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1.
Psychol Med ; : 1-11, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38523252

RESUMO

BACKGROUND: Although dopaminergic disturbances are well-known in schizophrenia, the understanding of dopamine-related brain dynamics remains limited. This study investigates the dynamic coactivation patterns (CAPs) associated with the substantia nigra (SN), a key dopaminergic nucleus, in first-episode treatment-naïve patients with schizophrenia (FES). METHODS: Resting-state fMRI data were collected from 84 FES and 94 healthy controls (HCs). Frame-wise clustering was implemented to generate CAPs related to SN activation or deactivation. Connectome features of each CAP were derived using an edge-centric method. The occurrence for each CAP and the balance ratio for antagonistic CAPs were calculated and compared between two groups, and correlations between temporal dynamic metrics and symptom burdens were explored. RESULTS: Functional reconfigurations in CAPs exhibited significant differences between the activation and deactivation states of SN. During SN activation, FES more frequently recruited a CAP characterized by activated default network, language network, control network, and the caudate, compared to HCs (F = 8.54, FDR-p = 0.030). Moreover, FES displayed a tilted balance towards a CAP featuring SN-coactivation with the control network, caudate, and thalamus, as opposed to its antagonistic CAP (F = 7.48, FDR-p = 0.030). During SN deactivation, FES exhibited increased recruitment of a CAP with activated visual and dorsal attention networks but decreased recruitment of its opposing CAP (F = 6.58, FDR-p = 0.034). CONCLUSION: Our results suggest that neuroregulatory dysfunction in dopaminergic pathways involving SN potentially mediates aberrant time-varying functional reorganizations in schizophrenia. This finding enriches the dopamine hypothesis of schizophrenia from the perspective of brain dynamics.

2.
Mol Psychiatry ; 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37443193

RESUMO

Across the major psychiatric disorders (MPDs), a shared disruption in brain physiology is suspected. Here we investigate the neural variability at rest, a well-established behavior-relevant marker of brain function, and probe its basis in gene expression and neurotransmitter receptor profiles across the MPDs. We recruited 219 healthy controls and 279 patients with schizophrenia, major depressive disorder, or bipolar disorders (manic or depressive state). The standard deviation of blood oxygenation level-dependent signal (SDBOLD) obtained from resting-state fMRI was used to characterize neural variability. Transdiagnostic disruptions in SDBOLD patterns and their relationships with clinical symptoms and cognitive functions were tested by partial least-squares correlation. Moving beyond the clinical sample, spatial correlations between the observed patterns of SDBOLD disruption and postmortem gene expressions, Neurosynth meta-analytic cognitive functions, and neurotransmitter receptor profiles were estimated. Two transdiagnostic patterns of disrupted SDBOLD were discovered. Pattern 1 is exhibited in all diagnostic groups and is most pronounced in schizophrenia, characterized by higher SDBOLD in the language/auditory networks but lower SDBOLD in the default mode/sensorimotor networks. In comparison, pattern 2 is only exhibited in unipolar and bipolar depression, characterized by higher SDBOLD in the default mode/salience networks but lower SDBOLD in the sensorimotor network. The expression of pattern 1 related to the severity of clinical symptoms and cognitive deficits across MPDs. The two disrupted patterns had distinct spatial correlations with gene expressions (e.g., neuronal projections/cellular processes), meta-analytic cognitive functions (e.g., language/memory), and neurotransmitter receptor expression profiles (e.g., D2/serotonin/opioid receptors). In conclusion, neural variability is a potential transdiagnostic biomarker of MPDs with a substantial amount of its spatial distribution explained by gene expressions and neurotransmitter receptor profiles. The pathophysiology of MPDs can be traced through the measures of neural variability at rest, with varying clinical-cognitive profiles arising from differential spatial patterns of aberrant variability.

3.
Sensors (Basel) ; 23(3)2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36772243

RESUMO

In speaker recognition tasks, convolutional neural network (CNN)-based approaches have shown significant success. Modeling the long-term contexts and efficiently aggregating the information are two challenges in speaker recognition, and they have a critical impact on system performance. Previous research has addressed these issues by introducing deeper, wider, and more complex network architectures and aggregation methods. However, it is difficult to significantly improve the performance with these approaches because they also have trouble fully utilizing global information, channel information, and time-frequency information. To address the above issues, we propose a lighter and more efficient CNN-based end-to-end speaker recognition architecture, ResSKNet-SSDP. ResSKNet-SSDP consists of a residual selective kernel network (ResSKNet) and self-attentive standard deviation pooling (SSDP). ResSKNet can capture long-term contexts, neighboring information, and global information, thus extracting a more informative frame-level. SSDP can capture short- and long-term changes in frame-level features, aggregating the variable-length frame-level features into fixed-length, more distinctive utterance-level features. Extensive comparison experiments were performed on two popular public speaker recognition datasets, Voxceleb and CN-Celeb, with current state-of-the-art speaker recognition systems and achieved the lowest EER/DCF of 2.33%/0.2298, 2.44%/0.2559, 4.10%/0.3502, and 12.28%/0.5051. Compared with the lightest x-vector, our designed ResSKNet-SSDP has 3.1 M fewer parameters and 31.6 ms less inference time, but 35.1% better performance. The results show that ResSKNet-SSDP significantly outperforms the current state-of-the-art speaker recognition architectures on all test sets and is an end-to-end architecture with fewer parameters and higher efficiency for applications in realistic situations. The ablation experiments further show that our proposed approaches also provide significant improvements over previous methods.


Assuntos
Algoritmos , Redes Neurais de Computação , Atenção
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(2): 268-274, 2023 Mar.
Artigo em Zh | MEDLINE | ID: mdl-36949684

RESUMO

Objective: To investigate hippocampal development deviation and its association with cognition in patients with major psychiatric disorders (MPDs), including schizophrenia, bipolar disorder and major depressive disorder. Methods: The T1-weighted MRI data of 174 first-episode drug-naïve schizophrenia (FES) atients, 169 bipolar disorder (BD) patients, 184 major depressive disorder (MDD) patients, and 321 healthy controls were collected and their hippocampal volume was extracted after preprocessing with Freesurfer 5.3. A normative neurodevelopment model was applied to calculate the hippocampal deviation scores. Data on cognitive functions, including visual memory, attention, spatial working memory, were collected. Comparison by different sexes was made to identify difference between the hippocampal development deviation scores of the control group and those of the disease groups. We also investigated the moderating effect of age on the deviation score and explored the association between the deviation score and cognitive function. Results: The hippocampal development deviation scores of patients with MPDs were significantly lower than those of the healthy controls (false discovery rate [FDR]-P<0.05). Analysis of the moderating effect of age revealed lower deviation scores in young patients (<[25.83-28.56] yr.) and higher deviation scores in old patients (>[35.87-54.35] yr.) in comparison with those of the healthy controls. The right hippocampal deviation scores in male FES patients were positively correlated with the number of errors for tasks concerning spatial working memory ( r=0.32, FDR-P=0.04). Conclusion: Our findings suggest abnormal hippocampal development in MPDs patients and its different distribution in MPDs patients of different age groups. The hippocampal development deviation score may provide a new perspective for further understanding of etiology in MPDs.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Esquizofrenia , Humanos , Masculino , Transtorno Depressivo Maior/complicações , Transtorno Bipolar/complicações , Hipocampo , Esquizofrenia/complicações , Cognição , Imageamento por Ressonância Magnética
5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(2): 281-286, 2023 Mar.
Artigo em Zh | MEDLINE | ID: mdl-36949686

RESUMO

Objective: To investigate frequency-specific alterations of spontaneous brain activity in first-episode drug-naïve schizophrenia (SZ) patients and the associations with clinical symptoms. Methods: We collected the resting-state functional MRI (rs-fMRI) data from 84 first-episode drug-naïve SZ patients and 94 healthy controls (HCs) and calculated the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of four frequency bands, including slow-2, slow-3, slow-4, and slow-5. Two-sample t-tests were used to evaluate the intergroup differences in ALFF and ReHo, while partial correlation analyses were conducted to explore the associations between abnormal ALFF and ReHo and the severity of clinical symptoms in the SZ group. Results: Compared with HCs, the SZ group showed reduced ALFF in superior cerebellum and cerebellar vermis across slow-2, slow-3, and slow-4 bands, while increased ALFF was found in left superior temporal gyrus, middle temporal gyrus, and superior temporal pole at slow-4 band. Moreover, reduced ReHo was observed in the right precentral and postcentral gyri at slow-3 band in the SZ group. Additionally, the ALFF of left superior temporal gyrus, middle temporal gyrus, and superior temporal pole in slow-4 band showed a trend of positive correlation with the excited factor score of Positive and Negative Syndrome Scale (PANSS) in the SZ group. Conclusion: Our results suggest that local alterations of spontaneous brain activity were frequency-specific in first-episode drug-naïve SZ patients.


Assuntos
Esquizofrenia , Humanos , Encéfalo , Mapeamento Encefálico , Lobo Temporal , Imageamento por Ressonância Magnética
6.
Int J Hyperthermia ; 38(2): 24-29, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34420449

RESUMO

OBJECTIVE: To compare the re-intervention rates of myomectomy, uterine artery embolization (UAE) and magnetic resonance-guided focused ultrasound surgery (MRgFUS) for uterine fibroids (UFs) in different follow-up time. METHODS: Two investigators searched PubMed for clinical studies published in English from 1 Jan 2000 to 31 Dec 2020, and independently examined the paper to select qualified studies, extracted relevant information and assessed the risk of bias. Meanwhile, a meta-analysis of 31 studies containing totally 42103 patients was conducted to compare the re-intervention rate of myomectomy, UAE and MRgFUS. RESULTS: In the meta-analysis of 42103 patients, the 12-month re-intervention rates of myomectomy, UAE and MRgFUS for UFs were 0.06 (95%CI, 0.01-0.11), 0.07 (95%CI, 0.06-0.09), and 0.12 (95%CI, 0.04-0.20) respectively. The 24-month re-intervention rates were 0.10 (95%CI, 0.04-0.16), 0.08 (95%CI, 0.01-0.17), and 0.14 (95%CI, 0.07-0.21) respectively. The 36-month re-intervention rates were 0.09 (95%CI, 0.05-0.13), 0.14 (95%CI, 0.05-0.23), and 0.22 (95%CI, 0.11-0.32) respectively. Additionally, the 60-month re-intervention rates were 0.19 (95%CI, 0.15-0.24), 0.21 (95%CI, 0.17-0.25), and 0.49 (95%CI, 0.21-0.77) respectively. CONCLUSIONS: The myomectomy has the lowest re-intervention rate of the three regimens in short time and long time while the MRgFUS has the highest. The rate of MRgFUS increased rapidly in the 60th month after the treatment.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Leiomioma , Embolização da Artéria Uterina , Miomectomia Uterina , Neoplasias Uterinas , Feminino , Humanos , Leiomioma/diagnóstico por imagem , Leiomioma/cirurgia , Resultado do Tratamento , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/cirurgia
7.
Bioprocess Biosyst Eng ; 37(12): 2425-36, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24890135

RESUMO

Steam explosion is the most promising technology to replace conventional acid hydrolysis of lignocellulose for biomass pretreatment. In this paper, a new screw-steam-explosive extruder was designed and explored for xylose production and lignocellulose biorefinery at the pilot scale. We investigated the effect of different chemicals on xylose yield in the screw-steam-explosive extrusion process, and the xylose production process was optimized as followings: After pre-impregnation with sulfuric acid at 80 °C for 3 h, corncob was treated at 1.55 MPa with 9 mg sulfuric acid/g dry corncob (DC) for 5.5 min, followed by countercurrent extraction (3 recycles), decoloration (activated carbon dosage 0.07 g/g sugar, 75 °C for 40 min), and ion exchange (2 batches). Using this process, 3.575 kg of crystal xylose was produced from 22 kg corncob, almost 90 % of hemicellulose was released as monomeric sugar, and only a small amount of by-products was released (formic acid, acetic acid, fural, 5-hydroxymethylfurfural, and phenolic compounds were 0.17, 1.14, 0.53, 0.19, and 1.75 g/100 g DC, respectively). All results indicated that the screw-steam-explosive extrusion provides a more effective way to convert hemicellulose into xylose and could be an alternative method to traditional sulfuric acid hydrolysis process for lignocellulose biorefinery.


Assuntos
Biomassa , Biotecnologia/métodos , Resíduos Industriais , Xilose/química , Zea mays/química , Carbono/química , Cristalização , Desenho de Equipamento , Concentração de Íons de Hidrogênio , Hidrólise , Íons , Lignina/química , Fenol/química , Polissacarídeos/química , Pressão , Vapor , Ácidos Sulfúricos/química , Temperatura , Fatores de Tempo , Águas Residuárias
8.
ScientificWorldJournal ; 2014: 214632, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25133211

RESUMO

Xylitol fermentation production from corncob acid hydrolysate has become an attractive and promising process. However, corncob acid hydrolysate cannot be directly used as fermentation substrate owing to various inhibitors. In this work, soaking in aqueous ammonia (SAA) pretreatment was employed to reduce the inhibitors in acid hydrolysate. After detoxification, the corncob acid hydrolysate was fermented by immobilized Candida tropicalis cell to produce xylitol. Results revealed that SAA pretreatment showed high delignification and efficient removal of acetyl group compounds without effect on cellulose and xylan content. Acetic acid was completely removed, and the content of phenolic compounds was reduced by 80%. Furthermore, kinetic behaviors of xylitol production by immobilized C. tropicalis cell were elucidated from corncob acid hydrolysate detoxified with SAA pretreatment and two-step adsorption method, respectively. The immobilized C. tropicalis cell showed higher productivity efficiency using the corncob acid hydrolysate as fermentation substrate after detoxification with SAA pretreatment than by two-step adsorption method in the five successive batch fermentation rounds. After the fifth round fermentation, about 60 g xylitol/L fermentation substrate was obtained for SAA pretreatment detoxification, while about 30 g xylitol/L fermentation substrate was obtained for two-step adsorption detoxification.


Assuntos
Amônia/química , Biotecnologia/métodos , Candida tropicalis/metabolismo , Carboidratos/química , Xilitol/biossíntese , Zea mays/química , Ácido Acético/química , Biodegradação Ambiental , Metabolismo dos Carboidratos , Fermentação , Hidrólise , Hidrolisados de Proteína/química , Hidrolisados de Proteína/metabolismo
9.
ScientificWorldJournal ; 2014: 498134, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24778586

RESUMO

Tremendous attentions have been attracted to the foods labeled with natural, green, organic, and nuisanceless conception of healthy diet. Therefore, it is of great significance to establish relative defining guidance for safe assessment of botanicals. Cyclocarya paliurus (Batal.) Iljinsk (family Cyclocaryaceae), called sweet tea tree, is a well-known edible and medicinal plant, which has been widely used in China as drug formulation for the treatment of hypertension and diabetes. Despite its benefits, no reports have been described on the safe assessment of C. paliurus leaves aqueous extract. In this study, we have conducted the genotoxicity assay (including Ames test, bone marrow polychromatic erythrocyte micronucleus test, and sperm abnormality test in mice) and traditional teratogenicity assay in rats (maternal toxicity, embryo toxicity, and teratogenicity test) to assess the genetic and teratogenic safety of aqueous extracts from C. paliurus leaves. Results of each assay show that the highest dose of C. paliurus leaves aqueous extract is considered relatively nonmutagenic and nonteratogenic, revealing that C. paliurus leaves possess safety and quality as a functional additional ingredient in food.


Assuntos
Juglandaceae/química , Mutagênicos/toxicidade , Extratos Vegetais/toxicidade , Folhas de Planta/química , Teratogênicos/toxicidade , Animais , Masculino , Camundongos , Testes de Mutagenicidade
10.
Int J Gen Med ; 17: 2877-2886, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947567

RESUMO

Background: The aim of this study was to describe the demographic and clinical characteristics of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC), analyse the risk factors associated with HBV-associated HCC, and to provide some references to the diagnosis and treatment of HCC. Methods: This study retrospectively enrolled 730 patients, including 390 patients with chronic hepatitis B (CHB) as controls, and 340 patients with CHB complicated with HCC as patients. Relevant information and medical records of these participants were collected, including age, sex, cigarette smoking, alcoholism, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), cirrhosis, occupation, ascites, HBV-DNA load, the qualitative analysis of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb serological markers, and levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), gamma-glutamyltransferase (GGT), TNM stage, tumor size and tumor number. The T test, Chi-square test, non-parametric rank-sum test, logistic regression analyses were used to explore the influencing factors and their degree of association with HCC in patients with HBV. Results: The proportion of smoking, alcoholism, married status, DM, hypertension, and the rate of HBV-DNA with a viral load of ≥500 copies/mL were significantly higher in the HCC group than in the controls (all p<0.05). Cirrhosis was more common among patients with CHB+HCC than in controls (p=0.013). The proportion of patients with HBsAg, HBeAb, and HBcAb positive was greater in CHB+HCC group than that in CHB group. Logistic regression analysis indicated that age ≥60 years (OR: 1.835, 95% CI: 1.020-3.302, p=0.043), HBeAb positive (OR: 9.105, 95% CI: 4.796-17.288, p<0.001), antiviral treatment with entecavir (OR: 2.209, 95% CI: 1.106-4.409, p=0.025), and GGT (OR: 1.004, 95% CI: 1.001-1.007, p=0.002) were risk factors for HCC in patients with CHB. Conclusion: Advanced age, HBeAb positive, antiviral treatment with entecavir, and GGT were independent risk factors for HCC in HBV patients.

11.
J Cancer ; 12(19): 5923-5928, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476006

RESUMO

Objectives: This study was to analyze the relationships between lymphocyte-to-monocyte ratio (LMR) alone or combined with serum CA125 (COLC) and advanced stage of ovarian cancer (OC). Methods: The receiver-operating characteristic (ROC) curves of LMR, CA125, and COLC staging OC were constructed by a retrospective study. Furthermore, a binary logistic regression model was used to assay the independent risk factors for OC staging. Results: Two hundred and twenty-five patients with OC were identified in this cohort. Eighty-five OC patients were diagnosed at an early stage, and 140 OC patients were diagnosed at an advanced stage. The median of LMR in the early stage was higher than that in advanced stage (4.4 vs. 2.8), and the median of serum CA125 was lower than that in advanced stage (80 U/mL vs. 251.3 U/mL). Multivariate logistic regression LMR≤3.7 (OR=0.299, 95% CI: 0.093-0.962, P=0.043) and CA125>95.7 U/mL (OR=4.317, 95% CI: 1.436-12.977, P=0.009) were risk factors for stage of advanced OC whether presence or absence of malignant ascites. Furthermore, the area under the curve of COLC was higher than that of LMR (0.782 vs. 0.732) or serum CA125 (0.782 vs. 0.708) in staging OC. The specificity of COLC was higher than that of LMR (87.1% vs. 70.6%) or serum CA125 (87.1% vs. 61.2%) in staging OC. Conclusion: LMR alone or in combination with serum CA125 might be associated with OC staging. Besides, as a predictive factor, COLC may have a high specificity in staging OC.

12.
Oncotarget ; 11(37): 3484-3485, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32973972

RESUMO

[This corrects the article DOI: 10.18632/oncotarget.23507.].

13.
J Cancer ; 11(11): 3165-3171, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32231720

RESUMO

Objectives: To investigate the role of inflammation-related factors, lymphocyte-to-monocyte ratio (LMR) alone and combined detection with cancer antigen 125 (CA125), in the prognostic assessment of ovarian cancer (OC). Methods: A retrospective clinicopathologic review was performed. The receiver-operating characteristic (ROC) curves of LMR, CA125, and COLC predicting mortality in OC patients were constructed. Besides, Kaplan-Meier and Cox logistic regression models were used to plot the survival curves and determine the independent prognostic factors. Results: A total of 214 OC patients were identified in this cohort. The mean duration of follow-up was 64 months (minimum 8 months, maximum 116 months). In this cohort, 135 cases died (63.1%), and the median progression-free survival (PFS) and overall survival (OS) were 20 and 39.5 months, respectively. Results of the multivariate Cox regression model showed that LMR≤3.8 (HR = 0.494, 95% CI: 0.329-0.742, P = 0.001) and CA125>34 U/ml (HR = 1.641, 95% CI: 1.057-2.550, P = 0.027) were significantly associated with poor PFS; and LMR≤3.8 (HR = 0.459, 95% CI: 0.306-0.688, P = <0.001) and CA125>34 U/ml (HR = 1.946, 95% CI: 1.256-3.015, P = 0.003) were significantly associated with OS. Furthermore, the area under the curve of COLC was higher (0.713) than that of LMR (0.709) or CA125 (0.583), the specificity of COLC was higher (75.9%) than that of LMR (62%) or CA125 (40.5%) in predicting mortality in OC patients. Conclusions: LMR alone and combined with CA125 might be used as predictive markers in OC. Furthermore, as a prognostic factor, COLC might have a higher specificity to predict the outcome.

14.
Int J Oncol ; 56(4): 867-878, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32319549

RESUMO

Glutathione S­transferase Pi (GSTP1) is an isozyme encoded by the GST pi gene that plays an important regulatory role in detoxification, anti­oxidative damage, and the occurrence of various diseases. The aim of the present study was to review the association between the expression of GSTP1 and the development and treatment of various cancers, and discuss GSTP1 methylation in several malignant tumors, such as prostate, breast and lung cancer, as well as hepatocellular carcinoma; to review the association between polymorphism of the GSTP1 gene and various diseases; and to review the effects of GSTP1 on electrophilic oxidative stress, cell signal transduction, and the regulation of carcinogenic factors. Collectively, GSTP1 plays a major role in the development of various diseases.


Assuntos
Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Glutationa S-Transferase pi/metabolismo , Neoplasias/patologia , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Animais , Glutationa S-Transferase pi/genética , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Transdução de Sinais
15.
DNA Cell Biol ; 38(4): 314-321, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30762444

RESUMO

The shortage of human hepatocytes continues to be a significant limitation for the widespread application of hepatocyte transplantation and bioartificial liver (BAL) support therapy. Recombinant activation gene 2 (Rag2) and fumarylacetoacetate hydrolase (Fah)-deficient mice could be highly repopulated with human hepatocytes. However, Fah/Rag2-deficient mice can only produce up to 1 × 108 human hepatocytes per mouse. We hypothesized that 2-10 × 1010 human hepatocytes can be produced per Fah/Rag2-deficient pig, which is an adequate supply for hepatocyte transplantation and BAL therapy. In a novel approach, we used stably transfected Cas9 cells and single-guide RNA adenoviruses containing fluorescent reporters to enrich porcine cells with Fah/Rag2 dual gene mutations. This resulted in the construction of Fah/Rag2 double knockout porcine iliac artery endothelial cells, which were subsequently used for generating Fah/Rag2-deficient pigs.


Assuntos
Adenoviridae/genética , Sistemas CRISPR-Cas/genética , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Técnicas de Inativação de Genes/métodos , Hidrolases/deficiência , Hidrolases/genética , Animais , Sequência de Bases , Linhagem Celular , Mutação , Suínos , Fatores de Tempo
16.
Oncotarget ; 9(2): 2515-2526, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29416788

RESUMO

Colorectal cancer is very common worldwide and advanced colorectal cancer exhibited very poor clinical outcome. Oxaliplatin (OXP) is one of the principal chemotherapeutic agents in colorectal cancer treatment presenting impressive anti-tumor ability, limited by adverse effect in clinical practice. Fibrin glue (FG) is a biocompatible formulation made of fibrinogen and thrombin, extensively used in surgery for hemostasis, tissue adhesion and sealing. In this study, FG was innovatively applied as OXP delivery system and results showed enhanced anti-tumor performance in subcutaneous model and abdominal metastasis model of murine colorectal cancer compared with that of OXP used alone. It is revealed that combination of OXP and FG could increase activated CD8+ T cells, reduce regulatory T (Treg) cells and increase interferon-γ (IFN-γ). Furthermore, results showed promoted tumor apoptosis, decreased proliferation and inhibited tumor angiogenesis by OXP and FG combination. No obvious systemic toxicity was observed in this study. Finally, our findings provided basis for promising application of OXP and FG combination in colorectal cancer treatment.

17.
Int J Pharm ; 552(1-2): 319-327, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30308269

RESUMO

Colorectal cancer (CRC) exhibited high incidence rate worldwide and the advanced CRC had a poor prognosis. Thereupon, seeking efficient treatment for CRC is critical. Apatinib is a novel vascular epithelial growth factor receptor (VEGFR) inhibitor with inspiring therapeutic effect in some malignant cancers. In our study, doxorubicin was mixed in fibrin gel and apatinib was encapsulated with self-synthesized liposome. The results showed liposomal apatinib (Lipo-Apatinib) could enhance the intracellular uptake of doxorubicin in vitro. Moreover, compared with doxorubicin loaded fibrin gel (DOX-FG) alone, the combination of DOX-FG and Lipo-Apatinib significantly improved the anti-tumor effect in mice CRC subcutaneous model and abdominal metastasis model Drug combination successfully inhibited tumor angiogenesis and tumor proliferation, and also promoted tumor apoptosis. Our data suggested that combined therapy of DOX-FG and Lipo-Apatinib would be a promising treatment approach for CRC.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Doxorrubicina/administração & dosagem , Fibrina/administração & dosagem , Piridinas/administração & dosagem , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Doxorrubicina/química , Combinação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Fibrina/química , Géis , Lipossomos , Camundongos Endogâmicos BALB C , Piridinas/química , Resultado do Tratamento
18.
J Ethnopharmacol ; 188: 229-33, 2016 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-27178631

RESUMO

ETHNOPHARMCOLOGICAL RELEVANCE: Lemonfragrant Angelica (Ostericum citriodorum (Hance) C. Q. Yuan & Shan) is a traditional Chinese herb for treatment of angina pectoris, stomach pain and abdominal pain. However, its active components and mechanisms of action were not well understood. AIMS OF THE STUDY: In this study, we investigated whether the isoapiole extracted from Lemonfragrant Angelica Root (LAR) could directly stimulate the production of nitric oxide (NO) in vascular endothelial cells (VECs) and lead to the vascular relaxation MATERIALS AND METHODS: Vascular activity experiments were performed in aortic rings isolated from Wistar rats using standard muscle bath procedures. Isoapiole was added with different concentrations (0.75, 2.5, 5µg/mL), and vessel relaxation of rat aortic rings pre-contracted with norepinephrine (NE) or potassium chloride was recorded. NO release from aortic rings exposed to isoapiole (5µg/mL) was measured by Griess method. The endothelial nitric oxide synthase (eNOS) expression in primary human umbilical vein endothelial cells (HUVECs) incubated with isoapiole was determined using Western blot and microplate reader assay. Classical receptor antagonists, channel and enzymatic inhibitors were used to check the mechanisms involved. RESULTS: Isoapiole (0.75, 2.5, 5µg/mL) inhibited norepinephrine-induced contraction in endothelium-intact rat aortic rings. However, a very weak relaxation of aortic rings was obtained in endothelium-denuded preparations. Isoapiole (0.75, 2.5, 5µg/mL) did not have vascular relaxative effect on neither endothelium-intact nor endothelium-denuded aortas pre-contracted with KCl (60mmol/L). The vasorelaxation effect of isoapiole on rat aortic rings was attenuated by the eNOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). This result suggested that suggested that the isoapiole action was at least partially mediated by promoting eNOS expression. It was further found that isoapiole (5µg/mL) increased NO production in isolated rat thoracic aorta rings. Isoapiole increased eNOS expression leading to NO production in HUVECs. CONCLUSION: Isoapiole stimulates NO production in the endothelium, leading to vascular dilatation.


Assuntos
Angelica/química , Aorta Torácica/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Aorta Torácica/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/isolamento & purificação , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Técnicas In Vitro , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Ratos Wistar , Fatores de Tempo , Vasodilatadores/isolamento & purificação
19.
Sci Rep ; 6: 23667, 2016 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-27020579

RESUMO

Nickel oxide (NiO) and phosphotungstic acid (PTA) supported on a ZIF-8 (NiO-PTA/ZIF-8) catalyst was first synthesized and it showed high activity and good selectivity for the hydrocracking of Jatropha oil. The catalyst was characterized by SEM, SEM-EDS, TEM, N2 adsorption, FT-IR, XRD and XPS. Compared with the NiO-PTA/Al2O3 catalyst, the selectivity of C15-C18 hydrocarbon increased over 36%, and catalytic efficiency increased 10 times over the NiO-PTA/ZIF-8 catalyst. The prepared NiO-PTA/ZIF-8 catalyst was stable for a reaction time of 104 h and the kinetic behavior was also analyzed. This catalyst was found to bypass the presulfurization process, showing promise as an alternative to sulfided catalysts for green diesel production.

20.
Sci Rep ; 5: 15576, 2015 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-26503896

RESUMO

The development of a novel non-sulfided catalyst with high activity for the hydrotreatment processing of plant oils, is of high interest as a way to improve the efficient production of renewable diesel. To attempt to develop such a catalyst, we first synthesized a high activity flower-like Ni-PTA catalyst used in the hydrotreatment processes of plant oils. The obtained catalyst was characterized with SEM, EDX, HRTEM, BET, XRD, H2-TPR, XPS and TGA. A probable formation mechanism of flower-like Ni(OH)2 is proposed on the basis of a range of contrasting experiments. The results of GC showed that the conversion yield of Jatropha oil was 98.95%, and the selectivity of C11-C18 alkanes was 70.93% at 360 °C, 3 MPa, and 15 h(-1). The activity of this flower-like Ni-PTA catalyst was more than 15 times higher than those of the conventional Ni-PTA/Al2O3 catalysts. Additionally, the flower-like Ni-PTA catalyst exhibited good stability during the process of plant oil hydrotreatment.


Assuntos
Biocombustíveis , Hidróxidos/química , Níquel/química , Óleos de Plantas/química , Catálise
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