高压氧预处理对大鼠脊髓损伤后PPAR-γ表达的影响

目的探讨高压氧预处理(HBOP)对大鼠脊髓损伤(SCI)后继发性损伤过程中过氧化物酶体增殖物激活受体-γ(PPAR-γ)表达的影响。方法将108只雄性SD大鼠随机分为对照组、SCI组和HBOP组,每组36只大鼠。SCI后1 d、3 d、1 w、2 w、4 w、8 w,分别采用荧光定量多聚酶链反应(FQ-PCR)和Western blot检测PPAR-γmRNA及蛋白的表达变化。结果与SCI组比较,HBOP组PPAR-γmRNA和蛋白表达明显增加(P<0.05),其表达高峰在2 w,其高水平表达持续4 w。结论 HBOP明显促进大鼠SCI后继发性损伤过程中PPAR-γ的表达。     

过氧化物酶体增殖活化体受体γ与支气管哮喘气道重塑相关细胞

气道重塑是支气管哮喘的重要病理表现,多种细胞在气道重塑的病理过程中起重要作用.过氧化物酶体增殖活化体受体γ可抑制多种气道重塑相关细胞的功能,从而减轻气道气道重塑.     

Inhibitory effects of SSRIs on IFN-γ induced microglial activation through the regulation of intracellular calcium

Microglia, which are a major glial component of the central nervous system (CNS), have recently been suggested to mediate neuroinflammation through the release of pro-inflammatory cytokines and nitric oxide (NO). Microglia are also known to play a critical role as resident immunocompetent and phagocytic cells in the CNS. Immunological dysfunction has recently been demonstrated to be associated with the pathophysiology of depression. However, to date there have only been a few studies on the relationship between microglia and depression. We therefore investigated if antidepressants can inhibit microglial activation in vitro. Our results showed that the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline significantly inhibited the generation of NO and tumor necrosis factor (TNF)-α from interferon (IFN)-γ-activated 6-3 microglia. We further investigated the intracellular signaling mechanism underlying NO and TNF-α release from IFN-γ-activated 6-3 microglia. Our results suggest that paroxetine and sertraline may inhibit microglial activation through inhibition of IFN-γ-induced elevation of intracellular Ca²⁺. Our results suggest that the inhibitory effect of paroxetine and sertraline on microglial activation may not be a prerequisite for antidepressant function, but an additional beneficial effect.     

大鼠癫持续状态后脑内PPARγ的表达

目的观察PPARγ在癫持续状态后大鼠脑内的表达。方法将雄性SD大鼠随机分为对照组和癫组(n=10),制备锂-匹罗卡品癫模型,采用免疫组化及蛋白质印迹分析方法,观察对照组和造模成功的癫大鼠脑内PPARγ的表达分布和变化情况。采用免疫组化及蛋白质印迹分析方法,观察锂-匹罗卡品模型大鼠脑内PPARγ的表达分布和变化情况。结果免疫组化显示PPARγ在正常大鼠脑内呈弱阳性表达,且主要表达在神经元上;癫持续状态后在星形胶质细胞上呈强阳性表达,神经元形态的细胞上亦有表达。蛋白质印迹分析显示癫持续状态后PPARγ的表达明显增加。结论大鼠癫持续状态后星形细胞上PPARγ表达增加,可能具有神经保护作用,这为癫的神经保护治疗提供了一个新的研究方向。     

过氧化物酶体增殖物激活受体-γ与肾脏纤维化的研究进展

慢性肾脏病发展至终末期可表现为肾小球硬化和（或）肾间质纤维化。有效抑制肾脏纤维化可显著延缓慢性肾脏病的进展。过氧化物酶体增殖物激活受体（PPARs）是配体激活的核转录因子超家族成员。PPAR-γ为PPARs的表型之一,在抑制肾脏纤维化方面的作用已成为当前研究的热点。文章就PPAR-γ及激动剂延缓肾脏纤维化研究新进展进行综述。     

MIG (CXCL9) is a more sensitive measure than IFN-gamma of vaccine induced T-cell responses in volunteers receiving investigated malaria vaccines

For many years the IFN-γ ex vivo ELISPOT has been a major assay for assessing human T-cell responses generated by malaria vaccines. The ELISPOT assay is a sensitive assay, but an imperfect correlate of protection against malaria. Monokine induced by gamma (MIG), or CXCL9, is a chemokine induced by IFN-γ and has the potential to provide amplification of the IFN-γ signal. MIG secretion could provide a measure of bio-active IFN-γ and a functional IFN-γ signalling pathway. We report that detecting MIG by flow cytometry and by RT-PCR can be more sensitive than the detection of IFN-γ using these methods. We also find that there is little inter-individual variability in MIG secretion when detected by flow cytometry and that the MIG assay may be used to estimate the amount of bio-active IFN-γ present. Measurement of MIG alongside IFN-γ may provide a fuller picture of Th1 type responses post-vaccination.     

Extension of the neuroprotective time window for thiazolidinediones in ischemic stroke is dependent on time of reperfusion

Stroke is a leading cause of death and disability but has limited therapeutic options. Thiazolidinediones (TZDs), agonists for the nuclear receptor, peroxisome proliferator-activated receptor (PPAR)γ, reduce infarct volume and improve neurologic function following transient middle cerebral artery occlusion (MCAO) in rats. Translation of these findings into clinical therapy will require careful assessment of dosing paradigms and effective time windows for treatment. Understanding the mechanisms by which TZDs protect the brain provides insight into how time windows for neuroprotection might be extended. We find that two TZDs, pioglitazone and rosiglitazone, significantly reduce infarct volume at doses similar to those used clinically (1 mg/kg for pioglitazone and 0.1 mg/kg for rosiglitazone). We also find that pioglitazone reduces infarction volume in a transient, but not a permanent MCAO model suggesting that reperfusion plays an important role in TZD mediated neuroprotection. Since PPARγ agonists reduce inflammation and oxidative stress, both of which are exacerbated by reperfusion, we hypothesized that TZDs would be most effective if administered prior to reperfusion. We administered TZDs 3 h after MCAO and found that infarction volume and neurologic function are significantly improved in animals reperfused at 3 h and 15 min (after TZD treatment), but not in animals reperfused at 2 h (before TZD treatment) when assessed either 24 h or 3 weeks after MCAO. While TZDs reduce intercellular adhesion molecule (ICAM) expression to a similar extent regardless of the time of reperfusion, leukocyte entry into brain parenchyma is more dramatically reduced when reperfusion is delayed until after drug treatment. The finding that delaying reperfusion until after TZD treatment is beneficial despite a longer period of ischemia, is dramatic given the widely held view that duration of ischemia is the most important determinate of injury.     

Ectopic B7-H4-Ig expression attenuates concanavalin A-induced hepatic injury

Previous studies demonstrate that both membrane B7-H4 and B7-H4-Ig fusion protein could inhibit T-cell responses. In the present study, we explored the potential effect of B7-H4-Ig on liver injury in a hepatitis mouse model induced by concanavalin A (ConA). A B7-H4-Ig construct was introduced into animals by the hydrodynamic gene delivery approach. It was found that ectopic expression of B7-H4-Ig could inhibit ConA-induced elevation of serum levels of ALT and AST, suppress liver necrosis and even mortality of mice. Furthermore, we observed that pretreatment of B7-H4-Ig dramatically decreased serum levels and the expression of mRNA for IL-2, IFN-γ and IL-4, but increased IL-10 in ConA-treated mice. Our results suggest that B7-H4-Ig may protect animals from liver injury induced by ConA, which could be associated with reduced serum levels for IL-2, IFN-γ and IL-4 as well as enhanced IL-10 production.     

Pomegranate peel and fruit extracts: A review of potential anti-inflammatory and anti-infective effects

Ethnopharmacological relevance

Punica granatum L. (Punicaceae) has been used for centuries in many cultures for the prevention and treatment of a wide number of health disorders such as inflammation, diabetes, diarrhea, dysentery, dental plaque and to combat intestinal infections and malarial parasites.

Aim of the review

This review aims at providing an up-to-date overview of the chemical constituents, traditional uses, phytochemistry, pharmacology and toxicology of Punica granatum L. Moreover, the focus of this review is the possible exploitation of this species to treat different diseases and to suggest future investigations.

Materials and methods

An extensive and systematic review of the extant literature was carried out, and the data under various sections were identified by using a computerized bibliographic search via PubMed, Web of Science and Google Scholar. All abstracts and full-text articles were examined. The most relevant articles were selected for screening and inclusion in this review.

Key findings

A variety of pomegranate ethnomedical uses have been recorded. Additionally, over the last decade, there has been a dramatic increase of interest in pomegranate as a medicinal and nutritional product due to its n1ewly identified potential health effects, which include treatment and prevention of cancer and cardiovascular diseases. From the toxicological perspective, pomegranate fruit juice, extracts and preparations have been proven to be safe.

Conclusions

The ethnopharmacological relevance of pomegranate is fully justified by the most recent findings indicating the fruit is a medicinal and nutritional agent useful for treating a wide range of human disorders and maladies. Further investigations are needed to fully understand the mode of action of the active constituents and to fully exploit pomegranate’s preventive and therapeutic potential.     

Bioassay-guided fractionation of a thymol-deprived hydrophilic thyme extract and its antispasmodic effect

Ethnopharmacological relevance

Extracts from Thymus vulgaris L. and Thymus zygis L. are traditionally used for bronchitis, catarrhs of the respiratory tract and supportive treatment of pertussis. A potential spasmolytic effect is thought to be due to the presence of the monoterpenoid phenols thymol and carvacrol in the extract. Based on previous data the present investigation aimed to clarify if thymol-deprived thyme extracts (as been in use within German drug market) have antispasmodic activity. Additionally compounds responsible for this effect had to be identified.

Materials and methods

Thyme fluid extract was subsequently fractionated by FCPC, LPLC, and HPLC and compounds isolated were identified by spectroscopic methods. Bioassay testing was done by quantification of antispasmodic activity in the preconstricted rat smooth muscle trachea model against papaverin as positive control.

Results

Thymol-deprived spissum extract (SE) had good antispasmodic activity (−37%, related to the maximum contraction). Bioassay-guided fractionation indicated that rosmarinic acid and apigenin do not contribute to this effect. Luteolin contributed significantly to the antispasmodic activity (−9%).

Conclusions

Thyme extracts have antispasmodic activity, which is at least due to synergistic effects of phenolic volatile oil compounds and the flavone luteolin. Specifications of thyme-containing preparations should refer to this flavone in addition to focusing on the volatile phenols.