通讯机构：
[Wei, Hua] L;[Wei, Hua] U;Lanzhou Univ, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Gansu, Peoples R China.;Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China.;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
摘要：
Cyclic polymers have outperformed their linear analogues for controlled release applications in terms of greater stability and better therapeutic efficiency due to the endless chain topology. However, to our knowledge, there have been thus far only a few examples of the fabrication of pH-sensitive cyclic polymers for drug delivery applications. To further improve the colloidal stability of the previously synthesized cyclic poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) for drug delivery applications via a facile yet efficient approach, it will be useful and straightforward to incorporate a hydrophilic monomer for copolymerization with DMAEMA. For this purpose, we reported in this study the preparation of pH-sensitive cyclic statistical copolymers, P(OEGMA-st-DMAEMA)s, with two different compositions by atom transfer radical polymerization (ATRP) of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) and DMAEMA and subsequent "intra-chain" click cyclization of the a-alkyne-.-azide linear precursor. A further comparison study on the micelle stability revealed that the spherical micelles self-assembled from c-P(OEGMA(4)-st-DMAEMA(38)) (C) with both smaller hydrodynamic size than that of the micelles of the linear analogue, l-P(OEGMA(4)-st-DMAEMA(38)) (L), and greater salt stability than that of the micelles of c-P (OEGMA(8)-st-DMAEMA(38)) were screened to be the optimal micelle construct for drug delivery applications. Flow cytometry (FCM) analysis confirmed greater cellular uptake efficiency of doxorubicin (DOX)loaded C (C@DOX) micelles than that of the L (L@DOX) ones. More importantly, the C@DOX micelles showed comparable in vitro cytotoxicity against the cancer cell line (HeLa cells) but lower in vitro cytotoxicity against the normal cell line (HUVEC cells) relative to the L@DOX formulation after 72 h of incubation. Therefore, this study not only developed a facile approach to improve the colloidal stability of a cyclic polycation, but also presented a pH-sensitive cyclic copolymer-based nanoplatform with great potential for anticancer drug delivery.
期刊：
PATHOLOGY RESEARCH AND PRACTICE,2019年215(2):229-234 ISSN：0344-0338
通讯作者：
Wu, Daichao;Tan, Sijie
作者机构：
[Liu, Yan; Zou, Ju] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Special Pathogens Prevent & Co, Dept Parasitol,Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.;[Tan, Sijie; Wu, Daichao] Univ South China, Hengyang Med Coll, Dept Histol & Embryol, Inst Clin Anat & Reprod Med, Hengyang 421001, Hunan, Peoples R China.;[Li, Tao; Wang, Xianwen] Univ South China, Hengyang Med Coll, Grade 2015 Clin Med, Hengyang 421001, Hunan, Peoples R China.;[Wu, Daichao; Tan, SJ] Univ South China, Hengyang Med Coll, Inst Clin Anat & Reprod Med, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Wu, DC; Tan, SJ] U;Univ South China, Hengyang Med Coll, Inst Clin Anat & Reprod Med, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
Cancer;Meta-analysis;PD-L1;SNP
摘要：
Programmed death ligand 1(PD-L1) mediated immune escape play important roles in the development of cancer. The gene polymorphism of PD-L1, in particular rs4143815 C > G, has been associated with the cancer risks, but with conflicting results. Therefore, this meta-analysis was aimed to assess the association between rs4143815 C > G and cancer susceptibility. A systematic literature search was performed to select the studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Eleven eligible studies containing 3711 cases and 3704 controls were enrolled in the meta-analysis. The results suggested that there is a strong association between rs4143815 C > G and the cancer risks (G vs. C: OR = 1.386, 95% CI: 1.132-1.696, p = 0.002; GG vs. CG + CC: OR = 1.843 95% CI: 1.300-2.613, p = 0.002; GG + CG vs. CC: OR = 1.280, 95% CI: 1.040-1.576, p = 0.020). Subgroup analysis based on cancer type suggested that PD-L1 rs4143815 C > G might increase the susceptibility to gastric cancer (G vs. C: OR = 1.842, 95% CI: 1.403-2.418, p < 0.001) and bladder cancer (G vs. C: OR = 2.015, 95% CI: 1.556-2.608, p < 0.001), and genotype GG carriers of PD-L1 rs4143815 C > G might have higher risks of HCC (GG vs. CG + CC: OR = 2.226 95% CI: 1.562-3.172, p < 0.001). PD-L1 rs4143815 C > G might confer an increased cancer risk, indicating this SNP may contribute to the pathogenesis of cancer and might be used as a potential biomarker to predict the susceptibility to cancer.
摘要：
A series of chrysin salicylate derivatives as potential antitumour agents were synthesised and evaluated their antitumour activities in vitro and in vivo. Most of the compounds exhibited moderate to good activities against MCF-7 cells, HepG2 cells, MGC-803cells and MFC cells. Among them, compound 3f showed the most potent activity against MGC-803 cells and MFC cells with IC50 values of 23.83 ± 3.68 and 27.34 ± 5.21 μM, respectively. The flow cytometry assay reconfirmed that compound 3f promoted the occurrence of tumour cells’ G1/S block under the inhibiting effect of compound 3f. Compound 3f possessed higher antitumour efficacy in tumour-bearing mice, compared with the positive control 5-Fu and the blank control saline.
通讯机构：
[Guo, Yu] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
摘要：
Genistein amino acid derivatives 4a–4d were synthesized and evaluated for their cytotoxic activities against MCF-7, Hela, MGC-803 and HCT-116 cell lines by MTT assays in vitro. The results revealed that compounds 4a–4d showed better activity than the parent compound genistein. Particularly, compound 4b displayed the most significant anticancer activity against MGC-803 with an IC50 value of 12.08 μM. In addition, the mechanisms of interaction between genistein, compounds 4a–4d and BSA were investigated via multi-spectroscopic techniques such as ultraviolet (UV) spectroscopy, fluorescence, circular dichroism (CD), and molecular docking under physiological conditions. The results suggested that endogenous fluorescence of BSA could be quenched by genistein and compounds 4a–4d via forming BSA-compound complex, which meant a static quenching mechanism was involved. The negative values of enthalpy (ΔH) and entropy (ΔS) indicated that interactions between BSA and the ligands were spontaneous, and hydrogen bonding and van der Waals interactions were involved in the BSA-compound complexion formation. The UV, synchronous and 3D fluorescence results revealed that the micro-environment of tryptophan and conformation of BSA were changed after binding to ligands. CD analysis demonstrated the variation in the secondary structure and that the α-helix content of BSA decreased. Eventually, molecular docking was executed to forecast the binding forces and binding sites between BSA and compounds 4a–4d.
作者机构：
[Wang, Zhe; Liu, Yunmei; Zou, Liu; Liu, Juan; Zheng, X; Tang, GT; Tang, Guotao; Zheng, Xing; Deng, Xiangping; Xie, Zhizhong; Lei, Xiaoyong; Xiong, Shujuan; Xiong, Runde; Cao, Xuan] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Chen, Yanming] Mu Dan Jiang You Bo Pharmacert Co Ltd, Mudanjiang, Peoples R China.
通讯机构：
[Zheng, X; Tang, GT] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang, Peoples R China.
关键词：
Chrysin;benzimidazole;synthesis;anticancer
摘要：
A series of chrysin benzimidazole derivatives were synthesised and evaluated for their anticancer activity in the search for potential anticancer agents. Among them, compound 18 displayed the most potent anti-proliferative activity against MFC cells with IC50 values of 25.72 ± 3.95 μM. The flow cytometry results displayed that compound 18 induced apoptosis of MFC cells in a dose-dependent manner and caused the cell cycle to be arrested in the G0/G1 phase. Furthermore, the preliminary anticancer activity in vivo was also studied in tumour-bearing mice, and the compound 18 exerted good inhibition effect on tumour growth. These results suggested that compound 18 had good anticancer activity, which could be a potential anticancer agent after further optimisation and evaluation.
摘要：
Minimally modified low density lipoprotein (mmLDL) is a risk factor for cardiovascular disease. This study investigated the effect of mmLDL on mouse mesenteric artery endothelin type B (ETB) receptors and its molecular mechanism. Mice were injected with normal saline (NS group), mmLDL in the tail vein (mmLDL group), or with both mmLDL and an intraperitoneal injection of the ERK1/2 pathway-specific inhibitor U0126 (mmLDL + U0126 group). The dose-response curve of mesenteric artery contraction induced by sarafotoxin 6c (S6c), the ETB receptor agonist, was measured using a sensitive myograph system. ELISAs, RT-PCR and Western blot were used to determine the serum concentrations of mouse oxidized low density lipoprotein (oxLDL), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) as well as the expression of ETB receptors, ICAM-1, VCAM-1 and phosphorylated-extracellular signal-regulated kinase 1/2 (p-ERK1/2). The S6c-induced contraction dose-response curve was significantly enhanced by mmLDL treatment and showed a significantly higher Emax value than in the NS group (P < 0.001), and the ETB receptor mRNA and protein expression in the vascular wall was significantly higher than in the NS group. The serum concentration and expression of ICAM-1 and VCAM-1 were also increased by mmLDL treatment, but intraperitoneal injection of U0126 inhibited these changes as well as the increase in p-ERK1/2 protein in the vessel wall caused by mmLDL. ICAM-1 and VCAM-1 serum concentrations were positively correlated with the S6c-induced maximum contraction of blood vessels. Increased in vivo levels of mmLDL increased the serum concentrations and expression of ICAM-1 and VCAM-1 by activating the ERK1/2 pathway, resulting in the expression of ETB receptors and the enhancement of contractile function in vascular smooth muscle. Understanding the effect of mmLDL on ETB receptors and its mechanism can provide ideas for cardiovascular disease prevention and treatment.
期刊：
Journal of Pharmacy and Pharmacology,2016年68(6):751-761 ISSN：0022-3573
通讯作者：
Tang Guotao
作者机构：
[Huang Rongbin] First Peoples Hosp Xiangtan City, Xiangtan, Peoples R China.;[Deng Xiangping; Xiang Lei; Cao Xuan; Li Lanfang; Tang Guotao; Liu Ying; Yu Cuiyun] Univ South China, Learning Key Lab Pharmacoprote, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Chen Yanming] Mu Dan Jiang You Bo Pharmacert Co Ltd, Mudanjiang, Peoples R China.
通讯机构：
[Tang Guotao] U;Univ South China, Learning Key Lab Pharmacoprote, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.
关键词：
benzoic-imine bond;pH-sensitive;micelle;drug delivery system
