Ex vivo relaxation effect of Cuscuta chinensis extract on rabbit corpus cavernosum

The effect of Cuscuta chinensis extract on the rabbit penile corpus cavernosum (PCC) was evaluated in the present study. Penises obtained from healthy male New Zealand white rabbits (2.5–3.0 kg) were precontracted with phenylephrine (Phe, 10 µmol l⁻¹) and then treated with various concentrations of Cuscuta chinensis extract (1, 2, 3, 4 and 5 mg ml⁻¹). The change in penile tension was recorded, and cyclic nucleotides in the PCC were measured by radioimmunoassay (RIA). The interaction between Cuscuta chinensis and sildenafil was also evaluated. The result indicated that the PCC relaxation induced by Cuscuta chinensis extract was concentration-dependent. Pre-treatment with an nitric oxide synthase (NOS) inhibitor (Nω nitro-L-arginine-methyl ester, L-NAME), a guanylyl cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ), or a protein kinase A inhibitor (KT 5720) did not completely inhibit the relaxation. Incubation of penile cavernous tissue with the Cuscuta chinensis extract significantly increased cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) in the PCC. Moreover, the Cuscuta chinensis extract significantly enhanced sildenafil-induced PCC relaxation. In conclusion, the Cuscuta chinensis extract exerts a relaxing effect on penile cavernous tissue in part by activating the NO-cGMP pathway, and it may improve erectile dysfunction (ED), which does not completely respond to sildenafil citrate.     

人胚胎干细胞来源的成纤维细胞支持无动物源污染条件下的人精原干细胞生长

精原干细胞在人出生后可以连续分裂以支持精子形成,将遗传信息传递给下一代。在本文中,我们成功地从睾丸组织中分离并鉴别人精原干细胞的一种新方法,并在人胚胎干细胞来源的成纤维细胞上扩增人精原干细胞。在这种人胚胎干细胞来源的成纤维细胞上可维持大量的人精原干细胞并且在组合生长因子,特别是胶质细胞来源的神经生长因子存在的条件下扩增至少2个月。细胞表面标志分析显示这些精原干细胞具有高水平的碱性磷酸酶的表达并保持了高水平的胚胎特异阶段抗原SSEA-1,OCT4和CD49f的表达。用逆转录PCR反应检测出OCT4,SOX3,STRA8基因的表达。这些数据清晰地表明运用人胚胎干细胞来源的成纤维细胞来支持人精原干细胞的一个新的策略,并排除了异源物种的污染。这个系统提供了新的机会去了解干细胞巢对于控制精原干细胞自我更新的调节机制,并将对于精原干细胞潜在的临床应用提供有用的精原干细胞。     

MIP-1α enhances Jurkat cell transendothelial migration by up-regulating endothelial adhesion molecules VCAM-1 and ICAM-1

The aim of this study is to evaluate the expression of macrophage inflammatory protein-1α (MIP-1α) in Jurkat cells and its effect on transendothelial migration. In the present study, human acute lymphoblastic leukemia Jurkat cells (Jurkat cells) were used as a model of T cells in human T-cell acute lymphoblastic leukemia (T-ALL), which demonstrated significantly higher MIP-1α expression compared with that in normal T-cell controls. The ability of Jurkat cells to cross a human brain microvascular endothelial cell (HBMEC) monolayer was almost completely abrogated by MIP-1α siRNA. In addition, the overexpression of MIP-1α resulted in the up-regulated expression of endothelial adhesion molecules, which enhanced the migration of Jurkat cells through a monolayer of HBMEC. MIP-1α levels in Jurkat cells appeared to be an important factor for its transendothelial migration, which may provide the theoretical basis to understand the mechanisms of brain metastases of T-ALL at cellular and molecular levels.     

The Antitumor Effect of a New Docetaxel-Loaded Microbubble Combined with Low-Frequency Ultrasound In Vitro: Preparation and Parameter Analysis

Purpose

To develop a novel docetaxel (DOC)-loaded lipid microbubbles (MBs) for achieving target therapy and overcoming the poor water-solubility drawback of DOC.

Methods

A novel DOC-loaded microbubble (DOC + MB) was prepared by lyophilization and the physicochemical properties including ultrasound contrast imaging of the liver were measured. The anti-tumor effect of the DOC + MBs combined with low-frequency ultrasound (LFUS; 0.8Hz, 2.56 W/cm², 50% cycle duty) on the DLD-1 cancer cell line was examined using an MTT assay.

Results

The physicochemical properties of the two tested formats of DOC + MBs (1.0 mg and 1.6 mg) was shown: concentration, (6.74?±?0.02)?×?10⁸ bubbles/mL and (8.27?±?0.15)?×?10⁸ bubbles/mL; mean size, 3.296?±?0.004 μm and 3.387?±?0.005 μm; pH value, 6.67?±?0.11 and 6.56?±?0.05; release rate, 3.41% and 12.50%; Zeta potential, ?37.95?±?7.84 mV and ?44.35?±?8.70 mV; and encapsulation efficiency, 54.9?±?6.21% and 46.3?±?5.69%, respectively. Compared with SonoVue, the DOC + MBs similarly enhanced the echo signal of the liver imaging. The anti-tumor effect of the DOC + MBs/LFUS group was significantly better than that of DOC alone and that of the normal MBs/LFUS groups.

Conclusions

The self-made DOC + MBs have potential as a new ultrasound contrast agent and drug-loaded microbubble, and can obviously enhance the antitumor effect of DOC under LFUS exposure.     

Therapeutic effect of the sulforaphane derivative JY4 on ulcerative colitis through the NF-κB-p65 pathway

Inflammopharmacology - The efficacy of the sulforaphane derivative JY4 was evaluated in acute and chronic mouse models of ulcerative colitis induced by dextran sodium sulfate. Oral administration...     

Perfluoroalkyl Substances in Water from the Yangtze River and Its Tributaries at the Dividing Point Between the Middle and Lower Reaches

The Yangtze River drainage basins are China’s most important economic development zones and also the locations of several large-scale fluorine chemical industries. In order to reveal the contribution from the tributaries at the dividing point between the middle and lower reaches of the Yangtze River with respect to perfluorinated substances (PFASs), 17 PFAS compounds in surface water, groundwater, and tap water samples were analyzed in the tributary system of the Jiujiang section of the Yangtze River. The total concentrations of PFASs in the surface waters ranged from 7.8 to 586.2 ng/L. High proportion of short-chain compound PFBS in surface waters in Nanchang City, Poyang Lake, and the Yangtze River was observed which is likely of WWTPs’ origin.     

不同氧浓度培养对小鼠骨髓造血干细胞生物活性的影响

本研究模拟人外周血造血干细胞(HSC)移植中HSC所经历的氧环境,研究不同氧浓度对小鼠骨髓HSC生物功能的影响及可能机制。采用体外扩增实验、定向分化实验、细胞周期分析、活性氧测定及亚致死量射线照射小鼠骨髓原始Lin-c-kit+Sca-1+HSC移植等方法,分别检测了Lin-c-kit+Sca-1+HSC的扩增能力,细胞周期,活性氧水平及造血重建能力。结果表明:低于常氧浓度,特别是乏氧的氧环境能降低活性氧的产生,增强原始骨髓HSC体外扩增能力,增加红系集落(BFU-E)、粒单集落(CFU-GM)、红系粒单系巨核系集落(CFU-GEMM)的数量,维持较多的HSC处于G0/G1期,进而明显促进移植后小鼠的脾集落(CFU-S)生长及提高移植小鼠存活数量。而暴露于常氧、不恒定且氧浓度变化剧烈的氧环境中的骨髓HSC能产生较高水平的活性氧,上述功能指标都较低。结论:骨髓HSC的活性氧水平与周围氧环境中氧浓度水平及稳定性密切相关,高水平的活性氧损害骨髓HSC的功能。在恒定的较低浓度的氧环境下培养及应用抗氧化剂对于骨髓HSC移植可能更有益。