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1.
J Nutr ; 2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39424071

RESUMEN

BACKGROUND: Nicotinamide adenine dinucleotide (NAD+) concentrations decline with age, and boosting it can improve multi-organ functions and lifespan. OBJECTIVES: Nicotinamide mononucleotide (NMN) is a natural NAD+ precursor with the ability to enhance NAD+ biosynthesis. Numerous studies have shown that a high-fat diet (HFD) can accelerate the process of aging and many diseases. We hypothesized that long-term administration of NMN could exert protective effects on adipose, muscle, and kidney tissues in mice on an HFD act by affecting the autophagic pathway. METHODS: Mice at 14 mo of age were fed an HFD, and NMN was added to their drinking water at a dose of 400 mg/kg for 7 mo. The locomotor ability of the mice was assessed by behavioral experiments such as grip test, wire hang test, rotarod, and beam-walking test. At the end of the behavioral experiments, the pathological changes of each peripheral organ and the expression of autophagy-related proteins, as well as the markers of the senescence and inflammaging were analyzed by pathological staining, immunohistochemical staining, and western blotting, respectively. RESULTS: We found that NMN supplementation increased NAD+ concentrations and ultimately attenuated age- and diet-related physiological decline in mice. NMN inhibited HFD-induced obesity, promoted physical activity, improved glucose and lipid metabolism, improved skeletal muscle function and renal damage, as well as mitigated the senescence and inflammaging as demonstrated by p16, interleukin 1ß, and tumor necrosis factor α concentrations. In addition, the present study further emphasizes the potential mechanisms underlying the bidirectional relationship between NAD+ and autophagy. We detected changes in autophagy concentrations in various tissue organs, and NMN may play a protective role by inhibiting excessive autophagy induced by HFD. CONCLUSIONS: Our findings demonstrated that NMN administration attenuated HFD-induced metabolic disorders and physiological decline in aging mice.

2.
Molecules ; 28(23)2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38067625

RESUMEN

MOF (metal organic framework) materials have been used as functional materials in a number of fields due to their diverse spatial tunability, which produces rich porous structures with stable and continuous pores and a high specific surface area. A triboelectric nanogenerator can convert trace mechanical energy into electrical energy, and the application of MOF materials to triboelectric nanogenerators has been intensively studied. In this work, we report on two MOFs with similar spatial structures, and the modulation of the end microstructures was achieved using the difference in F content. The output performance of friction power generation increases with the increase in F content, and the obtained polyacidic ligand materials can be used to construct self-powered corrosion protection systems, which can effectively protect metallic materials from corrosion.

3.
Pharm Biol ; 61(1): 1401-1412, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37667488

RESUMEN

CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-oxidative and anti-aging effects. OBJECTIVE: We evaluated the neuroprotective effects of SPJ on aging rats. MATERIALS AND METHODS: Sprague-Dawley rats (18-months-old) were randomly divided into aging and SPJ groups (n = 8). Five-month-old rats were taken as the adult control (n = 8). The rats were fed a normal chow diet or the SPJ-containing diet (10 or 30 mg/kg) for 4 months. An in vitro model was established by d-galactose (d-Gal) in the SH-SY5Y cell line and pretreated with SPJ (25 and 50 µg/mL). The neuroprotection of SPJ was evaluated via Nissl staining, flow cytometry, transmission electron microscopy and Western blotting in vivo and in vitro. RESULTS: SPJ improved the neuronal degeneration and mitochondrial morphology that are associated with aging. Meanwhile, SPJ up-regulated the protein levels of mitofusin 2 (Mfn2) and optic atrophy 1 (Opa1) and down-regulated the protein level of dynamin-like protein 1 (Drp1) in the hippocampus of aging rats (p < 0.05 or p < 0.01 vs. 22 M). The in vitro studies also demonstrated that SPJ attenuated d-Gal-induced cell senescence concomitant with the improvement in mitochondrial function; SPJ, also up-regulated the Mfn2 and Opa1 protein levels, whereas the Drp1 protein level (p < 0.05 or p < 0.01 vs. d-Gal group) was down-regulated. DISCUSSION AND CONCLUSIONS: Further research on the elderly population will contribute to the development and utilization of SPJ for the treatment of neurodegenerative disorders.


Asunto(s)
Neuroblastoma , Panax , Anciano , Humanos , Ratas , Animales , Ratas Sprague-Dawley , Envejecimiento , Galactosa , Mitocondrias
4.
Sensors (Basel) ; 22(23)2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36502250

RESUMEN

The problem of vehicle re-identification in surveillance scenarios has grown in popularity as a research topic. Deep learning has been successfully applied in re-identification tasks in the last few years due to its superior performance. However, deep learning approaches require a large volume of training data, and it is particularly crucial in vehicle re-identification tasks to have a sufficient amount of varying image samples for each vehicle. To collect and construct such a large and diverse dataset from natural environments is labor intensive. We offer a novel image sample synthesis framework to automatically generate new variants of training data by augmentation. First, we use an attention module to locate a local salient projection region in an image sample. Then, a lightweight convolutional neural network, the parameter agent network, is responsible for generating further image transformation states. Finally, an adversarial module is employed to ensure that the images in the dataset are distorted, while retaining their structural identities. This adversarial module helps to generate more appropriate and difficult training samples for vehicle re-identification. Moreover, we select the most difficult sample and update the parameter agent network accordingly to improve the performance. Our method draws on the adversarial networks strategy and the self-attention mechanism, which can dynamically decide the region selection and transformation degree of the synthesis images. Extensive experiments on the VeRi-776, VehicleID, and VERI-Wild datasets achieve good performance. Specifically, our method outperforms the state-of-the-art in MAP accuracy on VeRi-776 by 2.15%. Moreover, on VERI-Wil, a significant improvement of 7.15% is achieved.


Asunto(s)
Ambiente , Trabajo de Parto , Embarazo , Femenino , Humanos , Redes Neurales de la Computación
5.
BMC Bioinformatics ; 22(1): 272, 2021 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-34039273

RESUMEN

BACKGROUND: Biomedical question answering (QA) is a sub-task of natural language processing in a specific domain, which aims to answer a question in the biomedical field based on one or more related passages and can provide people with accurate healthcare-related information. Recently, a lot of approaches based on the neural network and large scale pre-trained language model have largely improved its performance. However, considering the lexical characteristics of biomedical corpus and its small scale dataset, there is still much improvement room for biomedical QA tasks. RESULTS: Inspired by the importance of syntactic and lexical features in the biomedical corpus, we proposed a new framework to extract external features, such as part-of-speech and named-entity recognition, and fused them with the original text representation encoded by pre-trained language model, to enhance the biomedical question answering performance. Our model achieves an overall improvement of all three metrics on BioASQ 6b, 7b, and 8b factoid question answering tasks. CONCLUSIONS: The experiments on BioASQ question answering dataset demonstrated the effectiveness of our external feature-enriched framework. It is proven by the experiments conducted that external lexical and syntactic features can improve Pre-trained Language Model's performance in biomedical domain question answering task.


Asunto(s)
Procesamiento de Lenguaje Natural , Redes Neurales de la Computación , Humanos , Lenguaje
6.
Biosci Biotechnol Biochem ; 84(8): 1645-1651, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32380907

RESUMEN

Oxaliplatin (L-OHP) is one of the effective chemotherapeutic drugs for colorectal cancer (CRC). Further investigation into the molecular mechanism of chemoresistance could improve outcomes for patients with colorectal cancer. Recently, microRNAs have been reported as a key in drug resistance of tumors. In this study, we aimed to investigate the effects of miR-153-5p in L-OHP-resistant CRC cells, and its underlying mechanism. Downregulation of miR-153-5p was observed in CRC cells, while upregulation of miR-153-5p enhances the chemosensitivity of CRC/L-OHP cells. The autophagy of CRC/L-OHP cells was markedly increased after exposure to L-OHP but abolished by the upregulation of miR-153-5p. Dual-luciferase reporter assays validated that Bcl-2 was a direct target of miR-153-5p. In conclusion, our data suggested that miR-153-5p was a mediator of cisplatin resistance in colorectal cancer by affecting Bcl-2-mediated autophagy, indicating a new therapeutic target for CRC treatment.


Asunto(s)
Antineoplásicos/farmacología , Autofagia/efectos de los fármacos , Resistencia a Antineoplásicos/genética , MicroARNs/genética , Oxaliplatino/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Antagomirs/genética , Antagomirs/metabolismo , Autofagia/genética , Emparejamiento Base , Secuencia de Bases , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Humanos , MicroARNs/agonistas , MicroARNs/antagonistas & inhibidores , MicroARNs/metabolismo , Oligorribonucleótidos/genética , Oligorribonucleótidos/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transducción de Señal
7.
Artículo en Inglés | MEDLINE | ID: mdl-39449346

RESUMEN

The liver, the largest internal organ in the human body, regulates multiple reactions and processes, including detoxification, regeneration, and immune defense. Liver diseases have emerged as a significant global public health issue. Numerous studies have indicated that the mitochondrial deacetylase SIRT3 has played various roles in the pathogenesis and pathological progression of liver diseases. Objectives: This review aims to explore the advances in the study of SIRT3 and liver disease and review possible mechanisms. Natural and chemical activators of SIRT3 are also discussed. The role of SIRT3 in the pathogenic mechanisms and therapeutic strategies of liver disease is summarized by reviewing Pubmed. SIRT3 alleviates liver diseases by regulating fatty acid metabolism, mitochondrial function, and immune-inflammatory response. Meanwhile, Withaferin A, lipoic acid, major royal jelly proteins, and berberine can activate SIRT3 or upregulate its expression, thereby alleviating liver damage. SIRT3 can effectively slow down the progression of liver disease and protect the liver from further damage. The use of SIRT3 as a pharmacological target for the treatment of liver disease is a potential therapeutic approach.

8.
J Pathol Clin Res ; 10(6): e70005, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39375998

RESUMEN

Molecular features are incorporated into the integrated diagnostic system for adult diffuse gliomas. Of these, copy number variation (CNV) markers, including both arm-level (1p/19q codeletion, +7/-10 signature) and gene-level (EGFR gene amplification, CDKN2A/B homozygous deletion) changes, have revolutionized the diagnostic paradigm by updating the subtyping and grading schemes. Shallow whole genome sequencing (sWGS) has been widely used for CNV detection due to its cost-effectiveness and versatility. However, the parallel detection of glioma-associated CNV markers using sWGS has not been optimized in a clinical setting. Herein, we established a model-based approach to classify the CNV status of glioma-associated diagnostic markers with a single test. To enhance its clinical utility, we carried out hypothesis testing model-based analysis through the estimation of copy ratio fluctuation level, which was implemented individually and independently and, thus, avoided the necessity for normal controls. Besides, the customization of required minimal tumor fraction (TF) was evaluated and recommended for each glioma-associated marker to ensure robust classification. As a result, with 1× sequencing depth and 0.05 TF, arm-level CNVs could be reliably detected with at least 99.5% sensitivity and specificity. For EGFR gene amplification and CDKN2A/B homozygous deletion, the corresponding TF limits were 0.15 and 0.45 to ensure the evaluation metrics were both higher than 97%. Furthermore, we applied the algorithm to an independent glioma cohort and observed the expected sample distribution and prognostic stratification patterns. In conclusion, we provide a clinically applicable algorithm to classify the CNV status of glioma-associated markers in parallel.


Asunto(s)
Algoritmos , Biomarcadores de Tumor , Neoplasias Encefálicas , Variaciones en el Número de Copia de ADN , Glioma , Secuenciación Completa del Genoma , Humanos , Glioma/genética , Glioma/patología , Glioma/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Biomarcadores de Tumor/genética , Estudios de Factibilidad
9.
Cancer Biol Ther ; 25(1): 2338955, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38680092

RESUMEN

Gliomas are the most common type of primary brain tumor. Despite advances in treatment, it remains one of the most aggressive and deadly tumor of the central nervous system (CNS). Gliomas are characterized by high malignancy, heterogeneity, invasiveness, and high resistance to radiotherapy and chemotherapy. It is urgent to find potential new molecular targets for glioma. The TRPM channels consist of TRPM1-TPRM8 and play a role in many cellular functions, including proliferation, migration, invasion, angiogenesis, etc. More and more studies have shown that TRPM channels can be used as new therapeutic targets for glioma. In this review, we first introduce the structure, activation patterns, and physiological functions of TRPM channels. Additionally, the pathological mechanism of glioma mediated by TRPM2, 3, 7, and 8 and the related signaling pathways are described. Finally, we discuss the therapeutic potential of targeting TRPM for glioma.


•TRPM channels are widely expressed in the human body and play an important role in gliomas.• Abnormal expression of TRPM2, 3, 7, and 8 channels in gliomas is associated with disease severity and prognosis.•TRPM2, 3, 7, and 8 channels are effective targets in glioma.


Asunto(s)
Neoplasias Encefálicas , Glioma , Canales Catiónicos TRPM , Humanos , Glioma/metabolismo , Glioma/patología , Glioma/genética , Glioma/tratamiento farmacológico , Canales Catiónicos TRPM/metabolismo , Canales Catiónicos TRPM/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Transducción de Señal , Animales
10.
Mol Med Rep ; 30(2)2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38940345

RESUMEN

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the cell invasion and migration assay data shown in Fig. 6 and the cell proliferation assay experiments shown in Fig. 2 were strikingly similar to data appearing in different form in other articles by different authors; furthermore, in Fig. 2, for the '10 mM metformin' experiment, certain of the glioma cells appeared to be strikingly similar to other cells contained within the same data panels. Owing to the fact that the contentious data in the above article had already been published elsewhere or were under consideration for publication prior to its submission to Molecular Medicine Reports, and owing to concerns with the authenticity of certain of the data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 20: 887­894, 2019; DOI: 10.3892/mmr.2019.10369].

11.
Artículo en Inglés | MEDLINE | ID: mdl-39185644

RESUMEN

INTRODUCTION: Nicotinamide Mononucleotide (NMN) has gained attention as a precursor to Nicotinamide Adenine Dinucleotide (NAD+) in recent years, commonly utilized in anti-aging therapies. The anti-aging effects of NMN on muscle and liver functions in middleaged and elderly people are still unclear. OBJECTIVE: Based on available randomized controlled trials, we conducted a meta-analysis to evaluate the impact of NMN on muscle and liver functions in middle-aged and elderly individuals. METHODS: We conducted searches on three electronic databases (PubMed, Embase, Web of Science) for randomized controlled trials involving NMN interventions in middle-aged and elderly populations. Through the Cochrane Handbook, we assessed the specific methodological quality. All statistical analyses were obtained by Stata15, and statistical significance was set as P<0.05. RESULTS: There were 412 participants from 9 studies in this meta-analysis. Based on changes in gait speed (SMD: 0.34 m/s, 95%CI [0.03, 0.66] p = 0.033), NMN had significant effects on muscle mass. Moreover, NMN had a better effect on ALT (SMD: -0.29 IU/L, 95%CI [-0.55, -0.03] p = 0.028). Subgroup analysis indicated that administering a small dose of NMN exerted the most prominent impact on Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). CONCLUSION: NMN has positive efficacy in enhancing muscle function, reducing insulin resistance and lowering aminotransferase levels in middle-aged and elderly individuals. NMN is an encouraging and considerable drug for anti-aging treatment.

12.
World J Clin Cases ; 12(16): 2862-2868, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38899292

RESUMEN

BACKGROUND: Rectal mucosal melanoma is a rare and highly aggressive disease. Common symptoms include anal pain, an anal mass, or bleeding. As such, the disease is usually detected on rectal examination of patients with other suspected anorectal diseases. However, due to its rarity and nonspecific symptoms, melanoma of the rectal mucosa is easily misdiagnosed. CASE SUMMARY: This report describes the case of a 58-year-old female patient who presented with a history of blood in her stool for the prior one or two months, without any identifiable cause. During colonoscopy, a bulge of approximately 2.2 cm × 2.0 cm was identified. Subsequently, the patient underwent endoscopic ultrasound (EUS) to characterize the depth of invasion of the lesions. EUS suggested a hypoechoic mucosal mass with involvement of the submucosal layer and heterogeneity of the internal echoes. Following surgical intervention, the excised tissue samples were examined and confirmed to be rectal malignant melanoma. The patient recovered well with no evidence of recurrence during follow-up. CONCLUSION: This case shows that colonoscopy with EUS and pathological examination can accurately diagnose rare cases of rectal mucosal melanoma.

13.
Sci Rep ; 14(1): 25448, 2024 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-39455808

RESUMEN

The emergence of nanogenerators, which have the ability to capture mechanical energy from the environment and to collect and transmit tiny energy, is rapidly becoming a hot research topic. The performance of electrode materials is the key to the efficiency of nanogenerators. Covalent organic skeletons (COFs), a class of crystalline organic porous materials with the advantages of large specific surface area, high porosity, tunable structure, and flexible tailorability, have very significant advantages in being used as nanogenerator materials. In this paper, we synthesised two COF materials to investigate the effect of the introduction of active metals on the friction power generation performance of COFs without changing their topology, COF-2 containing zinc ions is capable of generating a short-circuit current of 107.5 µA during friction. The porous structure increases the effective contact area to form a larger charge density, and the introduction of metal ions can accelerate the charge separation and transport. The two bidirectional synergistic effects of the materials significantly improve the output performance of the nanogenerator, and a simple and efficient method is explored for the enhancement of the output performance of COF-based triboelectric nanogenerators.

14.
IEEE/ACM Trans Comput Biol Bioinform ; 20(5): 2933-2944, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37030792

RESUMEN

Question answering (QA) plays a vital role in biomedical natural language processing. Among question answering tasks, the retrieval question answering (ReQA) aims to directly retrieve the correct answer from candidates and has attracted much attention in the community for its efficiency. Recently, researchers have introduced ReQA into the biomedical domain as BioReQA. Typically BioReQA models rely on the dual-encoder to gain semantic representation and are trained following the settings of dense retrieval. However, they normally utilize easy in-batch negative samples in training process to avoid the extra forwarding cost and GPU memory required by encoding additional negative samples. However, hard negative samples have been proved more important with regard to the overall performance of BioReQA tasks. Therefore in this research, we focus on effectively constructing hard in-batch negative samples. Inspired by the classic linear assignment problem, we propose an Iterative Linear Assignment Grouping (ILAG) algorithm to construct hard in-batch negative samples. To further enhance performance for given hard batches in a low-resource scenario, we also employ adversarial training to augment the difficulty of batches. Extensive experiments have shown our proposed method's promising potential in the area of biomedical retrieval question answering.


Asunto(s)
Algoritmos , Almacenamiento y Recuperación de la Información , Procesamiento de Lenguaje Natural , Semántica
15.
Artículo en Inglés | MEDLINE | ID: mdl-35316189

RESUMEN

Biomedical factoid question answering is an essential application for biomedical information sharing. Recently, neural network based approaches have shown remarkable performance for this task. However, due to the scarcity of annotated data which requires intensive knowledge of expertise, training a robust model on limited-scale biomedical datasets remains a challenge. Previous works solve this problem by introducing useful knowledge. It is found that the interaction between question and answer (QA-interaction) is also a kind of knowledge which could help extract answer accurately. This research develops a knowledge distillation framework for biomedical factoid question answering, in which a teacher model as the knowledge source of QA-interaction is designed to enhance the student model. In addition, to further alleviate the problem of limited-scale dataset, a novel adversarial knowledge distillation technique is proposed to robustly distill the knowledge from teacher model to student model by constructing perturbed examples as additional training data. By forcing the student model to mimic the predicted distributions of teacher model on both original examples and perturbed examples, the knowledge of QA-interaction can be learned by student model. We evaluate the proposed framework on the widely used BioASQ datasets, and experimental results have shown the proposed method's promising potential.


Asunto(s)
Difusión de la Información , Redes Neurales de la Computación , Humanos
16.
IEEE/ACM Trans Comput Biol Bioinform ; 20(3): 1864-1875, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36331640

RESUMEN

Retrieval Question Answering (ReQA) is an essential mechanism of information sharing which aims to find the answer to a posed question from large-scale candidates. Currently, the most efficient solution is Dual-Encoder which has shown great potential in the general domain, while it still lacks research on biomedical ReQA. Obtaining a robust Dual-Encoder from biomedical datasets is challenging, as scarce annotated data are not enough to sufficiently train the model which results in over-fitting problems. In this work, we first build ReQA BioASQ datasets for retrieving answers to biomedical questions, which can facilitate the corresponding research. On that basis, we propose a framework to solve the over-fitting issue for robust biomedical answer retrieval. Under the proposed framework, we first pre-train Dual-Encoder on natural language inference (NLI) task before the training on biomedical ReQA, where we appropriately change the pre-training objective of NLI to improve the consistency between NLI and biomedical ReQA, which significantly improve the transferability. Moreover, to eliminate the feature redundancies of Dual-Encoder, consistent post-whitening is proposed to conduct decorrelation on the training and trained sentence embeddings. With extensive experiments, the proposed framework achieves promising results and exhibits significant improvement compared with various competitive methods.


Asunto(s)
Almacenamiento y Recuperación de la Información , Almacenamiento y Recuperación de la Información/métodos , Aprendizaje Automático , Curaduría de Datos , Inteligencia Artificial
17.
IEEE/ACM Trans Comput Biol Bioinform ; 19(4): 2365-2376, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33974546

RESUMEN

Biomedical factoid question answering is an important task in biomedical question answering applications. It has attracted much attention because of its reliability. In question answering systems, better representation of words is of great importance, and proper word embedding can significantly improve the performance of the system. With the success of pretrained models in general natural language processing tasks, pretrained models have been widely used in biomedical areas, and many pretrained model-based approaches have been proven effective in biomedical question-answering tasks. In addition to proper word embedding, name entities also provide important information for biomedical question answering. Inspired by the concept of transfer learning, in this study, we developed a mechanism to fine-tune BioBERT with a named entity dataset to improve the question answering performance. Furthermore, we applied BiLSTM to encode the question text to obtain sentence-level information. To better combine the question level and token level information, we use bagging to further improve the overall performance. The proposed framework was evaluated on BioASQ 6b and 7b datasets, and the results have shown that our proposed framework can outperform all baselines.


Asunto(s)
Aprendizaje Automático , Procesamiento de Lenguaje Natural , Lenguaje , Aprendizaje , Reproducibilidad de los Resultados
18.
Genes (Basel) ; 13(10)2022 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-36292767

RESUMEN

Background: GBM astrocytes may adopt fetal astrocyte transcriptomic signatures involved in brain development and migration programs to facilitate diffuse tumor infiltration. Our previous data show that ETS variant 6 (ETV6) is highly expressed in human GBM and fetal astrocytes compared to normal mature astrocytes. We hypothesized that ETV6 played a role in GBM tumor progression. Methods: Expression of ETV6 was first examined in two American and three Chinese tissue microarrays. The correlation between ETV6 staining intensity and patient survival was calculated, followed by validation using public databases-TCGA and REMBRANDT. The effect of ETV6 knockdown on glioma cell proliferation (EdU), viability (AnnexinV labeling), clonogenic growth (colony formation), and migration/invasion (transwell assays) in GBM cells was tested. RNA sequencing and Western blot were performed to elucidate the underlying molecular mechanisms. Results: ETV6 was highly expressed in GBM and associated with an unfavorable prognosis. ETV6 silencing in glioma cells led to increased apoptosis or decreased proliferation, clonogenicity, migration, and invasion. RNA-Seq-based gene expression and pathway analyses revealed that ETV6 knockdown in U251 cells led to the upregulation of genes involved in extracellular matrix organization, NF-κB signaling, TNF-mediated signaling, and the downregulation of genes in the regulation of cell motility, cell proliferation, PI3K-AKT signaling, and the Ras pathway. The downregulation of the PI3K-AKT and Ras-MAPK pathways were further validated by immunoblotting. Conclusion: Our findings suggested that ETV6 was highly expressed in GBM and its high expression correlated with poor survival. ETV6 silencing decreased an aggressive in vitro phenotype probably via the PI3K-AKT and Ras-MAPK pathways. The study encourages further investigation of ETV6 as a potential therapeutic target of GBM.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glioblastoma/genética , Neoplasias Encefálicas/metabolismo , FN-kappa B/genética , Línea Celular Tumoral , Glioma/genética , Fenotipo
19.
World Neurosurg ; 165: e532-e545, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35760324

RESUMEN

OBJECTIVE: In recent years, numerous neurosurgical multimodal techniques have been utilized to maximize tumor resection safely and effectively. However, the synergetic effects of neurosurgical multimodalities on the survival of glioblastoma patients remain unclear. This study evaluated the role of intraoperative utilization of multimodalities in glioblastoma patients. METHODS: Data of 912 adult patients with glioblastoma were obtained from the Huashan Glioma Registry. The utilization of fewer than 2 (multimodality value < 2) intraoperative multimodal techniques was defined as the nonmultimodal group. In contrast, the utilization of 2 or more (multimodality value ≥ 2) intraoperative multimodal techniques was regarded as the multimodal group. The prognosis of the 2 cohorts was compared and further stratified based on the diagnosis date (2010-2014 or 2015-2019) to reveal the role of the application of multimodal techniques. RESULTS: The median overall survival (OS) and progression-free survival of glioblastoma patients were 17.70 months and 12.03 months, respectively. The OS time of the multimodal group was noticeably longer than that of the nonmultimodal group (21.0 months vs. 16.0 months, P < 0.001). Multimodal techniques were more frequently applied in surgery in the 2015-2019 group than in the 2010-2014 group. The popularity of multimodal techniques contributed to significant improvement in the prognosis of glioblastoma patients from 2010-2014 to 2015-2019 (OS, 16.0 months vs. 22.0 months, P < 0.001). CONCLUSIONS: This study indicated that the utilization of intraoperative multimodal techniques improved the extent of resection and elevated the survival for adult glioblastoma patients.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Adulto , Neoplasias Encefálicas/patología , Glioblastoma/diagnóstico por imagen , Glioblastoma/cirugía , Humanos , Procedimientos Neuroquirúrgicos/métodos , Pronóstico , Estudios Retrospectivos
20.
Chin Med ; 17(1): 42, 2022 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-35366928

RESUMEN

OBJECTIVE: To explore the effect of Ludangshen oral liquid for treatment of convalescent patients with coronavirus disease 2019 (COVID-19) with randomized, double-blind, placebo-controlled multicenter method. METHODS: 200 convalescent COVID-19 patients who had symptoms related to decreased digestive and respiratory function were randomly divided to either receive Ludangshen oral liquid or placebo for 2 weeks. The severity of clinical symptoms including fatigue, anorexia, abdominal distension, loose stools, and shortness of breath were assessed by visual analogue scale and observed at before and after treatment. The improvement and resolution rates of clinical symptoms were evaluated. Full analysis set (FAS) and per-protocol set (PPS) were used for statistical analyses. Adverse events were recorded during the study. RESULTS: 8 patients did not complete the study. After 2 weeks of treatment, both FAS and PPS results showed that patients in Ludangshen group had significantly lower score of fatigue, anorexia, loose stools, and shortness of breath than placebo group (P < 0.05), while there was no significant difference in distention (P > 0.05). The improvement rate of fatigue, anorexia, distension, loose stools and shortness of breath were significantly higher in Ludangshen group (P < 0.05), as well as the resolution rates (P < 0.05) except for shortness of breath (P > 0.05). There were two cases of adverse events, with one nose bleeding in Ludangshen group and one headache in placebo group. CONCLUSION: The study suggested that two weeks of Ludangshen oral liquid treatment may have certain effects for convalescent COVID-19 patients on improving digestive and respiratory symptoms including fatigue, anorexia, loose stools and shortness of breath, which may be one of the choices for management of convalescent COVID-19 patients with digestive and respiratory symptoms.

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