CARBOHYDRATE POLYMERS
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2021
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IF 9.381
Chunfan Huang,Xiaoqi Jing,Qianhu Wu,Kan Ding
Renal fibrosis is the final common result of a variety of progressive injuries leading to chronic renal failure. However, there are no effective clinical available drugs for the treatment. Notoginsenoside from Panax notoginseng could ameliorate renal fibrosis. We hypothesized that polysaccharide from this herb might have similar bioactivity. Here, we elucidated structure of a novel pectin-like polysaccharide designed SQD4S2 with a netty antenna backbone of glucogalacturonan substituted by glucoarabinan, glucurogalactan and galactose residues from this herb. Interestingly, SQD4S2 could reverse the morphological changes of human renal tubular HK-2 cells induced by TGF-β. Mechanism study suggested that this bioactivity might associate with N-cadherin (CDH2), Snail (SNAI1), Slug (SNAI2) depression and E-cadherin (CDH1) enhancement. In addition, SQD4S2 could impede critical fibrogenesis associated molecules such as α-SMA, fibronectin , vimentin , COL1A1, COL3A1, FN1 and ACTA2 expression induced by TGF-β in HK-2 cells. Current findings outline a novel leading polysaccharide for against renal fibrosis new drug development.
研究领域:
药理学
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肾病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
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2022
·
IF 6.59
Wenjuan Ning,Xiaoxiao Xu,Shican Zhou,Xiao Wu,Hang Wu,Yijie Zhang,Jichang Han,Junpeng Wang
This study explored the profibrotic impact of high glucose in the lung and potential mechanisms using latent TGF-β1-induced human epithelial cell pulmonary fibrosis and bleomycin (BLM)-induced pulmonary fibrosis models. Results demonstrated that high glucose administration induced epithelial-mesenchymal transition (EMT) in human epithelial cells in a dose-dependent manner via activating latent TGF-β1, followed by increased expression of mesenchymal-related proteins and decreased expression of epithelial marker protein E-cadherin. Further mechanism analysis showed that administration of high glucose dose-dependently promoted total and mitochondrial reactive oxygen species (ROS) accumulation in human epithelial cells, which promoted latent TGF-β1 activation. However, N -acetyl-L-cysteine, a ROS eliminator, inhibited such effects. An in vivo feed study found that mice given a high-glucose diet had more seriously pathological characteristics of pulmonary fibrosis in BLM-treated mice, including increasing infiltrated inflammatory cells, collagen I deposition, and the expression of mesenchymal-related proteins while decreasing the expression of the epithelial marker E-cadherin. In addition, high glucose intake further increased TGF-β1 concentration and upregulated p-Smad2/3 and snail in lung tissues from BLM-treated mice when compared to BLM-treated mice. Finally, supplementation with high glucose further increased the production of lipid peroxidation metabolite malondialdehyde and decreased superoxide dismutase activity in BLM-treated mice. Collectively, these findings illustrate that high glucose supplementation activates a form of latent TGF-β1 by promoting ROS accumulation and ultimately exacerbates the development of pulmonary fibrosis.
研究领域:
肺科学
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细胞生物学
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药理学
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病理学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
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2020
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IF 6.306
Jiaxin Wang,Xuening Lu,Jiaen Zhang,Zeheng Xiao
Lipids such as phosphatidylcholine (PC), 3- sn -phosphatidylethanolamine (PE), sphingomyelin (SM) and L-α-lysophosphatidylcholine (LPC) are the major components of biological membranes and play important roles in physiological functions. Here, PC, PE, SM, and LPC were extracted from golden apple snails (GAS, Pomacea canaliculata ) and GAS flesh (GASF) using an ethanol/hexane sequential scheme and quantified simultaneously using ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) to evaluate whether the GAS could be the source of the four lipids. Our results suggest that ethanol extracts contained the most crude lipids, and the yield of dry (evaporated) lipids were 3.45 g per 100 g fresh GASF and 1.82 g per 100 g of fresh GAS. Quantification of the lipids using UHPLC-ESI-MS/MS suggested that GAS contained PE, PC, SM and LPC, with SM being the most abundant lipid (after purification: 1.71 and 1.42 mg g −1 dry weight from 100 g of GASF and GAS, respectively). The method we used is cost-effective, and the recovery rates of ethanol and hexane ranged from 80−91% and 87−91% respectively. Overall, GAS and GASF are potential raw materials for lipids such as SM and PC extraction using the ethanol/hexane method. Comparatively, lipids extraction from the GAS is more effective and timesaving. Our finding would provide a way to utilize GAS and potentially control its invasion.
研究领域:
生物化学
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分析化学
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入侵生物学
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DOI
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Bei Wang,Hao Cheng,Zhongsheng Ji,Zijun Jiang,Rong Wang,Yang Ding,Jiang Ni
Collaboration of cancerous cells and microenvironment is the root for tumor spreading, leading to difficulty in complete metastasis blockage via mono-intervention. Herein, a triple-responsive nanoassembly is designed for orienting tumor cells and migration-driving M2 tumor associated macrophages (TAMs) in microenvironment for efficient anti-metastatic therapy. Structurally, a reactive oxygen species (ROS)-responsive crosslinked short-chain polyquaternium is synthesized to bridge graphene oxide (GO) scaffold with apolipoprotein A-I crown via borate-crosslinking, electrostatic adherence, and coordinative coupling. The protein-crowning polymeric GO nanoparticles could give multimodal shielding and triple-responsive release of doxorubicin and Snail-targeted siRNA. Tailor-made apolipoprotein A-I crown fulfills nanoparticles synergistically attacking tumor cells and M2 TAMs via binding with overexpressed scavenger receptors. The findings witness the targeted accumulation and potent cytotoxicity of the hybrid nanoparticles for M2 TAMs and tumor cells; especially, elimination of M2 TAMs in tumor microenvironment holds back Snail-enhancing transforming growth factor (TGF)-β signal pathway, which collaborates with Snail silencing in tumor cells to reverse epithelial mesenchymal transition (EMT) and metastasis-promoting niche. Collectively, the synergistic targeting therapeutic platform could provide a promising solution for metastatic tumor treatment.
研究领域:
肿瘤学
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纳米技术
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药学
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Healthcare Engineering
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2021
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IF 2.682
Yongyan Deng,Hongjin Li,Yujiao Tang
Aim. Taurine is believed to have antioxidant properties and has been implicated in the treatment of neurodegenerative disease, atherosclerosis, coronary heart disease, and prostate cancer. This research focused on taurine inhibition effects of expression related to migration and epithelial-mesenchymal transition- (EMT-) A549 study on related genes of human being non-small-cell lung cancer. Methods. MTT assays assessed cell viability and a RadiusTM assay showed that taurine also inhibited the lung cancer cell migration. Using RT-PCR and Western blot, the migration and EMT markers were identified and evaluated. Results. We found that taurine significantly decreased the expression of migration markers matrix metallopeptidase 9 (MMP-9) and vascular endothelial growth factor (VEGF). In contrast, TIMP metallopeptidase inhibitor 1 (TIMP-1) and TIMP metallopeptidase inhibitor 2 (TIMP-2) expressions were increased with taurine treatment. In addition, we found an association between taurine treatment and the expression of EMT markers. The expression of epithelial marker E-cadherin and the mesenchymal marker N-cadherin TWIST-1 was decreased, but the expression of zinc finger protein SNAIL-1 and E-zinc finger homeobox 1 (ZEB-1) was increased. Conclusion. Taken together, our study strongly suggests the therapeutic significance of taurine, which possesses antimigration activity and induces EMT markers expression in lung cancer cells.
研究领域:
肿瘤学
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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
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2020
·Vol. 24
·期 8
·4480-4493
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IF 4.486
Linhao Xu,Yanli Bi,Yizhou Xu,Zhuocheng Zhang,Wenjie Xu,Sisi Zhang,Jian Chen
Small cell lung cancer (SCLC) is a severe malignant with high morbidity; however, few effective and secure therapeutic strategy is used in current clinical practice. Oridonin is a small molecule from the traditional Chinese herb Rabdosia rubescens. This study mainly aimed to investigate the role of oridonin on inhibiting the process of H1688, a kind of small cell lung cancer cells from human. Oridonin could suppress H1688 cell proliferation and induce their apoptosis in a high dosage treatment (20 μmol/L). Meanwhile, cell migration was suppressed by oridonin (5 and 10 μmol/L) that did not affect cell proliferation and apoptosis. The expression level of E-cadherin was significantly increased, and the expression of vimentin, snail and slug was reduced after administration of oridonin. These expression changes were associated with the suppressed integrin β1, phosphorylation of focal adhesion kinase (FAK) and ERK1/2. In addition, oridonin (5 and 10 mg/kg) inhibited tumour growth in a nude mouse model; however, HE staining revealed a certain degree of cytotoxicity in hepatic tissue after treatment oridonin (10 mg/kg). Furthermore, the concentration of alanine aminotransferase (ALP) was significantly increased and lactate dehydrogenase (LDH) was reduced after oridonin treatment (10 mg/kg). Immunohistochemical analysis further revealed that oridonin increased E-cadherin expression and reduced vimentin and phospho-FAK levels in vivo. These findings indicated that oridonin can inhibit the migration and epithelial-to-mesenchymal transition (EMT) of SCLC cells by suppressing the FAK-ERK1/2 signalling pathway. Thus, oridonin may be a new drug candidate to offer an effect of anti-SCLC with relative safety.
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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细胞生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2021
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IF 4.539
Ying-Ying Guan,Shao-Qi Zeng,Yin Qin,Yan Mu,Hong Liu
To overcome cancer drug resistance and to reverse tumor immunosuppression, a vitamin E-tocopheryl polyethylene glycol succinate (TPGS) decorated polymer-based drug delivery system was developed. The effects of the drug delivery system on diverse proteins involved in cell apoptosis, cancer invasion, metastasis and immunosuppression were investigated to provides a more comprehensive understanding of TPGS modified drug delivery systems. Curcumin (CUR), a hydrophobic drug, was loaded in star poly(DL-lactide) with a cholic acid core, and then decorated with TPGS shell to obtain [email protected] /star poly(DL-lactide) nanoparticles ( [email protected] ). Cholic acid cored star poly(DL-lactide) is featured by a rapid degradation rate with a surface erosion characteristic. TPGS not only reverses tumor drug resistance through downregulating P-gp expression of tumor cells but also enhances the anti-tumor efficiency through combined TPGS/CUR therapeutic actions on reversal of tumor immunosuppression mediated by CD47 and PD-L1. As compared with the CUR loaded nanoparticles without TPGS decoration, [email protected] with TPGS decoration results in significantly enhanced intracellular drug accumulation to efficiently induce cell apoptosis in drug resistant tumor cells. More importantly, [email protected] possesses considerably improved efficacy in upregulating p53 and p21 as well as downregulating β-catenin, MMP-9, Snail, CD47 and PD-L1, indicating the TPGS decorated drug delivery system inhibits tumor development and metastasis much more efficiently.
研究领域:
药学
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肿瘤学
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药物递送系统
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免疫治疗
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产品关联
DOI
高影响因子
Biomed Research International
·
2022
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IF 3.246
Xiaomeng Zou,Tiantian Li,Yingxuan Mao,Mingwei Zhu,Xi Chen,Jiamei Niu,Tianxiu Dong,Jian Jiang,Xiuhua Yang
Objectives . Preparation of a multifunctional drug-loaded phase-change nanoparticle (NP), pirfenidone perfluoropentane liposome NPs (PPL NPs), and combined with low-intensity focused ultrasound (LIFU) to influence epithelial mesenchymal transition (EMT) for hepatocellular carcinoma (HCC) by inhibiting the activity of activated Hepatic Stellate Cells (a-HSCs ). Methods . PPL NPs were prepared by the thin film dispersion method. The appearance, particle size, zeta potential, encapsulation efficiency, drug loading rate, drug release in vitro, and stability of PPL NPs were tested. The role of a-HSCs in HCC metastasis was studied by CCK-8, colony formation assay, apoptosis, cellular uptake assay, wound healing assay, and Transwell assay. Western blot was used to detect the related protein expression levels. In vitro and vivo, the acoustic droplet vaporization (ADV) of PPL NPs was tested at different times and LIFU intensities. Biosafety of the PPL NPs was assessed by measuring nude mouse body weight and hematoxylin and eosin (H&E) staining . Results. The results showed that the PPL NPs had good biosafety, with an average particle size of 346.6 ± 62.21 nm and an average zeta potential of -15.23 mV. When the LIFU power is 2.4 W/cm 2 , it can improve the permeability of cells, further promote the uptake of drugs by cells, and improve the toxicity of drugs. In vitro experiments showed that PPL NPs could inhibit the proliferation of a-HSCs cells, thereby affecting the metastasis of HCC, and were related to the TGF β -Smad2/3-Snail signaling pathway. Both in vivo and in vitro PPL NPs enhanced ultrasound imaging by LIFU-triggered ADV . Conclusion. The PPL NPs designed and prepared in this study combined with LIFU irradiation could significantly alter the EMT of HCC by inhibiting LX2. Clinically, PPL NPs will also be considered a promising contrast agent due to their ultrasound imaging capabilities.
研究领域:
纳米技术
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肿瘤学
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药剂学
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超声成像
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2023
·
IF 5.1
Shuai Wang,Jian-Tao Shi,Xing-Rong Wang,Hong-Xia Mu,Xue-Ting Wang,Kai-Yan Xu,Qing-Shan Wang,Shi-Wu Chen
The PI3K/AKT/mTOR signaling pathway is one of the most common abnormal activation pathways in tumor cells, and has associated with multiple functions such as tumor cell growth, proliferation, migration, invasion, and tumor angiogenesis. Here, a series of 3-amino-1 H -indazole derivatives were synthesized, and their antiproliferative activities against HT-29, MCF-7, A-549, HepG2 and HGC-27 cells were evaluated. Among them, W24 exhibited the broad-spectrum antiproliferative activity against four cancer cells with IC 50 values of 0.43–3.88 μM. Mechanism studies revealed that W24 inhibited proliferation by affecting the DNA synthesis, induced G 2 /M cell cycle arrest and apoptosis by regulating Cyclin B1, BAD and Bcl-xL, meanwhile induced the change of intracellular ROS and mitochondrial membrane potential in HGC-27 cells. Moreover, W24 inhibited the migration and invasion of HGC-27 cells by decreasing EMT pathway related proteins and reducing the mRNA expression levels of Snail, Slug and HIF-1α. Furthermore, W24 displayed low tissue toxicity profile and good pharmacokinetic properties in vivo . Therefore, 3-amino-1 H -indazole derivatives might serve as a new scaffold for the development of PI3K/AKT/mTOR inhibitor and anti-gastric cancer reagent.
研究领域:
肿瘤学
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药理学
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化学
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细胞生物学
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分子生物学
✓ 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）