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BACKGROUND: Posterior capsular opacification (PCO) is a common complication following cataract surgery that leads to visual disturbances and decreased quality of vision. The aim of our study was to employ a machine-learning methodology to characterize and validate enhancements applied to the grey-level co-occurrence matrix (GLCM) while assessing its validity in comparison to clinical evaluations for evaluating PCO. METHODS: One hundred patients diagnosed with age-related cataracts who were scheduled for phacoemulsification surgery were included in the study. Following mydriasis, anterior segment photographs were captured using a high-resolution photographic system. The GLCM was utilized as the feature extractor, and a supported vector machine as the regressor. Three variations, namely, GLCM, GLCM+C (+axial information), and GLCM+V (+regional voting), were analyzed. The reference value for regression was determined by averaging clinical scores obtained through subjective analysis. The relationships between the predicted PCO outcome scores and the ground truth were assessed using Pearson correlation analysis and a Bland-Altman plot, while agreement between them was assessed through the Bland-Altman plot. RESULTS: Relative to the ground truth, the GLCM, GLCM+C, and GLCM+V methods exhibited correlation coefficients of 0.706, 0.768, and 0.829, respectively. The relationship between the PCO score predicted by the GLCM+V method and the ground truth was statistically significant (p < 0.001). Furthermore, the GLCM+V method demonstrated competitive performance comparable to that of two experienced clinicians (r = 0.825, 0.843) and superior to that of two junior clinicians (r = 0.786, 0.756). Notably, a high level of agreement was observed between predictions and the ground truth, without significant evidence of proportional bias (p > 0.05). CONCLUSIONS: Overall, our findings suggest that a machine-learning approach incorporating the GLCM, specifically the GLCM+V method, holds promise as an objective and reliable tool for assessing PCO progression. Further studies in larger patient cohorts are warranted to validate these findings and explore their potential clinical applications.
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Opacificação da Cápsula , Extração de Catarata , Cápsula do Cristalino , Humanos , Opacificação da Cápsula/etiologia , Opacificação da Cápsula/cirurgia , Cápsula do Cristalino/cirurgia , Extração de Catarata/efeitos adversos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Statistical correlation analysis is currently the most typically used approach for investigating the risk factors of type 2 diabetes mellitus (T2DM). However, this approach does not readily reveal the causal relationships between risk factors and rarely describes the causal relationships visually. RESULTS: Considering the superiority of reinforcement learning in prediction, a causal discovery approach with reinforcement learning for T2DM risk factors is proposed herein. First, a reinforcement learning model is constructed for T2DM risk factors. Second, the process involved in the causal discovery method for T2DM risk factors is detailed. Finally, several experiments are designed based on diabetes datasets and used to verify the proposed approach. CONCLUSIONS: The experimental results show that the proposed approach improves the accuracy of causality mining between T2DM risk factors and provides new evidence to researchers engaged in T2DM prevention and treatment research.
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Diabetes Mellitus Tipo 2 , Humanos , Fatores de Risco , Aprendizagem , Projetos de PesquisaRESUMO
BACKGROUND: The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia. METHODS: We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms. RESULTS: In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP. CONCLUSION: P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstract.
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Microglia , Hemorragia Subaracnóidea , Humanos , Fagocitose , Autofagia , Inflamação , Proteínas Quinases Associadas com Morte CelularRESUMO
KRAS mutant lung adenocarcinomas remain intractable for targeted therapies. Genetic interrogation of KRAS downstream effectors, including the MAPK pathway and the interphase CDKs, identified CDK4 and RAF1 as the only targets whose genetic inactivation induces therapeutic responses without causing unacceptable toxicities. Concomitant CDK4 inactivation and RAF1 ablation prevented tumor progression and induced complete regression in 25% of KRAS/p53-driven advanced lung tumors, yet a significant percentage of those tumors that underwent partial regression retained a population of CDK4/RAF1-resistant cells. Characterization of these cells revealed two independent resistance mechanisms implicating hypermethylation of several tumor suppressors and increased PI3K activity. Importantly, these CDK4/RAF1-resistant cells can be pharmacologically controlled. These studies open the door to new therapeutic strategies to treat KRAS mutant lung cancer, including resistant tumors.
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Adenocarcinoma de Pulmão/genética , Quinase 4 Dependente de Ciclina/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/metabolismo , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Quinase 4 Dependente de Ciclina/metabolismo , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Inativação Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Proteínas Proto-Oncogênicas c-raf/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína Supressora de Tumor p53/genéticaRESUMO
In recent years, laser engraving has received widespread attention as a convenient, efficient, and programmable method which has enabled high-quality porous graphene to be obtained from various precursors. Laser engraving is often used to fabricate the dielectric layer with a microstructure for capacitive pressure sensors; however, the usual choice of electrodes remains poorly flexible metal electrodes, which greatly limit the overall flexibility of the sensors. In this work, we propose a flexible capacitive pressure sensor made entirely of thermoplastic polyurethane (TPU) and laser-induced graphene (LIG) derived from wood. The capacitive pressure sensor consisted of a flexible LIG/TPU electrode (LTE), an LIG/TPU electrode with a microhole array, and a dielectric layer of TPU with microcone array molded from a laser-engraved hole array on wood, which provided high sensitivity (0.11 kPa-1), an ultrawide pressure detection range (20 Pa to 1.4 MPa), a fast response (~300 ms), and good stability (>4000 cycles, at 0-35 kPa). We believe that our research makes a significant contribution to the literature, because the easy availability of the materials derived from wood and the overall consistent flexibility meet the requirements of flexible electronic devices.
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INTRODUCTION: Surgery is still an effective treatment option for adult degenerative scoliosis (ADS), but how to predict patients' significant amount of the improvement in quality of life remains unclear. The previous studies included an inhomogeneous population. This study aimed to report the results about concentrating on the amount of immediate changes in spinopelvic radiographic parameters to predict the amount of mid-term improvement in quality of life in ADS patients. MATERIALS AND METHODS: Pre-operative and immediately post-operative radiographic parameters included Cobb angle, coronal vertical axis (CVA), sagittal vertical axis (SVA), lumbar lordosis (LL), thoracic kyphosis (TK), pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI) and LL/PI matching (PI-LL). Quality of life scores were evaluated pre-operatively and at the final follow-up using Oswestry Disability Index (ODI) and visual analogue scale (VAS). The amount of immediate changes in spinopelvic radiographic parameters (Δ) and the amount of mid-term improvement in quality of life (Δ) were defined, respectively. RESULTS: Patients showed significant change in radiographic parameters, ODI and VAS pre- and post-surgery, except CVA and PI. Univariate analysis showed a significant correlation between ΔTK, ΔLL, ΔCVA and the amount of mid-term improvement in quality of life, but multivariate analysis did not get a significant result. Univariate and multivariate analyses showed that ΔSVA was still a significant predictor of ΔVAS and ΔODI. The changes in the other radiographic parameters were not significant. The equations were developed by linear regression: ΔODI = 0.162 × ΔSVA - 21.592, ΔVAS = 0.034 × ΔSVA - 2.828. In the ROC curve for ΔSVA in the detection of a strong ΔODI or ΔVAS, the cut-off value of ΔSVA was - 19.855 mm and - 15.405 mm, respectively. CONCLUSIONS: This study shows that ΔSVA can predict the amount of mid-term improvement in quality of life in ADS patients. The changes in the other radiographic parameters were not significant. Two equations were yielded to estimate ΔODI and ΔVAS. ΔSVA has respective cut-off value to predict ΔODI and ΔVAS.
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Lordose , Escoliose , Animais , Humanos , Adulto , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgiaRESUMO
BACKGROUND: Clinical decision-making is considered an essential behaviour in clinical practice. However, no research has been done to examine the associations among midwives' clinical decision-making, work environment and psychological empowerment. Thus, this study aimed to determine the influence of work environment on midwives' clinical decision-making and confirm the mediating role of psychological empowerment. METHOD: This study was designed as a multicentre cross-sectional study, and included 602 registered midwives from 25 public hospitals in China. A sociodemographic questionnaire, Work Environment Scale, Psychological Empowerment Scale and Clinical decision-making Scale were applied. A structural equation model was conducted to estimate the hypothesis model of the clinical decision-making among midwives and explore the potential mediating mechanism of midwives' clinical decision-making. This model was employed maximum likelihood estimation method and bootstrapping to examine the statistical significance. RESULTS: The mean score of clinical decision-making among midwives was 143.03 ± 14.22, at an intermediate level. The data of this hypothesis model fitted well, and the results showed that work environment positively affected psychological empowerment, which in turn positively affected clinical decision-making; psychological empowerment partly mediated the relationship between work environment and clinical decision-making among midwives. CONCLUSIONS: Midwives' clinical decision-making could be promoted directly or indirectly by providing a healthy work environment and improving psychological empowerment. It is essential for hospital managers to pay attention to the assessment of the midwives' work environment and actively improve it, such as establishing a supportive, fair and just workplace, and maintaining effective communication with midwives. Furthermore, managers can also promote midwives' clinical decision-making behaviour by enhancing their psychological empowerment via enhancing job autonomy.
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We demonstrate the successful prediction of the continuous intensity time series and reproduction of the underlying dynamical behaviors for a chaotic semiconductor laser by reservoir computing. The laser subject to continuous-wave optical injection is considered using the rate-equation model. A reservoir network is constructed and trained using over 2 × 104 data points sampled every 1.19 ps from the simulated chaotic intensity time series. Upon careful optimization of the reservoir parameters, the future evolution of the continuous intensity time series can be accurately predicted for a time duration of longer than 0.6â ns, which is six times the reciprocal of the relaxation resonance frequency of the laser. Moreover, we demonstrate for the first time, to the best of our knowledge, that the predicted intensity time series allows for accurate reproduction of the chaotic dynamical behaviors, including the microwave power spectrum, probability density function, and the chaotic attractor. In general, the demonstrated approach offers a relatively high flexibility in the choice of reservoir parameters according to the simulation results, and it provides new insights into the learning and prediction of semiconductor laser dynamics based on measured intensity time series.
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Pigment cell composition, pigment content, tyrosinase content and activity analysis were investigated on three kinds of loaches Misgurnus anguillicaudatus: big blackspot loaches (BBL), small blackspot loaches (SBL) and non-blackspot loaches (NBL), from Poyang Lake. Results showed that there were three types of skin pigment cells, namely melanophores, xanthophores and iridophores. Melanophores in dorsum were more than those in abdomen. Melanophore cytosomes in BBL were larger than those in SBL and NBL, and melanosomes were the largest in stage four. The melanophores in dorsal skin of SBL or NBL were small cell bodies, spindle-like and in chain distribution. There was an extremely significant difference in melanin content in BBL between the dorsum and abdomen (P < 0.01). There were no significant differences in melanin abdominal content, lutein and carotenoid contents among three kinds of loaches (P > 0.05). In dorsal skin, tyrosinase content was the highest in BBL, and it was significantly lower in NBL than in BBL and SBL (P < 0.01). This study reveals the differences in pigment and tyrosinase content in three kinds of loaches and provides a theoretical basis for further study of the mechanism of black spot formation.
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Cipriniformes , Animais , Lagos , Melanóforos , Monofenol Mono-Oxigenase , PigmentaçãoRESUMO
Conductive fibers have received considerable interest due to their potential applications in the flexible electronics field. Fabricating a conductive fiber that can realize fast deformation with stretchability for multifunctional applications is still highly appealing. Here, we present a deformable conductive fiber (DCF) fabricated by injecting liquid metal (LM) into a hollow thermoplastic polyurethane (TPU) fiber; the DCF can be shaped into a 2D or 3D shape by an electrothermal method at the thermoplastic transition point of TPU. Combined with the solid-liquid phase transition characteristics of the LM at its melting point, the DCF exhibits a variable shape memory feature at two transition points. We have demonstrated that the double-torsional DCF and the helical DCF can act as a capacitive sensor and an inductive sensor, respectively, and they have both been used for human motion monitoring. In addition, the helical DCF can also act as a stretchable electrode with excellent electrical properties (resistance change <2%) under a maximal mechanical strain of 3300%. Overall, the DCF presents great potential for applications in human motion monitoring, soft robotics and smart electronic textiles.
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BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is the main pathological manifestation of cardiovascular diseases such as myocardial infarction. The potential therapeutic effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) and the participation of regulatory T cells (Tregs) in MIRI remains to be defined. METHODS: We used the experimental acute MIRI that was induced in mice by left ascending coronary ischemia, which were subsequently randomized to receive immunoglobulin G (IgG) or anti-CD25 antibody PC61 with or without intravenously injected BM-MSCs. The splenectomized mice underwent prior to experimental MIRI followed by intravenous administration of BM-MSCs. At 72 h post-MIRI, the hearts and spleens were harvested and subjected to cytometric and histologic analyses. RESULTS: CD25+Foxp3+ regulatory T cells were significantly elevated after MIRI in the hearts and spleens of mice receiving IgG + BM-MSCs and PC61 + BM-MSCs compared to the respective control mice (all p < 0.01). This was accompanied by upregulation of interleukin 10 and transforming growth factor ß1 and downregulation of creatinine kinase and lactate dehydrogenase in the serum. The post-MIRI mice receiving BM-MSCs showed attenuated inflammation and cellular apoptosis in the heart. Meanwhile, splenectomy compromised all therapeutic effects of BM-MSCs. CONCLUSION: Administration of BM-MSCs effectively alleviates MIRI in mice through inducing Treg activation, particularly in the spleen.
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Transplante de Células-Tronco Mesenquimais , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/imunologia , Baço/imunologia , Linfócitos T Reguladores/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Apoptose , Creatina Quinase/sangue , Modelos Animais de Doenças , Imunoglobulina G/farmacologia , Interleucina-10/sangue , L-Lactato Desidrogenase/sangue , Masculino , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/imunologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Necrose , Fenótipo , Baço/efeitos dos fármacos , Baço/metabolismo , Esplenectomia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta1/sangueRESUMO
OBJECTIVE: Head and neck are the predilection sites of arteriovenous malformations (AVMs). Although embolization is the first-line treatment for AVMs, complete surgical removal of the lesion still has its value due to the best outcome with low recurrence rate. Here, the authors made a retrospective analysis on the surgical treatment of AVMs in the head and neck. METHODS: From January 2006 to December 2019, a total of 18 patients with AVMs in the head and neck were enrolled in this study, including 10 males. The Schobinger clinical staging, Yakes' angioarchitecture type, and surgical treatment were analyzed. The follow-up data were collected. Then, individual treatment strategies were summarized. RESULTS: According to Schobinger clinical classification system, 6 patients were at stage I, 7 patients at stage II, and 5 patients at stage III. According to Yakes' AVM classification system, 3 Type I, 4 Type II, 5 Type III, and 3 Type IV were confirmed. 3 patients cannot be confirmed due to lacking of arteriographic data. Surgical treatments included simple surgical excision (8 patients), dilator therapy (6 patients), and skin grafting after surgical excision (4 patients). In the follow-up period, 2 patients had recurrence and accepted operation again. All patients were satisfied with the appearance. CONCLUSIONS: Individual surgical treatment based on the clinical stage and angioarchitecture type can achieve satisfactory results in AVMs in the head and neck.
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Malformações Arteriovenosas , Embolização Terapêutica , Malformações Arteriovenosas Intracranianas , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/cirurgia , Cabeça/cirurgia , Humanos , Masculino , Pescoço/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A luminescent coordination polymer based on Tb(III) has been synthesized with the tripodal carboxylic acid ligand containing N,O codonors (H2PBA = 5-[4-pyridin-3-yl-benzoylamino]-isophthalic acid) as ligand under solvothermal conditions. The chemical formula of this polymer is {[Tb2(PBA)3(H2O)3]·DMF·3H2O}n (1). Complex 1 has good sensitivity and selectivity to picric acid (PA). At 0-30 µmol/L, 1's quenching constant is 4.5 × 104 L/mol. In the biological function study, the motor function of spinal cord-injured animals after different treatments was evaluated using the blood-brain barrier (BBB) method. The trka expression level on the neural stem cells after treatment was measured to reveal the underlying mechanism.
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Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Modelos Animais de Doenças , Picratos/análise , Receptor trkA/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Complexos de Coordenação/síntese química , Luminescência , Células-Tronco Neurais/metabolismo , Polímeros/química , Polímeros/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor trkA/genética , Traumatismos da Medula Espinal/metabolismo , Térbio/química , Térbio/farmacologia , Regulação para Cima/efeitos dos fármacosRESUMO
Laparoscopic liver surgery is challenging to perform because of compromised ability of the surgeon to localize subsurface anatomy due to minimal invasive visibility. While image guidance has the potential to address this barrier, intraoperative factors, such as insufflations and variable degrees of organ mobilization from supporting ligaments, may generate substantial deformation. The navigation ability in terms of searching and tagging within liver views has not been characterized, and current object detection methods do not account for the mechanics of how these features could be applied to the liver images. In this research, we have proposed spatial pyramid based searching and tagging of liver's intraoperative views using convolution neural network (SPST-CNN). By exploiting a hybrid combination of an image pyramid at input and spatial pyramid pooling layer at deeper stages of SPST-CNN, we reveal the gains of full-image representations for searching and tagging variable scaled liver live views. SPST-CNN provides pinpoint searching and tagging of intraoperative liver views to obtain up-to-date information about the location and shape of the area of interest. Downsampling input using image pyramid enables SPST-CNN framework to deploy input images with a diversity of resolutions for achieving scale-invariance feature. We have compared the proposed approach to the four recent state-of-the-art approaches and our method achieved better mAP up to 85.9%.
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Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Fígado/diagnóstico por imagem , Fígado/cirurgiaRESUMO
A novel concentric spectrometer having one convex grating and one concave mirror, working at ${+}{1}$+1st order diffraction, and with a small size, high resolution, and high diffraction efficiency, is proposed. It can simultaneously achieve high resolution and compactness by increasing the grating groove density. A compact spectrometer operating at a wavelength of 740-790 nm with an excellent imaging quality is designed. Its spectral resolution reaches 0.049 nm, and its diffraction efficiency improves by 27% compared to the conventional Offner spectrometer with convex grating working at ${-}{1}$-1st order diffraction. This is suitable for small, light, and low-cost atmospheric gas monitoring satellites.
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BACKGROUND: Radiotherapy is an effective strategy for preventing cancer metastasis, including osteosarcoma. However, cancer radioresistance limits the efficiency of radiotherapy. Therefore, it is essential to investigate the mechanism of osteosarcoma radioresistance. METHODS: The osteosarcoma tissues and adjacent healthy tissues were collected from 53 osteosarcoma patients. The expression of LINC00210, miR-342-3p, and GFRA1 mRNA were determined using qRT-PCR. Cell viability, cell apoptosis, and cell surviving fraction were determined by MTT assay, flow cytometry, and colony formation assay, respectively. Western blot was performed to detect the protein levels. Luciferase assay was conducted to verify the relationship between LINC00210, miR-342-3p, and GFRA1. RESULTS: LINC00210 and GFRA1 were up-regulated, and miR-342-3p was down-regulated in osteosarcoma tissues and cells. The expression of LINC00210 in osteosarcoma was negatively related to miR-342-3p expression and positively associated with GFRA1. Besides, there was a negative correlation between LINC00210 and GFRA1 expression in osteosarcoma. Also, LINC00210 and GFRA1 were up-regulated, and miR-342-3p was down-regulated in osteosarcoma cells exposed to 4 Gy irradiation treatment. Furthermore, either LINC00210 knockdown or miR-342-3p overexpression enhanced the radiosensitivity of osteosarcoma cells. Moreover, LINC00210 increased GFRA1 expression via sponging miR-342-3p. Additionally, LINC00210 knockdown improved the radiosensitivity of osteosarcoma cells by regulating GFRA1 expression via sponging miR-342-3p. CONCLUSION: LINC00210 modulated the radiosensitivity of osteosarcoma cells via the miR-342-3p/GFRA1 axis, making LINC00210 a novel target for improving radiotherapy efficiency in osteosarcoma.
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Neoplasias Ósseas , MicroRNAs/genética , Osteossarcoma , RNA Longo não Codificante/genética , Tolerância a Radiação/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Humanos , MicroRNAs/metabolismo , Osteossarcoma/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia , RNA Longo não Codificante/metabolismoRESUMO
OBJECTIVE: To investigate the effect of Cuscuta chinensis flavonoids (CCF) on the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) in the testis of the rat with oligozoospermia (OZ). METHODS: Thirty SD male rats were randomly divided into three groups of equal number, blank control, OZ model control and CCF intervention. The OZ model was established in the latter two groups by intraperitoneal injection of cyclophosphamide at 30 mg/kg qd for 5 successive days. From the 6th day, the rats in the CCF intervention group were treated intragastrically with mixed suspension of CCF at 5 mL/kg and those in the other two groups with normal saline, all for 4 weeks. The epididymal sperm concentration and motility and the testicular morphology were examined and the expression of GM-CSF in the testis tissue detected with the SELDI Protein Chip. RESULTS: Compared with the rats in the blank control and CCF intervention groups, the OZ model controls showed dramatically decreased epididymal sperm concentration and motility (both P < 0.01) and significant morphological changes in the testis with deformed seminiferous tubules and reduced number and disordered arrangement of spermatogenic cells. Normal testicular morphology was observed in the CCF intervention group and there were no statistically significant differences in sperm concentration and motility between the CCF intervention and blank control groups (P > 0.05). The expression of GM-CSF was significantly up-regulated in the testis tissue of the OZ model controls but lower than the minimum value obtained with the SELDI Protein Chip in the blank control and CCF intervention groups. CONCLUSIONS: Cuscuta chinensis flavonoids can significantly down-regulate the expression of GM-CSF in the testis of the rats with cyclophosphamide-induced oligozoospermia.
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Cuscuta/química , Flavonoides/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Oligospermia , Testículo/efeitos dos fármacos , Animais , Masculino , Oligospermia/induzido quimicamente , Oligospermia/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Ratos , Ratos Sprague-Dawley , Espermatozoides , Testículo/metabolismoRESUMO
Colorectal cancer (CRC) is the third most common malignancy, and the metabolic properties of CRC cells include enhanced aerobic glycolysis (the Warburg effect). Nicotinamide phosphoribosyl transferase (NAMPT) is one of the crucial enzymes that regulate the activity of nicotinamide adenine dinucleodinucleotide dependent enzymes. Targeting NAMPT is a potential method of CRC therapy. Nevertheless, the underlying clinical implications and regulatory mechanisms of NAMPT in CRC remain unclear. In this study, we showed that NAMPT protein expression was increased in subjects with rectal localization compared with those with colon localization, and NAMPT was a poor prognostic marker for the overall survival rate in patients with CRC. In addition, the NAMPT inhibitor FK866 or lentivirus-mediated silencing induced CRC cell growth inhibition. Mechanistically, NAMPT regulated Sirt1 and P53 expression and induced G0/G1 cell cycle arrest, along with the upregulation of downstream p21 and downregulation of cyclin D1, cyclin E1, and cyclin E2 expression. FK866 administration or knockdown of NAMPT induced CRC cell apoptosis via upregulation of caspase-3. In conclusion, NAMPT regulated Sirt1/P53 signaling during CRC cell growth and warrants further investigation for clinical administration in CRC.
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Proliferação de Células , Neoplasias Colorretais/enzimologia , Citocinas/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Acrilamidas/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Citocinas/antagonistas & inibidores , Citocinas/genética , Inibidores Enzimáticos/farmacologia , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Nicotinamida Fosforribosiltransferase/genética , Piperidinas/farmacologia , Transdução de Sinais , Sirtuína 1/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Chronic neuroinflammation is a common feature of the ageing brain and some neurodegenerative disorders. However, the molecular and cellular mechanisms underlying the regulation of innate immunity in the central nervous system remain elusive. Here we show that the astrocytic dopamine D2 receptor (DRD2) modulates innate immunity through αB-crystallin (CRYAB), which is known to suppress neuroinflammation. We demonstrate that knockout mice lacking Drd2 showed remarkable inflammatory response in multiple central nervous system regions and increased the vulnerability of nigral dopaminergic neurons to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. Astrocytes null for Drd2 became hyper-responsive to immune stimuli with a marked reduction in the level of CRYAB. Preferential ablation of Drd2 in astrocytes robustly activated astrocytes in the substantia nigra. Gain- or loss-of-function studies showed that CRYAB is critical for DRD2-mediated modulation of innate immune response in astrocytes. Furthermore, treatment of wild-type mice with the selective DRD2 agonist quinpirole increased resistance of the nigral dopaminergic neurons to MPTP through partial suppression of inflammation. Our study indicates that astrocytic DRD2 activation normally suppresses neuroinflammation in the central nervous system through a CRYAB-dependent mechanism, and provides a new strategy for targeting the astrocyte-mediated innate immune response in the central nervous system during ageing and disease.
Assuntos
Astrócitos/imunologia , Astrócitos/metabolismo , Inflamação/imunologia , Receptores de Dopamina D2/metabolismo , Cadeia B de alfa-Cristalina/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/citologia , Microglia/imunologia , Fármacos Neuroprotetores/metabolismo , Quimpirol/farmacologia , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D2/deficiência , Receptores de Dopamina D2/genética , Substância Negra/citologia , Substância Negra/efeitos dos fármacos , Cadeia B de alfa-Cristalina/genéticaRESUMO
This study aimed to investigate the association of SDH gene mutations and promoter methylation with succinate dehydrogenase-deficient gastrointestinal stromal tumors (SDH-deficient GISTs) and to further discuss the potential molecular mechanisms underlying SDHB expression loss in these tumors. First, a total of 26 patients with SDH-deficient GISTs were selected by identifying the loss of SDHB protein expression and wild-type for KIT and PDGFRa mutations. Then SDH gene mutations and promoter methylation were detected by DNA sequencing and methylation-specific polymerase chain reaction, respectively, and the clinical and pathological data of SDH-deficient GISTs patients were collected and analyzed accordingly. The results of genetic testing demonstrated that 38.46% (10/26) of these patients harbored mutations in SDHB, SDHC, and SDHD genes (3 cases with double mutations). Besides, aberrant promoter methylation of SDH genes was detected in 10 out of 26 cases (38.46%), including 8 cases in SDHA gene, 3 cases in SDHB gene, 1 case in both SDHA and SDHB genes. It is suggested that SDH gene mutations and promoter methylation may contribute to the loss of SDH protein expression in sporadic SDH-deficient GISTs. This study indicated that the genetic and epigenetic alterations of SDH genes may occur during tumor formation.