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This Letter presents results of a search for the mixing of a sub-eV sterile neutrino with three active neutrinos based on the full data sample of the Daya Bay Reactor Neutrino Experiment, collected during 3158 days of detector operation, which contains 5.55×10^{6} reactor ν[over ¯]_{e} candidates identified as inverse beta-decay interactions followed by neutron capture on gadolinium. The analysis benefits from a doubling of the statistics of our previous result and from improvements of several important systematic uncertainties. No significant oscillation due to mixing of a sub-eV sterile neutrino with active neutrinos was found. Exclusion limits are set by both Feldman-Cousins and CLs methods. Light sterile neutrino mixing with sin^{2}2θ_{14}â³0.01 can be excluded at 95% confidence level in the region of 0.01 eV^{2}â²|Δm_{41}^{2}|â²0.1 eV^{2}. This result represents the world-leading constraints in the region of 2×10^{-4} eV^{2}â²|Δm_{41}^{2}|â²0.2 eV^{2}.
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Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.
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Reatores Nucleares , UrânioRESUMO
OBJECTIVES: Supplementation of high protein oral nutrition shakes supplemented with ß-hydroxy-ß-methylbutyrate (HP-HMB) has been shown to improve muscle mass, muscle strength, and physical performance in older adults, but the roles of HP-HMB supplementation on the intramuscular adiposity remained unknown. This 12-week randomized controlled trial evaluated the changes of muscle mass, muscle strength, physical performance and intramuscular adiposity among community-dwelling pre-frail older persons. METHODS: This was an open-label, parallel group, randomized controlled trail that enrolled 70 community-dwelling pre-frail older persons without active or uncontrolled conditions, disability or dementia. The intervention group was provided with two services of HP HMB (Ensure® Plus Advance containing 3g HMB) per day for 12 weeks, and the control group was provided with professional nutritional counselling for sufficient protein intake. All participants received functional assessments, laboratory tests and magnetic resonance imaging (MRI) of the dominant leg before and after study. Intramuscular adipose tissue (IMAT) and the mid-thigh cross-sectional area (CSA) of muscle were obtained by MRI, and the IMAT-to-CSA ratio was calculated to evaluate intramuscular adiposity. RESULTS: Overall, 62 participants (mean age: 71.1±3.8 years, 69.4% female) completed the study (HP-HMB group: 29, control group: 33) and comparisons of baseline characteristics between groups were not statistically different. For the primary outcome, HP-HMB group showed significant improvements in the CSA of mid-thigh muscle (mean increase of CSA: 149.1±272.3 for HMB group vs -22.9±309.1 mm2 for control group, P=0.045). The improvement of MNA-SF was borderline (0.28±0.75 vs. -0.15±0.94, P=0.064), but serum levels of Vit D were significantly increased in the HMB group (3.83±8.18 vs. -1.30±4.81 ng/mL, P=0.002). Moreover, the body weight and BMI were significantly increased in the HMB group (1.10±1.18 vs. 0.24±1.13 kg, P=0.005; 0.56±0.68 vs. 0.22±0.47 kg/m2, P=0.019). In particular, the IMAT-to-CSA ratio was reduced in the HMB group (-0.38±1.21 vs. -0.02±2.56 %, P=0.06). Using the generalized estimating equation, we found that SPPB score in chair rise test was significantly improved (ß=0.71, 95% C.I.0.09-1.33, P=0.026). CONCLUSIONS: The 12-week supplementation with high protein oral nutrition shake supplemented with 3g HMB per day significantly increased muscle mass, as well as nutritional status and physical performance, and ameliorated the intramuscular adiposity of pre-frail older persons. Further study is needed to explore the long-term benefits of HP-HMB supplementation on muscle and metabolic health for older adults.
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Idoso Fragilizado , Estado Nutricional , Adiposidade , Idoso , Feminino , Humanos , Masculino , Desempenho Físico Funcional , ValeratosRESUMO
OBJECTIVE: To understand the cognition and behavior of drug safety in Beijing middle school students and provide advice for relevant education. METHODS: A cross-sectional survey using paper questionnaires was carried out on the student body of nine Beijing middle schools. Multi-stage proportionate stratified cluster sampling was adopted to enroll participants. In addition to demographic questions, the questionnaire included 17 questions assessing the cognition and behavior of safe drug use, prioritizing questions that aligned with the health education guideline for primary and secondary school students from Chinese Ministry of Education. Descriptive statistical methods were applied using the SAS 9.2 software. RESULTS: Of the 4 220 students investigated, 2 097(49.7%) were males and 2 123(50.3%) were females. The average age was (14.3±1.7) years. 2 030(48.1%) students were from downtown areas, 1 511(35.8%) were from urban-rural linking areas and 679(16.1%) were from rural areas. Half (51.5%) of the respondents were junior high school students, and the others were from senior high schools (34.2%) and vocational high schools (14.3%). Most of the students (89.6%) lived off campus. The awareness rate of drug safety knowledge was 74.4%, the median score of drug safety behavior was 4 points (full score was 5 points) and there was a statistically positive correlation between the two (Spearman's correlation coefficient was 0.156, P<0.001). Both the awareness rates and the drug safety behavior scores were statistically different among the students in different regions, different school types and different residence types (P<0.001). Multiple factors analysis demonstrated the correlation between the cognition degrees of both drug safety knowledge, behavior and the above factors. Of all the students, 80.4% agreed that any drug could have adverse drug reactions; 40.5% were aware that antibiotics couldn't kill viruses; as many as 49.6% mistook aspirin as antibiotic; 97.4% would read drug instructions before taking them; Only 42.4% put expired drugs into special recycling bins; 49.8% would deviate from the suggested dosage and frequency of their medication when they were sick with common diseases. CONCLUSION: Overall, the cognition of drug safety in Beijing middle school students is good, but problems still exist in medication adherence, the management of expired drugs and the antibiotics cognition, which need to be fixed through specific, pointed way of education. And more efforts should be made to improve the cognition in rural regions, vocational high schools and on campus students.
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Cognição , Instituições Acadêmicas , Estudantes , Adolescente , Pequim , Criança , Estudos Transversais , Feminino , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , População Rural , Inquéritos e QuestionáriosRESUMO
Objective: To evaluate the effect of enzyme replacement therapy (ERT) on glycogen storage disease typeâ ¡(GSDâ ¡). Method: The clinical data of three juvenile onset and two infant onset GSDâ ¡patients were collected from First Affiliated Hospital of Sun Yat-sen University in October 2015 to July 2016.Patient 1 was female, the age of onset was 15 months. Patient 2 was male, the age of onset was 20 months. Patient 3 was female, the sister of patient 2, the age of onset was 47 months. Patient 4 was male, the age of onset was 5 months. Patient 5 was male, the age of onset was 1 month.The age at the start of ERT of the 5 patients was 32, 31, 56, 34, and 3 months respectively and the duration of ERT was 19, 9, 4, 5, 5 doses respectively.ERT was administered at 20 mg/kg every 2 weeks.Dexamethasone was regularly given before each infusion. Result: ERT was well tolerated, only one time, Patient 1 developed tachycardia and hypertension without using dexamethasone.Patient 2 underwent successfully ventilator weaning.Patient 1 underwent a tracheotomy, also needed mechanical ventilation treatment.Patient 4 noninvasive ventilation was tried. Conclusion: Recombinant human alpha-glucosidase treatment was effective and well tolerated in patients with GSDâ ¡.
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Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , alfa-Glucosidases/uso terapêutico , Terapia de Reposição de Enzimas , Feminino , Humanos , Lactente , Masculino , Resultado do TratamentoAssuntos
Antivirais/farmacologia , Hepatite C/tratamento farmacológico , Janus Quinase 2/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Antivirais/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Linhagem Celular , Desenho de Fármacos , Descoberta de Drogas , Hepacivirus/enzimologia , Hepacivirus/genética , Hepatite C/enzimologia , Hepatite C/virologia , Hong Kong , Humanos , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/química , Relação Estrutura-AtividadeRESUMO
BACKGROUND AND PURPOSE: Although the genetic contribution to stroke risk is well known, it remains unclear if young-onset stroke has a stronger genetic contribution than old-onset stroke. This study aims to compare the heritability of ischaemic stroke risk between young and old, using common genetic variants from whole-genome array data in population-based samples. METHODS: This analysis included 4050 ischaemic stroke cases and 5765 controls from six study populations of European ancestry; 47% of cases were young-onset stroke (age < 55 years). To quantify the heritability for stroke risk in these unrelated individuals, the pairwise genetic relatedness was estimated between individuals based on their whole-genome array data using a mixed linear model. Heritability was estimated separately for young-onset stroke and old-onset stroke (age ≥ 55 years). RESULTS: Heritabilities for young-onset stroke and old-onset stroke were estimated at 42% (±8%, P < 0.001) and 34% (±10%, P < 0.001), respectively. CONCLUSIONS: Our data suggest that the genetic contribution to the risk of stroke may be higher in young-onset ischaemic stroke, although the difference was not statistically significant.
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Isquemia Encefálica/genética , Predisposição Genética para Doença , Acidente Vascular Cerebral/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Acidente Vascular Cerebral/epidemiologia , População Branca/genéticaRESUMO
INTRODUCTION: Intrauterine growth restriction complicates 5-10% of pregnancies. This study aims to test the hypothesis that Chinese herbal formula, JLFC01, affects pregnancy and fetal development by modulating the pro-inflammatory decidual micro-environment. METHODS: Human decidua from gestational age-matched elective terminations or incomplete/missed abortion was immunostained using anti-CD68 + anti-CD86 or anti-CD163 antibodies. qRT-PCR and Luminex assay measured the effects of JLFC01 on IL-1ß- or TNF-α-induced cytokine expression in first trimester decidual cells and on an established spontaneous abortion/intrauterine growth restriction (SA/IUGR)-prone mouse placentae. The effect of JLFC01 on human endometrial endothelial cell angiogenesis was evaluated by average area, length and numbers of branching points of tube formation. Food intake, litter size, fetal weight, placental weight and resorption rate were recorded in SA/IUGR-prone mouse treated with JLFC01. qRT-PCR, Western blot and immunohistochemistry assessed the expression of mouse placental IGF-I and IGF-IR. RESULTS: In spontaneous abortion, numbers of decidual macrophages expressing CD86 and CD163 are increased and decreased, respectively. JLFC01 reduces IL-1ß- or TNF-α-induced GM-CSF, M-CSF, C-C motif ligand 2 (CCL2), interferon-γ-inducible protein-10 (IP-10), CCL5 and IL-8 production in first trimester decidual cells. JLFC01 suppresses the activity of IL-1ß- or TNF-α-treated first trimester decidual cells in enhancing macrophage-inhibited angiogenesis. In SA/IUGR-prone mice, JLFC01 increases maternal food intake, litter size, fetal and placental weight, and reduces fetal resorption rate. JLFC01 induces IGF-I and IGF-IR expression and inhibits M-CSF, CCL2, CCL5, CCL11, CCL3 and G-CSF expression in the placentae. DISCUSSION: JLFC01 improves gestation by inhibiting decidual inflammation, enhancing angiogenesis and promoting fetal growth.
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Aborto Espontâneo/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Desenvolvimento Fetal/efeitos dos fármacos , Retardo do Crescimento Fetal/prevenção & controle , Placenta/efeitos dos fármacos , Aborto Espontâneo/imunologia , Animais , Microambiente Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Interleucina-1beta/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos CBA , Neovascularização Fisiológica/efeitos dos fármacos , Placenta/metabolismo , Gravidez , Somatomedinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BTG3 (B-cell translocation gene 3) is a p53 target that also binds and inhibits E2F1. Although it connects two major growth-regulatory pathways functionally and is downregulated in human cancers, whether and how BTG3 acts as a tumor suppressor remain largely uncharacterized. Here we present evidence that BTG3 binds and suppresses AKT, a kinase frequently deregulated in cancers. BTG3 ablation results in increased AKT activity that phosphorylates and inhibits glycogen synthase kinase 3ß. Consequently, we also observed elevated ß-catenin/T-cell factor activity, upregulation of mesenchymal markers, and enhanced cell migration. Consistent with these findings, BTG3 overexpression suppressed tumor growth in mouse xenografts, and was associated with diminished AKT phosphorylation and reduced ß-catenin in tissue specimens. Significantly, a short BTG3-derived peptide was identified, which recapitulates these effects in vitro and in cells. Thus, our study provides mechanistic insights into a previously unreported AKT inhibitory pathway downstream of p53. The identification of an AKT inhibitory peptide also unveils a new avenue for cancer therapeutics development.
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Progressão da Doença , Neoplasias/metabolismo , Neoplasias/patologia , Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Técnicas de Cultura de Células , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Membrana Celular/enzimologia , Proliferação de Células , Transição Epitelial-Mesenquimal , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Peptídeos/metabolismo , Fosforilação , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ligação Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismoRESUMO
We experimentally demonstrate the recently predicted effect of near-field focusing for light beams from flat dielectric subwavelength gratings (SWGs). This SWGs were designed for visible light 532 nm and fabricated by direct laser writing in a negative photoresist, with the refractive index n=1.5 and the period d=314 nm. The laterally invariant gratings can focus light beams without any optical axis to achieve the transversal invariance. We show that focal distances can be obtained up to 13 µm at normal reflection for TE polarization.
RESUMO
The control of spatial propagation properties of narrow light beams such as divergence, focusing or imaging are main objectives in optics and photonics. In this letter, we propose and demonstrate experimentally a flat focusing mirror, based on an especially designed dielectric structure without any optical axis. More generally, it also enables imaging any light pattern in reflection. The flat focusing mirror with a transversal invariance can largely increase the applicability of structured photonic materials for light beam propagation control in small-dimension photonic circuits.
RESUMO
We hypothesized that competition between nucleotide reverse-transcriptase inhibitor triphosphate and endogenous deoxyribonucleotide triphosphate (dNTP) may lead to depletion of dNTP pools and mitochondrial dysfunction independent of polymerase-γ (pol-γ) inhibition. We collected peripheral blood mononuclear cells from 75 adults (25 cases: HIV-infected patients with mitochondrial toxicity, 25 HIV-infected positive controls, and 25 HIV-negative controls). We observed statistically significant individual and group differences in ribonucleotide (RN) and deoxyribonucleotide (dRN) pools. The median values for the RN pools were 10,062 (interquartile range (IQR): 7,090-12,590), 4,360 (IQR: 3,058-6,838), and 2,968 (IQR: 2,538-4,436) pmol/10(6) cells for negative controls, positive controls, and cases, respectively. Cases had significantly higher absolute mitochondrial DNA copy number as compared with negative controls (P < 0.05). Moreover, cases had significantly higher expression levels of pol-γ, nucleotide transporters, cellular kinases, and adenosine triphosphate (ATP)-binding cassette (ABC) proteins as compared with controls. Antiretroviral therapy (ART) perturbs RN and dRN pools. Depletion of RN and dRN pools may be associated with ART-induced mitochondrial toxicity independent of pol-γ inhibition.
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Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Inibidores da Síntese de Ácido Nucleico , Nucleotídeos/efeitos adversos , Inibidores da Transcriptase Reversa/efeitos adversos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Estudos de Casos e Controles , DNA Polimerase gama , DNA Mitocondrial/sangue , DNA Polimerase Dirigida por DNA/metabolismo , Desoxirribonucleotídeos/sangue , Feminino , Dosagem de Genes , Infecções por HIV/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas de Transporte de Nucleotídeos/metabolismo , Ribonucleotídeos/sangueRESUMO
The objectives of this study were to evaluate the safety, tolerability and pharmacokinetics (PK) of BMS-986001 as a single oral dose in healthy male subjects. Sixty-four healthy male subjects were randomized to receive a single dose of BMS-986001 or placebo in this single-blind, placebo-controlled, sequential ascending-dose study. There were eight treatment groups (10, 30, 100, 300, 600, and 900 mg fed; and 100 and 300 mg fasted) of eight subjects each (BMS-986001 n = 6/placebo n = 2). BMS-986001 was well tolerated, with no serious adverse events (AEs), deaths, or discontinuations due to AEs reported. AEs were experienced by 14.6% of subjects receiving BMS-986001; however, these did not appear to be dose related and were not considered to be related to study drug. BMS-986001 was rapidly absorbed and exhibited a linear dose-exposure relationship across the dose range studied. PK appeared similar whether administered with or without food. Administration of BMS-986001 as a single dose was generally safe and well tolerated. A linear dose-exposure relationship was seen across all doses studied, with no apparent food effect. Further clinical development is warranted.
Assuntos
Fármacos Anti-HIV/farmacocinética , Interações Alimento-Droga , Inibidores da Transcriptase Reversa/farmacocinética , Timidina/análogos & derivados , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/urina , Relação Dose-Resposta a Droga , Jejum/metabolismo , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/sangue , Inibidores da Transcriptase Reversa/urina , Método Simples-Cego , Timidina/efeitos adversos , Timidina/sangue , Timidina/farmacocinética , Timidina/urina , Adulto JovemRESUMO
A novel nucleoside analogue, 1-[(2S,4S-2-(hydroxymethyl)-1,3-dioxolan-4-yl]5-vinylpyrimidine-2,4(1H,3H)-dione, or HDVD, was evaluated against a wide variety of herpesviruses and was found to be a highly selective inhibitor of replication of the gammaherpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). HDVD had also a pronounced inhibitory activity against murine herpesvirus 68 (MHV-68) and herpes simplex virus 1 (HSV-1). In contrast, replication of herpesvirus saimiri (HVS), HSV-2, and varicella-zoster virus (VZV) was weakly inhibited by the compound, and no antiviral activity was determined against human cytomegalovirus (HCMV) and rhesus rhadinovirus (RRV). The HDVD-resistant virus phenotype contained point mutations in the viral thymidine kinase (TK) of HSV-1, MHV-68, and HVS isolates. These mutations conferred cross-resistance to other TK-dependent drugs, with the exception of an MHV-68 mutant (E358D) that exhibited resistance only to HDVD. HSV-1 and HVS TK-mutants isolated under selective pressure with bromovinyldeoxyuridine (BVDU) also showed reduced sensitivity to HDVD. Oral treatment with HDVD and BVDU was assessed in an intranasal model of MHV-68 infection in BALB/c mice. In contrast to BVDU treatment, HDVD-treated animals showed a reduction in viral DNA loads and diminished viral gene expression during acute viral replication in the lungs in comparison to levels in untreated controls. The valyl ester prodrug of HDVD (USS-02-71-44) suppressed the latent infection in the spleen to a greater extent than HDVD. In the present study, HDVD emerged as a highly potent antiviral with a unique spectrum of activity against herpesviruses, in particular, gammaherpesviruses, and may be of interest in the treatment of virus-associated diseases.
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Antivirais/farmacologia , Gammaherpesvirinae/efeitos dos fármacos , Nucleosídeos/farmacologia , Nucleosídeos de Pirimidina/farmacologia , Pirimidinas/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/metabolismo , Aotidae , Primers do DNA/genética , Fibroblastos , Gammaherpesvirinae/genética , Humanos , Macaca mulatta , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Mutação/genética , Células NIH 3T3 , Nucleosídeos/química , Nucleosídeos/metabolismo , Nucleosídeos de Pirimidina/metabolismo , Pirimidinas/química , Pirimidinas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Rhadinovirus/efeitos dos fármacos , Especificidade da Espécie , Estatísticas não Paramétricas , Timidina Quinase/genéticaRESUMO
To improve susceptibility quantification, a threshold-based k-space/image domain iterative approach that uses geometric information from the susceptibility map itself as a constraint to overcome the ill-posed nature of the inverse filter is introduced. Simulations were used to study the accuracy of the method and its robustness in the presence of noise. In vivo data were processed and analyzed using this method. Both simulations and in vivo results show that most streaking artifacts inside the susceptibility map caused by the ill-defined inverse filter were suppressed by the iterative approach. In simulated data, the bias toward lower mean susceptibility values inside vessels has been shown to decrease from around 10% to 2% when choosing an appropriate threshold value for the proposed iterative method. Typically, three iterations are sufficient for this approach to converge and this process takes less than 30 s to process a 512×512×256 dataset. This iterative method improves quantification of susceptibility inside vessels and reduces streaking artifacts throughout the brain for data collected from a single-orientation acquisition. This approach has been applied to vessels alone as well as to vessels and other structures with lower susceptibility to generate whole brain susceptibility maps with significantly reduced streaking artifacts.
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Algoritmos , Encéfalo/anatomia & histologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Reconhecimento Automatizado de Padrão/métodos , Humanos , Aumento da Imagem/métodos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Peroxisome proliferator-activated receptor gamma (PPARγ) belongs to a family of ligand-activated transcription factors, and its ligands are known to control many physiological and pathological conditions. The hypothesis of our study was that the PPARγ agonist (rosiglitazone) could mediate tumor necrosis factor alpha (TNFα) related to the regulation of human neural stem cells (hNSCs), by which TNFα possibly fulfills important roles in neuronal impairment. The results show that PPARγ mediates the cell viability of hNSCs via the downregulation of the activity of caspase 3, indicating that this rescue effect of PPARγ could improve the reduced levels of two mitochondrial regulators, adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1) in the hNSCs with TNFα. The stimulation of mitochondrial function by PPARγ was associated with activation of the PPAR coactivator1 alpha (PGC1α) pathway by up-regulation of oxidative defense and mitochondrial systems. The above protective effects appeared to be exerted by a direct activation of the rosiglitazone, because it protected hNSCs from TNFα-evoked oxidative stress and mitochondrial deficiency. Here we show that the rosiglitazone protects hNSCs against Aß-induced apoptosis and promotes cell survival. These findings extend our understanding of the central role of PPARγ in TNFα-related neuronal impairment, which probably increases risks of neurodegenerative diseases. The anti-inflammatory effects of PPARγ in the hNSCs with TNFα, and the involved mechanisms were also characterized.
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Mitocôndrias/metabolismo , Células-Tronco Neurais/metabolismo , PPAR gama/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Trifosfato de Adenosina/metabolismo , Adenilato Quinase/metabolismo , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cromanos/farmacologia , Humanos , Mitocôndrias/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , PPAR gama/agonistas , Pioglitazona , Espécies Reativas de Oxigênio/metabolismo , Rosiglitazona , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sirtuína 1/metabolismo , Tiazolidinedionas/farmacologia , Troglitazona , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Matrix-assisted laser desorption/ionization mass spectrometry is an established soft ionization method that is widely applied to analyze biomolecules. The UV-absorbing organic matrix is essential for biomolecule ionization; however, it also creates matrix background interference, which results in problematic analyses of biomolecules of less than 700 Da. Therefore, this study investigates hydrophilic, hydrophobic cationic, anionic and immobilized metal ion surface chemical modifications to advance nanostructured silicon mass spectrometry performance (nSi-MS). This investigation provides information required for a possible novel mass spectroscopy that combines surface-enhanced and nanostructured silicon surface-assisted laser desorption/ionization mass spectrometry for the selective detection of specific compounds of a mixture.