Cartilage Oligomeric Matrix Protein,Diseases, and Therapeutic Opportunities

Cartilage oligomeric matrix protein (COMP) is an extracellular matrix (ECM) glycoprotein that is critical for collagen assembly and ECM stability. Mutations of COMP cause endoplasmic reticulum stress and chondrocyte apoptosis, resulting in rare skeleton diseases. The bouquet-like structure of COMP allows it to act as a bridging molecule that regulates cellular phenotype and function. COMP is able to interact with many other ECM components and binds directly to a variety of cellular receptors and growth factors. The roles of COMP in other skeleton diseases, such as osteoarthritis, have been implied. As a well-established biochemical marker, COMP indicates cartilage turnover associated with destruction. Recent exciting achievements indicate its involvement in other diseases, such as malignancy, cardiovascular diseases, and tissue fibrosis. Here, we review the basic concepts of COMP and summarize its novel functions in the regulation of signaling events. These findings renew our understanding that COMP has a notable function in cell behavior and disease progression as a signaling regulator. Interestingly, COMP shows distinct functions in different diseases. Targeting COMP in malignancy may withdraw its beneficial effects on the vascular system and induce or aggravate cardiovascular diseases. COMP supplementation is a promising treatment for OA and aortic aneurysms while it may induce tissue fibrosis or cancer metastasis.     

Immunofluorescent Evidence for Nuclear Localization of Aromatase in Astrocytes in the Rat Central Nervous System

Estrogens regulate a variety of neuroendocrine, reproductive and also non-reproductive brain functions. Estradiol biosynthesis in the central nervous system (CNS) is catalyzed by the enzyme aromatase, which is expressed in several brain regions by neurons, astrocytes and microglia. In this study, we performed a complex fluorescent immunocytochemical analysis which revealed that aromatase is colocalized with the nuclear stain in glial fibrillary acidic protein (GFAP) positive astrocytes in cell cultures. Confocal immunofluorescent Z-stack scanning analysis confirmed the colocalization of aromatase with the nuclear DAPI signal. Nuclear aromatase was also detectable in the S100β positive astrocyte subpopulation. When the nuclear aromatase signal was present, estrogen receptor alpha was also abundant in the nucleus. Immunostaining of frozen brain tissue sections showed that the nuclear colocalization of the enzyme in GFAP-positive astrocytes is also detectable in the adult rat brain. CD11b/c labelled microglial cells express aromatase, but the immunopositive signal was distributed only in the cytoplasm both in the ramified and amoeboid microglial forms. Immunostaining of rat ovarian tissue sections and human granulosa cells revealed that aromatase was present only in the cytoplasm. This novel observation suggests a new unique mechanism in astrocytes that may regulate certain CNS functions via estradiol production.     

An Ultra-Low Dose of ∆9-Tetrahydrocannabinol Alleviates Alzheimer’s Disease-Related Cognitive Impairments and Modulates TrkB Receptor Expression in a 5XFAD Mouse Model

Alzheimer’s disease (AD) is the most common form of dementia, but there is still no available treatment. Δ9-tetrahydrocannabinol (THC) is emerging as a promising therapeutic agent. Using THC in conventional high doses may have deleterious effects. Therefore, we propose to use an ultra-low dose of THC (ULD-THC). We previously published that a single injection of ULD-THC ameliorated cognitive functioning in several models of brain injuries as well as in naturally aging mice. Here, 5xFAD AD model mice received a single treatment of ULD-THC (0.002 mg/kg) after disease onset and were examined in two separate experiments for cognitive functions, neurotropic, and inflammatory factors in the hippocampus. We show that a single injection of ULD-THC alleviated cognitive impairments in 6- and 12-month-old 5xFAD mice. On the biochemical level, our results indicate an imbalance between the truncated TrkB receptor isoform and the full receptor, with AD mice showing a greater tendency to express the truncated receptor, and ULD-THC improved this imbalance. We also investigated the expression of three AD-related inflammatory markers and found an ameliorating effect of ULD-THC. The current research demonstrates for the first time the beneficial effects of a single ultra-low dose of THC in a mouse model of AD after disease onset.     

Identification and Functional Analysis of Key Autophosphorylation Residues of Arabidopsis Senescence Associated Receptor-like Kinase

Reversible protein phosphorylation mediated by protein kinases and phosphatases plays important roles in the regulation of leaf senescence. We previously reported that the senescence-associated leucine-rich repeat receptor-like kinase AtSARK autophosphorylates on both serine/threonine and tyrosine residues and functions as a positive regulator of Arabidopsis leaf senescence; the senescence-suppressed protein phosphatase SSPP interacts with and dephosphorylates the cytoplasmic domain of AtSARK, thereby negatively regulating leaf senescence. Here, 27 autophosphorylation residues of AtSARK were revealed by mass spectrometry analysis, and six of them, including two Ser, two Thr, and two Tyr residues, were further found to be important for the biological functions of AtSARK. All site-directed mutations of these six residues that resulted in decreased autophosphorylation level of AtSARK could significantly inhibit AtSARK-induced leaf senescence. In addition, mutations mimicking the dephosphorylation form of Ser384 (S384A) or the phosphorylation form of Tyr413 (Y413E) substantially reduced the interaction between AtSARK and SSPP. All results suggest that autophosphorylation of AtSARK is essential for its functions in promoting leaf senescence. The possible roles of S384 and Y413 residues in fine-tuning the interaction between AtSARK and SSPP are discussed herein.     

蛋清蛋白、大豆分离蛋白及其美拉德反应产物膜包裹对核桃仁脂质过氧化作用的比较研究

本文通过测定核桃油酸价、过氧化值、丙二醛含量、碘值和DPPH自由基清除率五个指标的变化研究比较蛋清蛋白膜、大豆分离蛋白膜及其与木糖美拉德反应产物膜包裹对核桃仁脂质过氧化的影响。结果表明,随着反应时间（0⁸d）的增加,核桃仁酸价、过氧化值和丙二醛含量均呈现上升趋势,DPPH自由基清除率均呈现下降趋势,而碘值则变化不明显。加热第8d时,四种膜包裹核桃仁的酸价、过氧化值和丙二醛含量均小于未包膜的核桃仁,DPPH自由基清除率高于未包膜的核桃仁。四种膜包裹核桃仁的酸价无显著性差异（p>0.05）;而过氧化值中以蛋清蛋白膜组较高,且其余三组的无显著性差异（p>0.05）;四种膜包裹核桃仁的丙二醛含量均明显低于未包膜组,延缓丙二醛含量上升的效果依次为:大豆分离蛋白-木糖膜>蛋清蛋白-木糖膜>大豆分离蛋白膜>蛋清蛋白膜;大豆分离蛋白-木糖膜包裹核桃仁保留的DPPH自由基清除率明显高于其它三种膜。综上所述,两种蛋白及其美拉德反应产物膜包裹均可延缓核桃仁脂质过氧化,综合各项指标其效果依次为:大豆分离蛋白-木糖膜>蛋清蛋白-木糖膜>大豆分离蛋白膜>蛋清蛋白膜。      

萌芽黑豆中蛋白质组分分子量分布及其抗氧化活性研究

本文目的是研究萌芽黑豆中不同蛋白质组分的分子量分布,以及各组分的抗氧化活性。采用碱提酸沉法获得萌芽黑豆中的蛋白质,通过硫酸铵盐析法逐级分离各蛋白质组分,SDS-PAGE法测定各蛋白质组分分子量分布,并从清除自由基和抗人皮肤成纤维细胞氧化损伤两个方面研究了各蛋白质组分的抗氧化活性。萌芽黑豆中蛋白质组分可以集中分离为三个部分,其分子量分布为140.0¹66.0、45.0⁷2.0、17.0²3.0ku;清除自由基和抗人皮肤成纤维细胞氧化损伤的实验结果均表明分子量在17.0²3.0ku的蛋白质组分具有最优的抗氧化活性,说明低分子量的萌芽黑豆蛋白质具有更强的抗氧化活性。      

卷烟及烟草薄片原料、半成品、成品的成分对比研究

对比分析了卷烟、烟草薄片原料、半成品、成品中的还原糖、可溶性糖、淀粉和蛋白质等物质,寻找烟草薄片工艺改进方向。分别采用经典的DNS法对上述样品中的还原糖、可溶性糖、淀粉等成分进行定量分析,采用国家标准GB5009.5-2010对其中蛋白质进行定量分析。同一样品平行性较好,四种成分在卷烟、烟梗、烟末、木纤维、片基、未烤薄片、薄片中含量有明显差别。结果表明,水溶性成分在薄片加工过程中损失率加大。与卷烟相比,薄片原料及半成品、成品中的淀粉、蛋白质等不良组分含量较低。      

响应面法优化齐口裂腹鱼肉蛋白酶解工艺的研究

以齐口裂腹鱼肉为原料,采用不同蛋白酶水解鱼肉蛋白,筛选出最佳水解用酶为动物蛋白水解酶。在单因素实验基础上,根据Box-Benhnken中心组合实验设计原理,选择对实验结果影响较大的四个因素（水解时间、水解温度、加酶量、料液比）做响应面优化实验,以齐口裂腹鱼肉的水解度为响应值建立数学模型,依据回归分析各因素的影响和交互作用,得出齐口裂腹鱼肉水解最佳工艺条件为:水解时间为4.5h,水解温度为54℃,加酶量为5080U/g,料液比为1∶3.2（g/mL）,pH为8.0,在此条件下做验证实验,得到水解度为13.67%,与理论预测值13.33%相比,其相对误差约为2.55%。响应面法优化齐口裂腹鱼肉水解工艺能为实践提供一定的指导意义。      

不同大豆原料形成蛋白纤维聚合物的比较

4种通过不同加工处理得到的大豆蛋白,在低pH条件下90℃加热10h所形成的聚合物形态存在很大不同。利用硫磺素T（Th T）荧光强度、差量扫描仪（DSC）和SDS-PAGE凝胶电泳分析了来自不同原料大豆蛋白的聚合动力学和组成差异。结果表明,4种大豆原料因其加工工艺不同,蛋白质组成存在差异,在本实验的条件下,11S的存在尤其是碱性亚基会抑制纤维聚合物的形成。此外,离子强度也是纤维形成的一个必要条件。