Regulation of replanted progesterone on stress signal in endoplasmic reticulum stress during menstruation in mice at different periods / 医学研究生学报

Objective　Endoplasmic reticulum stress may be involved in the menstrual process, but the detailed mechanism is unclear. This article is to explore the effect of progesterone replantation at different periods on the endoplasmic reticulum stress-induced autophagy and apoptosis in mice during menstruation.　Methods　Mice were divided into 12h replantation group, 16h replantation group and the withdrawal group according to random number table, with 10 mice in each group. 12h (12h replantation group) and 16h (16h replantation group) after the withdrawal of progesterone, replanted respectively with progesterone tube, and withdrawal group were not replanted. Mice in each group were sacrificed 24h after the withdrawal of progesterone and were collected bilateral uterine horns. The expression and localization of t-PERK, p-PERK, t-eIF2α, p-eIF2α, ATF4, CHOP and Caspase12 mRNA and proteins in mouse endometrial tissues were detected by qPCR, Western blot and immunohistochemistry.　Results　At the mRNA level, the PERK and eIF2α(1.000 ± 0.000) of the 12h replantation group were significantly higher than those of the 16h replantation group (0.450 ± 0.049, 0.330 ± 0.015) and the withdrawal group (0.260 ± 0.233, 0.195 ± 0.014). The difference was statistically significant (P<0.05), and the 16h replantation group was higher than the withdrawal group (P<0.05). At the protein level, p-PERK / t-PERK (0.606 ± 0.051) and p-eIF2α / t-eIF2α (0.795 ± 0.074) in 12h replantation group were significantly higher than those in 16h replantation group (0.367 ± 0.019, 0.503 ± 0.038) and withdrawal group (0.243 ± 0.020, 0.293 ± 0.020). The difference was statistically significant (P<0.05) and the 16h replantation group was significantly higher than the withdrawal group. At the mRNA and protein levels, ATF4 of 12h replantation group were higher than 16h replantation group and the withdrawal group (P <0.05) , and the 16h replantation group was higher than the withdrawal group. The proteins of p-PERK, p-eIF2α and ATF4 are mainly expressed in the cytoplasm of decidual stromal cells which located at the junction of basal layer and decidualized stromal cells. At mRNA and protein levels, the expression levels of CHOP and Caspase12 in 12h replantation group were significantly lower than those in 16h replantation group , were also lower than the withdrawal group, and the 16h replantation group was lower than the withdrawal group (P<0.05). The proteins of CHOP and Caspase12 are mainly localized in cytoplasm of adequately decidualized stromal cells and the glandular epithelium cells.　Conclusion　Replantation of progesterone before the critical period of menstruation (12h) can effectively block the onset of menstruation in mice, which may be achieved by maintaining the expression of PERK/eIF2α/ATF4 signal and blocking the expression of apoptotic signaling pathway members CHOP and Caspase 12 in endometrial stromal cells. And this effect can only be partially achieved by progesterone replantationing after the critical period of menstruation (16h).

Chemical constituents of Euphorbia dracunculoides / 中国中药杂志

Sixteen compounds including daphnoretin (1), isofraxidin (2), scopoletin (3), kaempferol (4), quercetin (5), guaijaverin (6), astragalin (7), quercetin-3-O-β-D-glucopyranoside (8), naringenin-7-O-β-D-glucopyranoside (9), 5-O-methylapi- genin-7-O-β-D-glucopyranoside (10), methyl gallate (11), prionitiside A (12), (2S)-2,3-dihydroxypropyl-1,6,8-trihydroxy-3- methyl-9,10- dioxoanthracene-2-carboxylate (13), 3,3'-di-O-methyl ellagic acid (14), 3'-O-methyl-3,4-O,O-metheneellagic acid-4'-O-β-D- glucopyranoside (15) and 3,4-methylenedioxy-3'-O-methylellagic acid (16), were isolated from the 70% acetone extract of Euphorbia dracunculoides Lam. Among them, compounds 1-3, 6-9, 11, and 14 were isolated from E. dracunculoides for the first time, and compounds 10, 12, 13, 15, and 16 were firstly obtained from the genus Euphorbia. Their structures were elucidated by spectroscopic analysis, including 1H-NMR, 13C-NMR, and ESI-MS.

Predicting pharmacokinetics of anti-cancer drug, famitinib in human using physiologically based pharmacokinetic model / 药学学报

This study is to establish physiologically based pharmacokinetic (PBPK) models of famitinib in rat and monkey, and then to predict the pharmacokinetics and tissue distribution of famitinib in human based on the PBPK models. According to published paper, previous studies and the chemical properties of famitinib predicted by ACD/ADME suite and SimCYP, the PBPK models of rat and monkey were established and optimized using GastroPlus. And then, the PBPK models were applied to predict the pharmacokinetic and tissue distribution of famitinib in human. The results showed that the PBPK models of rat and monkey can fit the observed data well, and the AUC0-∞, ratios of observed and calculated data in rat and monkey were 1.00 and 0.97, respectively. The AUC0-∞, ratios of observed and predicted data in human were 1.63 (rat to human) and 1.57 (monkey to human), respectively. The rat and monkey PBPK models of famitinib were well established, and the PBPK models were applied in predicting pharmacokinetic of famitinib in human successfully. Hence, the PBPK model of famitinib in human could be applied in future drug-drug interaction study.

Radiolabeling LyP-1 peptide and preliminary biodistribution evaluation in mice bearing MDA-MB-435 xenografts / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent studies have shown the LyP-1 peptide can home to either tumor lymphatics or the tumor cells and be internalized by targeted cells. This study aimed to investigate the possibility of using Na(131)I labeled LyP-1 peptide as an imaging agent or a therapeutic radiopharmaceutical in breast carcinoma and its metastasis.</p><p><b>METHODS</b>The 10-mer cyclic peptide contained the LyP-1 sequence (YCGNKRTRGC) was synthesized by the solid phase method. Disulfide bonds between the cysteines maintain the cyclic structure. The LyP-1 peptide was labeled with Na(131)I using the chloramine-T method. The [(131)I] LyP-1 peptide and a [(131)I] control peptide were injected via tail vein into nude mice bearing MDA-MB-435 tumor xenografts. Biodistribution and imaging results in vivo were obtained.</p><p><b>RESULTS</b>The labeling efficiencies of LyP-1 peptide reached 80% ± 5% (n = 5). The radiochemical purity was about 96%. The radiochemical purity of the labeled compound remains 92% at 24 hours in human serum at 37°C. In the biodistribution studies, the [(131)I] LyP-1 peptide accumulated in the tumor to a higher level than in other organs. The [(131)I] LyP-1 peptide can successfully image the tumor in nude mice bearing MDA-MB-435 tumor xenografts.</p><p><b>CONCLUSIONS</b>The LyP-1 peptide could be effectively labeled with Na(131)I and the labeled compound is stable in human serum at 37°C for 24 hours. The high specificity of [(131)I] LyP-1 peptide suggests it may be a promising new radiotracer for identifying tumors.</p>