Anti-hypercholesterolemic impacts of barley and date palm fruits on the ovary of Wistar albino rats and their offspring

A high cholesterol diet is related to ovarian dysfunction and infertility which has been increased among young ages consuming processed food products. The present study was conducted to evaluate the role of a high cholesterol diet on the ovaries of young female rats via assessments of histopathology, immunohistochemistry, oxidative stress and apoptic markers. Also, mating of hypercholesterolemic female rats was carried out to measure the fertility and numbers of their offspring. At the same time, phytotherapy was carried out through supplementing the diet with barley and/ or date palm fruits (10%) during the experiment to assess the phyto-therapeutic impacts in attenuation of drastic hypercholesterolemic effects.Hypercholesterolemic diet-fed rats exhibited damage of the ovarian follicles and increased follicular atresia. Furthermore, expression of cleaved caspase-3 was upregulated, while PCNA was downregulated in granulosa, theca and stroma cells. Hypercholesterolemic female rats showed marked depletion of antioxidative enzymes, increased lipid peroxidation and apoptotic markers. Alterations to the female serum hormones were detected. Offspring maternally fed on hypercholesterolemic diet showed a significant decrease of body weight and altered sex ratio. However, concomitant supplementation of barley and or date fruits to hypercholesterolemic groups revealed marked improvement of ovarian structure and function.On the basis of these evidences, it is believed that the enhanced synergistic effects of barley and/or date palm fruits in the amelioration of ovarian structure and functions were elicited by the potential antioxidant activity of their phytomicronutrients, polyphenols, β-glucan and trace elements. These materials scavenge free radicals from inflamed cells that can be used to establish an effective and novel therapeutic strategy for activating ovarian cell regeneration.     

winged eye Induces Transdetermination of Drosophila Imaginal Disc by Acting in Concert with a Histone Methyltransferase,Su(var)3-9

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Effects of C10‐ and C12‐chain length alkyl analogs of monochamol on attraction of longhorn pine sawyer Monochamus saltuarius (Coleoptera: Cerambycidae)

The aggregation pheromone of Monochamus (Coleoptera: Cerambycidae) beetles, 2‐(undecyloxy) ethanol (hereafter referred to as monochamol), has gained considerable attention because of its usefulness in monitoring and population control of pine sawyer beetles. The hydroxyether structural motif is conserved in pheromones of the subfamily Lamiinae of the Cerambycidae. In this study, we investigated the effects of C10‐ and C12‐chain length alkyl analogs of monochamol, 2‐(decyloxy) ethanol and 2‐(dodecyloxy) ethanol, on attracting M. saltuairus in Andong, Gyeongsangbuk‐do, Korea. The C10 and C12 analogs attracted M. saltuarius when used in combination with α‐pinene and ethanol, but the responses of these alkyl chain analogs were lower than those of monochamol. Furthermore, the addition of either C10 or C12 analog to the use of monochamol with α‐pinene and ethanol had no effect on attraction of M. saltuarius, indicating high sensitivity of M. saltuarius to monochanol. Taken together, the results of this study suggest that chemical communication within a Monochamus species depends not only on monochamol, but also on other semiochemicals.     

Structural basis for assembly of the CBF3 kinetochore complex

Eukaryotic chromosomes contain a specialised region known as the centromere, which forms the platform for kinetochore assembly and microtubule attachment. The centromere is distinguished by the presence of nucleosomes containing the histone H3 variant, CENP‐A. In budding yeast, centromere establishment begins with the recognition of a specific DNA sequence by the CBF3 complex. This in turn facilitates CENP‐A^Cse4 nucleosome deposition and kinetochore assembly. Here, we describe a 3.6 Å single‐particle cryo‐EM reconstruction of the core CBF3 complex, incorporating the sequence‐specific DNA‐binding protein Cep3 together with regulatory subunits Ctf13 and Skp1. This provides the first structural data on Ctf13, defining it as an F‐box protein of the leucine‐rich‐repeat family, and demonstrates how a novel F‐box‐mediated interaction between Ctf13 and Skp1 is responsible for initial assembly of the CBF3 complex.     

miR-613通过靶向VEGFA抑制神经胶质瘤细胞的增殖、侵袭和血管生成

摘要 目的：旨在探究miR-613在胶质瘤中的表达及对细胞增殖、侵袭和血管生成的影响。方法：根据细胞转染将实验分组为对照miRNA组（Control组）、miR-613模拟物组（mimics组）和miR-613 mimics+VEGFA组（VEGFA组）。采用逆转录定量聚合酶链反应（RT-qPCR）检测胶质瘤细胞和组织中miR-613和VEGFA mRNA的表达水平;采用荧光素酶报告基因分析miR-613与血管内皮生长因子（VEGF）的关系;采用Western blotting检测VEGFA蛋白的表达水平;通过体外实验检测转染细胞的增殖能力、侵袭能力和管状形成能力。结果：与正常组织样本相比,胶质瘤I-II期组样本的肿瘤细胞呈现异形,具有深核染色,并且肿瘤细胞密度适度较低,而胶质瘤III-IV期组样本的肿瘤细胞的核分裂活跃,具有明显的微血管增殖和明显的细胞异型性;miR-613在胶质瘤I-IV期组织样本中显著降低（P<0.05）。在U87和U251细胞系的VEGFA-WT组中,与Control组相比,mimics组的荧光素酶活性显著降低（P<0.05）。与Control组相比,U87和U251细胞系中mimics组VEGFA的mRNA和蛋白表达水平均显著降低（P<0.05）。克隆形成实验、血管生成实验和细胞侵袭实验结果表明,与Control组相比,mimics组的克隆形成数量、细胞侵袭数、内皮细胞HUVEC的管状形成数和Ang-2蛋白表达水平均显著降低（P<0.05）;与mimics组相比,VEGFA组克隆形成数量、细胞侵袭数、内皮细胞HUVEC的管状形成数和Ang-2蛋白表达水平均显著升高（P<0.05）。结论：miR-613通过靶向VEGFA抑制了神经胶质瘤细胞的侵袭、增殖和血管生成,提示miR-613可能成为未来治疗胶质瘤的潜在靶点。     

Intrinsic Bent DNA Sites in the Developmentally Amplified C3-22 Gene Promoter of Rhynchosciara americana (Diptera: Sciaridae)

The Rhynchosciara americana C3-22 gene is located in an amplified domain and is developmentally expressed. The aim of the present work was to identify intrinsically bent DNA sites in a segment containing the gene promoter and downstream sequence. The results indicated that this gene is flanked by intrinsically bent DNA sites. Three bent DNA sites (b^?3, b^?2, and b^?1) were localized in the promoter, and one was localized downstream of the gene (b⁺¹). These sites had helical parameters that confirmed the curved structure, as well as segments with left-handed superhelical writhe. In silico analysis of the promoters of four other insect genes, which encode secreted polypeptides, showed that they all had curved structures and similar helical parameters. Correlation with other results indicates that the detected intrinsically bent DNA sites that flank the C3-22 gene might be a consensus feature of the gene structure in the amplified domains.     

Syntheses,biological evaluation and SAR of ingenol mebutate analogues for treatment of actinic keratosis and non-melanoma skin cancer

Ingenol mebutate is the active ingredient in Picato® a new drug for the treatment of actinic keratosis. A number of derivatives related to ingenol mebutate were prepared by chemical synthesis from ingenol with the purpose of investigating the SAR and potency in assays relating to pro-inflammatory effects (induction of PMN oxidative burst and keratinocyte cytokine release), the potential of cell death induction, as well as the chemical stability. By modifications of the ingenol scaffold several prerequisites for activity were identified. The chemical stability of the compounds could be linked to an acyl migration mechanism. We were able to find analogues of ingenol mebutate with comparable in vitro properties. Some key features for potent and more stable ingenol derivatives have been identified.     

Synthesis and evaluation of a [18F]formyl–Met–Leu–Phe derivative: A positron emission tomography imaging probe for bacterial infections

The tripeptide formyl–Met–Leu–Phe (fMLF) is a prototype of N-formylated chemotactic peptides for neutrophils owing to its ability to bind and activate the G protein-coupled formyl peptide receptor (FPR). Here, we developed an ¹⁸F-labeled fMLF derivative targeting FPR as a positron emission tomography (PET) imaging probe for bacterial infections. The study demonstrates that the fMLF derivative fMLFXYk(FB)k (X?=?Nle) has a high affinity for FPR (Ki?=?0.62?±?0.13?nM). The radiochemical yield and purity of [¹⁸F]fMLFXYk(FB)k were 16% and >96%, respectively. The in vivo biodistribution study showed that [¹⁸F]fMLFXYk(FB)k uptake was higher in the bacterial infected region than in the non-infected region. We observed considerably higher infection-to-muscle ratio of 4.6 at 60?min after [¹⁸F]fMLFXYk(FB)k injection. Furthermore, small-animal PET imaging studies suggested that [¹⁸F]fMLFXYk(FB)k uptake in the bacterial infected region was clearly visualized 60?min after injection.