Activity

Therapeutic potential of metformin in obese/diabetic patients has been associated to its ability to combat insulin resistance. However, it remains largely unknown the signaling pathways involved and whether some cell types are particularly relevant for its beneficial effects. M1-activation of macrophages by bacterial lipopolysaccharide (LPS) promotes a paracrine activation of hypoxia-inducible factor-1α (HIF1α) in brown adipocytes which reduces insulin signaling and glucose uptake, as well as β-adrenergic sensitivity. Addition of metformin to M1-polarized macrophages blunted these signs of brown adipocyte dysfunction. At the molecular level, metformin inhibits an inflammatory program executed by HIF1α in macrophages by inducing its degradation through the inhibition of mitochondrial complex I activity, thereby reducing oxygen consumption in a reactive oxygen species (ROS)-independent manner. In obese mice, metformin reduced inflammatory features in brown adipose tissue (BAT) such as macrophage infiltration, proinflammatory signaling and gene expression, and restored the response to cold exposure. In conclusion, the impact of metformin on macrophages by suppressing a HIF1α-dependent proinflammatory program is likely responsible for a secondary beneficial effect on insulin-mediated glucose uptake and β-adrenergic responses in brown adipocytes.Ferroptosis is a form of regulated cell necrosis, as a consequence of Fe(II)-dependent lipid peroxidation. Although ferroptosis has been linked to cancer cell death, neurodegeneration and reperfusion injury, physiological roles of ferroptosis have not been elucidated to date mostly due to the lack of appropriate methodologies. Here, we show that 4-hydroxy-2-nonenal (HNE)-modified proteins detected by a HNEJ-1 mouse monoclonal antibody is a robust immunohistochemical technology to locate ferroptosis in tissues in combination with morphological nuclear information, based on various models of ferroptosis, including erastin-induced cysteine-deprivation, conditional Gpx4 knockout and Fe(II)-dependent renal tubular injury, as well as other types of regulated cell death. Specificity of HNEJ-1 with ferroptosis was endorsed by non-selective identification of HNE-modified proteins in an Fe(II)-dependent renal tubular injury model. We further comprehensively searched for signs of ferroptosis in different developmental stages of Fischer-344 rats from E9.5-2.5 years of age. We observed that there was a significant age-dependent increase in ferroptosis in the kidney, spleen, liver, ovary, uterus, cerebellum and bone marrow, which was accompanied by iron accumulation. Not only phagocytic cells but also parenchymal cells were affected. Epidermal ferroptosis in ageing SAMP8 mice was significantly promoted by high-fat or carbohydrate-restricted diets. During embryogenesis of Fischer-344 rats, we found ferroptosis in nucleated erythrocytes at E13.5, which disappeared in enucleated erythrocytes at E18.5. click here Administration of a ferroptosis inhibitor, liproxstatin-1, significantly delayed erythrocyte enucleation. Therefore, our results demonstrate for the first time the involvement of ferroptosis in physiological processes, such as embryonic erythropoiesis and aging, suggesting the evolutionally acquired mechanism and the inevitable side effects, respectively.The breast cancer 1 protein (BRCA1) facilitates DNA repair, preventing embryolethality and protecting the fetus from reactive oxygen species (ROS)-induced developmental disorders mediated by oxidatively damaged DNA. Alcohol (ethanol, EtOH) exposure during pregnancy causes fetal alcohol spectrum disorders (FASD), characterized by aberrant behaviour and enhanced ROS formation and proteasomal protein degradation. Herein, ROS-producing NADPH oxidase (NOX) activity was higher in Brca1 +/- vs. +/+ fetal and adult brains, and further enhanced by a single EtOH exposure. EtOH also enhanced catalase and proteasomal activities, while conversely reducing BRCA1 protein levels without affecting Brca1 gene expression. EtOH-initiated adaptive postnatal freezing behaviour was lost in Brca1 +/- progeny. Pretreatment with the free radical spin trap and ROS inhibitor phenylbutylnitrone blocked all EtOH effects, suggesting ROS-dependent mechanisms. This is the first in vivo evidence of NOX regulation by BRCA1, and of EtOH-induced, ROS-mediated depletion of BRCA1, revealing novel mechanisms of BRCA1 protection in FASD.Piezoelectric materials have received much attention due to their great potential in environmental remediation by utilizing vibrational energy. In this paper, a novel piezoelectric catalyst, CoOx nanoparticles anchored BiFeO3 nanodisk composite, was intentionally synthesized via a photodeposition method and applied in piezocatalytic degradation of rhodamine B (RhB) under ultrasonic vibration. The as-synthesized CoOx/BiFeO3 composite presents high piezocatalytic efficiency and stability. The RhB degradation rate is determined to be 1.29 h-1, which is 2.38 folds higher than that of pure BiFeO3. Via optimizing the reaction conditions, the piezocatalytic degradation rate of the CoOx/BiFeO3 can be further increased to 3.20 h-1. A thorough characterization was implemented to investigate the structure, piezoelectric property, and charge separation efficiency of the CoOx/BiFeO3 to reveal the nature behind the high piezocatalytic activity. It is found that the CoOx nanoparticles are tightly adhered and uniformly dispersed on the surface of the BiFeO3 nanodisks. Strong interaction between CoOx and BiFeO3 triggers the formation of a heterojunction structure, which further induces the migration of the piezoinduced holes on the BiFeO3 to CoOx nanoparticles. The recombination of electron-hole pairs is retarded, thereby increasing the piezocatalytic performance greatly. This work may offer a new paradigm for the design of high-efficiency piezoelectric catalysts.Caffeoylquinic acids are existed in many plant species with various biological and pharmacological activities. 3-O-caffeoylquinic acid and 4-O-caffeoylquinic acid are two isomers of caffeoylquinic acids, which may be degraded and transformed to their isomers in processing. The present paper found that the stability of 3- and 4-O-caffeoylquinic acid had decreased with the increasing solution alkalinity. 3-O-caffeoylquinic acid was more stable than 4-O-caffeoylquinic acid at the same condition. During degradation, 3- and 4-O-caffeoylquinic acid were partially converted to their isomers. Additionally, ultrasonic effects on the degradation and isomerization of 3- and 4-O-caffeoylquinic acid at different pH were studied. Ultrasound facilitated the degradation and isomerization of these compounds. The degradation kinetics were described by the Weibull equation. The protective effect of ascorbic acid and epigallocatechin gallate were also explored. Ascorbic acid and epigallocatechin gallate could alleviate the degradation of 3- and 4-O-caffeoylquinic acid under certain conditions.In this work casein (CN) was used as a carrier system for the hydrophobic agent α-tocopherol (α-TOC), and an amphiphilic self-assembling micellar nanostructure was formed with ultrasound treatment. The interaction mechanism was detected with UV-Vis spectroscopy, fluorescence spectroscopy, proton spectra, and Fourier transform infrared spectroscopy (FTIR). The stability of the nanoparticles was investigated by using typical processing and storage conditions (thermal, photo, 20 ± 2 °C and 4 ± 2 °C). Oil-in-water emulsions containing the self-assembled nanoparticles and grape seed oil were prepared, and the effect of emulsion oxidation stability was studied using the accelerated Rancimat method. The results indicated that the UV-Vis spectra of α-TOC/CN nanoparticles complexes were different for ultrasonic treatments performed with different combinations of power (100, 200, 300 W) and time (5, 10, and 15 min). The results of UV-Vis fluorescence spectrum data indicated that the secondary structure of casein changed in the presence of α-TOC. The nanoparticles exhibited the chemical shifts of conjugated double bonds. Interactions between α-TOC and casein at different molar concentrations resulted in a quenching of the intrinsic fluorescence at 280 nm and 295 nm. Moreover, by performing FTIR deconvolution analysis and multicomponent peak modeling, the relative quantitative amounts of α-helix and β-sheet protein secondary structures were determined. The self-assembled nanoparticles can improve the stability of α-TOC by protecting them against degradation caused by light and oxygen. The antioxidant activity of the nanoparticles was stronger than those of the two free samples. Lipid hydroperoxides remained at a low level throughout the course of the study in emulsions containing 200 mg α-TOC/kg oil with the nanoparticles. The presence of 100 and 200 mg α-TOC/kg oil led to a 78.54 and 63.54 μmol/L inhibition of TBARS formation with the nanoparticles, respectively, vs the free samples containing control after 180 mins.This study evaluated the application of ultrasound alone or combined with chlorine dioxide (ClO2) for Salmonella Typhimurium and Escherichia coli inactivation in poultry processing chiller tank water. A Full Factorial Design (FFD) 22 was conducted for each microorganism to evaluate the effect of ultrasound exposure time (x1 1 to 9 min; fixed 37 kHz; 330 W; 25 °C) using a bath, and ClO2 concentration (x2 1 to 17 mg L-1) on microorganism count expressed in log CFU mL-1 in distilled water. Variable x2 had a negative effect on Salmonella Typhimurium (-5.09) and Escherichia coli (-2.00) count, improving the inactivation; while a x1 increase present no inactivation improvement, explaining the use of x1 lower level (1 min) and x2 higher level (17 mg L-1). The best condition for microorganism inactivation based on FFD was evaluated in chiller tank water (with organic matter) at 25, 16, and 4 °C; x1 was kept (1 min), however x2 was adjusted to obtain the same residual free chlorine (2.38 mg L-1) considering the ClO2 consumption by organic matter, achieving the value of 30 mg L-1. An inactivation of 49% and 31% were observed for Salmonella Typhimurium and Escherichia coli. When ultrasound was replaced by a simple agitation in the presence of ClO2, there was no inactivation for both microorganisms. Moreover, at poultry carcass pre-chilling (16 °C) and chilling (4 °C) conditions, the synergism of ultrasound combined with ClO2 was more pronounced, with microorganisms’ reductions up to 100%.In an aim of developing portable biosensor for SARS-CoV-2 pandemic, which facilitates the point-of-care aptasensing, a strategy using 10 μm gap-sized gold interdigitated electrode (AuIDE) is presented. The silane-modified AuIDE surface was deposited with ∼20 nm diamond and enhanced the detection of SARS-CoV-2 nucleocapsid protein (NCP). The characteristics of chemically modified diamond were evidenced by structural analyses, revealing the cubic crystalline nature at (220) and (111) planes as observed by XRD. XPS analysis denotes a strong interaction of carbon element, composed ∼95% as seen in EDS analysis. The C-C, CC, CO, CN functional groups were well-refuted from XPS spectra of carbon and oxygen elements in diamond. The interrelation between elements through FTIR analysis indicates major intrinsic bondings at 2687-2031 cm-1. The aptasensing was evaluated through electrochemical impedance spectroscopy measurements, using NCP spiked human serum. With a good selectivity the lower detection limit was evidenced as 0.