Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides

Background

The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA), claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP) in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP), lipid peroxidation (measured as malondialdehyde; MDA) and leukocytic count (LC). Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein.

Results

EAC-bearing mice exhibited markedly elevated LC (2-fold), CRP (11-fold) and MDA levels (2.7-fold). DHA (125, 250 mg/kg) elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively), as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg). Interestingly, DHA (125 mg/kg) markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85) and leukocytosis (r = 0.89), thus attesting to a diagnostic/prognostic role for CRP. On the other hand, a single CP dose (10 mg/kg) induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold), a rise in serum creatinine/urea levels (2–5-fold) after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg) survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81), TNF-α ) r = 0.92) and GSH (r = -0.82); implying causal relationships.

Conclusion

DHA elicited prominent chemopreventive effects on its own, and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels (thus implying a diagnostic/prognostic role for CRP). Further, this study is the first to reveal that DHA can obliterate the lethal CP-induced nephrotoxicity and renal tissue injury. At the molecular level, DHA appears to act by reducing leukocytosis, systemic inflammation, and oxidative stress.     

Chitotriosidase - a putative biomarker for sporadic amyotrophic lateral sclerosis

Background

Potential biomarkers to aid diagnosis and therapy need to be identified for Amyotrophic Lateral Sclerosis, a progressive motor neuronal degenerative disorder. The present study was designed to identify the factor(s) which are differentially expressed in the cerebrospinal fluid (CSF) of patients with sporadic amyotrophic lateral sclerosis (SALS; ALS-CSF), and could be associated with the pathogenesis of this disease.

Results

Quantitative mass spectrometry of ALS-CSF and control-CSF (from orthopaedic surgical patients undergoing spinal anaesthesia) samples showed upregulation of 31 proteins in the ALS-CSF, amongst which a ten-fold increase in the levels of chitotriosidase-1 (CHIT-1) was seen compared to the controls. A seventeen-fold increase in the CHIT-1 levels was detected by ELISA, while a ten-fold elevated enzyme activity was also observed. Both these results confirmed the finding of LC-MS/MS. CHIT-1 was found to be expressed by the Iba-1 immunopositive microglia.

Conclusion

Elevated CHIT-1 levels in the ALS-CSF suggest a definitive role for the enzyme in the disease pathogenesis. Its synthesis and release from microglia into the CSF may be an aligned event of neurodegeneration. Thus, high levels of CHIT-1 signify enhanced microglial activity which may exacerbate the process of neurodegeneration. In view of the multifold increase observed in ALS-CSF, it can serve as a potential CSF biomarker for the diagnosis of SALS.     

Meta-analysis of the literature on diagnostic accuracy of SPECT in parkinsonian syndromes

Background  

Parkinson's disease (PD) is the second most common neurodegenerative disorder. One of the most widely used techniques to diagnose PD is a Single Photon Emission Computer Tomography (SPECT) scan to visualise the integrity of the dopaminergic pathways in the brain. Despite this there remains some discussion on the value of SPECT in the differential diagnosis of PD. We did a meta-analysis of all the existing literature on the diagnostic accuracy of both pre- and post-synaptic SPECT imaging in the differential diagnosis of PD.     

沿干旱梯度樟子松人工林针叶和枝条非结构性碳水化合物及氮含量的变化

选取沿内蒙古科尔沁沙地自然干旱梯度分布的6个樟子松人工林样点(辉南、西丰、付家、章古台、奈曼和乌兰敖都)为研究对象,测定当年生和1年生针叶和枝条中非结构性碳水化合物(NSCs)和氮(N)含量的变化,以探究干旱条件下樟子松的碳供需状态和养分贮存策略。结果表明: 随干旱加剧,樟子松针叶和枝条中的NSCs和可溶性糖含量显著降低。从最湿润样点(辉南)到最干旱样点(乌兰敖都),樟子松当年生和1年生针叶中可溶性糖含量分别由12.8%和12.5%下降到9.0%和9.5%,而当年生枝条中可溶性糖含量由15.6%下降到9.2%。随干旱加剧,樟子松针叶和枝条中淀粉含量变化不显著,当年生和1年生针叶可溶性糖和淀粉的比值降低,当年生和1年生枝条中N含量显著增加。科尔沁沙地樟子松在干旱条件下显著消耗可溶性糖存储,存在“碳饥饿”致死风险。樟子松倾向维持稳定的淀粉含量以及在枝条中积累N以应对长期的干旱胁迫。     

基因佐剂的研究进展

基因佐剂是免疫佐剂家族的成员之一,随着研究的深入逐渐发现基因佐剂在佐剂应用中的重要价值.简要概括基因佐剂的概念和作用机制,同时总结了基因佐剂候选靶基因的几个发展方向,对基因佐剂的应用前景也进行了简单探讨,以期为基因佐剂在畜禽疾病防治和医学中的深入研究和应用提供参考.     

不同带长微喷带灌溉对土壤水分布与冬小麦耗水特性及产量的影响

于2010-2012年度冬小麦生长季,选用高产冬小麦品种济麦22,采用测墒补灌方式,设置40 m(T₄₀)、60 m(T₆₀)和80 m(T₈₀)3种带长的微喷带灌溉处理,研究不同带长微喷带灌溉对土壤水分分布及冬小麦耗水特性和产量的影响.结果表明： 拔节期和开花期采用微喷带补灌,随微喷带带长缩短,灌溉水在土壤中的水平分布均匀系数显著增加.拔节期补灌,T₄₀和T₆₀处理在距畦首0～40 m范围内各小麦行间的0～200 cm土层土壤含水量均无显著差异;T₈₀处理在距畦首38～40 m、58～60 m和78～80 m处各小麦行间的0～200 cm各土层土壤含水量变化规律一致,均表现为随距微喷带的距离增加而减小.T₄₀处理的小麦在拔节至开花期间和开花至成熟期间分别对40～60 cm和20～80 cm土层土壤贮水的消耗量显著高于T₆₀和T₈₀处理,而对深层土壤贮水消耗量和总土壤贮水消耗量、开花期补灌水量、总灌水量和总耗水量显著低于T₆₀和T₈₀处理.随微喷带带长缩短,小麦籽粒产量、产量水分利用效率显著升高,而流量降低,在灌水量一定的情况下,单位时间内的有效灌溉面积减小.综合考虑小麦籽粒产量、水分利用效率和流量,40和60 m是本试验条件下的适宜微喷带带长.     

CDK2蛋白质分子结构与其入核转运过程关系的初步分析

应用重组技术构建野生型及缺失型CDK2基因的真核表达载体,分别使野生型及缺失型(2DK2蛋白与增强型绿色荧光蛋白(Enhanced-green Fluorescent Protein,EGFP)形成融合蛋白。通过脂质体介导的方法将载体转染人宫颈癌细胞系HeLa和中华仓鼠卵巢细胞系CHO,经过细胞周期同步化处理后于荧光显微镜下观察EGFP的亚细胞定位以示踪野生型及缺失型CDK2基因的表达。结果表明,野生型CDK2基因的表达产物定位于细胞核．而两种缺失型CDK2基因分别编码的CDK2蛋白N-端1～201及98～298多肽均主要定位于细胞质。以上结果提示,CDK2蛋白序列中不含有与核定位直接相关的信号,其入核过程可能是由其N-端1～97及202～298多肽范围内的部分氨基酸共同形成高级结构,并依赖此高级结构与其他含有入核信号的蛋白形成复合物,从而被带动进入细胞核的     

A MEDIUM FOR THE CULTIVATION OF LACTOBACILLI

SUMMARY: An improved growth medium for lactobacilli is described. It supports good growth of lactobacilli generally and also is particularly useful for a number of fastidious strains which grow only poorly in other general media. In addition, tomato juice, a highly variable material, is not required. In a slightly modified form, it can also be used as a basal medium for fermentation tests.