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Hyperuricemic nephropathy (HN) is characterized by renal fibrosis and tubular necrosis caused by elevated uric acid levels. Ferroptosis, an iron-dependent type of cell death, has been implicated in the pathogenesis of kidney diseases. The objective of this study was to explore the role of ferroptosis in HN and the impact of a ferroptosis inhibitor, ferrostatin-1 (Fer-1). The study combined adenine and potassium oxonate administration to establish a HN model in mice and treated HK-2 cells with uric acid to simulate HN conditions. The effects of Fer-1 on the renal function, fibrosis, and ferroptosis-associated molecules were investigated in HN mice and HK-2 cells treated with uric acid. The HN mice presented with renal dysfunction characterized by elevated tissue iron levels and diminished antioxidant capacity. There was a significant decrease in the mRNA and protein expression levels of SLC7A11, GPX4, FTL-1 and FTH-1 in HN mice. Conversely, treatment with Fer-1 reduced serum uric acid, serum creatinine, and blood urea nitrogen, while increasing uric acid levels in urine. Fer-1 administration also ameliorated renal tubule dilatation and reduced renal collagen deposition. Additionally, Fer-1 also upregulated the expression levels of SLC7A11, GPX4, FTL-1, and FTH-1, decreased malondialdehyde and iron levels, and enhanced glutathione in vivo and in vitro. Furthermore, we first found that Fer-1 exhibited a dose-dependent inhibition of URAT1, with the IC50 value of 7.37 ± 0.66 µM. Collectively, the current study demonstrated that Fer-1 effectively mitigated HN by suppressing ferroptosis, highlighting the potential of targeting ferroptosis as a therapeutic strategy for HN.
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Ciclohexilaminas , Ferroptosis , Hiperuricemia , Enfermedades Renales , Fenilendiaminas , Ratones , Animales , Ácido Úrico , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/metabolismo , Enfermedades Renales/tratamiento farmacológico , Fibrosis , HierroRESUMEN
Recently, the lead-free piezoelectric material Bi0.5Na0.5TiO3 (BNT) has been adopted for piezo-catalysis and synergistic catalysis, such as piezo-photocatalysis. Nonetheless, the catalytic effect of single BNT is too weak to degrade multifarious contaminants. Here, BNT and multi-walled carbon nanotubes (MWCNTs) composite were prepared and the catalytic performance of BNT was prominently boosted by introducing MWCNTs as the electron capturer. Particularly, the degradation rate of Rhodamine B (RhB, a typical contaminant) could reach 90% within 30 min, with a high rate constant of 0.0805 min-1. The specific degradation pathway of RhB was analyzed. The formation of oxygen vacancies was confirmed by XPS analysis, and the vital role of oxygen vacancies in the separation of photo-generated carriers was elucidated. Meanwhile, the BNT/MWCNTs composites manifested stronger transient current response compared to single BNT under the action of light irradiation and ultrasonic vibration, respectively. According to impedance analysis, the composites exhibited lower carrier transport resistance. Eventually, the mechanism of enhanced piezo-photocatalysis was explained in detail. This study provides an effective route to break the shackle of carrier recombination and speed up the carrier transport in piezo-photocatalytic materials.
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Nanotubos de Carbono , Catálisis , Iones , Oxígeno , Rodaminas , SodioRESUMEN
BACKGROUNDCytochrome P450 family 8 subfamily B member 1 (CYP8B1) generates 12α-hydroxylated bile acids (BAs) that are associated with insulin resistance in humans.METHODSTo determine whether reduced CYP8B1 activity improves insulin sensitivity, we sequenced CYP8B1 in individuals without diabetes and identified carriers of complete loss-of-function (CLOF) mutations utilizing functional assays.RESULTSMutation carriers had lower plasma 12α-hydroxylated/non-12α-hydroxylated BA and cholic acid (CA)/chenodeoxycholic acid (CDCA) ratios compared with age-, sex-, and BMI-matched controls. During insulin clamps, hepatic glucose production was suppressed to a similar magnitude by insulin, but glucose infusion rates to maintain euglycemia were higher in mutation carriers, indicating increased peripheral insulin sensitivity. Consistently, a polymorphic CLOF CYP8B1 mutation associated with lower fasting insulin in the AMP-T2D-GENES study. Exposure of primary human muscle cells to mutation-carrier CA/CDCA ratios demonstrated increased FOXO1 activity, and upregulation of both insulin signaling and glucose uptake, which were mediated by increased CDCA. Inhibition of FOXO1 attenuated the CDCA-mediated increase in muscle insulin signaling and glucose uptake. We found that reduced CYP8B1 activity associates with increased insulin sensitivity in humans.CONCLUSIONOur findings suggest that increased circulatory CDCA due to reduced CYP8B1 activity increases skeletal muscle insulin sensitivity, contributing to increased whole-body insulin sensitization.FUNDINGBiomedical Research Council/National Medical Research Council of Singapore.
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Resistencia a la Insulina , Esteroide 12-alfa-Hidroxilasa , Humanos , Esteroide 12-alfa-Hidroxilasa/genética , Resistencia a la Insulina/genética , Insulina/genética , Haploinsuficiencia , Ácidos y Sales Biliares , Ácido Cólico , GlucosaRESUMEN
Prior experimental work showed that Bi2Se3, as a sister compound of the best room-temperature thermoelectric material Bi2Te3, has remarkably improved thermoelectric performance by Sb-Br codoping. But the relationship between its crystalline structure and thermoelectric properties is still unclear to date. Here, we use first-principles calculations to explore the possible reasons for such improvement. The electronic structures of Bi2-x Sb x (Se1-y Br y )3 (x = 0, 1, 2; y = 0, 0.08) are systematically investigated. Significant effects of 8% Br codoping in BiSbSe3 are found. First, the Br atom acts as an electron donor, thus greatly increasing the carrier concentration. Second, similar to the effect of Sb doping, Br codoping further improves greatly the degeneracy of the conduction band edge, which leads to a remarkably increased density-of-states effective mass without deterioration of the carrier mobility, and simultaneously preserves a large Seebeck coefficient of â¼-254 µV K-1 at 800 K. In addition, the Br codoping softens the chemical bonds, which enhances anharmonic scattering and further reduces the lattice thermal conductivity. We predict that the maximum zT of BiSb(Se0.92Br0.08)3 at 800 K can reach 0.96 with the carrier concentration of 9.22 × 1019 cm-3. This study rationalizes a potential strategy to improve the thermoelectric performance of Bi2Se3-based thermoelectric materials.
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Lipids are hydrophobic and amphiphilic molecules involved in diverse functions such as membrane structure, energy metabolism, immunity, and signaling. However, altered intra-cellular lipid levels or composition can lead to metabolic and inflammatory dysfunction, as well as lipotoxicity. Thus, intra-cellular lipid homeostasis is tightly regulated by multiple mechanisms. Since most peripheral cells do not catabolize cholesterol, efflux (extra-cellular transport) of cholesterol is vital for lipid homeostasis. Defective efflux contributes to atherosclerotic plaque development, impaired ß-cell insulin secretion, and neuropathology. Of these, defective lipid efflux in macrophages in the arterial walls leading to foam cell and atherosclerotic plaque formation has been the most well studied, likely because a leading global cause of death is cardiovascular disease. Circulating high density lipoprotein particles play critical roles as acceptors of effluxed cellular lipids, suggesting their importance in disease etiology. We review here mechanisms and pathways that modulate lipid efflux, the role of lipid efflux in disease etiology, and therapeutic options aimed at modulating this critical process.
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Enfermedades Cardiovasculares/metabolismo , Metabolismo de los Lípidos , Animales , Enfermedades Cardiovasculares/terapia , Humanos , Lipoproteínas HDL/metabolismoRESUMEN
Four DNA extraction methods namely SDS-hyperhaline method (I), modified SDS-hyperhaline method (II), indirect method (III), alkaline lysis method (IV) were evaluated by comparing DNA yield, spectrophotometric quality, genomic integrity and PCR suitability in this paper. The results showed that high DNA yields were obtained by method I, II and IV. However, higher quality of DNA was gained by method III and IV. Based on the results of the Pulsed-Field Gel Electrophoresis (PFGE), the completeness of DNA extracted by method IV was the best. About 6.0 microg DNA can be recovered from 1.0 g soil by method IV which involved to lysis cell by SDS and to precipitate impurities by adding potassium acetate and magnesium chloride Therefore, it is confirmed that method IV is a novel, reliable and versatile method for large-scale DNA extraction involving less purification steps for various soil samples.