RESUMEN
Transcriptionally controlled tumor protein (TCTP) is a highly conserved protein performing a large number of cellular functions by binding with various partner proteins. The importance of its roles in many diseases requires an assay method to find regulatory compounds. However, the molecular characteristics of TCTP made it difficult to search for chemicals interacting with it. In this study, a tryptophan-based assay method was designed and Y151W mutant TCTP was constructed to search binding chemicals. Since there is no tryptophan in the native sequence of TCTP, the incorporation of tryptophan in the Y151W mutant was very effective to establish the method. A flavonoid library was employed to the assay with the method. With the native and Y151W mutant TCTPs, three flavonoids such as morin, myricetin and isobavachalcone have been found to interact with TCTP. Combined with native gel electrophoresis, the binding region of isobavachalcone was suggested to be the flexible loop of TCTP. This approach can be easily applicable to find binding compounds of proteins with similar molecular characteristics of TCTP.
Asunto(s)
Neoplasias , Triptófano , Humanos , Biomarcadores de Tumor/metabolismo , Proteína Tumoral Controlada Traslacionalmente 1 , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismoRESUMEN
Various shipping emissions controls have recently been implemented at both local and national scales. However, it is difficult to track the effect of these on PM2.5 levels, owing to the non-linear relationship that exists between changes in precursor emissions and PM components. Positive Matrix Factorisation (PMF) identifies that a switch to cleaner fuels since January 2020 results in considerable reductions in shipping-source-related PM2.5, especially sulphate aerosols and metals (V and Ni), not only at a port site but also at an urban background site. CMAQ sensitivity analysis reveals that the reduction of secondary inorganic aerosols (SIA) further extends to inland areas downwind from ports. In addition, mitigation of secondary organic aerosols (SOA) in coastal urban areas can be anticipated either from the results of receptor modelling or from CMAQ simulations. The results in this study show the possibility of obtaining human health benefits in coastal cities through shipping emission controls.
RESUMEN
Translationally controlled tumor protein (TCTP), a highly conserved protein present in most eukaryotes, is involved in numerous biological processes. Only the dimeric form of TCTP (dTCTP) formed during inflammatory conditions exhibits cytokine-like activity. Therefore, dTCTP is considered as a therapeutic target for allergic diseases. Because monomeric TCTP (mTCTP) and dTCTP share a high topological similarity, we hypothesized that small molecules interacting with mTCTP would also bind to dTCTP and interfere with dTCTP-based cellular processes. In this study, nine compounds listed in the literature as interacting with mTCTP were investigated for their ability to suppress the activity of extracellular dTCTP in bronchial epithelial cells. It was found that one of the nine, meclizine, a piperazine-derivative antihistamine, significantly reduced IL-8 release and suppressed the NF-κB pathway. The direct interaction of meclizine with dTCTP was confirmed by surface plasmon resonance (SPR). Also, we found that meclizine can attenuate ovalbumin (OVA)-induced airway inflammation in mice. Therefore, meclizine might be a potential anti-allergic drug as an inhibitor for dTCTP.
Asunto(s)
Hipersensibilidad , Proteína Tumoral Controlada Traslacionalmente 1 , Ratones , Animales , Piperazina/farmacología , Meclizina/uso terapéutico , Biomarcadores de Tumor/metabolismo , Hipersensibilidad/tratamiento farmacológico , Modelos Animales de Enfermedad , Ovalbúmina , Antagonistas de los Receptores Histamínicos/uso terapéutico , Ratones Endogámicos BALB CRESUMEN
BACKGROUND/OBJECTIVES: Translationally controlled tumor protein (TCTP) exhibits numerous biological functions. It has been shown to be involved in the regulation of glucose. However, its specific role in metabolism has not yet been clearly elucidated. Here, we aimed to assess the effect of TCTP overexpression on metabolic tissues and systemic energy metabolism. SUBJECTS/METHODS: We investigated whether TCTP can ameliorate the metabolic imbalance that causes obesity using TCTP-overexpressing transgenic (TCTP TG) mice. The mice were subjected to biochemical, morphological, physiological and protein expression studies to define the role of TCTP in metabolic regulation in response to normal chow diet (NCD) compared to high-fat diet (HFD) conditions, and cold environment. RESULTS: We found that TCTP TG mice show improved metabolic homeostasis under both of NCD and HFD conditions with simultaneous enhancements in glucose tolerance and insulin sensitivity. In particular, we found coincident increases in energy expenditure with significant upregulation of uncoupling protein 1 (UCP1) in the brown adipose tissue (BAT). Moreover, TCTP overexpressing mice exhibit significantly enhanced adaptive thermogenesis of BAT in response to cold exposure. CONCLUSIONS: Overexpression of TCTP ameliorated systemic metabolic homeostasis by stimulating UCP1-mediated thermogenesis in the BAT. This suggests that TCTP may function as a modulator of energy expenditure. This study suggests TCTP may serve as a therapeutic target for obesity and obesity-associated metabolic disorders including type 2 diabetes.
Asunto(s)
Metabolismo Energético/genética , Obesidad/metabolismo , Proteína Tumoral Controlada Traslacionalmente 1/genética , Animales , Dieta Alta en Grasa , Resistencia a la Insulina/genética , Ratones , Ratones Transgénicos , Obesidad/fisiopatología , Termogénesis/genéticaRESUMEN
Translationally controlled tumor protein (TCTP) is highly conserved in eukaryotic organisms and plays multiple roles regulating cellular growth and homeostasis. Because of its anti-apoptotic activity and its role in the regulation of cancer metastasis, TCTP has become a promising target for cancer therapy. Moreover, growing evidence points to its clinical role in cancer prognosis. How TCTP regulates cellular growth in cancer has been widely studied, but how it regulates cellular homeostasis has received relatively little attention. This review discusses how TCTP is related to cancer and its potential as a target in cancer therapeutics, including its novel role in the regulation of autophagy. Regulation of autophagy is essential for cell recycling and scavenging cellular materials to sustain cell survival under the metabolic stress that cancer cells undergo during their aggressive proliferation.
Asunto(s)
Autofagia , Biomarcadores de Tumor/metabolismo , Carcinogénesis/metabolismo , Carcinogénesis/patología , Animales , Homeostasis , Humanos , Modelos Biológicos , Neoplasias/patología , Neoplasias/terapia , Proteína Tumoral Controlada Traslacionalmente 1RESUMEN
Long-term atmospheric measurement of 17 total (gaseous and particulate) polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) has been made from 2007 to 2016â¯at five industrial and urban sites in Busan, South Korea, based on their persistence, bioaccumulation, and toxicity. In the present study, two pooled datasets covering a combination of 2 industry sites and 3 urban sites have been subjected to positive matrix factorization (PMF) to identify and quantify the major sources of PCDD/Fs. Additionally, PMF has been applied to the industrial urban dataset consisting of both polycyclic aromatic hydrocarbons (PAHs) and PCDD/Fs. The results show that the sum of PCDD/F mass (Σ17PCDD/Fs) at the industrial sites is determined by five major sources: non-ferrous metal production (33.7%), diesel vehicle emissions (30.2%), ferrous metal production (22.4%), other industrial emissions (11.1%), and traffic emissions (2.6%), while the PAH mass (Σ16PAHs) is predominantly associated with emissions from coal combustion, followed by traffic emissions. At the urban sites, the largest contribution to the Σ17PCDD/Fs was observed from transported emissions being emitted from metallurgical industry (75.5%), followed by diesel vehicle emissions (24.5%). The application of congener-specific toxicity to PCDD/F mass (Σ17fg I-TEQ Sm-3) indicates enhanced contributions from the ferrous metallurgical emission factor associated with penta- and hexa-chlorinated furans across the study sites.
Asunto(s)
Contaminantes Atmosféricos/análisis , Dibenzofuranos Policlorados/análisis , Monitoreo del Ambiente/métodos , Industrias , Dibenzodioxinas Policloradas/análisis , Carbón Mineral/efectos adversos , República de Corea , Urbanización , Emisiones de VehículosRESUMEN
Thermoelectric generators (TEGs) fabricated using additive manufacturing methods are attractive because they offer the advantages of scalability, lower cost, and potentially higher power density than conventional TEGs. Additive manufacturing of TEGs requires active thermoelectric particles to be dispersed in a polymer binder to synthesize printable slurries, and printed films to be subsequently subjected to a long and high temperature curing to enhance their thermoelectic properties. A large amount of polymer binder present in composite films results in a sizable loss in the electrical conductivity. In addition, a long and high-temperature film curing results is a slow and energy intensive fabrication process. In this work, we demonstrate the feasibility of using a small amount (≤10-3 wt ratio) of novel nanofiber cellulose (NFC) as a binder to provide sufficient adhesion strength to hold the TE particles together in the composite films. We also demonstrate a pressure induced densification process to enhance the thermoelectic properties of printed composite films. This novel approach has the potential to fundamentally transform the manufacting method for printing TEGs by eliminating the need of long-duration and high-temperature curing. A higher applied pressure leads to a compact packing and densification of films resulting in an improvement in the electrical conductivity. The highest power factor achieved for best performing p-type thermoelectric-NFC composite film subjected to pressure induced densification is 611 µW/m-K2.
RESUMEN
Magnéli phase titanium oxides (MPTOs), possess high electrical conductivity and chemical stability, are promising support materials for the development of novel electrocatalyst in polymer electrolyte fuel cells (PEFCs). Despite MPTO's extremely low specific surface area (1 m2/g or less), high Pt loading (40 wt%) and excellent Pt particle-size distribution were obtained by the modified borohydride method. The reasons were discussed and compared with polyol method. Membrane electrode assembly (MEA) performance of those Pt/MPTO catalysts were found to be 169.7 and 366.2 mA/cm2 at 0.7 V for H2/air and H2/O2, respectively. The accelerated stress tests (ASTs) showed superior durability of the Pt/MPTO catalyst as a cathode electrode. After 10,000 cycles of high-voltage cycling test from 0.9 V and 1.3 V RHE, no significant performance degradation of the Pt/MPTO electrode was observed comparing with Pt/C. Thus, MPTOs can be considered as a good substitute of carbon supports in fuel cells.
RESUMEN
Measurements of 14 polycyclic aromatic hydrocarbons (PAH) have been made in Jeddah, Saudi Arabia, with a view to establishing the concentrations in this major city, and quantifying the contributions of major sources. Particulate and vapour forms have been sampled and analysed separately. The concentrations are compared to measurements from other sites in the Middle Eastern region and are towards the lower end of the range, being far lower than concentrations reported from Riyadh (Saudi Arabia), Assiut (Egypt) and Tehran (Iran) but broadly similar to those measured in Damascus (Syria) and higher than those measured in Kuwait. The partitioning between vapour and particle phases is similar to that in data from Egypt and China, but with many compounds showing a higher particle-associated percentage than in Birmingham (UK) possibly reflecting a higher concentration of airborne particulate matter in the former countries. Concentrations in Jeddah were significantly higher at a site close to the oil refinery and a site close to a major ring road than at a suburban site to the north of the city. Application of positive matrix factorisation to the pooled data elicited three factors accounting respectively for 17%, 33% and 50% of the measured sum of PAH and these are interpreted as arising from gasoline vehicles, industrial sources, particularly the oil refinery, and to diesel/fuel oil combustion.