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1.
Int Immunopharmacol ; 134: 112143, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38692016

RESUMO

Chronic inflammation is a significant contributor to hypertensive heart failure. Carnosol (Car), primarily derived from the sage plant (Salvia carnosa), exhibits anti-inflammatory properties in a range of systems. Nevertheless, the influence of angiotensin II (Ang II) on cardiac remodeling remains uncharted. Car was shown to protect mice's hearts against Ang II-induced heart damage at dosages of 20 and 40 mg/kg/d. This protection was evident in a concentration-related decrease in the remodeling of the heart and dysfunction. Examination of the transcriptome revealed that the pivotal roles in mediating the protective effects of Car involved inhibiting Ang II-induced inflammation and the activation of the mitogen-activated protein kinase (MAPK) pathway. Furthermore, Car was found to inhibit p38 phosphorylation, therefore reducing the level of inflammation in cultured cardiomyocytes and mouse hearts. This effect was attributed to the direct binding to p38 and inhibition of p38 protein phosphorylation by Car both in vitro and in vivo. In addition, the effects of Car on inflammation were neutralized when p38 was blocked in cardiomyocytes.


Assuntos
Abietanos , Angiotensina II , Anti-Inflamatórios , Camundongos Endogâmicos C57BL , Miócitos Cardíacos , Remodelação Ventricular , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Angiotensina II/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Masculino , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Camundongos , Abietanos/farmacologia , Abietanos/uso terapêutico , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Remodelação Ventricular/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/induzido quimicamente , Fosforilação/efeitos dos fármacos , Células Cultivadas
2.
Artigo em Inglês | MEDLINE | ID: mdl-38723713

RESUMO

OBJECTIVES: The aim of this study is to characterize an NDM-1-producing Acinetobacter seifertii isolates from a patient in South Korea. METHODS: Antibiotic susceptibility testing and genotyping using multigene sequencing were performed and whole plasmid sequences were determined. RESULTS: The genotype of A. seifertii was ST1899, and was resistant to ceftazidime, trimethoprim-sulfamethoxazole, and piperacillin-tazobactam, in addition to carbapenem. blaNDM-1 was surrounded by ISAba125 insertion sequence within the structure of Tn125 in the 47 kb-sized plasmid. The plasmid exhibited a structure similar to that of other plasmids of diverse Acinetobacter species found worldwide. Transconjugation and growth curve indicated that the plasmid was adapted to A. seifertii rather than other closely related Acinetobacter species. CONCLUSION: Acquisition of the carbapenem resistance by horizontal transfer of the blaNDM-1-carrying plasmid from another Acinetobacter species with no growth defect.

3.
Neurosci Bull ; 40(2): 241-254, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37755677

RESUMO

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Parkinson , Príons , Humanos , Doenças Neurodegenerativas/patologia , Peptídeos beta-Amiloides , alfa-Sinucleína , Proteínas tau
4.
Cell Adh Migr ; 17(1): 1-14, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37749865

RESUMO

The LMNA gene encoding lamin A/C is amplified in some clear cell renal cell carcinoma (ccRCC) samples. Our data showed that depletion of the tumor suppressor PBRM1 can upregulate lamin A/C levels, and lamin A/C could interact with PBRM1. However, the role of lamin A/C in ccRCC is not yet fully understood. Our functional assays showed that although the proliferation ability was slightly impaired after LMNA depletion, the migration and invasion of ccRCC cells were significantly inhibited. This suppression was accompanied by a reduction in MMP2, MMP9, AKT/p-AKT, and Wnt/ß-catenin protein levels. Our data therefore suggest that lamin A/C, as an interaction partner of the tumor suppressor PBRM1, plays a crucial role in tumor invasion and metastasis in ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , beta Catenina/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
5.
Front Psychol ; 14: 1169845, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37388659

RESUMO

Introduction: The COVID-19 pandemic has significantly impacted global economies and individual health. This study uses data from the China Family Panel Data (CFPS) in 2018 (before the pandemic) and 2020 (during the pandemic) to a) estimate the relationships between the perceived risk of unemployment and individuals' mental health, physical health, and health behaviors; and b) explore the variations of these relationships between rural and urban adults in China. Methods: Ordinary linear regression models or Logit models are employed, depending on the nature (continuous vs. discrete) of the dependent variables. Results: We find that the perceived risk of unemployment was statistically and positively associated with the risk of depression, and the association was greater for rural adults than for urban adults. Rural-urban variations were observed in various dimensions. For rural adults, the perceived risk of unemployment was statistically and negatively associated with life satisfaction, the probability of gaining weight and becoming obese, the probability of having adequate sleep, and computer-based screen time. These associations were statistically insignificant for urban adults. On the other hand, the perceived risk of unemployment was statistically and negatively associated with self-rated very-good-to-excellent health condition and health-compromising behaviors (e.g., smoking and drinking) for urban adults; but such associations were statistically insignificant for rural adults. Discussion: These findings suggest that rural and urban adults exhibited different psychological and behavioral responses to the unemployment risk during the COVID-19 pandemic. Public policies aiming to improve health and employment should be strategically designed to address the unique needs of urban and rural populations.

6.
Int J Rehabil Res ; 46(1): 92-97, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36727671

RESUMO

The aim of this study is to explore the factors influencing early mobilisation behaviours and patients' needs in critically ill patients after liver transplantation (LT). This interview study used phenomenological research, and Pender's health promotion model (HPM) was used to construct the interview guide. With the use of purposeful sampling, a total of 19 critically ill patients who experienced early mobilisation after LT were recruited at three tertiary hospitals in Beijing from August to November 2022. Data were collected through semi-structured interviews and analysed using Colaizzi's seven-step method. Nine themes were categorised into the three domains of Pender's HPM. The first domain was individual characteristics and experiences: (1) symptoms of end-stage liver disease limiting premobility behaviours and (2) previous treatment experience affecting understanding of early mobilisation after LT. The second domain was behaviour-specific cognition and affect: (3) coexistence of benefits and concerns in early mobilisation after LT, (4) barriers to early mobilisation after LT, (5) high self-efficacy in early mobilisation after LT, (6) individual differences in early mobilisation and (7) support and encouragement from family, wardmates and medical staff. The final domain was behavioural outcomes: (8) the need for sufficient staff, a quiet environment, safety, goals, guidance and family participation and (9) a strong willingness to comply with early mobilisation plans. The three areas and nine themes extracted in this study are helpful for the long-term development of early mobilisation in patients after LT.


Assuntos
Deambulação Precoce , Transplante de Fígado , Humanos , Estado Terminal , Promoção da Saúde , Pesquisa Qualitativa
7.
Injury ; 54(2): 778-783, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36481053

RESUMO

PURPOSE: The study aimed to introduce anterior superior iliac spine distraction to treat severe and recalcitrant diabetic foot ulcers. For comparison, we also included another group of diabetic foot ulcers treated with proximal tibial cortex transverse distraction. METHODS: From February 1998 to February 2020, 87 patients (87 feet) with severe and recalcitrant diabetic foot ulcers were treated. The mean age of patients at surgery was 64 years (range, 47 to 87 years). The severity of the narrowed artery was assessed using the ankle-brachial index test. For comparison, another group of 91 patients (91 diabetic foot ulcers) treated with proximal tibial cortex transverse distraction was included. RESULTS: The mean preoperative ankle-brachial indexes of the two groups were 0.41±0.07 and 0.39±0.05 (OR 0.65 [95% CI -0.77 to 1.58]; P=0.62), respectively. The mean preoperative limb pain was 3.42±2.84 cm and 3.52±3.11 cm (OR 1.54 [95% CI -077 to 1.35]; P=0.083), respectively. At the 2-year follow-up visit, ulcers healed in 72 (83%) and 74 (81%) patients, respectively (P=0.188). The mean postoperative limb pain was 0.52±0.23 cm and 0.49±0.41 cm (OR 2.32 [95% CI -0.27 to 1.66]; P=0.078), respectively. Pin-site infection occurred in 2 patients and 8 patients (P=0.09), respectively. Ulcer recurrence occurred in 13 (15%) patients and 15 (16%) patients (P=0.205), respectively. CONCLUSIONS: Anterior superior iliac spine transverse distraction may be an effective alternative treatment for severe and recalcitrant diabetic foot ulcers. It may be associated with fewer distraction-site complications than proximal tibial cortex transverse distraction. LEVEL OF EVIDENCE: Therapeutic study, Level IIa.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pé Diabético/cirurgia , Cicatrização , , Tíbia/cirurgia , Resultado do Tratamento , Dor
8.
Opt Express ; 30(12): 21698-21709, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-36224883

RESUMO

Based on a single-beam injection distributed feedback semiconductor laser (DFB-SL) combining with optical heterodyne, a photonic scheme for generating dual-linear chirp microwave (dual-LCM) signal with identical or complementary chirp is proposed and experimentally demonstrated. For such a scheme, a continuous-wave (CW) light with a frequency of finj is split into two parts. One part is passing through a Mach-Zehnder modulator (MZM) driven by a modified sawtooth signal, and then its intensity varies with time as a sawtooth wave. Such a light is injected to a DFB-SL for generating a single linearly chirped microwave (single-LCM) signal. The other part of the CW light with frequency of finj is sent to a phase modulator (PM) driven by a sinusoidal signal, and one of higher-order sidebands is selected by a tunable optical filter and taken as the referenced light. Through heterodyning the referenced light with the single-LCM signal, a dual-LCM signal with identical (or complementary) chirp can be obtained. The experimental results demonstrate that, by adjusting the injection parameters and the frequency of the sinusoidal signal loaded on the PM, the central frequency of the generated dual-LCM signal can be widely tuned. For the period of the sawtooth signal at 10 µs, the bandwidth for each frequency band included in the generated dual-LCM signal is 19.36 GHz under identical chirp and 16.98 GHz under complementary chirp, respectively. Correspondingly, the time bandwidth product (TBWP) for each frequency band can reach 1.936 × 105 under identical chirp and 1.698 × 105 under complementary chirp, respectively.

9.
J Cell Mol Med ; 26(14): 3837-3849, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672925

RESUMO

The PBRM1 (PB1) gene which encodes the specific subunit BAF180 of the PBAF SWI/SNF complex, is highly mutated (~ 40%) in clear cell renal cell carcinoma (ccRCC). However, its functions and impact on cell signalling are still not fully understood. Aerobic glycolysis, also known as the 'Warburg Effect', is a hallmark of cancer, whether PB1 is involved in this metabolic shift in clear cell renal cell carcinoma remains unclear. Here, with established stable knockdown PB1 cell lines, we performed functional assays to access the effects on 786-O and SN12C cells. Based on the RNA-seq data, we selected some genes encoding key glycolytic enzymes, including PFKP, ENO1, PKM and LDHA, and examined the expression levels. The AKT-mTOR signalling pathway activity and expression of HIF1α were also analysed. Our data demonstrate that PB1 deficiency promotes the proliferation, migration, Xenograft growth of 786-O and SN12C cells. Notably, knockdown of PB1 activates AKT-mTOR signalling and increases the expression of key glycolytic enzymes at both mRNA and protein levels. Furthermore, we provide evidence that deficient PB1 and hypoxic conditions exert a synergistic effect on HIF 1α expression and lactate production. Thus, our study provides novel insights into the roles of tumour suppressor PB1 and suggests that the AKT-mTOR signalling pathway, as well as glycolysis, is a potential drug target for ccRCC patients with deficient PB1.


Assuntos
Carcinoma de Células Renais , Proteínas de Ligação a DNA , Neoplasias Renais , Fatores de Transcrição , Animais , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Glicólise/genética , Humanos , Neoplasias Renais/patologia , Vício Oncogênico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
J AOAC Int ; 105(5): 1319-1329, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-35451477

RESUMO

BACKGROUND: At present, the research on achiral drug and pesticide residue detection methods is still the mainstay at home and abroad, and there is still a lack of systematic research on the enantiomeric analysis of chiral drugs and pesticides. OBJECTIVE: In order to prepare a novel chiral stationary phase, whose "multi-mode" chiral separation chromatographic performance and its utility was verified. METHOD: An S-(-)-2-benzylamino-1-phenylethanol mono-derivative ß-cyclodextrin bonded stationary phase (BzCSP) was prepared based on the "thiol-ene" addition reaction. The chiral compounds including four types of chiral compounds were used as "probes," and their chiral chromatographic properties were evaluated. Furthermore, a new LC-MS/MS method for the determination of the enantiomeric residues of three chiral pesticides in five kinds of fruits and vegetables was established. RESULTS: The study found that the novel stationary phase was suitable for a variety of chromatographic modes (normal phase mode, reversed-phase mode, polar organic mode). The resolutions of hexaconazole (Hex), tebuconazole (Teb), and triticonazole (Trit) enantiomers could be up to 2.31, 1.68, and 1.48, respectively, within 30 min under reversed-phase chromatography. Based on the optimal chromatographic and mass spectrum conditions, a new LC-MS/MS quantitative method for the Hex, Teb, and Trit enantiomers was established by multi-reaction positive ion monitoring (MRM). The detection limits (LODs) of enantiomers were less than 0.89 µg/kg for Hex, 0.93 µg/kg for Teb, and 0.93 µg/kg for Trit, and the averaged recoveries of enantiomers were in the range of 75.8-106.3% for Hex, 77.4-116.3% for Teb, and 78.7-113.4% for Trit. The method had good reproducibility with the RSDs (<5%) for intraday and (<7%) for interday. CONCLUSIONS: The established method had the characteristics of good selectivity, high sensitivity, strong resistance to matrix interference, and good reproducibility. It is indicated that the stationary phase prepared by the "thiol-ene" addition reaction is a new type of multi-mode stationary phase, which has a good development value. HIGHLIGHTS: The study reported a new method for the rapid preparation of a rare "multi-mode" chiral stationary phase BzCSP based on the "thiol-ene" addition reaction and verified the practicability of BzCSP including good selectivity, high sensitivity, strong resistance to matrix interference, and good reproducibility.


Assuntos
Praguicidas , beta-Ciclodextrinas , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Frutas/química , Praguicidas/análise , Reprodutibilidade dos Testes , Estereoisomerismo , Compostos de Sulfidrila/análise , Espectrometria de Massas em Tandem/métodos , Verduras/química , beta-Ciclodextrinas/análise , beta-Ciclodextrinas/química
11.
Opt Express ; 29(16): 26265-26274, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34614936

RESUMO

Frequency-modulated continuous-wave (FMCW) can be acquired by using a distributed feedback semiconductor laser (DFB-SL) operating at period-one (P1) oscillation under an optical injection modulated by a Mach-Zehnder modulator (MZM). In this work, through introducing another MZM to establish cascade-modulated optical injection, an improved photonic scheme for generating high-quality FMCW is proposed and experimentally demonstrated. The experimental results indicate that, under appropriate injection parameters, the central frequency of the generated FMCW is widely tunable, and the bandwidth is larger than that obtained under a single MZM modulation. Further introducing optical feedback for suppressing the phase noise, the frequency comb contrast of the generated FMCW can be improved obviously.

12.
Materials (Basel) ; 14(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207222

RESUMO

As a major component of lignocellulosic biomass, lignin is one of the largest natural resources of biopolymers and, thus, an abundant and renewable raw material for products, such as high-performance fibers for industrial applications. Direct conversion of lignin has long been investigated, but the fiber spinning process for lignin is difficult and the obtained fibers exhibit unsatisfactory mechanical performance mainly due to the amorphous chemical structure, low molecular weight of lignin, and broad molecular weight distribution. Therefore, different textile spinning techniques, modifications of lignin, and incorporation of lignin into polymers have been and are being developed to increase lignin's spinnability and compatibility with existing materials to yield fibers with better mechanical performance. This review presents the latest advances in the textile fabrication techniques, modified lignin-based high-performance fibers, and their potential in the enhancement of the mechanical performance.

13.
BMJ Glob Health ; 5(8)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32792408

RESUMO

INTRODUCTION: Living-donor kidney transplantation is the gold standard treatment for patients with end-stage kidney disease. However, potential donors ubiquitously face financial as well as logistical barriers. To remove these disincentives from living kidney donations, the governments of 23 countries have implemented reimbursement programmes that shift the burdens of non-medical costs from donors to the governments or private entities. However, scientific evidence for the effectiveness of these programmes is scarce. The present study investigates whether these reimbursement programmes designed to ease the financial and logistical barriers succeeded in increasing the number of living kidney donations at the country level. The study examined within-country variations in the timing of such reimbursement programmes. METHOD: The study applied the difference-in-difference (two-way panel fixed-effect) technique on the Poisson distribution to estimate the effects of these reimbursement programmes on a 17 year long (2000-2016) dataset covering 109 countries where living donor kidney transplants were performed. RESULTS: The results indicated that reimbursement programmes have a statistically significant positive effect. Overall, the model predicted that reimbursement programmes increased country-level donation numbers by a factor of 1.12-1.16. CONCLUSION: Reimbursement programmes may be an effective approach to alleviate the kidney shortage worldwide. Further analysis is warranted on the type of reimbursement programmes and the ethical dimension of each type of such programmes.


Assuntos
Transplante de Rim , Doadores Vivos , Humanos , Rim
14.
Appl Opt ; 59(9): 2935-2941, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32225845

RESUMO

Based on a three-level model for quantum dot (QD) lasers, the characteristics of the photonic microwave generated by a QD laser simultaneously subject to optical injection and optical feedback are numerically investigated. First, the performance of the microwave signal generated by an optical injected QD laser operating at period one state are analyzed, and the mappings of the frequency and intensity of the generated microwave in the parameter space of the frequency detuning and injection strength are given, which are roughly similar to those reported experimentally. Next, an optical feedback loop is further introduced to the optically injected QD laser for compressing the linewidth of the microwave signal, and the results demonstrate that the linewidth of the generated microwave can be reduced by at least 1 order of magnitude under suitable feedback parameters. Finally, the effect of the linewidth enhancement factor on the generated microwave signal is analyzed.

15.
Am J Health Promot ; 34(1): 83-86, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31359763

RESUMO

OBJECTIVE: Examining associations of mother's behaviors and home/neighborhood physical activity (PA) environments with preschoolers' PA and screen time. DESIGN: Cross-sectional online survey. SETTING: Mothers with a 2 to 5 years old preschooler were recruited from the US panel members of Survey Sampling International. PARTICIPANTS: Five hundred thirty-one mothers with a preschool child aged 2 to 5 years old. OUTCOME MEASURE: Child daily screen time and PA, mother-child inside- and outside-home co-PA. ANALYSIS: K-mean cluster analysis and Logit and negative binomial regressions. RESULTS: Mothers' healthy behaviors, such as decreased screen time, healthy eating habits, and increased PA, and perceived importance for PA were significantly (P < .05) associated with preschoolers' decreased screen time and increased PA. Available toys (P < .01) and maternal perceived neighborhood safety (P < .05) were negatively correlated with preschoolers' screen time, while available room space (P < .01) was positively correlated with preschoolers' PA. Variables positively correlated with mother-child co-PA included mothers' PA (P < .001) and healthy eating habits (P < .05), and home room space (P < .05) for inside-home, and yard space and quality (P < .05) for outside-home. CONCLUSIONS: Mother's role modeling and home PA environment were positively associated with preschoolers' PA behavior.


Assuntos
Comportamento Infantil , Exercício Físico , Comportamentos Relacionados com a Saúde , Características de Residência , Adulto , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Relações Mãe-Filho , Tempo de Tela , Inquéritos e Questionários
16.
Opt Express ; 27(14): 19931-19939, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31503747

RESUMO

Via Santa Fe time series prediction and nonlinear channel equalization tasks, the performances of a reservoir computing (RC) system based on an optical feedback semiconductor laser (SL) under electrical information injection are numerically investigated. The simulated results show that the feedback delay time and strength seriously affect the performances of this RC system. By adopting a current-related optimized feedback delay time and strength, the RC can achieve a good performance for an SL biased within a wide region of 1.1-3.5 times its threshold. The prediction errors are smaller than 0.01 when implementing the Santa Fe tests, and the symbol error rates (SERs) are very low on the order of 10-5 for accomplishing nonlinear channel equalization tests under a signal-to-noise ratio (SNR) of 32 dB. Moreover, under a given RC performance level, the information processing rate of the RC can be improved by increasing the SL current.

17.
Assay Drug Dev Technol ; 16(2): 115-122, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29470101

RESUMO

Human glutamate dehydrogenase (GDH) plays an important role in neurological diseases, tumor metabolism, and hyperinsulinism-hyperammonemia syndrome (HHS). However, there are very few inhibitors known for human GDH. Recently, Ebselen was reported to crosslink with Escherichia coli GDH at the active site cysteine residue (Cys321), but the sequence alignment showed that the corresponding residue is Ala329 in human GDH. To investigate whether Ebselen could be an inhibitor for human GDH, we cloned and expressed an N-terminal His-tagged human GDH in E. coli. The recombinant human GDH enzyme showed expected properties such as adenosine diphosphate activation and nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate dual recognition. Further, we developed a 2-(3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H-tetrazol-3-ium-5-yl) benzenesulfonate sodium salt (EZMTT)-based assay for human GDH, which was highly sensitive and is suitable for high-throughput screening for potent GDH inhibitors. In addition, ForteBio binding assays demonstrated that Ebselen is a reversible active site inhibitor for human GDH. Since Ebselen is a multifunctional organoselenium compound in Phase III clinical trials for inflammation, an Ebselen-based GDH inhibitor might be valuable for future drug discovery for HHS patients.


Assuntos
Azóis/farmacologia , Domínio Catalítico/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Glutamato Desidrogenase/antagonistas & inibidores , Glutamato Desidrogenase/química , Compostos Organosselênicos/farmacologia , Azóis/química , Biocatálise/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Escherichia coli/enzimologia , Glutamato Desidrogenase/isolamento & purificação , Glutamato Desidrogenase/metabolismo , Humanos , Isoindóis , Modelos Moleculares , Estrutura Molecular , Compostos Organosselênicos/química , Relação Estrutura-Atividade
18.
Matern Child Nutr ; 14(2): e12540, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28994511

RESUMO

This study examined how food-related behaviours differed in mothers and their preschool children by levels of family functioning (cohesion and conflict) and household disorganization (chaos). A nationally representative sample of mothers of preschoolers completed an online survey assessing food-related behaviours of themselves and their children. Maternal and child diet, eating behaviours, and health status; household availability of fruits/vegetables, salty/fatty snacks, and sugar-sweetened beverages; family mealtime atmosphere; and family conflict, cohesion, and household chaos were assessed with valid, reliable scales. Cluster analyses assigned families into low, middle, and high conflict, cohesion, and chaos groups. Participants (n = 550) were 72% White, and 82% had some post-secondary education. Regression analysis examining the association of cluster grouping levels on diet-related behaviour measures revealed that positive home environments (i.e., low family conflict, high family cohesion, and low household chaos) were associated with healthier food-related behaviours (e.g., increased fruits/vegetables intake), whereas negative home environments (i.e., high family conflict, low family cohesion, and high household chaos) were associated with unhealthy food-related behaviours (e.g., greater % total calories from fat) even after controlling for sociodemographic and related behavioural factors. Findings suggest family functioning and household chaos are associated with food-related behaviours. This frequently overlooked component of family interaction may affect intervention outcomes and objectives of educational and interventional initiatives.


Assuntos
Fenômenos Fisiológicos da Nutrição Infantil , Dieta/métodos , Dieta/psicologia , Relações Familiares/psicologia , Comportamento Alimentar/psicologia , Fenômenos Fisiológicos da Nutrição Materna , Adolescente , Adulto , Pré-Escolar , Análise por Conglomerados , Conflito Familiar/psicologia , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Mães/psicologia , Adulto Jovem
19.
ACS Chem Biol ; 12(12): 3003-3011, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29072450

RESUMO

Ebselen modulates target proteins through redox reactions with selenocysteine/cysteine residues, or through binding to the zinc finger domains. However, a recent contradiction in ebselen inhibition of kidney type glutaminase (KGA) stimulated our interest in investigating its inhibition mechanism with glutamate dehydrogenase (GDH), KGA, thioredoxin reductase (TrxR), and glutathione S-transferase. Fluorescein- or biotin-labeled ebselen derivatives were synthesized for mechanistic analyses. Biomolecular interaction analyses showed that only GDH, KGA, and TrxR proteins can bind to the ebselen derivative, and the binding to GDH and KGA could be competed off by glutamine or glutamate. From the gel shift assays, the fluorescein-labeled ebselen derivative could co-migrate with hexameric GDH and monomeric/dimeric TrxR in a dose-dependent manner; it also co-migrated with KGA but disrupted the tetrameric form of the KGA enzyme at a high compound concentration. Further proteomic analysis demonstrated that the ebselen derivative could cross-link with proteins through a specific cysteine at the active site of GDH and TrxR proteins, but for KGA protein, the binding site is at the N-terminal appendix domain outside of the catalytic domain, which might explain why ebselen is not a potent KGA enzyme inhibitor in functional assays. In conclusion, ebselen could inhibit enzyme activity by binding to the catalytic domain or disruption of the protein complex. In addition, ebselen is a relatively potent selective GDH inhibitor that might provide potential therapeutic opportunities for hyperinsulinism-hyperammonemia syndrome patients who have the mutational loss of GTP inhibition.


Assuntos
Azóis/farmacologia , Glutamato Desidrogenase/antagonistas & inibidores , Glutaminase/antagonistas & inibidores , Compostos Organosselênicos/farmacologia , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Sequência de Aminoácidos , Azóis/química , Clonagem Molecular , Escherichia coli/metabolismo , Glutamato Desidrogenase/química , Glutamato Desidrogenase/metabolismo , Glutaminase/química , Glutaminase/classificação , Glutaminase/metabolismo , Isoindóis , Modelos Moleculares , Compostos Organosselênicos/química , Conformação Proteica , Proteômica , Tiorredoxina Dissulfeto Redutase/genética , Tiorredoxina Dissulfeto Redutase/metabolismo
20.
Int J Environ Res Public Health ; 12(11): 14640-68, 2015 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-26593930

RESUMO

The objective of this study was to examine the correlation between self-perception of being overweight and weight loss intentions, eating and exercise behaviors, as well as extreme weight-loss strategies for U.S. adolescents. This study uses 50,241 observations from the Youth Risk Behavior Surveillance Survey (YRBSS) 2001-2009, which were nationally representative sample of 9th- through 12th-grade students in both public and private schools in the US. This study finds that, irrespective of the weight status base on self-reported weight and height, adolescents who perceive themselves as overweight have a stronger intention to lose weight, but do not develop better eating and exercise habits, compared with their counterparts of same gender and reported weight status. Normal-weight adolescents, if they perceive themselves as overweight, are more likely to engage in health-compromising weight-loss methods. This study shows that it is critical to transform weight-loss intentions into actual behaviors among overweight/obese adolescents and improve the efficacy of behavioral interventions against childhood obesity. It also highlights the need of establishing a correct perception of body weight among normal weight adolescents to curb extreme weight-loss methods.


Assuntos
Imagem Corporal/psicologia , Dieta/psicologia , Sobrepeso/psicologia , Autoimagem , Estudantes/psicologia , Redução de Peso , Percepção de Peso , Adolescente , Atitude Frente a Saúde , Peso Corporal , Feminino , Humanos , Masculino , Obesidade Infantil/psicologia , Assunção de Riscos , Autorrelato , Fatores Sexuais , Inquéritos e Questionários , Estados Unidos , Adulto Jovem
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