CDK2 and up-regulated p21 expression, which contributed to S arrest. Moreover, SeCS increased the level of Bax and decreased the expression of Bcl-2, resulting in the release of cytochrome C from mitochondria and activating caspase-3/8/9 for caspase-dependent apoptosis. Meanwhile, intracellular reactive oxygen species (ROS) levels were elevated after SeCS treatment, suggesting that ROS might be upstream of SeCS-induced S-phase arrest and cell apoptosis. These data show that SeCS has anti-tumor effects and possesses the potential to become a new therapeutic agent or adjuvant therapy for cancer patients. Practical Application In our previous study, we used chondroitin sulfate to stabilize nano-selenium to obtain SeCS to improve the bioactivity and stability of nano-selenium. We found that it possessed an inhibitory effect on HeLa cells. However, the molecular mechanism remains unclear. This study elucidated the mechanism of SeCS damage to HeLa cells. SeCS has the potential to become a new therapeutic agent or adjuvant therapy for cancer patients.
研究领域:
肿瘤学
·
纳米技术
·
细胞生物学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
·
IF 4.259
Hu Dongfang,Cao Shengliang,Zhang Guihua,Xiao Yihong,Liu Sidang,Shang Yingli
Florfenicol (FLO) is one of the most popular antibiotics used in veterinary clinic and aquaculture. FLO can inhibit both bacterial and mitochondrial protein synthesis. However, the effects of FLO on mitochondrial function and cellular homeostasis remain unclear. Here we show that FLO inhibits expression of mitochondrial DNA-encoded proteins, decreases mitochondrial membrane potential, and promotes generation of reactive oxygen species (ROS) in vitro . As a result, activities of mitochondrial respiratory chain complex I and IV and the cellular ATP level are decreased and mitochondrial morphology is damaged. FLO represses cell growth and proliferation by suppression of phosphorylation of p70S6K through AMPK/mTOR/p70S6K pathway. Furthermore, FLO also induces G0/G1 cell cycle arrest via increase of p21 levels through activating ROS/p53/p21 pathway. Moreover, the clearance of damaged mitochondria by autophagy is impaired, leading to cell proliferation inhibition and promotes cell senescence. In addition, FLO-induced upregulation of cytosolic p53 may contribute to mitophagy deficiency via regulation of Parkin recruitment. In summary, our data suggest that florfenicol is an inhibitor of mitochondrial protein synthesis that can induce noticeable cytotoxicity. Thus, these findings can be useful for guiding the proper use of FLO and the development of safe drugs.
研究领域:
兽医学
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细胞生物学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2023
·Vol. 9
·期 7
·e18046
·
IF 4
Weijie Zhang,Lei Shi,Wei Zhou,Xin Liu,Yuan Xi,Xinyin Wang,Ya Li,Xia Xu,Youcai Tang
Breast cancer is one of the most common cancers. Oridonin, a traditional Chinese medicine, is believed to inhibit tumor growth, but its particular effects on breast cancer remain unknown. In this study, we examined oridonin's effects on 4T1, MCF-7, and MDAMB-231 cellular activity using CCK8. Scratch assays were used to detect oridonin's effects on cellular migration. Oridonin's effects on the breast cancer cell cycle were studied using flow cytometry, and expression of cell cycle related proteins p53, CDK2, and p21 was detected using Western blot assays. Metabolomics assays were used to detect changes in small molecule metabolites and metabolic pathways in breast cancer cells after treatment with oridonin. Oridonin's effects on breast cancer growth were also studied using xenograft mice. Metabolomics assays were used to detect changes in metabolites and metabolic pathways in xenograft mouse plasma in a control group, model group, and drug administration group. Experimental results showed that oridonin could significantly inhibit breast cancer growth both in vivo and in vitro. Scratch experiments showed that oridonin could inhibit breast cancer cell migration. Oridonin was also able to arrest cells in S phase by affecting several cell cycle-related proteins, including p53, CDK2, and p21. Metabolomic analysis of 4T1 cells identified a total of 33 differential metabolites, including multiple amino acids (such as l-Glutamic acid, l-Asparagine, l-Histidine, l-Valine, and l-Isoleucine). KEGG pathway enrichment analysis showed significant changes in aminoacyl-tRNA biosynthesis, and in multiple amino acid metabolic pathways. Plasma metabolomic analyses of xenograft mice revealed 28 differentially-expressed metabolites between the different animal model groups, including multiple amino acids. KEGG pathway analysis showed significant alterations in multiple amino acid metabolic pathways in oridonin-treated mice. Additionally, changes in the expression of PI3K, AKT and mTOR proteins, as well as in branched amino acids, suggest that oridonin affects the PI3K/AKT/mTOR signaling pathway by inhibiting the biosynthesis of valine, leucine and isoleucine. Taken together, our results suggest that oridonin has strong anti-tumor activity in vitro and in vivo, and has potential as an adjuvant to breast cancer treatment regimens.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
代谢组学
✓ 已验证
DOI
PubMed
高影响因子
Metallomics
·
2018
·Vol. 10
·期 6
·838-845
·
IF 4.069
Sun Pengcheng,Wang Song,Wang Jian,Sun Jing,Peng Min,Shi Ping
Chemerin exhibits a tumor-inhibitory role in hepatocellular carcinoma. However, the effect of chemerin on essential metal elements in hepatic cells remains unclear. In our study, the contents of six important metal ions, including potassium, calcium, sodium, magnesium, iron and zinc, were detected in human hepatoma SMMC7721 and immortal hepatic QSG7701 cells by ICP-AES. The data showed that chemerin only decreases the content of intracellular iron in SMMC7721 cells. The reduction was due to the blockage of iron entry through the decrease in the mRNA levels of divalent metal transporter 1, iron regulatory proteins and transferrin receptors. Furthermore, the reduction of the cellular iron content induced alterations of p53–p27–p21 signaling to arrest the cell cycle at S phase in SMMC7721 cells treated by chemerin. Conversely, iron addition led to recovery from the inhibitory effect of chemerin on SMMC7721 cells. The results suggest that chemerin plays an important role in inhibiting the cell proliferation of hepatocellular carcinomas by interfering with cellular iron homeostasis in this type of tumors.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2025
·
IF 5.1
Kang Wei,Yiran Shi,Min Wang,Lu He,Huanhuan Xu,Haijie Wang,Langjie Chai,Ling Zhou,Yi Zou,Liang Guo
Keloids (KD) are noncancerous fibroproliferative tumors exhibiting cancer-like traits, encompass aggressive unregulated growth, absence of natural regression, and a significantly high rate of recurrence. The precise molecular mechanisms underlying KD pathology remain poorly understood. In this study, we employed single-cell sequencing to examine the characteristics of cells in KD and normal scar (NS) tissue. We evaluated Schwann cells and their secretory protein IGFBP5 function in KD. Then, the recombinant IGFBP5 protein was employed to elucidate the regulatory roles of IGFBP5 in the proliferation, migration, invasion, angiogenesis, and cell cycle of keloids fibroblasts (KF). The rabbit ear scar model was utilized to ascertain the function of IGFBP5 in vivo. We demonstrated that in KD, the proportion of Schwann cells was 4.13 times that of NS. Besides, the IGFBP5 gene exhibited an expression level that was 8.02 times higher in KD Schwann cells compared to those in NS Schwann cells. High IGFBP5 expression was positively associated with the cell proliferation, migration, invasion, angiogenesis, and cell cycle of KF. Additionally, the p53/p21/Cyclin D1 pathway regulated cell cycle and promoted cell proliferation, which was suppressed after rIGFBP5 administration. These findings suggest that Schwann cells infiltrate in KD and secrete IGFBP5 protein to promote KD growth, and targeting IGFBP5 or Schwann cell infiltration could offer novel therapeutic strategies for KD.
研究领域:
皮肤病学
·
分子生物学
·
细胞生物学
·
肿瘤生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancer Nanotechnology
·
2020
·Vol. 11
·期 1
·1-17
·
IF 4.7
Pisano S.,Wang X.,Garcia-Parra J.,Gazze A.,Edwards K.,Feltracco V.,Hu Y.,He L.,Gonzalez D.,Francis L. W.,Conlan R. S.,Li C.
Background Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigenetic-driven anti-cancer effect in several tumor types. SAHA-loaded nanomicelles were prepared using a thin-film drying method and characterized for size, surface charge, drug content, and drug release properties. Loaded particles were tested for in vitro activity and their effect on cell cycle and markers of cancer progression.Results Following detailed particle characterization, cell proliferation experiments demonstrated that SAHA-loaded nanomicelles more effectively inhibited the growth of HeLa and MCF-7 cell lines compared with free drug formulations. The 30 nm SAHA containing nanoparticles were able to release up to 100% of the encapsulated drug over a 72 h time window. Moreover, gene and protein expression analyses suggested that their cytoreductive effect was achieved through the regulation of p21 and p53 expression. SAHA was also shown to up-regulate E-cadherin expression, potentially influencing tumor migration.Conclusion sThis study highlights the opportunity to exploit pluronic-based nanomicelles for the delivery of compounds that regulate epigenetic processes, thus inhibiting cancer development and progression.
研究领域:
药学
·
癌症生物学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
·
2015
·
IF 3.628
Y.N. Lin,R. Jia,Y.H. Liu,Y. Gao,L.L. Wang,J.P. Kou,B.Y. Yu
Ruscogenin, a natural steroidal sapogenin, presents in both food and medicinal plants. It has been found to exert significant anti-inflammatory activities. Considering that activation of neutrophil is a key feature of inflammatory diseases, this study was performed to investigate the inhibitory effect of ruscogenin and its underlying mechanisms responsible for neutrophil activation. Ruscogenin displayed potent antioxidative effects against Formyl-Met-Leu-Phe (FMLP)-induced extra- and intracellular superoxide generation in mouse bone marrow neutrophils, with IC 50 values of 1.07 ± 0.32 μM and 1.77 ± 0.46 μM, respectively. Phorbol myristate acetate (PMA)-elicited extra- and intracellular superoxide generation were also suppressed by ruscogenin, with IC 50 values of 1.56 ± 0.46 μM and 1.29 ± 0.49 μM, respectively. However, ruscogenin showed weak inhibition in NaF-induced response. Inhibition of superoxide generation was mediated neither by a superoxide-scavenging ability nor by a cytotoxic effect. Furthermore, ruscogenin inhibited the membrane translocation of p47phox and p67phox. It reduced FMLP-induced phosphorylation of cytosolic phospholipase A 2 (cPLA 2 ) and p21-activated kinase (PAK). The cellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) expression were increased by ruscogenin. Moreover, ruscogenin inhibited phosphorylation of protein kinase B (Akt), p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK). In addition, the inhibitory effects of ruscogenin on superoxide production and the phosphorylation of Akt, p38MAPK, and ERK1/2 were reversed by PKA inhibitor (H89), suggesting a PKA-dependent mechanism. In summary, our data suggest that ruscogenin inhibits activation of neutrophil through cPLA 2 , PAK, Akt, MAPKs, cAMP, and PKA signaling pathways. Increased PKA activity is associated with suppression of the phosphorylation of Akt, p38MAPK, and ERK1/2 pathways.
研究领域:
药理学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2023
·
IF 8.8
Zhen-Ning Zhang,Dan-Lei Yang,Hai Liu,Jue Bi,Ya-Bo Bao,Jiao-Yang Ma,Qin-Xiang Zheng,Dao-Lei Cui,Wei Chen,Ping Xiang
Tris(2-chloroisopropyl) phosphate (TCPP) and Tris(2-chloroethyl) phosphate (TCEP) are the widely used organophosphorus flame retardants indoors and easily accessible to the eyes as the common adhesive components of dust and particle matter, however, hardly any evidence has demonstrated their corneal toxicity. In this study, the adverse effects of TCPP, TCEP, and TCPP + TCEP exposure on human corneal epithelial cells (HCECs) were investigated. The cell viability and morphology, intracellular reactive oxygen species (ROS), cell cycle, and the expressions of cell cycle and pyroptosis-related genes were assessed to explain the underlying mechanisms. Compared to individual exposure, co-exposure to TCPP 20 +TCEP 20 showed higher cytotoxicity with a sharp decrease of >30% in viability and more serious oxidative damage by increasing ROS production to 110.92% compared to the control group. Furthermore, the cell cycle arrested at the S phase (36.20%) was observed after combined treatment, evidenced by the upregulation of cyclin D1 , CDK2 , CDK4 , CDK6 , p21, and p27 . Interestingly, pyroptosis-related genes GSDMD , Caspase-1 , NLRP3 , IL-1β , IL-18 , NLRP1, and NLRC4 expressions were promoted with cell swelling and glowing morphology. Oxidative stress and cell cycle arrest probably acted as a key role in TCPP 20 +TCEP 20 -induced cytotoxicity and pyroptosis in HCECs. Our results suggested that TCPP 20 +TCEP 20 co-exposure induced severer corneal damage, further illustrating its significance in estimating indoor health hazards to humans.
研究领域:
毒理学
·
细胞生物学
·
眼科学
·
环境健康
✓ 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）