RESUMEN
The absolute band edge positions and work function (Φ) are the key electronic properties of metal oxides that determine their performance in electronic devices and photocatalysis. However, experimental measurements of these properties often show notable variations, and the mechanisms underlying these discrepancies remain inadequately understood. In this work, we focus on ceria (CeO2), a material renowned for its outstanding oxygen storage capacity, and combine theoretical and experimental techniques to demonstrate environmental modifications of its ionization potential (IP) and Φ. Under O-deficient conditions, reduced ceria exhibits a decreased IP and Φ with significant sensitivity to defect distributions. In contrast, the IP and Φ are elevated in O-rich conditions due to the formation of surface peroxide species. Surface adsorbates and impurities can further augment these variabilities under realistic conditions. We rationalize the shifts in energy levels by separating the individual contributions from bulk and surface factors, using hybrid quantum mechanical/molecular mechanical (QM/MM) embedded-cluster and periodic density functional theory (DFT) calculations supported by interatomic-potential-based electrostatic analyses. Our results highlight the critical role of on-site electrostatic potentials in determining the absolute energy levels in metal oxides, implying a dynamic evolution of band edges under catalytic conditions.
RESUMEN
Radiotherapy has unique immunostimulatory and immunosuppressive effects. Although high-dose radiotherapy has been found to have systemic antitumor effects, clinically significant abscopal effects were uncommon on the basis of irradiating single lesion. Low-dose radiation therapy (LDRT) emerges as a novel approach to enhance the antitumor immune response due to its role as a leverage to reshape the tumor immune microenvironment (TIME). In this article, from bench to bedside, we reviewed the possible immunomodulatory role of LDRT on TIME and systemic tumor immune environment, and outlined preclinical evidence and clinical application. We also discussed the current challenges when LDRT is used as a combination therapy, including the optimal dose, fraction, frequency, and combination of drugs. The advantage of low toxicity makes LDRT potential to be applied in multiple lesions to amplify antitumor immune response in polymetastatic disease, and its intersection with other disciplines might also make it a direction for radiotherapy-combined modalities.
Asunto(s)
Neoplasias , Humanos , Neoplasias/radioterapia , Predicción , Inmunidad , Terapia Combinada , Inmunomodulación , Inmunoterapia , Microambiente TumoralRESUMEN
BACKGROUND: There is inconclusive evidence to suggest that the expression of programmed cell death ligand 1 (PD-L1) is a putative predictor of response to EGFR-TKI therapy in advanced EGFR-mutant non-small cell lung cancer (NSCLC). We evaluated the heterogeneity in PD-L1 expression in the primary lung site and metastatic lymph nodes to analyze the association between PD-L1 expression and response for patients treated with EGFR-TKI. METHODS: This study reviewed 184 advanced NSCLC patients with EGFR mutations who received first-generation EGFR-TKI as first-line treatment from 2020 to 2021 at Shanghai Chest Hospital. The patients were divided into the primary lung site group (n = 100) and the metastatic lymph nodes group (n = 84) according to the biopsy site. The patients in each group were divided into TPS < 1%, TPS 1-49%, and TPS ≥ 50% groups according to PD-L1 expression. RESULTS: The median PFS was 7 (95% CI: 5.7-8.3) months, and the median OS was 26 (95% CI: 23.5-28.5) months for all patients. No correlation existed between PFS or OS and PD-L1 expression. The median PFS in the primary lung site group was 11 months (95% CI: 9.6-12.4) in the TPS < 1% group, 8 months (95% CI: 6.6-9.4) in TPS 1-49% group, and 4 months (95% CI: 3.2-4.8) in TPS ≥ 50% group, with statistically significant differences (p = 0.000). The median OS of the TPS < 1% group and TPS ≥ 50% group showed a statistically significant difference (p = 0.008) in the primary lung site group. In contrast, PD-L1 expression in the lymph nodes of EGFR-mutant patients was unrelated to PFS or OS after EGFR-TKI therapy. CONCLUSION: PD-L1 expression from the primary lung site might predict clinical benefit from EGFR-TKI, whereas PD-L1 from metastatic lymph nodes did not. TRIAL REGISTRATION: This retrospective study was approved by the Ethics Committee of Shanghai Chest Hospital (ID: IS23060) and performed following the Helsinki Declaration of 1964 (revised 2008).
Asunto(s)
Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Metástasis Linfática , Inhibidores de Proteínas Quinasas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Antígeno B7-H1/biosíntesis , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Receptores ErbB/biosíntesis , Receptores ErbB/genética , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inhibidores , Anciano , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Ganglios Linfáticos/patología , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/metabolismo , Adulto , Anciano de 80 o más Años , Resultado del Tratamiento , Valor Predictivo de las Pruebas , Mutación , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisisRESUMEN
Major depressive disorder (MDD) is a severe mental illness. Decreased brain plasticity and dendritic fields have been consistently found in MDD patients and animal models; however, the underlying molecular mechanisms remain to be clarified. Here, we demonstrate that the deletion of cancerous inhibitor of PP2A (CIP2A), an endogenous inhibitor of protein phosphatase 2A (PP2A), leads to depression-like behaviors in mice. Hippocampal RNA sequencing analysis of CIP2A knockout mice shows alterations in the PI3K-AKT pathway and central nervous system development. In primary neurons, CIP2A stimulates AKT activity and promotes dendritic development. Further analysis reveals that the effect of CIP2A in promoting dendritic development is dependent on PP2A-AKT signaling. In vivo, CIP2A deficiency-induced depression-like behaviors and impaired dendritic arborization are rescued by AKT activation. Decreased CIP2A expression and impaired dendrite branching are observed in a mouse model of chronic unpredictable mild stress (CUMS). Indicative of clinical relevance to humans, CIP2A expression is found decreased in transcriptomes from MDD patients. In conclusion, we discover a novel mechanism that CIP2A deficiency promotes depression through the regulation of PP2A-AKT signaling and dendritic arborization.
Asunto(s)
Trastorno Depresivo Mayor , Humanos , Ratones , Animales , Trastorno Depresivo Mayor/genética , Fosfatidilinositol 3-Quinasas , Neuronas , Plasticidad NeuronalRESUMEN
BACKGROUND: Iron deficiency (ID) is the most prevalent nutritional deficiency disease in preterm infants, significantly affecting their growth and development. For preterm infants to flourish physically and neurologically, timely iron supplementation is essential. The main goals of this study were to determine whether the present iron supplementation regimen results in iron overload in late preterm infants and whether it can meet the growth requirements of early preterm infants for catch-up. METHODS: We conducted a prospective follow-up study on preterm infants at the Department of Child Health, West China Second University Hospital, Sichuan University, from January 1, 2020, to August 31, 2020. In this study, 177 preterm infants were divided into two groups based on gestational age-early preterm infants (gestational age < 34 weeks) and late preterm infants (gestational age ≥ 34 weeks and < 37 weeks)-to compare the incidence of iron deficiency, iron status, and physical growth of preterm infants receiving iron supplements (2-4 mg/kg/d). RESULTS: Iron supplementation considerably reduced the incidence of iron deficiency in preterm infants. The prevalence of iron deficiency in early preterm infants and late preterm infants was 11.3% and 5.1%, respectively, at the corrected gestational age of 3 months; at the corrected gestational age of 6 months, the prevalence was 5.3% and 6.3%, respectively. No preterm infants with iron deficiency were detected in either group at the corrected gestational age of 12 months. Ferritin was substantially lower in early preterm infants (36.87 ± 31.57 ng/ml) than in late preterm infants (65.78 ± 75.76 ng/ml) at the corrected gestational age of 3 months (p < 0.05). A multifactorial regression analysis of factors influencing iron metabolism levels in preterm infants revealed a positive relationship between log10hepcidin, birth weight, and ferritin, with higher birth weights resulting in higher ferritin levels. CONCLUSIONS: Postnatal iron supplementation at 2-4 mg/kg/d in preterm infants significantly decreases the incidence of ID. There were substantial differences in iron levels across preterm infants of varying gestational ages. A tailored iron supplementation plan based on growth, birth weight, and gestational age may be a more suitable route for iron supplementation. Although the current study found that the postnatal iron status of early preterm infants differed from that of late preterm infants, the actual mechanism of action remains unknown, and large-sample, multicenter clinical studies are required to investigate this further.
Asunto(s)
Anemia Ferropénica , Suplementos Dietéticos , Edad Gestacional , Recien Nacido Prematuro , Hierro , Humanos , Recién Nacido , Estudios Prospectivos , Femenino , Masculino , Anemia Ferropénica/prevención & control , Anemia Ferropénica/epidemiología , Anemia Ferropénica/sangre , Estudios de Seguimiento , Hierro/administración & dosificación , Hierro/sangre , Lactante , Enfermedades del Prematuro/prevención & control , Enfermedades del Prematuro/epidemiología , China/epidemiología , IncidenciaRESUMEN
Spontaneous intracerebral hemorrhage (ICH) constitutes a significant portion of acute stroke incidents worldwide, often leading to post-stroke dysphagia (PSD), affecting 50-77% of survivors and worsening patient morbidity. This study aimed to identify predictive variables for PSD among patients with spontaneous ICH. A retrospective cohort study was conducted on adult patients with acute spontaneous ICH, confirmed by brain computed tomography, from June 2019 to June 2023. We analyzed demographic, neuroimaging, and stroke-specific characteristics and rehabilitation indicators. PSD was evaluated using nasogastric (NG) tube retention and the Functional Oral Intake Scale (FOIS) levels at 4 and 12 weeks post-ICH. Statistical analyses involved univariate and multivariate logistic regression to identify PSD predictors. A total of 310 ICH patients were included in the study. At 4 weeks, significant predictors for NG tube retention included 24-hour National Institute of Health Stroke Scale (NIHSS) scores, estimated glomerular filtration rate and sitting balance. At 12 weeks, hospital stay duration and ICH score were significant predictors for NG tube retention. Regarding the FOIS, significant predictors at 4 weeks included higher 24-hour NIHSS scores, compromised sitting balance, immobility-related complications, initial hematoma volume and intraventricular hemorrhages. At 12 weeks, older age and higher 24-hour NIHSS scores significantly predicted lower FOIS levels. Our findings demonstrate that PSD in ICH patients is influenced by a complex interplay of factors, including stroke severity, renal function, and physical impairment. The study highlights the importance of early neurological assessment, physical function, and comprehensive management in improving swallowing outcomes, emphasizing a multifaceted approach to enhancing outcomes for ICH survivors.
RESUMEN
The copper-exchanged zeolite Cu-CHA has received considerable attention in recent years, owing to its application in the selective catalytic reduction (SCR) of NOx species. Here, we study the NH3-SCR reaction mechanism on Cu-CHA using the hybrid quantum mechanical/molecular mechanical (QM/MM) technique and investigate the effects of solvent on the reactivity of active Cu species. To this end, a comparison is made between water- and ammonia-solvated and bare Cu species. The results show the promoting effect of solvent on the oxidation component of the NH3-SCR cycle since the formation of important nitrate species is found to be energetically more favorable on the solvated Cu sites than in the absence of solvent molecules. Conversely, both solvent molecules are predicted to inhibit the reduction component of the NH3-SCR cycle. Diffuse reflectance infrared fourier-transform spectroscopy (DRIFTS) experiments exploiting (concentration) modulation excitation spectroscopy (MES) and phase-sensitive detection (PSD) identified spectroscopic signatures of Cu-nitrate and Cu-nitrosamine (H2NNO), important species which had not been previously observed experimentally. This is further supported by the QM/MM-calculated harmonic vibrational analysis. Additional insights are provided into the reactivity of solvated active sites and the formation of key intermediates including their formation energies and vibrational spectroscopic signatures, allowing the development of a detailed understanding of the reaction mechanism. We demonstrate the role of solvated active sites and their influence on the energetics of important species that must be explicitly considered for an accurate understanding of NH3-SCR kinetics.
Asunto(s)
Nitratos , Zeolitas , Amoníaco/química , Zeolitas/química , Solventes , Óxidos de Nitrógeno/química , Espectroscopía de Resonancia Magnética , CatálisisRESUMEN
Differently from epidermal growth factor receptor (EGFR) 19Del and L858R mutations, the panoramic description of uncommon EGFR mutations is far from mature. Our understanding of its population characteristics, treatment response, and drug resistance mechanisms needs urgent expansion and deepening. Our study enrolled 437 patients with non-small-cell lung cancer from four clinical centers and who had uncommon EGFR mutations. The clinical characteristics of all patients and the treatment outcomes of 190 advanced patients who received pharmacotherapy were analyzed. Moreover, the acquired resistance mechanisms were explored based on 53 tissue or liquid re-biopsy data in 45 patients. Patients with EGFR 20ins had a shorter survival time compared with patients with non-20ins mutations. In total, 149 cases had received EGFR-tyrosine kinase inhibitors (TKI); afatinib was significantly superior to other EGFR-TKIs both in ORR and mPFS in all uncommon mutations and especially in the L861Q group. The most common acquired drug resistance mechanism was MET amplification, followed by EGFR T790M, which was significantly different from common EGFR mutations.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Receptores ErbB/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , MutaciónRESUMEN
MOTIVATION: The identification of mutated driver genes and the corresponding pathways is one of the primary goals in understanding tumorigenesis at the patient level. Integration of multi-dimensional genomic data from existing repositories, e.g., The Cancer Genome Atlas (TCGA), offers an effective way to tackle this issue. In this study, we aimed to leverage the complementary genomic information of individuals and create an integrative framework to identify cancer-related driver genes. Specifically, based on pinpointed differentially expressed genes, variants in somatic mutations and a gene interaction network, we proposed an unsupervised Bayesian network integration (BNI) method to detect driver genes and estimate the disease propagation at the patient and/or cohort levels. This new method first captures inherent structural information to construct a functional gene mutation network and then extracts the driver genes and their controlled downstream modules using the minimum cover subset method. RESULTS: Using other credible sources (e.g. Cancer Gene Census and Network of Cancer Genes), we validated the driver genes predicted by the BNI method in three TCGA pan-cancer cohorts. The proposed method provides an effective approach to address tumor heterogeneity faced by personalized medicine. The pinpointed drivers warrant further wet laboratory validation. AVAILABILITY AND IMPLEMENTATION: The supplementary tables and source code can be obtained from https://xavieruniversityoflouisiana.sharefile.com/d-se6df2c8d0ebe4800a3030311efddafe5. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Asunto(s)
Genómica , Neoplasias , Teorema de Bayes , Redes Reguladoras de Genes , Genómica/métodos , Humanos , Mutación , Neoplasias/genéticaRESUMEN
To improve the color conversion performance, we study the nanoscale-cavity effects on the emission efficiency of a colloidal quantum dot (QD) and the Förster resonance energy transfer (FRET) from quantum well (QW) into QD in a GaN porous structure (PS). For this study, we insert green-emitting QD (GQD) and red-emitting QD (RQD) into the fabricated PSs in a GaN template and a blue-emitting QW template, and investigate the behaviors of the photoluminescence (PL) decay times and the intensity ratios of blue, green, and red lights. In the PS samples fabricated on the GaN template, we observe the efficiency enhancements of QD emission and the FRET from GQD into RQD, when compared with the samples of surface QDs, which is attributed to the nanoscale-cavity effect. In the PS samples fabricated on the QW template, the FRET from QW into QD is also enhanced. The enhanced FRET and QD emission efficiencies in a PS result in an improved color conversion performance. Because of the anisotropic PS in the sample surface plane, the polarization dependencies of QD emission and FRET are observed.
RESUMEN
Talaromycosis is a fatal mycosis caused by the thermally dimorphic fungus Talaromyces marneffei (T. marneffei). The pathogenic mechanisms of talaromycosis are still poorly understood. This work combined metabolomics, transcriptomics, and verification experiments in vivo and in vitro to detect metabolic proï¬les and differentially expressed genes (DEGs) in T. marneffei infected and uninfected macrophages to explore possible pathogenesis and underlying mechanisms. A total of 256 differential metabolites (117 up-regulated and 148 down-regulated) and 1320 DEGs (1286 up-regulated and 34 down-regulated) were identified between the two groups. Integrative metabolomics and transcriptomics analysis showed sphingolipid signaling pathway is the most inï¬uential. Veriï¬cation experiments showed that compared with the control group, the production of sphingosine-1-phosphate (S1P) and the expression of the S1PR1, S1PR2, phosphor-PI3K, and phosphor-Akt genes involved in the sphingolipid signaling pathway have signiï¬cantly increased in the T. marneffei infection group (p < 0.05). T. marneffei activates the S1PR2/PI3K/Akt pathways in J774A.1 macrophage, regulation of the S1P singling might serve as a promising therapeutic strategy for talaromycosis.
Asunto(s)
Proteínas Proto-Oncogénicas c-akt , Talaromyces , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Transcriptoma , Macrófagos/microbiología , Metabolómica , Esfingolípidos/metabolismo , Talaromyces/genéticaRESUMEN
Vibrational spectroscopy is one of the most well-established and important techniques for characterizing chemical systems. To aid the interpretation of experimental infrared and Raman spectra, we report on recent theoretical developments in the ChemShell computational chemistry environment for modelling vibrational signatures. The hybrid quantum mechanical and molecular mechanical approach is employed, using density functional theory for the electronic structure calculations and classical forcefields for the environment. Computational vibrational intensities at chemical active sites are reported using electrostatic and fully polarizable embedding environments to achieve more realistic vibrational signatures for materials and molecular systems, including solvated molecules, proteins, zeolites and metal oxide surfaces, providing useful insight into the effect of the chemical environment on the signatures obtained from experiment. This work has been enabled by the efficient task-farming parallelism implemented in ChemShell for high-performance computing platforms. This article is part of a discussion meeting issue 'Supercomputing simulations of advanced materials'.
RESUMEN
Hybrid quantum mechanical/molecular mechanical (QM/MM) methods are a powerful computational tool for the investigation of all forms of catalysis, as they allow for an accurate description of reactions occurring at catalytic sites in the context of a complicated electrostatic environment. The scriptable computational chemistry environment ChemShell is a leading software package for QM/MM calculations, providing a flexible, high performance framework for modelling both biomolecular and materials catalysis. We present an overview of recent applications of ChemShell to problems in catalysis and review new functionality introduced into the redeveloped Python-based version of ChemShell to support catalytic modelling. These include a fully guided workflow for biomolecular QM/MM modelling, starting from an experimental structure, a periodic QM/MM embedding scheme to support modelling of metallic materials, and a comprehensive set of tutorials for biomolecular and materials modelling.
RESUMEN
In biomedical literature, cross-sentence texts can usually express rich knowledge, and extracting the interaction relation between entities from cross-sentence texts is of great significance to biomedical research. However, compared with single sentence, cross-sentence text has a longer sequence length, so the research on cross-sentence text information extraction should focus more on learning the context dependency structural information. Nowadays, it is still a challenge to handle global dependencies and structural information of long sequences effectively, and graph-oriented modeling methods have received more and more attention recently. In this paper, we propose a new graph attention network guided by syntactic dependency relationship (SR-GAT) for extracting biomedical relation from the cross-sentence text. It allows each node to pay attention to other nodes in its neighborhood, regardless of the sequence length. The attention weight between nodes is given by a syntactic relation graph probability network (SR-GPR), which encodes the syntactic dependency between nodes and guides the graph attention mechanism to learn information about the dependency structure. The learned feature representation retains information about the node-to-node syntactic dependency, and can further discover global dependencies effectively. The experimental results demonstrate on a publicly available biomedical dataset that, our method achieves state-of-the-art performance while requiring significantly less computational resources. Specifically, in the "drug-mutation" relation extraction task, our method achieves an advanced accuracy of 93.78% for binary classification and 92.14% for multi-classification. In the "drug-gene-mutation" relation extraction task, our method achieves an advanced accuracy of 93.22% for binary classification and 92.28% for multi-classification. Across all relation extraction tasks, our method improves accuracy by an average of 0.49% compared to the existing best model. Furthermore, our method achieved an accuracy of 69.5% in text classification, surpassing most existing models, demonstrating its robustness in generalization across different domains without additional fine-tuning.
Asunto(s)
Investigación Biomédica , Lenguaje , Almacenamiento y Recuperación de la InformaciónRESUMEN
PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by recurrent upper airway disturbances during sleep leading to episodes of hypopnea or apnea, followed by hypoxemia and subsequent reoxygenation. It is believed that this reoxygenation/reperfusion stage leads to oxidative stress, which then leads to inflammation and cardiovascular diseases. The treatments of patient with OSAHS include surgical and non-surgical therapies with various side effects and common complaints. Therefore, it is important to develop a new, safe, and effective therapeutic treatment. As a small-molecule multifunctional protein, thioredoxin (TRX) has antioxidant and redox regulatory functions at the active site Cys-Gly-Pro. TRX prevents inflammation by suppressing the production of pro-inflammatory cytokines rather than suppressing the immune response. METHODS: We review the papers on the pathophysiological process of OSAHS and the antioxidative and anti-inflammatory effects of TRX. RESULTS: TRX may play a role in OSAHS by scavenging ROS, blocking the production of inflammatory cytokines, inhibiting the migration and activation of neutrophils, and controlling the activation of ROS-dependent inflammatory signals by regulating the redox state of intracellular target particles. Furthermore, TRX regulates the synthesis, stability, and activity of hypoxia-inducible factor 1 (HIF-1). TRX also has an inhibitory effect on endoplasmic reticulum- and mitochondria-induced apoptosis by regulating the expression of BAX, BCL2, p53, and ASK1. CONCLUSION: Understanding the function of TRX may be useful for the treatment of OSAHS.
Asunto(s)
Apnea Obstructiva del Sueño , Humanos , Especies Reactivas de Oxígeno/metabolismo , Apnea Obstructiva del Sueño/terapia , Apnea Obstructiva del Sueño/metabolismo , Antioxidantes , Citocinas , Inflamación , TiorredoxinasRESUMEN
Lung cancer is the leading cause of cancer-related death. In particular, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Due to tumor resistance and the toxicity of chemotherapeutic agents, it is increasingly critical to discover novel, potent antitumorigenic drugs for treating NSCLC. Lutein, a carotenoid, has been reported to exert toxic effects on cells in several tumor types. However, the detailed functions and underlying mechanisms of lutein in NSCLC remain elusive. The present study showed that lutein significantly and dose-dependently inhibited cell proliferation, arrested the cell cycle at the G0/G1 phase, and induced apoptosis in NSCLC cells. RNA-sequencing analysis revealed that the p53 signaling pathway was the most significantly upregulated in lutein-treated A549 cells. Mechanistically, lutein exerted antitumorigenic effects by inducing DNA damage and subsequently activating the ATR/Chk1/p53 signaling pathway in A549 cells. In vivo, lutein impeded tumor growth in mice and prolonged their survival. In conclusion, our findings demonstrate the antitumorigenic potential of lutein and reveal its molecular mechanism of action, suggesting that lutein is a promising candidate for clinical NSCLC treatment.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Luteína/metabolismo , Luteína/farmacología , Luteína/uso terapéutico , Proteína p53 Supresora de Tumor/metabolismo , Línea Celular Tumoral , Transducción de SeñalRESUMEN
The roles of long non-coding RNA TDRG1 have been revealed in several tumors, especially its roles in CSC progression have been recently elucidated; However, its effects in lung CSC progression have not been revealed. In the present study, we collected 3D non-adherent spheres as the CSC model to measure lncRNA TDRG1 level in lung CSC and the parental lung cancer cells, and found that TDRG1 level was significantly upregulated in lung CSCs compared to that of parental lung cancer cells. Then we constructed the lung CSCs with or without TDRG1 stable knockdown and lung cancer cells with or without TDRG1 stable overexpression. It was found that TDRG1 positively regulated lung cancer stemness. Mechanistically, we identified that TDRG1 directly bound to Sox2 mRNA, which is a critical stemness regulator, enhanced its mRNA stability, and thus increased Sox2 expression. Indeed, we demonstrated that TDRG1 aggravated lung cancer stemness dependent on Sox2 expression. Thus, this study suggests that TDRG1 is a critical stemness promoter of lung cancer cells by acting as a stabilizer for Sox2 mRNA.
Asunto(s)
Neoplasias Pulmonares , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Línea Celular Tumoral , ARN Mensajero/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción SOXB1/genéticaRESUMEN
OBJECTIVES: This study aimed to investigate the functions of 19 types of Wnt ligands during the process of osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs), with particular attention to WNT3A and WNT4. MATERIALS AND METHODS: The expression levels of 19 types of Wnt ligands were examined using real-time quantitative polymerase chain reaction (real-time qPCR) during hPDLSCs osteogenic differentiation at 7, 10, and 14 days. Knockdown of WNT3A and WNT4 expression was achieved using adenovirus vectors, and conditioned medium derived from WNT3A and WNT4 overexpression plasmids was employed to investigate their roles in hPDLSCs osteogenesis. Osteogenic-specific genes were analyzed using real-time qPCR. Alkaline phosphatase (ALP) and alizarin red S activities and staining were employed to assess hPDLSCs' osteogenic differentiation ability. RESULTS: During hPDLSCs osteogenic differentiation, the expression of 19 types of Wnt ligands varied, with WNT3A and WNT4 showing significant upregulation. Inhibiting WNT3A and WNT4 expression hindered hPDLSCs' osteogenic capacity. Conditioned medium of WNT3A promoted early osteogenic differentiation, while WNT4 facilitated late osteogenesis slightly. CONCLUSION: Wnt ligands, particularly WNT3A and WNT4, play an important role in hPDLSCs' osteogenic differentiation, highlighting their potential as promoters of osteogenesis. CLINICAL RELEVANCE: Given the challenging nature of alveolar bone regeneration, therapeutic strategies that target WNT3A and WNT4 signaling pathways offer promising opportunities. Additionally, innovative gene therapy approaches aimed at regulating of WNT3A and WNT4 expression hold potential for improving alveolar bone regeneration outcomes.
Asunto(s)
Osteogénesis , Ligamento Periodontal , Humanos , Osteogénesis/genética , Medios de Cultivo Condicionados/farmacología , Medios de Cultivo Condicionados/metabolismo , Células Madre , Diferenciación Celular/genética , Células CultivadasRESUMEN
PURPOSE: Emergence agitation is a common postoperative complication during recovery in children. The purpose of this study is to explore whether the use of ice popsicle could prevent emergence agitation in children undergoing oral surgery with sevoflurane anaesthesia. DESIGN AND METHODS: In this prospective randomized controlled study, 100 children undergoing oral surgery were randomly assigned to Group 1 which received ice popsicle after emergence (intervention, n = 50) or Group 2 which received verbal encouragement from their parents (control, n = 50). The primary outcome was the 2-hour postoperative incidence of EA. RESULTS: Group 1 had a significant lower incidence of emergence agitation (22% vs 58%, P < 0.001) compared with Group 2. The mean agitation score was significantly lower in Group 1 vs Group 2 at 10 minutes (1.64 vs 2.12, P = 0.024) and 20 min (1.60 vs 2.14, P = 0.004) after emergence. The peak agitation and pain scores were significantly lower in Group 1 than in Group 2 (P < 0.001). CONCLUSIONS: Findings from this study suggest that ice popsicle is an effective, cheap, pleasurable, and easily administered method for alleviating emergence agitation in paediatric patients after oral surgery under general anaesthesia. These results are worthy of confirmation in other surgeries. PRACTICE IMPLICATIONS: This approach is highly accepted by both children and their parents, and our findings support the effectiveness of ice popsicle in relieving emergence agitation and pain after oral surgery in children. CLINICAL TRIALS REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800015634.
Asunto(s)
Anestésicos por Inhalación , Delirio del Despertar , Éteres Metílicos , Procedimientos Quirúrgicos Orales , Niño , Humanos , Sevoflurano , Hielo , Estudios Prospectivos , Anestesia General , DolorRESUMEN
ADHD is a prevalent neurodevelopmental disorder that affects children's behavior, academic performance, and social interactions. This review aims to evaluate the existing evidence for Sandplay therapy, a nonverbal psychodynamic approach, as a complementary treatment for children with ADHD. Ten studies suggest Sandplay therapy improves ADHD symptoms, such as hyperactivity, impulsivity, and inattention, through symbolic expression, play, and mindfulness. Despite its promise, ethical and practical considerations, including therapist training and treatment cost, must be addressed. Further research is needed to determine long-term effectiveness and optimal patient population for this treatment, which may benefit children unresponsive to or experiencing side effects from traditional treatments.