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Bisphenol A (BPA) and its substitute bisphenol S (BPS) are desirable materials widely used in manufacturing plastic products but can pose carcinogenic risks to humans. A new conductive iron-based metal-organic framework (Fe-HHTP)-modified pencil graphite electrode (PGE) for electrochemically sensing BPA and BPS was prepared and fully characterized by SEM, TEM, FT-IR, XRD, and XPS. Results showed that the optimal conditions for preparing Fe-HHTP/PGE were a pH of 6.5, a Fe-HHTP concentration of 2 mg·mL-1, a deposition potential of 0 V, and a deposition time of 100 s. The Fe-HHTP/PGE prepared under such conditions harbored a significant electrocatalytic activity with a detection limit of 0.8 nM for BPA and 1.7 nM for BPS (S/N = 3). Correspondingly, the electrochemical response current was linearly correlated to BPA and BPS, ranging from 0.01 to 100 µM. Fe-HHTP/PGE also obtained satisfactory recoveries by 93.8-102.1% and 96.0-101.3% for detecting BPA and BPS in plastic food packaging samples. Our work has provided a novel electrochemical tool to simultaneously detect BPA and BPS in food packaging samples and environmental matrixes.
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Grafite , Estruturas Metalorgânicas , Fenóis , Humanos , Grafite/química , Espectroscopia de Infravermelho com Transformada de Fourier , Compostos Benzidrílicos/química , EletrodosRESUMO
Picromerus lewisi Scott (Hemiptera: Pentatomidae) is a widely used natural enemy, through this study, we proved that its complete mitochondrial genome of it had similar characteristics to those of other Hemiptera. The mitogenome of P. lewisi is a circular molecule of 18,123 bp with 74.0% A + T content, containing 13 protein-coding genes (PCGs), 22 tRNAs, 2 rRNAs, and one control region. Phylogenetic tree based on 13 PCGs from 17 Panheteroptera species (two species of the Cimicomorpha are used as outgroup, 15 species belong to the Pentatomomorpha) suggested that P. lewisi has a closer relationship with E. thomsoni within Pentatomidae family.
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Background: Better survival for overweight and obese patients after ST-segment elevation myocardial infarction (STEMI) has been demonstrated. The association between body mass index (BMI), microvascular obstruction (MVO), and area at risk (AAR) after STEMI was evaluated. Methods: A prospective observational study was performed to enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for STEMI and cardiac magnetic resonance was performed within 5-7 days. Patients were classified as normal weight (18.5 ≤BMI <24.0 kg/m2), overweight (24.0 ≤BMI <28.0 kg/m2), or obese (BMI ≥28 kg/m2). Results: Among 225 patients undergoing pPCI, 67 (30.00%) were normal weight, 113 (50.22%) were overweight, and 45 (20.00%) were obese. BMI ≥28 kg/m2 was significantly associated with less risk of MVO when compared with a normal BMI after multivariable adjustment (overweight: HR 0.29, 95% CI 0.13-0.68, p = 0.004). Compared with normal weight patients, obese and overweight patients tend to have larger hearts (greater left ventricular end-diastolic volume [LVEDV] and left ventricular [LV] mass). In adjusted analysis, increased BMI was significantly associated with a smaller AAR. In addition, obese patients had a smaller AAR (ß = -0.252, 95% CI -20.298- -3.244, p = 0.007) and AAR, % LV mass (ß = -0.331, 95% CI -0.211- -0.062, p < 0.001) than normal weight patients. Conclusion: Obesity (BMI ≥28 kg/m2) is independently associated with lower risks of MVO and a smaller AAR, % LV mass than normal weight patients among subjects undergoing pPCI for STEMI.
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The electronic conductive metal-organic frameworks (EC-MOFs) based on a single ligand are not suitable for the accurate detection of bisphenol A (BPA) due to the limitations of their electron-transfer-based sensing mechanism. To overcome this drawback, we developed EC-MOFs with novel dual-ligands, 2,3,6,7,10,11-hexahydroxy-sanya-phenyl (HHTP) and tetrahydroxy 1,4-quinone (THQ), and metal ions. A new class of 2D π-conjugation-based EC-MOFs (M-(HHTP)(THQ)) was synthesized by a self-assemble technique. Its best member (Cu-(HHTP)(THQ)) was selected and combined with reduced graphene (rGO) to form a Cu-(HHTP)(THQ)@rGO composite, which was thoroughly characterized by X-ray diffraction, field scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Cu-(HHTP)(THQ)@rGO was drop-cast onto a glassy carbon electrode (GCE) to obtain a sensor for BPA detection. Cyclic voltammetry and electrochemical impedance tests were used to evaluate the electrode performance. The oxidation current of BPA on the Cu-(HHTP)(THQ)@rGO/GCE was substantially higher than on unmodified GCE, which could be explained by a synergy between Cu-(HHTP)(THQ) (which provided sensing and adsorption) and rGO (which provided fast electron conductivity and high surface area). Cu-(HHTP)(THQ)@rGO/GCE exhibited a linear detection range for 0.05-100 µmol·L-1 of BPA with 3.6 nmol·L-1 (S/N = 3) detection limit. We believe that our novel electrode and BPA sensing method extends the application perspectives of EC-MOFs in the electrocatalysis and sensing fields.
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Grafite , Estruturas Metalorgânicas , Compostos Benzidrílicos , Carbono/química , Técnicas Eletroquímicas/métodos , Eletrodos , Eletrônica , Grafite/química , Ligantes , Estruturas Metalorgânicas/química , FenóisRESUMO
Objective: This study aims to understand primary school students' behavior and awareness of sun exposure and sunscreen in Beijing, China. Methods: A questionnaire survey was conducted of 232 students in grades 4-6 at a public primary school in Beijing, including 129 boys (55.6%) and 103 girls (44.4%). The contents of the questionnaire included awareness about ultraviolet rays, sun exposure, sunscreen habits, and the understanding and use of sunscreen. Results: The majority of the subjects (75.0%) said they had never been sunburned, and 26.3% had never been tanned. Only 7.3% of the primary school students had a comprehensive and correct understanding that sunlight will burn, cause cancer, tan, and age the skin. Sunscreen (47.8%), sunshades (47.4%), sun hats (44.4%), avoiding going out at noon (37.5%), and sunglasses (30.2%) were the most frequently used sunscreen means. Furthermore, 47.8% of primary school students used topical sunscreen for light protection, higher than other measures. The proportion of girls using sunscreen at least once a day was more than boys. Conclusion: Primary school students in Beijing, China, do not have a comprehensive understanding of ultraviolet rays, and there are deficiencies in protective behavior. Their awareness and use of sunscreen need to be improved.
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The filamentous actin (F-actin) cytoskeleton is progressively damaged after status epilepticus (SE), which is related to delayed neuronal death, aberrant recurrent circuits and epileptogenesis. Glucocorticoids regulate dendritic spine remodeling by acting on glucocorticoid receptors and the dynamics of the F-actin cytoskeleton. Our previous study showed that administration of dexamethasone (DEX) in the latent period of the pilocarpine epileptic model reduces damage to the hippocampal filamentous actin cytoskeleton and the loss of hippocampal neurons and aids in maintaining the synaptic structures, but it is not sufficient to stop epileptogenesis. In this work, we focused on the role of glucocorticoids in regulating the hippocampal F-actin cytoskeleton during SE. We examined the abundance of synaptic F-actin, analyzed the hippocampal F-actin/G-actin (F/G) ratio and pCofilin, and evaluated the number of hippocampal neurons and pre/postsynaptic markers in pilocarpine-induced status epilepticus mice with or without administration of dexamethasone (DEX). We found that the latency of Stage 3 seizures increased, the mortality decreased, the damage to the synaptic F-actin cytoskeleton in the hippocampal subfields was significantly attenuated, and a greater number of postsynaptic structures were retained in the hippocampal subfields after treatment with DEX. These results indicate that treatment with dexamethasone stabilizes the synaptic F-actin cytoskeleton and reduces the damage to the brain due to SE. This approach is expected to be beneficial in alleviating delayed neuron damage and the process of epileptogenesis.
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Citoesqueleto de Actina/genética , Dexametasona/farmacologia , Hipocampo/metabolismo , Estado Epiléptico/tratamento farmacológico , Actinas/genética , Animais , Modelos Animais de Doenças , Hipocampo/patologia , Humanos , Camundongos , Neurônios/metabolismo , Neurônios/patologia , Pilocarpina/toxicidade , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/genética , Estado Epiléptico/patologiaRESUMO
Patients with obstructive jaundice are prone to develop cardiovascular complications during surgery. However, the underlying mechanisms remain largely unknown. The present study was aimed to investigate the role of p38 MAPK-pHsp27 pathway in vascular hyporesponsiveness induced by obstructive jaundice. Firstly, an experimental rat obstructive jaundice model was established by bile duct ligation (BDL). We found that the thoracic aorta rings isolated from BDL rats showed decreased response to norepinephrine and acetylcholine, while continuous intraperitoneal injection with SB203580, a selective P38 MAPK inhibitor, could significantly prevented BDL-induced hyporeactivity. Also, the immunohistochemistry and Western blot assays revealed that the up-regulation of pHsp27 and F-actin in thoracic aorta rings from BDL rats and bilirubin-treated vascular smooth muscle cells (VSMCs) were also inhibited by SB203580. Moreover, we identified that bilirubin could induced decreased cell proliferation of VSMCs by using CCK8 assay and which was also prevented by SB203580. All these data demonstrated that p38 MAPK-pHsp27 mediates vascular hyporesponsiveness in rats with obstructive jaundice by modulating the expression level of pHsp27 and F-actin, and that inhibition of p38 MAPK signaling could remodel the vascular activity.
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Aorta Torácica/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Actinas/metabolismo , Animais , Bilirrubina , Linhagem Celular , Proliferação de Células , Imidazóis/farmacologia , Masculino , Músculo Liso Vascular , Fosforilação/efeitos dos fármacos , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND: Lifestyle and risk factor management may improve outcomes in patients with atrial fibrillation (AF). We aim to evaluate the prevalence of modifiable risk factors and how these factors impact clinical outcomes in patients with AF. METHODS AND RESULTS: Data on 17 898 AF cohort patients with AF enrolled between 2011 and 2016 was analyzed. A healthy lifestyle was defined as not smoking, not drinking, a healthy body mass index (BMI), untreated total cholesterol less than 200 mg/dL, untreated blood pressure (BP) less than 120/80 mm Hg, and untreated fasting plasma glucose (FPG) less than 100 mg/dL. The association between risk factors and risk of the composite endpoint of all-cause mortality and nonfatal ischemic stroke were assessed using Cox proportional hazards regression model. Only 4.0% of patients achieved a healthy lifestyle. In multivariate analysis, current smoking, a low BMI, not well-controlled FPG were independently and significantly associated with higher risk of all-cause mortality and nonfatal ischemic stroke, with corresponding hazard ratio (HR) estimates 1.22 (95% confidence interval [CI], 1.00-1.47), HR = 1.72 (95% CI, 1.34-2.20), and HR = 1.25 (95% CI, 1.06-1.46), respectively. High BP was also associated with higher risk with the outcomes (HR = 1.15, 95% CI, 1.00-1.34). Compared with patients with no risk factor, those who failed to maintained or achieved optimal risk factor control had a progressively higher risk of death and nonfatal ischemic stroke (HR for 1 risk factor = 1.44; 95% CI, 1.07-1.92; and more than 2 risk factors = 1.75; 95% CI, 0.99-3.09). CONCLUSIONS: Maintenance of well-controlled risk factors may substantially lower the risk of death and ischemic stroke in patients with AF.
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Fibrilação Atrial/epidemiologia , Estilo de Vida Saudável , Comportamento de Redução do Risco , Acidente Vascular Cerebral/epidemiologia , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/terapia , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , China/epidemiologia , Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , não Fumantes , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Proteção , Sistema de Registros , Medição de Risco , Fatores de Risco , Abandono do Hábito de Fumar , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Fatores de TempoRESUMO
Rogressive deconstruction of filament actin (F-actin) in hippocampal neurons in the epileptic brain have been associated with epileptogenesis. Previous clinical studies suggest that glucocorticoids treatment plays beneficial roles in refractory epilepsy. Glucocorticoids treatment affects dendritic spine morphology by regulating local glucocorticoid receptors and F-actin cytoskeleton dynamics. However, how glucocorticoids regulate epileptogenesis by controlling F-actin cytoskeleton is not clear yet. Here we study the function of glucocorticoids in epileptogenesis by examining F-actin abundance, hippocampal neuron number, and synaptic markers in pilocarpine-induced epileptic mice in the presence or absence of dexamethasone (DEX) treatment. We found that spontaneous seizure duration was significantly reduced; F-actin damage in hippocampal subfields was remarkably attenuated; loss of pyramidal cells was dramatically decreased; more intact synaptic structures indicated by pre- and postsynaptic markers were preserved in multiple hippocampal regions after DEX treatment. However, the number of ZNT3 positive particles in the molecular layer in the hippocampus of pilocarpine epileptic mice was not altered after DEX treatment. Although not sufficient to cease epileptogenesis, our results suggest that dexamethasone treatment ameliorates the damage of epileptic brain by stabilizing F-actin cytoskeleton in the pilocarpine epileptic mice.
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Citoesqueleto de Actina/metabolismo , Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Epilepsia/metabolismo , Hipocampo/metabolismo , Pilocarpina/toxicidade , Citoesqueleto de Actina/química , Animais , Anti-Inflamatórios/farmacologia , Dexametasona/farmacologia , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Hipocampo/química , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
Climate and weather are important factors that determine winter tourism destinations and snow resources and temperature affect the income of the winter tourism industry. Against the background of climate change, abnormal fluctuations in climate elements bring a series of challenges for winter tourism and cause potential losses to the tourism industry. To effectively assess and plan winter tourism destinations, this study establishes the snow abundance and meteorological suitability indices from snow resource and weather conditions to express winter tourism resources, respectively. The coupling relationship of the two indices was used to analyze the spatial suitability of winter tourism destinations based on the copula function. By case analysis, it was found that the Frank copula one is the best fitting function for winter tourism suitability analysis. The Yushuâ»Jiutaiâ»Yitongâ»Dongliao line is the boundary of spatial suitability in the study area. The eastern areas of the boundary have great potential for winter tourism and could strive to develop ice-snow projects, whereas the western regions are relatively weak. This study has guiding significance for winter tourism destination development and resource spatial layout.
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Modelos Estatísticos , Estações do Ano , Viagem/estatística & dados numéricos , Mudança Climática , Monitoramento Ambiental , Meteorologia/estatística & dados numéricos , Neve , Tempo (Meteorologia)RESUMO
Background Previous studies have provided conflicting results as to whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation ( AF ). We investigated whether women with AF were at higher risk of ischemic stroke in the China-AF (China Atrial Fibrillation Registry) Study. Methods and Results A total of 19 515 patients were prospectively enrolled between August 2011 and December 2016 in the China- AF Study. After exclusion of patients receiving anticoagulation or ablation therapy, 6239 patients (2574 women) with results from at least 6 months of follow-up were used for the analysis. Cox proportional hazards models were performed to evaluate whether female sex was an independent risk factor for thromboembolism after multivariate adjustment. The primary outcome was the time to the first occurrence of ischemic stroke or systemic embolism. After a mean follow-up of 2.81±1.46 years, 152 female patients reached the primary outcome, as compared with 172 male patients. Crude incidence rates of thromboembolism between women and men were of borderline statistical significance (2.08 versus 1.68 per 100 patient-years, P=0.058). After multivariable analysis, female sex was not independently associated with an increased thromboembolism risk (hazard ratio 1.09, 95% confidence interval 0.86-1.39). There was no significant difference in thromboembolism risk by sex stratified by age and presence or absence of risk factors ( P for interaction all >0.1). Conclusions Although crude incidence rates of thromboembolism were higher in Chinese female patients with AF compared with male patients, female sex did not emerge as an independent risk factor for thromboembolism on multivariate analysis. Clinical Trial Registration URL : http://www.chictr.org.cn/ . Unique identifier: Chi CTR - OCH -13003729.
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Fibrilação Atrial/complicações , Isquemia Encefálica/epidemiologia , Sistema de Registros , Medição de Risco/métodos , Tromboembolia/epidemiologia , Idoso , Isquemia Encefálica/etiologia , China/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Fatores de Risco , Distribuição por Sexo , Fatores Sexuais , Tromboembolia/etiologiaRESUMO
BACKGROUND: Anti-coagulant therapy satisfaction for patients with atrial fibrillation is a critical issue, which impacts on their treatment adherence and clinical outcomes. The disadvantages of long-term warfarin treatment are well-described, and novel oral anti-coagulants have become an alternative option. MATERIALS AND METHODS: We compared patient-reported treatment satisfaction with dabigatran versus warfarin in non-valvular atrial fibrillation (NVAF) patients in China. Treatment satisfaction was assessed using the Anti-Clot Treatment Scale (ACTS) questionnaire, which included a 12-item ACTS Burdens scale and a 3-item ACTS Benefits scale. RESULTS: Among 834 patients, 246 patients (29.5%) were taking dabigatran and the others were on warfarin. Propensity score matching was employed to identify 182 patient pairs with balanced baseline characteristics. The global ACTS Burdens score and the global ACTS Benefits score were comparable between the dabigatran and warfarin groups (44.86 ± 3.95 vs. 44.28 ± 3.51, p = 0.423; 11.49 ± 2.92 vs. 11.42 ± 3.03, p = 0.194, respectively). The monthly cost of dabigatran was significantly higher compared with that of warfarin due to a lack of insurance coverage (USD 176.78 ± 9.15 vs. USD 2.49 ± 0.76, p = 0.000). The discontinuation rate of dabigatran was significantly higher than warfarin at the 6-month follow-up (33.5% vs. 19.2%, p = 0.003). Adjusted logistic regression showed that dabigatran was associated with a significant greater odds of non-persistence (odds ratio: 2.13, 95% confidence interval: 1.27-3.59, p = 0.004). CONCLUSION: Dabigatran therapy in patients with NVAF in China associated with no improvement in satisfaction and a higher discontinuation rate compared with warfarin therapy largely due to increased economic burden.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/epidemiologia , Dabigatrana/uso terapêutico , Satisfação do Paciente , Varfarina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/tratamento farmacológico , China/epidemiologia , Custos e Análise de Custo , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Autorrelato , Inquéritos e QuestionáriosRESUMO
Phthalate acid esters (PAEs) are suspected to cause wide environmental pollution and have adverse effects on human health. Three priority control phthalates, namely dimethyl phthalate (DMP), diethyl phthalate (DEP), and dibutyl phthalate (DBP), were determined in 45 water samples from the largest drinking water source in Jilin Province. Chromophoric-dissolved organic matter (CDOM), which are composed of complex compounds and are a proxy for water quality, can be monitored using a fluorometer. This study attempted to understand the correlations of the CDOM fluorescence regional integration (FRI) components with PAEs and CDOM characteristics under seasonal and spatial variations in the Erlong Lake. The characteristics of the CDOM absorption parameters in different water samples showed a higher aromatic content and molecular weight in October because of increased terrestrial inputs. The Σ3PAEs concentrations ranged from 0.231 mg L-1 to 0.435 mg L-1 in water, and DEP contributed to more than 90% of the Σ3PAEs. The FRI method identified five fluorescence components: one tyrosine-like (R1), one tryptophan-like (R2), one fulvic-like (R3), one microbial protein-like (R4), and one humic-like (R5) component. However, significant relationships exist between DEP and R3 (R² = 0.78, p < 0.001), R4 (R² = 0.77, p < 0.001), and R5 (R² = 0.58, p < 0.001). Quantifying the relationship between CDOM and PAEs was highly significant, because the results will simplify the componential analysis of pollutants from a spatiotemporal perspective as compared to traditional chemical measurements. The human health risk assessment results revealed no human health risk (HQ < 1) in the Erlong Lake basin.
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Monitoramento Ambiental/métodos , Lagos/química , Ácidos Ftálicos/efeitos adversos , Ácidos Ftálicos/análise , Compostos de Policloroterfenilo/efeitos adversos , Compostos de Policloroterfenilo/análise , Poluentes Químicos da Água/análise , China , Humanos , Medição de Risco , Espectrometria de Fluorescência , Qualidade da ÁguaRESUMO
Glioblastoma multiforme (GBM) is a prevalent and aggressive disease, and the development of a novel therapy to better treat advanced GBM is urgently required. Lactate dehydrogenase A (LDHA), which functions as a key enzyme in transforming pyruvate into lactate, has attracted more attention in recent years due to its critical role in various types of advanced cancer. Previous data derived from the Oncomine database have shown that the expression of LDHA is higher in GBM tissues than that in corresponding normal control tissues. However, the association of LDHA levels with glioma clinical grades and the possible mechanisms of LDHA in GBM progression have not been investigated. The present study showed that there is a significant positive correlation between LDHA expression levels and tumor clinical stages. The knockdown of LDHA inhibited cell growth by inhibiting cell cycle progression and inducing apoptosis in glioma cell lines. Upon investigating the molecular mechanism, LDHA knockdown via siRNA treatment was associated with decreased cyclin D1 expression, increased cleavage of PARP, and altered B-cell lymphoma 2 and B-cell lymphoma 2-associated protein X expression. In addition, LDHA knockdown led to the marked downregulation of matrix metalloproteinase (MMP)-2, MMP-9, VE-Cadherin and vascular endothelial growth factor expression levels. Furthermore, knock down of LDHA enhanced the chemosensitivity of glioma cells to temozolomide (TMZ), a second-generation alkylating agent with activity against recurrent high-grade glioma. These findings support LDHA as a novel target for developing effective therapeutic strategies to treat GBM.
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Water environmental risk is the probability of the occurrence of events caused by human activities or the interaction of human activities and natural processes that will damage a water environment. This study proposed a water environmental risk index (WERI) model to assess the water environmental risk in the Yinma River Basin based on hazards, exposure, vulnerability, and regional management ability indicators in a water environment. The data for each indicator were gathered from 2000, 2005, 2010, and 2015 to assess the spatial and temporal variations in water environmental risk using particle swarm optimization and the analytic hierarchy process (PSO-AHP) method. The results showed that the water environmental risk in the Yinma River Basin decreased from 2000 to 2015. The risk level of the water environment was high in Changchun, while the risk levels in Yitong and Yongji were low. The research methods provide information to support future decision making by the risk managers in the Yinma River Basin, which is in a high-risk water environment. Moreover, water environment managers could reduce the risks by adjusting the indicators that affect water environmental risks.
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Modelos Teóricos , Rios , Poluição da Água , China , Monitoramento Ambiental , Humanos , Medição de Risco , Água , Poluentes Químicos da Água , Qualidade da ÁguaRESUMO
Our previous study has shown heme oxygenase-1 (HO-1) protects human lens epithelial cells (LECs) against H2O2-induced oxidative stress and apoptosis. Nrf2, the major regulator of HO-1, is triggered during the mutual induction of oxidative stress and ER stress. In response to ER stress, unfolded protein response (UPR) serves as a program of transcriptional and translational regulation mechanism with PERK involved. Both Nrf2 and ATF4 are activated as the downstream effect of PERK signaling coordinating the convergence of dual stresses. However, the ways in which Nrf2 interacting with ATF4 regulates deteriorated redox state have not yet been fully explored. Here, the transfected LECs with Nrf2 overexpression illustrated enhanced resistance in morphology and viability upon H2O2 treatment condition. Intracellular ROS accumulation arouses ER stress, initiating PERK dependent UPR and inducing the downstream signal Nrf2 and ATF4 auto-phosphorylation. Further, converging at target promoters, ATF4 facilitates Nrf2 with the expression of ARE-dependent phase II antioxidant and detoxification enzymes. According to either Nrf2 or ATF4 gene modification, our data suggests a novel interaction between Nrf2 and ATF4 under oxidative and ER stress, thus drives specific enzymatic and non-enzymatic reactions of antioxidant mechanisms maintaining redox homeostasis. Therapies that restoring Nrf2 or ATF4 expression might help to postpone LECs aging and age-related cataract formation.
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Fator 4 Ativador da Transcrição/metabolismo , Estresse do Retículo Endoplasmático , Células Epiteliais/citologia , Cristalino/citologia , Fator 2 Relacionado a NF-E2/fisiologia , Estresse Oxidativo , Western Blotting , Catalase/metabolismo , Linhagem Celular , Citoproteção , Células Epiteliais/metabolismo , Citometria de Fluxo , Técnica Indireta de Fluorescência para Anticorpo , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Cristalino/metabolismo , Oxidantes/toxicidade , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Superóxido Dismutase/metabolismo , Transfecção , Resposta a Proteínas não Dobradas/fisiologia , eIF-2 Quinase/metabolismoRESUMO
The healing of Bone tissue consists of a complex process. Hence, we designed our study to evaluate chondrial diseases, which are as they have a very low healing capacity. Seventy two elderly osteoarthritis (OA) and 54-paediatric juvenile idiopathic arthritis (JIA) patients were included. The group was divided as 24 OA patients and 18 JIA patients in each group. Group I received Hyualuronic acid and glucocorticoides. Group II received platelet rich plasma and fibrin glue. Group III received PRP, fibrin glue, and MSC. 40 control patients received only PRP treatment. Out of 72 OA patients 35 (48.6%) male and 37 (51.4%) female with mean age of 48 ± 6.5 years. 64 (88.9%) Patients had pain and swelling. 52 (72.2%) lacked flexibility. 42 (58.3%) had hypertrophy. 28 (38.9%) had less cartilage thickness. 34 (47.2%) were in grade 3, grade 2 has 28 (38.9%) and grade 1 has 10 (13.9%) patients respectively. Among 54 JIA patients 28 (51.9%) male and 26 (48.1%) female patients with mean, age 4.6 ± 3.8 years. 39 (72.2%) had pain and swelling. 32 (59.3%) lacked flexibility. 29 (53.7%) children's had functional disability. Group I patients showed 30% improvement with no statistical significance (P < 0.21). Group II showed 45% improvement with statistical significance (P < 0.01). In Group III 80%, improvement was observed with statistical significance (P < 0.001). In 40 control patients, 60% improvement was observed. In conclusion, use of these MSC, PRP, and PPP are safe and less cost effective for treating OA and JIA.
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MicroRNAs (miRNAs) play a critical role in glioblastoma initiation and progression. PIWIL1, a human homolog of the PIWI family, has a critical effect on glioblastoma progression. In present study, we found that the expression of miR-154-5p was significantly lower in glioblastoma. Our results suggested that the overexpression of miR-154-5p suppressed proliferation and metastasis, induced apoptosis, whereas inhibiting the expression of miR-154-5p significantly promoted proliferation and metastasis of glioblastoma. We further proved that miR-154-5p directly integrated with the 3'-UTR of PIWIL1 and reintroduction of PIWIL1 can rescue the phenotype changes induced by miR-154-5p. Taken together, our study reveals that miR-154-5p can counteract the malignant phenotypes of glioblastoma by targeting PIWIL1, which might be beneficial to reveal new therapeutic targets for glioblastoma.
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Proliferação de Células/fisiologia , Glioblastoma/metabolismo , MicroRNAs/metabolismo , Metástase Neoplásica/fisiopatologia , Animais , Antineoplásicos/administração & dosagem , Apoptose/fisiologia , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Encéfalo/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/administração & dosagem , Invasividade Neoplásica/fisiopatologia , Transplante de NeoplasiasRESUMO
Severe hand-foot-and-mouth disease (HFMD) caused by Enterovirus 71 (EV71) always accompanies with inflammation and neuronal damage in the central nervous system (CNS). During neuronal injuries, cell surface-exposed calreticulin (Ecto-CRT) is an important mediator for primary phagocytosis of viable neurons by microglia. Our data confirmed that brainstem neurons underwent neuronophagia by glia in EV71-induced death cases of HFMD. EV71 capsid proteins VP1, VP2, VP3, or VP4 did not induce apoptosis of brainstem neurons. Interestingly, we found VP1-activated endoplasmic reticulum (ER) stress and autophagy could promote Ecto-CRT upregulation, but ER stress or autophagy alone was not sufficient to induce CRT exposure. Furthermore, we demonstrated that VP1-induced autophagy activation was mediated by ER stress. Meaningfully, we found dexamethasone treatment could attenuate Ecto-CRT upregulation by alleviating VP1-induced ER stress. Altogether, these findings identify VP1-promoted Ecto-CRT upregulation as a novel mechanism of EV71-induced neuronal cell damage and highlight the potential of the use of glucocorticoids to treat severe HFMD patients with CNS complications.