Hypolipidemic Activity of Okra is Mediated Through Inhibition of Lipogenesis and Upregulation of Cholesterol Degradation

Little is known about the hypolipidemic activity of okra; therefore, we investigated the hypolipidemic activity of okra and its interaction with gene expression of several key components involved in lipid homeostasis. Male C57BL/6 mice were randomly divided into three groups and fed with hyperlipidemic diet or two hyperlipidemic diets supplemented with 1% or 2% okra powder for eight weeks. Results demonstrated that okra dose‐dependently decreased serum and hepatic total cholesterol and triglyceride, and enhanced fecal excretion of bile acids. Gene expression analysis revealed that okra upregulated cholesterol 7α‐hydroxylase (CYP7A1) expression, downregulated expression of sterol regulatory element‐binding protein 1c (SREBP1c) and fatty acid synthase (FAS), with no effect on sterol regulatory element‐binding protein 2 (SREBP2), 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGR), low‐density lipoprotein receptor (LDLR) and carnitine palmitoyltransferase‐1A (CPT1A). It was suggested that hypolipidemic activity of okra was mediated most likely by upregulation of cholesterol degradation through CYP7A1 and by inhibition of lipogenesis through SREBP1c and FAS. Okra raw and fractionated polysaccharide showed strong bile acid binding capacity in vitro, which may contribute to the hypolipidemic activity observed. In conclusion, okra has potential application in the management of hyperlipidemia and its associated metabolic disorders. Copyright © 2013 John Wiley & Sons, Ltd.     

Human kallikrein 2 (KLK2) promotes prostate cancer cell growth via function as a modulator to promote the ARA70-enhanced androgen receptor transactivation

Recent data suggested that tissue human kallikrein 2 (KLK2) might be involved in the carcinogenesis and tumor metastasis of prostate cancer (PCa). However, the detailed pathophysiological roles of KLK2 in PCa remain unclear. We report here that KLK2 may be treated as a potential therapeutic target in castration-resistant PCa (CRPC). Histologic analyses show that the increased KLK2 expression is correlated with higher cell proliferation rate and lower cell apoptosis index in CRPC specimens. Adding functional KLK2 cDNA into high passage LNCaP cells led to increased cell growth, and knockdown of KLK2 expression with KLK2-siRNA in LNCaP cells resulted in increased cell apoptosis with cell growth arrest at the G1 phase. Results from in vitro colony formation assay and in vivo xenografted PCa tissues also demonstrated that targeting KLK2 led to suppressed growth of PCa in the castration-resistant stage. Further mechanism dissection shows that KLK2 may cooperate with the AR coregulator, ARA70, to enhance AR transactivation that may result in alteration of PCa formation. Together, these results suggested KLK2 might become a new therapeutic target to battle the CRPC and KLK2-siRNA may be developed as an alternative approach to suppress PCa growth.     

牙髓干细胞在组织工程研究中的应用

背景：牙髓干细胞是来源于牙髓组织中的一种成体干细胞,该种细胞具有高度增殖、自我更新的能力和多向分化潜能.通过对牙髓干细胞的深入研究,有助于人类为组织工程研究提供可能的细胞来源,进而指导临床相关治疗与预防.目的：就牙髓干细胞的研究现状及其在组织工程中的应用作一综述.方法：应用计算机检索CNKI和Pubmed数据库中2000年1月至2012年5月关于牙髓干细胞的文章,在标题和中以“牙髓干细胞,诱导,培养,分化”或“dental pulp stem cel s,culture,induced, differentiation”为检索词进行检索.选择文章内容与牙髓干细胞有关者,同一领域文献则选择近期发表或发表在权威杂志文章.初检得到205篇文献,根据纳入标准选择关于牙周局部缓释剂的44篇文献进行综述.结果与结论：相比较其他成体干细胞,牙髓干细胞的研究尚面临许多问题.但随着科学技术的日益进步,随着这些问题的深入探讨和逐步解决,牙髓干细胞的研究将日趋完善.牙髓干细胞有望成为牙组织工程、骨组织工程和神经组织工程的种子细胞,在牙髓再生、牙体的修复等方面有着广阔的应用前景.     

透析方式对肾移植术后的影响

目的　探讨不同透析方式对肾移植术的影响。方法　透析时间大于 3个月的肾移植患者 5 16例 ,按照透析方式分为两组 ,血液透析 (HD)组 (n =394 )与腹膜透析 (PD)组 (n =12 2 ) ;记录两组患者肾移植术后 1年内并发症发生情况。结果　HD组与PD组患者肾移植术后超急性排斥的发生率差异无显著性 (P >0 0 5 ) ;两组患者急性排斥的发生率分别为 13 5 8%和 2 3 97% (P =0 0 0 5 ) ,细菌感染的发生率分别为 8 4 6 %和 15 7% (P <0 0 5 ) ,活动CMV感染的发生率分别为 2 5 13%和 16 5 3% (P <0 0 5 ) ,CMV肺炎的发生率分别为 7 4 4 %和 2 4 8% ,差异均有显著性 (P <0 0 5 )。HD组患者因超急性排斥切除移植肾 4例 ,急性排斥反应切除移植肾 3例 ,严重感染切除移植肾 1例 ,因败血症死亡 1例 ,因CMV肺炎呼吸衰竭死亡 4例 ,因心力衰竭死亡 2例 ;PD组患者因超急性排斥及急性排斥反应切除移植肾各 1例 ;因化脓性腹膜炎及真菌性败血症死亡各 1例 ;其余患者经治疗预后良好。结论　PD患者的免疫活性高于HD患者 ,并更易发生感染 ,在肾移植术围手术期应注意透析方式造成的影响。     

脂代谢相关基因在低密度脂蛋白受体基因缺失幼龄小鼠肝脏中的表达分析

目的 探讨脂代谢相关基因在低密度脂蛋白受体(LDLR)基因缺失(LDLR-/-)小鼠肝脏中的表达特征及其与血脂紊乱和动脉粥样硬化早期病变的关系.方法 应用RT-PCR技术分析14、30、60和90天龄LDLR-/-与野生型(WT)小鼠靶基因表达差异,并进行血生化及主动脉形态学检测.结果 与同龄WT小鼠相比,LDLR-/-小鼠肝脏中载脂蛋白AⅣ、脂肪酸转运酶和肉碱棕榈酰转移酶Ⅰ的mRNA水平在14天龄时即显著下调(P＜0.05);30天龄时载脂蛋白A Ⅰ显著上调,载脂蛋白F则显著下调(P＜0.05);60天龄时肝X受体α显著升高(P＜0.05),酰基辅酶A氧化酶1在90天龄时显著下调(P＜0.05);载脂蛋白A Ⅴ、载脂蛋白E、过氧化物增殖物激活受体α和血管生成素样蛋白3差异无统计学意义(P＞0.05).血清总胆固醇、甘油三酯和低密度脂蛋白C含量从14天龄起均显著高于同龄WT小鼠(均P＜0.05),并随年龄增长持续升高.结论 上述脂代谢相关基因在幼龄小鼠即发生表达水平的改变,与血脂紊乱及主动脉病变发生过程呈正相关,说明其可能共同参与幼龄小鼠的脂质代谢紊乱,进而影响动脉内皮细胞功能改变乃至动脉粥样硬化早期病变的发生.     

Activation of group I metabotropic glutamate receptors induces long-term depression in the hippocampal CA1 region of adult rats in vitro

Previous studies have implicated that long-term depression (LTD) was developmentally regulated since LTD can be readily induced by low frequency stimulation (LFS) in acute hippocampal slices prepared from juvenile but not adult animals. Here, we have examined the LTD induced by LFS (1Hz, 900 pulses) paired with a certain pattern at the Schaffer collateral-CAl synapse in adult hippocampal slices. We found that, in the 90-day-old rat hippocampus, LTD could be induced reliably by LFS paired with stronger stimulus intensity than that used during baseline recording. However, this synaptic depression could be completely abolished by application of metabotropic glutamate receptor (mGluR) antagonist (S)-amethyl-4-carboxyphenylglycine (MCPG) which had no effect on that induced by the same protocol in the 16-day-old rat hippocampus. Furthermore, preincubation with group I mGluR antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and (S)-2-methyl-4-carboxyphenylglycine (LY367385), also completely prevented the LFS-induced LTD. In contrast, group II mGluR antagonist (2S)-a-ethylglutamic acid (EGLU), N-methyl-d-aspartate (NMDA) receptor antagonist APV and voltage-gated calcium channel antagonist nimodipine had no effect on the LFS-induced LTD. Taken together, these observations suggest that LFS paired with strong stimulus strength can efficiently induce group I mGluR-dependent LTD in the adult hippocampal CA1 region, proving insight into the functional significance of hippocampal mGluR-mediated LTD in learning and memory.     

DNA microarray technology for simultaneous detection and species identification of seven human herpes viruses

The aim of the study was to develop a multiplex PCR-based DNA microarray technology for simultaneous detection and species identification of seven human herpes viruses, namely herpes simplex virus type 1, type 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus 6 (HHV-6A, HHV-6B), and to apply this technology to accurate diagnosis of herpesvirus-associated diseases. Primers and oligonucleotide probes were designed and synthesized based on the highly conserved regions of the DNA polymerase gene in human herpes viruses. DNA microarrays were made by printing the oligonucleotide probes onto special glass slides. After amplification and labeling with CY5, the PCR products were hybridized with the DNA microarrays and species identified. Sixty-one cerebrospinal fluid (CSF) and 132 blood specimens were analyzed by this technique, and the results were compared with those of TaqMan PCR. Several specimens were sequenced further after cloning. The PCR products of the seven human herpes viruses ranged from 224 to 252 bp, and could be species identified with DNA microarrays. The detection limits were 10(1) copies/microl for each virus. And the test showed no cross-reaction to DNA extracted from S. aureus, E. coli, hepatitis B virus, Cryptococcus neoformans, Candida albicans and human genome. Among 132 blood and 61 CSF specimens, 55 were tested positive for human herpes virus DNA. Compared with the results of TaqMan PCR, the sensitivity and specificity of the DNA microarray technology was 96.2% and 99.3%, respectively. This multiplex PCR-based DNA microarray technology, which is rapid, specific and sensitive, serves as an effective technique for simultaneous detection and species identification of seven human herpes viruses.     

Synergistic activity of ceftobiprole and vancomycin in a rat model of infective endocarditis caused by methicillin-resistant and glycopeptide-intermediate Staphylococcus aureus

The therapeutic activity of ceftobiprole medocaril, the prodrug of ceftobiprole, was compared to that of vancomycin, daptomycin, and the combination of a subtherapeutic dose of ceftobiprole and vancomycin in a rat model of infective endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300) or glycopeptide-intermediate Staphylococcus aureus (GISA) (NRS4 and HIP 5836) strains. The minimum bactericidal concentrations of ceftobiprole, vancomycin, and daptomycin at bacterial cell densities similar to those encountered in the cardiac vegetation in the rat endocarditis model were 2, >64, and 8 μg/ml, respectively, for MRSA ATCC 43300 and 4, >64, and 8 μg/ml, respectively, for the GISA strain. Ceftobiprole medocaril administered in doses of 100 mg/kg of body weight given intravenously (i.v.) twice a day (BID) every 8 h (q8h) (equivalent to a human therapeutic dose of ceftobiprole [500 mg given three times a day [TID]) was the most effective monotherapy, eradicating nearly 5 log(10) CFU/g MRSA or 6 log(10) CFU/g GISA organisms from the cardiac vegetation and had the highest incidence of sterile vegetation compared to the other monotherapies in the endocarditis model. In in vitro time-kill studies, synergistic effects were observed with ceftobiprole and vancomycin on MRSA and GISA strains, and in vivo synergy was noted with combinations of subtherapeutic doses of these agents for the same strains. Additionally, sterile vegetations were achieved in 33 and 60%, respectively, of the animals infected with MRSA ATCC 43300 or GISA NRS4 receiving ceftobiprole-vancomycin combination therapy. In summary, ceftobiprole was efficacious both as monotherapy and in combination with vancomycin in treating MRSA and GISA infections in a rat infective endocarditis model and warrants further evaluation.     

An analysis of discrepancy between point-of-care and central laboratory international normalized ratio testing in ED patients with cerebrovascular disease

Objective

Our objective was to identify demographic, clinical, and operational variables associated with discrepancy between point-of-care (POC) and central laboratory international normalized ratio (INR) results in emergency department (ED) patients with acute cerebrovascular disease.

Methods

We conducted a retrospective, observational cohort study of a series of 637 patients with acute cerebrovascular disease over 30 months who underwent simultaneous POC, using the i-STAT POC analyzer (Abbott, Princeton, NJ), and central laboratory INR testing at ED presentation. Point-of-care INR results greater than ± 0.25 INR units from the central laboratory INR value were considered discrepant. We analyzed potential predictors of POC INR discrepancy from demographic, clinical, and operational variables using multivariable logistic regression. We evaluated the change in POC INR discrepancy incidence over the study interval using analysis of variance methodology.

Results

The final diagnoses of the 637 subjects were acute ischemic stroke (n = 427), transient ischemic attack (n = 105), and intracranial hemorrhage (n = 105). Discrepant POC INR results occurred in 21.5% (137/637) of subjects. The mean bias between POC and central laboratory INR was 0.24 ± 0.69 (range, 0-11.3). Significant covariates of POC INR discrepancy were oral anticoagulant use (odds ratio, 3.03; confidence interval, 1.37-6.68) and increasing activated partial thromboplastin time (aPTT) (odds ratio, 1.07; confidence interval, 1.02-1.12). We observed a significant reduction trend in the incidence of POC-central laboratory discrepancy over the study period, decreasing on average at 0.42% per month (F = 5.59, P = .025).

Conclusion

In this retrospective study, oral anticoagulant use and increasing aPTT were significantly associated with POC INR discrepancy in ED patients with acute cerebrovascular disease. Point-of-care INR discrepancy incidence decreased over the study interval.