白癜风患者皮肤成纤维细胞铜含量的变化

对2例白癜风患者皮损区、周围区的皮肤成纤维细胞进行培养,以阳极溶出伏安法进行铜含量测定。皮损区的细胞铜含量低于周围区,与对照组比较铜含量低于或在均值范围内。白癜风并非铜的缺少而引起,因此用铜治疗无效。皮肤成纤维细胞中铜含量的变化可能与控制铜代谢的基因异常有关。     

Copper-carbohydrate interaction in maternal, fetal and neonate rat

The present study was undertaken to determine whether the same type of interaction between dietary fructose and copper that affects young growing male rats also affects the fetus and the neonate. Female rats were fed copper-deficient (0.6 μg Cu/g) or adequate (6.0 μg/g) diets containing 62% carbohydrate as fructose or starch either for 8 weeks prior to conception, and during mating, gestation and lactation, or just during gestation. Fetuses were killed at days 14, 18 or 21 of gestation and newborn pups were killed at days 0, 10, or 21 postpartum. Regardless of the duration of dietary copper deprivation, feeding the fructose diet deficient in copper during pregnancy resulted in either fetal resorption or mortality of all newborn pups during the first few hours postpartum. In contrast, copper-deficient rats fed the starch-containing diets delivered live pups. However, 40% of their pups died during the first 2 days postpartum and occurred only when dams had been fed the deficient diet for 12–13 weeks. When fed the deficient diet for a total of 3 weeks only, during pregnancy, all copper-deficient rats fed starch delivered live pups and no mortality occurred during the lactation period. Feeding the copper-adequate fructose diet during lactation resulted in a lower hepatic copper concentration of suckling pups compared with starch feeding. Female pups had higher levels of copper and iron than male pups. The data show that fetal resorption and mortality of the neonate pup was dependent on the type of dietary carbohydrate fed to copper-deficient animals during pregnancy.     

Dysregulated copper transport in multiple sclerosis may cause demyelination via astrocytes

Demyelination is a key pathogenic feature of multiple sclerosis (MS). Here, we evaluated the astrocyte contribution to myelin loss and focused on the neurotrophin receptor TrkB, whose up-regulation on the astrocyte finely demarcated chronic demyelinated areas in MS and was paralleled by neurotrophin loss. Mice lacking astrocyte TrkB were resistant to demyelination induced by autoimmune or toxic insults, demonstrating that TrkB signaling in astrocytes fostered oligodendrocyte damage. In vitro and ex vivo approaches highlighted that astrocyte TrkB supported scar formation and glia proliferation even in the absence of neurotrophin binding, indicating TrkB transactivation in response to inflammatory or toxic mediators. Notably, our neuropathological studies demonstrated copper dysregulation in MS and model lesions and TrkB-dependent expression of copper transporter (CTR1) on glia cells during neuroinflammation. In vitro experiments evidenced that TrkB was critical for the generation of glial intracellular calcium flux and CTR1 up-regulation induced by stimuli distinct from neurotrophins. These events led to copper uptake and release by the astrocyte, and in turn resulted in oligodendrocyte loss. Collectively, these data demonstrate a pathogenic demyelination mechanism via the astrocyte release of copper and open up the possibility of restoring copper homeostasis in the white matter as a therapeutic target in MS.

Astrocytes are the largest population of glial cells in the central nervous system (CNS) and are essential for brain homeostasis as they provide metabolites and growth factors to neurons, support synapse formation and plasticity, contribute to the blood brain barrier (BBB) structure and function, and support myelination (1, 2). Following CNS injury they undergo molecular and functional changes, which foster acquisition of an inflammatory phenotype, migration toward damaged areas, and proliferation and organization into the scar (1). These events are fundamental for tissue repair but bear the potential of hindering damage resolution if dysregulated under pathologic conditions (3). Multiple sclerosis (MS) is a chronic inflammatory disorder of the CNS characterized by demyelination, inflammation, and neuroaxonal damage (4). While active MS plaques are rich in infiltrating immune cells, activated microglia and macrophages throughout the partially demyelinated astrogliotic lesion, chronic inactive MS plaques lack T cell infiltration and are fully demyelinated sites with sharply demarcated borders, very low myeloid cell numbers, severe axonal injury, and dense astrocytic scars (5, 6). In vivo studies with transgenic animals have highlighted detrimental vs. protective signaling perturbations in astrocytes during CNS neuroinflammation (3), but the precise causal mechanisms linking the target to distinct neuropathological outcomes (e.g., immune cell infiltration, neurodegeneration, or demyelination) remain mostly ill-defined. For example, the neurotrophin receptor TrkB is up-regulated on astrocytes in chronic inactive MS lesions, where it promotes neurodegeneration via glial production of nitric oxide (NO) (7); however no information is available about the impact of TrkB signaling in astrocytes during demyelination. Further, astrocytes are concomitantly exposed to diverse stimuli within the scar (3, 8) and can activate an intricate network of intracellular events, with a net result remaining difficult to predict until relevant molecular and functional checkpoints are identified.Here, we describe a demyelination mechanism resulting from astrocyte-dependent copper redistribution in the white matter of MS patients and experimental models of MS. The relevant molecular checkpoint in astrocytes is TrkB, which can operate downstream of inflammatory or toxic insults, even in the absence of neurotrophin binding, and trigger astrocytosis and copper uptake and release following injury.     

Investigations on Melt Flow Rate and Tensile Behaviour of Single,Double and Triple-Sized Copper Reinforced Thermoplastic Composites

Thermoplastic composite materials are emerging rapidly due to the flexibility of attaining customized mechanical and melt flow properties. Due to high ductility, toughness, recyclability, and thermal and electrical conductivity, there is ample scope of using copper particles in thermoplastics for 3d printing applications. In the present study, an attempt was made to investigate the Melt Flow Index (MFI), tensile strength, and electrical and thermal conductivity of nylon 6 and ABS (acrylonitrile butadiene styrene) thermoplastics reinforced with copper particles. Thus, the experiments were conducted by adding different-sized copper particles (100 mesh, 200 mesh, and 400 mesh) in variable compositions (0% to 10%) to ABS and nylon 6 matrix. The impact of single, double, and triple particle-sized copper particles on MFI was experimentally investigated followed by FTIR and SEM analysis. Also, the tensile, electrical, and thermal conductivity testing were done on filament made by different compositions. In general, higher fluidity and mechanical strength were obtained while using smaller particles even with higher concentrations (up to 8%) due to improved bonding strength and adhesion between the molecular chains. Moreover, thermal and electrical conductivity was improved with an increase in concentration of copper particles.     

泡沫铜负载氧化铜/钴锰氢氧化物复合纳米线阵列的制备及其电化学性能

以泡沫铜为基体,采用简单的热氧化和恒压电沉积两步法在基体表面生长分级结构的氧化铜（Cu_xO）/钴锰层状双金属氢氧化物（Co-Mn LDH）复合纳米线阵列。对制得的复合材料的结构及形貌进行了表征,并研究了其电化学性能。结果表明：在泡沫铜基体上生长了长度约为5~10 μm,直径约为50 nm的纳米线阵列。复合纳米线阵列作为超级电容器电极材料在1 A/g的电流密度下,其比电容达305.0 F/g;当电流密度增大至10 A/g时,比电容保持率仍达到70.7%。在1 A/g的电流密度下,复合电极材料经2 000次充放电循环后,仍有80.4%的比电容保持率。     

银屑病患者血清铜蓝蛋白和铜水平

本文测定了70例寻常性银屑病(PV)患者和30例正常人血清铜蓝蛋白(CP)和铜(Cu)水平。结果发现患者血清CP和Cu水平均高于正常人,差异显著。两指标增高程度与疾病活动和严重性有关,而与病程长短无关。     

Cellular distribution of copper to superoxide dismutase involves scaffolding by membranes

Efficient delivery of copper ions to specific intracellular targets requires copper chaperones that acquire metal cargo through unknown mechanisms. Here we demonstrate that the human and yeast copper chaperones (CCS) for superoxide dismutase 1 (SOD1), long thought to exclusively reside in the cytosol and mitochondrial intermembrane space, can engage negatively charged bilayers through a positively charged lipid-binding interface. The significance of this membrane-binding interface is established through SOD1 activity and genetic complementation studies in Saccharomyces cerevisiae, showing that recruitment of CCS to the membrane is required for activation of SOD1. Moreover, we show that a CCS:SOD1 complex binds to bilayers in vitro and that CCS can interact with human high affinity copper transporter 1. Shifting current paradigms, we propose that CCS-dependent copper acquisition and distribution largely occur at membrane interfaces and that this emerging role of the bilayer may reflect a general mechanistic aspect of cellular transition metal ion acquisition.Although often neglected, the powerful and flexible redox and coordination chemistries of copper ions play pivotal roles in cellular processes such as respiration, iron transport, and antioxidant defense (1–3). Although essential for life, the same chemical properties pose threats to cellular functions because if uncontrolled, copper ions can participate in Fenton chemistry and catalyze the production of reactive oxygen species (ROS), which can cause cellular damage and cell death (4–6). In response to this threat, eukaryotic cells have developed complex regulatory mechanisms to tightly control copper metabolism and homeostasis (7, 8). Not surprisingly, breakdowns in copper homeostasis have been associated with several human diseases, most notably Wilson disease, Menkes disease, Parkinson, Alzheimer’s, and familial amyotrophic lateral sclerosis (9–13). The correlation of devastating diseases with defects in copper transport and distribution emphasize the importance of mechanistic studies aimed at understanding the molecular basis of copper homeostasis.During the last 20 y, genetic and molecular approaches revealed a multilayered system of protein components that regulate every aspect of copper movement through the body, including copper transport across membranes and copper distribution within cells. Related to copper distribution, three small proteins known as antioxidant 1 copper chaperone (ATOX1), CCS, and cytochrome c oxidase copper chaperone 17 (COX17) have been identified that, in eukaryotic cells, serve to sequester the chemical reactivity of copper ions and to facilitate their delivery to specific downstream processes via direct protein–protein interactions (14, 15). Mechanistic understanding of how copper chaperones bind and transfer copper to intracellular targets has made great advances as a result of the emergence of high-resolution crystal structures and spectroscopic data (16). However, the question of how copper chaperones initially acquire their cargo has remained elusive because the cellular localization of the chaperones within the cytosol or mitochondrial intermembrane space did not provide clear prompts to guide mechanistic studies. Addressing this bottleneck, our studies were focused on the copper chaperone CCS, which delivers copper to superoxide dismutase 1 (SOD1), a Cu/Zn-containing antioxidant enzyme that converts radical superoxide to molecular oxygen and hydrogen peroxide (17). Here we describe the surprising finding that cellular membranes play an important role in initial copper acquisition by CCS. The idea that the bilayer represents a functional component in the CCS-dependent pathway of copper trafficking challenges existing mechanistic models for cellular copper acquisition, and may have further implications for other metal transport mechanisms used by eukaryotic cells.     

含铜抗菌不锈钢的抗菌机制及其应用

在不锈钢生产过程中,通过特殊的处理工艺,添加一定含量的抗菌金属元素铜,可以赋予不锈钢的抗菌性能。因为这些铜元素在一定的温、湿度条件下,在接触细菌后可对其产生毒杀作用。因此,含铜抗菌不锈钢可在保持普通不锈钢的抗腐蚀性能和机械加工性能的同时,还具有抗细菌微生物性能。本文综述了含铜不锈钢的抗菌机制、抗菌模式、抗菌效能的影响因素及其应用前景。     

PEP-1-SOD1融合蛋白抑制血管紧张素Ⅱ诱导的大鼠心脏成纤维细胞Ⅰ型胶原的合成

目的研究穿透肽(PEP-1)介导的铜-锌超氧化物歧化酶1(SOD1)(PEP-1-SOD1)融合蛋白对血管紧张素Ⅱ(ANGⅡ)诱导的大鼠心脏成纤维细胞(CFbs)Ⅰ型胶原合成的影响,并探讨其机制。方法利用基因工程技术表达和纯化PEP-1-SOD1融合蛋白。提取原代大鼠CFbs并传代培养,采用2～5代细胞进行实验,实验分为对照组、ANGⅡ诱导组、SOD1预处理组和PEP-1-SOD1预处理组。SOD1预处理组和PEP-1-SOD1预处理组细胞分别以2μmol.L-1的SOD1和PEP-1-SOD1预处理2 h后,再给1μmol.L-1的ANGⅡ诱导24 h,用免疫荧光法检测细胞内超氧阴离子(O2-)水平,微量丙二醛(MDA)检测试剂盒检测各组细胞MDA含量。结果 Western blot和细胞免疫荧光结果显示PEP-1-SOD1成功穿透入CFbs;Western blot结果显示,与ANGⅡ诱导组比较,PEP-1-SOD1预处理组Ⅰ型胶原和α平滑肌肌动蛋白表达显著降低(P<0.01),细胞内O2-和MDA水平也显著降低(P<0.01)。结论 PEP-1-SOD1融合蛋白穿透入大鼠心脏CFbs内,通过降低细胞内O2-水平,抑制CFbs的激活,减少Ⅰ型胶原的合成。     

Serum copper and the risk of cardiovascular disease death in Finnish men

Background and aimsCopper (Cu) is a component of enzymes catalyzing oxidation-reduction reactions. With the persisting burden of cardiovascular disease (CVD), there is evident need to identify biomarkers and potential risk factors for CVD. We therefore examined the association between serum Cu levels and the risk of CVD death in Finnish men and across different body mass index (BMI) categories.Methods and resultsThis Finnish prospective study is based on 1911 men aged 42–60 years who were free of coronary heart disease at baseline. Cu concentrations (mg/l) were determined using atomic absorption spectrometer and categorized into quartiles (<1.0; 1 to <1.1; 1.1 to <1.21; ≥1.21). Participants were categorized into normal weight <25 kg/m², pre-obesity 25–29.9 kg/m², and obesity >30 kg/m². The association between Cu and CVD death was analyzed using multivariable Cox regression models. During a median follow-up of 25.8 years, 358 CVD deaths occurred. The risk of CVD death increased continuously with increasing Cu levels (for non-linearity, p = 0.64). Using the first quartile as reference after adjustment for covariates, the hazard ratios (HR) (95% confidence interval (CI)) for CVD death for Cu concentrations in second, third and fourth quartiles were 1.45(1.05–2.01), 1.69(1.25–2.27), and 1.68(1.23–2.29), respectively. Obese men in the third quartile of serum Cu concentrations had highest risk of CVD death (HR (95%CI) 2.71(1.27–5.78)).ConclusionElevated serum Cu level was associated with increased risk of CVD death across all BMI categories in middle-aged and older Finnish men. Serum Cu may have prognostic implication for CVD mortality risk; however, further studies are needed.