Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
ChemSusChem ; : e202400378, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570922

RESUMO

Converting lignin into aromatic chemicals is a promising strategy for the high-value utilization of lignocellulosic feedstock. However, the inherent heterogeneity of lignin poses a significant obstacle to achieving efficient conversion and optimal product yields within bio-refinery systems. Herein, we employed a one-step fractionation method to enhance lignin homogeneity and utilized the THF/DMSO-EtONa (tetrahydrofuran/dimethyl sulfoxide-sodium ethoxide) system to depolymerize the fractionated lignin. Three protic and three aprotic solvents were used for fractionation. The impact of the solvent properties on the structure and the depolymerization efficiency of the fractionated lignin was investigated. Methanol-fractionated lignin generated the benzoic acid compounds with a yield of 30 wt%, 50 % higher than that of the unfractionated lignin. The polarities (δP), hydrogen bonding abilities (δH), and viscosities (η) of selected protic solvents showed strong linear correlation with molecular weight (Mw), polymer dispersity index (PDI), and syringyl/guaiacyl ratio (S/G ratio) of the fractionated lignin, as well as the total yield of benzoic acid compounds derived from the ß-O-4 bond cleavage. This study elucidates the relationship between solvent properties and lignin structure and proposes a promising approach for refining lignin to enhance utilization efficiency, thereby presenting a potential strategy for value-added application of complex lignin polymers.

2.
Acta Biomater ; 175: 341-352, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38122883

RESUMO

Cuproptosis is a recently identified copper-dependent form of nonapoptotic cell death and holds great prospect in cancer treatment. One of the most intriguing aspects of cuproptosis is its ability to synergize with apoptosis-based cancer treatments. Herein, we presented a novel approach using copper-coordinated nanoassemblies (CCNAs) that were constructed by incorporating a photosensitizer Zinc Phthalocyanine (ZnPc)-chemotherapeutic (DOX) prodrug with a thioketal (TK) spacer and an IDO inhibitor (1-methyl tryptophan, 1-MT) as building blocks for Cu2+-coordination self-assembly to achieve combinational apoptosis-cuproptosis and immunotherapy. Upon NIR laser irradiation, the ZnPc component of CCNAs exhibited a photodynamic effect that generated reactive oxygen species (ROS). This triggered the release of DOX, leading to enhanced tumor cell apoptosis. Additionally, the presence of Cu2+ in the CCNAs not only enhanced the photodynamic process by catalyzing oxygen generation but also promoted the aggregation of toxic mitochondrial proteins, leading to cell cuproptosis. Importantly, the intensified cuproptosis-apoptosis effect triggered an immunogenic cell death (ICD) response. The released 1-MT complemented this response by reversing the immunosuppressive tumor microenvironment (ITM), synergistically amplifying anti-tumor immunity and suppressing the growth of primary and distant tumors. The findings of this study provide a new perspective on potential cancer treatments based on cuproptosis-apoptosis synergistic immunotherapy and stimulate further research in the design of advanced metal-coordinated nanomedicines. STATEMENT OF SIGNIFICANCE: The combination of cuproptosis and apoptosis that act with different mechanisms holds enormous potential in cancer treatment. Here, copper-coordinated nanoassemblies (CCNAs) based on photosensitizer-chemo prodrugs and checkpoint inhibitors were constructed for mediating cuproptosis-apoptosis and subsequently promoting cancer immunotherapy. CCNAs not only promoted the photodynamic effect and activation of chemotherapy through catalyzing the generation of oxygen but also induced toxic mitochondrial protein aggregation, leading to cell cuproptosis. These synergistic antitumor effects triggered robust immune responses with the aid of immune checkpoint blockade, almost eradicating primary tumors and inhibiting distant tumors by around 83 % without systemic toxicity.


Assuntos
Fármacos Fotossensibilizantes , Pró-Fármacos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Pró-Fármacos/farmacologia , Cobre/farmacologia , Linhagem Celular Tumoral , Apoptose , Imunoterapia , Oxigênio
3.
Environ Sci Technol ; 57(48): 19990-19998, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37943716

RESUMO

As wildland fires become more frequent and intense, fire smoke has significantly worsened the ambient air quality, posing greater health risks. To better understand the impact of wildfire smoke on air quality, we developed a modeling system to estimate daily PM2.5 concentrations attributed to both fire smoke and nonsmoke sources across the contiguous U.S. We found that wildfire smoke has the most significant impact on air quality in the West Coast, followed by the Southeastern U.S. Between 2007 and 2018, fire smoke contributed over 25% of daily PM2.5 concentrations at ∼40% of all regulatory air monitors in the EPA's air quality system (AQS) for more than one month per year. People residing outside the vicinity of an EPA AQS monitor (defined by a 5 km radius) were subject to 36% more smoke impact days compared with those residing nearby. Lowering the national ambient air quality standard (NAAQS) for annual mean PM2.5 concentrations to between 9 and 10 µg/m3 would result in approximately 35-49% of the AQS monitors falling in nonattainment areas, taking into account the impact of fire smoke. If fire smoke contribution is excluded, this percentage would be reduced by 6 and 9%, demonstrating the significant negative impact of wildland fires on air quality.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Incêndios , Incêndios Florestais , Estados Unidos , Humanos , Poluentes Atmosféricos/análise , Fumaça/análise , Poluição do Ar/análise , Sudeste dos Estados Unidos , Material Particulado
4.
Res Sq ; 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37790383

RESUMO

As wildfires become more frequent and intense, fire smoke has significantly worsened ambient air quality, posing greater health risks. To better understand the impact of wildfire smoke on air quality, we developed a modeling system to estimate daily PM2.5 concentrations attributed to both fire smoke and non-smoke sources across the Continental U.S. We found that wildfire smoke has the most significant impact on air quality in the West Coast, followed by the Southeastern U.S. Between 2007 and 2018, fire smoke affected daily PM2.5 concentrations at 40% of all regulatory air monitors in EPA's Air Quality System (AQS) for more than one month each year. People residing outside the vicinity of an EPA AQS monitor were subject to 36% more smoke impact days compared to those residing nearby. Lowering the national ambient air quality standard (NAAQS) for annual mean PM2.5 concentrations to between 9 and 10 µg/m3 would result in approximately 29% to 40% of the AQS monitors falling in nonattainment areas without taking into account the contribution from fire smoke. When fire smoke impact is considered, this percentage would rise to 35% to 49%, demonstrating the significant negative impact of wildfires on air quality.

5.
JAMA Oncol ; 9(9): 1214-1220, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37498574

RESUMO

Importance: With a changing climate, wildfire activity in the US has increased dramatically, presenting multifaceted and compounding health hazards. Individuals discharged from the hospital following surgical resection of non-small cell lung cancer (NSCLC) are potentially at higher risk from wildfires' health hazards. Objective: To assess the association between wildfire exposure and postoperative long-term overall survival among patients with lung cancer in the US. Design, Setting, and Participants: In this cohort study, individuals who underwent curative-intent NSCLC resection between January 1, 2004, and December 31, 2019, were selected from the National Cancer Database. Daily wildfire information was aggregated at the zip code level from the National Aeronautics and Space Administration Fire Information for Resource Management System. The data analysis was performed between July 19, 2022, and April 14, 2023. Exposure: An active wildfire detected at the zip code of residence between 0 and 3, 4 and 6, or 7 and 12 months after NSCLC surgery. Main Outcome: Overall survival was defined as the interval between age at hospital discharge and age at death, last contact, or study end, whichever came first. Cox proportional hazards were used for estimating hazard ratios (HRs) adjusted for sex, region, metropolitan category, health insurance type, comorbidities, tumor size, lymph node involvement, era, and facility type. Results: A total of 466 912 individuals included in the study (249 303 female and [53.4] and 217 609 male [46.6%]; mean [SD] age at diagnosis, 67.3 [9.9] years), with 48 582 (10.4%) first exposed to a wildfire between 0 and 3 months, 48 328 (10.6%) between 4 and 6 months, and 71 735 (15.3%) between 7 and 12 months following NSCLC surgery. Individuals exposed to a wildfire within 3 months (adjusted HR [AHR], 1.43; 95% CI, 1.41-1.45), between 4 and 6 months (AHR, 1.39; 95% CI, 1.37-1.41), and between 7 and 12 months (AHR, 1.17; 95% CI, 1.15-1.19) after discharge from the hospital following stage I to III NSCLC resection had worse overall survival than unexposed individuals. Conclusions: In this cohort study, wildfire exposure was associated with worse overall survival following NSCLC surgical resection, suggesting that patients with lung cancer are at greater risk from the health hazards of wildfires and need to be prioritized in climate adaptation efforts.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Incêndios Florestais , Humanos , Masculino , Feminino , Criança , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos de Coortes , Estadiamento de Neoplasias
6.
Biomed Pharmacother ; 165: 115072, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37390712

RESUMO

Septic gut damage is critical in the progression of sepsis and multiple organ failure, characterized by gut microbiota dysbiosis and epithelium deficiency in the gut barrier. Recent studies highlight the protective effects of Erythropoietin (EPO) on multiple organs. The present study found that EPO treatment significantly alleviated the survival rate, suppressed inflammatory responses, and ameliorated intestine damage in mice with sepsis. EPO treatment also reversed sepsis-induced gut microbiota dysbiosis. The protective role of EPO in the gut barrier and microbiota was impaired after EPOR knockout. Notably, we innovatively demonstrated that IL-17 F screened by transcriptome sequencing could ameliorate sepsis and septic gut damage including gut microbiota dysbiosis and barrier dysfunction, which was verified by IL-17 F-treated fecal microbiota transplantation (FMT) as well. Our findings highlight the protection effects of EPO-mediated IL-17 F in sepsis-induced gut damage by alleviating gut barrier dysfunction and restoring gut microbiota dysbiosis. EPO and IL-17 F may be potential therapeutic targets in septic patients.


Assuntos
Eritropoetina , Microbioma Gastrointestinal , Sepse , Camundongos , Animais , Disbiose/terapia , Interleucina-17 , Eritropoetina/farmacologia , Sepse/complicações
7.
Biochem Biophys Res Commun ; 662: 93-103, 2023 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-37104884

RESUMO

Natural antisense transcripts (NATs) are endogenous RNAs opposite to sense transcripts, and they can significantly contribute to regulating various biological processes through multiple epigenetic mechanisms. NATs can affect their sense transcripts to regulate the growth and development of skeletal muscle. Our analysis of third-generation full-length transcriptome sequencing data revealed that NATs represented a significant portion of the lncRNA, accounting for up to 30.19%-33.35%. The expression of NATs correlated with myoblast differentiation, and genes expressing NATs were mainly involved in RNA synthesis, protein transport, and cell cycle. We found a NAT of MYOG (MYOG-NAT) in the data. We found that the MYOG-NAT could promote the differentiation of myoblasts in vitro. Additionally, knockdown of MYOG-NAT in vivo led to muscle fiber atrophy and muscle regeneration retardation. Molecular biology experiments demonstrated that MYOG-NAT enhances the stability of MYOG mRNA by competing with miR-128-2-5p, miR-19a-5p, and miR-19b-5p for binding to MYOG mRNA 3'UTR. These findings suggest that MYOG-NAT plays a critical role in skeletal muscle development and provides insights into the post-transcriptional regulation of NATs.


Assuntos
MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Antissenso/genética , Regiões 3' não Traduzidas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Músculo Esquelético/metabolismo , Sítios de Ligação , Desenvolvimento Muscular/genética
8.
Sci Total Environ ; 882: 163305, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37054798

RESUMO

Microplastic (MP) pollution has become one of the global environmental concerns, but the contamination and effect of MP on chicken skeletal muscle are scarcely researched. Here, we found MP contamination in the chicken skeletal muscles, which were directly collected from a large-scale chicken farm. Using Pyrolysis-Gas Chromatography-Mass Spectrometry and Agilent 8700 laser direct infrared imaging spectrometer, we found that polystyrene (PS) and polyamide are the significant type of MPs detected in chicken skeletal muscle. Constant PS-MP oral feeding for >21 days increases the content of MP deposited in chicken breast muscle, but the MP content in the leg muscle was gradually decreased. Surprisingly, the chicken's body and skeletal muscle weight was increased after constant PS-MP feeding. Physiological results showed that PS-MP exposure inhibited energy and lipid metabolism, induced oxidative stress, and potential for neurotoxicity in the skeletal muscle. Metabolomic analysis of the liquid chromatography-tandem mass spectrometry and gas chromatography coupled with the mass spectrometer results showed that PS-MP exposure changed the metabolomic profile and reduced meat quality. In vitro, experimental results showed that PS-MP exposure induced chicken primary myoblasts proliferation and apoptosis but decreased myoblasts differentiation. Transcriptome analysis of the skeletal muscle indicates that PS-MP exposure affects skeletal muscle function by regulating genes involved in neural function and muscle development. Considering that chicken is one of the most important meat foods in the world, this study will provide an essential reference for protecting meat food safety.


Assuntos
Microplásticos , Plásticos , Animais , Microplásticos/metabolismo , Plásticos/metabolismo , Galinhas/genética , Cromatografia Gasosa-Espectrometria de Massas , Músculo Esquelético/metabolismo , Poliestirenos/toxicidade , Carne/análise
9.
Lab Invest ; 103(1): 100028, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36748190

RESUMO

Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel anti-inflammatory and proresolving lipid mediator biosynthesized from docosahexaenoic acid. Excessive activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and consequent pyroptosis are involved in diverse inflammatory diseases. However, how PCTR1 affects NLRP3 inflammasome activation and pyroptosis are still unclear. Here, we demonstrated that PCTR1 inhibited NLRP3 inflammasome activation and pyroptosis. These results show that PCTR1 dose-dependently inhibited gasdermin D cleavage in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin stimulation. Additionally, PCTR1 treatment after LPS priming inhibited caspase-1 activation and subsequent mature interleukin-1ß release independent of the nuclear factor-kappa B pathway. PCTR1 exerted its inhibitory effects by blocking NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC) interaction and ASC oligomerization, thereby restricting NLRP3 inflammasome assembly. However, the inhibitory effect of PCTR1 could be reversed by KH7 and H89, which are the inhibitors of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway. Moreover, PCTR1 treatment alleviated lung tissue damage and improved mouse survival in LPS-induced sepsis. Our study unveils the molecular mechanism of negative regulation of NLRP3 inflammasome activation and pyroptosis by a novel lipid mediator and suggests that PCTR1 may serve as a potential treatment option for NLRP3-inflammasome driven diseases.


Assuntos
Inflamassomos , Sepse , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Antígenos CD59/metabolismo , Antígenos CD59/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Sepse/tratamento farmacológico , Sepse/metabolismo , Interleucina-1beta/metabolismo , Caspase 1/metabolismo
10.
Animals (Basel) ; 12(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36359079

RESUMO

Chinese Shitou goose is a type of large goose with high meat yield. Understanding the genetic regulation of muscle development in Shitou goose would be beneficial to improve the meat production traits of geese. Muscle development is regulated by genes related to myoblast proliferation and differentiation. In this study, the RNA-seq method was used to construct the mRNA and lncRNA expression profiles of Shitou goose myoblasts and myotubes. A total of 1664 differentially expressed (DE) mRNAs and 244 DE-lncRNAs were identified. The alternative mRNA splicing in proliferation and differentiation stages was also analyzed. Notably, pathways enriched in DE-mRNAs, DE-splicing transcripts, and DE-lncRNAs all point to the Wnt signaling pathway, indicating that the Wnt signaling is a key regulatory pathway of muscle development in Shitou goose. We also constructed the interactive network of DE-lncRNAs and DE-mRNAs and revealed some key genes of lncRNAs regulating the proliferation and differentiation of myoblasts. These results provide new insights for the study of the muscle development of the Shitou goose.

11.
Carbohydr Polym ; 294: 119809, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35868769

RESUMO

Moisture-trigged electricity generator (MEG) that can convert ubiquitous moisture into electricity are highly desirable for developing renewable energy supply and ameliorating the crisis in energy. Constructing an asymmetric ordered, namely gradient ordered porous membrane has great potential in MEG. Herein, a series of cellulose acetate (CA)-based membranes with ordered asymmetric honeycomb membranes were fabricated by Breath Figure method, along with silver nanowires (AgNWs) coating. The asymmetric gradient honeycomb pores were achieved by graft modification of lauroyl chloride and adjustment of relative humidity, which not only endowed the MEG with sensitive sensing signals transport under tension and humidity fluctuations but also enhanced voltages generation speed under flowing moisture. The current study provides a facile and scalable strategy for constructing asymmetric gradient ordered porous materials and creates more possibilities for MEG self-powered flexible wearable electronic devices.


Assuntos
Nanofios , Dispositivos Eletrônicos Vestíveis , Celulose , Eletricidade , Umidade
12.
Oncol Lett ; 24(2): 254, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35765272

RESUMO

Cutaneous squamous cell carcinoma (CSCC) is one of the most common non-melanoma skin cancers worldwide. Fatty acid-binding protein 7 (FABP7) has been reported to be involved in the occurrence, development, metastasis and prognosis of various tumors. In addition, downregulated FABP7 expression was demonstrated in cutaneous malignant melanoma in a previous study. Therefore, we speculated that FABP7 may be a biomarker for CSCC diagnosis. The aim of the present study was to determine the molecular mechanism underlying the effects of FABP7 in CSCC, which may provide a new diagnostic biomarker or treatment target for CSCC. Reverse transcription-PCR, western blotting and immunohistochemistry assays were performed to detect the expression levels of FABP7 in CSCC tissues and cells. Overexpression of FABP7 was achieved in A431 and colo-16 cell lines by transfection with an overexpression vector (oeFABP7). Cell proliferation, colony formation, migration and invasion were detected by Cell Counting Kit-8, crystal violet, scratch and Transwell assays, respectively. Following FABP7 overexpression, western blotting was used to determine the expression levels of proliferation-, invasion- and Notch pathway-associated proteins, including Snail, N-cadherin, Twist, matrix metalloproteinase (MMP)-2, MMP-7, Notch 1 and Notch 3. In addition a CSCC model in nude mice was constructed. Immunohistochemistry was used to determine the expression levels of FABP7, Ki67, Notch 1 and Notch 3. It was demonstrated that FABP7 expression levels were significantly reduced in human CSCC tissues and cells compared with normal samples. Overexpression of FABP7 inhibited the proliferation, invasion and migration abilities of A431 and colo-16 cells compared with those in the negative control group. In addition, transfection with oeFABP7 reduced the expression levels of proliferation-, invasion- and Notch pathway-associated proteins compared with those in the negative control group. Overexpression of FABP7 also reduced the growth of CSCC tumors in vivo and inhibited the expression of Ki67, Notch 1 and Notch 3. Therefore, the results of the present study suggested that FABP7 may inhibit the proliferation and invasion of CSCC cells via the Notch signaling pathway.

13.
Cryogenics (Guildf) ; 1272022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37842207

RESUMO

Superconducting magnets used for Magnetic Resonance Imaging (MRI) scanners need to keep temperature gradients minimized in order to retain thermal and operating current margin. We have used 3D finite element analysis (FEA) simulation in COMSOL Multiphysics software that includes both conductive heat transfer and radiative heating to calculate the temperature distribution both along the winding direction and across the cross-section of an MRI segment coil at its equilibrium operating temperature. We have also modelled the evolution of the thermal properties during cool-down from ambient temperature. The heat capacity and thermal conductivity of the magnet winding were computed for use within this simulation. The heat capacity as a function of temperature was calculated using a rule of mixtures. This procedure was also used for the thermal conductivity along the direction of the wire. However, the thermal conductivity within the composite cross section (x- and y-directions) was computed using a 2D FEA model. Based on this, a time-dependent, 3D coil model was built to calculate the coil temperature throughout the winding during cool-down in our test cryostat system. The model included a heat leak component to the coil current contacts via conduction through the current leads as well as a radiative component from the surfaces of the cryostat. A key result was that a maximum coil ΔTmax = 5.1 K (=maximum temperature within the winding -minimum temperature in the winding) was seen and a coil Ic margin of 12.75 A was predicted at steady state, with our first current lead design. A second set of more optimized current leads significantly lowered the ΔTmax within the coil at the steady state. The coil Ic margin has been analyzed for different current lead designs.

14.
Remote Sens Environ ; 2662021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34776543

RESUMO

Exposure to fine particulate matter (PM2.5) has been linked to a substantial disease burden globally, yet little has been done to estimate the population health risks of PM2.5 in South Africa due to the lack of high-resolution PM2.5 exposure estimates. We developed a random forest model to estimate daily PM2.5 concentrations at 1 km2 resolution in and around industrialized Gauteng Province, South Africa, by combining satellite aerosol optical depth (AOD), meteorology, land use, and socioeconomic data. We then compared PM2.5 concentrations in the study domain before and after the implementation of the new national air quality standards. We aimed to test whether machine learning models are suitable for regions with sparse ground observations such as South Africa and which predictors played important roles in PM2.5 modeling. The cross-validation R2 and Root Mean Square Error of our model was 0.80 and 9.40 µg/m3, respectively. Satellite AOD, seasonal indicator, total precipitation, and population were among the most important predictors. Model-estimated PM2.5 levels successfully captured the temporal pattern recorded by ground observations. Spatially, the highest annual PM2.5 concentration appeared in central and northern Gauteng, including northern Johannesburg and the city of Tshwane. Since the 2016 changes in national PM2.5 standards, PM2.5 concentrations have decreased in most of our study region, although levels in Johannesburg and its surrounding areas have remained relatively constant. This is anadvanced PM2.5 model for South Africa with high prediction accuracy at the daily level and at a relatively high spatial resolution. Our study provided a reference for predictor selection, and our results can be used for a variety of purposes, including epidemiological research, burden of disease assessments, and policy evaluation.

15.
Curr Drug Metab ; 22(3): 232-239, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33397228

RESUMO

BACKGROUND: Praziquantel (PZQ), which possesses an asymmetric center, is classified as a pyrazinoisoquinoline and has been the mainstay in the treatment of schistosomiasis since 1980. PZQ undergoes a pronounced first-pass metabolism in the liver through the CYP450 system which could be mediated by nuclear receptors. OBJECTIVE: The purpose of this study was to investigate the possible different induction effects of CYP3A4 by PZQ racemate and enantiomers via the pregnane X receptor (PXR) and the effect of PXR polymorphism on the induction potency of PZQs. METHODS: The dual-luciferase reporter gene systems constructed in HepG2 cells were used to measure the abilities of PZQs to induce CYP3A4 expression mediated by PXR. The mRNA and protein levels of CYP3A4 were evaluated by polymerase chain reaction (PCR) and western blotting, respectively. RESULTS: In HepG2 cells transfected with PXRwt, PXR158, PXR163, PXR370 or PXR403 expression plasmids, PZQ racemate and its enantiomers up-regulated the luciferase activity in a concentration-dependent manner, while reaching saturation after transfected with PXR379 expression plasmids. The mRNA and protein expression of CYP3A4 was effectively activated in PXR-transfected HepG2 cells. The induction ability of CYP3A4 mediated by PXR activation by PZQ racemate and its enantiomers were statistically different between the same PXR group and different PXR groups. CONCLUSION: The enantioselective induction effects of PZQs on CYP3A4 were related to the enantioselective activations of PXR by PZQs and were influenced by the PXR gene polymorphism. These findings provide a basis for further understanding the enantiomeric metabolism and the variable efficacy of PZQs.


Assuntos
Indutores do Citocromo P-450 CYP3A/farmacologia , Citocromo P-450 CYP3A/metabolismo , Praziquantel/farmacologia , Receptor de Pregnano X/metabolismo , Indutores do Citocromo P-450 CYP3A/química , Células Hep G2 , Humanos , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Praziquantel/química , Receptor de Pregnano X/genética , Estereoisomerismo
16.
Physica C Supercond ; 5782020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33776209

RESUMO

Three (MgB2)1-x (SnO2) x samples with x ranging from 0 to 5 wt% were prepared by the in situ route to study the effect of tin dioxide additions on the superconducting properties of MgB2 bulk materials. All of the reacted samples were slightly Mg deficient although the starting Mg:B precursor powder ratio was 1:2. A heat treatment (HT) temperature of 700 °C with a dwell time of 30 min was used. XRD results showed evidence of peak shifts for MgB2 phases with SnO2 addition. The magnitude of the a-axis lattice constant change (0.361 ± 0.075 %) calculated for the 3 wt% doped samples is comparable in magnitude to that seen previously for the C-doped MgB2 bulks which exhibited enhanced B C2 . The upper critical fields (B C2 ) and the irreversibility fields (B irr ) were measured resistively in fields up to 14 T at 5 K to T c . The best B C2 value at 20 K (15.2 T based on extrapolation) was seen for sample IS3 (x = 3 wt%), and was comparable to the best B C2 values (≈ 15 T at 20 K) seen for C-doped MgB2 bulks. IS3 had a corresponding B irr = 10.8 T (20 K). The superconducting transition temperature (T c ) appeared to increase slightly with doping, although within the range of error bars (37.4 K to 37.6 K for 1.6 T B C2 increase at 20 K), in contrast to C doping which is accompanied by a significant decrease in T c (39 K to 36 K for 3.8 % C doped MgB2 bulk). We attribute the observed increase in both B C2 and B irr for SnO2-additions to lattice strain caused by the introduction of precipitates within the grains.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34707692

RESUMO

MgB2 superconducting wires and bulks with nano-La2O3 addition have been studied. A series of MgB2 superconducting bulk samples with nano-La2O3 addition levels of 0, 5, 7, 18wt% were prepared. AC resistivity data showed slight increases of Bc 2 and unchanged B irr for the bulk samples with doping levels lower than 7 wt% and decreased critical fields for the heavily doped (18 wt%) bulk. X-ray diffraction (XRD) showed the presence of LaB6 in the nano-La2O3 doped MgB2 bulk samples and decreased MgB2 grain size in nano-La2O3 doped bulks. Monocore powder-in-tube (PIT) MgB2 wires without and with 5 wt% nano-La2O3 addition (P-05) were prepared for transport property measurement. 2mol%C-doped Specialty Materials Inc. (SMI) boron powder was used for wire P-05 and previously prepared control wires (control wires were made without the addition of nano-La2O3 powder, W-00 and P2). Low field magnetic properties were obtained from magnetization loop (M-H), transport critical current density (J c ) was measured at 4.2 K for the nano-La2O3 doped PIT wire (P-05) and the control samples (P2 and W-00). The transport critical current density J c (B) of P-05 at 4.2 K and 8 T (6.0 ×104 A/cm2) was twice that of the control wire. The critical magnetic fields (Bc 2 and B irr ) of P-05 and the control sample P2 were compared. The critical fields of P-05 were slightly less than those of P2. Kramer-Dew-Hughes plots indicated a change from surface pinning to a mixture of volume pinning and surface pinning. It is shown that enhancement of P-05's transport properties is due to additional flux pinning by the fine-size rare-earth borides rather than enhanced Bc 2 or B irr .

18.
Artigo em Inglês | MEDLINE | ID: mdl-32489243

RESUMO

A series of SnO2 added MgB2 bulk superconductors were prepared by in situ route to study the effect of oxygen doping on superconducting and structural properties of MgB2. Several (MgB2)1-x (SnO2) x samples were fabricated with x ranging from 0, 3 wt%, 4 wt%, and 6 wt%. Upper critical field (B C2) and irreversible field (B irr) were measured by physical property measurement system. Thermal analysis was performed on the as-received SnO2 powder. Critical current densities (J cm ) were obtained at 4.2 K using magnetic measurement. X-ray diffraction results showed evidence of full SnO2 decomposition in all the doped bulk samples and a shift of a-axis in MgB2 lattice was seen. Oxygen was successfully released during heat treatment, yet no enhancement of B C2 or B irr was seen, indicating that oxygen atoms did not end up in the host lattice. Further exploration of different processing procedures is still needed in order to get oxygen substitution on the host lattice sites.

20.
Artigo em Inglês | MEDLINE | ID: mdl-28222334

RESUMO

Praziquantel is the drug of first choice for the control and treatment of all forms of schistosomiasis. Praziquantel is administered as a racemate, including R-enantiomer and S-enantiomer. Among them, R-enantiomer has main contribution to schistosomicidal activity. In this study, a sensitive and rapid liquid chromatography with tandem mass spectrometry was established and validated to determine the concentration of racemate praziquantel and R-enantiomer in rat plasma after oral administration. Chromatographic separation was performed on an Agilent Zorbax SB-C18 column. An entire run time for chromatographic separation was no more than 5min. The present method for analytes manifested that high sensitivity (the lower limit of quantification was 3.0ng/mL), satisfactory accuracy (relative error ≤±15%) and precision (relative standard deviation ≤15%) were achieved. There was no obvious matrix effect found. The average recoveries of racemate praziquantel and R-enantiomer were both above 85%. Then, the developed method had a successful application to comparative pharmacokinetic study of racemate praziquantel and R-enantiomer. Meanwhile, the differences in their pharmacokinetic parameters were compared and analyzed. The present quantification method and comparative pharmacokinetic study would provide a useful reference for the drug development of enantiopure schistosomicidal R-enantiomer as a replacement of racemate praziquantel for treatment of schistosomiasis.


Assuntos
Anti-Helmínticos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Praziquantel/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Anti-Helmínticos/análise , Cromatografia Líquida de Alta Pressão/economia , Limite de Detecção , Masculino , Praziquantel/análise , Ratos , Ratos Wistar , Esquistossomose/tratamento farmacológico , Estereoisomerismo , Espectrometria de Massas em Tandem/economia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...