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1.
Nano Lett ; 24(37): 11559-11566, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39240172

RESUMO

Fine-tuning of microstructures enables the modulation of optical properties at multiple scales from metasurfaces to geometric optics. However, a dynamic system with a significant deformation range and topology transformation remains challenging. Owing to its magnetic controllability, ferrofluid has proven to be fertile ground for a wide range of engineering and technological applications. Here, we demonstrate a series of intelligent optical surfaces based on ferrofluid, through which multiple optical functions inspired by nature can be realized. The tunability is based on the topological transition of the ferrofluid between the flat state and cone array upon magnetic actuation. In the visible band, a tunable visual appearance is realized. In the mid-infrared band, active manipulation of reflection is realized based on the gradient-index (GRIN) effect. This system also features low latency response and straightforward manufacturability, and it may open opportunities for novel technologies such as smart windows, color displays, infrared camouflage, and other infrared-related technologies.

2.
EMBO J ; 39(10): e103111, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32187724

RESUMO

The homeostatic link between oxidative stress and autophagy plays an important role in cellular responses to a wide variety of physiological and pathological conditions. However, the regulatory pathway and outcomes remain incompletely understood. Here, we show that reactive oxygen species (ROS) function as signaling molecules that regulate autophagy through ataxia-telangiectasia mutated (ATM) and cell cycle checkpoint kinase 2 (CHK2), a DNA damage response (DDR) pathway activated during metabolic and hypoxic stress. We report that CHK2 binds to and phosphorylates Beclin 1 at Ser90/Ser93, thereby impairing Beclin 1-Bcl-2 autophagy-regulatory complex formation in a ROS-dependent fashion. We further demonstrate that CHK2-mediated autophagy has an unexpected role in reducing ROS levels via the removal of damaged mitochondria, which is required for cell survival under stress conditions. Finally, CHK2-/- mice display aggravated infarct phenotypes and reduced Beclin 1 p-Ser90/Ser93 in a cerebral stroke model, suggesting an in vivo role of CHK2-induced autophagy in cell survival. Taken together, these results indicate that the ROS-ATM-CHK2-Beclin 1-autophagy axis serves as a physiological adaptation pathway that protects cells exposed to pathological conditions from stress-induced tissue damage.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteína Beclina-1/metabolismo , Quinase do Ponto de Checagem 2/metabolismo , AVC Isquêmico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Autofagia , Linhagem Celular , Modelos Animais de Doenças , Células HCT116 , Células HEK293 , Células HeLa , Humanos , Camundongos , Estresse Oxidativo , Fosforilação
3.
BMC Palliat Care ; 23(1): 147, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872168

RESUMO

PURPOSE: This study aimed to assess the therapeutic efficacy of Reiki therapy in alleviating anxiety. METHODS: In adherence to academic standards, a thorough search was conducted across esteemed databases such as PubMed, Web of Science, Science Direct, and the Cochrane Library. The primary objective of this search was to pinpoint peer-reviewed articles published in English that satisfied specific criteria: (1) employing an experimental or quasi-experimental study design, (2) incorporating Reiki therapy as the independent variable, (3) encompassing diverse patient populations along with healthy individuals, and (4) assessing anxiety as the measured outcome. RESULTS: The study involved 824 participants, all of whom were aged 18 years or older. Reiki therapy was found to have a significant effect on anxiety intervention(SMD=-0.82, 95CI -1.29∼-0.36, P = 0.001). Subgroup analysis indicated that the types of subjects (chronically ill individuals and the general adult population) and the dosage/frequency of the intervention (≤ 3 sessions and 6-8 sessions) were significant factors influencing the variability in anxiety reduction. CONCLUSION: Short-term Reiki therapy interventions of ≤ 3 sessions and 6-8 sessions have demonstrated effectiveness in reducing health and procedural anxiety in patients with chronic conditions such as gastrointestinal endoscopy inflammation, fibromyalgia, and depression, as well as in the general population. It is important to note that the efficacy of Reiki therapy in decreasing preoperative anxiety and death-related anxiety in preoperative patients and cancer patients is somewhat less consistent. These discrepancies may be attributed to individual pathophysiological states, psychological conditions, and treatment expectations.


Assuntos
Ansiedade , Toque Terapêutico , Humanos , Ansiedade/terapia , Ansiedade/psicologia , Toque Terapêutico/métodos , Adulto
4.
J Minim Access Surg ; 20(2): 201-206, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37843160

RESUMO

OBJECTIVE: The objective of this study was to explore the influence of traditional laparoscopic surgery and transumbilical single-port laparoscopic surgery on ovarian function in patients with benign ovarian tumours. MATERIALS AND METHODS: Forty-four patients with benign ovarian tumours who were treated in our hospital from January 2020 to June 2021 were selected and randomly divided into two groups, with 22 cases in each group according to random number table. The conventional group was treated with conventional laparoscopic surgery, while the modified group was treated with transumbilical single-port laparoscopic surgery. The measurement method was t -test, and the enumeration method was two tests. The clinical operation-related indicators, ovarian function (follicle-stimulating hormone, E 2 and luteinising hormone), complication incidence, Visual Analogue Scale (VAS) and landscaping satisfaction scores of the two groups were compared. RESULTS: There were no significant differences in complications and operation duration between the two groups ( P > 0.05). After treatment, the ovarian function indexes and beautification satisfaction scores of the modified group were significantly superior to those of the conventional group ( P < 0.05). Besides, the intraoperative bleeding volume, post-operative exhaust time, hospital stay and three-dimensional VAS scores on day 1 and day 3 after surgery of the modified group were lower than those of the conventional group ( P < 0.05). CONCLUSION: Transumbilical single-port laparoscopic surgery for benign ovarian tumours has a significant clinical effect, which can effectively reduce bleeding during the operation, improve ovarian function, relieve surgical pain, promote rapid post-operative recovery and improve patients' satisfaction with landscaping. It is worthy of clinical application.

5.
BMC Genomics ; 24(1): 84, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36814191

RESUMO

BACKGROUND: Methyl-binding domain (MBD) is a class of methyl-CpG-binding domain proteins that affects the regulation of gene expression through epigenetic modifications. MBD genes are not only inseparable from DNA methylation but have also been identified and validated in various plants. Although MBD is involved in a group of physiological processes and stress regulation in these plants, MBD genes in Eleutherococcus senticosus remain largely unknown. RESULTS: Twenty EsMBD genes were identified in E. senticosus. Among the 24 chromosomes of E. senticosus, EsMBD genes were unevenly distributed on 12 chromosomes, and only one tandem repeat gene existed. Collinearity analysis showed that the fragment duplication was the main motif for EsMBD gene expansion. As the species of Araliaceae evolved, MBD genes also evolved and gradually exhibited different functional differentiation. Furthermore, cis-acting element analysis showed that there were numerous cis-acting elements in the EsMBD promoter region, among which light response elements and anaerobic induction elements were dominant. The expression motif analysis revealed that 60% of the EsMBDs were up-regulated in the 30% water content group. CONCLUSIONS: By comparing the transcriptome data of different saponin contents of E. senticosus and integrating them with the outcomes of molecular docking analysis, we hypothesized that EsMBD2 and EsMBD5 jointly affect the secondary metabolic processes of E. senticosus saponins by binding to methylated CpG under conditions of drought stress. The results of this study laid the foundation for subsequent research on the E. senticosus and MBD genes.


Assuntos
Eleutherococcus , Saponinas , Eleutherococcus/química , Eleutherococcus/genética , Eleutherococcus/metabolismo , Simulação de Acoplamento Molecular , Desmetilação do DNA , Secas , Metilação de DNA
6.
Neuroendocrinology ; 113(1): 80-91, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36030776

RESUMO

INTRODUCTION: Fat mass and obesity-associated (FTO) gene is strongly associated with obesity which brings a major health threat. Altered expression of its encoded protein FTO in the hypothalamus has been identified to contribute to central control of appetite and body weight. However, its molecular mechanisms remain elusive. METHODS: Mouse hypothalamic POMC cell line N43/5 was treated with FTO inhibitor rhein, FTO shRNA, or extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126 to inhibit FTO or ERK1/2. Rhein and U0126 were injected into lateral ventricle of the mice by intracerebroventricular cannulation. Western blotting and immunofluorescent assays were performed to monitor protein level. RESULTS: This study identified that inhibition of FTO in N43/5 cells led to phosphorylation of signal transducer and activator of transcription 3 (STAT3) at S727 site and induced p-STAT3-S727 nuclear translocation. We further showed that FTO inhibition promoted phosphorylation of ERK1/2; specific inhibition of ERK1/2 signaling by U0126 could abolish the effect of FTO inhibition on STAT3-S727 phosphorylation and nuclear translocation. Furthermore, we found that inhibition of hypothalamic FTO promoted STAT3-S727 phosphorylation in the hypothalamic arcuate nucleus, and the mice showed reductions in food intake and body weight. In addition, inhibition of hypothalamic ERK1/2 could abolish the effects of FTO inhibition on STAT3-S727 phosphorylation, reductions of food intake and body weight. CONCLUSION: Our in vitro and in vivo data suggest that the inhibition of hypothalamic FTO could activate STAT3 through ERK1/2, which is potentially associated with reductions in food intake and body weight.


Assuntos
Sistema de Sinalização das MAP Quinases , Fator de Transcrição STAT3 , Camundongos , Animais , Fator de Transcrição STAT3/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Hipotálamo/metabolismo , Peso Corporal , Obesidade/metabolismo , Ingestão de Alimentos , Fosforilação , Leptina/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo
7.
Bioorg Chem ; 132: 106356, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36669357

RESUMO

The mammalian target of rapamycin (mTOR) has been proved to be an effective target for cancer therapy. Two kinds of mTOR inhibitors, the rapalogs and mTOR kinase inhibitors (TORKi), have been developed and clinically validated in several types of malignancies. Compared with rapalogs, TORKi can exert better antitumor activity by inhibiting both mTORC1 and mTORC2, but the clinical development of current TORKi candidates has been relative slow, more TORKi with novel scaffold need to be developed to expand the current pipelines. In this study, a series of 9-methyl-9H-purine and thieno[3, 2-d]pyrimidine derivatives were designed, synthesized and biological evaluation. Most of these compounds exhibited good mTOR kinase inhibitory activity and selectivity over PI3Kα. Subsequent antiproliferative assay allowed us to identify the lead compound 15i, which display nanomolar to low micromolar IC50s against six human cancer cell lines. 15i could induce cell cycle arrest of MCF-7, PC-3 and A549 cells at the G0/G1 phase and suppress the migration and invasion of these cancer cells by suppressing the phosphorylation of AKT and P70S6 kinase. It could also regulate autophagy-related proteins to induce autophagy. Therefore, 15i would be a starting point for the development of new TORKi as anticancer drug.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Inibidores de MTOR , Inibidores de Proteínas Quinases , Serina-Treonina Quinases TOR/metabolismo , Neoplasias/tratamento farmacológico , Purinas/farmacologia , Pirimidinas , Proliferação de Células , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Relação Estrutura-Atividade
8.
Brief Bioinform ; 21(5): 1776-1786, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31686106

RESUMO

Genes are unique in functional role and differ in their sensitivities to genetic defects, but with difficulties in pathogenicity prediction. This study attempted to improve the performance of existing in silico algorithms and find a common solution based on individualization strategy. We initiated the individualization with the epilepsy-related SCN1A variants by sub-regional stratification. SCN1A missense variants related to epilepsy were retrieved from mutation databases, and benign missense variants were collected from ExAC database. Predictions were performed by using 10 traditional tools with stepwise optimizations. Model predictive ability was evaluated using the five-fold cross-validations on variants of SCN1A, SCN2A, and KCNQ2. Additional validation was performed in SCN1A variants of damage-confirmed/familial epilepsy. The performance of commonly used predictors was less satisfactory for SCN1A with accuracy less than 80% and varied dramatically by functional domains of Nav1.1. Multistep individualized optimizations, including cutoff resetting, domain-based stratification, and combination of predicting algorithms, significantly increased predictive performance. Similar improvements were obtained for variants in SCN2A and KCNQ2. The predictive performance of the recently developed ensemble tools, such as Mendelian clinically applicable pathogenicity, combined annotation-dependent depletion and Eigen, was also improved dramatically by application of the strategy with molecular sub-regional stratification. The prediction scores of SCN1A variants showed linear correlations with the degree of functional defects and the severity of clinical phenotypes. This study highlights the need of individualized optimization with molecular sub-regional stratification for each gene in practice.


Assuntos
Variação Genética , Simulação por Computador , Bases de Dados Genéticas , Humanos , Canal de Potássio KCNQ2/genética , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Canal de Sódio Disparado por Voltagem NAV1.2/genética
9.
Cell Mol Neurobiol ; 42(3): 777-790, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33058074

RESUMO

Arachidonic acid (AA), a polyunsaturated fatty acid, is involved in the modulation of neuronal excitability in the brain. Arachidonate lipoxygenase 3 (ALOXE3), a critical enzyme in the AA metabolic pathway, catalyzes the derivate of AA into hepoxilins. However, the expression pattern of ALOXE3 and its role in the brain has not been described until now. Here we showed that the levels of Aloxe3 mRNA and protein kept increasing since birth and reached the highest level at postnatal day 30 in the mouse hippocampus and temporal cortex. Histomorphological analyses indicated that ALOXE3 was enriched in adult hippocampus, somatosensory cortex and striatum. The distribution was restricted to the neurites of function-specific subregions, such as mossy fibre connecting hilus and CA3 neurons, termini of Schaffer collateral projections, and the layers III and IV of somatosensory cortex. The spatiotemporal expression pattern of ALOXE3 suggests its potential role in the modulation of neural excitability and seizure susceptibility. In fact, decreased expression of ALOXE3 and elevated concentration of AA in the hippocampus was found after status epilepticus (SE) induced by pilocarpine. Local overexpression of ALOXE3 via adeno-associated virus gene transfer restored the elevated AA level induced by SE, alleviated seizure severities by increasing the latencies to myclonic switch, clonic convulsions and tonic hindlimb extensions, and decreased the mortality rate in the pilocarpine-induced SE model. These results suggest that the expression of ALOXE3 is a crucial regulator of AA metabolism in brain, and potentially acts as a regulator of neural excitability, thereby controlling brain development and seizure susceptibility.


Assuntos
Convulsões , Estado Epiléptico , Animais , Encéfalo/metabolismo , Hipocampo/metabolismo , Camundongos , Pilocarpina , Convulsões/induzido quimicamente , Convulsões/genética , Convulsões/metabolismo , Estado Epiléptico/induzido quimicamente
10.
Anal Chem ; 93(3): 1310-1316, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33356153

RESUMO

An innovative and versatile microextraction technique based on nanoconfined solvent on carbon nanofibers has been conceived, realized, optimized, and presented here. The extraction capabilities of this technique toward polar, medium polar, and/or nonpolar substances can be easily modulated based on the nanoconfined solvent used. The so-called nanoconfined liquid phase nanoextraction showed excellent characteristics in terms of extraction recoveries, extraction time (≤1 min), reliability, and versatility. A needle-tip device has been realized on the base of this extraction process to allow direct extraction procedures and minimally invasive testing: this device guarantees a safe insertion in aqueous or soft samples, and it allows a fast and minimally invasive analyte extraction. Due to its versatility, chemical stability, and mechanical flexibility, nanoconfined liquid phase nanoextraction can be considered a powerful candidate for high-throughput analyses of biological samples.

11.
Cell Mol Neurobiol ; 41(6): 1257-1269, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32500354

RESUMO

Valproate (VPA), a widely-used antiepileptic drug, is a selective inhibitor of histone deacetylase (HDAC) that play important roles in epigenetic regulation. The patient with different diseases receiving this drug tend to exhibit weight gain and abnormal metabolic phenotypes, but the underlying mechanisms remain largely unknown. Here we show that VPA increases the Fto mRNA and protein expression in mouse hypothalamic GT1-7 cells. Interestingly, VPA promotes histone H3/H4 acetylation and the FTO expression which could be reversed by C646, an inhibitor for histone acetyltransferase. Furthermore, VPA weakens the FTO's binding and enhances the binding of transcription factor TAF1 to the Fto promoter, and C646 leads to reverse effect of the VPA, suggesting an involvement of the dynamic of histone H3/H4 acetylation in the regulation of FTO expression. In addition, the mice exhibit an increase in the food intake and body weight at the beginning of 2-week treatment with VPA. Simultaneously, in the hypothalamus of the VPA-treated mice, the FTO expression is upregulated and the H3/H4 acetylation is increased; further the FTO's binding to the Fto promoter is decreased and the TAF1's binding to the promoter is enhanced, suggesting that VPA promotes the assembly of the basal transcriptional machinery of the Fto gene. Finally, the inhibitor C646 could restore the effects of VPA on FTO expression, H3/H4 acetylation, body weight, and food intake; and loss of FTO could reverse the VPA-induced increase of body weight and food intake. Taken together, this study suggests an involvement of VPA in the epigenetic upregulation of hypothalamic FTO expression that is potentially associated with the VPA-induced weight gain.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/biossíntese , Epigênese Genética/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Ácido Valproico/farmacologia , Aumento de Peso/efeitos dos fármacos , Animais , Anticonvulsivantes/farmacologia , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Epigênese Genética/fisiologia , Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia , Aumento de Peso/fisiologia
12.
Biochem Genet ; 59(2): 491-505, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33135088

RESUMO

Chalcone Isomerase (CHI) catalyzes the biosynthesis of flavonoids and secondary metabolism in plants. Currently, there is no systematic analysis of CHIs gene family in Fagaceae which is available. In this study, twenty-two CHI proteins were identified in five species of the Fagaceae family. The CHI superfamily in Fagaceae can be classified into three subfamilies and five groups using phylogenetic analysis, analysis of physicochemical properties, and structural prediction. Results indicated that serine (Ser) and isoleucine (Ile) residues determine the substrate preferred by active Type I Fagaceae CHI, and the chalcone isomerase-like (CHIL) of Fagaceae had active site residues. Adaptive analysis of CHIs showed that CHIs are subject to selection pressure. The active CHI gene of Fagaceae was located in the cytoplasm, and it had the typical gene structure of CHI and contains four exons. All the twenty-two identified CHIs had the conserved domain motif 3, and the different groups had their own structural characteristics. In the process of fatty acid binding protein (FAP) evolution to CHIL and CHI, the physical and chemical properties of proteins also had significant differences in addition to changes in protein functions.


Assuntos
Fagaceae/genética , Liases Intramoleculares/genética , Filogenia , Proteínas de Plantas/genética , Fagaceae/enzimologia
13.
BMC Ophthalmol ; 20(1): 146, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295555

RESUMO

BACKGROUND: The prevalence of myopia and associated risk factors among children in Chongqing has not yet been determined. This study investigated the prevalence of myopia and possible relationships between myopia and several related factors among school children in Chongqing. METHODS: This cross-sectional study assessed a sample of 997 children (7-13 years of age) attending primary school in Chongqing. Data were obtained from visual acuity and refractive error measurements and a structured questionnaire. Myopia was defined as visual acuity < 5.0 and refractive error (spherical equivalent) of < - 0.50 diopters (D) in either eye. Multilevel modeling was applied to investigate potential risk factors. RESULTS: The overall prevalence of myopia was 33.9% [95% confidence interval (CI) = 31.0-36.8]; myopia prevalence significantly increased with age. Girls were at a higher risk of myopia than boys [odds ratio (OR) = 1.449, 95% CI = 1.060-1.979]. Children with paternal myopia (OR = 2.130, 95% CI = 1.376-3.297) or maternal myopia (OR = 1.861, 95% CI =1.153-3.002) had a higher risk of myopia than those without myopic parents. Children who spent more than 1 h daily outdoors were less likely to have myopia; meanwhile, children who did homework more than 3 h daily (OR = 2.237, 95% CI = 1.041-4.804), watched television more than 3 h daily (OR = 2.106, 95% CI = 1.200-3.697), or played electronics more than 1 h daily (OR = 2.983, 95% CI = 2.088-4.262) had a higher risk of myopia. CONCLUSIONS: Myopia in school children is a serious public health problem in Chongqing. Myopia was significantly positively associated with higher age, female sex, parental myopia, and spending a long time indoors; notably, playing with electronics had the greatest influence on the risk of myopia.


Assuntos
Povo Asiático/estatística & dados numéricos , Miopia/epidemiologia , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Miopia/diagnóstico , Exame Físico , Prevalência , Refração Ocular , Fatores de Risco , População Rural/estatística & dados numéricos , Instituições Acadêmicas , Inquéritos e Questionários , População Urbana/estatística & dados numéricos , Acuidade Visual/fisiologia
14.
J Neuroinflammation ; 16(1): 230, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747905

RESUMO

BACKGROUND: It is widely accepted that mitochondria have a direct impact on neuronal function and survival. Oxidative stress caused by mitochondrial abnormalities play an important role in the pathophysiology of lipopolysaccharide (LPS)-induced memory impairment. Elamipretide (SS-31) is a novel mitochondrion-targeted antioxidant. However, the impact of elamipretide on the cognitive sequelae of inflammatory and oxidative stress is unknown. METHODS: We utilized MWM and contextual fear conditioning test to assess hippocampus-related learning and memory performance. Molecular biology techniques and ELISA were used to examine mitochondrial function, oxidative stress, and the inflammatory response. TUNEL and Golgi-staining was used to detect neural cell apoptosis and the density of dendritic spines in the mouse hippocampus. RESULTS: Mice treated with LPS exhibited mitochondrial dysfunction, oxidative stress, an inflammatory response, neural cell apoptosis, and loss of dendritic spines in the hippocampus, leading to impaired hippocampus-related learning and memory performance in the MWM and contextual fear conditioning test. Treatment with elamipretide significantly ameliorated LPS-induced learning and memory impairment during behavioral tests. Notably, elamipretide not only provided protective effects against mitochondrial dysfunction and oxidative stress but also facilitated the regulation of brain-derived neurotrophic factor (BDNF) signaling, including the reversal of important synaptic-signaling proteins and increased synaptic structural complexity. CONCLUSION: These findings indicate that LPS-induced memory impairment can be attenuated by the mitochondrion-targeted antioxidant elamipretide. Consequently, elamipretide may have a therapeutic potential in preventing damage from the oxidative stress and neuroinflammation that contribute to perioperative neurocognitive disorders (PND), which makes mitochondria a potential target for treatment strategies for PND.


Assuntos
Antioxidantes/farmacologia , Inflamação , Mitocôndrias/efeitos dos fármacos , Oligopeptídeos/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos
15.
Protein Expr Purif ; 163: 105452, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31301428

RESUMO

General control nonderepressible 2 (GCN2) can phosphorylate the α subunit of eukaryotic initiation factor eIF2 (eukaryotic translation initiation factor 2) to down-regulateprotein synthesis in response to various biotic and abiotic stresses. However, the kinase activity of plant GCN2 has not been well-characterized in vitro. In this study, the kinase domain of Nicotiana tabacum GCN2 (NtGCN2) was inserted into the pET15b vector for prokaryotic expressionin Escherichia coli BL21-CodonPlus-(DE3)-RIPL after induction by 0.5 mmol L-1 IPTG for 13 h at 16 °C. The soluble protein was collected and purified by Ni2+-NTA agarose column, anion exchange, and molecular sieve, and the purified proteinwas used for kinase assays and the preparation of a polyclonal antibody. Enzyme-linked immunosorbent assay results showed that the titer of the antiserum was 1:520K. Western blot analysis showed that the prepared antibody reacted with GCN2 in tobacco. Additionally, the kinase activity of NtGCN2 was characterized by using recombinant NteIF2α protein as a substrate in vitro. The results showed that NtGCN2 phosphorylated NteIF2α in vitro, with the level of phosphorylation positively correlated with the NtGCN2 concentration and reaction time. Our study has prepared a specific antibody, and proves NtGCN2 can phosphorylate NteIF2α in vitro, which lays a foundation for further study of the function and interaction network of NtGCN2.


Assuntos
Nicotiana/enzimologia , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/isolamento & purificação , Anticorpos/imunologia , Clonagem Molecular , Ensaio de Imunoadsorção Enzimática , Escherichia coli , Fator de Iniciação 2 em Eucariotos/metabolismo , Vetores Genéticos , Fosforilação , Domínios Proteicos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo
16.
Ecotoxicol Environ Saf ; 162: 35-41, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-29960120

RESUMO

To identify possible cadmium (Cd) accumulators or hyperaccumulators among ornamental plants, a pot experiment involving increasing Cd concentration (0, 5, 15, 30, 60, and 100 mg kg-1) was conducted among seven species. The principal objective was to screen for ornamental plants with an exceptional ability to accumulate and translocate Cd ions as well as sufficient biomass for harvesting. Regarding shoot biomass, root biomass, plant height and tolerance index (TI), Malva rotundifolia showed high tolerance to Cd and Malva crispa, Sida rhombifolia, Celosia argentea and Celosia cristata medium tolerance; Althaea rosea and Abutilon theophrasti were more sensitive to Cd than the other plants. A hormetic response was induced by Cd in M. crispa, C. argentea, C. cristata and M. rotundifolia. Based on its capacity for Cd accumulation, bioaccumulation coefficients (BCFs) and translocation factors (TFs), M. rotundifolia was selected from candidate plants after 60 days of exposure to Cd-contaminated soil and found to have accumulated more than 200 mg kg-1 Cd in its roots and 900 mg kg-1 in its shoots. Moreover, M. rotundifolia BCFs and TFs were higher than 1.0, with the former ranging from 1.41 to 3.31 and the latter from 1.03 to 7.37. Taken together, these results indicate that M. rotundifolia can be classified as a model hyperaccumulator.


Assuntos
Cádmio/metabolismo , Malva/metabolismo , Poluentes do Solo/metabolismo , Biodegradação Ambiental , Biomassa , Cádmio/toxicidade , Malva/efeitos dos fármacos , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Plantas/efeitos dos fármacos , Plantas/metabolismo , Poluentes do Solo/toxicidade
17.
J Offender Rehabil ; 57(5): 330-342, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31649474

RESUMO

Black Americans are overrepresented among incarcerated individuals and those infected with sexually transmitted infections. We assessed unprotected sexual behavior among 165 formerly incarcerated Black Americans in New York City, New York. Most participants (63%) reported engaging in unprotected sexual behavior post-incarceration. According to our regression results, less time spent in jail and reporting multiple sexual partnerships were associated with a greater likelihood of engaging in unprotected sexual behavior. High rates of unprotected sexual behavior may place formerly incarcerated Black Americans at risk for sexually transmitted infections. Discharge planning programs that include STI/HIV prevention information and education may be useful for this population.

18.
Biochim Biophys Acta Mol Basis Dis ; 1863(6): 1492-1499, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28433711

RESUMO

Voltage-gated sodium channel α-subunit type I (NaV1.1, encoded by SCN1A gene) plays a critical role in the excitability of brain. Downregulation of SCN1A expression is associated with epilepsy, a common neurological disorder characterized by recurrent seizures. Here we reveal a novel role of malate dehydrogenase 2 (MDH2) in the posttranscriptional regulation of SCN1A expression under seizure condition. We identified that MDH2 was an RNA binding protein that could bind two of the four conserved regions in the 3' UTRs of SCN1A. We further showed that knockdown of MDH2 or inactivation of MDH2 activity in HEK-293 cells increased the reporter gene expression through the 3' UTR of SCN1A, and MDH2 overexpression decreased gene expression by affecting mRNA stability. In the hippocampus of seizure mice, the upregulation of MDH2 expression contributed to the decrease of the NaV1.1 levels at posttranscriptional level. In addition, we showed that the H2O2 levels increased in the hippocampus of the seizure mice, and H2O2 could promote the binding of MDH2 to the binding sites of Scn1a gene, whereas ß-mercaptoethanol decreased the binding capability, indicating an important effect of the seizure-induced oxidation on the MDH2-mediated downregulation of Scn1a expression. Taken together, these data suggest that MDH2, functioning as an RNA-binding protein, is involved in the posttranscriptional downregulation of SCN1A expression under seizure condition.


Assuntos
Regiões 3' não Traduzidas , Regulação para Baixo , Malato Desidrogenase/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.1/biossíntese , Proteínas de Ligação a RNA/metabolismo , Convulsões/metabolismo , Animais , Células HEK293 , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Malato Desidrogenase/genética , Camundongos , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Proteínas de Ligação a RNA/genética , Convulsões/genética , Convulsões/patologia
19.
Mol Divers ; 21(4): 957-966, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28791568

RESUMO

By combining triazenes with chalcones, we designed and synthesized 12 novel glycosides. The antiproliferative activity of all products was screened using an MTT assay against MGC803 cells and PC-3 cells. Compound [Formula: see text] displayed more potent antiproliferative activity than dacarbazine. Furthermore, we explored the preliminary structure activity relationship of all target compounds. The derivatives in this work might serve as bioactive fragments and lead compounds for developing more potent cytotoxic agents.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Chalconas/química , Glicosídeos/síntese química , Glicosídeos/farmacologia , Triazenos/química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Glicosídeos/química , Humanos , Modelos Moleculares , Conformação Molecular , Relação Estrutura-Atividade
20.
Zhongguo Zhong Yao Za Zhi ; 42(4): 675-679, 2017 Feb.
Artigo em Zh | MEDLINE | ID: mdl-28959836

RESUMO

The sweet taste and health effect of Lithocarpus polystachyus are mainly related flavonoid. To obtain Lithocarpus transcriptome database and flavonoid biosynthesis-related genes, the RNA-Seq techology (Illumina HiSeq 4000) was used to sequence its transcriptome. Six Gb database was assembled after assembly steps, and 41 043 of L. polystachyus unigenes were obtained. With blasting them with 7 data banks, all unigenes were involved in 51 GO-terms and 237 metabolic pathways. And furthermore 28 genes of the flavonoid biosynthesis-related were found. After using the MicroSatallite, 18 161 SSR were obtained, the single-nucleotide-repeated was the richest at 7 346. These data represent abundant messages about transcripts and provide valuable genome data sources in molecular biology of L. polystachyus.


Assuntos
Fagaceae/metabolismo , Flavonoides/biossíntese , Genes de Plantas , Transcriptoma , Vias Biossintéticas , Fagaceae/genética , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala
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