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OBJECTIVES: The prognostic value of fluid-attenuated inversion recovery vessel hyperintensity (FVH) remains controversial in acute ischemic stroke (AIS). The objective was to investigate whether the presence of FVH could predict long-term functional outcomes in patients with AIS receiving medical therapy. METHODS: Consecutive AIS patients with anterior circulation large vessel stenosis (LVS) in multiple centers between January 2019 and December 2020 were studied. Presence of FVH was identified and evaluated as FVH (+). Quantification of FVH was performed using an FVH-Alberta Stroke Program Early CT Score (ASPECTS) system and divided into grades: FVH-ASPECTS of 0 = grade 0; 1-2 = grade 1; 3-7 = grade 2. Poor functional outcome was defined as modified Rankin scale > 2 at 3 months. RESULTS: Overall, 175 patients were analyzed (age, 64.31 ± 13.47 years; men, 65.1%), and 78.9% patients presented with FVH. Larger infarct volume (19.90 mL vs. 5.50 mL, p < 0.001), higher rates of FVH (+) (92.0% vs. 65.9%, p < 0.001), and higher FVH grades (grade 2, 34.5% vs. 10.2%, p < 0.001) were more prone to be observed in patients with poor functional outcomes. FVH (+) with infarct volume larger than 6.265 mL (adjusted odds ratio [aOR] 6.03, 95% confidence interval [CI] 1.82-19.98) and FVH grade (grade 1, aOR 3.07, 95% CI 1.12-8.43; grade 2, aOR 5.80, 95% CI 1.59-21.11) were independently associated with poor functional outcomes. CONCLUSION: FVH (+) combined with large infarct volume and high FVH grade can predict poor long-term functional outcomes in patients with LVS who receive medical therapy. KEY POINTS: ⢠FVH is expected to be a contrast agent-independent alternative for assessing hemodynamic status in the acute stage of stroke. ⢠FVH (+) and high FVH grade, quantified by FVH-ASPECTS rating system and grades, are associated with large infarct volume. ⢠The combination of FVH and DWI-based infarct volume has independent predictive value for long-term functional outcomes in AIS patients with large artery stenosis treated with medical therapy.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anciano , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Constricción Patológica , Humanos , Infarto , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológicoRESUMEN
It has been identified that arginine vasopressin (AVP), vasopressin receptor 2(V2R), and the aquaporin 2 (AQP2) signaling pathway in the inner ear play important roles in hearing and balance functions through regulating the endolymph equilibrium; however, the contributions of this signaling pathway to the development of motion sickness are unclear. The present study was designed to investigate whether the activation of the AVP-V2R-AQP2 signaling pathway in the inner ear is involved in the induction of motion sickness and whether mozavaptan, a V2R antagonist, could reduce motion sickness. We found that both rotatory stimulus and intraperitoneal AVP injection induced conditioned taste aversion (a confirmed behavioral index for motion sickness) in rats and activated the AVP-V2R-AQP2 signaling pathway with a responsive V2R downregulation in the inner ears, and AVP perfusion in cultured epithelial cells from rat endolymphatic sacs induced similar changes in this pathway signaling. Vestibular training, V2R antagonist mozavaptan, or PKA inhibitor H89 blunted these changes in the V2R-AQP2 pathway signaling while reducing rotatory stimulus- or DDAVP (a V2R agonist)-induced motion sickness in rats and dogs. Therefore, our results suggest that activation of the inner ear AVP-V2R-AQP2 signaling pathway is potentially involved in the development of motion sickness; thus, mozavaptan targeting AVP V2Rs in the inner ear may provide us with a new application option to reduce motion sickness. SIGNIFICANCE STATEMENT: Motion sickness affects many people traveling or working. In the present study our results showed that activation of the inner ear arginine vasopressin-vaspopressin receptor 2 (V2R)-aquaporin 2 signaling pathway was potentially involved in the development of motion sickness and that blocking V2R with mozavaptan, a V2R antagonist, was much more effective in reducing motion sickness in both rat and dog; therefore, we demonstrated a new mechanism to underlie motion sickness and a new candidate drug to reduce motion sickness.
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Acuaporina 2/fisiología , Arginina Vasopresina/fisiología , Oído Interno/fisiología , Mareo por Movimiento/etiología , Receptores de Vasopresinas/fisiología , Animales , Antagonistas de los Receptores de Hormonas Antidiuréticas/uso terapéutico , Arginina Vasopresina/sangre , Benzazepinas/uso terapéutico , Células Cultivadas , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Perros , Femenino , Masculino , Mareo por Movimiento/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley , Transducción de Señal/fisiologíaRESUMEN
Xanthomonas campestris pv. campestris is the causative agent of black rot disease in crucifer plants. This Gram-negative bacterium utilizes the type III secretion system (T3SS), encoded by the hrp gene cluster, to aid in its resistance to host defenses and the ability to cause disease. The T3SS injects a set of proteins known as effectors into host cells that come into contact with the bacterium. The T3SS is essential for the virulence and hypersensitive response (HR) of X. campestris pv. campestris, making it a potential target for disease control strategies. Using a unique and straightforward high-throughput screening method, we examined a large collection of diverse small molecules for their potential to modulate the T3SS without affecting the growth of X. campestris pv. campestris. Screening of 13,129 different compounds identified 10 small molecules that had a significant inhibitory influence on T3SS. Moreover, reverse transcription-quantitative PCR (qRT-PCR) assays demonstrated that all 10 compounds repress the expression of the hrp genes. Interestingly, the effect of these small molecules on hrp genes may be through the HpaS and ColS sensor kinase proteins that are key to the regulation of the T3SS in planta Five of the compounds were also capable of inhibiting X. campestris pv. campestris virulence in a Chinese radish leaf-clipping assay. Furthermore, seven of the small molecules significantly weakened the HR in nonhost pepper plants challenged with X. campestris pv. campestris. Taken together, these small molecules may provide potential tool compounds for the further development of antivirulence agents that could be used in disease control of the plant pathogen X. campestris pv. campestris.IMPORTANCE The bacterium Xanthomonas campestris pv. campestris is known to cause black rot disease in many socioeconomically important vegetable crops worldwide. The management and control of black rot disease have been tackled with chemical and host resistance methods with variable success. This has motivated the development of alternative methods for preventing this disease. Here, we identify a set of novel small molecules capable of inhibiting X. campestris pv. campestris virulence, which may represent leading compounds for the further development of antivirulence agents that could be used in the control of black rot disease.
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Enfermedades de las Plantas/prevención & control , Sistemas de Secreción Tipo III/genética , Xanthomonas campestris/fisiología , Proteínas Bacterianas/genética , Productos Agrícolas/microbiología , Regulación Bacteriana de la Expresión Génica , Enfermedades de las Plantas/microbiología , Factores de Transcripción/genética , Sistemas de Secreción Tipo III/metabolismo , Virulencia , Xanthomonas campestris/química , Xanthomonas campestris/genética , Xanthomonas campestris/patogenicidadRESUMEN
This paper aims to investigate the influence of lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, darapladib, on insulin resistance (IR) in streptozotocin (STZ)-induced diabetic pregnant rats. The rat models were divided into Control (normal pregnancy), STZ + saline (STZ-induced diabetic pregnant rats), STZ + Low-dose and STZ + High-dose darapladib (STZ-induced diabetic pregnant rats treated with low-/high-dose darapladib) groups. Pathological changes were observed by Hematoxylin-eosin (HE) and Immunohistochemistry staining. Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). An automatic biochemical analyzer was used to measure the serum levels of biochemical indicators, and homeostatic model assessment for insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were calculated. Western blot was applied to determine levels of inflammatory cytokines. Compared with Control group, rats in the STZ + saline group were significantly decreased in body weight, the number of embryo implantation, the number of insulin positive cells and pancreatic islet size as well as the islet endocrine cells, and high-density lipoprotein (HDL-C) level, but substantially increased in Lp-PLA2, low-density lipoprotein (LDL-C), fatty acids (FFA), serum total cholesterol (TC), triglyceride (TG) levels. Moreover, the increased fasting plasma glucose (FPG) and HOMA-IR and inflammatory cytokines but decreased fasting insulin (FINS) and ISI were also found in diabetic pregnant rats. On the contrary, rats in the darapladib-treated groups were just opposite to the STZ + saline group, and STZ + High-dose group improved better than STZ + Low-dose group. Thus, darapladib can improve lipid metabolism, and enhance insulin sensitivity of diabetic pregnant rats by regulating inflammatory cytokines.
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1-Alquil-2-acetilglicerofosfocolina Esterasa/antagonistas & inhibidores , Benzaldehídos/farmacología , Diabetes Mellitus Experimental/metabolismo , Inhibidores Enzimáticos/farmacología , Resistencia a la Insulina , Oximas/farmacología , Embarazo en Diabéticas/metabolismo , Animales , Benzaldehídos/uso terapéutico , Glucemia/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Femenino , Insulina/sangre , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Masculino , Oximas/uso terapéutico , Embarazo , Embarazo en Diabéticas/tratamiento farmacológico , Embarazo en Diabéticas/patología , Ratas , Ratas Sprague-Dawley , EstreptozocinaRESUMEN
To investigate the chemical constituents from Barringtonia racemosa, twelve compounds were isolated by chromatography methods and identified as 3ß-p-E-coumaroymaslinic acid (1), cis-careaborin (2), careaborin (3), maslinic acid (4), 2α, 3ß, 19α-trihydroxyolean-12-ene-24, 28-dioic acid (5), 3ß-p-Z-coumaroylcorosolic acid (6), corosolic acid (7), 1α, 2α, 3ß, 19α-tetrahydroxyurs-12-en-28-oic acid (8), 19α-hydroxyl ursolic acid (9), 3α, 19α-dihydroxyurs-12-en-24, 28-dioic acid (10), tormentic acid (11), 3-hydroxy-7, 22-dien-ergosterolï¼12ï¼ by the NMR and MS data analysis. Among them, compounds 1-4,7-12 were obtained from the genus Barringtonia for the first time. All the compounds didn't show nocytotoxic activity against MCF-7 and A549 cell lines (IC50>50 mgâ¢L⻹).
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Barringtonia/química , Extractos Vegetales/análisis , Triterpenos/análisis , Estructura Molecular , Fitoquímicos/análisisRESUMEN
CONTEXT: Previous studies from our laboratory indicated that both acute and subchronic administration of Fructus Akebiae (FAE) [the fruit of Akebiae quinata (Thunb.) Decne, (Lardizabalaceae)] produce antidepressant-like effects in animal depressive behavior tests. FAE contains approximately 70% of hederagenin (HG) as its main chemical component. OBJECTIVE: This study compared the antidepressant ability of FAE with that of HG in mice and further investigated the antidepressant-like effects and potential mechanisms of HG in rats subjected to unpredictable chronic mild stress (UCMS). MATERIALS AND METHODS: Mice received FAE (50 mg/kg) and HG (20 mg/kg) once a day via intragastric administration (i.g.) for 3 weeks. The anxiolytic and antidepressant activities of FAE and HG were compared using elevated plus maze (EPM) and behavioral despair tests including tail suspension test (TST) and forced swimming test (FST), respectively. Antidepressant effects of HG (5 mg/kg) were assessed using the UCMS depressive rat model. Moreover, the levels of monoamine neurotransmitters and relevant gene expression in UCMS rats' hippocampi were determined through high-performance liquid chromatography with electrochemical detection and real-time polymerase chain reaction techniques. RESULTS: The results of our preliminary screening test suggest that HG at 20 mg/kg, while not FAE at 50 mg/kg, significantly decreased the immobility in both TST and FST compared with the vehicle group when administered chronically; however, there were no significant differences observed between the HG and the FAE group. Chronic administration of HG failed to significantly reverse the altered crossing and rearing behavioral performance, time spent in the open arm and closed entries in the EPM, even if they showed an increased tendency, but HG significantly increased the percent of sucrose preference in the sucrose preference test (SPT) and decreased the immobility time in the FST. HG showed that significant increases of norepinephrine and serotonin levels and exhibited a tendency to increase the expression of 5-hydroxytryptamine (serotonin) 1A receptor mRNA, and to significantly decrease the expression of the mRNA for the serotonin transporter (5-HTT). However, there were no significant differences in the expression of the brain-derived neurotrophic factor. CONCLUSION: These findings confirm the antidepressant-like effects of HG in a behavioral despair test and UCMS rat model, which may be associated with monoamine neurotransmitters and 5-HTT mRNA expression.
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Antidepresivos/uso terapéutico , Depresión/metabolismo , Norepinefrina/metabolismo , Ácido Oleanólico/análogos & derivados , Serotonina/metabolismo , Estrés Psicológico/metabolismo , Animales , Antidepresivos/farmacología , Enfermedad Crónica , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ácido Oleanólico/farmacología , Ácido Oleanólico/uso terapéutico , Ratas , Ratas Sprague-Dawley , Estrés Psicológico/tratamiento farmacológico , Resultado del TratamientoRESUMEN
To develop an ophthalmic preparation of Shedan, an in situ forming gel was prepared with the formulation containing 18% of poloxamer 407 and 5% of poloxamer 188 by response surface designs plus central composite designs. The rheology results showed that LVE range gamma should limited within 0.5%, Shedan high-frequency region, and the thixotropy recovery time is less than 5 seconds. The phase transition temperature was 33.25 °C according to curve of storage modulus and loss modulus determined by temperature scanning. Surface tension and osmometer of it determined by surface tension meter and dew point osmometer were 36.43 mN · m(-1), and 320.6 mOsm · kg(-1), respectively. Fluorescein sodium was selected as the marker to monitor the corneal residence time, and the results showed that Shedan gel could prolong drug residence for 180 min. In line with zero-order kinetics, releases of muscone and salvianolic acid B in vitro depends on gels erosion. The results of rabbit ocular irritation experiments suggested that Shedan in situ forming gel was biocompatible and nonirritant. In conclusion, a novel Shedan in situ forming gel was developed and characterized for potential drug treatment of retinal vein occlusion.
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Cicloparafinas/química , Poloxámero/química , Animales , Benzofuranos/química , Femenino , Geles/química , Masculino , Soluciones Oftálmicas , Conejos , Oclusión de la Vena Retiniana/tratamiento farmacológico , ViscosidadRESUMEN
PURPOSE: To evaluate the effect of Clinpro XT Varnish (VXT) paste-liquid, resin-modified glass-ionomer and the resinous dentin desensitizing varnish and Gluma Dentin Desensitizer (Gluma) in treating dentin hypersensitivity (DH). METHODS: This short-term (4-week) randomized, double-blind, placebo-controlled, split-mouth study included a total of 119 teeth from 31 individuals which were randomized into three groups: VXT, Gluma, and placebo (warm water). Dentin sensitivity was evaluated by subjects' perception of DH determined by pretreatment tooth sensitivity score (TSS) measured on a 0-10 visual analogue scale (VAS) after tactile (probe) or thermal/evaporative (blast of air) stimuli. TSS was scored at baseline, immediately after treatment (Day 0), after 1 week and after 4 weeks. RESULTS: For both stimuli, mean TSS was significantly decreased in the VXT and Gluma groups at all time points (all, P < 0.001) compared with baseline. Regarding comparisons of TSS between treatment groups, the VXT group had significantly lower mean TSS compared with the Gluma group (P< 0.05) and placebo control group (P< 0.05) at all time points after treatment regardless of stimuli. Group Effect, Time Effect, and Group x Time Effect were all significantly different (all, P < 0.001).
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Desensibilizantes Dentinarios/uso terapéutico , Sensibilidad de la Dentina/tratamiento farmacológico , Adulto , Aire , Sensibilidad de la Dentina/clasificación , Método Doble Ciego , Femenino , Estudios de Seguimiento , Cementos de Ionómero Vítreo/uso terapéutico , Glutaral/uso terapéutico , Humanos , Masculino , Metacrilatos/uso terapéutico , Persona de Mediana Edad , Dimensión del Dolor , Placebos , Cementos de Resina/uso terapéutico , Cuello del Diente/efectos de los fármacos , Tacto , Resultado del Tratamiento , Escala Visual AnalógicaRESUMEN
We investigated the changes of soil nutrients and plant communities in the artificial sand fixation forests of Caragana korshinskii with different ages. The results showed that soil organic carbon and soil total nitrogen contents increased with the stand ages, and were significantly higher in 40 and 50 year-old than other ages. Soil organic carbon and total nitrogen contents recovered much faster in the surface layer (0-10 cm) than in others. Soil nutrient stoichiometric ratios (C:P, N:P) in the 0-10 cm soil layer differed significantly among different stand ages. With the increases of stand age, C and N contents in C. korshinskii leaves increased significantly, and reached the maximum at 50 year-old. Leaf P content increased first and then decreased, being maximum at 18 year-old. Leaf C:N first increased and then decreased, being maximum at 12 year-old. The contents of photosynthetic pigments and leaf C:P and N:P decreased first and then increased, being minimum at 18 year-old. C. korshinskii was mainly influenced by N availability before 40 year-old, but mainly limited by P after. The species number, density, and vegetation cover of annual and perennial herbaceous plants increased with stand ages, and the community shifted from a simple shrub plant community to a complex shrub-herb community. The biomass of C. korshinskii and herbaceous plants increased significantly with stand age, and had a significant positive correlation with the contents of soil organic carbon, total nitrogen and N:P.
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Caragana , Suelo , Arena , Carbono/análisis , China , NitrógenoRESUMEN
OBJECTIVE: This study was designed to investigate the role of 8-oxoguanine DNA glycosylase 1 (OGG1) in preventing atherosclerosis-induced vascular EC injury, thereby providing a theoretical basis for the exploration of drug targets and treatment methods for atherosclerosis. METHODS: Human umbilical vein cell line (EA.hy926) was treated with ox-LDL to construct an in vitro atherosclerotic cell model. pcDNA3.1-OGG1 was transfected into EA.hy926 cells to overexpress OGG1. qRT-PCR, CCK-8 assay, flow cytometry, oil red O staining, ELISA, comet assay and western blot were used to evaluate the OGG1 expression, viability, apoptosis level, lipid droplet content, 8-OHdG level and DNA damage of cells in each group. RESULTS: Compared with the Control group, ox-LDL stimulation of endothelial cells significantly decreased cell viability, promoted apoptosis and DNA damage, and increased intracellular levels of 8-OHdG and γH2AX, while decreasing protein levels of PPARγ, FASN, FABP4, RAD51 and POLB. However, overexpression of OGG1 can significantly inhibit ox-LDL damage to endothelial cells, promote lipid metabolism, decrease lipid droplet content, and improve DNA repair function. CONCLUSION: Over-expression of OGG1 improves DNA repair. Briefly, OGG1 over-expression enhances the DNA damage repair of ECs by regulating the expression levels of γH2AX, RAD51 and POLB, thereby enhancing cell viability and reducing apoptosis.
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Aterosclerosis , Daño del ADN , ADN Glicosilasas , Reparación del ADN , Células Endoteliales de la Vena Umbilical Humana , Humanos , ADN Glicosilasas/metabolismo , ADN Glicosilasas/genética , Aterosclerosis/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Apoptosis/efectos de los fármacos , Lipoproteínas LDL/metabolismo , Supervivencia Celular/efectos de los fármacosRESUMEN
To investigate the strengthening effects and mechanisms of bioaugmentation on the microbial remediation of uranium-contaminated groundwater via bioreduction coupled to biomineralization, two exogenous microbial consortia with reducing and phosphate-solubilizing functions were screened and added to uranium-contaminated groundwater as the experimental groups (group B, reducing consortium added; group C, phosphate-solubilizing consortium added). ß-glycerophosphate (GP) was selected to stimulate the microbial community as the sole electron donor and phosphorus source. The results showed that bioaugmentation accelerated the consumption of GP and the proliferation of key functional microbes in groups B and C. In group B, Dysgonomonas, Clostridium_sensu_stricto_11 and Clostridium_sensu_stricto_13 were the main reducing bacteria, and Paenibacillus was the main phosphate-solubilizing bacteria. In group C, the microorganisms that solubilized phosphate were mainly unclassified_f_Enterobacteriaceae. Additionally, bioaugmentation promoted the formation of unattached precipitates and alleviated the inhibitory effect of cell surface precipitation on microbial metabolism. As a result, the formation rate of U-phosphate precipitates and the removal rates of aqueous U(VI) in both groups B and C were elevated significantly after bioaugmentation. The U(VI) removal rate was poor in the control group (group A, with only an indigenous consortium). Propionispora, Sporomusa and Clostridium_sensu_stricto_11 may have played an important role in the removal of uranium in group A. Furthermore, the addition of a reducing consortium promoted the reduction of U(VI) to U(IV), and immobilized uranium existed in the form of U(IV)-phosphate and U(VI)-phosphate precipitates in group B. In contrast, U was present mainly as U(VI)-phosphate precipitates in groups A and C. Overall, bioaugmentation with an exogenous consortium resulted in the rapid removal of uranium from groundwater and the formation of U-phosphate minerals and served as an effective strategy for improving the treatment of uranium-contaminated groundwater in situ.
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Agua Subterránea , Uranio , Fosfatos/metabolismo , Uranio/metabolismo , Oxidación-Reducción , Bacterias/metabolismo , Biodegradación AmbientalRESUMEN
High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O2 to investigate these mechanisms. Our findings indicate that HH significantly boosts erythropoiesis, leading to erythrocytosis and splenic changes, including initial contraction to splenomegaly over 14 days. A notable decrease in red pulp macrophages (RPMs) in the spleen, essential for RBCs processing, was observed, correlating with increased iron release and signs of ferroptosis. Prolonged exposure to hypoxia further exacerbated these effects, mirrored in human peripheral blood mononuclear cells. Single-cell sequencing showed a marked reduction in macrophage populations, affecting the spleen's ability to clear RBCs and contributing to splenomegaly. Our findings suggest splenic ferroptosis contributes to decreased RPMs, affecting erythrophagocytosis and potentially fostering continuous RBCs production in HAPC. These insights could guide the development of targeted therapies for HAPC, emphasizing the importance of splenic macrophages in disease pathology.
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Mal de Altura , Ferroptosis , Animales , Ratones , Humanos , Bazo , Esplenomegalia , Leucocitos Mononucleares , Macrófagos , HipoxiaRESUMEN
BACKGROUND: Despite the genotype 4 has become the dominant cause of hepatitis E disease in China, none antigen derived from genotype 4 of hepatitis E virus (HEV) was used in current commercial anti-HEV immunoassay, and the serological reactivity of antigen derive from genotype 4 is not well-charactered. METHODS: We expressed and purified the 4 main immuno-dominant epitopes derived from genotype 1 and 4 including ORF2 (410-621aa) of genotype 4, ORF3 (47-114aa) of genotype 4, ORF2 (396-606aa) of genotype 1 and ORF3 (56-123aa) of genotype 4. RESULTS: The ORF2 of genotype 4 displayed good diagnostics performance according to ROC analysis using in-house panel, and the immunoassays based the ORF2 of genotype 4 was then developed to detect the anti-HEV IgG antibodies and evaluated further in 530 anti-HEV IgG positive specimens and 380 negative specimens. The sensitivity and the specificity is 98.1% (520/530) and 94.7% (360/380) for immunoassay based on ORF2 of genotype 4, 96.6% (512/530) and 92.6% (352/380) for commercial immunoassay based on genotype 1. It is noted that all of the positive samples will be detected by combing two assays together. The anti-HEV immunoassays based on genotype 4 are in accordance with Chinese anti-HEV national standard,and show an good agreement of 95.8% with commercial assay (kappa=0.913, P=0.014). CONCLUSIONS: The immunoassay based on ORF2G4 displays good performance, and combining assay based on genotype 1 together with genotype 4 will benefit the HEV diagnosis in large scale samples.
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Antígenos Virales , Pruebas Diagnósticas de Rutina/métodos , Anticuerpos Antihepatitis/sangre , Virus de la Hepatitis E/inmunología , Hepatitis E/diagnóstico , Epítopos Inmunodominantes , Virología/métodos , Antígenos Virales/genética , China , Humanos , Inmunoensayo/métodos , Epítopos Inmunodominantes/genética , Proteínas Recombinantes/genética , Sensibilidad y EspecificidadRESUMEN
Tumor-remodeled endothelial cells not only facilitate the formation of tumor angiogenesis but also promote tumorigenesis. In this study, we aimed to explore the interaction between glioma-associated endothelial cells (GAEs) and glioma cells. We found that different subtypes of glioma owned distinct GAE abundance. Glioma patients with high GAE abundance exhibited poor prognosis. Both the results of the bioinformatics analysis and the in vitro co-culture system assay revealed that GAE promoted glioma cell invasion. Besides, anti-vascular endothelial growth factor (VEGF) therapy partially abolished the effects of GAE on gliomas. Moreover, anti-VEGF therapy upregulated IL-2 expression in GAE, and exogenous IL-2 administration inhibits GAE-induced glioma cell invasion. Collectively, our present study provides a novel outstanding of the interaction between GAE and glioma cells.
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Neoplasias Encefálicas , Glioma , Humanos , Factores de Crecimiento Endotelial/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Células Endoteliales/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Interleucina-2/farmacología , Glioma/tratamiento farmacológico , Glioma/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Línea Celular TumoralRESUMEN
DL-3-n-butylphthalide (NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke. NBP has shown recent potential as a treatment for Parkinson's disease. However, the underlying mechanism of action of NBP remains poorly understood. In this study, we established a rat model of Parkinson's disease by intraperitoneal injection of rotenone for 28 successive days, followed by intragastric injection of NBP for 14-28 days. We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson's disease, inhibited loss of dopaminergic neurons and aggregation of α-synuclein, and reduced iron deposition in the substantia nigra and iron content in serum. These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor, ferritin light chain, and transferrin 1. NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson's disease. Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition, oxidative stress, and ferroptosis in the substantia nigra.
RESUMEN
The histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)-mediated trimethylation of histone H3 lysine 27 (H3K27me3) regulates neural stem cell proliferation and fate specificity through silencing different gene sets in the central nervous system. Here, we explored the function of EZH2 in early post-mitotic neurons by generating a neuron-specific Ezh2 conditional knockout mouse line. The results showed that a lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and increased dendritic spine density. Transcriptome analysis revealed that neuronal EZH2-regulated genes are related to neuronal morphogenesis. In particular, the gene encoding p21-activated kinase 3 (Pak3) was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of the dominant negative Pak3 reversed Ezh2 knockout-induced higher dendritic spine density. Finally, the lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 acts to control multiple steps of neuronal morphogenesis during development, and has long-lasting effects on cognitive function in adult mice.
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Proteína Potenciadora del Homólogo Zeste 2 , Plasticidad Neuronal , Neuronas , Animales , Ratones , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Histona Metiltransferasas/metabolismo , Histonas/genética , Morfogénesis , Neuronas/metabolismoRESUMEN
The present study was designed to investigate the neuroprotective effect of ginseng total saponins (GTSs) and its underlying mechanisms in a rat model of traumatic brain injury (TBI). Rats were injected with GTSs (20 mg/kg, i.p.) or vehicle for 14 days after TBI. Neurological functions were determined using beam balance and prehensile traction tests at 1-14 days after trauma. Brain samples were extracted at 1 day after trauma for determination of water content, Nissl staining, enzyme-linked immunosorbent assay, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling, and measurement of oxidative stress variables and inflammatory cytokines. Moreover, the dose response of the neuroprotective effect and time window of the efficacy of GTSs were also determined. We found that treatment of GTSs 1) improved the neurological function with an effective dosage of 5-80 mg/kg and an efficacy time window of 3-6 hr after TBI; 2) reduced brain water content and neuronal loss in the hippocampal CA3 area; 3) increased the activity of superoxide dismutase and decreased the activity of nitric oxide synthase and the amount of malondialdehyde and nitric oxide; 4) down-regulated interleukin-1ß, interleukin-6, and tumor necrosis factor-α and upregulated interleukin-10 in the cortical area surrounding the injured core; and 5) inhibited the apoptotic cell death and expression of caspase-3 and bax and raised the expression of bcl-2. These findings suggest that administration of GTSs after TBI could reduce the secondary injury through inhibiting oxidative and nitrative stress, attenuating inflammatory response, and reducing apoptotic cell death.
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Lesiones Encefálicas/tratamiento farmacológico , Corteza Cerebral/lesiones , Panax/química , Saponinas/farmacología , Animales , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/metabolismo , Edema Encefálico/patología , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Especies de Nitrógeno Reactivo/metabolismoRESUMEN
PURPOSE: To explore the feasibility of adhesive thiomer calcium alginate composite hydrogel (ZIF-8@CHA-SH) containing metal-organic framework for the treatment of periodontitis in rats. METHODS: Preparation and characterization of ZIF-8@CHA-SH were performed, and the morphology and chemical composition were observed. The antibacterial properties were detected by plate coating method and scanning electron microscope. CCK-8 and live/dead cell fluorescence staining were used to evaluate the toxicity of ZIF-8@CHA-SH on gingival fibroblasts. The anti-inflammatory and tissue repair promoting effects of ZIF-8@CHA-SH were verified by animal experiments. GraphPad Prism 7.0 software was used for statistical analysis. RESULTS: The successful synthesis of ZIF-8@CHA-SH was proved by scanning electron microscopy, energy spectrum analysis, Fourier transform infrared spectroscopy and X-ray diffraction. ZIF-8@CHA-SH had excellent antibacterial ability, and the antibacterial rates against Escherichia coli, Staphylococcus aureus and Streptococcus mutans were (99.88±0.12)%, (99.81±0.32)% and (95.53±3.08)%, respectivelyï¼P<0.001ï¼. The cell viability rate of ZIF-8@CHA-SH was (91.64±3.66)% after 5 days of co-culture with human gingival fibroblasts (P=0.6). In vivo experiments showed that ZIF-8@CHA-SH could reduce the infiltration of inflammatory cells and the expression of pro-inflammatory factor IL-6 in rats with periodontitis. CONCLUSIONS: ZIF-8@CHA-SH has excellent biological performance, which can effectively treat periodontitis caused by bacteria, and provids a new strategy for the treatment of periodontal diseases in the future.
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Periodontitis , Zeolitas , Ratas , Animales , Humanos , Zinc , Zeolitas/química , Hidrogeles/química , Alginatos , Antibacterianos/farmacología , Periodontitis/tratamiento farmacológico , Imidazoles/químicaRESUMEN
Knowledge distillation (KD) is a popular method to train efficient networks ("student") with the help of high-capacity networks ("teacher"). Traditional methods use the teacher's soft logits as extra supervision to train the student network. In this paper, we argue that it is more advantageous to make the student mimic the teacher's features in the penultimate layer. Not only the student can directly learn more effective information from the teacher feature, feature mimicking can also be applied for teachers trained without a softmax layer. Experiments show that it can achieve higher accuracy than traditional KD. To further facilitate feature mimicking, we decompose a feature vector into the magnitude and the direction. We argue that the teacher should give more freedom to the student feature's magnitude, and let the student pay more attention on mimicking the feature direction. To meet this requirement, we propose a loss term based on locality-sensitive hashing (LSH). With the help of this new loss, our method indeed mimics feature directions more accurately, relaxes constraints on feature magnitudes, and achieves state-of-the-art distillation accuracy. We provide theoretical analyses of how LSH facilitates feature direction mimicking, and further extend feature mimicking to multi-label recognition and object detection.
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Algoritmos , Aprendizaje , HumanosRESUMEN
We investigated the morphological characteristics of C. korshinskii seeds with three different sizes under plantations with different stand ages (6, 12, 18, 40 and 50 years old) in the typical sandy-hilly region of northwest Shanxi Province, to explore the restoration potential of artificial vegetation from the perspective of reproduction strategies. The results showed that seed production of C. korshinskii plantation increased with stand age, reaching the maximum (584 grain·plant-1) in 50-year-old stand. Seed length, seed width, and seed shape index decreased with stand age, reaching the minimum (5.09 mm, 2.76 mm and 0.05) in 50-year-old stand. Seed germination percentage showed an upward-downward-upward fluctuating trend, reaching the maximum (97.2%) at 12-year-old stand. Seed production was significantly negatively correlated with seed weight. Seed germination percentage was closely related to seed weight. Seeds with low weight had a low germination percentage and were easier to form a persistent seed bank. In addition, seed production was significantly positively correlated with the height of mother plant, aboveground biomass and belowground biomass, while the shape index of C. korshinskii seeds was significantly negatively correlated with number of new branches. It indicated that with the increases of stand age, the reproduction strategy of C. korshinskii changed from the K strategy with larger seeds in the early stage (6-12 year-old) to the r strategy of small seeds in the later stage (18-50 year-old). Specifically, C. korshinskii kept both the high number and high persistence of seeds by producing a larger number of small and round seeds.