Synthesis and Neuroprotective Action of Xyloketal Derivatives in Parkinson’s Disease Models

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting people over age 55. Oxidative stress actively participates in the dopaminergic (DA) neuron degeneration of PD. Xyloketals are a series of natural compounds from marine mangrove fungus strain No. 2508 that have been reported to protect against neurotoxicity through their antioxidant properties. However, their protection versus 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity is only modest, and appropriate structural modifications are necessary to discover better candidates for treating PD. In this work, we designed and synthesized 39 novel xyloketal derivatives (1–39) in addition to the previously reported compound, xyloketal B. The neuroprotective activities of all 40 compounds were evaluated in vivo via respiratory burst assays and longevity-extending assays. During the zebrafish respiratory burst assay, compounds 1, 9, 23, 24, 36 and 39 strongly attenuated reactive oxygen species (ROS) generation at 50 μM. In the Caenorhabditis elegans longevity-extending assay, compounds 1, 8, 15, 16 and 36 significantly extended the survival rates (p < 0.005 vs. dimethyl sulfoxide (DMSO)). A total of 15 compounds were tested for the treatment of Parkinson’s disease using the MPP+-induced C. elegans model, and compounds 1 and 8 exhibited the highest activities (p < 0.005 vs. MPP⁺). In the MPP+-induced C57BL/6 mouse PD model, 40 mg/kg of 1 and 8 protected against MPP+-induced dopaminergic neurodegeneration and increased the number of DA neurons from 53% for the MPP+ group to 78% and 74%, respectively (p < 0.001 vs. MPP+ group). Thus, these derivatives are novel candidates for the treatment of PD.     

Fish Oil,Se Yeast,and Micronutrient-Enriched Nutrition as Adjuvant Treatment during Target Therapy in a Murine Model of Lung Cancer

Despite the effectiveness of primary treatment modalities for cancer, the side effects of treatments, medication resistance, and the deterioration of cachexia after disease progression lead to poor prognosis. A supportive treatment modality to overcome these limitations would be considered a major breakthrough. Here, we used two different target drugs to demonstrate whether a nutraceutical formula (fish oil, Se yeast, and micronutrient-enriched nutrition; NuF) can interfere with cancer cachexia and improve drug efficacy. After Lewis lung cancer (LLC) tumor injection, the C57BL/6 mice were orally administered targeted therapy drugs Iressa and Sutent alone or combined with NuF for 27 days. Sutent administration effectively inhibited tumor size but increased the number of lung metastases in the long term. Sutent combined with NuF had no significant difference in tumor weight and metastasis compare with Sutent alone. However, NuF slightly attenuated metastases number in lung may via mesenchymal marker N-cadherin suppression. NuF otherwise increased epithelial-like marker E-cadherin expression and induce NO-mediated intrinsic apoptotic pathway in tumor cells, thereby strengthening the ability of the targeted therapy drug Iressa for inhibiting tumor progression. Our results demonstrate that NuF can promote the anticancer effect of lung cancer to targeted therapy, especially in Iressa, by inhibiting HIF-1α and epithelial-mesenchymal transition (EMT) and inducing the apoptosis of lung cancer cells. Furthermore, NuF attenuates cancer-related cachectic symptoms by inhibiting systemic oxidative stress.     

Regulation of C/N Interaction in Model Plant Species

Summary

Carbon (C) and nitrogen (N) metabolisms are two major metabolic pathways which have been intensively studied in plants. Both N and C metabolisms are tightly linked in numerous plant biochemical pathways. Therefore the C to N ratio has to be carefully regulated to ensure proper functioning of the huge metabolic network. In order to maintain a viable C/N status under a large range of growth conditions plants have evolved complex mechanisms to regulate the delicate network of these two major assimilatory pathways. C and N metabolisms are both highly regulated. We will present the current knowledge on the regulation of N and C metabolisms by sugars and N metabolites. Players involved in these regulatory processes are just starting to be uncovered and possible signaling molecules involved in these regulations as well as known or potential candidate regulatory genes willbe discussed.     

连续不同施氮对小麦-玉米轮作农田土壤理化性状的影响

为明确施氮量对农田土壤理化形状的影响,以小麦-玉米轮作体系为研究对象,通过4年连续定位试验,比较了连续不同施氮处理对不同土层土壤理化指标的影响。结果表明,连续不同施氮处理对土壤有机质和全氮含量、碳氮比、土壤容重有显著影响,但对pH的影响较小。在0~30cm土层,土壤有机质和全氮含量随施氮量的增加而增加,当施氮量为240kg·hm~(-2)时,有机质含量增加速率最快,当施氮量为360kg·hm~(-2)时,土壤全氮含量最高。在30~60cm和60~90cm土层,不同施氮处理对土壤有机质、全氮含量的影响降低。综合土壤碳氮比和容重等指标,本区域推荐施氮量为240kg·hm~(-2)。     

基于冠层反射光谱的夏玉米叶片碳氮比监测

基于不同夏玉米品种在2个年份不同施氮水平下的田间试验,研究夏玉米叶片碳氮比随生育期的变化模式及其与冠层反射光谱的定量关系,建立玉米叶片碳氮比的定量监测模型。结果表明,夏玉米叶片碳氮比随施氮量的增加而降低,随生育进程呈"高-低-高"动态变化趋势。利用冠层反射光谱监测叶片碳氮比的适宜时期为孕穗期至吐丝期。13个光谱参数与2个品种叶片碳氮比有较好的相关性。通过比较模型的拟合决定系数(R2)和预测标准误(SE),确定转换型植被指数(TVI)与叶片碳氮比的线性回归方程为最佳监测模型。经不同年际独立试验数据的检验,叶片碳氮比监测模型的预测精确,相关系数(r)为0.682 4,根均方差(RMSE)为0.405 2,表明夏玉米冠层反射光谱可用来定量估测叶片碳氮比的变化状况。     

Therapeutic Potential of Phlorotannin-Rich Ecklonia cava Extract on Methylglyoxal-Induced Diabetic Nephropathy in In Vitro Model

Advanced glycation end-products (AGEs) play a vital role in the pathogenesis of diabetic complications. Methylglyoxal (MGO), one of the major precursors of AGEs, is a highly reactive dicarbonyl compound that plays an important role in the pathogenesis of diabetic nephropathy. This study was designed to evaluate the therapeutic potential of phlorotannin-rich Ecklonia cava extract (ECE) on MGO-induced diabetic nephropathy in in vitro models using mouse glomerular mesangial cells. ECE showed anti-glycation activity via breaking of AGEs-collagen cross-links and inhibition of AGEs formation and AGE-collagen cross-linking formation. The renoprotective effects were determined by assessing intracellular reactive oxygen species (ROS) and MGO accumulation, cell apoptosis, and the Nrf-2/ARE signaling pathway. MGO-induced renal damage, intracellular ROS production level, and MGO-protein adduct accumulation were significantly decreased by pretreating ECE. Moreover, ECE pretreatment exhibited preventive properties against MGO-induced dicarbonyl stress via activation of the Nrf2/ARE signaling pathway and reduction of RAGE protein expression in mouse glomerular mesangial cells. Collectively, these results indicated potential anti-glycation properties and prominent preventive effects of ECE against MGO-induced renal damage. Additionally, ECE may be utilized for the management of AGE-related diabetic nephropathy.     

鹿茸多肽对冈田酸诱导的小鼠海马神经元HT22细胞损伤模型中PI3K、AKT、Caspase-9表达的影响

目的观察鹿茸多肽对冈田酸(OA)诱导的小鼠海马神经元HT22细胞损伤模型中磷脂酰肌醇-3激酶(PI3K)、蛋白激酶B(AKT)、半胱氨酸蛋白酶-9(Caspase-9)表达的影响,探讨鹿茸多肽对HT22细胞损伤模型的保护作用机制。方法采用含10%胎牛血清(FBS)培养液(DMEM/F12)传代培养HT22细胞7d后,分为正常对照组、二甲基亚砜(DMSO)对照组、OA细胞损伤模型组、鹿茸多肽高、中、低剂量组。正常对照组给予含10%FBS的DMEM/F12,DMSO对照组给予DMSO终浓度<0.01%的DMEM/F12,OA细胞损伤模型组给予10nmol OA的DMEM/F12,鹿茸多肽高、中、低剂量组分别给予50、500、1000μg/ml的DMEM/F12,于37℃、5%CO2条件下孵育24h。利用噻唑蓝(MTT)比色法检测细胞存活率,酶联免疫法(ELISA)检测各组实验细胞内PI3K、AKT含量,蛋白质印迹法(Western Blot)检测各组实验细胞内PI3K、AKT、Caspase-9表达水平。结果MTT比色法检测结果表明,与OA细胞损伤模型组比较,鹿茸多肽能够明显提高细胞存活率(P<0.05);ELISA检测结果表明,与OA细胞损伤模型组比较,鹿茸多肽能够明显提高受损HT22细胞内PI3K、AKT含量(P<0.05或P<0.01);Western Blot检测结果表明,与OA细胞损伤模型组比较,鹿茸多肽能够明显提高受损HT22细胞内PI3K、AKT、Caspase-9表达水平(P<0.05或P<0.01)。结论鹿茸多肽对OA诱导的HT22细胞损伤模型具有保护作用,作用机制可能与调节受损HT22细胞内PI3K、AKT、Caspase-9表达水平相关。     

基于GF-6/WFV卫星遥感的大田冬小麦叶片氮素含量估测

为对大田冬小麦叶片氮素含量（LNC）进行快速、准确及无损监测,通过在江苏省泰州泰兴市、盐城大丰区和南通如皋市布设冬小麦遥感监测大田试验,在获取试验样点冬小麦冠层红光波段反射率（RED_ref）、近红外波段反射率（NIR_ref）和计算的十个光谱指数（RVI、NDVI、DVI、SAVI、OSAVI、MSR、RDVI、EVI2、NLI和SVI）基础上,将12个遥感光谱指标与冬小麦LNC进行相关分析,选出与LNC相关性较好的作为模型输入变量,构建基于BP神经网络的冬小麦LNC估测模型, 并利用GF-6/WFV卫星遥感影像对县域冬小麦LNC的空间分布开展监测。结果表明,12个遥感光谱指标与冬小麦LNC之间存在不同程度的相关性,其中NDVI、RVI、MSR、OSAVI和NLI与冬小麦LNC的相关性较好（相关系数不低于0.65）。将优选的5个遥感光谱指标作为模型输入变量,构建基于BP神经网络的冬小麦LNC估测模型（LNC-BPEM）,模型的估测精度r²=0.866,RMSE=0.246%,ARE=12.9%。将冬小麦LNC-BPEM估测模型和GF-6/WFV影像结合对县域冬小麦LNC的空间信息监测,获得了如皋县域冬小麦LNC的空间分布特征,该区域冬小麦LNC范围在0.9%~2.0%（长势正常）的种植面积为29 693.3 hm²,占冬小麦总种植面积的74%。这说明利用GF-6/WFV卫星的多个遥感光谱指标与神经网络结合建模可有效估测县域大田冬小麦叶片氮素含量。     

Immunomodulatory activities of non-prolamin proteins in wheat germ and gluten

Albumin (Alb), globulin (Glo), glutelin (Gll) and glutenin (Gln) were separately extracted from wheat germ and wheat gluten. Amino acisd composition, molecular weight distribution, solubility, in vitro digestibility, and immunomodulatory activities were all analyzed. Gll and Gln have similar molecular weight distributions, which differed from those of Alb and Glo. Alb showed the highest solubility at various pH values (except pH 4.0), whereas Glo showed the highest in vitro digestibility. Glo and Gll have the highest proportion of essential to total amino acids, while Alb and Gll have the highest protein digestibility-corrected amino acid scores. Gll had the strongest immunomodulatory effects in terms of stimulation of RAW 264.7 cells to produce IL-6, TNF-α, and IL-10, and good stimulatory effects on splenocyte proliferation, production of IL-2, phagocytosis, and secretion of nitric oxide in RAW 264.7 cells. Gll can be considered a good protein source for use in health foods.