Human IRP1 Translocates to the Nucleus in a Cell-Specific and Iron-Dependent Manner

Iron regulatory protein 1 (IRP1) is a bifunctional protein with mutually exclusive RNA-binding or enzymatic activities that depend on the presence of a 4Fe-4S cluster. While IRP1 is a well-established cytosolic protein, work in a Drosophila model suggested that it may also exhibit nuclear localization. Herein, we addressed whether mammalian IRP1 can likewise translocate to the nucleus. We utilized primary cells and tissues from wild type and Irp1^−/− mice, as well as human cell lines and tissue biopsy sections. IRP1 subcellular localization was analyzed by Western blotting, immunofluorescence and immunohistochemistry. We did not detect presence of nuclear IRP1 in wild type mouse embryonic fibroblasts (MEFs), primary hepatocytes or whole mouse liver. However, we observed IRP1-positive nuclei in human liver but not ovary sections. Biochemical fractionation studies revealed presence of IRP1 in the nucleus of human Huh7 and HepG2 hepatoma cells, but not HeLa cervical cancer cells. Importantly, nuclear IRP1 was only evident in iron-replete cells and disappeared following pharmacological iron chelation. These data provide the first experimental evidence for nuclear IRP1 expression in mammals, which appears to be species- and cell-specific. Furthermore, they suggest that the nuclear translocation of IRP1 is mediated by an iron-dependent mechanism.     

Methotrexate-Induced Liver Injury Is Associated with Oxidative Stress,Impaired Mitochondrial Respiration,and Endoplasmic Reticulum Stress In Vitro

Low-dose methotrexate (MTX) is a standard therapy for rheumatoid arthritis due to its low cost and efficacy. Despite these benefits, MTX has been reported to cause chronic drug-induced liver injury, namely liver fibrosis. The hallmark of liver fibrosis is excessive scarring of liver tissue, triggered by hepatocellular injury and subsequent activation of hepatic stellate cells (HSCs). However, little is known about the precise mechanisms through which MTX causes hepatocellular damage and activates HSCs. Here, we investigated the mechanisms leading to hepatocyte injury in HepaRG and used immortalized stellate cells (hTERT-HSC) to elucidate the mechanisms leading to HSC activation by exposing mono- and co-cultures of HepaRG and hTERT-HSC to MTX. The results showed that at least two mechanisms are involved in MTX-induced toxicity in HepaRG: (i) oxidative stress through depletion of glutathione (GSH) and (ii) impairment of cellular respiration in a GSH-independent manner. Furthermore, we measured increased levels of endoplasmic reticulum (ER) stress in activated HSC following MTX treatment. In conclusion, we established a human-relevant in vitro model to gain mechanistical insights into MTX-induced hepatotoxicity, linked oxidative stress in HepaRG to a GSH-dependent and -independent pathway, and hypothesize that not only oxidative stress in hepatocytes but also ER stress in HSCs contribute to MTX-induced activation of HSCs.     

The interaction mechanism between microorganisms and substrate in the biodegradation of polycaprolactone

The present work concerns the interplay of the degradation mechanism and the nature of the interaction between microorganisms and substrate. The biodegradation of polycaprolactone films by a pure strain of microorganisms isolated from an industrial composting unit for household refuse was studied in minimal medium with the polymer as sole carbon source. In conditions where the polymer surface is colonized and a biofilm is formed (under a low stirring rate), polymer weight loss is limited, whereas total degradation is observed when stirring conditions prevent biofilm formation. In the first case, holes are observed in the degraded film and a polysaccharide responsible for microorganism adhesion was identified by FTIR. SEM observation of the polymer surface as a function of the degradation time suggests that the crystalline and amorphous phase are degraded at about the same rate in the first case, whereas the amorphous phase is preferentially degraded in the latter. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 1334–1340, 2002     

Characterization of aqueous micellar solutions of amphiphilic block copolymers of poly(acrylic acid) and polystyrene prepared via ATRP. Toward the control of the number of particles in emulsion polymerization

A series of diblock, triblock and star-block copolymers composed of polystyrene and poly(acrylic acid) were synthesized by ATRP. The structure of the copolymers, the size of the blocks and the composition were varied, keeping however a short polystyrene block and a poly(acrylic acid) content larger than 60 mol% to allow solubility in alkaline water. Their micellization was studied by static and dynamic light scattering and the influence of their structural characteristics on the aggregation number, N_agg, was examined at low salt concentration and alkaline pH. It was shown that micelles were in thermodynamic equilibrium and that N_agg followed the power law N_agg∼N_A^−0.9N_S² (with N_A, the total number of acrylic acid units in the copolymer and N_S, the total number of styrene units), that is characteristic of amphiphile micelles formed from strongly segregated block copolymers. Moreover, N_agg was independent of salt concentration in the investigated range. The same copolymers were previously used as stabilizers in emulsion polymerization [Macromolecules 34 (2001) 4439]. The final latex particle concentration, N_p, was compared with N_m, the initial micelle concentration. This enabled us to conclude that among the block copolymers studied, those with high acid content behaved like low molar mass surfactants. In contrast, those with low acid content formed stable micelles that could be directly nucleated to create latex particles, allowing a good control over N_p.     

Influence of water content of the pulp on the extraction and the physicochemical properties of Canarium schweinfurthii oil

With the aim of contributing to the valorization of the Canarium schweinfurthii Engl. fruit pulp, through the extraction of its oil, we have studied the influence of the Canarium pulp's water content after drying at 45 °C on the yield of extraction using hexane. Furthermore we studied the physicochemical properties of the oil. It was observed that the oil's extraction yield is significantly influenced (p <0.01) by water content of the pulp. Maximum extraction yield (30.6 g fat/100 g) is obtained at a moisture content of 6.3%. The acid, saponification and peroxide values of the oils obtained were significantly influenced (p <0.05) by the humidity. The maximum acid values of 8.88 corresponded to a moisture content of 17.5%. Likewise, the saponification value showed a maximum of 154.1 for humidity content of 43.3% at the beginning of the drying step. The pulp oil's peroxide value initially at 3.7 meqO₂/kg increased progressively until attaining 51.0 O₂/kg at the end of drying. The iodine value was not influenced by humidity. A moisture content of 7.7% has been determined as the optimal value for optimizing both oil extraction yield and physicochemical property of the oil obtained.     

便携式医疗设备中的信号调整

现今的医疗便携设备方便病人自行诊疗、自由走动,甚至可在外出时使用设备。便携式电子医疗设备要实现方便携带的特色功能,就必须具备微型化和低功耗的特性。此外,这些设备还要有极高的精度以确保病人的安全。医疗设备采用多种不同的传感器来监视病人的健康状况,然后传感器将生理信号转换成电子信号供电子设备分析使用。由于医疗设备中传输的信号都比较微弱,而且还会受到诸多     

Comparison between microwave hydrodiffusion and pressing for plum juice extraction

Microwave (MW) hydrodiffusion and gravity, a process initially developed for extraction of phytonutrients, can be adapted for production of an organoleptically pleasant juice, which is compared here with classically extracted juice.Clear and cloudy juices were produced from plums cv. ‘Najbolia’ by enzymatic treatment and pressing. Juice yield were 550 g kg^?1 for clear juice, from 670 to 684 g kg^?1 for cloudy juice with or without ascorbic acid (AA), and from 344 to 461 g kg^?1 for MW juice.MW juice was richest in procyanidins (334 mg kg^?1) while the cloudy juice and clear juice with AA were richest in anthocyans (80 and 90 mg kg^?1 respectively), and phenolic acids (from 450 to 510 mg kg^?1 respectively).The MW process was clearly more rapid and simpler, though yields were lower. This process could be an alternative to produce fruit juice where professionals of juice are confronted to extraction problem.