Synthesis,Stability and Direct Antiproliferative Effect of New Cysteine Modified GnRH Analogs

International Journal of Peptide Research and Therapeutics - It is demonstrated that gonadotropin-releasing hormone (GnRH) analogs can directly inhibit the proliferation of reproductive tissue...     

Genome-wide analysis of primary auxin-responsive Aux/IAA gene family in maize (Zea mays. L.)

The phytohormone auxin is important in various aspects of organism growth and development. Aux/IAA genes encoding short-lived nuclear proteins are responsive primarily to auxin induction. Despite their physiological importance, systematic analysis of Aux/IAA genes in maize have not yet been reported. In this paper, we presented the isolation and characterization of maize Aux/IAA genes in whole-genome scale. A total of 31 maize Aux/IAA genes (ZmIAA1 to ZmIAA31) were identified. ZmIAA genes are distributed in all the maize chromosomes except chromosome 2. Aux/IAA genes expand in the maize genome partly due to tandem and segmental duplication events. Multiple alignment and motif display results revealed major maize Aux/IAA proteins share all the four conserved domains. Phylogenetic analysis indicated Aux/IAA family can be divided into seven subfamilies. Putative cis-acting regulatory DNA elements involved in auxin response, light signaling transduction and abiotic stress adaption were observed in the promoters of ZmIAA genes. Expression data mining suggested maize Aux/IAA genes have temporal and spatial expression pattern. Collectively, these results will provide molecular insights into the auxin metabolism, transport and signaling research.     

Modulation of DNA end joining by nuclear proteins

DNA double strand breaks in mammalian cells are primarily repaired by homologous recombination and non-homologous end joining (NHEJ). NHEJ may either be error-free or mutagenic with deletions or insertions at the joint. Recent studies showed that DNA ends can also be joined via microhomologous sequences flanking the break point especially when proteins responsible for NHEJ, such as Ku, are absent. Microhomology-mediated end joining (MHEJ) is always accompanied by a deletion that spans one of the two homologous sequences and the intervening sequence, if any. In this study we evaluated several factors affecting the relative contribution of MHEJ to DNA end joining using nuclear extracts and DNA substrates containing 10-bp repeats at the ends. We found that the occurrence of MHEJ is determined by the relative abundance of nuclear proteins. At low DNA/protein ratios, an error-free end-joining mechanism predominated over MHEJ. As the DNA/protein ratio increased, MHEJ became predominant. We show that the nuclear proteins that contribute to the inhibition of the error-prone MHEJ include Ku and histone H1. Treatment of extracts with flap endonuclease 1 antiserum significantly reduced MHEJ. Addition of a 17-bp intervening sequence between the microhomologous sequences significantly reduced the efficiency of MHEJ. Thus, this cell-free assay provides a platform for evaluating factors modulating end joining.     

A multiscale model for multiple platelet aggregation in shear flow

Biomechanics and Modeling in Mechanobiology - We developed a multiscale model for simulating aggregation of multiple, free-flowing platelets in low–intermediate shear viscous flow, in which...     

LDL coating pVEGF/polyethylenimine complex enhances vascular endothelial growth factor expression

The major limitations to non-viral gene delivery are relatively low efficiency and cytotoxicity, which need to be addressed in the design of new vectors. In this study, negatively charged low density lipoproteins (LDL) were coated onto positively charged pVEGF/PEI complexes to form pVEGF/PEI/LDL terplexes by a two-step procedure. The biocompatible LDL was introduced to reduce the cytotoxicity of the gene delivery system and increase its affinity to cells. The successful formation of pVEGF/PEI/ LDL terplexes was confirmed by their near-neutral and slightly negative surface charges. The pVEGF/PEI/LDL terplexes were well-defined sub-micron spherical particles. On the cell viability assay, both of the PEI/LDL combined vector and pVEGF/PEI/LDL terplexes exhibited much lower cytotoxicity to HeLa cells and HUVE cells than those of PEI and pVEGF/PEI complexes, attributed to the shielding effect of the LDL. pEGFP/PEI/LDL terplexes showed significantly higher transfection efficiency in comparison to pEGFP/PEI complexes in serum-containing medium. pVEGF/PEI/LDL terplexes at their optimal N/P ratio and LDL/PEI weigh ratio induced higher expression levels of VEGF protein in HUVE cells than those of pVEGF/PEI complexes. Therefore, the pVEGF/PEI/LDL terplexes could be used as a promising gene delivery system to enhance VEGF protein expression.     

Retrospective Analysis of 234 Nasopharyngeal Carcinoma Patients with Distant Metastasis at Initial Diagnosis: Therapeutic Approaches and Prognostic Factors

Purpose

The purpose of this retrospective study was to identify the independent prognostic factors and optimize the treatment for nasopharyngeal carcinoma (NPC) patients with distant metastasis at initial diagnosis.

Methods

A total of 234 patients referred between January 2001 and December 2010 were retrospectively analyzed. Among the 234 patients, 94 patients received chemotherapy alone (CT), and 140 patients received chemoradiotherapy (CRT). Clinical features, laboratory parameters and treatment modality were examined with univariate and multivariate analyses.

Results

The median overall survival (OS) time was 22 months (range, 2-125 months), and the 1-year, 2-year, 3-year overall survival rates were 82.2%, 51.3% and 34.1%. The overall response and disease control rates of metastatic lesions after chemotherapy were 56.0% and 89.8%. The factors associated with poor response were karnofsky performance score (KPS) <80, liver metastasis, lactate dehydrogenase (LDH)>245 IU/L, and number of chemotherapy cycles <4. The 3-year OS of patients receiving CRT was higher than those receiving CT alone (48.2% vs. 12.4%, p<0.001). Subgroup analysis showed that significantly improved survival was also achieved by radiotherapy of the primary tumor in patients who achieved complete remission (CR)/partial remission (PR) or stable disease (SD) of metastatic lesions after chemotherapy. Significant independent prognostic factors of OS were KPS, liver metastasis, levels of LDH, and multiple metastases. Treatment modality, response to chemotherapy and chemotherapy cycles were also associated with OS.

Conclusion

A combination of radiotherapy and chemotherapy seems to have survival benefits for selected patients with distant metastases at initial diagnosis. Clinical and laboratory characteristics can help to guide treatment selection. Prospective randomized studies are needed to confirm the result.     

Dynamic Regulation of Host Restriction Factor Expression over the Course of HIV-1 Infection In Vivo

In this study, we investigated the expression levels of host restriction factors in six untreated HIV-1-positive patients over the course of infection. We found that the host restriction factor gene expression profile consistently increased over time and was significantly associated with CD4⁺ T cell activation and viral load. Our data are among the first to demonstrate the dynamic nature of host restriction factors in vivo over time.     

油藏嗜热菌与膨润土的相互作用及其对储层防膨的意义

[目的]本文从胜利油田沾3区块的高温油藏的原油采出液中分离得到一株嗜热菌,通过其与膨润土的相互作用,尝试探讨油藏微生物作为油藏储层中水敏性矿物（如蒙皂石）改性剂的可能性。[意义]研究结果将在降低水敏矿物的膨胀性能,为解决水驱采油中遇到的水敏效应的瓶颈问题提供微生物的新途径。[结果]所得菌株为革兰氏阳性菌,呈杆状,具芽孢,兼性厌氧,鉴定为Geobacillus icigianus SL-1。菌株SL-1在厌氧条件下能够还原蒙皂石的结构铁。扫描电镜（SEM）结果显示,无菌对照体系中,蒙皂石呈不规则薄片状。而经微生物作用后,除薄片状蒙皂石外,另有板状次生矿物的生成。进一步能谱（EDS）分析表明,与薄片状蒙皂石相比,板状矿物含有较高的Al/Si比值,且含有明显的K⁺信号。XRD结果显示,经过微生物作用后,固相物质中蒙皂石的百分比下降至47.7%,伊利石百分比上升至29.1%,而无菌对照组中蒙皂石的百分含量则为70.4%,伊利石的百分比则为19.8%。XRD物相分析和EDS结果均证实经过微生物作用后,部分蒙皂石转化成了伊利石。膨胀性能的分析进一步揭示菌株SL-1作用后,矿物膨胀性较初始矿物显著降低,缩膨率达到25.9%。以上结果为油藏储层防膨提供了重要的实验依据。