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Hui Zhang,1 Wen-Ting Tong,2 Chang-Rong Zhang,1 Jun-Long Li,1 Hao Meng,3 Hai-Gan Yang,3 Min Chen31The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pharmacy, The First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi, People’s Republic of China; 3Department of Andrology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Min ChenDepartment of Andrology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 12 Ji-chang Road, Guangzhou 51000, Guangdong, People’s Republic of ChinaTel +86 203 659 1359Fax +86 203 659 1127Email wiiiiiki@gmail.comObjective: To investigate the effect of gross saponins of Tribulus terrestris (GSTT) on erectile function in rats resulting from type 2 diabetes mellitus (T2DMED).Methods: The T2DMED model was constructed by high-fat and high-sugar feeding and streptozotocin injection. After 4 weeks of GSTT intervention. Intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured in each group. The level of nitric oxide (NO) in the cavernous tissue was detected using the nitrate reductase method. The production of reactive oxygen species (ROS) was detected using DHE fluorescent probe detection. Cyclic adenosinemonophosphate (cGMP) level was detected by enzyme-linked immunosorbent assay, and endothelial nitricoxide synthase (eNOS) was detected using immunohistochemistry. Masson staining was used to detect the cavernosal smooth muscle/collagen ratio. Apoptosis in endothelial cells was measured using TUNEL. Western blotting method to detect the protein expression level of eNOS, TIMP-1, cleaved caspase 3, and cleaved caspase 9.Results: After treatment, the ICP and ICP/MAP values of the GSTT were significantly higher than those of the T2DMED group (P0.05), and the mixed group had higher levels than these two groups (P

Yuan Ding,1,* Dan Sun,1,* Gui-Ling Wang,1 Hong-Ge Yang,1 Hai-Feng Xu,1 Jian-Hua Chen,2 Ying Xie,1,3 Zhi-Qiang Wang4 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 2School of Medicine, Jianghan University, Wuhan, 3State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People’s Republic of China; 4Department of Chemistry and Biochemistry, Kent State University Geauga, Burton, OH, USA *These authors contributed equally to this work Abstract: Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future. Keywords: long circulation, pharmacokinetics, lysosome escape, nanocarrier, pH-sensitive liposomes

Abstract: Objective: Velocity vector imaging (VVI) is widely used to quantify cardiac mechanical deformation. This study sought to determine whether VVI could be used to evaluate the stiffness of maternal peripheral arteries in women with pre-eclampsia. Study design: Twenty-four women with pre-eclampsia and 34 normotensive pregnant women were recruited. Longitudinal and circumferential peak velocity, strain and strain rate of the right common carotid artery (CCA) were measured. All measurements were averaged from three consecutive cardiac cycles and expressed as mean±standard deviation. Results: Longitudinal velocity, strain and strain rate of the anterior and posterior walls of the CCA were significantly lower in women with pregnancy-induced hypertension compared with normotensive pregnant women [velocity: 0.22±0.09cm/s vs 0.29±0.09cm/s (p <0.01) and 0.24±0.10cm/s vs 0.34±0.13cm/s (p <0.01); strain: 8.50±4.92% vs 12.2±6.21% (p <0.01) and 10.11±5.02% vs 14.21±6.48% (p <0.05); strain rate: 1.62±1.14s–1 vs 2.24±1.13s–1 (p <0.05) and 1.91±0.99s–1 vs 2.45±0.97s–1 (p <0.05)]. Similar results were also found for circumferential velocity, strain and strain rate of the anterior and posterior walls, and the interior and exterior lateral walls of the CCA. Conclusions: Stiffness of the maternal CCA was significantly greater in women with pre-eclampsia compared with normotensive pregnant women. VVI may have potential for quantitative assessment of vascular mechanical deformation in the clinical setting. [Copyright &y& Elsevier]