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1.
PLoS Pathog ; 20(1): e1011967, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38271479

RESUMEN

Given the serious neurological complications and deaths associated with enterovirus 71 (EV71) infection, there is an urgent need to develop effective antivirals against this viral infection. In this study, we demonstrated that two Cathelicidin-derived peptides, LL-18 and FF-18 were more potent against EV71 infection than the parent peptide LL-37, which is the mature and processed form of Cathelicidin. These peptides could directly bind to the EV71 virus particles, but not to coxsackievirus, indicative of their high specificity. The binding of peptides with the virus surface occupied the viral canyon region in a way that could block virus-receptor interactions and inhibit viral uncoating. In addition, these peptide analogues could also relieve the deleterious effect of EV71 infection in vivo. Therefore, Cathelicidin-derived peptides might be excellent candidates for further development of antivirals to treat EV71 infection.


Asunto(s)
Enterovirus Humano A , Infecciones por Enterovirus , Enterovirus , Humanos , Catelicidinas/farmacología , Internalización del Virus , Antivirales/metabolismo
2.
Biochem Biophys Res Commun ; 722: 150172, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-38805788

RESUMEN

BACKGROUND: Colon cancer is a prevalent invasive neoplasm in the gastrointestinal system with a high degree of malignancy. Despite extensive research, the underlying mechanisms of its recurrence and metastasis remain elusive.Rho GTPase activating protein 4 (ARHGAP4), a member of the small GTPases protein family, may be closely related to tumor metastasis, and its expression is increased in colon cancer. However, the role of ARHGAP4 in colon cancer metastasis is uncertain. This study investigates the impact of ARHGAP4 on the metastasis of colon cancer cells. Our objective is to determine the role of ARHGAP4 in regulating the invasive behavior of colon cancer cells. METHODS: We downloaded colon adenocarcinoma (COAD) data from the Cancer Genome Atlas (TCGA), and performed differential analysis and survival analysis. By using the CIBERSORT algorithm, we evaluated the proportion of infiltrating immune cells in colon cancer. We further analyzed whether ARHGAP4 is associated with T cell exhaustion. Finally, we investigated the impact of ARHGAP4 knockdown on the migration and invasion of colon cancer cells through in vitro cell experiments. Additionally, we utilized western blotting to assess the expression of protein related to the TGF-ß signaling pathway and epithelial-mesenchymal transition (EMT). RESULTS: We found that ARHGAP4 is upregulated in colon cancer. Subsequent survival analysis revealed that the high-expression group had significantly lower survival rates compared to the low-expression group. Immune infiltration analysis showed that ARHGAP4 was not only positively correlated with CD8+ T cells, but also positively correlated with T cell exhaustion markers programmed cell death 1 (PDCD-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and lymphocyte activating 3 (LAG-3). In vitro cell experiments, the knockdown of ARHGAP4 inhibited the migration and invasion of colon cancer cells. Among EMT-related proteins, when ARHGAP4 was knocked down, the expression of E-cadherin was increased, while the expression of N-cadherin and Vimentin was decreased. Meanwhile, the expression of TGF-ß1, p-Smad2, and p-Smad3, which are associated with the TGF-ß/Smad pathway, all decreased. CONCLUSION: ARHGAP4 promotes colon cancer metastasis through the TGF-ß/Smad signaling pathway and may be associated with T cell exhaustion. It plays an important role in the progression of colon cancer and may serve as a potential target for diagnosis and treatment of colon cancer.


Asunto(s)
Neoplasias del Colon , Transición Epitelial-Mesenquimal , Proteínas Activadoras de GTPasa , Transducción de Señal , Factor de Crecimiento Transformador beta , Humanos , Neoplasias del Colon/patología , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Proteínas Activadoras de GTPasa/metabolismo , Proteínas Activadoras de GTPasa/genética , Factor de Crecimiento Transformador beta/metabolismo , Transición Epitelial-Mesenquimal/genética , Línea Celular Tumoral , Movimiento Celular/genética , Metástasis de la Neoplasia , Linfocitos T/metabolismo , Linfocitos T/inmunología , Linfocitos T/patología , Invasividad Neoplásica , Regulación Neoplásica de la Expresión Génica , Agotamiento de Células T
3.
BMC Cancer ; 24(1): 204, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38350902

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is an aggressive tumor of the gastrointestinal tract, which is a major public health concern worldwide. Despite numerous studies, the precise mechanism of metastasis behind its progression remains elusive. As a member of the containing olfactomedin domains protein family, olfactomedin 2 (OLFM2) may play a role in tumor metastasis. It is highly expressed in colorectal cancer, and its role in the metastasis of CRC is still unclear. As such, this study seeks to explore the function of OLFM2 on CRC metastasis and its potential mechanisms. METHODS: Real-time fluorescence quantitative PCR and western blotting were used to study the expression of OLFM2 in human CRC and adjacent normal tissues. Knockdown and overexpression OLFM2 cell lines were constructed using siRNA and overexpression plasmids to explore the role of OLFM2 in the migration and invasion of CRC through transwell, and wound healing experiments. Finally, the expression of epithelial-mesenchymal transition (EMT) -related proteins and TGF-ß/Smad signaling pathway-related proteins was investigated using western blotting. RESULTS: In this study, we observed an elevation of OLFM2 expression levels in CRC tissues. To investigate the function of OLFM2, we overexpressed and knocked down OLFM2. We discovered that OLFM2 knockdown inhibited migration and invasion of colon cancer cells. Furthermore, E-cadherin expression increased while N-cadherin and Vimentin expression were opposite. It is no surprise that overexpressing OLFM2 had the opposite effects. We also identified that OLFM2 knockdown resulted in reduced TGF-ßR1 and downstream molecules p-Smad2 and p-Smad3, which are related to the TGF-ß / Smad pathway. In contrast, overexpressing OLFM2 significantly boosted their expression levels. CONCLUSION: The protein OLFM2 has been identified as a crucial determinant in the progression of CRC. Its mechanism of action involves the facilitation of EMT through the TGF-ß/Smad signaling pathway. Given its pivotal role in CRC, OLFM2 has emerged as a promising diagnostic and therapeutic target for the disease. These results indicate the potential of OLFM2 as a valuable biomarker for CRC diagnosis and treatment and highlight the need for further research exploring its clinical significance.


Asunto(s)
Neoplasias Colorrectales , Humanos , Línea Celular Tumoral , Movimiento Celular/genética , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Transducción de Señal , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta/metabolismo
4.
J Org Chem ; 89(6): 3907-3911, 2024 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-38427963

RESUMEN

A catalytic enantioselective synthesis of bicalutamide derivatives with promising potentials in prostate cancer treatment has been disclosed. The key intermediates, α-hydroxy-ß-keto esters, were efficiently constructed through cinchoninium-mediated asymmetric oxohydroxylation of easily accessible alkenes with potassium permanganate. Good yields and high levels of asymmetric induction are achieved. This method provides a new synthetic route to bicalutamide analogues with high structural diversity, which will beneficially support subsequent structure-activity relationship studies and boost prostate cancer drug development.


Asunto(s)
Anilidas , Nitrilos , Neoplasias de la Próstata , Compuestos de Tosilo , Masculino , Humanos , Estructura Molecular , Estereoisomerismo , Relación Estructura-Actividad
5.
AIDS Care ; 36(4): 561-568, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38088933

RESUMEN

This study used a self-administered questionnaire to investigate the relationship between HIV/AIDS knowledge, social discrimination, HIV self-efficacy, sexual behavioral characteristics and HIV testing behavior among young students with a history of sexual activity in Chongqing. Propensity score matching was used to construct a control group with similar demographic characteristics to the HIV testing group, only without HIV testing behaviors. Structural equation modeling was used to conduct chain-mediated effect analysis. The HIV testing rate among young students with a history of sexual behavior was 17.16%. Young students with HIV testing behavior had higher levels of HIV/AIDS knowledge, lower social discrimination, better self-efficacy, and no difference in sexual behavior characteristic scores between the two groups (P = 0.062). The mediated effect values of social discrimination and self-efficacy were 0.022 and 0.063, respectively, while their chain mediated effect value was 0.007. There was no mediated effect of sexual behavior characteristics. The level of young students' HIV/AIDS knowledge does not directly influence their HIV testing behavior but plays a complete chain mediating effect on HIV testing behavior through social discrimination and self-efficacy. HIV testing behavior should be promoted through the perspectives of enhancing HIV/AIDS knowledge level, reducing social discrimination, and improving self-efficacy.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Humanos , Infecciones por VIH/diagnóstico , Autoeficacia , Análisis de Mediación , Conocimientos, Actitudes y Práctica en Salud , Conducta Sexual , Encuestas y Cuestionarios , Estudiantes , Prueba de VIH , Discriminación Social
6.
BMC Infect Dis ; 24(1): 76, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38212685

RESUMEN

BACKGROUND: Brucellosis poses a significant public health concern. This study explores the spatial and temporal dynamic evolution of human brucellosis in China and analyses the spatial heterogeneity of the influencing factors related to the incidence of human brucellosis at the provincial level. METHODS: The Join-point model, centre of gravity migration model and spatial autocorrelation analysis were employed to evaluate potential changes in the spatial and temporal distribution of human brucellosis in mainland China from 2005 to 2021. Ordinary Least Squares (OLS), Geographically Weighted Regression (GWR), and Multi-scale Geographically Weighted Regression (MGWR) models were constructed to analyze the spatial and temporal correlation between the incidence rate of human brucellosis and meteorological and social factors. RESULTS: From 2005 to 2021, human brucellosis in China showed a consistent upward trend. The incidence rate rose more rapidly in South, Central, and Southwest China, leading to a shift in the center of gravity from the North to the Southwest, as illustrated in the migration trajectory diagram. Strong spatial aggregation was observed. The MGWR model outperformed others. Spatio-temporal plots indicated that lower mean annual temperatures and increased beef, mutton, and milk production significantly correlated with higher brucellosis incidence. Cities like Guangxi and Guangdong were more affected by low temperatures, while Xinjiang and Tibet were influenced more by beef and milk production. Inner Mongolia and Heilongjiang were more affected by mutton production. Importantly, an increase in regional GDP and health expenditure exerted a notable protective effect against human brucellosis incidence. CONCLUSIONS: Human brucellosis remains a pervasive challenge. Meteorological and social factors significantly influence its incidence in a spatiotemporally specific manner. Tailored prevention strategies should be region-specific, providing valuable insights for effective brucellosis control measures.


Asunto(s)
Brucelosis , Animales , Bovinos , Humanos , China/epidemiología , Análisis Espacial , Brucelosis/epidemiología , Regresión Espacial , Ciudades , Incidencia , Análisis Espacio-Temporal
7.
Cereb Cortex ; 33(21): 10723-10735, 2023 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-37724433

RESUMEN

Based on acoustoelectric effect, acoustoelectric brain imaging has been proposed, which is a high spatiotemporal resolution neural imaging method. At the focal spot, brain electrical activity is encoded by focused ultrasound, and corresponding high-frequency acoustoelectric signal is generated. Previous studies have revealed that acoustoelectric signal can also be detected in other non-focal brain regions. However, the processing mechanism of acoustoelectric signal between different brain regions remains sparse. Here, with acoustoelectric signal generated in the left primary visual cortex, we investigated the spatial distribution characteristics and temporal propagation characteristics of acoustoelectric signal in the transmission. We observed a strongest transmission strength within the frontal lobe, and the global temporal statistics indicated that the frontal lobe features in acoustoelectric signal transmission. Then, cross-frequency phase-amplitude coupling was used to investigate the coordinated activity in the AE signal band range between frontal and occipital lobes. The results showed that intra-structural cross-frequency coupling and cross-structural coupling co-occurred between these two lobes, and, accordingly, high-frequency brain activity in the frontal lobe was effectively coordinated by distant occipital lobe. This study revealed the frontooccipital long-range interaction mechanism of acoustoelectric signal, which is the foundation of improving the performance of acoustoelectric brain imaging.


Asunto(s)
Encéfalo , Lóbulo Frontal , Lóbulo Frontal/diagnóstico por imagen , Mapeo Encefálico
8.
BMC Health Serv Res ; 24(1): 756, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38907246

RESUMEN

BACKGROUND: This study reviews the research status of Diagnosis-related groups (DRGs) payment system in China and globally by analyzing topical issues in this field and exploring the evolutionary trends of DRGs in different developmental stages. METHODS: Abstracts of relevant literature in the field of DRGs were extracted from the China National Knowledge Infrastructure (CNKI) database and the Web of Science (WoS) core database and used as text data. A probabilistic distribution-based Latent Dirichlet Allocation (LDA) topic model was applied to mine the text topics. Topical issues were determined by topic intensity, and the cosine similarity of the topics in adjacent stages was calculated to analyze the topic evolution trend. RESULTS: A total of 6,758 English articles and 3,321 Chinese articles were included. Foreign research on DRGs focuses on grouping optimization, implementation effects, and influencing factors, whereas research topics in China focus on grouping and payment mechanism establishment, medical cost change evaluation, medical quality control, and performance management reform exploration. CONCLUSIONS: Currently, the field of DRGs in China is developing rapidly and attracting deepening research. However, the implementation depth of research in China remains insufficient compared with the in-depth research conducted abroad.


Asunto(s)
Grupos Diagnósticos Relacionados , China
9.
BMC Med Educ ; 24(1): 314, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38509547

RESUMEN

BACKGROUND: Colleges and universities face an increased risk of public health emergencies. Among them, medical colleges and universities deserve more attention as they serve as the play a fundamental role in providing public health emergency services and in cultivating medical professionals. Effectively managing infectious disease prevention and control, as well as responding to public health emergencies in medical colleges and universities, is of great importance for enhancing the capacity of social emergency governance and improving the completeness of the public health system. This study aims to understand the management of public health emergencies in medical colleges in a city in southwest China, explore the factors associated with medical college students' evaluations, and provide recommendations for emergency management mechanisms in colleges and universities. METHODS: In total, 781 medical college students were selected through stratified random sampling and surveyed using a questionnaire. The main factors affecting students' evaluation of emergency management were analyzed using multiple linear regression and structural equation modeling. RESULTS: The overall emergency management situation in medical colleges was relatively complete, with satisfactory results. Medical college students' satisfaction with the timeliness of prevention measures was the highest, while the publicity and education were the lowest. Multiple linear regression analysis showed that grades, emergency education, -simulation training, -information reporting, and dynamic adjustment measures were associated with the evaluation of emergency management by medical students. CONCLUSIONS: Although the evaluation of emergency management in medical colleges was generally positive, certain limitations still existed. To improve the development of the public health system, colleges and universities should constantly reform and innovate emergency management mechanisms according to the important links in the prevention and control processes.


Asunto(s)
Estudiantes de Medicina , Humanos , Salud Pública , Estudios Transversales , Urgencias Médicas , Universidades , China
10.
Eur J Haematol ; 111(3): 356-364, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37294015

RESUMEN

BACKGROUND: Patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) have poor outcomes and few treatment options. We report the preliminary results of the efficacy and safety of PD-1 monoclonal antibody (mab) plus Rituximab for r/r DLBCL. METHODS: In this single-center, single-arm phase 2 and retrospective study, r/r DLBCL patients received PD-1 mab and Rituximab every 3 weeks. Immunohistochemistry, fluorescence in situ hybridization, and probe capture-based high-resolution sequencing were performed. Efficacy, safety and prognostic factors were analyzed. RESULTS: Between October 16th, 2018, and July 10th, 2022, 36 patients (10 patients in retrospective study and 26 patients in phase 2 study) were enrolled and received at least one dose of PD-1 mab combined with Rituximab. The objective response rate was 52.8%. The median progression free survival (PFS) and overall survival was 2.8 and 19.6 months, respectively. The median duration of response was 18.7 months. Rare grade 3 or 4 treatment related adverse events were observed. B2M mutations correlated with a significantly poor PFS (p = .013) and OS (p = .009) in DLBCL patients treated with this regimen. CONCLUSION: PD-1 mab combined with Rituximab could be a potential treatment option for r/r DLBCL with manageable safety profile.


Asunto(s)
Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Rituximab/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Receptor de Muerte Celular Programada 1 , Estudios Retrospectivos , Hibridación Fluorescente in Situ , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico
11.
Entropy (Basel) ; 25(7)2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37509966

RESUMEN

This study aims to unravel the resource allocation problem (RAP) by using a consensus-based distributed optimization algorithm under dynamic event-triggered (DET) strategies. Firstly, based on the multi-agent consensus approach, a novel one-to-all DET strategy is presented to solve the RAP. Secondly, the proposed one-to-all DET strategy is extended to a one-to-one DET strategy, where each agent transmits its state asynchronously to its neighbors. Furthermore, it is proven that the proposed two types of DET strategies do not have Zeno behavior. Finally, numerical simulations are provided to validate and illustrate the effectiveness of the theoretical results.

12.
J Org Chem ; 87(12): 7945-7954, 2022 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-35671227

RESUMEN

An unprecedented multicomponent domino reaction of [60]fullerene, indole, and DMSO/HCl has been developed for the one-pot efficient synthesis of diverse N-substituted [60]fulleroindole derivatives. This methodology features simple operation, low cost, and transition-metal-circumvented and good functional group tolerance in indole.

13.
Phys Chem Chem Phys ; 24(44): 27173-27183, 2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36321450

RESUMEN

Herein, we have employed linear-response time dependent density functional theory (LR-TDDFT)-based nonadiabatic dynamics simulations to investigate the ultrafast charge transfer in a nonfullerene all-small-molecule donor-acceptor (D-A) system formed by a porphyrin small-molecule donor ZnP and a recently developed nonfullerene small-molecule acceptor 6TIC, during which the optimally tuned range-separated hybrid (OT-RSH) functional was adopted. In combination with static electronic structure calculations, several important conclusions were drawn. Firstly, the ZnP and 6TIC are more likely combined together non-covalently in parallel rather than in perpendicular to form ZnP-6TIC due to the much larger adsorption energies, i.e. -44.6 kcal mol-1vs. -25.2 kcal mol-1. Secondly, the excited state properties obtained by OT-RSH functionals seem more consistent with the experimental results compared to their untuned versions. Specifically, the energy of the lowest charge transfer (CT) state was predicted to be smaller than the lowest lying local excitation (LE) states using the OT-RSH functional-based LR-TDDFT calculations, which is beneficial for the charge transfer process that might be crucial for the high power conversion efficiency (PCE) achieved experimentally. In contrast, the untuned RS functionals all predict higher CT state energies, which is contradictory to the high PCE obtained in the experiment. Moreover, strong hybridization upon excitation between these states was revealed, which might be one of the reasons responsible for the high PCE observed in the experiment. Finally, ultrafast excited state relaxation can be completed within 500 fs due to the small energy gaps and the strong nonadiabatic couplings between these states, which is accompanied by ultrafast photoinduced electron transfer from ZnP to 6TIC and photoinduced hole transfer the other way around. The efficient charge transfer processes and the involvement of two charge generation channels might be another cause resulting in the excellent photovoltaic performance of ZnP-6TIC based OSCs. Our present work not only provides solid evidence for elucidating the underlying mechanism observed in previous experiments, but also suggests that the combination of OT-RSH functionals and LR-TDDFT-based nonadiabatic dynamics simulations might be a powerful tool for investigating the excited state dynamics of organic D-A systems, which is crucial for the theoretical design of novel OSCs with better performances in the future.

14.
Phys Chem Chem Phys ; 24(36): 22115-22121, 2022 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-36074741

RESUMEN

The device performance is reported for three compounds which show both thermally activated delayed fluorescence and liquid crystallinity, and use the donor 3,6-bis(3,4-didodecyloxyphenyl)carbazole. Two of the compounds, whose photophysics were reported previously, are based on a terephthalonitrile acceptor. A third and new compound is based on an isophthalonitrile acceptor and shows a more temperature-accessible mesophase and enhanced solution emission quantum yield. Two of the compounds show device external quantum efficiencies of between 2-3% and exhibit very small efficiency roll off. The responses are evaluated in terms of the specific nature of the materials.

15.
Prep Biochem Biotechnol ; 52(6): 648-656, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34694209

RESUMEN

In the present study, ultrasound-assisted extraction was employed to extract the general flavone from celery leaves using response surface methodology and BP neural network model with a genetic algorithm (GA). The effects of temperature, time, solid-liquid ratio, and ethanol concentration on the extraction results were assessed by Box-Behnken design. Further optimization of the process was performed by GA-BP. Our results showed that the optimal conditions were an ethanol concentration of 70.31%, a temperature of 67.2 °C and an extraction time of 26.6 min. In addition, significant antioxidant activity and in vitro bacteriostasis were observed. We found that the total flavonoids of the celery leaves exerted a strong inhibitory effect on Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. Additionally, considerable DPPH· and ·OH scavenging effects were exerted by flavonoids. Therefore, flavonoids from celery leaves can be considered natural antioxidants and bacterial inhibitors.


Asunto(s)
Apium , Flavonoides , Extractos Vegetales , Hojas de la Planta , Algoritmos , Apium/química , Bacillus subtilis/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Etanol/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Redes Neurales de la Computación , Extractos Vegetales/farmacología , Hojas de la Planta/química , Staphylococcus aureus/efectos de los fármacos , Temperatura , Factores de Tiempo
16.
Nanotechnology ; 31(13): 135209, 2020 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-31860898

RESUMEN

In this paper, wafer-scale dense and meosoporous TiO2 films are fabricated via spin-coating and thermal treatment. A photo-curable resin, acrylated polytitanoxane tetramer (Ti-resin), is synthesized as the precursor of TiO2 to deposit dense films. The refractive index of TiO2 films at 500 nm is tuned from 2.17 (dense) to 1.49 (porous) by changing film porosity via adding different amount of polystyrene (PS) to the precursor solvent. A reactive compatibilizer containing one mercapto group and three benzyl rings is synthesized to reduce phase separation and prevent film crack of porous films during the calcinations. The deposition protocol is optimized to prevent infiltration of dense TiO2 layers into porous TiO2 layers. Film thicknesses of both dense and porous TiO2 films can be linearly tuned by changing deposition number. All-TiO2 1D photonic crystals with different structural colors are successfully fabricated on quartz and silicon wafers with reflectivity of at least 90%, covering the spectrum from 400 to 800 nm.

17.
Cancer Sci ; 110(5): 1676-1685, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30838724

RESUMEN

Long noncoding RNA (lncRNA) DLEU2 has been shown to be dysregulated in several type of tumor. However, the potential biological roles and molecular mechanisms of DLEU2 in pancreatic cancer (PC) progression are poorly understood. In this study, we found that the DLEU2 level was substantially upregulated in PC tissues and PC cell lines, and significantly associated with poor clinical outcomes in PC patients. Overexpression of DLEU2 significantly induced PC cell proliferation and invasion, whereas knockdown of DLEU2 impaired cell proliferation and invasion in vitro. Furthermore, bioinformatics analysis, luciferase reporter assay, and RNA immunoprecipitation assay revealed that DLEU2 directly bond to microRNA-455 (miR-455) and functioned as an endogenous sponge for miR-455, which could remarkably suppress cell growth and invasion. We also determined that SMAD2 was a direct target of miR-455, and the restoration of SMAD2 rescued cell growth and invasion that were reduced by DLEU2 knockdown or miR-455 overexpression. In addition, low miR-455 expression and high SMAD2 expression was correlated with poor patient survival. These results indicate that DLEU2 is an important promoter of PC development, and targeting the DLEU2/miR-455/SMAD2 pathway could be a promising therapeutic approach in the treatment of PC.


Asunto(s)
MicroARNs/genética , Neoplasias Pancreáticas/genética , Proteína Smad2/genética , Proteínas Supresoras de Tumor/genética , Regulación hacia Arriba , Regiones no Traducidas 3' , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , Invasividad Neoplásica , Neoplasias Pancreáticas/metabolismo , ARN Largo no Codificante , Análisis de Supervivencia , Transferasas , Proteínas Supresoras de Tumor/metabolismo
18.
Biochem Biophys Res Commun ; 495(1): 1122-1128, 2018 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29175212

RESUMEN

AIMS: An unhealthy diet is a major risk factor for cardiac diseases. Most researches focus on high fat diet, little is known about the detrimental effects of starvation on heart. METHODS: Mice were fed 100%, 40% and 20% of ad libitum to mimic the situation of moderate and severe caloric restriction (CR). To further evaluate the different effect of CR and starvation on cardiomyocyte, AC16 cells were treated with different concentrations of serum or glucose. TUNEL staining was performed to evaluate DNA damage in AC16 cells. HE and Masson staining were performed to detect the morphology and degree of fibrosis in myocardium from mice. Immunohistochemical staining, immunofluorescence staining, western blot and real-time PCR were used to detect the protein and mRNA expression of caspase-1, IL-1ß and IL-18. RESULTS: CR and starvation decrease body weight of mice in a concentration dependent manner. The starvation group showed a remarkable myocardial fibrosis with no significant alteration between control and CR groups. CR inhibited the activation of caspase-1 as well as the expression of IL-1ß and IL-18. On the contrary, starvation plays completely opposite effects, which was in accordance with histological changes. Similarly, different levels of serum and glucose deprivation were used to mimic the effect of CR and starvation in vitro. Moderate level of serum and glucose deprivation exerts protective effect on AC16 cells through the inhibition of pyroptosis, whereas high level of serum and glucose deprivation induces cell injury through the induction of pyroptosis. CONCLUSION: CR alleviates pyroptosis, whereas starvation promotes the progression of pyroptosis in myocardial tissues and cells.


Asunto(s)
Restricción Calórica/métodos , Corazón/fisiopatología , Miocardio/patología , Piroptosis , Inanición/patología , Inanición/fisiopatología , Animales , Peso Corporal , Masculino , Ratones , Ratones Endogámicos C57BL
19.
Psychopathology ; 51(3): 167-176, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29444522

RESUMEN

AIMS: This study aimed to investigate the mediating pathway of 3 factors (psychotic symptoms, attitude toward medication, and cognitive processing speed) on the effect of insight on personal-social functioning in patients with schizophrenia. METHODS: Chinese inpatients with schizophrenia (n = 168; mean age 18 ± 50 years) diagnosed according to the DSM-IV were randomly assigned to treatment with antipsychotic medication alone or combined treatment. Positive and Negative Syndrome Scale (PANSS), Drug Attitude Inventory (DAI), Assessment of Insight (SAI), and Social-Personal Performance Scale (PSPS) scores were evaluated at baseline and at 3, 6, and 12 months. Cognitive function was assessed at baseline. Multiple mediation analyses were conducted with baseline data, end point data, and changes-in-scale scores between baseline and the end point, respectively. RESULTS: At baseline and at 12 months, only psychotic symptoms mediated the effect of insight on personal-social functioning. For changes-in-scale scores over the 12-month follow-up, in patients receiving treatment with medication alone, the effect of improved insight on improved personal-social function was mediated by psychotic symptoms only; in patients receiving a combined treatment, the effect of improved insight on improved personal-social functioning was mediated by both psychotic symptoms and attitudes toward medication, independently. CONCLUSIONS: The link between insight and personal-social functions is mainly mediated by psychotic symptoms. Psychosocial intervention improves the predicting effect of insight on personal-social function by improving both the attitude toward medication and psychotic symptoms independently.


Asunto(s)
Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/diagnóstico , Ajuste Social , Adolescente , Adulto , Anciano , Antipsicóticos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/patología , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
20.
Environ Sci Technol ; 51(10): 5572-5581, 2017 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-28426211

RESUMEN

A limited number of ground measurements of dry particulate nitrate deposition (NO3-) makes it difficult and challenging to fully know the status of the spatial and temporal variations of dry NO3- depositions over China. This study tries to expand the ground measurements of NO3- concentrations at monitoring sites to a national scale, based on the Ozone Monitoring Instrument (OMI) NO2 columns, NO2 profiles from an atmospheric chemistry transport model (Model for Ozone and Related chemical Tracers, version 4, MOZART-4) and monitor-based sources, and then estimates the NO3- depositions on a regional scale based on an inferred model. The ground NO2 concentrations were first derived from NO2 columns and the NO2 profiles, and then the ground NO3- concentrations were derived from the ground NO2 concentrations and the relationship between NO2 and NO3- based on Chinese Nationwide Nitrogen Deposition Monitoring Network (NNDMN). This estimated dry NO3- depositions over China will be helpful in determining the magnitude and pollution status in regions without ground measurements, supporting the construction plan of environmental monitoring in future.


Asunto(s)
Contaminantes Atmosféricos , Monitoreo del Ambiente , Nitratos , China , Nitrógeno
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