RESUMEN
The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) is a critical regulator of glycolysis and plays a key role in modulating the inflammatory response, thereby contributing to the development of inflammatory diseases such as sepsis. Despite its importance, the development of strategies to target PFKFB3 in the context of sepsis remains challenging. In this study, we employed a miRNA-based approach to decrease PFKFB3 expression. Through multiple meta-analyses, we observed a downregulation of miR-106a-5p expression and an upregulation of PFKFB3 expression in clinical sepsis samples. These changes were also confirmed in blood monocytes from patients with early sepsis and from a mouse model of lipopolysaccharide (LPS)-induced sepsis. Overexpression of miR-106a-5p significantly decreased the LPS-induced increase in glycolytic capacity, inflammatory response, and pyroptosis in macrophages. Mechanistically, we identified PFKFB3 as a direct target protein of miR-106a-5p and demonstrated its essential role in LPS-induced pyroptosis and inflammatory response in macrophages. Furthermore, treatment with agomir-miR-106a-5p conferred a protective effect in an LPS mouse model of sepsis, but this effect was attenuated in myeloid-specific Pfkfb3 KO mice. These findings indicate that miR-106a-5p inhibits macrophage pyroptosis and inflammatory response in sepsis by regulating PFKFB3-mediated glucose metabolism, representing a potential therapeutic option for the treatment of sepsis.
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Inflamación , Lipopolisacáridos , Macrófagos , MicroARNs , Fosfofructoquinasa-2 , Piroptosis , Sepsis , Fosfofructoquinasa-2/metabolismo , Fosfofructoquinasa-2/genética , Animales , Sepsis/metabolismo , Sepsis/genética , Sepsis/patología , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Ratones , Macrófagos/metabolismo , Inflamación/metabolismo , Inflamación/genética , Glucólisis , Masculino , Ratones Endogámicos C57BLRESUMEN
The recycling of industrial solid by-products such as red mud (RM) has become an urgent priority, due to their large quantities and lack of reutilization methods can lead to resource wastage. In this work, RM was employed to fabricate green hydrochar (HC) to prepare zero-valent iron (ZVI) modified carbonous materials, and conventional iron salts (IS, FeCl3) was applied as comparison, fabricated HC labeled as RM/HC and IS/HC, respectively. The physicochemical properties of these HC were comprehensively characterized. Further, hexavalent chromium (Cr(VI)) removal performance was assessed (375.66 and 337.19â¯mg/g for RM/HC and IS/HC, respectively). The influence of dosage and initial pH were evaluated, while isotherms, kinetics, and thermodynamics analysis were also conducted, to mimic the surface interactions. The stability and recyclability of adsorbents also verified, while the practical feasibility was assessed by bok choy-planting experiment. This work revealed that RM can be used as a high value and green fabricant for HC the effective removal of chromium contaminants from the wastewater.
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Aguas Residuales , Contaminantes Químicos del Agua , Hierro/química , Contaminantes Químicos del Agua/análisis , Cromo/análisis , Carbono , AdsorciónRESUMEN
Radiotherapy is an important treatment modality for cancer patients. Ionizing radiation kills cancer cells by inducing DNA damage. However, it remains unclear how this process affects the biomechanical properties of cells and how cellular mechanics affect DNA damage and repair. In this study, the effects of ionizing radiation on cell mechanics were investigated by precisely measuring the compressibility of cells in suspension using an in-house developed microfluidic device. We found that cell compressibility significantly increased after irradiation, depending on cell type and radiation dose. Radiation-induced DNA damage response (DDR) is an important process that alters cell mechanics, and this association was confirmed experimentally by inhibiting the DDR process. Furthermore, the mechanisms involved in changes in cell compressibility were investigated from the perspective of the nucleus and cytoplasm. Experiments showed that radiation reduced H3K9me3 staining intensity but had no effect on F-actin. This suggested that chromatin decondensation caused by radiation-induced DDR is the primary cause of changes in cell compressibility after radiation. The effects of cell mechanics on radiation-induced DNA damage were also investigated. The addition of blebbistatin reduced cytoskeletal forces on the nucleus, which resulted in a reduction in radiation-induced DNA damage. Collectively, this study elucidated reciprocal mechanisms of radiation-induced DNA damage and cell mechanics.
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Reparación del ADN , Traumatismos por Radiación , Núcleo Celular , Cromatina , Daño del ADN , Humanos , Radiación IonizanteRESUMEN
Sepsis is life-threatening organ dysfunction due to dysregulated systemic inflammatory and immune response to infection, often leading to cognitive impairments. Growing evidence shows that artemisinin, an antimalarial drug, possesses potent anti-inflammatory and immunoregulatory activities. In this study we investigated whether artemisinin exerted protective effect against neurocognitive deficits associated with sepsis and explored the underlying mechanisms. Mice were injected with LPS (750 µg · kg-1 · d-1, ip, for 7 days) to establish an animal model of sepsis. Artemisinin (30 mg · kg-1 · d-1, ip) was administered starting 4 days prior LPS injection and lasting to the end of LPS injection. We showed that artemisinin administration significantly improved LPS-induced cognitive impairments assessed in Morris water maze and Y maze tests, attenuated neuronal damage and microglial activation in the hippocampus. In BV2 microglial cells treated with LPS (100 ng/mL), pre-application of artemisinin (40 µΜ) significantly reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-6) and suppressed microglial migration. Furthermore, we revealed that artemisinin significantly suppressed the nuclear translocation of NF-κB and the expression of proinflammatory cytokines by activating the AMPKα1 pathway; knockdown of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin in BV2 microglial cells. In conclusion, atemisinin is a potential therapeutic agent for sepsis-associated neuroinflammation and cognitive impairment, and its effect is probably mediated by activation of the AMPKα1 signaling pathway in microglia.
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Artemisininas/uso terapéutico , Microglía/efectos de los fármacos , Trastornos Neurocognitivos/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Sepsis/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Antiinflamatorios/uso terapéutico , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/patología , Muerte Celular/efectos de los fármacos , Línea Celular , Movimiento Celular/efectos de los fármacos , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/etiología , Inflamación/metabolismo , Lipopolisacáridos , Masculino , Ratones Endogámicos C57BL , Microglía/metabolismo , Prueba del Laberinto Acuático de Morris/efectos de los fármacos , Trastornos Neurocognitivos/etiología , Trastornos Neurocognitivos/metabolismo , Neuronas/efectos de los fármacos , Sepsis/inducido químicamente , Sepsis/complicaciones , Sepsis/metabolismoRESUMEN
Recent studies demonstrated that FoxO3 circular RNA (circFoxO3) plays an important regulatory role in tumourigenesis and cardiomyopathy. However, the role of circFoxO3 in neurodegenerative diseases remains unknown. The aim of this study was to examine the possible role of circFoxO3 in neurodegenerative diseases and the underlying mechanisms. To model human neurodegenerative conditions, hippocampus-derived neurons were treated with glutamate. Using molecular and cellular biology approaches, we found that circFoxO3 expression was significantly higher in the glutamate treatment group than that in the control group. Furthermore, silencing of circFoxO3 protected HT22 cells from glutamate-induced oxidative injury through the inhibition of the mitochondrial apoptotic pathway. Collectively, our study demonstrates that endogenous circFoxO3 plays a key role in inducing apoptosis and neuronal cell death and may act as a novel therapeutic target for neurodegenerative diseases.
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Apoptosis/efectos de los fármacos , Ácido Glutámico/farmacología , Hipocampo/metabolismo , Mitocondrias/metabolismo , ARN Circular/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis/fisiología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Proteína Forkhead Box O3/genética , Ácido Glutámico/metabolismo , Ratones , Mitocondrias/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
Background and Purpose: Oxidative stress is involved in the development of infections. However, whether oxidative stress indicators can be used as markers of stroke-associated infection (SAI) is still unclear. The purpose of this study was to test the predictive values of superoxide dismutase (SOD) and malondialdehyde (MDA) levels for SAI incidence.Methods: A total of 45 consecutive patients with ischemic stroke who were admitted to our hospital were enrolled. A prospective study was carried out to observe the occurrence of SAI during the first 7 days after stroke. Accordingly, the patients were divided into SAI and non-SAI groups. The relationship between SOD and MDA serum levels and SAI was analyzed.Results: The patients in the SAI group had significantly higher serum SOD levels than those in the non-SAI group (41.638 ± 3.428 U/ml vs. 36.542 ± 9.114 U/ml, p = 0.033). However, there were no significant differences in MDA levels between the SAI and non-SAI group (p > 0.05). The discriminating ability of serum SOD level for SAI was measured using an ROC curve. Serum level of SOD >38.16 U/ml was useful in diagnosing SAI with a sensitivity of 88% and a specificity of 61%. Kaplan-Meier curves showed that the group with serum SOD level >38.16 U/ml had higher rates of SAI incidence (χ2 = 9.688, p = 0.002; log rank test). Furthermore, Cox regression analysis indicated that a serum SOD level >38.16 U/ml was an independent risk factor for SAI (hazard ratio = 5.836; 95% CI, 1.298-26.244; p = 0.021).Conclusions: Acute-phase serum SOD level could be a predictor of SAI.
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Isquemia Encefálica/sangre , Infecciones/sangre , Infecciones/diagnóstico , Inflamación/sangre , Estrés Oxidativo , Accidente Cerebrovascular/sangre , Superóxido Dismutasa/sangre , Anciano , Biomarcadores/sangre , Isquemia Encefálica/complicaciones , Femenino , Humanos , Infecciones/etiología , Inflamación/etiología , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Estrés Oxidativo/fisiología , Estudios Prospectivos , Sensibilidad y Especificidad , Accidente Cerebrovascular/complicacionesRESUMEN
BACKGROUND: Efficient assessment of patients after ischemic stroke has important reference value for doctors to choose appropriate treatment for patients. Our study aimed to develop a new prognostic model for predicting outcomes 3 months after ischemic stroke among Chinese Population. METHODS: A prospective observational cohort study among ischemic stroke patients presenting to Emergency Department in the Second Affiliated Hospital of Guangzhou Medical University was conducted from May 2012 to June 2013. Demographic data of ischemic stroke patients, assessment of NIHSS and laboratory results were collected. Based on 3-month modified Rankin Scale (mRS) ischemic stroke patients were divided into either favorable outcome (mRS: 0-2) or unfavorable outcome groups (mRS: 3-6). The variables closely associated with prognosis of ischemic stroke were selected to develop the new prognostic model (NAAP) consisted of 4 parameters: NIHSS, age, atrial fibrillation, and prealbumin. The prognostic value of the modified prognostic model was then compared with NIHSS alone. RESULTS: A total of 454 patients with suspected stroke were recruited. One hundred eighty-six patients with ischemic stroke were included in the final analysis. A new prognostic model, NAAP was developed. The area under curve (AUC) of NAAP was .861 (95%confidence interval: .803-.907), whilst the AUC of NIHSS was .783 (95%CI: .717-.840), (Pâ¯=â¯.0048). Decision curve analysis showed that NAAP had a higher net benefit for threshold probabilities of 65% for predictive risk of poor outcomes. CONCLUSIONS: The modified prognostic model, NAAP may be a better prognostic tool for predicting 3-month unfavorable outcomes for ischemic stroke than NIHSS alone.
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Isquemia Encefálica/diagnóstico , Accidente Cerebrovascular/diagnóstico , Anciano , Isquemia Encefálica/terapia , China , Técnicas de Apoyo para la Decisión , Femenino , Humanos , Masculino , Pronóstico , Estudios Prospectivos , Accidente Cerebrovascular/terapia , Factores de TiempoRESUMEN
BACKGROUND AND PURPOSE: We aimed to develop and validate a grading scale for predicting 30-day mortality and 90-day functional outcome in patients with primary pontine hemorrhage (PPH). METHODS: We retrospectively reviewed records of consecutive patients with first-ever pontine hemorrhage from 3 teaching hospitals between 2005 and 2012. Independent factors associated with 30-day mortality were identified by logistic regression to establish a risk stratification scale, named the new PPH score. For validation of the new PPH score, we prospectively recruited subjects from 10 units between December 2014 and November 2015. The performance of the new PPH score was presented as discrimination and calibration, measured by area under the curve of the receiver operating characteristic and Hosmer-Lemeshow goodness-of-fit, respectively. RESULTS: Data of 171 patients were available for scale development. The new PPH score consisted of 2 independent factors with individual points assigned as follows: Glasgow Coma Scale score 3 to 4 (=2 points), 5 to 7 (=1 point), and 8 to 15 (=0 point); PPH volume >10 mL (=2 points), 5 to 10 mL (=1 point), and <5 mL (=0 point). An independent cohort of 98 patients was applied as an external validation of the new PPH score. Results showed that the new PPH score was discriminative in predicting both 30-day mortality (area under the curve, 0.902) and 90-day good outcome (area under the curve, 0.927). Furthermore, the new PPH score revealed a good calibration (χ2=1.387; P=0.846) in 30-day mortality prediction. CONCLUSIONS: The new PPH score is simple and reliable in predicting short-term and long-term outcome for PPH patients. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org.cn. Unique identifier: ChiCTR-OOC-14005533.
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Hemorragias Intracraneales/diagnóstico , Puente/patología , Índice de Severidad de la Enfermedad , Adulto , Anciano , Escala de Coma de Glasgow/normas , Humanos , Hemorragias Intracraneales/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
Cerebral infarction (CI) is a common clinical cerebrovascular disease, and to explore the pathophysiological mechanisms and seek effective treatment means are the hotspot and difficult point in medical research nowadays. Numerous studies have confirmed that uric acid plays an important role in CI, but the mechanism has not yet been clarified. When treating HT22 and BV-2 cells with different concentrations of uric acid, uric acid below 450 µM does not have significant effect on cell viability, but uric acid more than 500 µM can significantly inhibit cell viability. After establishing models of OGD (oxygen-glucose deprivation) with HT22 and BV-2 cells, uric acid at a low concentration (50 µM) cannot improve cell viability and apoptosis, and Reactive oxygen species (ROS) levels during OGD/reoxygenation; a suitable concentration (300 µM) of uric acid can significantly improve cell viability and apoptosis, and reduce ROS production during OGD/reoxygenation; but a high concentration (1000 µM) of uric acid can further reduce cell viability and enhance ROS production. After establishing middle cerebral artery occlusion of male rats with suture method, damage and increase of ROS production in brain tissue could be seen, and after adding suitable concentration of uric acid, the degree of brain damage and ROS production was reduced. Therefore, different concentrations of uric acid should have different effect, and suitable concentrations of uric acid have neuroprotective effect, and this finding may provide guidance for study on the clinical curative effect of uric acid.
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Apoptosis/efectos de los fármacos , Isquemia Encefálica/patología , Glucosa/deficiencia , Oxígeno/química , Daño por Reperfusión/patología , Ácido Úrico/farmacología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/patología , Masculino , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Several prior studies have linked serum prealbumin (PA) as a predictor for perioperative infection. However, whether peripheral blood PA levels can be used as an indicator of stroke-associated infection (SAI) is still unclear. In this study, we attempt to find whether serum PA is a meaningful predictor in SAI after an ischemic stroke, so as to provide theoretical basis for clinical treatment. METHODS: Consecutive patients with acute ischemic stroke who were admitted to our hospital were enrolled and serum PA was collected. A prospective study was conducted to observe the predictive value of PA in the SAI incident in ischemic stroke patients. RESULTS: Of 104 patients, 29 (27.9%) developed an SAI after 7 d of follow-up. The stroke with SAI group had significantly lower PA levels than the stroke without SAI group ( p < 0.05). The optimal cutoff value for predicting SAI was PA ≤ 191 mg/L, with sensitivity and specificity of 58.62% and 81.33%, respectively. Kaplan-Meier survival analysis showed that stroke patients with low serum PA level (PA ≤ 191 mg/L) had a higher SAI rates (log-rank test, χ2 = 16.870, p < 0.001). Cox regression analysis showed that PA ≤ 191 mg/L (hazard ratio = 3.207; 95% CI, 1.430-7.190, p = 0.005) was an independent risk factor for SAI. CONCLUSIONS: Early detection of serum PA during the acute phase of ischemic stroke may help us to identify at-risk SAI patients, and hence rapidly guide the intervention to prevent SAI.
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Isquemia Encefálica/sangre , Infecciones/sangre , Prealbúmina/metabolismo , Accidente Cerebrovascular/sangre , Anciano , Biomarcadores/sangre , Isquemia Encefálica/complicaciones , Femenino , Humanos , Infecciones/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Accidente Cerebrovascular/complicacionesRESUMEN
BACKGROUND AND PURPOSE: Detecting cardioembolic stroke soon after acute cerebral ischemia has a major impact on secondary stroke prevention. Recently, the Score for the Targeting of Atrial Fibrillation (STAF) was introduced to identify stroke patients at risk of atrial fibrillation. However, whether the STAF score could be a useful approach to differentiate cardioembolic stroke from other stroke subtypes is unclear. METHODS: Consecutive patients with acute ischemic stroke that were admitted to our stroke center were enrolled. Each patient was assessed (age, baseline National Institutes of Health Stroke Scale, left atrial dilatation and absence of vascular etiology) to calculate the STAF score. A follow-up visit was conducted for each patient during hospitalization to determine the diagnosed stroke etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. RESULTS: The median and interquartile range of the STAF score was significantly higher in the cardioembolic than in the non-cardioembolic group [6 (2) vs. 2 (3), p < 0.001]. The discriminating ability of the STAF score model was good as demonstrated by the receiver operating characteristic curve. The area under the curve (AUC) of STAF score (AUC = 0.98; 95% CI, 0.96-0.99) was significantly greater than B-type natriuretic peptide (AUC = 0.87; 95% CI, 0.83-0.91) (p < 0.05). The optimal STAF cut-off value was ≥ 5, which diagnosed cardioembolic stroke with a sensitivity of 90% and specificity of 95%. CONCLUSIONS: The STAF score is a simple and accurate tool that can discriminate the cardioembolic stroke from other types during hospitalization for acute ischemic stroke.
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Embolia Intracraneal/complicaciones , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etiología , Adulto , Anciano , Anciano de 80 o más Años , China , Estudios de Cohortes , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROCRESUMEN
BACKGROUND: Aquaporin-4 (AQP4) antibody sero-positivity is critically important in neuromyelitis optica (NMO). However, the sensitivity of different assays is highly variable. Repeating detection with a highly sensitive assay in a large population is necessary in the case of so-called negative NMO. METHODS: Retrospective analysis where AQP4 antibodies were detected by commercial cell-based assay (CBA), in-house M23-CBA and in-house M1-CBA. RESULTS: Of the 1011 serum samples, 206 (20.4%) were sero-positive by primary commercial CBA. In the retest, all 206 participants positive by primary commercial CBA also yielded positive results by in-house M23-CBA and the second commercial CBA again, but only 124 positive in in-house M1-CBA. Among the 805 participants negative by primary commercial CBA, 71 participants were positive for in-house M23-CBA, of which 20 participants were positive for the second commercial CBA, and none were positive by in-house M1-CBA. Of the 171 cerebral spinal fluid samples, 75 (43.9%) were positive by primary commercial CBA. All 75 participants positive by primary commercial CBA also yielded positive results by in-house M23-CBA and the second commercial CBA. Forty-nine (65.3%) of these 75 participants were positive by in-house M1-CBA. Among the 96 participants negative by primary commercial CBA, 15 participants were positive for in-house M23-CBA and none were positive by in-house M1-CBA and the second commercial CBA. CONCLUSIONS: Different AQP4 isoforms in CBA result in different detection effects, and in-house M23-CBA is the most sensitive method. Some AQP4 antibody-negative NMO may be subject to diagnostic uncertainty due to limitations of the assays.
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Acuaporina 4/inmunología , Autoanticuerpos/sangre , Neuromielitis Óptica/sangre , Neuromielitis Óptica/diagnóstico , Adolescente , Adulto , Acuaporina 4/genética , Autoanticuerpos/líquido cefalorraquídeo , China/epidemiología , Femenino , Células HEK293 , Humanos , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/líquido cefalorraquídeo , Neuromielitis Óptica/inmunología , Estudios Retrospectivos , Estadísticas no Paramétricas , Transfección , Adulto JovenRESUMEN
Cerebral ischemia-reperfusion injury (IRI) is a common clinical pathological process, and it is a key step in causing further ischemic organ damage. The mechanism of cerebral IRI is still not fully understood, leading to a lack of effective treatment. It has been demonstrated that circular RNAs (circRNAs) can act as miRNA sponges and play an important role in regulating gene expression through a circRNA-miRNA-gene pathway. The specific role of circRNAs in the pathogenesis of cerebral IRI, however, is still unclear. Thus, in the present study, we investigated circRNA expression differences in HT22 cells with oxygen-glucose deprivation/reoxygenation (OGD/R) versus normal controls. The results from circRNA microarrays revealed that 15 circRNAs were significantly altered in the OGD/R model (p < 0.05) compared with the control group. Among them, 3 were significantly up-regulated, and the other 12 were down-regulated. Furthermore, the up-regulated expression of mmu-circRNA-015947 was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics analysis revealed that up-regulated expression of mmu-circRNA-015947 could interact with miRNAs (mmu-miR-188-3p, mmu-miR-329-5p, mmu-miR-3057-3p, mmu-miR-5098 and mmu-miR-683) and thereby enhance target gene expression. KEGG pathway analysis predicted that mmu-circRNA-015947 may participate in apoptosis-related, metabolism-related and immune-related pathways, which are known to be involved in the pathogenesis of IRI. This research suggests that the overlapping expression of mmu-circRNA-015947 might be involved in the process of cerebral IRI and presents a novel molecular target for clinical therapy.
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Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Neuronas/metabolismo , Neuronas/patología , ARN/genética , ARN/metabolismo , Animales , Secuencia de Bases , Línea Celular , Ratones , Datos de Secuencia Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , ARN Circular , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patologíaRESUMEN
OBJECTIVE: To analyze changes in magnetic resonance imaging (MRI) of spinal cord lesions in neuromyelitis optica (NMO) and the correlation between segmental length of spinal cord lesions and expanded disability status scale (EDSS) scores. METHODS: Twenty-five patients with confirmed NMO were examined from the Second Affiliated Hospital of Guangzhou Medical University, China. The information collected included their treatment, MRI, laboratory tests, and EDSS scores at different stages. RESULTS: All cases exhibited spinal cord lesions, with 23 (92%) having longitudinally extensive transverse myelitis (extending ≥3 vertebral segments). There was a positive correlation between segmental length of spinal cord lesions and EDSS scores: during the acute phase, r = 0.430 (P = 0.032); during remission, r = 0.605 (P = 0.002). Enlarged spinal cord lesions and swelling were found in 18 cases (72%) during the acute phase, and 4 cases (16%, P = 0.000) after 6 months of treatment. Lesion enhancements were found in 17 cases (68%) during the acute phase, and 8 cases (32%, P = 0.023) after 6 months of treatment. Leptomeningeal enhancement was found in three cases during the acute phase, which disappeared after treatment. Atrophy of spinal cord lesions occurred in two cases. Change in lesions was statistically significant (P = 0.006) after 12 months of treatment. CONCLUSION: Positive correlation was found between segmental length of spinal cord lesions and EDSS scores, which was more significant during remission. After 6 months of regular treatment, restorative changes compared with the acute phase were found by MRI.
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Mielitis Transversa/patología , Neuromielitis Óptica/patología , Médula Espinal/patología , Adulto , Atrofia/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause and affects mainly the spine, but can also affect other joints. Disease progression may result in loss of mobility and function. Sulfasalazine is a disease-modifying antirheumatic drug used in the treatment of AS. However, its efficacy remains unclear. This is an update of a Cochrane review first published in 2005. OBJECTIVES: To evaluate the benefits and harms of sulfasalazine for the treatment of ankylosing spondylitis (AS). SEARCH METHODS: We searched for relevant randomized and quasi-randomized trials in any language, using the following sources: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 11); MEDLINE (2003 to 28 November 2013); EMBASE (2003 to 27 November 2013); CINAHL (2003 to 28 November 2013); Ovid MEDLINE data, World Health Organization International Clinical Trials Registry Platform (28 November 2013); and the reference sections of retrieved articles. SELECTION CRITERIA: We evaluated randomized and quasi-randomized trials examining the benefits and harms of sulfasalazine on AS. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed unblinded trial reports according to the selection criteria. Disagreements on the inclusion of the studies were resolved, when necessary, by recourse to a third review author. The same authors independently assessed the risk of bias of included trials and entered the data extracted from the included trials. We combined results using mean difference (MD) or standardised mean difference (SMD) for continuous data, and risk ratio (RR) for dichotomous data.We restructured outcome measures for this update based on recommendations from the editorial group. Major outcomes included: pain, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis function index (BASFI), Bath ankylosing spondylitis metrology index (BASMI), radiographic progression, total number of withdrawals due to adverse events, and serious adverse events. MAIN RESULTS: We did not add any new studies to this review following the updated search. In the original review, we included 11 studies in the analysis, involving 895 participants in total. All included studies compared sulfasalazine with placebo. We judged most of the studies as low risk of bias or unclear risk of bias in five domains (random sequence generation, allocation concealment, blinding of outcome assessment, selective reporting, and other sources of bias). However, for incomplete outcome data, we only judged one trial at low risk of bias.None of the included trials assessed BASDAI, BASFI, BASMI or radiographic progression. Different parameters were used to assess pain. The pooled MD for back pain measured on a 0 to 100 mm visual analogue scale was -2.96 (95% confidence interval (CI) -6.33 to 0.41; absolute risk difference 3%, 95% CI 1% to 6%; 6 trials). Compared to placebo, a significantly higher rate of withdrawals due to adverse effects (RR 1.50, 95% CI 1.04 to 2.15; absolute risk difference 4%, 95% CI 0.4% to 8.8%; 11 trials) was found in the sulfasalazine group. A serious adverse reaction was reported in one patient taking sulfasalazine (Peto odds ratio 7.50, 95% CI 0.15 to 378.16). AUTHORS' CONCLUSIONS: There is not enough evidence to support any benefit of sulfasalazine in reducing pain, disease activity, radiographic progression, or improving physical function and spinal mobility in the treatment of AS. A statistically significant benefit in reducing the erythrocyte sedimentation rate and easing spinal stiffness was mentioned in the previous version. However, the effect size was very small and not clinically meaningful. More withdrawals because of side effects occurred with sulfasalazine. Further studies, with larger sample sizes, longer duration, and using validated outcome measures are needed to verify the uncertainty of sulfasalazine in AS.
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Antirreumáticos/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Sulfasalazina/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The thermal-coupled levels (TCLs) of lanthanides have attracted great attention in the field of optical thermometer, offering an efficient method to achieve non-contect temperatuer feedback in complex environment. However, the iner 4f electrons are shielded, which becomes the core obstacle in improving the sensing performance. This issue is now circumvented by constructing an electron transfer pathway between Tm3+(1D2) and Eu3+(5D0) configurations. As a result, the electron transfer barrier is related to the relative temperature sensitivity, giving an insight into the modulation mechanism. Compared to the conventional TCLs systems, the relative temperature sensitivity of this strategy is highly concentration-responsive, increasing from 5.56 to 10.1 % K-1 as the Eu3+ molar concentration rises from 0.3 to 0.5 mol%. This work reveals the inner emission mechanism based on IVCT-supported emission mode, and presents the highly adjustability of sensing performance.
RESUMEN
Optical thermometers based on lanthanide thermal-coupled levels have attracted great attention owing to its fundamental importance in the fields of public health, biology, and integrated circuit. However, the inherent structural properties (shielded effect on 4f configurations, intense non-radiation relaxation) strictly suppress the sensing performance, limiting the relative temperature sensitivity (SR). To circumvent these limitations, we propose an intervalence charge transfer mashup strategy by inducing d0 electron configured transition metals. Specifically, transition metals Ta5+ is incorporated in Tm3+/Eu3+:LiNbO3, which improves the SR from 5.30 to 11.16% K-1. The validity of this component-modulation behavior is observed on other oxide crystals (NaY(Mo1-zWzO4)2) as well. Furthermore, the observed regulation is well explained by DFT calculation that indicates the d-orbit component at valence band minimum remains the core factor governing the electron transfer process. We successfully relate the SR to the band structure of luminescence carrier, offering a novel perspective for the collocation design of lanthanide configurations.
RESUMEN
Several genetic polymorphisms in endothelial nitric oxide synthase (eNOS) are associated with the pathogenesis of rheumatoid arthritis (RA). This study explored the effect of eNOS gene polymorphism on genetic susceptibility of RA in Chinese Han population. Patients with RA (n=236) and healthy volunteers (n=240) were enrolled in this study. Genotyping of eNOS T-786C and G894T polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. Genotyping and gene frequency distribution of eNOS T-786C and G894T polymorphisms were evaluated. RA patients showed higher frequencies of mutated TC and CC genotypes of eNOS T-786C polymorphism and mutated GT and TT genotypes of G894T polymorphism than healthy controls. More specifically, the genotype frequencies of eNOS T-786C polymorphism were significantly different between RA patients and controls. The expression of eNOS was enhanced in RA patients compared with controls. Further, eNOS expression was enhanced after C was replaced with T in T-786C polymorphism in the promoter. Overall, the individuals with mutations in T-786C and G894T of eNOS may have an increased risk of RA, and T-786C and G894T polymorphisms of eNOS are associated with genetic susceptibility of RA in Chinese Han population.
Asunto(s)
Artritis Reumatoide , Predisposición Genética a la Enfermedad , Óxido Nítrico Sintasa de Tipo III , Humanos , Artritis Reumatoide/genética , Pueblos del Este de Asia , Frecuencia de los Genes , Genotipo , Óxido Nítrico Sintasa de Tipo III/genética , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Accumulation of glutamate damages neurons via the reactive oxygen species (ROS) injury, which was involved in the development of neurodegenerative diseases. However, the mechanism of neuronal oxidative stress damage caused by glutamate and the intervention targets still needs to be further studied. This study explored whether 5' adenosine monophosphate-activated protein kinase (AMPK)-induced glucose metabolic and mitochondrial dysfunction were related to glutamate-dependent ROS injury of the neuron. METHODS: Neuronal oxidative stress injury was induced by glutamate treatment in HT-22 cells. Western blotting was used to evaluate the phosphorylation of the AMPK. The XF24 Flux Analyzer was used to measure the effect of glutamate and Compound C (a well-known pharmacological inhibitor of AMPK phosphorylation) on the cellular oxygen consumption rate (OCR) of HT-22 cells. Glucose uptake, intracellular ROS, mitochondrial potential, apoptosis and cell viability were quantified using biochemical assays. RESULTS: Glutamate caused the phosphorylation of AMPK and subsequently promoted the glucose uptake. Furthermore, AMPK-mediated glucose uptake enhanced OCR and increased the intracellular ROS levels in neurons. The pharmacological inhibition of AMPK phosphorylation by Compound C attenuated glutamate-induced toxicity in HT22 cells by regulating the glucose uptake/mitochondrial respiration/ROS pathway. CONCLUSIONS: The AMPK phosphorylation/glucose uptake/mitochondrial respiration/ROS pathway was involved in glutamate-induced excitotoxic injury in HT22 cells. The inhibition of AMPK phosphorylation may be a potential target for the development of therapeutic agents for treating the glutamate-induced neurotoxicity.
Asunto(s)
Ácido Glutámico , Fármacos Neuroprotectores , Especies Reactivas de Oxígeno/metabolismo , Ácido Glutámico/metabolismo , Ácido Glutámico/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Línea Celular , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo , Apoptosis , Mitocondrias/metabolismo , Glucosa/metabolismoRESUMEN
Since the advent of coronavirus disease 2019 (COVID-19), healthcare workers (HCWs) wearing personal protective equipment (PPE) has become a common phenomenon. COVID-19 outbreaks overlap with heat waves, and healthcare workers must unfortunately wear PPE during hot weather and experience excessive heat stress. Healthcare workers are at risk of developing heat-related health problems during hot periods in South China. The investigation of thermal response to heat stress among HCWs when they do not wear PPE and when they finish work wearing PPE, and the impact of PPE use on HCWs' physical health were conducted. The field survey were conducted in Guangzhou, including 11 districts. In this survey, HCWs were invited to answer a questionnaire about their heat perception in the thermal environment around them. Most HCWs experienced discomfort in their back, head, face, etc., and nearly 80% of HCWs experienced "profuse sweating." Up to 96.81% of HCWs felt "hot" or "very hot." The air temperature had a significant impact on thermal comfort. Healthcare workers' whole thermal sensation and local thermal sensation were increased significantly by wearing PPE and their thermal sensation vote (TSV) tended towards "very hot." The adaptive ability of the healthcare workers would decreased while wearing PPE. In addition, the accept range of the air temperature (T a) were determined in this investigation. Graphical Abstract.