淀粉样前体蛋白修饰、转运及其剪切加工研究进展

阿尔茨海默病（Alzheimer disease,AD）是一种常见的神经系统退行性疾病,其患病率随着年龄的增加而升高。越来越多的研究结果表明,淀粉样蛋白前体蛋白（amyloid precursor protein,APP）经β-,γ-分泌酶切割产生β淀粉样蛋白（β-amyloid,Aβ）的代谢过程异常是AD形成的主要原因。近年来,人们对APP的修饰及加工过程进行了大量的研究,取得了重要的进展,为AD的防治提供了新的靶点和思路。本文就有关APP修饰及剪切加工的研究进展做一综述。     

壳聚糖的化学改性及其衍生物的抗氧化活性研究进展

摘 要壳聚糖是一种天然无毒的生物聚合物,主要经甲壳素的脱乙酰作用制得,具有良好的生物相容性、独特的抗氧化活性及生物可降解性等。由于壳聚糖在中性和碱性溶液中溶解性较差,其应用受到了一定限制,通常对其进行多种改性,拓宽其应用范围,提高其利用价值。近年来具有抗氧化能力的壳聚糖及壳聚糖衍生物表现出了优越的医用价值。本文综述了几种壳聚糖常用的改性方法,并介绍了壳聚糖及其衍生物作为抗氧化剂应用的研究进展。     

细胞色素P450 3A4表达调控机制的研究进展

细胞色素P450 3A4(CYP3A4)的表达具有很强的个体间特异性,会引起复杂的药物相互作用。故明确CYP3A4的表达调控机制,对于指导临床合理用药意义重大。本文从转录前、转录后、翻译后修饰3个阶段对CYP3A4的调控机制进行综述。     

Modification of Solventless‐Synthesized Benzoxazine Resin by Phthalonitrile Group: An Effective Approach for Enhancing Thermal Stability of Polybenzoxazines

Although the solventless method for synthesizing benzoxazine resins has the advantage of low cost, the impurities involved in the products such as oligomers and original phenols significantly weaken the properties of polybenzoxazines. Herein, the commercialized BA‐a (benzoxazine derived from bisphenol‐A, aniline, and formaldehyde) resin obtained from a solventless method is modified by phthalonitrile through the reaction between phenol groups and 4‐nitrophtahlonitrile. The structures of obtained resins have been confirmed by ¹H and ¹³C nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR). In addition, the ring‐opening polymerization behavior of each resin has been studied by differential scanning calorimetry and in situ FTIR. Furthermore, the thermal properties of the cross‐linked thermosets were measured by thermomechanical analysis and thermogravimetric analysis. The phthalonitrile‐functionalized benzoxazine resin shows a low polymerization temperature with the maximum of exothermic peak centered at 218.7 °C, and its corresponding polybenzoxazine exhibits excellent thermal stability, with a high Td₅ value (346 °C) and high char yield (42.78%).     

Graphene oxide regulates cox2 in human embryonic kidney 293T cells via epigenetic mechanisms: dynamic chromosomal interactions

To extend the applications of engineered nanomaterials, such as graphene oxide (GO), it is necessary to minimize cytotoxicity. However, the mechanisms underlying this cytotoxicity are unclear. Dynamic chromosomal interactions have been used to illustrate the molecular bases of gene expression, which offers a more sensitive and cutting-edge technology to elucidate complex biological processes associated with epigenetic regulations. In this study, the role of GO-triggered chromatin interactions in the activation of cox2, a hallmark of inflammation, was investigated in normal human cells. Using chromosome conformation capture technology, we showed that GO triggers physical interactions between the downstream enhancer and the cox2 promoter in human embryonic kidney 293T (293T) via p65 and p300 complex-mediated dynamic chromatin looping, which was required for high cox2 expression. Moreover, tumor necrosis factor-α (TNF-α), located upstream of the p65 signaling pathway, contributed to the regulation of cox2 activation through dynamic chromatin architecture. Compared with pristine GO and aminated GO (GO-NH₂), poly (acrylic acid)-functionalized GO (GO-PAA) induced a weaker inflammatory response and a weaker effect on chromatin architecture. Our results mechanistically link GO-mediated chromatin interactions with the regulation of cox2 and suggest that GO derivatives may minimize toxicity in practical applications.     

Why do studies show different associations between intrauterine exposure to maternal smoking and age at menarche?

Purpose

Studies suggests that intrauterine exposure to maternal smoking both accelerates or delays age at menarche. We hypothesize that these opposing findings relate to different infant and childhood growth patterns across cohorts.

A Bayesian semiparametric latent variable approach to causal mediation

In assessing causal mediation effects in randomized studies, a challenge is that the direct and indirect effects can vary across participants due to different measured and unmeasured characteristics. In that case, the population effect estimated from standard approaches implicitly averages over and does not estimate the heterogeneous direct and indirect effects. We propose a Bayesian semiparametric method to estimate heterogeneous direct and indirect effects via clusters, where the clusters are formed by both individual covariate profiles and individual effects due to unmeasured characteristics. These cluster‐specific direct and indirect effects can be estimated through a set of regression models where specific coefficients are clustered by a stick‐breaking prior. To let clustering be appropriately informed by individual direct and indirect effects, we specify a data‐dependent prior. We conduct simulation studies to assess performance of the proposed method compared to other methods. We use this approach to estimate heterogeneous causal direct and indirect effects of an expressive writing intervention for patients with renal cell carcinoma.     

Skeletal effects of bite jumping therapy on the mandible - removable vs. fixed functional appliances

AUTHORS: Shen G, Hagg U, Darendeliler MA. OBJECTIVE: Based on an extensive review of the literature, the aim of this study was to explore the mainstream consensus on the controversial topic of whether the bite jumping treatment could enhance mandibular growth. DESIGN: The data for removable and fixed functional appliances were respectively comprehended and analyzed with regard to their attributes in mandibular growth modification. Furthermore, numerous reported findings were assessed by relating them to some important factors influencing the effects of bite jumping, such as treatment timing, treatment duration and post-treatment follow-up, to allow for a more objective and accurate evaluation. RESULTS: The key differences between removable and fixed appliances are working hours (intermittent vs. continuous), length of treatment time (long vs. short), optimal treatment timing (before puberty growth vs. at or after puberty spurt), and mode of bite-jumping (considerable vertical opening vs. limited vertical opening). These different features lead to different treatment effects on mandibular and TMJ growth, such as the intensity of possibly increased growth (clinically less significant vs. significant), the direction of enhanced growth (vertical vs. horizontal), and the stability of treatment changes (unstable vs. stable). The short-term or long-term post-treatment relapse mainly relates to the rebound of dental position. CONCLUSION: The immediate effects of bite jumping functional appliances on the mandibular growth enhancement are convincing during actual treatment. This extra gain of growth might be sustainable during the short-term and long-term post-treatment period.     

In vitro antimicrobial and resistance-modifying activities of aqueous crude khat extracts against oral microorganisms

OBJECTIVES: To assess antimicrobial activities of aqueous crude khat (Catha edulis) extracts against a panel of oral microorganisms and to test their ability to modify bacterial resistance to tetracycline and penicillin in vitro. DESIGN: Lyophilized aqueous extracts were prepared from three khat cultivars. The agar dilution method of the NCCLS was used to test the extracts, at concentrations of 20-1.25 mg/ml, against 33 oral strains. MIC was defined as the lowest concentration at which there was no visible growth. Slight growth was defined as marked growth reduction (MGR). The E-test was used to determine the MICs of tetracycline and penicillin-G for three resistant strains in absence and presence of a sub-MIC of the khat extracts (5mg/ml). RESULTS: Eighteen strains (55%) were sensitive to the extracts (MICs 5-20 mg/ml). Most of these were periodontal pathogens with Porphyromonas gingivalis and Tannerella forsythensis being the most susceptible (MIC 5-10mg/ml). Veillonella parvula, Actinomyces israelii and some streptococci were not sensitive. Except for Lactobacillus acidophilus that showed MGR at 1mg/ml, cariogenic species were neither sensitive. The extracts were active against Streptococcus pyogenes (MIC 10-20 mg/ml) but not against Candida albicans and Staphylococcus aureus. The presence of the khat extracts at a sub-MIC resulted in a 2-4-fold potentiation of the tested antibiotics against the resistant strains. CONCLUSIONS: Khat has water-soluble constituents possessing selective antibacterial activity against oral bacteria. There is preliminary evidence for presence of an antibiotic resistance-modifying component. Further investigation is needed to identify the active components and assess their clinical relevance.     

纯钛表面酸碱处理及生物矿化的初步研究

目的:探讨不同的酸、碱处理条件下纯钛表面生物矿化沉积磷灰石层的差异。方法:对商用纯钛分别采用磨光处理、酸处理、酸碱处理或酸碱及热处理,然后放入模拟体液(SBF)中矿化处理7天;采用SEM观察试样表面的形貌,采用XRD分析试样表面沉积层的相组成。结果:经酸碱处理后纯钛形成微粗糙表面,随着碱液浓度的升高和采用热处理,试样表面的粗糙度增加且更均匀;经碱液处理的试样矿化后其表面出现磷灰石沉积层;而未处理组未发现磷灰石沉积层;XRD图谱分析发现矿化表面沉积物为HCA,钙磷比为1.37。结论:碱液处理有利于磷灰石层的形成,而改变碱液浓度和是否采用热处理对磷灰石沉积能力有影响。