JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2021
·
IF 3.981
Qikang Tian,Qianqian Han,Xin Zhu,Lan Zhang,Kun Chen,Zhishen Xie,Pan Wang,Xiangxiang Wu,Zhenqiang Zhang,Huahui Zeng
Celastrol is a promising drug candidate for treating diet-induced obesity, but the cytotoxicity and poor water solubility limit its clinical application. We prepared a novel celastrol conjugate (Cel-CMCS) with excellent water solubility (33.94 mg/mL), and then investigated its anti-obesity and toxic activities in diet-induced obese mice. Just as the parent celastrol, Cel-CMCS reduced body weight and body fat mass in an equally effective manner, but with lower toxicity. Collectively, Cel-CMCS provides a possible solution for the treatment of obesity in humans. In addition, the present study provided a practical experience of the development of carboxymethyl chitosan-based delivery system for poorly water-soluble drugs.
研究领域:
药学
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生物医学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2021
·Vol. 26
·期 14
·4361
·
IF 4.412
Ya Wang,Xiao-Jing Shen,Fa-Wu Su,Yin-Rong Xie,Li-Xia Wang,Ning Zhang,Yi-Long Wu,Yun Niu,Dong-Ying Zhang,Cheng-Ting Zi,Xuan-Jun Wang,Jun Sheng
Lung cancer is one of the most commonly occurring cancer mortality worldwide. The epidermal growth factor receptor (EGFR) plays an important role in cellular functions and has become the new promising target. Natural products and their derivatives with various structures, unique biological activities, and specific selectivity have served as lead compounds for EGFR. D-glucose and EGCG were used as starting materials. A series of glucoside derivatives of EGCG (7–12) were synthesized and evaluated for their in vitro anticancer activity against five human cancer cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480. In addition, we investigated the structure-activity relationship and physicochemical property–activity relationship of EGCG derivatives. Compounds11and12showed better growth inhibition than others in four cancer cell lines (HL-60, SMMC-7721, A-549, and MCF), with IC50values in the range of 22.90–37.87 μM. Compounds11and12decreased phosphorylation of EGFR and downstream signaling protein, which also have more hydrophobic interactions than EGCG by docking study. The most active compounds11and12, both having perbutyrylated glucose residue, we found that perbutyrylation of the glucose residue leads to increased cytotoxic activity and suggested that their potential as anticancer agents for further development.Keywords:EGCG;synthesis;cytotoxicity;EGFR;molecular docking
研究领域:
药理学
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肿瘤学
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMERS FOR ADVANCED TECHNOLOGIES
·
2017
·Vol. 29
·期 1
·442-450
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IF 1.907
Suchen Jiang,Huanchao Liu,Xue Zhang,Yajun Ren,Xinxiang Cui,Xiaofeng Song
Electrospun biodegradable fiber mesh is a promising alternative scaffold for delivering progenitor cells for repairing damaged or diseased tissue, but its cripple mechanical stability has not met the requirement of tissue engineering yet. In this work, the well-defined poly(ε-caprolactone)-branched poly(methyl methacrylate- co -hydroxyethylmethacrylate) (PCL-PMH) has been successfully synthesized to toughen electrospun poly( l -lactide) (PLLA) fiber membrane. Characterization of the obtained nanofibrous meshes indicates that PCL-PMH and PLLA can be well blended to make smooth fibers, and fibrous diameter vary little with blending PCL-PMH. The aggregation state of two macromolecules is closely correlated with blend ratio, molecular structure, and molecular weight of PCL-PMH, and only when PCL-PMH and PLLA form good interfacial adhesion can PMH give full play to its potential for toughening the fiber membrane. The tensile strength and elongation at break of the blend are 6.20 MPa and 63.40% under the optimal conditions, respectively, and it also exhibits the representative feature of toughness materials. The blending fiber membrane is as no cytotoxic as original PLLA. This work will provide a new way for toughness of electrospun fiber membrane in practice.
研究领域:
生物材料学
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组织工程学
✓ 已验证
DOI
高影响因子
Sensors & Diagnostics
·
2023
·Vol. 3
·期 1
·135-146
·
IF 0
Ke Gao,Yuying Du,Na Pan,Xuewei Zhou,Liping Lu,Xiayan Wang
Cadmium (Cd) can cause cell oxidative stress and cytotoxicity. Few studies have focused on inhibitory effects on Cd2+-induced oxidative stress and related cytotoxicity. Scanning electrochemical microscopy (SECM) is a highly sensitive and non-invasive electrochemical analytical method. However, no information exists on inhibitory effects on Cd2+-induced cell oxidative stress using SECM technology. Herein, we studied the effects of ascorbic acid (AsA), zinc chloride (ZnCl2), and calcium chelator 1,2-bis (2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid tetraethoxy methyl ester (BAPTA-AM) on cell oxidative stress with SECM. Subsequently, we studied the inhibitory effects of AsA, ZnCl2, and BAPTA-AM on Cd2+-induced cell oxidative stress. Consequently, 50 μmol L−1 AsA, 5 μmol L−1 ZnCl2, and 5 μmol L−1 BAPTA-AM did not produce reactive oxygen species (ROS) and had little effect on cell viability. However, they could significantly reduce Cd2+-induced excessive ROS and alleviate apoptosis (P < 0.01). Additionally, AsA had the strongest inhibitory effects on Cd2+-induced oxidative stress, followed by BAPTA-AM and ZnCl2. The inhibitory effects of AsA, ZnCl2, and BAPTA-AM on Cd2+-induced cytotoxicity might result from directly scavenging ROS and inhibiting oxidative stress-mediated signal transduction, enhancing antioxidant activities and maintaining cell membrane stabilities, and chelating excess calcium2+ (Ca2+) to hinder its subsequent signal transduction, respectively. Scavenging excessive ROS and inhibiting cellular oxidative stress-mediated signal transduction might be the most effective way to alleviate Cd2+-induced cytotoxicity. Our study provides empirical evidence on the inhibitory effects of AsA, ZnCl2, and BAPTA-AM as specialized inhibitors against Cd2+-induced cellular oxidative stress and cytotoxicity, providing precious ideas for detoxifying toxic environmental metal pollutants.
研究领域:
生物化学
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毒理学
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环境科学
✓ 已验证
DOI
Materials Science & Engineering C-Materials for Biological Applications
·
2016
·
IF 3.42
Shuang Gao,Zhiguo Yuan,Weimin Guo,Mingxue Chen,Shuyun Liu,Tingfei Xi,Quanyi Guo
The objectives of this study were to fabricate porous scaffolds using decellularized meniscus, and to explore a preferable crosslinking condition to enhance mechanical properties of scaffolds. Moreover, the microstructure, porosity, biodegradation and cytotoxicity were also evaluated. EDAC or GTA in different concentration was used to crosslink scaffolds. FTIR demonstrated functional groups change in crosslinking process. SEM photography showed that crosslinked scaffolds had blurry edges, which resulted scaffolds crosslinked by 1.2 mol/l EDAC had smaller porosity than other groups. The structure change enhanced antidegradation property. After immersing in enzyme solution for 96 h, scaffolds crosslinked by GTA and EDAC could maintain their mass > 70% and 80%. Most importantly, mechanical properties of crosslinked scaffolds were also improved. Uncrosslinked Scaffolds had only 0.49 kPa in compression modulus and 12.81 kPa in tensile modulus. The compression and tensile modulus of scaffolds crosslinked by 1.0% GTA were 1.42 and 567.44 kPa respectively. The same value of scaffolds crosslinked by 1.2 mol/l EDAC were 1.49 and 532.50 kPa. Scaffolds crosslinked by 1.0% and 2.5% GTA were toxic to cells, while EDAC groups showed no cytotoxicity. Chondrocytes could proliferate and infiltrate within scaffolds after seeding. Overall, 1.2 mol/l EDAC was a preferable crosslinking condition.
研究领域:
组织工程学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 6
·2531
·
IF 4.6
Da Song,Jia-Jun Liang,Shi-Biao Pu,Pan-Pan Zhang,Yun-Lin Peng,Xia Liu,Ting-Ting Feng,Xiang Pu,Ying Zhou,Xiong-Wei Liu,Xin Wei
Two new monoterpenoid indole alkaloids, gelselegandines F (1) and G (2), were isolated from the aerial parts ofGelsemium elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. The ECD calculations were conducted at the B3LYP/6-311G(d,p) level and NMR calculations were carried out using the Gauge-Including Atomic Orbitals (GIAO) method. Structurally, the two new compounds possessed rare, cage-like, monoterpenoid indole skeletons. All isolated compounds and the total alkaloids extract were tested for cytotoxicity against four different tumor cell lines. The total alkaloids extract ofG. elegansexhibited significant antitumor activity with IC50values ranging from 32.63 to 82.24 ug/mL. In order to discover anticancer leads from the active extraction, both new indole compounds (1–2) were then screened for cytotoxicity. Interestingly, compound2showed moderate cytotoxicity against K562 leukemia cells with an IC50value of 57.02 uM.Keywords:gelselegandines F and G;cytotoxicity;leukemic cells;Gelsemium elegans
研究领域:
药理学
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有机化学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2023
·Vol. 58
·期 31
·12685-12705
·
IF 4.5
Shen Jiadi,Ma Ming,Huang Yun,Miao Haochen,Wei Xin
This study aimed to evaluate the effects of the combined application of dimethylaminohexadecyl methacrylate (DMAHDM) and 10-methacryloyloxydecyl dihydrogen phosphate (MDP) on dentin bonding and its antimicrobial properties. DMAHDM was incorporated into the adhesives at 5% by mass, where two commercial adhesives were used: (1) MDP-free adhesive (single bond 2); (2) MDP-containing adhesive (single bond universal, SBU). The microtensile bond strength (μTBS) and nanoleakage were analyzed on the combination. The effects of DMAHDM on the interaction between MDP and hydroxyapatite and the degree of conversion were assessed by Fourier transform infrared spectroscopy (FTIR). Antimicrobial properties were examined by live/dead staining assay, colony-forming units (CFU), and metabolic activity, and cytotoxicity was measured using cell counting kit-8 (CCK-8) assay. 5% DMAHDM or MDP-containing groups showed increased immediate μTBS compared with the control group. Nanoleakage showed that 5% DMAHDM or MDP-containing groups presented little amount of silver penetration, while the control group exhibited extensive silver uptake along the bonding interface after water storage aging. FTIR showed that the interaction between MDP and hydroxyapatite was not affected by DMAHDM, besides DMAHDM did not hamper the polymerization of the bonding agents. The adhesives added with DMAHDM inhibited biofilm formation and reduced the biofilm CFU and metabolic activity of Candida albicans and Streptococcus mutans ( P < 0.05). No cytotoxic or slight cytotoxic effect was detected for the experimental materials used (MDP and 5% DMAHDM). The addition of DMAHDM along with MDP can obtain improved dentin bonding with increased antimicrobial performance.
研究领域:
牙科材料学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Soft Matter
·
2019
·Vol. 15
·期 9
·2051-2056
·
IF 3.399
Funing Liu,Hongli Zhang,Junjie Cheng,Jingang Hu,Chenlu He,Qijin Zhang,Gang Zou
Herein, we study the enantioselective cytotoxicity of vesicles self-assembled by optically active linear polymers (LNPs) and hyperbranched polymers (HBPs). Compared to HBP vesicles, LNP vesicles exhibit properties such as a higher surface charge density and more violent interaction with simulated biomembranes which results in larger cytotoxicity against HeLa cells. Specifically, racemic-LNP vesicles exhibit the largest cytotoxicity of all. More interestingly, there is no significant enantioselective dependence of HBP vesicles on the abovementioned properties. Overall, we proved that the cytotoxicity of vesicles is deeply related to chirality and topological-structures. This research is of great fundamental value for the design of novel bio-interface materials.
研究领域:
材料科学
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生物医学工程
·
聚合物化学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLANTA MEDICA
·
2022
·Vol. 88
·期 14
·1299-1310
·
IF 3.007
Xiaogang Peng,Qianxi Ouyang,Jiao Pei,Jinling Chang,Chunlun Qin,Hanli Ruan
Seven undescribed cytochalasins, multirostratins K – Q (2–8), together with one known analogue, cytochalasin Z3 (1), were isolated from the culture of Phoma multirostrata XJ-2-1, an endophytic fungus obtained from the root of Parasenecio albus. Their structures with absolute configurations were determined by 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), electronic circular dichroism (ECD), single-crystal X-ray crystallography, and chemical methods. The structure of ascochalasin was revised from Δ13 to Δ21 by detailed analysis of the NMR data and by comparison with the data for 7. In a TRAIL (tumor necrosis factor related apoptosis inducing ligand)-resistance-overcoming experiment, co-treatment of 2 or 6 with TRAIL reduced the cell viability of A549 cells by 30.3% and 27.5% at 10 µM, respectively.
研究领域:
药理学
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有机化学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
ACS Omega
·
2020
·
IF 2.87
Tian Tian,Zhiming Zhu,Yalong Ding,Guoli Li,Nan Li,Tong Shen
The first total synthesis of sanjoseolide (1), which was originally obtained from Dalea frutescens A, was achieved via an efficient route with a longest linear sequence of six steps from the commercially available 2,4-dihydroxyacetophenone in 8.6% overall yield. Meanwhile, a series of sanjoseolide representative analogues were synthesized and assessed for their antiproliferative potency against cancer cells of different origins. Compound 8e inhibited the survival of all tested cancer cell lines in a dose-dependent manner, the IC50 values of the treatment were about 12.8 μM for human cholangiocarcinoma cell lines RBE and 12.7 μM for human cholangiocarcinoma cell lines HCCC-9810, which was more active than sanjoseolide (1). Analysis of the structure–activity relationships revealed that the presence of a trifluoromethyl group may be beneficial in terms of both RBE and HCCC-9810 inhibition.
研究领域:
有机化学
·
肿瘤学
·
药物化学
✓ 已验证
DOI
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2024
·
IF 4.2
Zhengsheng Mao,Youjia Yu,Gen Ba,Hongmei Zhao,Qifang Shi,Yue Cao,Weiran Xie,Jinsong Zhang,Hao Sun,Feng Chen
Diquat (DQ) poisoning has garnered attention in recent years, primarily due to the rising incidence of cases worldwide, coupled with the absence of a viable antidote for its treatment. Despite the fact that diquat monopyridone (DQ-M) has been identified as a significant metabolite of DQ, the enzyme responsible for its formation remains unknown. In this study, we have identified aldehyde oxidase (AOX) as a vital enzyme involved in DQ oxidative metabolism . The metabolism of DQ to DQ-M was significantly inhibited by AOX inhibitors including raloxifene and hydralazine . The source of oxygen incorporated into DQ-M was proved to be from water through a H2 18 O incubation experiment which further corroborated DQ-M formation via AOX metabolism. The product of DQ-M in vitro generated by fresh rat tissues co-incubation was consistent with its AOX expression. The result of the molecular docking analysis of DQ and AOX protein showed that DQ is capable of binding to AOX. Furthermore, the cytotoxicity of DQ was significantly higher than DQ-M at the same concentration tested in six cell types. This work is the first to uncover the involvement of aldehyde oxidase, a non-cytochrome P450 enzyme, in the oxidative metabolic pathway of diquat, thus providing a potential target for the development of detoxification treatment.
研究领域:
药理学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Polymer Science
·
2019
·
IF 1.892
Wei Xiong,Yue-kun Shen,Peng Dong,Ying Xiao,Xiong-qing Huang,Wen-qi Huang,Lu Yang,Xia Feng
Sustained release of anesthesia has shown great promise in the treatment of chronic pain in patients. In this research, we used neutralized ropivacaine as an anesthesia and poly(ε-caprolactone) (PCL) with different architectures to systematically study how these architectures affect the release of ropivacaine. After optimizing the parameters of the preparation of microspheres, ropivacaine-loaded 1-PCL microspheres and 4-PCL microspheres were obtained. Fourier Transform infrared spectra (FT-IR) and X-ray diffraction spectra (XRD) confirmed that ropivacaine was encapsulated within the microsphere rather than inserted on the surface of the microsphere. Ropivacaine was found to be buried deeper in the 1-PCL microsphere than in the 4-PCL microsphere. In vitro release assay revealed that small crystalline grains interfered with ropivacaine release in 4-PCL microspheres during the initial release period, but then two kinds of microspheres showed a similar ropivacaine release rate. We basically proved that the architecture of PCL has a negligible effect on ropivacaine release. Cell proliferation test revealed that the release of products from the microspheres resulted in insignificant toxicity towards mammalian cells.
研究领域:
药剂学
·
材料科学
·
疼痛管理
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）