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1.
Technol Health Care ; 32(S1): 95-105, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38759040

RESUMO

BACKGROUND: Cardiovascular diseases (CVDs) are the leading global cause of mortality, necessitating advanced diagnostic tools for early detection. The electrocardiogram (ECG) is pivotal in diagnosing cardiac abnormalities due to its non-invasive nature. OBJECTIVE: This study aims to propose a novel approach for ECG signal classification, addressing the challenges posed by the complexity of ECG signals associated with various diseases. METHODS: Our method integrates Discrete Wavelet Transform (DWT) for feature extraction, capturing salient features of cardiovascular diseases. Subsequently, the gcForest model is employed for efficient classification. The approach is tested on the MIT-BIH Arrhythmia Database. RESULTS: The proposed method demonstrates promising results on the MIT-BIH Arrhythmia Database, achieving a test accuracy of 98.55%, recall of 98.48%, precision of 98.44%, and an F1 score of 98.46%. Additionally, the model exhibits robustness and low sensitivity to hyper-parameters. CONCLUSION: The combined use of DWT and the gcForest model proves effective in ECG signal classification, showcasing high accuracy and reliability. This approach holds potential for improving early detection of cardiovascular diseases, contributing to enhanced cardiac healthcare.


Assuntos
Arritmias Cardíacas , Eletrocardiografia , Análise de Ondaletas , Eletrocardiografia/métodos , Humanos , Arritmias Cardíacas/diagnóstico , Algoritmos , Processamento de Sinais Assistido por Computador , Reprodutibilidade dos Testes , Doenças Cardiovasculares/diagnóstico
2.
Acta Biochim Biophys Sin (Shanghai) ; 56(4): 597-606, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38404179

RESUMO

The aryl hydrocarbon receptor (AHR) has been identified as a significant driver of tumorigenesis. However, its clinical significance in acute myeloid leukemia (AML) remains largely unclear. In this study, RNA-Seq data from AML patients (bone marrow samples from 173 newly diagnosed AML patients) obtained from the TCGA database, and normal human RNA-Seq data (bone marrow samples from 70 healthy individuals) obtained from the GTEX database are downloaded for external validation and complementarity. The data analysis reveals that the AHR signaling pathway is activated in AML patients. Furthermore, there is a correlation between the expressions of AHR and mitochondrial oxidative phosphorylation genes. In vitro experiments show that enhancing AHR expression in AML cells increases mitochondrial oxidative phosphorylation and induces resistance to cytarabine. Conversely, reducing AHR expression in AML cells decreases cytarabine resistance. These findings deepen our understanding of the AHR signaling pathway's involvement in AML.


Assuntos
Citarabina , Leucemia Mieloide Aguda , Humanos , Citarabina/farmacologia , Fosforilação Oxidativa , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo
3.
Sensors (Basel) ; 24(3)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38339566

RESUMO

In recent years, the problem of cyber-physical systems' remote state estimations under eavesdropping attacks have been a source of concern. Aiming at the existence of eavesdroppers in multi-system CPSs, the optimal attack energy allocation problem based on a SINR (signal-to-noise ratio) remote state estimation is studied. Assume that there are N sensors, and these sensors use a shared wireless communication channel to send their state measurements to the remote estimator. Due to the limited power, eavesdroppers can only attack M channels out of N channels at most. Our goal is to use the Markov decision processes (MDP) method to maximize the eavesdropper's state estimation error, so as to determine the eavesdropper's optimal attack allocation. We propose a backward induction algorithm which uses MDP to obtain the optimal attack energy allocation strategy. Compared with the traditional induction algorithm, this algorithm has lower computational cost. Finally, the numerical simulation results verify the correctness of the theoretical analysis.

4.
Neuropsychologia ; 191: 108721, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37918479

RESUMO

Impaired associative memory function in patients with schizophrenia has received considerable attention. However, previous studies have primarily concentrated on unisensory materials, which limits our understanding of the broader implications of this impairment. In this study, we sought to expand on this knowledge by examining two types of associative memory domains in individuals with schizophrenia, leveraging both visual (Vis) and auditory (Aud) materials. A total of 32 patients with schizophrenia and 29 healthy controls were recruited to participate in the study. Each participant participated in an experiment composed of three paradigms in which different abstract materials (Aud-Aud, Aud-Vis, and Vis-Vis) were presented. Subsequently, the discriminability scores of the two groups were calculated and compared in different modal tasks. Results from the study indicated that individuals with schizophrenia demonstrated varying degrees of associative memory dysfunction in both the same and cross-modalities, with the latter having a significantly lower score than healthy controls (t = 4.120, p < 0.001). Additionally, the cross-modal associative memory function was significantly and negatively correlated with the severity of negative symptoms among individuals diagnosed with schizophrenia (r = -0.362, p = 0.042). This study provides evidence of abnormalities in the processing and memorization of information that integrates multiple sensory modalities in individuals with schizophrenia. This is of great significance for further understanding the cognitive symptoms and pathological mechanisms of schizophrenia, potentially guiding the development of relevant interventions and treatment methods.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/complicações , Esquizofrenia/patologia , Transtornos da Memória/etiologia , Transtornos da Memória/diagnóstico
5.
World J Gastroenterol ; 29(34): 5082-5090, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37753367

RESUMO

BACKGROUND: Neuroendocrine tumors (NET) are rare heterogeneous tumors that arise from neuroendocrine cells throughout the body. Acromegaly, a rare and slowly progressive disorder, usually results from a growth hormone (GH)-secreting pituitary adenoma. CASE SUMMARY: We herein describe a 38-year-old patient who was initially diagnosed with diabetes. During colonoscopy, two bulges were identified and subsequently removed through endoscopic submucosal dissection. Following the surgical intervention, the excised tissue samples were examined and confirmed to be grade 2 NET. 18F-ALF-NOTATATE positron emission tomography-computed tomography (PET/CT) and 68Ga-DOTANOC PET/CT revealed metastases in the peri-intestinal lymph nodes, prompting laparoscopic low anterior resection with total mesorectal excision. The patient later returned to the hospital because of hyperglycemia and was found to have facial changes, namely a larger nose, thicker lips, and mandibular prognathism. Laboratory tests and magnetic resonance imaging (MRI) suggested a GH-secreting pituitary adenoma. The pituitary adenoma shrunk after treatment with octreotide and was neuroendoscopically resected via a trans-sphenoidal approach. Whole-exome sequencing analysis revealed no genetic abnormalities. The patient recovered well with no evidence of recurrence during follow-up. CONCLUSION: 18F-ALF-NOTATE PET/CT and MRI with pathological analysis can effectively diagnose rare cases of pituitary adenomas complicated with rectal NET.


Assuntos
Adenoma , Tumores Neuroendócrinos , Neoplasias Hipofisárias , Neoplasias Retais , Humanos , Adulto , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Neoplasias Retais/cirurgia
7.
J Am Chem Soc ; 145(11): 6123-6134, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36912066

RESUMO

Boron dipyrromethene (also known as bodipy), as a class of versatile and robust fluorophores and a structural analogue of porphyrins, has received a great deal of interests in the field of light-harvesting and energy-transfer processes. However, the fabrication of bodipy monomers into metal-organic frameworks (MOFs) and the exploitation of their potential still lags behind the porphyrin MOFs. In this work, two bodipy-based MOFs, BMOF 1D with 1D chain structure and BMOF 2D with 2D layer structure, were assembled by using dicarboxyl-functionalized bodipy ligands. BMOF 1D can also be converted to BMOF 2D by inserting additional ligands into BMOF 1D to cross-link the adjacent chains into the rhombic grid layer. During this process, spontaneous exfoliation occurred simultaneously and resulted in the formation of several hundred nanometer thickness BMOF 2D (nBMOF 2D), which can be further exfoliated into one-layer MOF nanosheets (BMON 2D) by using the ultrasonic liquid exfoliation method in a high yield. Featuring the distinct bodipy scaffolds in the porous frameworks, both BMOF 2D and BMON 2D displayed high reactivity and recyclability in the photocatalytic inverse hydroboration and cross-dehydrogenative coupling reactions to afford α-amino organoborons and α-amino amides in moderate to high yields. This work not only highlights the cascade utilization of ligand installation and ultrasonic liquid exfoliation methods to provide the single-layer MOF sheets in high yields but also advances the bodipy-based MOFs as a new type of heterogeneous photocatalysts in the forging of C-B and C-C bonds driven by visible light.

8.
J Neural Eng ; 20(1)2023 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-36669203

RESUMO

Background. Low-intensity transcranial ultrasound stimulation (TUS) could induce both immediate and long-lasting neuromodulatory effects in human brains. Interhemispheric imbalance at prefrontal or motor cortices generally associates with various cognitive decline in aging and mental disorders. However, whether TUS could modulate the interhemispheric balance of excitability in human brain remains unknown.Objective. This study aims to explore whether repetitive TUS (rTUS) intervention can modulate the interhemispheric balance of excitability between bilateral motor cortex (M1) in healthy subjects.Approach. Motor evoked potentials (MEPs) at bilateral M1 were measured at 15 min and 0 min before a 15 min active or sham rTUS intervention on left M1 and at 0 min, 15 min and 30 min after the intervention, and the Chinese version of brief neurocognitive test battery (C-BCT) was conducted before and after the intervention respectively. Cortical excitability was quantified by MEPs, and the long-lasting changes of MEP amplitude was used as an index of plasticity.Results. In the active rTUS group (n= 20), the ipsilateral MEP amplitude increased significantly compared with baselines and lasted for up to 30 min after intervention, while the contralateral MEP amplitude decreased lasting for 15 min, yielding increased laterality between bilateral MEPs. Furthermore, rTUS intervention induced changes in some C-BCT scores, and the changes of scores correlated with the changes of MEP amplitudes induced by rTUS intervention. The sham rTUS group (n= 20) showed no significant changes in MEPs and C-BCT scores. In addition, no participants reported any adverse effects during and after the rTUS intervention, and no obvious temperature increase appeared in skull or brain tissues in simulation.Significance. rTUS intervention modulated the plasticity of ipsilateral M1 and the interhemispheric balance of M1 excitability in human brain, and improved cognitive performance, suggesting a considerable potential of rTUS in clinical interventions.


Assuntos
Transtornos Mentais , Córtex Motor , Humanos , Córtex Motor/fisiologia , Estimulação Magnética Transcraniana/métodos , Potencial Evocado Motor/fisiologia , Lateralidade Funcional/fisiologia
9.
Angew Chem Int Ed Engl ; 62(3): e202214460, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36383091

RESUMO

Satoh-Miura reaction is an important method for extending π-systems by forging multi-substituted benzene rings via double aryl C-H activation and annulation with alkynes. However, the development of highly enantioselective Satoh-Miura reaction remains rather challenging. Herein, we report an asymmetric Satoh-Miura reaction between 1-aryl benzo[h]isoquinolines and internal alkynes enabled by a SCpRh-catalyst. Judiciously choosing the counteranion of the Rh-catalyst is crucial for the desired reactivity over the competitive formation of azoniahelicenes. Detailed mechanistic studies support the proposal of counteranion-directed switching of reaction pathways in Rh-catalyzed asymmetric C-H activation.

10.
J Psychiatr Res ; 156: 705-712, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36410309

RESUMO

Altered network organization and aberrant neurometabolic levels have been associated with schizophrenia. However, modular alterations of functional-neurometabolic coupling in various stages of schizophrenia remain unclear. This longitudinal study enrolled 34 drug-naïve first-episode schizophrenia (FES) patients and 30 healthy controls (HC). The FES patients underwent resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy (1H-MRS) at baseline, 2 months, and 6 months of treatment. For 1H-MRS, the concentrations of γ-aminobutyric acid (GABA), N-acetylaspartate (NAA) and glutamate + glutamine in the ventromedial prefrontal cortex region were measured. A graph theoretical approach was applied for functional connectivity-based modular parcellation. We found that intra-default mode network (DMN) connectivity, inter-modular connectivity between the DMN and the hippocampus, and inter-modular connectivity between the DMN and the frontoparietal module were significantly different across 6-month treatment in the FES patients. The inter-module connectivity of the DMN and hippocampus correlated positively with NAA concentration in the HC group, while this correlation was absent in FES patients. This exploratory study suggests an altered modular connectivity in association with neurometabolite concentrations in FES patients and provides insights into multimodal neuroimaging biomarkers in schizophrenia. Future studies with larger sample sizes are needed to consolidate our findings.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Estudos Longitudinais
11.
Int J Endocrinol ; 2022: 9743654, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35942151

RESUMO

Objective: The main study objective was to investigate the correlation between the color Doppler ultrasound grading of hyperthyroidism and the biochemical data of thyroid function. Methods: Seventy-six patients were diagnosed with hyperthyroidism based on clinical and laboratory data at our hospital. The patients were examined using color Doppler ultrasound and laboratory investigations before starting 131I treatment. First, patients were divided into two groups based on the blood flow distribution determined by ultrasound. If the blood flow signal in the parenchyma was scattered and thinned, with dispersive points and discontinuous streaky distribution, the blood flow distribution area in the sample frame was less than or equal to 1/2 of the sample frame area and was judged to be level 1. If the parenchyma was filled with diffuse blood flow signals or if most areas had depicted rich blood flow distribution when the area of blood flow distribution in the sampling frame was greater than 1/2 of the sampling frame area, it was judged to be level 2. Then, the correlations between color Doppler ultrasound grading and biochemical data of thyroid function were analyzed. The indices included FT3, FT4, TSH, anti-TG, anti-TPO, and TRAb. Parameters of thyroid homeostasis, including thyroid's secretory capacity (SPINA-GT), the total deiodinase activity (SPINA-GD), Jostel's TSH index, and the thyrotroph thyroid hormone sensitivity index (TTSI), were calculated and compared. Results: Correlations were noted between color Doppler ultrasound grading and FT3, FT4, TRAb, SPINA-GT, TSHI, and TTSI. Moreover, FT3, FT4, TRAb, SPINA-GT, TSHI, and TTSI were higher in level 2 patients compared with level 1 patients. Conclusion: Correlations were noted between color Doppler ultrasound grading and biochemical data of thyroid function.

12.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(3): 255-259, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-35574741

RESUMO

OBJECTIVE: To analyze the risk factors of acute kidney injury (AKI) in patients with septic shock in intensive care unit (ICU), construct a predictive model, and explore the predictive value of the predictive model. METHODS: The clinical data of patients with septic shock who were hospitalized in the ICU of the Affiliated Hospital of Jining Medical College from April 2015 to June 2019 were retrospectively analyzed. According to whether the patients had AKI within 7 days of admission to the ICU, they were divided into AKI group and non-AKI group. 70% of the cases were randomly selected as the training set for building the model, and the remaining 30% of the cases were used as the validation set. XGBoost model was used to integrate relevant parameters to predict the risk of AKI in patients with septic shock. The predictive ability was assessed through receiver operator characteristic curve (ROC curve), and was correlated with acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), procalcitonin (PCT) and other comparative verification models to verify the predictive value. RESULTS: A total of 303 patients with septic shock were enrolled, including 153 patients with AKI and 150 patients without AKI. The incidence of AKI was 50.50%. Compared with the non-AKI group, the AKI group had higher APACHE II score, SOFA score and blood lactate (Lac), higher dose of norepinephrine (NE), higher proportion of mechanical ventilation, and tachycardiac. In the XGBoost prediction model of AKI risk in septic shock patients, the top 10 features were serum creatinine (SCr) level at ICU admission, NE use, drinking history, albumin, serum sodium, C-reactive protein (CRP), Lac, body mass index (BMI), platelet count (PLT), and blood urea nitrogen (BUN) levels. Area under the ROC curve (AUC) of the XGBoost model for predicting the risk of AKI in patients with septic shock was 0.816, with a sensitivity of 73.3%, a specificity of 71.7%, and an accuracy of 72.5%. Compared with the APACHE II score, SOFA score and PCT, the performance of the model improved significantly. The calibration curve of the model showed that the goodness of fit of the XGBoost model was higher than the other scores (the calibration curve had the lowest score, with a score of 0.205). CONCLUSIONS: Compared with the commonly used clinical scores, the XGBoost model can more accurately predict the risk of AKI in patients with septic shock, which helps to make appropriate diagnosis, treatment and follow-up strategies while predicting the prognosis of patients.


Assuntos
Injúria Renal Aguda , Sepse , Choque Séptico , Injúria Renal Aguda/diagnóstico , Feminino , Humanos , Unidades de Terapia Intensiva , Aprendizado de Máquina , Masculino , Norepinefrina , Pró-Calcitonina , Prognóstico , Curva ROC , Estudos Retrospectivos , Choque Séptico/diagnóstico
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(2): 577-582, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35396000

RESUMO

OBJECTIVE: To explore the changes of Ⅻ antithrombin (FⅫa-AT), thrombospondin-1 (TSP-1), and lupus anticoagulant (LA) ratio in the peripheral blood factor of patients with systemic lupus erythematosus (SLE) and the clinical value of combined diagnosis of thrombotic events. METHODS: A total of 133 SLE patients treated in Xingtai People's Hospital were selected and divided into simple SLE group (105 cases) and SLE complicated with thrombosis group (28 cases) according to whether thrombotic events occurred, and 102 cases of healthy people in the same period were selected as control. The clinical data of the 3 groups, the level of peripheral blood FⅫa-AT, TSP-1, and LA ratio were compared, the relationship between each peripheral blood index and SLE disease activity index (SLEDAI) score were analyzed. The influencing factors of thrombotic events in SLE patients were analyzed, and the value of each peripheral blood index in the diagnosis of SLE complicated with thrombotic events were evaluated. RESULTS: The proportion of the patients with age ≥60 year, hypertension, and smoking history in SLE complicated with thrombosis group was higher than those in simple SLE group and control group (P<0.05). The SLEDAI score, peripheral blood FⅫa-AT, TSP-1, LA ratio levels of the patients in SLE complicated with thrombosis group were significantly higher than those in simple SLE group and control group, and the simple SLE group was significantly higher than the control group (P<0.05). FⅫa-AT, TSP-1, LA ratio in peripheral blood of SLE patients were positively correlated with SLEDAI score (r=0.663, 0.578 and 0.625). Age, blood pressure, smoking history, peripheral blood FⅫa-AT, TSP-1, LA ratio were the important influencing factors of thrombotic events in SLE patients (P<0.05). The AUC diagnosed by the FⅫa-AT, TSP-1, and LA ratio in peripheral blood was 0.881, the 95% CI was 0.813-0.931, the sensitivity was 82.14%, and the specificity was 91.43%, which was superior to each index alone (P<0.05). CONCLUSION: Peripheral blood FⅫa-AT, TSP-1, LA ratio level changes in SLE patients are significantly related to disease activity, and the combined diagnosis of thrombotic events is more reliable.


Assuntos
Lúpus Eritematoso Sistêmico , Trombose , Humanos , Lúpus Eritematoso Sistêmico/complicações , Fatores de Risco , Trombose/etiologia , Trombospondina 1
14.
J Mater Sci Mater Med ; 33(4): 33, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35303193

RESUMO

Poly-L-lactic acid (PLLA) is considered to be a promising candidate material for biodegradable vascular scaffolds (BVS) in percutaneous coronary intervention (PCI). But, PLLA-BVS also faces the challenge of thrombosis (ST) and in-stent restenosis (ISR) caused by in-stent neo-atherosclerosis (ISNA) associated with inflammatory reactions in macrophage-derived foam cells. Our previous studies have confirmed that curcumin alleviates PLLA-induced injury and inflammation in vascular endothelial cells, but it remains unclear whether curcumin can alleviate the effect of inflammatory reactions in macrophage-derived foam cells while treated with degraded product of PLLA. In this study, PLLA-BVS was implanted in the porcine coronary artery to examine increased macrophages and inflammatory cytokines such as NF-κb and TNF-α by histology and immunohistochemistry. In vitro, macrophage-derived foam cells were induced by Ox-LDL and observed by Oil Red Staining. Foam cells were treated with pre-degraded PLLA powder, curcumin and PPARγ inhibitor GW9662, and the expression of IL-6, IL-10, TNF-α, NF-κb, PLA2 and PPARγ were investigated by ELISA or RT-qPCR. This study demonstrated that the macrophages and inflammatory factors increased after PLLA-BVS implantation in vivo, and foam cells derived from macrophages promoted inflammation by products of PLLA degradation in vitro. This present study was found that the inflammation of foam cells at the microenvironment of PLLA degraded products were significantly increased, and curcumin can attenuate the inflammation caused by the PLLA degradation via PPARγ signal pathway. In addition, curcumin should be further studied experimentally in vivo experiments on animal models as a potential therapeutic to reduce ISNA of PLLA-BVS. Graphical abstract.


Assuntos
Aterosclerose , Curcumina , Intervenção Coronária Percutânea , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Curcumina/farmacologia , Curcumina/uso terapêutico , Células Endoteliais , Células Espumosas/patologia , Inflamação/patologia , Macrófagos/metabolismo , PPAR gama/metabolismo , PPAR gama/farmacologia , PPAR gama/uso terapêutico , Poliésteres , Transdução de Sinais , Suínos
15.
Gene ; 822: 146317, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35182680

RESUMO

Kinesin family member 4A (KIF4A), located in the human chromosome band Xq13.1, is aberrantly overexpressed in various cancers. Our study intended to assess the expression of KIF4A in insulinoma and to gain new insights into the molecular mechanisms of this rare disease. First, KIF4A was significantly recruited in pancreatic endocrine cells relative to other cell types. A significant correlation existed between the overexpression of KIF4A and the poor survival of pancreatic adenocarcinoma patients. As revealed by CCK-8, TUNEL assay, flow cytometry, wound healing, Matrigel-transwell, senescence-associated ß-galactosidase staining, ELISA, and subcutaneous tumor formation analysis in nude mice, knocking down KIF4A significantly inhibited the growth and metastasis of insulinoma cells in vivo and in vitro. Mechanistically, we observed that KIF4A promoter sequences had reduced H3K27me3 modifications, and decline in enhancer of zeste homolog-2 (EZH2) expression promoted KIF4A expression by reducing the modification, thus leading to insulinoma. Moreover, EZH2 knockdown-induced insulinoma cell proliferation was dependent on KIF4A overexpression since KIF4A knockdown eradicated shEZH2-induced proliferation of insulinoma cells. In summary, KIF4A was identified as a possible therapeutic target for insulinoma.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/genética , Histonas/metabolismo , Insulinoma/patologia , Cinesinas/genética , Neoplasias Pancreáticas/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Código das Histonas , Humanos , Insulinoma/genética , Insulinoma/metabolismo , Camundongos , Transplante de Neoplasias , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Regiões Promotoras Genéticas , Regulação para Cima
16.
Org Lett ; 24(2): 564-569, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34985290

RESUMO

A rhodium-catalyzed asymmetric oxidative C-H/C-H cross-coupling reaction between 1-aryl isoquinolines and indolizines is disclosed. With a matched pair of SCpRh complex and chiral carboxylic acid, enantioselective two-fold C-H/C-H cross-coupling reactions between 1-aryl isoquinolines and indolizines provide a variety of axially chiral bi(hetero)aryls in excellent yields and enantioselectivity (up to 96% yield and 98% ee). Mechanistic studies suggest that both C-H cleavages are likely reversible.

18.
Cardiovasc Eng Technol ; 11(6): 636-645, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33108646

RESUMO

PURPOSE: Our previous studies have confirmed the safety and efficacy of the novel fully bioresorbable PLLA scaffold (PowerScaffold®) at 12 months implantation. In the present study, the scaffold absorption and coronary vessel remodeling at 4 years were evaluated. METHODS: After PowerScaffold® were implanted into 13 coronary arteries of 6 miniature pigs, quantitative coronary angiography (QCA) was performed at 15 days and 4 years follow-up to measure the mean lumen diameter (MLD), late lumen loss (LLL), and % stenosis of the coronary arteries. Optical coherence tomography (OCT) was performed to obtain the strut footprints at 4 years before euthanization for histological analysis. In addition, 2 PowerScaffold® were implanted into 2 miniature pigs for 2 years as supplementary data. All stented arteries were dissected and stained with HE, Masson, EVG, and Alcian blue to observe struts, cells, fibrinoid, elastin, and proteoglycans, respectively. RESULTS: There were no significant differences in MLD, LLL and % stenosis in stented coronary arteries between 15 days and 4 years by QCA. At 4 years, most strut sites were indiscernible and replaced by extracellular matrix and connective tissue by histology. Both strut/vessel wall interaction and strut coverage were shown 100% by OCT. CONCLUSION: At 4 years, the scaffold struts were completely embedded into vessel wall and mostly replaced by regenerated tissue. There was no sign of in-stent stenosis in all stented arteries.


Assuntos
Implantes Absorvíveis , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Intervenção Coronária Percutânea/instrumentação , Poliésteres/química , Tomografia de Coerência Óptica , Remodelação Vascular , Animais , Vasos Coronários/fisiopatologia , Feminino , Masculino , Valor Preditivo dos Testes , Desenho de Prótese , Suínos , Porco Miniatura , Fatores de Tempo
19.
Hum Gene Ther ; 31(21-22): 1203-1213, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32829653

RESUMO

Oncolytic viruses are emerging as important tools for immunotherapy for cancer treatment; however, most of the clinically tested oncolytic candidates are still administered by intratumoral injection, and new viruses capable of intravenous injection are urgently needed. The M1 virus is a positive-sense single-stranded RNA virus that belongs to the alphavirus family, and it was identified as an oncolytic virus that can selectively replicate in and kill tumor cells after intravenous injection. To further develop M1 for clinical research through intravenous injection, we systematically investigated the biodistribution characteristics of the M1 virus in normal rats, cynomolgus monkeys, and tumor-bearing immunocompromised mice. The data showed that the M1 virus was eliminated gradually from normal tissue but replicated and increased rapidly in tumor tissue. More importantly, the virus also infiltrated the blood-brain barrier and specifically replicated in and killed malignant glioma in immunocompetent mice. Our data proved the tumor selectivity and safety of the M1 virus, supporting its further clinical development.


Assuntos
Encéfalo/metabolismo , Glioma/terapia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/metabolismo , Animais , Feminino , Glioma/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Camundongos SCID , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
20.
Cell Biochem Funct ; 38(8): 1017-1024, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32495394

RESUMO

The study aimed to investigate the role of miR-124-3p and its potential molecular mechanism in papillary thyroid cancer (PTC). The expression of miR-124-3p and mitogen-activated protein kinase 4 (MAP2K4) in human thyroid follicular epithelial cell line (NTHY-ORI3-1) and human papillary thyroid carcinoma cell lines (SW1736, BCPAP, TPC-1 and K1) was measured by RT-qPCR. Cell proliferation was measured by CCK-8, while cell cycle and apoptosis rate were measured by flow cytometry. Invasive ability and migrative ability were measured by transwell assay and wound healing assay, respectively. Western blot was used to detect the levels of relative proteins. In vivo, TPC-1 cells transfected with miR-124-3p mimic were subcutaneously injected into the flank of the mice to form tumour. After successful modelling, mice were divided into two groups (n = 10): Control group and miR-124-3p mimic group. The present study showed that miR-124-3p was lowly expressed, while MAP2K4 was highly expressed in PTC cell lines. Besides, miR-124-3p targeted MAP2K4 and negatively regulated MAP2K4 in TPC-1 cells. In addition, miR-124-3p inhibited the proliferation and motility, and induced apoptosis and cell cycle arrest of TPC-1 cells by inactivating MAP2K4/JNK/JunD pathway. Furthermore, miR-124-3p inhibited tumour formation by downregulating MAP2K4 level in vivo. In conclusion, the study provided a novel molecular mechanism of miR-124-3p in the progress of PTC. SIGNIFICANCE OF THE STUDY: Papillary thyroid cancer (PTC) is the most important pathological type of thyroid cancer, accounting for 80% of thyroid cancer. miR-124-3p exhibited significant inhibitory role in the transformation and development of malignant tumours. However, in PTC, the roles and its potential molecular mechanism are unclear. Here, the study investigated the roles of miR-124-3p in the progress of PTC and its potential molecular mechanism. We found that miR-124-3p inhibited the proliferation and motility, and induced apoptosis and cell cycle arrest in PTC cells. This study provided a novel molecular mechanism of miR-124-3p in the progress of PTC.


Assuntos
Carcinogênese/metabolismo , MAP Quinase Quinase 4/metabolismo , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , RNA Neoplásico/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Humanos , MicroRNAs/genética , Proteínas de Neoplasias/genética , RNA Neoplásico/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
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