Ubiquinone and tocopherol: dissimilar siblings

Research on antioxidants and their potential health benefits expanded over the last decades from basic science to the medical and nutritional fields. This included supplementation studies of both vitamin E compounds and the endogenous antioxidant ubiquinone, to prevent or alleviate cardiovascular diseases and their pathophysiological consequences. In many of these studies, only one antioxidant or one group of antioxidants was considered, disregarding the pharmacological and toxicological properties of their metabolites as well as possible cooperative and competitive effects on the overall physiological response. There are many--often indirect--effects, especially in gene regulation, observed on administration of both compound groups in cells, which have been assigned to these molecules without identifying the cellular targets. Therefore, this article focuses on direct chemical and biochemical effects of ubiquinone- and alpha-tocopherol-related compounds, which are evident from direct binding studies or direct interaction leading to chemical modification of the compounds. These groups include para-benzoquinones (ubiquinone and alpha-tocopheryl quinone) and chroma(e)nols (alpha-tocopherol and bicyclic ubiquinone derivatives). Their effects as antioxidants, co-antioxidants, and pro-oxidants as well as direct interactions with proteins are considered, pointing out similarities and dissimilarities of the two compound groups in a wider context. The review of the isolated findings about one or a few of these compounds in the literature, disregarding structurally related compounds, suggests that comprehensive structure/activity relationship studies including related compounds would promote the understanding of biological functions and pharmacological effects of ubiquinone- and alpha-tocopherol-related compounds.     

LPS-induced CCL2 expression and macrophage influx into the murine central nervous system is polyamine-dependent

Increased polyamine production is observed in a variety of chronic neuroinflammatory disorders, but in vitro and in vivo studies yield conflicting data on the immunomodulatory consequences of their production. Ornithine decarboxylase (ODC) is the rate-limiting enzyme in endogenous polyamine production. To identify the role of polyamine production in CNS-intrinsic inflammatory responses, we defined CNS sites of ODC expression and the consequences of inhibiting ODC in response to intracerebral injection of LPS ± IFNγ. In situ hybridization analysis revealed that both neurons and non-neuronal cells rapidly respond to LPS ± IFNγ by increasing ODC expression. Inhibiting ODC by co-injecting DFMO decreased LPS-induced CCL2 expression and macrophage influx into the CNS, without altering LPS-induced microglial or macrophage activation. Conversely, intracerebral injection of polyamines was sufficient to trigger macrophage influx into the CNS of wild-type but not CCL2KO mice, demonstrating the dependence of macrophage influx on CNS expression of CCL2. Consistent with these data, addition of putrescine and spermine to mixed glial cultures dramatically increased CCL2 expression and to a much lesser extent, TNF expression. Addition of all three polyamines to mixed glial cultures also decreased the numbers and percentages of oligodendrocytes present. However, in vivo, inhibiting the basal levels of polyamine production was sufficient to induce expression of apolipoprotein D, a marker of oxidative stress, within white matter tracts. Considered together, our data indicate that: (1) CNS-resident cells including neurons play active roles in recruiting pro-inflammatory TREM1-positive macrophages into the CNS via polyamine-dependent induction of CCL2 expression and (2) modulating polyamine production in vivo may be a difficult strategy to limit inflammation and promote repair due to the dual homeostatic and pro-inflammatory roles played by polyamines.     

An herbal fruit, Amomum xanthoides, ameliorates thioacetamide-induced hepatic fibrosis in rat via antioxidative system

Aim of the study

Amomum xanthoides is a well-known traditional herbal medicine mainly for diverse digestive system disorders in Asia for a long time. In the present study, we investigate the effects and action mechanism of methanol fraction of Amomum xanthoides (MFAX) on thioacetamide (TAA)-induced liver fibrosis in rat model.

Materials and methods

TAA (200 mg/kg, ip on twice a week for 14 weeks) treated rats were orally administered with MFAX (25, 50 or 100 mg/kg) once a day from the 7th week until 14th week.

Result

Significantly elevated serum bilirubin, liver tissue hydroxyproline and malondialdehyde (MDA) in liver fibrosis were ameliorated by MFAX treatment. Further, MFAX treatment attenuated the reactive oxygen species (ROS) levels and restored glutathione (GSH) content and glutathione-peroxidase (GPx) activity. Histopathological data showed that MFAX treatment inhibited collagen accumulation and activation of hepatocyte stellate cells (HSCs) in the liver tissue. Compared to the TAA group, activation of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), platelet-derived growth factor beta (PDGF-β) mRNAs and the level of pro-fibrotic cytokines PDGF-β and connective tissue growth factor (CTGF) in the liver tissue were attenuated in MFAX treated groups.

Conclusion

The above evidences collectively indicate that MFAX is a potential herb which can be used as an anti-hepatofibrotic remedy.     

外燥对小鼠肺组织NF-κB活性的影响

目的:观察外燥对小鼠肺组织NF-κB活性的影响.方法:120只SPF级昆明种小鼠随机分为温燥组、凉燥组、常温常温组、常温燥组各30只,模拟外燥"温度-相对湿度-风"综合刺激进行造模,造模后第6、第12、第18天检测各组小鼠肺组织NF-κB活性.结果:温燥组、凉燥组第6、第12、第18天肺组织NF-κB活性均低于常温常湿...     

Medioventral part of the posterior thalamus in the mouse

The posterior thalamus (Po) consists of heterogeneous groups of cells, which have not been clearly defined. In the present study, we focused on a part of the Po in the mouse brain, which is located caudally to the ventral posterior nucleus and rostromedially to the medial geniculate nucleus and shows distinct calretinin immunoreactivity. While we found the region had a considerable unity on the cytoarchitectural and histochemical grounds, it did not correspond to any particular nucleus but partially involved three structures in a widely used brain atlas (Franklin and Paxinos, 2008). Therefore, we tentatively designated the region as the medioventral part of the posterior thalamus (PoMV) and examined its anatomical features with immunohistochemistry and retrograde tract-tracing. The PoMV was appreciated as a reticular structure with prominent calretinin immunoreactivity, especially in horizontal sections, and displayed apparent differences in the cytoarchitecture from its surrounding regions. The PoMV had two divisions: the dorsal division (PoMVd), which contained parvalbuminimmunoreactive fibers, and the ventral division (PoMVv), which lacked these fibers. The tract-tracing studies showed that the somata retrogradely labeled from the injections in the insular cortex and some of the extended amygdalar regions were fairly concentrated within the PoMV, especially in the PoMVd. On the other hand, the labeling from the medial hypothalamus injections was found predominantly within the PoMVv. These findings indicate that the PoMV can be regarded as a distinct structure within the Po, and it may play a role in the emotional aspect of somatosensory processing.     

肝癌组织中DNA倍体、SPF、PI值测定的临床意义

目的 了解原发性肝癌组织中DNA倍体,SPF、PI值,与临床分期的关系。方法应用流式细胞仪（FCM）测定石蜡包埋的原发性肝细胞癌组织标本120例,检测DNA倍体,SPF、PI值。结果随着原发性肝细胞癌临床分期的发展,临床Ⅰ～Ⅱ与Ⅲ～Ⅳ期肿瘤的异倍体率（Ⅰ～Ⅱ33．3％,Ⅲ-Ⅳ期42．8％）,SPF、PI值均增高,其与正常肝组织均有统计学意义。但肿瘤各临床分期Ⅰ-Ⅱ与Ⅲ-Ⅳ期之间并无统计学意义。结论测定原发性肝细胞癌组织的DNA倍体,SPF、PI值能了解其某些分子生物学特性,从而从分子水平上了解其增殖活性。对肿瘤的诊断及预后的评估有积极的临床意义。     

Sulfated modification can enhance the adjuvanticity of lentinan and improve the immune effect of ND vaccine

The purpose of this research is to study the effect of sulfated lentinan (sLNT) on immune effect of Newcastle disease (ND) vaccine. In immune response test, 14-day-old chickens were vaccinated with ND vaccine then grouped respectively to inject three sLNTs at two doses, once a day for three successive days, taking non-sulfated lentinan (LNT) as the control. The changes of serum antibody titer and peripheral lymphocyte proliferation were determined before and after vaccination. In immune protection test, 35-day-old chickens were challenged with ND virus (NDV) after treated similar to above mentioned. The morbidity and mortality of chickens were observed, and the changes of serum antibody titer and peripheral lymphocyte proliferation were measured before and after challenge. The results showed that three modified sLNTs could significantly enhance serum antibody titer and promote lymphocyte proliferation in two experimental chickens, and reduce morbidity and mortality of chickens challenged with NDV, which were better than that of non-modified LNT. Their high doses in enhancing antibody titer and low doses in promoting lymphocyte proliferation were more preferable. These results indicated that sulfated modification could enhance the adjuvanticity of LNT and improve the immune effect of ND vaccine. sLNT₂ possessed the best efficacy and would be expected as the candidate of a new-type immune adjuvant.     

Dietary cholesterol lowers plasma and cecal equol concentrations in mice

This study examined the effects of cholesterol on mouse intestinal microflora and on isoflavonoids in the cecum and plasma. Dietary cholesterol affects bile acid metabolism and bile acids can influence the intestinal microorganisms. Intestinal microflora appear to play an important role in isoflavone metabolism. We hypothesized that dietary cholesterol changes the metabolism of isoflavonoids and intestinal microorganisms in mice. Male mice were randomly divided into two groups, which were fed a cholesterol-daidzein (CDA) or daidzein (DA) diet (control diet) for 60d. Plasma equol and cecal equol concentrations were significantly higher in the DA group (control group) than in the CDA group. However, plasma cholesterol concentrations were significantly higher in the CDA group compared to the DA group. The composition of cecal microorganisms differed between the two dietary groups. The occupation ratios of Clostridium cluster XI, Clostridium subcluster XIVa, and Lactobacillales were significantly higher in the CDA group. The occupation ratio of Bifidobacterium was significantly lower in the CDA group. This study suggests that dietary cholesterol has the potential to affect the metabolism of equol from daidzein by altering the metabolic activity of the intestinal microorganisms and gut physiological function.