Inflammatory stress exacerbates lipid-mediated renal injury in ApoE/CD36/SRA triple knockout mice

Both lipids and inflammation play important roles in the progression of kidney disease. This study was designed to investigate whether inflammation exacerbates lipid accumulation via LDL receptors (LDLr), thereby causing renal injury in C57BL/6J mice, apolipoprotein E (ApoE) knockout (KO) mice, and ApoE/CD36/scavenger receptor A triple KO mice. The mice were given a subcutaneous casein injection to induce inflammatory stress. After 14 wk, terminal blood samples were taken for renal function, lipid profiles, amyloid A (SAA), and IL-6 assays. Lipid accumulation in kidneys was visualized by oil red O staining. Fibrogenic molecule expression in kidneys was examined. There was a significant increase in serum SAA and IL-6 in the all casein-injected mice compared with respective controls. Casein injection reduced serum total cholesterol, LDL cholesterol, and HDL cholesterol and caused lipid accumulation in kidneys from three types of mice. The expression of LDLr and its regulatory proteins sterol-responsive element-binding protein (SREBP) 2 and SREBP cleavage-activating protein (SCAP) were upregulated in inflamed mice compared with controls. Casein injection induced renal fibrosis accompanied by increased expression of fibrogenic molecules in the triple KO mice. These data imply that inflammation exacerbates lipid accumulation in the kidney by diverting lipid from the plasma to the kidney via the SCAP-SREBP2-LDLr pathway and causing renal injury. Low blood cholesterol levels, resulting from inflammation, may be associated with high risk for chronic renal fibrosis.     

心脏的再生性研究进展

心力衰竭(心衰)是由多种心血管疾病引起的心功能不全,最终出现心肌局部坏死和不可逆转的纤维化。传统的药物治疗、介入和外科治疗方案都存在着一定的局限性。随着转化医学的发展,心脏再生和修复无疑是解决以上临床问题的最佳方案,基础研究的成果正在为临床实践提供理论基础。文章从心脏再生性修复策略、心肌细胞来源、重编程和模式动物等几个方面的进展概括了整个心脏再生领域的发展。     

Phenological dynamics of Dasineura mali (Diptera: Cecidomyiidae) and its parasitoid Platygaster demades (Hymenoptera: Platygasteridae) in apple orchards

The midge Dasineura mali Kieffer (Diptera: Cecidomyiidae) is an important pest of apple (Malus domestica Borkh.) and a potential fresh fruit contaminant, causing quarantine concerns. The phenological dynamics of D. mali and its egg parasitoid Platygaster demades Walker (Hymenoptera: Platygasteridae) were studied in the field in Palmerston North, New Zealand, for 2 yr. Both shoot infestation rate by D. mali and D. mali density per shoot sharply increased in the second generation, reaching approximately 65% and 100-200 eggs, respectively. However, although the infestation rate in the third generation remained as high as in the second generation, the pest density per shoot significantly decreased to 40-60 eggs in the third generation. In the fourth generation, both infestation rate and pest density per shoot decreased to approximately 30% and 10 eggs. Due to the simultaneous decline of the apple shoot number and D. mali density in the third and fourth D. mali generations, the absolute number of D. mali in the orchard also has declined proportionally during the same period. The parasitism and superparasitism rates significantly increased as the season progressed, from 45 to 55 and 37% in the first generation to 87 and 82% in the fourth generation, respectively. Our results suggest that P. demades contributes to the continuous decline of D. mali numbers in the field; it is a good searcher, particularly when its hosts become increasingly scarcer over the season, and it avoids overshooting the host population later in the season by increasing superparasitism. The frequency of P. demades aestivation increases from late spring to midsummer and then decreases during the late summer and early autumn. Although the emergence of P. demades was approximately 2 to 3 wk behind that of D. mali in each generation, the increasing parasitism rates from the first to the fourth generations indicate that P. demades is synchronized with D. mali in the field.     

Synthesis and cytotoxicity evaluation of novel indolylpyrimidines and indolylpyrazines as potential antitumor agents

Novel indolylpyrimidines and indolylpyrazines have been synthesized as potential antitumor agents. They were screened in a panel of 60 human tumor cell lines in vitro. Compounds 7, 9, 10, 15, 21 exhibited efficiently cytotoxic activities with GI(50) values in the low micromolar range against a variety of human cancer cell lines. 2,4-Bis(3'-indolyl)pyrimidine 8 displayed selective cytotoxic activity against IGROV1 tumor cell line with the GI(50) value below 0.01 microM.     

Salvia petrophila sp. nov. (Lamiaceae) from north Guangxi and south Guizhou,China

Salvia petrophila G. X. Hu, E. D. Liu & Yan Liu, a new species from the Chinese provinces of north Guangxi and south Guizhou, is described and illustrated. The new species is similar to S. miltiorrhiza, but can easily be distinguished by its shorter, unbranched stem, subsucculent simple leaf, longer pedicel and corolla tube, oblong‐entire middle lobe of lower corolla lip and larger oblate pollen. It is included in S. sect. Drymosphace on the basis of its falcate‐compressed upper corolla lip and connivent posterior connectives. Trichome and pollen micromorphology of the new species and similar species are described and compared. Additionally, assessment of the conservation status, current geographical distribution and notes on ecology of the new species are given.     

Identification of novel knockout and up-regulated targets for improving isoprenoid production in E. coli

Discovery of novel potential genetic targets to increase the supply of isoprenoid precursors, isopentyl/dimethylallyl diphosphate, is of importance for microbial production of isoprenoids. Here, to improve isoprenoid precursor supply, a flux distribution comparison analysis, based on the genome-scale model, was utilized to simultaneously predict the knockout, down- and up-regulated targets in Escherichia coli. 51 targets were in silico discovered. All knockout and up-regulated targets were experimentally tested to enhance lycopene production. Five knockout targets (deoB, yhfw, yahI, pta and eutD) and four up-regulated targets (ompN, ompE, ndk and cmk) led to 10–45 % increases of lycopene yield, respectively, which had not been uncovered in previous studies. When engineering of the five most significant targets gdhA, eutD, tpiA, ompE and ompN, were combined the lycopene titer improved by 174 % in shake-flask and 81 % in bioreactor fermentations with a maximum yield of 454 mg l^?1.     

Absolute Configurations of Four Resorcylic Acid Lactones,Paecilomycins J − M,by CD/TDDFT Calculations

The absolute configurations of four resorcylic acid lactones (RALs), paecilomycins J ? M ( 1 ? 3 and 5 ), were assigned by Time‐Dependent Density‐Functional Theory (TDDFT) calculations of their electronic circular dichroism (CD) spectra. The previously reported structure 4 for paecilomycin M was found to be incorrect and should be changed to structure 5 . Analysis of structure‐spectrum relationship for this group of RALs suggested that V′‐shape conformations give type I CD spectra (two negative Cotton effects around 300 and 260 nm, a positive Cotton effect around 220 nm) while V‐shape conformations yield type II spectra (signs of three Cotton effects were opposite to those in type I). Chirality 26:44–50, 2013. © 2013 Wiley Periodicals, Inc.