Lack of Antinociceptive Cross-Tolerance With Co-Administration of Morphine and Fentanyl Into the Periaqueductal Gray of Male Sprague-Dawley Rats

Tolerance to the antinociceptive effect of mu-opioid receptor agonists, such as morphine and fentanyl, greatly limits their effectiveness for long-term use to treat pain. Clinical studies have shown that combination therapy and opioid rotation can be used to enhance opioid-induced antinociception once tolerance has developed. The mechanism and brain regions involved in these processes are unknown. The purpose of this study was to evaluate the contribution of the ventrolateral periaqueductal gray (vlPAG) to antinociceptive tolerance and cross-tolerance between administration and co-administration of morphine and fentanyl. Tolerance was induced by pretreating rats with morphine or fentanyl or low-dose combination of morphine and fentanyl into the vlPAG followed by an assessment of the cross-tolerance to the other opioid. In addition, tolerance to the combined treatment was assessed. Cross-tolerance did not develop between repeated vlPAG microinjections of morphine and fentanyl. Likewise, there was no evidence of cross-tolerance from morphine or fentanyl to the co-administration of morphine and fentanyl. Co-administration did not cause cross-tolerance to fentanyl. Cross-tolerance was only evident to morphine or morphine and fentanyl combined in rats pretreated with co-administration of low doses of morphine and fentanyl. This finding is consistent with the functionally selective signaling that has been reported for antinociception and tolerance after morphine and fentanyl binding to the mu-opioid receptor. This research supports the notion that combination therapy and opioid rotation may be useful clinical practices to decrease opioid tolerance and other side effects.PerspectiveThis preclinical study shows that there is a decrease in cross-tolerance between morphine and fentanyl within the periaqueductal gray, which is a key brain region in opioid antinociception and tolerance.     

中药复方配伍的研究方法及其进展

中药复方是由2味或2味以上中药遵循中医理论组合而成的方剂。多味中药在合适的剂量配比之下,协同发挥作用,实现中医的整体调节治疗。研究中药复方的配伍对推动中药现代化发展、新药开发以及临床应用有着重要意义。近年来,研究者们在传统的"七情和合"与"君臣佐使"的基础上,运用新技术和新方法对中药复方的成分、药效活性和药代动力学性质等进行了研究,从不同角度探讨了中药复方配伍的科学内涵。同时,多种数理方法和模型的建立、网络药理学和数据挖掘方法的发展与应用,也对中药复方配伍研究提供了很大帮助。研究方法的发展虽促进了中药复方配伍的科学研究,但还需进一步建立适合中药复方配伍复杂关系的研究方法,以阐明中药复方及其成分/组分配伍的内在规律,进而构建新的现代中药复方,这也是目前中药复方配伍研究的重点任务。     

Chemosensory Cell-Derived Acetylcholine Drives Tracheal Mucociliary Clearance in Response to Virulence-Associated Formyl Peptides

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cDNA基因芯片数据分析软件的研发进展

数据分析与挖掘是基因芯片研究的关键和难点,而软件是数据分析方法实现的主要手段。我们从以下几个方面对cDNA基因芯片分析软件进行了综述。首先介绍了芯片数据的获取及分析的软件,然后概述了不同统计软件在芯片数据分析中的应用,并详细介绍几种常用的芯片数据分析软件,最后简述了基因网络分析及数据挖掘方面的软件。     

系统生物学和信息医学在中西医结合中的应用

20世纪中期的观点认为,生物体是由“物质和能量”所组成的,但现在的人们已逐渐认识到人体是一个复杂的巨系统,生物系统最重要的特点在于其各个部分之间的高度协调。在一个细胞中,在同一时刻有条不紊地进行着数千个代谢过程,细胞之间亦同时进行着各种协调与整合,如此才会最终形成各种脏器和系统井然有序的功能表现。显然,这些高度协调、密切相关的过程只有通过交换信息才能实现。固然,物质和能量仍是生物体的生存要素。在细胞中,核糖体拥有氨基酸组建模块以及ATP合成为ADP过程中释放的能量,但如果没有细胞核中DNA所携带的信息,同样无法合…     

Rutin exhibits hepatoprotective effects in a mouse model of non-alcoholic fatty liver disease by reducing hepatic lipid levels and mitigating lipid-induced oxidative injuries

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of hepatic lipids and oxidative injury of hepatocytes. Rutin is a natural flavonoid with significant roles in combating cellular oxidative stress and regulating lipid metabolism. The current study aims to investigate the molecular mechanisms underlying rutin's hypolipidemic and hepatoprotective effects in nonalcoholic fatty liver disease. Rutin treatment was applied to male C57BL/6 mice maintained on a high-fat diet and HepG2 cells challenged with oleic acid. Hepatic lipid accumulation was evaluated by triglyceride assay and Oil Red O staining. Oxidative hepatic injury was assessed by malondialdehyde assay, superoxide dismutase assay and reactive oxygen species assay. The expression levels of various lipogenic and lipolytic genes were determined by quantitative real-time polymerase chain reactions. In addition, liver autophagy was investigated by enzyme-linked immunosorbent assay. In both fat-challenged murine liver tissues and HepG2 cells, rutin treatment was shown to significantly lower triglyceride content and the abundance of lipid droplets. Rutin was also found to reduce cellular malondialdehyde level and restore superoxide dismutase activity in hepatocytes. Among the various lipid-related genes, rutin treatment was able to restore the expression of peroxisome proliferator-activated receptor alpha (PPAR-α) and its downstream targets, carnitine palmitoyltransferase 1 and 2 (CPT-1 and CPT-2), while suppressing those of sterol regulatory element-binding protein 1c (SREBP-1c), diglyceride acyltransfase 1 and 2 (DGAT-1 and 2), as well as acyl-CoA carboxylase (ACC). In addition, rutin was shown to repress the autophagic function of liver tissues by down-regulating key autophagy biomarkers, including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β). The experimental data demonstrated that rutin could reduce triglyceride content and mitigate oxidative injuries in fat-enriched hepatocytes. The hypolipidemic properties of rutin could be attributed to its ability to simultaneously facilitate fatty acid metabolism and inhibit lipogenesis.     

Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, characterized by highly hypoxic tumor microenvironment. Hypoxia-inducible factor-1α (HIF-1α) is a major regulator involved in cellular response to changes of oxygen levels, supporting the adaptation of tumor cells to hypoxia. Bruceine D (BD) is an isolated natural quassinoid with multiple anti-cancer effects. Here, we identified BD could significantly inhibit the HIF-1α expression and its subsequently mediated HCC cell metabolism. Using biophysical proteomics approaches, we identified inhibitor of β-catenin and T-cell factor (ICAT) as the functional target of BD. By targeting ICAT, BD disrupted the interaction of β-catenin and ICAT, and promoted β-catenin degradation, which in turn induced the decrease of HIF-1α expression. Furthermore, BD could inhibit HCC cells proliferation and tumor growth in vivo, and knockdown of ICAT substantially increased resistance to BD treatment in vitro. Our data highlight the potential of BD as a modulator of β-catenin/HIF-1α axis mediated HCC metabolism.     

Effect of Tai Ji Quan training on self-reported sleep quality in elderly Chinese women with knee osteoarthritis: a randomized controlled trail

ObjectiveThe purpose of this study was to explore the effects of a 24-week Tai Ji Quan training program on sleep quality, quality of life, and physical performance among elderly Chinese women with knee osteoarthritis (OA).MethodsA 24-week randomized, controlled trial of 46 elderly women with knee OA. Participants were randomly assigned to either a Tai Ji Quan group (n = 23) or a control group (n = 23). Participants in the Tai Ji Quan group completed training sessions three times per week, while those in the control group had bi-weekly educational classes. The primary outcome was total score of the Pittsburgh Sleep Quality of Index (PSQI). Secondary outcomes were: seven subscales of the PSQI; sleep latency; total sleep time; sleep efficiency; physical component summary (PCS) and mental component summary (MCS) of the 36-item Short Form Health Survey (SF-36); Berg Balance Scale (BBS); and Timed Up and Go (TUG).ResultsCompared with the control group, participants in the Tai Ji Quan group had significantly improved primary outcome (global PSQI score, p = 0.006) and secondary outcomes, including three PSQI sub-scores (sleep latency, p = 0.031; sleep duration, p = 0.043; daytime dysfunction, p = 0.007), total sleep time (p = 0.033), and SF-36 PCS (p = 0.006). The Tai Ji Quan group also had significant improvements compared with baseline in three PSQI sub-scores (sleep latency, p = 0.031; habitual sleep efficiency, p = 0.049; sleep disturbance, p = 0.016), sleep latency (p = 0.003), BBS (p = 0.001), and TUG (p = 0.006).ConclusionTai Ji Quan training is an effective treatment approach to improve sleep quality and quality of life in elderly Chinese women with knee OA.Trial registration: Chinese Clinical Trial Registry (June 16, 2013): ChiCTR-TRC-13003264.