黄连素抑制GRP78表达促进三阴乳腺癌细胞凋亡的研究

[目的]通过检测黄连素对三阴乳腺癌(triple-negative breast cancer,TNBC)细胞株MDA-MB-231细胞凋亡及葡萄糖调节蛋白78(glucose regulated protein 78,GRP78)表达的影响,探讨黄连素抗TNBC的机制。[方法]以MTT法检测不同浓度黄连素对MDA-MB-231细胞增殖的影响,筛选黄连素的处理浓度。将MDA-MB-231细胞分为对照组、40μmol·L~(-1)黄连素组、60μmol·L~(-1)黄连素组、免疫球蛋白重链结合蛋白诱导剂X(immunoglobulin heavy chain binding protein inducer X,BiX)组,以及BiX联合40μmol·L~(-1)黄连素组、BiX联合60μmol·L~(-1)黄连素组。相应药物处理24h后,应用流式细胞术检测细胞凋亡情况,并以Western blot检测细胞GRP78和凋亡相关基因Bcl-2、Bax的表达。[结果]40μmol·L~(-1)以上浓度的黄连素可剂量依赖性抑制MDA-MB-231细胞增殖。与对照组比较,BiX组细胞凋亡率降低(P0.05)、GRP78和Bcl-2表达增高(P0.01,P0.001)、Bax表达减低(P0.05)。与BiX组比较,BiX联合40、60μmol·L~(-1)黄连素组细胞凋亡率增加(P0.01),GRP78和Bcl-2表达减低(P0.01,P0.01),Bax表达增加(P0.01)。[结论]黄连素可以促进MDA-MB-231细胞凋亡,其机制可能是通过下调GRP78的表达,从而降低Bcl-2表达,并促进Bax的表达。     

Accuracy of self‐reported hypertension in Brazilian adolescents: Analysis of the Study of Cardiovascular Risk in Adolescents

Given the high prevalence of hypertension in adolescents, it is important to investigate alternatives for estimating the magnitude of the disease. Our objective was to investigate the accuracy of self‐reported hypertension. The study assessed participants of the Study of Cardiovascular Risk in Adolescents (ERICA). The following were calculated: sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The associations between inaccurate self‐reporting and socioeconomic factors were investigated. The accuracy of self‐reported hypertension had a sensitivity of 7.5% (95% CI, 6.9‐8.2), a specificity of 96.6% (95% CI, 96.5‐96.7), a PPV of 18.9% (95% CI, 17.4‐20.5), and a NPV of 90.8% (95% CI, 90.6‐91.0). The prevalence of inaccurate self‐reported hypertension was smaller among girls (PR 0.68; 95% CI, 0.55‐0.83) and younger boys (PR 0.68; 95% CI, 0.54‐0.86) who were attending private schools. The use of self‐reported hypertension was not a good strategy for investigating the hypertension in adolescents.     

Body Adiposity Index,but not Visceral Adiposity Index,Correlates with Inflammatory Markers in Sarcopenic Obese Elderly Women

Background/Study Context: The association of body adiposity index (BAI) and visceral adiposity index (VAI) with inflammatory markers has yet to be understood. The aim of this work was to investigate the association of BAI and VAI with inflammatory markers in elderly women with sarcopenic obesity (SO).

Methods: A total of 130 women (age: 66.7 ± 5.2 years) underwent body composition analysis by dual-energy x-ray absorptiometry (DEXA). Volunteers were classified according to SO definition. BAI, VAI, and waist-to-hip ratio (WHR) were calculated. Blood samples were collected for C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6) measurements.

Results: SO prevalence was 20.8%. BAI correlated with the DEXA-derived body fat content (r_S = .90), CRP (r_S = .55), and IL-6 (r_S = .53), whereas WHR correlated with CRP (r_S = .60) only (all p < .01). VAI did not correlate with any of the inflammatory variables.

Conclusion: Simple and cheap anthropometric indices such as BAI and WHR may be better predictors of low-grade inflammation than VAI in elderly women with SO.     

The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats

BACKGROUND AND PURPOSE

Resolution of inflammation is mediated by endogenous molecules with anti-inflammatory and pro-resolving activities and they have generated new possibilities for the treatment of inflammatory diseases. Here, we have investigated the possible anti-hyperalgesic effects of two lipids, aspirin-triggered resolvin D1 (AT-RvD1) and its precursor, 17(R)-hydroxy-4Z,7Z,10Z,13Z,15E,17R,19Z-docosahexaenoic acid (17(R)HDoHE).

EXPERIMENTAL APPROACH

The anti-hyperalgesic effects of both lipid mediators were evaluated, using mechanical and thermal stimuli, at different time-points in adjuvant-induced arthritis in rats. Cytokine levels were measured, and immunohistochemistry and real-time PCR for pro-inflammatory mediators were also performed.

KEY RESULTS

The precursor of resolvin D series, 17(R)HDoHE, given systemically, inhibited the development and the maintenance of mechanical hyperalgesia in acute inflammation. Such effects were likely to be associated with modulation of both NF-κB and COX-2 in dorsal root ganglia and spinal cord. 17(R)HDoHE was also effective against sub-chronic pain. Unexpectedly, repeated treatment with 17(R)HDoHE did not modify paw and joint oedema in the sub-chronic model, while joint stiffness was prevented. Notably, AT-RvD1 exhibited marked anti-hyperalgesic effects in acute inflammation when given systemically. The efficacy of long-term treatment with either 17(R)HDoHE or AT-RvD1 was partly related to decreased production of TNF-α and IL-1β in rat hind paw.

CONCLUSIONS AND IMPLICATIONS

Our findings provide fresh evidence for the anti-hyperalgesic properties of 17(R)HDoHE and its pro-resolution metabolite AT-RvD1. Such lipid mediators might be useful for treating pain associated with acute or chronic inflammation.

LINKED ARTICLE

This article is commented on by Xu and Ji, pp. 274–277 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01348.x     

Chronic coffee and caffeine ingestion effects on the cognitive function and antioxidant system of rat brains

Coffee is a popular beverage consumed worldwide and its effect on health protection has been well studied throughout literature. This study investigates the effect of chronic coffee and caffeine ingestion on cognitive behavior and the antioxidant system of rat brains. The paradigms of open field and object recognition were used to assess locomotor and exploratory activities, as well as learning and memory. The antioxidant system was evaluated by determining the activities of glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD), as well as the lipid peroxidation and reduced glutathione content. Five groups of male rats were fed for approximately 80 days with different diets: control diet (CD), fed a control diet; 3% coffee diet (3%Co) and 6% coffee diet (6%Co), both fed a diet containing brewed coffee; 0.04% caffeine diet (0.04%Ca) and 0.08% caffeine diet (0.08%Ca), both fed a control diet supplemented with caffeine. The estimated caffeine intake was approximately 20 and 40 mg/kg per day, for the 3%Co-0.04%Ca and 6%Co-0.08%Ca treatments, respectively. At 90 days of life, the animals were subjected to the behavioral tasks and then sacrificed. The results indicated that the intake of coffee, similar to caffeine, improved long-term memory when tested with object recognition; however, this was not accompanied by an increase in locomotor and exploratory activities. In addition, chronic coffee and caffeine ingestion reduced the lipid peroxidation of brain membranes and increased the concentration of reduced-glutathione. The activities of the GR and SOD were similarly increased, but no change in GPx activity could be observed. Thus, besides improving cognitive function, our data show that chronic coffee consumption modulates the endogenous antioxidant system in the brain. Therefore, chronic coffee ingestion, through the protection of the antioxidant system, may play an important role in preventing age-associated decline in the cognitive function.     

Cytotoxic clerodane diterpenes from Casearia rupestris

Four new clerodane diterpenes, casearupestrins A-D (1-4), were isolated from the leaves of Casearia rupestris. Compounds 1 and 4 were acetylated to yield 2,7-di-O-acetylcasearupestrin A (5) and 2,6-di-O-acetylcasearupestrin D (6). All compounds were evaluated for cytotoxicity against a small panel of human cancer cell lines. Casearupestrin A (1) exhibited the most potent activity against MDA/MB-435 (human melanoma) and SF-295 (human glioblastoma) cells, superior to that of the standard drug doxorubicin.