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Eulophidae and Pteromalidae are parasitic wasps with a global distribution and import for the biological control of pests. They can be distributed in different altitude regions, but their morphological and genetic adaptations to different altitudes are unclear. Here, we collected specimens that belong to Eulophidae and Pteromalidae from various altitudinal gradients, based on integrated taxonomic approaches to determine the species composition, and we analyzed their body shape and size from different altitudes using geometric morphometrics. Then, we performed an analysis of the D. isaea population's haplotype genes to illustrate their genetic diversity. As a result, eight species that belong to two genera, Diglyphus Walker (Eulophidae) and Pachyneuron Walker (Pteromalidae), were identified, including two newly recorded species from China (D. chabrias and D. sabulosus). Through a geometric morphometrics analysis of body shape, we found that a narrow forewing shape and a widened thorax are the significant characteristics of adaptation to high-altitude environments in D. isaea and P. aphidis. Additionally, the body size studies showed a principal relationship between centroid size and altitude; the size of the forewings and thorax increases at higher altitudes. Next, using haplotype analysis, 32 haplotypes were found in seven geographic populations with high genetic diversity of this species. Our research provides preliminary evidence for the morphological and genetic diversity adaptation of parasitic wasps to extreme environments, and these data can provide important references for investigations on the ecological adaptability of parasitic wasps.
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Psoriasis, a chronic inflammatory skin disorder, is associated with comorbidities such as acute myocardial infarction (AMI). However, the molecular mechanisms connecting these conditions are unclear. In this study, we conducted bioinformatics analyses using gene expression datasets to identify differentially expressed genes and hub genes associated with both psoriasis and AMI. Our findings emphasize the involvement of immune-related pathways in the pathogenesis of both conditions. Furthermore, we investigated the expression levels of hub genes in AMI patients and myocardial infarction (MI) mice. ELISA measurements revealed significantly higher levels of CXCL8, IL1B, S100A9, and S100A12 in the serum of AMI patients compared to normal individuals. Immunohistochemical staining of heart tissue from MI mice showed a progressive increase in the expression of CXCL8 and IL-1B as MI advanced, while S100A9 exhibited high expression at day 3 post-MI. mRNA expression analysis validated these findings. Additionally, we explored the skin lesions of psoriasis patients and found significantly higher expression of CXCL8, IL-1B, S100A9, and S100A12 in the affected skin areas compared to unaffected regions. These results highlight the consistent upregulation of hub genes in both AMI and psoriasis patients, as well as in myocardial infarction mice, underscoring their potential as reliable markers for disease diagnosis. Moreover, molecular docking simulations revealed potential interactions between simvastatin and key target proteins, suggesting a potential therapeutic avenue. Overall, our study uncovers shared molecular signatures and potential therapeutic targets, providing a foundation for future investigations targeting common pathways in psoriasis and AMI.
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Calgranulina B , Infarto del Miocardio , Psoriasis , Psoriasis/genética , Psoriasis/metabolismo , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Animales , Humanos , Ratones , Calgranulina B/genética , Calgranulina B/metabolismo , Interleucina-8/metabolismo , Interleucina-8/genética , Simulación del Acoplamiento Molecular , Simvastatina/farmacología , Simvastatina/uso terapéutico , Proteína S100A12/genética , Proteína S100A12/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Masculino , Modelos Animales de Enfermedad , Biología Computacional/métodos , Perfilación de la Expresión Génica , Femenino , BiomarcadoresRESUMEN
Cadmium (Cd) is a heavy metal that significantly impacts human health and the environment. Microorganisms play a crucial role in reducing heavy metal stress in plants; however, the mechanisms by which microorganisms enhance plant tolerance to Cd stress and the interplay between plants and microorganisms under such stress remain unclear. In this study, Oceanobacillus picturae (O. picturae) was isolated for interaction with soybean seedlings under Cd stress. Results indicated that Cd treatment alone markedly inhibited soybean seedling growth. Conversely, inoculation with O. picturae significantly improved growth indices such as plant height, root length, and fresh weight, while also promoting recovery in soil physiological indicators and pH. Metabolomic and transcriptomic analyses identified 157 genes related to aspartic acid, cysteine, and flavonoid biosynthesis pathways. Sixty-three microbial species were significantly associated with metabolites in these pathways, including pathogenic, adversity-resistant, and bioconductive bacteria. This research experimentally demonstrates, for the first time, the growth-promoting effect of the O. picturae strain on soybean seedlings under non-stress conditions. It also highlights its role in enhancing root growth and reducing Cd accumulation in the roots under Cd stress. Additionally, through the utilization of untargeted metabolomics, metagenomics, and transcriptomics for a multi-omics analysis, we investigated the impact of O. picturae on the soil microbiome and its correlation with differential gene expression in plants. This innovative approach unveils the molecular mechanisms underlying O. picturae's promotion of root growth and adaptation to Cd stress.
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Cadmio , Glycine max , Plantones , Estrés Fisiológico , Glycine max/crecimiento & desarrollo , Glycine max/efectos de los fármacos , Glycine max/microbiología , Glycine max/metabolismo , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Cadmio/toxicidad , Estrés Fisiológico/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/microbiología , Raíces de Plantas/metabolismo , Bacillaceae/crecimiento & desarrollo , Bacillaceae/metabolismo , Bacillaceae/genética , Bacillaceae/efectos de los fármacos , Microbiología del SueloRESUMEN
The glycated hemoglobin (HbA1c) level, which is defined as the ratio of HbA1c to total hemoglobin (tHb, including glycated and unglycated hemoglobin), is considered one of the preferred indicators for diabetes monitoring. Generally, assessment of the HbA1c level requires separate determination of tHb and HbA1c concentrations after a complex separation step. This undoubtedly increases the cost of the assay, and the loss or degradation of HbA1c during the separation process results in a decrease in the accuracy of the assay. Therefore, this study explored a dual-signal acquisition method for the one-step simultaneous evaluation of tHb and HbA1c. Quantification of tHb: graphene adsorbed carbon quantum dots and methylene blue were utilized as the substrate material and linked to the antibody. tHb was captured on the substrate by the antibody. The unique heme group on tHb catalyzed the production of â¢OH from H2O2 to degrade methylene blue on the substrate, and a quantitative relationship between the tHb concentration and the methylene blue oxidation current signal was constructed. Quantification of HbA1c: complex labels with HbA1c recognition were made of ZIF-8-ferrocene-gold nanoparticles-mercaptophenylboronic acid. The specific recognition of the boronic acid bond with the unique cis-diol structure of HbA1c establishes a quantitative relationship between the oxidation current of the label-loaded ferrocene and the concentration of HbA1c. Thus, the HbA1c level can be assessed with only one signal readout. The sensor exhibited extensive detection ranges (0.200-600 ng/mL for tHb and 0.100-300 ng/mL for HbA1c) and low detection limits (4.00 × 10-3 ng/mL for tHb and 1.03 × 10-2 ng/mL for HbA1c).
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Hemoglobina Glucada , Azul de Metileno , Hemoglobina Glucada/análisis , Humanos , Azul de Metileno/química , Grafito/química , Oro/química , Nanopartículas del Metal/química , Puntos Cuánticos/química , Hemoglobinas/análisis , Hemoglobinas/química , Ácidos Borónicos/química , Compuestos Ferrosos/química , Metalocenos/química , Límite de Detección , Técnicas Electroquímicas/métodos , Peróxido de Hidrógeno/químicaRESUMEN
The sensitivity of electrochemical (EC) sensors has been improved through the development of multiple approaches. However, the majority of EC sensors were limited in their practical application by high costs or tedious procedures. Herein, based on ethylenediaminetetraacetic acid (EDTA)-Pb2+ complexation reaction, a facile and affordable immunosensor was designed. Pb2+-magnesium silicate hydrate was served as the sensing substrate. The immunorecognition process was carried out in the Eppendorf tube, and antibody-functionalized Pb2+-polydopamine was utilized as immunoprobe. In the tube, the quantitative and appropriate excess of EDTA was introduced to complex with Pb2+ on the immunoprobes. The remaining EDTA was added to the sensing substrate surface to coordinate with some Pb2+ in it. This leaded to the reduction of the EC signal of Pb2+, which was related to the antigen concentration. Using prostate-specific antigen as the model analyte, the sensitive detection was realized with a low limit of detection (30.49 fg mL-1). Remarkably, the assay results were available within 24 min, sensibly faster than the most existing EC sensors.
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Técnicas Biosensibles , Nanopartículas del Metal , Humanos , Masculino , Ácido Edético , Técnicas Electroquímicas/métodos , Límite de Detección , Plomo , Técnicas Biosensibles/métodos , Inmunoensayo/métodos , OroRESUMEN
Detection and segmentation of neural synapses in electron microscopy images are the committed steps for analyzing neural ultrastructure. To date, manual annotation of the structure in synapses has been the primary method, which is time-consuming and restricts the throughput of data acquisition. Recent studies have utilized a series of deformations based on a segmentation model for the detection and segmentation of transmission electron microscope images. However, the analysis of synaptic segmentation and statistics still lacks sufficient automation and high-throughput. Therefore, we developed a dual-channel neural network instance segmentation model with weighted top-down and multi-scale bottom-up schemes, which aid in accurately detecting and segmenting synaptic vesicles and their active zones within presynaptic membranes in complex environments. In addition, we proposed a masked self-supervised pre-training model based on the latest convolutional architecture to improve performance in downstream segmentation tasks. By comparing our model to other state-of-the-art methods, we determined its viability and accuracy. The applicability of our model is thoroughly demonstrated by distinct application scenarios for neurobiological research. These findings indicate that the dual-channel neural network could facilitate the analysis of synaptic structures for the advancement of biomedical research and electron microscope reconstruction techniques.
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Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación , Procesamiento de Imagen Asistido por Computador/métodos , Sinapsis , Microscopía , AutomatizaciónRESUMEN
Three undescribed isosteroidal alkaloids, przewalskines A-C (1-3), as well as seven known alkaloids (4-10) were obtained from Fritillaria przewalskii bulbs. Their structures were deduced by extensive HRESIMS, 1D NMR, and 2D NMR analyses, and their bioactivities were evaluated involving the anti-inflammatory and inhibitory potencies on AChE, BChE, and Aß aggregation. Compound 4 revealed the potent effect on inhibiting Aß aggregation activity with IC50 value of 33.1â µM, AChE activity with IC50 value of 6.9â µM, and also showed NO release inhibitory acitivity with IC50 value of 32.6â µM. These findings contribute new multi-.target anti-AD agents and embody the chemical diversity of F. przewalskii.
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Alcaloides , Fritillaria , Fritillaria/química , Alcaloides/farmacología , Alcaloides/químicaRESUMEN
AIM: Senescence of alveolar type II (AT2) cells is an important driver of pulmonary fibrosis. This study aimed to investigate whether and how dysregulation of hydrogen sulfide (H2 S) production affected AT2 cell senescence, and then explored the effect of H2 S on the communication between AT2 and fibroblasts. METHODS: ICR mice were intratracheally administered with bleomycin (3 mg/kg). Sodium hydrosulfide (NaHS, 28 µmol/kg/d) was intraperitoneally injected for 2 weeks. The H2 S-generating enzyme cystathionine-ß-synthase (CBS) knockout heterozygous (CBS+/- ) mice were used as a low H2 S production model. RESULTS: Analysis of microarray datasets revealed downregulation of H2 S-generating enzymes in lung tissues of patients with pulmonary fibrosis. Decreased H2 S production was correlated with higher levels of cell senescence markers p53 and p21 in bleomycin-induced lung fibrosis. CBS+/- mice exhibited increased levels of p53 and p21. The numbers of AT2 cells positive for p53 and p21 were increased in CBS+/- mice as compared to control mice. H2 S donor NaHS attenuated bleomycin-induced AT2 cell senescence both in vivo and in vitro. H2 S donor suppressed bleomycin-induced senescence-associated secretory phenotype (SASP) of AT2 cells via inhibiting p53/p21 pathway, consequently suppressing proliferation and myofibroblast transdifferentiation of fibroblasts. Mechanically, H2 S suppressed p53 expression by enhancing the mouse double-minute 2 homologue (MDM2)-mediated ubiquitination and degradation of p53. CONCLUSION: H2 S inactivated p53-p21 pathway, consequently suppressing AT2 cell senescence as well as cell communication between senescent AT2 cells and fibroblasts. Aberrant H2 S synthesis may contribute to the development of pulmonary fibrosis through promoting the activation loop involving senescent AT2 cells and activated fibroblasts.
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Sulfuro de Hidrógeno , Fibrosis Pulmonar , Humanos , Ratones , Animales , Fibrosis Pulmonar/inducido químicamente , Sulfuro de Hidrógeno/farmacología , Sulfuro de Hidrógeno/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Ratones Endogámicos ICR , Senescencia Celular , Bleomicina/metabolismo , Bleomicina/farmacología , Proteínas Proto-Oncogénicas c-mdm2RESUMEN
Saline and alkali stress affects the growth and development, survival rate, and final yield of rice, while new nano materials can have a positive effect on rice growth. In order to investing the effects of carboxymethyl multi walled carbon nanotubes (MWCNTs) on the growth and development of rice seedlings under salt alkali stress, rice seedlings were cultured using rice variety "Songjing 3" using nutrient solution water culture method. The effects of MWCNTs on water absorption capacity, leaf photosynthesis, and sucrose metabolism of rice seedlings under 50 mmol/L saline-alkali stress (1NaCl: 9Na2SO4: 9NaHCO3: 1Na2CO3) conditions were investigated. The results showed that MWCNTs can improve the water use ability of roots and leaves, especially the water absorption ability of roots, which provides a guarantee for the improvement of rice biomass and the enhancement of leaf photosynthetic capacity under adverse conditions. After treatment with MWCNTs, the photosynthetic rate (Pn), stomatal conductance (gs), and transpiration rate (Tr) of leaves increased significantly, and the photochemical quenching value (qP), photochemical quantum efficiency value (Fv/Fm), and electron transfer rate value (ETR) of chlorophyll fluorescence parameters increased significantly, which is beneficial to the improvement of the PSII photosynthetic system. MWCNTs treatment promoted the increase of photosynthetic pigment content in leaves under salt and alkali stress, improved the ratio of Chla and Chlb parameters, increased the activities of key photosynthetic enzymes (RUBPCase and PEPCase) in leaves, increased the value of total lutein cycle pool (VAZ), and significantly enhanced the deepoxidation effect of lutein cycle (DEPS), which can effectively alleviate the stomatal and non stomatal constraints on leaf photosynthesis caused by salt and alkali stress. MWCNTs treatment significantly enhanced the activities of sucrose phosphate synthase (SPS) and sucrose synthase (SS) under salt and alkali stress, and decreased the activities of soluble acid invertase (SAInv) and alkaline/neutral invertase (A/N-Inv), indicating that MWCNTs promoted sucrose synthesis while inhibiting sucrose decomposition, thereby promoting sucrose accumulation in rice leaves. This study can provide theoretical and experimental basis for the application of MWCNTs to the production of rice under salt and alkali stress, and can find a new way for rice production in saline and alkaline lands.
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Nanotubos de Carbono , Oryza , Plantones/metabolismo , Oryza/metabolismo , Clorofila/metabolismo , Álcalis/metabolismo , Luteína/metabolismo , Luteína/farmacología , Fotosíntesis , Cloruro de Sodio/farmacología , Agua/metabolismo , Hojas de la Planta/metabolismoRESUMEN
OBJECTIVE: The aim of the study was to discern the disparities in the aerobic capacity of female athletes occupying various positions within a soccer team, and to understand the physical characteristics of the athletes in different positions. It is critical to understand that the physical demands for players vary depending on their positions on the field, a factor that greatly influences their training and gameplay. MATERIAL AND METHODS: The study engaged a sample of 25 female soccer players, average age of 22.72 (±2.69 SD), all of whom were active participants in the Chinese Women's Super League. The sample was distributed across several playing positions, including forwards, midfielders, and defenders. To gather pertinent data on oxygen uptake, a progressive load test was administered on a treadmill, coupled with a gas analyzer to amass respiratory indices (JAEGER, Germany). RESULTS: The study revealed that there was a notable variance in the maximum oxygen uptake among players in different positions. The midfielders exhibited the highest VO2 max at 63.24±7.04 ml/kg/min, followed by the forwards who averaged at 58.92±7.70 ml/kg/min, and finally the defenders who recorded the smallest average at 55.73±4.40 ml/kg/min. CONCLUSIONS: The outcomes of this study indicate that the positional role of a player in a team correlates with their aerobic capacity. Therefore, the positional demands significantly shape the player's physical characteristics, influencing their training and gameplay. This understanding is vital for the optimal conditioning of athletes in different positions in the sport of soccer.
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Rendimiento Atlético , Fútbol , Humanos , Femenino , Adulto Joven , Adulto , Consumo de Oxígeno , Oxígeno , AtletasRESUMEN
BACKGROUND: Lumbar facet joint pain is a common disorder. The main symptom is chronic lumbar pain, which can reduce quality of life. Radiofrequency has often been used to treat lumbar facet joint pain. However, the effectiveness of this technique has been controversial. This study was conducted to compare the effectiveness of pulsed radiofrequency (PRF) and radiofrequency denervation (RD) for lumbar facet joint pain. METHODS: One hundred and forty-two patients with lumbar facet joint pain were allocated to two treatment groups: PRF group (N = 72) and RD group (N = 70). Patients enrolled in the study were assessed using a visual analogue scale (VAS), Roland-Morris questionnaire (RMQ), Oswestry disability index (ODI) and Short-Form 36 (SF-36) questionnaire before therapy, 3 months and 12 months later. RESULTS: There were no significant differences in VAS, RMQ score, ODI score and SF-36 score at 3 months (p > 0.05). Significant differences in pain control were observed in both groups at 12 months (3.09 ± 1.72 vs. 2.37 ± 1.22, p = 0.006). There was a significant difference in RMQ score (11.58 ± 3.58 vs. 8.17 ± 2.34, p < 0.001) and ODI score (43.65 ± 11.01 vs. 35.42 ± 11.32, p < 0.001) at 12 months. The total SF-36 score was higher in the RD group than in the PRF group at 12 months (58.45 ± 6.97 vs. 69.36 ± 6.43, p < 0.001). In terms of complications, skin numbness occurred in three patients. Mild pain such as burning and pinking at the puncture site in two patients. One patient experienced a decrease in back muscle strength and back muscle fatigue. These complications disappeared in 3 weeks without any treatment. There were no serious adverse events in the PRF group. CONCLUSION: Radiofrequency is an effective and safe treatment option for patients with lumbar facet joint pain. RD could provide good and lasting pain relief, with significant improvement in lumbar function and quality of life at long-term follow-up.
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Dolor de la Región Lumbar , Tratamiento de Radiofrecuencia Pulsada , Articulación Cigapofisaria , Humanos , Articulación Cigapofisaria/cirugía , Tratamiento de Radiofrecuencia Pulsada/métodos , Calidad de Vida , Punción Espinal , Dolor de la Región Lumbar/cirugía , Dolor de la Región Lumbar/diagnóstico , Artralgia/etiología , Artralgia/cirugía , Desnervación/métodos , Resultado del TratamientoRESUMEN
To investigate the structural information differences of Ziziphus Jujuba cv. Muzao polysaccharides, ten samples were successfully extracted from aqueous and alkaline solutions, prepared via DEAE-Sepharose Fast Flow through different eluents and Sephacryl S-300 columns, and systematically analyzed. Their characteristics were studied and then compared using chemical testing, high-performance gel permeation chromatography (HPGPC), gas chromatography (GC), methylation analysis, and NMR spectroscopy. The data achieved demonstrated that different jujube polysaccharide fractions possessed different structural characteristics, and most of them belonged to pectic polysaccharides. Overall, the structural information difference of jujube polysaccharides was preliminarily illuminated, which could not only promote the potential application of Z. Jujuba cv. Muzao polysaccharides but also provide an effective way to analyze the structures of polysaccharides from other genera jujube fruit.
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Ziziphus , Ziziphus/química , Antioxidantes/química , Extractos Vegetales/química , Frutas/química , Polisacáridos/químicaRESUMEN
More and more evidences have showed that the unnatural expression of long non-coding RNA (lncRNA) is relevant to varieties of human diseases. Therefore, accurate identification of disease-related lncRNAs can help to understand lncRNA expression at the molecular level and to explore more effective treatments for diseases. Plenty of lncRNA-disease association prediction models have been raised but it is still a challenge to recognize unknown lncRNA-disease associations. In this work, we have proposed a computational model for predicting lncRNA-disease associations based on geometric complement heterogeneous information and random forest. Firstly, geometric complement heterogeneous information was used to integrate lncRNA-miRNA interactions and miRNA-disease associations verified by experiments. Secondly, lncRNA and disease features consisted of their respective similarity coefficients were fused into input feature space. Thirdly, an autoencoder was adopted to project raw high-dimensional features into low-dimension space to learn representation for lncRNAs and diseases. Finally, the low-dimensional lncRNA and disease features were fused into input feature space to train a random forest classifier for lncRNA-disease association prediction. Under five-fold cross-validation, the AUC (area under the receiver operating characteristic curve) is 0.9897 and the AUPR (area under the precision-recall curve) is 0.7040, indicating that the performance of our model is better than several state-of-the-art lncRNA-disease association prediction models. In addition, case studies on colon and stomach cancer indicate that our model has a good ability to predict disease-related lncRNAs.
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More and more studies have proved that microRNAs (miRNAs) play a critical role in gene expression regulation, and the irregular expression of miRNAs tends to be associated with a variety of complex human diseases. Because of the high cost and low efficiency of identifying disease-associated miRNAs through biological experiments, scholars have focused on predicting potential disease-associated miRNAs by computational methods. Considering that the existing methods are flawed in constructing negative sample set, we proposed a clustering-based sampling method for miRNA-disease association prediction (CSMDA). Firstly, we integrated multiple similarity information of miRNA and disease to represent miRNA-disease pairs. Secondly, we performed a clustering-based sampling method to avoid introducing potential positive samples when constructing negative sample set. Thirdly, we employed a random forest-based feature selection method to reduce noise and redundant information in the high-dimensional feature space. Finally, we implemented an ensemble learning framework for predicting miRNA-disease associations by soft voting. The Precision, Recall, F1-score, AUROC and AUPR of the CSMDA achieved 0.9676, 0.9545, 0.9610, 0.9928, and 0.9940, respectively, under five-fold cross-validation. Besides, case study on three cancers showed that the top 20 potentially associated miRNAs predicted by the CSMDA were confirmed by the dbDEMC database or literatures. The above results demonstrate that the CSMDA can predict potential disease-associated miRNAs more accurately.
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Melanocortin 4 receptor (MC4R) in the paraventricular nucleus of the hypothalamus (PVH) shows bidirectional characterization in modulating food intake and energy homeostasis. We demonstrate that MC4R knockdown (KD) in the PVH can attenuate AMPA receptor (AMPAR)-mediated postsynaptic responses by altering the phosphorylation of AMPAR GluA1 subunit through the protein kinase A (PKA)-dependent signaling cascade and simultaneously lead to rapid body weight gain. Furthermore, PKA KD in the PVH engendered similar electrophysiological and behavioral phenotypes as in MC4R KD mice. Importantly, we observed that the reduction of AMPAR GluA1 expression not only led to attenuated synaptic responses but also caused body weight gain, suggesting that the aberration of synaptic responses may be one of the crucial pathogeny of obesity. Our study provides the synaptic and molecular explanations of how body weight is regulated by MC4R in the PVH.
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Obesidad , Receptor de Melanocortina Tipo 4 , Animales , Ratones , Peso Corporal , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Obesidad/metabolismo , Receptor de Melanocortina Tipo 4/genética , Receptor de Melanocortina Tipo 4/metabolismo , Receptores AMPA/genética , Receptores AMPA/metabolismo , Transmisión SinápticaRESUMEN
Background: Autophagy is activated during the pathogenesis of endothelial dysfunction and sepsis-associated acute lung injury (ALI). This study aimed to investigate whether autophagy affected endothelial barrier dysfunction and lung injury in a murine model of lipopolysaccharide (LPS)-induced ALI, and then further clarify whether forkhead box O1 (FOXO1), an autophagy-related transcriptional factor, contributed to autophagy activation and ALI induced by LPS. Methods: Male C57BL/6 mice were treated with LPS (30 mg/kg), and then were allocated to a control group and an LPS group with or without FOXO1 inhibitor (AS1842856) treatment, respectively. Primary cultured mouse lung vascular endothelial cells (MLVECs) were treated with LPS, autophagy inhibitor 3-methyladenine (3-MA), AS1842856, and small interfering RNA (siRNA) targeting autophagy-related gene 5 (ATG5) or FOXO1. Endothelial autophagic flux was assessed by transfection of MLVECs with red fluorescent protein (RFP)-green fluorescent protein (GFP) tandem fluorescent-tagged LC3 (RFP-GFP-LC3) adenovirus. Endothelial permeability was analyzed by the diffusion of fluorescein isothiocyanate-carboxymethyl (FITC)-dextran through the endothelial monolayer. Evans blue albumin tracer was used to measure the pulmonary transvascular permeability, and hematoxylin and eosin (H&E) staining was used to observe pathological changes in the lung tissues. Immunofluorescence staining was also used to detect the expression of zonula occludens-1 (ZO-1) and FOXO1. Results: This study found autophagy induction in lung tissues of endotoxemic mice and LPS-treated MLVECs, as evidenced by elevated expression of light chain 3 II (LC3-II) and Unc-51-like kinase (ULK1) and autophagic flux. LPS treatment decreased vascular endothelial (VE)-cadherin and ZO-1 expression and increased endothelial permeability in MLVECs, which were significantly alleviated by autophagy inhibitor 3-MA and ATG5 siRNA. It was found that both phosphorylated FOXO1 and FOXO1 were upregulated in the lung tissues of endotoxemic mice and LPS-treated MLVECs. Both FOXO1 inhibitor AS1842856 and FOXO1 siRNA suppressed LPS-induced autophagy and endothelial cell injury in MLVECs. Moreover, FOXO1 inhibition profoundly alleviated autophagy, lung endothelial hyperpermeability, and ALI in endotoxemic mice. Conclusions: This work demonstrated that FOXO1 upregulation is an important contributor to LPS-induced autophagy in pulmonary VE cells. The detrimental effects of FOXO1 in endotoxemia-associated endothelial dysfunction and ALI are partly due to its potent pro-autophagic property. Inhibition of FOXO1 may be a potential therapeutic option for the treatment of ALI.
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BACKGROUND: Pulsed radiofrequency (PRF) of the Gasserian ganglion is a common surgical intervention used to treat trigeminal postherpetic neuralgia (PHN). Dexamethasone has been reported to possess anti-inflammatory effects and potential analgesic benefits. OBJECTIVES: The primary objective of our study was to compare the therapeutic efficacies of PRF alone versus a combination of PRF and dexamethasone for trigeminal PHN. STUDY DESIGN: A prospective, double-blind, randomized controlled trial. SETTING: Department of Pain Management, Wuhan First Hospital. METHODS: A total of 103 patients diagnosed with trigeminal PHN were randomly assigned into 2 groups (the PRF group and PRF plus dexamethasone [PRF+D] group). Digital subtraction angiography-guided puncture of the Gasserian ganglion was performed. All patients received PRF of the Gasserian ganglion first, and then a local injection was administered into the Gasserian ganglion. Patients in the PRF+D group received PRF therapy and one mL of 5 mg dexamethasone in the Gasserian ganglion, while patients in the PRF group received PRF therapy and one mL of normal saline in the Gasserian ganglion. The primary outcome was pain intensity, measured by the visual analog scale (VAS). The secondary outcome was quality of life, assessed by the Short Form-36 questionnaire (SF-36). The dosage of pregabalin administered was recorded to assess treatment effectiveness. RESULTS: Compared with the PRF group in this study, the PRF+D group showed more promising outcome results in pain relief as measured by the VAS; quality of life enhancement, as measured by the SF-36; and a reduced requirement for antiepileptic drugs (P < 0.01). LIMITATIONS: Single center study, relatively small number of patients. CONCLUSIONS: The therapeutic efficacy of PRF combined with a dexamethasone injection into the Gasserian ganglion was superior to that of PRF{and saline injection} alone of the Gasserian ganglion for trigeminal PHN.
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Neuralgia Posherpética , Tratamiento de Radiofrecuencia Pulsada , Neuralgia del Trigémino , Dexametasona/uso terapéutico , Humanos , Neuralgia Posherpética/terapia , Estudios Prospectivos , Tratamiento de Radiofrecuencia Pulsada/métodos , Calidad de Vida , Neuralgia del Trigémino/terapiaRESUMEN
In this study, BM-Fe (black sesame melanin-iron complex) was prepared and characterized. The results showed that the carboxyl hydroxyl group of BSM (black sesame melanin) participated in the chelation of iron ions. EDS (energy dispersive spectroscopy) and XPS (X-ray photoelectron spectroscopy) results confirmed the presence of iron ions in BM-Fe. The results of DLS (dynamic light scattering) showed that the average particle sizes of BSM and BM-Fe were 844.9 nm and 294.3 nm, respectively, indicating that the structure of BM-Fe with a smaller particle size was formed after the binding of iron ions with the active group on BSM. Finally, the in vitro iron dissolution, iron ion identification, in vitro iron ion reduction, antioxidant activity, cytotoxicity and moisture resistance properties of BM-Fe and FST (ferrous sulfate tablets, a commonly used iron supplement) were comprehensively compared. The results showed that BSM combined with iron instead of physically mixing, and BM-Fe was easily reduced in the gastrointestinal environment. BM-Fe had good bioavailability and retained the excellent characteristics (such as oxidation resistance and biocompatibility) of BSM, and had the potential to be applied in the treatment of iron-deficiency-related diseases. In summary, BM-Fe prepared in this study not only retained the excellent characteristics of BSM but also had a good effect on iron supplementation, high bioavailability and low side effects. Comprehensive analysis showed that the performance of BM-Fe prepared in this study was similar to or even better than that of the control (FST). Thus, BM-Fe is expected to become a new comprehensive multi-functional iron supplement and has a broad developmental prospect.
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Hierro , Melaninas , Disponibilidad Biológica , Radical Hidroxilo/química , Hierro/metabolismo , Melaninas/metabolismo , Espectroscopía de FotoelectronesRESUMEN
Voltage-gated sodium (NaV) channels play fundamental roles in initiating and propagating action potentials. NaV1.3 is involved in numerous physiological processes including neuronal development, hormone secretion and pain perception. Here we report structures of human NaV1.3/ß1/ß2 in complex with clinically-used drug bulleyaconitine A and selective antagonist ICA121431. Bulleyaconitine A is located around domain I-II fenestration, providing the detailed view of the site-2 neurotoxin binding site. It partially blocks ion path and expands the pore-lining helices, elucidating how the bulleyaconitine A reduces peak amplitude but improves channel open probability. In contrast, ICA121431 preferentially binds to activated domain IV voltage-sensor, consequently strengthens the Ile-Phe-Met motif binding to its receptor site, stabilizes the channel in inactivated state, revealing an allosterically inhibitory mechanism of NaV channels. Our results provide structural details of distinct small-molecular modulators binding sites, elucidate molecular mechanisms of their action on NaV channels and pave a way for subtype-selective therapeutic development.
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Canal de Sodio Activado por Voltaje NAV1.7 , Bloqueadores del Canal de Sodio Activado por Voltaje , Sitios de Unión , Humanos , Canal de Sodio Activado por Voltaje NAV1.7/química , Estructura Secundaria de Proteína , Sodio/metabolismo , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacologíaRESUMEN
CaMKII has long been known to be a key effector for synaptic plasticity. Recent studies have shown that a variety of modulators interact with the subunits of CaMKII to regulate the long-term potentiation (LTP) of hippocampal neurons. However, whether long non-coding RNAs modulate the activity of CaMKII and affect synaptic plasticity is still elusive. Here, we identify a previously uncharacterized long non-coding RNA Carip that functions as a scaffold, specifically interacts with CaMKIIß, and regulates the phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptor subunits in the hippocampus. The absence of Carip causes dysfunction of synaptic transmission and attenuates LTP in hippocampal CA3-CA1 synapses, which further leads to impairment of spatial learning and memory. In summary, our findings demonstrate that Carip modulates long-term synaptic plasticity by changing AMPA receptor and NMDA receptor activities, thereby affecting spatial learning and memory in mice.