REACTIVE & FUNCTIONAL POLYMERS
·
2020
·
IF 3.333
Chao Yu,Xing Tan,Zhenzhu Xu,Guodian Zhu,Wenqi Teng,Qingzhen Zhao,Zhong Liang,Zhimin Wu,Di Xiong
A series of amphiphilic polymer mPEG-PUSS-mPEG were developed by a combination of ring opening polymerization (ROP) and polyaddition reaction and its self-assembled micelles were developed for hydrophobic anticancer drugs delivery. Polymeric critical micellar concentration (CMC) values in aqueous solution were about 2.8–5.5 mg/L. And the partition equilibrium constant ( K v ) of pyrene in micellar solutions ranged from 1.52 × 10 5 to 2.20 × 10 5 . The average sizes of the self-assembled blank and DOX-loaded micelles were 160–180 nm determined by dynamic light scattering (DLS). The morphology of the DOX-loaded micelles was spherical by transmission electron microscopy (TEM) and scanning electron microscopy (SEM).The in vitro drug release behaviors of DOX and PTX from mPEG-PUSS-mPEG micelles were investigated at different simulated conditions. We found that the PTX release was significantly accelerated by redox stimuli compared with DOX-loaded reduction-sensitive PU micelles. The change of the size of this system under different conditions was further evaluated by DLS. DOX-loaded mPEG-PUSS-mPEG micelles in 50% fetal bovine serum (FBS) were evaluated the hemocompatibility. In addition, the self-assembly process of polymers mPEG-PUSS-mPEG in aqueous solution for micellar formation was also investigated by means of dissipative particle dynamics (DPD) simulations.AndCCK-8 assays revealed that the mPEG-PUSS-mPEG materials had low toxicity, but the DOX-loaded micelles showed a high cytotoxicity against HepG2 tumor cells. All results demonstrate that mPEG-PUSS-mPEG self-assembled micelles are a very promising for hydrophobic anticancer drugs delivery.
研究领域:
材料科学
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药剂学
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生物医学工程
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癌症研究
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DOI
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Li Jingyan,Wu Bingmin,Zeng Lishan,Lin Ying,Chen Qiuhe,Wang Haixia,An Lin,Zhang Jiajun,Chen Siyan,Huang Junying,Zhan Ruoting,Zhang Guifang
Background: The present study aimed to investigate the protective effect of the water extract of Amydrium sinense (Engl.) H. Li (ASWE) against hepatic fibrosis (HF) and clarify the underlying mechanism.Methods: The chemical components of ASWE were analysed by a Q-Orbitrap high-resolution mass spectrometer. In our study, an in vivo hepatic fibrosis mouse model was established via an intraperitoneal injection of olive oil containing 20% CCl4. In vitro experiments were conducted using a hepatic stellate cell line (HSC-T6) and RAW 264.7 cell line. A CCK-8 assay was performed to assess the cell viability of HSC-T6 and RAW264.7 cells treated with ASWE. Immunofluorescence staining was used to examine the intracellular localization of signal transducer and activator of transcription 3 (Stat3). Stat3 was overexpressed to analyse the role of Stat3 in the effect of ASWE on HF.Results: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that candidate targets of ASWE, associated with protective effects against hepatic fibrosis, were related to inflammation response. ASWE ameliorated CCl4-induced liver pathological damage and reduced the liver index and alanine transaminase (ALT) and aspartate transaminase (AST) levels. ASWE also decreased the serum levels of collagen Ⅰ (Col Ⅰ) and hydroxyproline (Hyp) in CCl4-treated mice. In addition, the expression of fibrosis markers, including α-SMA protein and Acta2, Col1a1, and Col3a1 mRNA, was downregulated by ASWE treatment in vivo. The expression of these fibrosis markers was also decreased by treatment with ASWE in HSC-T6 cells. Moreover, ASWE decreased the expression of inflammatory markers, including the Tnf-α, Il6 and Il1β, in RAW264.7 cells. ASWE decreased the phosphorylation of Stat3 and total Stat3 expression and reduced the mRNA expression of the Stat3 gene in vivo and in vitro. ASWE also inhibited the nuclear shuttling of Stat3. Overexpression of Stat3 weakened the therapeutic effect of ASWE and accelerated the progression of HF.Conclusion: The results show that ASWE protects against CCl4-induced liver injury by suppressing fibrosis, inflammation, HSC activation and the Stat3 signaling pathway, which might lead to a new approach for preventing HF.
研究领域:
药理学
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肝病学
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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
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2020
·Vol. 52
·期 8
·842-852
·
IF 2.836
Zhang Liang,Wang Xin,Liu Xin,Lv Mingyue,Shen Erdong,Zhu Guolian,Sun Zhe
Esophageal cancer (EC) is one of the most common aggressive malignant diseases worldwide. miR-28-5p plays important regulatory roles in many cancers including human EC. However, the molecular mechanism and potential role of miR-28-5p in EC remain uncertain. In this study, qRT-PCR and western blot analysis revealed that miR-28-5p expression was up-regulated and metastasis suppressor-1 (MTSS1) was down-regulated in EC tissues relative to matched para-cancer tissues. Cell counting kit-8 (CCK-8) assay demonstrated that miR-28-5p mimics increased cell viability, and miR-28-5p inhibitor decreased it. Flow cytometry (FCM) assay indicated that miR-28-5p mimics promoted cell cycle entry, while miR-28-5p inhibitor reduced it and induced cell apoptosis. Moreover, miR-28-5p mimics up-regulated the expressions of cyclin A, cyclin dependent kinase 2 (CDK2), cyclin D1, and cyclin E but down-regulated the expressions of cleaved caspase-3 and cleaved caspase-9, which was abolished by miR-28-5p inhibitor. Furthermore, luciferase reporter assay verified that miR-28-5p directly targeted MTSS1 3′UTR and down-regulated its expression. MTSS1 overexpression in TE-1 cells inhibited cell proliferation and promoted apoptosis induced by miR-28-5p mimics, whereas silencing of MTSS1 reversed cell progression induced by miR-28-5p inhibitor. We also demonstrated that miR-28-5p could promote esophageal tumor formation in vivo. Hematoxylin–eosin staining, immunohistochemistry, and TUNEL assays confirmed that miR-28-5p antagomir inhibited cell growth and accelerated apoptosis. Our results suggest that miR-28-5p may induce cell proliferation and suppress apoptosis to promote EC tumor formation via decreasing MTSS1 expression. Thus, miR-28-5p may be a potential target for human EC therapy.
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
✓ 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
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民族药理学
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胃肠病学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2021
·
IF 6.244
Yang Jianru,Jia Yang,Wang Bing,Yang Shengrong,Du Kun,Luo Yujie,Li Yunhe,Zhu Bing
Background: The effects of up-regulated CircCHST15 on lung cancer remained unclear. In this study, the role of CircCHST15 in lung cancer was investigated.Methods: Dual-luciferase reporter verified the bioinformatics prediction that CircCHST15 targeted miR-155-5p and miR-194-5p. The correlation between CircCHST15 and PD-L1 was analyzed by Pearson analysis. CCK-8 and colony formation was performed to determine the viability and proliferation of lung cancer cells. After the lung cancer (subcutaneous-xenotransplant) model was established in mice, the T cell subtype and related cytokines in mouse tumor tissues were detected by flow cytometry and ELISA. Moreover, the expressions of CircCHST15, miR-155-5p, miR-194-5p, immune-related, and proliferation-related factors of the lung cancer cells or mice tumor tissues were detected by immunohistochemistry, RT-qPCR, or Western blot.Results: CircCHST15 and PD-L1 were high-expressed in lung cancer, and the two was positively correlated. CircCHST15 targeted miR-155-5p and miR-194-5p, the later further targeted PD-L1. Lung cancer cell viability and proliferation were increased by miR-155-5p and inhibited by miR-194-5p. CircCHST15 located in the cytoplasm promoted tumor growth, down-regulated the expressions of miR-155-5p and miR-194-5p, and up-regulated the expressions of PD-L1, Ki-67, PCNA, CCL17, CCL22, IFN-γ, TNF-β, and IL-10. Also, CircCHST15 decreased the CD8+ cells in mouse blood and tumor, but increased the Tregs in mouse tumor. PD-L1 inhibitor showed an opposite effect to CircCHST15 on mouse tumors.Conclusion: CircCHST15 sponged miR-155-5p and miR-194-5p to promote the PD-L1-mediated immune escape of lung cancer cells.
研究领域:
肿瘤学
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Jin Zhang,Shangzhi Wang,Mingrui Yang,Jinming Ding,Yizhen Huang,Yangdong Zhu,Ming Zhou,Bin Yan
This experiment examined the antiviral activity of polysaccharides from Sargassum fusiforme against respiratory syncytial virus (RSV) in vitro, including their mechanism of action and preliminary structural analysis. Four polysaccharides (SFP1, SFP2, SFP3, and SFP4) were purified from Sargassum fusiforme using a DEAE-52 cellulose column and an NW Super 150 gel column. CCK-8 and western blot were utilized to study the antiviral activities and mechanisms of the polysaccharides. Preliminary structural analysis was conducted using HPLC and NMR techniques. The findings suggest that SFP4 (120 kD) is an acidic chemical compound composed of 88.8 % total sugars, 0.13 % proteins, 10.8 % glucuronidic acids, and 21.1 % sulfates. It contains at least ten monosaccharides, primarily mannuronic acid and fucose. Among the four polysaccharides, SFP4 had the highest anti-RSV activity, with a therapeutic index (TI) exceeding 139. SFP4 exhibited noteworthy antiviral efficacy in both upper and lower respiratory cells that were infected, especially when administered as a prophylactic treatment 2 h in advance. Furthermore, SFP4 showed a dose-dependent antiviral effect, with the highest therapeutic index (TI > 320) observed at a concentration of 7.81 μg·mL −1 during the prophylactic phase. It was speculated that SFP4's antiviral effect is due to its ability to inhibit the attachment of G-proteins to cells.
研究领域:
药理学
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病毒学
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海洋生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF ORAL BIOLOGY
·
2020
·
IF 1.931
Ying Bian,Juan Xiang
Background Osteogenic differentiation of human periodontal ligament cells (hPDLCs) is crucial for regenerate periodontal tissues. In this study, we investigated the function of salvianolic acid B (Sal B) in osteogenesis of hPDLCs. Methods HPDLCs were isolated from healthy third molar roots. HPDLCs at passage 3 were identified by morphological observation and immunohistochemistry of vimentin . The viability of hPDLCs incubated with Sal B at concentrations of 0μM, 0.1μM, 0.5μM, 1μM and 5μM were measured by CCK-8 assay. To evaluate the effect of Sal B on osteogenic differentiation of hPDLCs, the alkaline phosphatase (ALP) activity, osteogenic differentiation markers, and mineralized nodules were determined by ALP kit, qRT-PCR and alizarin red S staining, respectively. To confirm the function of Sal B in hPDLCs involved in Wnt/β-catenin signaling pathway , hPDLCs were incubated with Sal B or co-incubated with Sal B and DKK-1 (a inhibitor of Wnt/β-catenin). The levels of Wnt/β-catenin signaling pathway and osteogenic differentiation-associated indicators were then determined. Results HPDLCs showed a typical fibroblast-like and spindle-shaped, with vimentin-positive. The viability of hPDLCs had no obvious change with stimulation of Sal B at various doses. Sal B promoted the increase of ALP activity, osteogenic differentiation markers levels, mineralized nodules and activation of Wnt/β-catenin signaling pathway, and DKK-1 could block those effects of Sal B on hPDLCs. Conclusion Sal B promoted osteogenesis of hPDLCs through Wnt/β-catenin signaling pathway, which providing a potential drug for periodontitis treatment .
研究领域:
牙科学
·
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
VACUUM
·
2023
·
IF 4
Zhihua Liu,Qiaoling Liu,Xiaoyu He,Yihai Zhu,Qunlong Pan,Rongmou Zhang,Haiming Yu
Failure of surgical treatment is usually the result of bacterial colonization around the implant. This subsequently brings about various diseases such as peri-implantitis and sepsis. The purpose of this study was to develop and evaluate the antimicrobial properties of polydopamine adhered eggshell powder-loaded copper sulfide antimicrobial coatings. Here, we used eggshell powder-loaded copper sulfide as an antimicrobial agent to form an antimicrobial coating on the surface of titanium alloy screws using the chelating action of polydopamine. The coating showed good antibacterial effects against both Gram-positive and Gram-negative bacteria represented by Staphylococcus aureus and Escherichia coli . A series of subsequent characterizations confirmed the perfect loading of the material on the screws, and subsequent friction experiments on porcine femurs also demonstrated the good adhesion of the antimicrobial coating. Meanwhile, cytotoxicity assessment was performed by the CCK-8 method, confirming cellular biosafety. This work explores the value of eggshell-loaded CuS nanomaterial coatings in the prevention and treatment of orthopedic endothelial infections, which contributes to the translational application of novel antimicrobial materials in the clinical setting and has important social and economic value.
研究领域:
材料科学
·
生物材料
·
生物医学工程
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抗菌技术
·
骨科
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6
Xufeng Qin,Weifeng Xu,Jiangnan Hu,Yong Dong,Renbo Ding,Shuheng Huang,Zhendong Zhao,Hong Chang,Xiaokun Wang,Shuai Dong
Glioma, a common primary brain tumor, is highly infiltrative and invasive, often leading to drug resistance and recurrence. Therefore, the development of novel therapeutic agents is urgently needed. Pseudellone C is a novel marine triindole alkaloid. Screening of its antiproliferative activity against 55 cell lines revealed its anti-CNS cancer potential. A total of 42 derivatives of Pseudellone C were designed and synthesized, and their inhibitory activities against two human glioma cell lines (U-87MG and LN-229) were evaluated using the CCK-8 assay. Ten derivatives exhibited potent antiproliferative activity with IC 50 values below 10 μmol, which are 18- to 39- fold more potent than Pseudellone C. Among these, derivative 4o demonstrated favorable blood-brain barrier permeability. Mechanistic studies revealed that 4o induces apoptosis primarily by activating the downstream caspase 3 cascade via the TNF/TNFR pathway. Structure-activity relationship correlations were systematically analyzed, and a pharmacophore model for further rational design was constructed.
研究领域:
药理学
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肿瘤学
·
药物化学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2017
·Vol. 35
·期 8
·924-938
·
IF 1.692
Lu Bei-bei,Wei Lu-lu,Meng Gui-hua,Hou Jun,Liu Zhi-yong,Guo Xu-hong
Well-defined pH-responsive poly( ε -caprolactone)-graft- β -cyclodextrin-graft-poly(2-(dimethylamino)ethylmethacrylate)- co -poly(ethylene glycol) methacrylate amphiphilic copolymers (PCL- g - β -CD- g -P(DMAEMA- co -PEGMA)) were synthesized using a combination of atom transfer radical polymerization (ATRP), ring opening polymerization (ROP) and “click” chemistry. Successful synthesis of polymers was confirmed by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance ( 1 H-NMR), and gel permeation chromatography (GPC). Then, the polymers could selfassemble into micelles in aqueous solution, which was demonstrated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The pH-responsive self-assembly behavior of these copolymers in water was investigated at different pH values of 7.4 and 5.0 for controlled doxorubicin (DOX) release, and these results revealed that the release rate of DOX could be effectively controlled by altering the pH, and the release of drug loading efficiency (DLE) was up to 88% ( W / W ). CCK-8 assays showed that the copolymers had low toxicity and possessed good biodegradability and biocompatibility, whereas the DOX-loaded micelles remained with high cytotoxicity for HeLa cells. Moreover, confocal laser scanning microscopy (CLSM) images revealed that polymeric micelles could actively target the tumor site and the efficient intracellular DOX release from polymeric micelles toward the tumor cells further confirmed the anti-tumor effect. The DOX-loaded micelles could easily enter the cells and produce the desired pharmacological action and minimize the side effect of free DOX. These results successfully indicated that pH-responsive polymeric micelles could be potential hydrophobic drug delivery carriers for cancer targeting therapy with sustained release.
研究领域:
聚合物化学
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药学
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纳米技术
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生物医学工程
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Genomics
·
2023
·
IF 2.9
Yi Zhu,Xiaofeng Tian,Yan Wang,Chengxiang Wang,Naiquan Yang,Lianghong Ying,Hongyan Niu
Vascular smooth muscle cells (VSMCs) are critical elements of the vascular wall and play a crucial role in the genesis and development of atherosclerosis (AS). Increasingly, studies have indicated that long noncoding RNAs (lncRNAs) regulate VSMC proliferation, apoptosis, and other biological processes. Nevertheless, the role of lncRNA NFIA-AS1 (hereinafter referred to as NFIA-AS1) in VSMCs and AS remains unclear. Quantitative real-time PCR (qRT-PCR) was performed to analyze the messenger RNA (mRNA) levels of NFIA-AS1 and miR-125a-3p. CCK-8 and EdU staining were performed to detect VSMC proliferation. VSMC apoptosis was evaluated by flow cytometry. The expression of various proteins was detected using western blotting. The levels of inflammatory cytokines secreted by VSMCs were measured by enzyme linked immunosorbent assay (ELISA). The binding sites of NFIA-AS1 and miR-125a-3p, as well as miR-125a-3p and AKT1, were analyzed using bioinformatics methods and validated using a luciferase reporter assay. The function of NFIA-AS1/miR-125a-3p/AKT1 in VSMCs was clarified through loss- and gain-of-functional experiments. We confirmed that NFIA-AS1 was highly expressed in AS tissues and VSMCs induced by oxidized low-density lipoprotein (Ox-LDL). Knockdown of NFIA-AS1 restrained the exceptional growth of Ox-LDL-induced VSMCs, promoted their apoptosis, and decreased the secretion of inflammatory factors and expression of adhesion factors. In addition, NFIA-AS1 regulated the proliferation, apoptosis, and inflammatory response of VSMCs through the miR-125a-3p/AKT1 axis, suggesting that NFIA-AS1 may be a potential therapeutic target for AS.
研究领域:
心血管疾病
·
分子生物学
·
细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science of Advanced Materials
·
2024
·Vol. 16
·期 11
·1157-1166
·
IF 0.9
Li Yezhou,Tang Chengjian
This research investigated the application of alginate-collagen hydrogel (ACH) in rat cartilage injury (CI) repair and its related mechanisms through in vitro and in vivo experiments. Alginate solution and modified collagen solution were mixed to prepare the ACH. The obtained
samples were characterized and their sustained release properties were determined. L929 mouse fibroblasts were assigned into a blank control group (BC group, untreated), a positive control group (PC group, treated with 6.4% phenol), a negative control group (NC group, treated with tissue culture
polystyrene), and an ACH group (treated with ACH). Cell viability was assessed using the MTT assay. Meanwhile, the cytotoxicity of the ACH and its impact on cell proliferation and cell attachment capabilities were analyzed. Thirty 4-week-old specific pathogen-free (SPF) Sprague Dawley (SD)
rats were randomly grouped into a chondrocyte group (5 rats, chondrocytes collected and cultured), a cPAGE group (5 rats, chondrocytes treated with ACH), a model group (10 rats, CI model), and a mPAGE group (10 rats, CI model treated with CAH). The influence of CAH on chondrocyte proliferation
and the type II collagen (COLII) expression were assessed using the cell counting kit 8 (CCK-8) assay and immunofluorescence staining. Furthermore, the impacts of CAH on chondrocyte tissue and COL-II expression were analyzed using Safranin O-Fast Green (SOFG) staining, the International Cartilage
Repair Society (ICRS) score, and COL-II tissue staining. Immunoblotting was utilized to detect the TNF-α, NF-κB, matrix metalloproteinase 13 (MMP-13), and COL-II proteins in cartilage tissue. The results showed that release rate (RR) of the constructed ACH reached
over 85% within 72 hours and achieved degradation equilibrium within 5 days with a weight loss (WL) rate of over 60%. L929 fibroblasts culture results showed that the ACH posed no significant cytotoxicity, and cell attachment results were not obviously different from those on tissue culture
plates (P >0.05). MTT assay results demonstrated that the ACH exerted no adverse effects on L929 cell proliferation and growth, indicating a good biocompatibility. CCK-8 and COL-II results indicated that chondrocyte proliferation in cPAGE group was much higher in contrast to that in chondrocyte
group (P <0.05). Besides, the animal experiments unveiled that in comparison to the CI group, the mPAGE group had more chondrocytes, upregulated COL-II, and higher ICRS scores (P <0.05). MMP-13, NF-κB, and TNF-α were downregulated, and COL-II was
upshifted in the mPAGE group, with remarkable differences (P <0.05). In conclusion, ACH exhibited excellent biocompatibility and low cytotoxicity, promoted cell proliferation and growth, facilitated chondrocyte proliferation in rat CI repair, offering a valuable research foundation
for CI treatment.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
骨科
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）