Developmental History Provides a Roadmap for the Emergence of Tumor Plasticity

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Anti-Oxidative Effects of Melatonin Receptor Agonist and Omega-3 Polyunsaturated Fatty Acids in Neuronal SH-SY5Y Cells: Deciphering Synergic Effects on Anti-Depressant Mechanisms

Omega-3 polyunsaturated fatty acids (n-3 or omega-3 PUFAs) and melatonin receptor agonist ramelteon (RMT) both display antidepressant effects, while their cellular effects on anti-oxidative and neuroprotective mechanisms might be different. In this study, we aimed to decipher the individual and synergistic actions of n-3 PUFAs and RMT, as compared with the conventional antidepressant fluoxetine (FLX), in a cellular model of oxidative stress, which might play an important role in the pathophysiology of depression and associated disorders. We investigated the rescue and prevention effects of FLX, RMT, and n-3 PUFAs, e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), by using cell viability in SH-SY5Y cells under oxidative stress along with measurements of key cellular markers of oxidative stress, inflammatory, and neuroprotection. The results revealed that the RMT and EPA combination significantly increased the cell viability in a dose-dependent manner. RMT showed preventive effects, FLX and DHA possessed rescue effects, while EPA showed both rescue and preventive effects. We observed the dose-dependent activation and translocation of nuclear factor-κB to the nucleus augmented by the expressions of peroxisome proliferator activator receptor-gamma, tyrosine hydroxylase, c-Fos expression, and reactive oxygen species, implying that RMT and EPA combination reversed oxidative and neuroinflammatory pathophysiology and protected the neuronal cells from further damage. The results demonstrated that RMT and EPA synergistically provide effective neuroprotective, anti-oxidative/inflammatory effect against oxidative stress. Our study provides pre-clinical evidence to conduct future clinical trials of using n-3 PUFAs/RMT combination in depressive disorders.     

Discovery of 3(S)-thiomethyl pyrrolidine ERK inhibitors for oncology

Compound 5 (SCH772984) was identified as a potent inhibitor of ERK1/2 with excellent selectivity against a panel of kinases (0/231 kinases tested @ 100?nM) and good cell proliferation activity, but suffered from poor PK (rat AUC PK @10?mpk?=?0?μM?h; F%?=?0) which precluded further development. In an effort to identify novel ERK inhibitors with improved PK properties with respect to 5, a systematic exploration of sterics and composition at the 3-position of the pyrrolidine led to the discovery of a novel 3(S)-thiomethyl pyrrolidine analog 28 with vastly improved PK (rat AUC PK @10?mpk?=?26?μM?h; F%?=?70).     

Differential roles of glucosinolates and camalexin at different stages of Agrobacterium‐mediated transformation

Agrobacterium tumefaciens is the causal agent of crown gall disease in a wide range of plants via a unique interkingdom DNA transfer from bacterial cells into the plant genome. Agrobacterium tumefaciens is capable of transferring its T‐DNA into different plant parts at different developmental stages for transient and stable transformation. However, the plant genes and mechanisms involved in these transformation processes are not well understood. We used Arabidopsis thaliana Col‐0 seedlings to reveal the gene expression profiles at early time points during Agrobacterium infection. Common and differentially expressed genes were found in shoots and roots. A gene ontology analysis showed that the glucosinolate (GS) biosynthesis pathway was an enriched common response. Strikingly, several genes involved in indole glucosinolate (iGS) modification and the camalexin biosynthesis pathway were up‐regulated, whereas genes in aliphatic glucosinolate (aGS) biosynthesis were generally down‐regulated, on Agrobacterium infection. Thus, we evaluated the impacts of GSs and camalexin during different stages of Agrobacterium‐mediated transformation combining Arabidopsis mutant studies, metabolite profiling and exogenous applications of various GS hydrolysis products or camalexin. The results suggest that the iGS hydrolysis pathway plays an inhibitory role on transformation efficiency in Arabidopsis seedlings at the early infection stage. Later in the Agrobacterium infection process, the accumulation of camalexin is a key factor inhibiting tumour development on Arabidopsis inflorescence stalks. In conclusion, this study reveals the differential roles of GSs and camalexin at different stages of Agrobacterium‐mediated transformation and provides new insights into crown gall disease control and improvement of plant transformation.     

Repurposing Pan-HDAC Inhibitors for ARID1A-Mutated Ovarian Cancer

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The Divalent Elements Changes in Early Stages of Chronic Kidney Disease

As the glomerular filtration rate (GFR) decreases, it can cause imbalance in some divalent elements. These imbalances can cause increased oxidative stress in patients with renal impairment. The aim of present study was to investigate the changes of these divalent elements with CKD progression. One hundred and ninety-four patients with chronic kidney diseases (CKD) were divided into five stages, stage 1, 2, 3a, 3b, 4, and were recruited into this study. The divalent elements, calcium, magnesium, phosphorus, as well as iron, zinc, and copper were determined in clinical chemistry analyzer. Higher CKD stages were found to be associated with increased levels of phosphorus and copper; P_trend values were 0.002 and 0.004, respectively. Also, higher CKD stages were associated with decreased levels of zinc; P_trend value was 0.002, after adjustment for age, gender, smoke, education, diabetes, hypertension, and BMI. Decreased levels of zinc and elevated levels of phosphorus and copper might increase the oxidative stress and complications in CKD patients. Future randomized studies are needed to show whether adjusting dietary intake of phosphorus, copper, and zinc might affect the progression of CKD.     

小麦干尖叶的遗传研究初报

小麦干尖叶是近年在小麦育种中所发现的一种叶部坏死性状,直接影响小麦的产量。本文以具有干尖叶与正常叶这一相对性状的部分小麦品种(系)为基本材料,采用正反杂交、正反回交及杂种后代分析和异源细胞质替换,首次对干尖叶的遗传及性状传递规律进行了研究。结果表明:干尖叶性状与一般杂种坏死与黄化截然不同, 并非仅杂种所具有,能作为纯系稳定遗传; 其表型受核内一对主效显性基因所控制,即使采用异源细胞质替换, 以特定质核互作也难以克服这一性状的对外表达,只有通过杂交与后代选择,纯化与稳定隐性正常叶方可克服。 Abstract:In this paper,the inheritance and transmission law of the character for wheat leaf-tip necrosis were firstly investigated with the contrasting character of leaf-tip necrosis and normal leaf in wheat varieties for basic test materials by reciprocal crosses and backcrosses,hybrid progeny analysis and aliencytoplasm substitution.The results indicated that the wheat leaf-tip necrosis is abviously different from the hybrid necrosis and hybrid chlorosis.It is not only expressed in hybrid but also stable inheritance as pureline.Its phenotype is conditioned by a pair major dominant gene.It is not overcome even if special interaction of nucleus-cytoplasm after alien cytoplasm substitution.Only be the varieties or lines with normal leaf obtained by crossing and selecting stable normal leaf character with recessive gene.     

胡萝卜与烟草原生质体的低温保存

在较长的时间内,可保持正常生理状态与细胞活性的原生质体的制备及保存技术是进行空间细胞融合实验的前提条件。本研究以0.7ml/L的葡萄糖作渗透压,在6-8℃低温条件下经过72小时保存后,供试原生质体的存活率仍可达81%,并保持了其长壁与分裂的特性。 Abstract:Storage duration and acativity of isolated protoplasts are important problem for experiment on plant cell fusion in space.We have achieved preliminary success using glucose as osmotic reagent,The survival protopasts after 72 hour storage in 0.7mol/L glucose at 6~8℃ reached 81% and maintained a very high activity of division.     

Expression of the Bacillus licheniformis PWD-1 keratinase gene in B. subtilis

The kerA gene which encodes the enzyme keratinase was isolated from the feather-degrading bacterium Bacillus licheniformis PWD-1. The entire gene, including pre-, pro- and mature protein regions, was cloned with P_ker, its own promoter, P43, the vegetative growth promoter, or the combination of P43-P_ker into plasmid pUB18. Transformation of the protease-deficient strain B. subtilis DB104 with these plasmids generated transformant strains FDB-3, FDB-108 and FDB-29 respectively. All transformants expressed active keratinase in both feather and LB media, in contrast to PWD-1, in which kerA was repressed when grown in LB medium. With P43-P_ker upstream of kerA, FDB-29 displayed the highest activity in feather medium. Production of keratinase in PWD-1 and transformants was further characterized when glucose or casamino acids were supplemented into the feather medium. These studies help understand the regulation of kerA expression and, in the long run, can help strain development and medium conditioning for the production of this industrially important keratinase. Received 31 December 1996/ Accepted in revised form 23 June 1997