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1.
Small ; : e2405550, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39240003

RESUMEN

The exploration of new properties and functionality of covalent organic frameworks (COFs) rely mostly on the covalent modification of the starting building blocks or linkages. Noncovalent forces that guide the assembly and adhesion of layers to develop two-dimensional (2D) COFs and improve their bulk properties and functionalities, however, are rarely explored. Herein, the "conformational lock" (CL) effect in 2D hydrazine-linked COFs with intralayer F-H interaction is discovered and regulated to stabilize interlayer adhesion and develop a facile strategy to increase their stability, promote selectivity and efficiency in reactive singlet oxygen (1O2)-triggered photocatalytic transformation when acting as photocatalysts. The CL strategy endows the fluorinated COFs with an efficient intersystem crossing process for 1O2 generation and strong interlayer π-π stacking interaction. The 4F-COF with the strongest F-H noncovalent interaction exhibits the highest photocatalytic conversion and selectivity (exceeding 98%) in typical 1O2-dependent transformations, even over 7 continuous photocatalytic cycles. This work demonstrates that promoting intralayer noncovalent interaction in 2D-COFs can impart high photocatalytic activity and stability, and would vigorously inspire their developments in heterogeneous catalysis.

2.
Future Oncol ; : 1-19, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39129672

RESUMEN

Aim: Vascular endothelial growth factor receptor inhibitors (VEGFRIs) have been common used for recurrent ovarian cancer (ROC), but insufficient high-level evidence on verifying its efficacy and safety. Methods: Randomized controlled trials (RCTs) were searched under eight electronic databases. Stata 14.0 and Review Manager 5.3 were used for data analysis. Certainty of the evidence was assessed using the GRADE profiler. This systematic review (SR) was registered under INPLASY (INPLASY202120019). Conclusion: Totally 23 RCTs involving 2810 patients were included in this SR. Current evidence revealed that VEGFRIs had better efficacy, survival and quality of life in the treatment of ROC. Though VEGFRIs increase some drug-related adverse events (AEs), all the AEs could be manageable in the clinical practice.


The expression of VEGF/VEGF receptors (VEGFRs) in ovarian cancer (OC) tissue was found to be higher than in benign or normal ovarian tissue. Therefore angiogenesis inhibitors play an essential role in OC treatment. Many anti-angiogenic agents have been developed in recent years. The role of small-molecule inhibitors of VEGFRs for recurrent OC (ROC) has demonstrated significant antitumor efficacy. These drugs include Nintedanib, Axitinib, Pazopanib, Sorafenib, Vandetanib, Sunitinib, Cediranib, Ramucirumab and Apatinib, and more are in the way. However, insufficient high-level evidence from systematic reviews (SRs) focused on VEGFRIs for ROC. Therefore, we performed an SR to investigate the efficacy and safety of VEGFRIs for patients with ROC. This SR was registered under INPLASY (INPLASY202120019). Totally 23 RCTs involving 2810 patients were included in this SR. The results indicate that VEGFRIs have better efficacy and survival in the treatment of ROC. Though VEGFRIs increase some drug-related adverse events, all the adverse events could be manageable in clinical practice.

3.
Angew Chem Int Ed Engl ; 63(28): e202402694, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38679569

RESUMEN

Solar-driven upgrading of biomass-derived 5-hydroxylmethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) holds great promise for sustainable production of bio-plastics and resins. However, the process is limited by poor selectivity and sluggish kinetics due to the vertical coordination of HMF at relatively strong metal sites. Here, we purposely developed a Cu(II) porphyrin framework featuring side-chain incorporated urea linkages, denoted as TBUPP-Cu MOF, to render HMF a weak hydrogen bond at the urea site and flat adsorption via π-π stacking with the benzene moiety. The unique configuration promotes the approaching of -CHO of HMF to the photoexcited porphyrin ring towards kinetically and thermodynamically favourable intermediate formation and subsequent desorption. The charge localisation and orbital energy alignment enable the selective activation of O2 over the porphyrin to generate ⋅O2 - and 1O2 instead of highly oxidative H2O2 and ⋅OH via spin-flip electron transfer, which drive the ambient oxidation of proximal -CHO. The effective utilisation of redox species and circumvented over-oxidation facilitate a FDCA selectivity of >90 % with a high turnover number of 193 molHMF molCu -1. The facile purification of high-purity FDCA and zero-waste recycling of intermediates and durable catalyst feature TBUPP-Cu MOF a promising photo-oxidation platform towards net-zero biorefining and organic transformations.

4.
J Environ Manage ; 344: 118756, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37573697

RESUMEN

Microplastics (MPs), as an emerging pollutant, pose a significant threat to humans and ecosystems. However, traditional MPs characterization methods are limited by sample requirements and characterization time. Machine Learning (ML) has emerged as a vital technology for analyzing MPs pollution due to its accuracy, broad application, and powerful feature extraction. Nevertheless, environmental scientists require threshold knowledge before using ML, restricting the ML application in MPs research. Furthermore, imbalanced development of ML in MPs research is a pressing concern. In order to achieve a wide ML application in MPs research, in this review, we comprehensively discussed the size and sources of MPs datasets in relevant literature to help environmental scientists deepen their understanding of the construction of MPs datasets. Commonly used ML algorithms are analyzed from the perspective of interpretability and the need for computer facilities. Additionally, methods for improving and evaluating ML model performance, such as dataset pre-processing, model optimization, and model assessment metrics, are discussed. According to datasets and characterization techniques, MPs identification using ML was divided into three categories in this work: spectral identification, image identification, and spectral imaging identification. Finally, other applications of ML in MPs studies, including toxicity analysis, pollutants adsorption, and microbial colonization, are comprehensively discussed, which reveals the great application potential of ML. Based on the discussion above, this review suggests an algorithm selection strategy to assist researchers in selecting the most suitable ML algorithm in different situations, improving efficiency and decreasing the costs of trial and error. We believe that this work sheds light on the application of ML in MPs study.


Asunto(s)
Contaminantes Ambientales , Contaminantes Químicos del Agua , Humanos , Microplásticos , Plásticos , Ecosistema , Contaminación Ambiental/análisis , Contaminantes Ambientales/análisis , Contaminantes Químicos del Agua/análisis
5.
J Cell Mol Med ; 25(3): 1633-1644, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33449451

RESUMEN

Glioblastoma (GBM) is a malignant brain tumour with poor prognosis. The potential pathogenesis and therapeutic target are still need to be explored. Herein, TCGA expression profile data and clinical information were downloaded, and the WGCNA was conducted. Hub genes which closely related to poor prognosis of GBM were obtained. Further, the relationship between the genes of interest and prognosis of GBM, and immune microenvironment were analysed. Patients from TCGA were divided into high- and low-risk group. WGCNA was applied to the high- and low-risk group and the black module with the lowest preservation was identified which could distinguish the prognosis level of these two groups. The top 10 hub genes which were closely related to poor prognosis of patients were obtained. GO analysis showed the biological process of these genes mainly enriched in: Cell cycle, Progesterone-mediated oocyte maturation and Oocyte meiosis. CDCA5 and CDCA8 were screened out as the genes of interest. We found that their expression levels were closely related to overall survival. The difference analysis resulted from the TCGA database proved both CDCA5 and CDCA8 were highly expressed in GBM. After transfection of U87-MG cells with small interfering RNA, it revealed that knockdown of the CDCA5 and CDCA8 could influence the biological behaviours of proliferation, clonogenicity and apoptosis of GBM cells. Then, single-gene analysis was performed. CDCA5 and CDCA8 both had good correlations with genes that regulate cell cycle in the p53 signalling pathway. Moreover, it revealed that high amplification of CDCA5 was correlated with CD8+ T cells while CDCA8 with CD4+ T cells in GBM. These results might provide new molecular targets and intervention strategy for GBM.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Perfilación de la Expresión Génica/métodos , Glioblastoma/genética , Glioblastoma/mortalidad , Apoptosis/genética , Neoplasias Encefálicas/patología , Biología Computacional/métodos , Bases de Datos Genéticas , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Glioblastoma/patología , Humanos , Pronóstico , Reproducibilidad de los Resultados , Transcriptoma
6.
Biochem Biophys Res Commun ; 578: 77-83, 2021 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-34547627

RESUMEN

Lysine crotonylation (Kcr) is a newly identified protein translational modification and is involved in major biological processes including glycolysis, but its role in colorectal cancer (CRC) is unknown. Here, we found that the Kcr of α enolase (ENO1) was significantly elevated in human CRC tissues compared with the paratumoral tissues. CREB-binding protein (CBP) functioned as a crotonyltranferase of ENO1, and SIRT2 was involved in the decrotonylation of ENO1. Using quantitative mass spectrometry for crotonylomics analysis, we further found that K420 was the main Kcr site of ENO1 and ENO1 K420 Kcr promoted the growth, migration, and invasion of CRC cells in vitro by enhancing the activity of ENO1 and regulating the expression of tumor-associated genes. Our study reveals an important mechanism by which ENO1 regulates CRC through crotonylation.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Proteína de Unión a CREB/metabolismo , Neoplasias Colorrectales/metabolismo , Proteínas de Unión al ADN/metabolismo , Lisina/metabolismo , Fosfopiruvato Hidratasa/metabolismo , Procesamiento Proteico-Postraduccional , Sirtuina 2/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Biomarcadores de Tumor/genética , Proteína de Unión a CREB/genética , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Proteínas de Unión al ADN/genética , Humanos , Espectrometría de Masas , Metástasis de la Neoplasia , Fosfopiruvato Hidratasa/genética , Sirtuina 2/genética , Proteínas Supresoras de Tumor/genética , Regulación hacia Arriba
7.
J Toxicol Pathol ; 34(1): 95-99, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33627949

RESUMEN

Glioblastoma (GBM) is a highly aggressive central nervous system cancer. Its extracranial metastases have rarely been reported in the past few decades. Moreover, the pathogenesis of extracranial GBM metastases remains unclear. Here, we report a case of pulmonary metastasis in a male Wistar rat of C6 GBM model. This reported Wistar male rat was one of the experimental control group without any other intervention except for C6 GBM cells orthotopic implantation. On postoperative day 15, the animal which was reported in this study showed highly cellular, pleomorphic, tumor with nuclear atypia in the brain (Ki67, approximately 65.7%) and lungs (Ki67, 49.5%). Tumor cells in the lung showed immunoreactivity for glial fibrillary acidic protein. Inflammatory CD68+ cell infiltration, weakly positive E-cadherin, and strongly positive staining for vimentin were observed both in tumors in the brain and lungs. Based on further morphological analysis, we speculate that the potential metastatic route into the lung might be hematogenous metastasis.

8.
Comput Intell Neurosci ; 2022: 5718050, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35958743

RESUMEN

In order to explore the real effect of art mental health therapy, this paper proposes a feature selection algorithm based on genetic algorithm. The algorithm takes college students as the research object and discusses the effect of psychotherapy on college students through painting art therapy. The results showed that there were extremely significant differences in EPQ extraversion factors among the people treated with the educational intervention of art psychology course (P < 0.01), and there was no significant change in other factors (P > 0.05). There was no significant change in total depression score and depression index (P > 0.05). There were significant differences in social avoidance factors and social anxiety (P < 0.05), and there were relatively significant differences in the total score of sadness (P < 0.01). It is concluded that the use of artistic elements can effectively help people express themselves and express their psychological emotions, which has a certain effect in mental health treatment.


Asunto(s)
Arte , Psicoterapia , Algoritmos , Emociones , Humanos , Psicoterapia/métodos , Estudiantes
9.
Artículo en Inglés | MEDLINE | ID: mdl-35886247

RESUMEN

Air pollution is a major health hazard. The traditional habits and unique ethnic fire culture in Hunan Tujia region result in the long-term exposure of residents, especially elderly people, to pollutants. In this study, we conducted field monitoring and assessment of indoor pollutants in the residential houses of Hunan Tujia families and subsequently visualised and simulated fire pollutants in representative residential houses by using fire-dynamic-simulator software. Pollutant-control strategies, using passive smoke collectors and resizing windows, were proposed and simulated for validation. The results revealed that passive smoke collectors reduced the pollutant concentration in the hall house by 43.96%. Furthermore, the optimal window size was 1500 mm × 1500 mm, and the most reasonable windowsill height of the firepit was 1800 mm. The results of the study can be used to improve the indoor air quality of Tujia dwellings and mitigate the adverse health effects of exposure to indoor air pollution without restricting ethnic beliefs and traditional customs.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Contaminación del Aire , Anciano , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , China , Humanos , Material Particulado/análisis
10.
Artículo en Inglés | MEDLINE | ID: mdl-36078529

RESUMEN

This study uses behavioral observation, interviews, and questionnaire research to investigate the residential environment. It also evaluates the elderly in four representative ancient towns of Xiangxi, namely, Liye Ancient Town, Furong Ancient Town, Liexi Ancient Town, and Xichehe Ancient Town. It includes indoor air (CO2, PM2.5, PM10) and light intensity monitoring for the residential environment. The results showed that the elderly had a significant sense of frustration and loneliness. Of the elderyly, 70% believed the current living environment had an impact on healthy living, and 45% believed the safety and convenience of the living environment should be improved. More than 80% of the elderly were dissatisfied with their indoor acoustic environment, and more than 70% were dissatisfied with their home transportation. More than 85% of the elderly considered traditional wooden components and spaces to be the source of cultural identity. Furthermore, the average indoor PM2.5 concentration during the fire pit fire was 350-600 µg/m3, about 4.7-8 times the Chinese standard value. The average concentration of PM10 in all rooms was more than 400 µg/m3, approximately three times the Chinese standard value. Also, targeted environmental improvement strategies were proposed. The study results provided actual information to develop a systematic approach and a targeted design based on the needs to improve the residential environment of the elderly in ancient cities.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Anciano , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Ciudades , Monitoreo del Ambiente/métodos , Humanos , Tamaño de la Partícula , Material Particulado/análisis , Encuestas y Cuestionarios
11.
Inflamm Res ; 60(2): 169-74, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20963624

RESUMEN

OBJECTIVE AND DESIGN: The carbohydrate moieties of glycoprotein are associated with some inflammatory diseases by affecting a wide range of biological functions of cells. This study aimed to investigate the role of ß-1,4-galactosyltransferase-I (ß-1,4-GalT-I) in adhesion of Schwann cells during inflammation. SUBJECTS: A rat Schwann cell line, RSC 96 was used. METHODS: We used western blotting to detect the expression of ß-1,4-GalT-I. Flow cytomety was used to measure the galactosylation of glycoproteins on cell surfaces. Immunofluorescent staining was used to examine the expression of α6 integrin, focal adhesion kinase (FAK) and F-actin. Tyrosine phosphorylation of FAK was detected by immunoprecipitation. An adhesion assay was performed to investigate the adhesion of Schwann cells. One-way ANOVA was used to compare differences between the operated and the control group. RESULTS: Schwann cell adhesion was induced by LPS stimulation and was accompanied by upregulation of ß-1,4-GalT-I expression and galactosylation of glycoproteins. There was a change of localization of FAK and cytoskeleton organization in LPS treated cells compared with control cells. The pretreated cells enhanced tyrosine phosphorylation of FAK compared with control cells in the adhesion process. With the increased cell surface expression of α6 integrin and ß-1,4-GalT-I, the adhesion of Schwann cells on laminin was increased as well. CONCLUSIONS: These results suggested that ß-1,4-GalT-I may play an important role in adhesion of Schwann cells during inflammation.


Asunto(s)
Adhesión Celular/efectos de los fármacos , Lipopolisacáridos/farmacología , N-Acetil-Lactosamina Sintasa/metabolismo , Células de Schwann/efectos de los fármacos , Células de Schwann/fisiología , Animales , Línea Celular , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Integrina alfa6/metabolismo , Laminina/metabolismo , Glicoproteínas de Membrana/metabolismo , Ratas , Células de Schwann/citología , Transducción de Señal/fisiología , Tirosina/metabolismo
12.
J Cancer ; 12(11): 3257-3264, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33976735

RESUMEN

Purpose: Tumor blood vessels exhibit morphological and functional aberrancies. Its maturity and functionality are closely associated with colon cancer progression and therapeutic efficacy. The direct evidence proving whether oridonin (ORI) has vascular normalization promoting effect from which combination therapies will benefit is still lacking. Methods: We established a subcutaneous xenograft model of human colon cancer. The animals were divided into the Control and ORI-treated groups. Immunohistochemical analysis and TUNEL staining was applied to evaluate the proliferation, apoptosis and angiogenesis. Western blot analysis was employed to characterize the angiogenesis-related factors and JAK2/STAT3 signaling. Then, vascular normalization and macrophage reprogramming were assessed by immunofluorescence analysis. Results: The results showed that ORI obviously reduced tumor growth, diminished the numbers of Ki67+ cells and CD31+ microvessel density, while increased the numbers of TUNEL+ cells. The expression levels of VEGF and bFGF proteins were dramatically down-regulated while the angiostatin and endostatin levels were increased in the ORI-treated group. Moreover, ORI therapy remarkably promoted the pericyte coverage of tumor vessels from days 5 to 10, with the highest pericyte coverage rate occurred at day 7. In the time window of vascular normalization, hypoxia of the tumor microenvironment was improved by ORI, the expression of HIF-1a was downregulated. Moreover, CD206+ macrophage cells were diminished in the ORI-treated group. These anticancer effects of ORI maybe partly mediated by suppressing JAK2/STAT3 signaling pathway. Conclusions: These results highlight the potential effect of ORI on anti-angiogenesis and inducing vessel normalization roles of ORI, and probably provide optimum time point for the ORI therapy in conjunction with the chemoradiotherapy or immunotherapy.

13.
Medicine (Baltimore) ; 100(49): e27850, 2021 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-34889235

RESUMEN

INTRODUCTION: CRC, the incidence of the fourth highest among males and the third among females, is one of the malignant tumors that seriously threaten human health. The principle of treatment for advanced stage CRC is a multidisciplinary and comprehensive treatment based on chemotherapy, which always bring significant toxic side effects. CHM has advantages in the treatment of tumors with the effect on improving clinical symptoms and reducing side effects. GGQL formula is mainly used for treating abnormal defecates caused by damp-heat, so we will evaluate the clinical efficacy and safety of modified GGQL formula for patients with advanced CRC with the type of damp-heat in this study. METHODS: Multicenter RCT with two parallel groups in three hospitals planning to recruit 120 CRC patients with the type of damp-heat will be conducted. The control group will be treated by basic antitumor therapy and the treatment group will use modified GGQL formula plus basic antitumor therapy. The primary outcomes will be quality of life, TCM symptom score, PFS and OS, and the secondary outcomes will be performance status, size of tumor, tumor marker in the serum, tumor microenvironment and immune status. All analyses will be based on an intention-to-treat principle. This study was approved by the Human Research Ethics Committee of Shanxi Province Hospital of Traditional Chinese medicine (2021Y-06017). The results will be published in relevant journal. DISCUSSION: The results of this RCT will contribute to Chinese herbal medicine for treating CRC patients with the type of damp heat accumulation. TRIAL REGISTRATION: ChiCTR2100050754 (September 4, 2021).


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/psicología , Método Doble Ciego , Femenino , Calor , Humanos , Masculino , Medicina Tradicional China , Persona de Mediana Edad , Calidad de Vida/psicología , Resultado del Tratamiento , Microambiente Tumoral
14.
J Neurosci Res ; 88(9): 1858-71, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20155814

RESUMEN

Src-suppressed C kinase substrate (SSeCKS) is involved in inflammation in the central nervous system (CNS), and plays a role in control of cell signaling and cytoskeletal arrangement. However, the expression and function of SSeCKS and its function in multiple sclerosis (MS) and its common animal model, experimental autoimmune encephalomyelitis (EAE) remained to be elucidated. In the present study, we first reported that SSeCKS was remarkably increased in astrocytes of EAE rats in vivo. TNF-alpha and NO were significantly induced in astrocytes stimulated with LPS/IFN-gamma in vitro, which was blocked in astrocytes transfected with SSeCKS siRNA. These results indicated that SSeCKS played a role in the production of TNF-alpha and NO in astrocytes with inflammatory stimulation. As excessive release of TNF-alpha and NO were major mediators in autoimmune diseases and correlated with oligodendrocyte cell death, we further investigated whether SSeCKS participated in oligodendrocyte apoptosis. Conditioned media (CM) from astrocytes treated with LPS/IFN-gamma decreased oligodendrocyte cell viability, while siRNA targeted to SSeCKS in astrocytes inhibited oligodendrocyte cell death. The results from antibody neutralization and NO inhibition suggested that the oligodendrocyte apoptosis may be due to the production of astrocyte-derived proinflammatory factors (TNF-alpha and NO). These findings revealed that there was a pathogenic interaction between SSeCKS expression in astrocytes and oligodendrocyte apoptosis. Understanding the mechanism of SSeCKS in the pathogenesis of EAE may contribute to the development of new therapeutic strategies against EAE and MS.


Asunto(s)
Proteínas de Anclaje a la Quinasa A/metabolismo , Apoptosis , Proteínas de Ciclo Celular/metabolismo , Encefalomielitis Autoinmune Experimental/fisiopatología , Neuroglía/fisiología , Óxido Nítrico/metabolismo , Oligodendroglía/fisiología , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas de Anclaje a la Quinasa A/genética , Animales , Astrocitos/metabolismo , Proteínas de Ciclo Celular/genética , Células Cultivadas , Medios de Cultivo Condicionados , Femenino , Cobayas , Interferón gamma/metabolismo , Lipopolisacáridos/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Endogámicas Lew , Ratas Sprague-Dawley , Médula Espinal/fisiopatología
15.
Inflamm Res ; 59(11): 921-9, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20495845

RESUMEN

OBJECTIVE: The aim of this paper was to investigate the inhibitory effect of peroxisome proliferator-activated receptor-gamma (PPARγ) agonist pioglitazone on microglia inflammation induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: Highly aggressively proliferating immortalized cells were used from a rat microglial cell line. Expression of PPARγ, inducible NO synthase (iNOS), the p42/44 extracellular signal-regulated kinase (ERK) MAPKs, c-Jun NH2-terminal kinases (JNKs) and p38 MAPK were determined by Western blot analysis. The protein levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were determined by enzyme-linked immunosorbent assay. The production of nitric oxide (NO) was determined by a Nitric Oxide Assay Kit. The subcellular localization of PPARγ was studied by immunofluorescence microscopy analysis and nuclear-cytosolic fractionation technology, respectively. The transcriptional activity of PPARγ was detected by PPRE-Luciferase transcription assay. RESULTS: Pioglitazone effectively inhibited NO, iNOS, TNF-α, IL-6, IL-1ß production in LPS-stimulated microglial cells. Additionally, pioglitazone suppressed PPARγ loss; enhanced transcriptional activity of PPARγ; and inhibited nucleus-export of PPARγ in microglia induced by LPS. And p38 MAPK inhibitor SB203580 had the similarity effects with pioglitazone. Signal transduction studies indicated that pioglitazone blocked the phosphorylation of p38 MAPK challenged by LPS. CONCLUSION: The results show that pioglitazone can inhibit LPS-stimulated microglia inflammation by blocking p38 MAPK signaling pathway.


Asunto(s)
Inflamación/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Microglía/efectos de los fármacos , Microglía/patología , PPAR gamma/agonistas , Tiazolidinedionas , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Animales , Línea Celular , Citocinas/inmunología , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Interleucina-1beta/biosíntesis , Interleucina-6/biosíntesis , Lipopolisacáridos/farmacología , Microglía/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , PPAR gamma/metabolismo , Pioglitazona , Ratas , Tiazolidinedionas/farmacología , Tiazolidinedionas/uso terapéutico , Factor de Necrosis Tumoral alfa/biosíntesis
16.
Oncol Res ; 27(8): 871-877, 2019 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-30832751

RESUMEN

Second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), afatinib, has been approved for treating EGFR mutant lung cancer patients, but the mechanism of acquired resistance to afatinib has not been well studied. In this study, we established afatinib acquired resistant cell lines. Gene array technology was used to screen changes in gene expression between afatinib-resistant lung cancer cells and parental cells. Our results showed that secreted phosphoprotein 1 (SPP1) was significantly increased in afatinib-resistant lung cancer cells. To study the effect of SPP1 on afatinib resistance, siSPP1 was used to knock down SSP1 in afatinib-resistant lung cancer cells. Then sensitivity to afatinib and invasive ability were studied. We found that knockdown of SPP1 increased sensitivity of lung cancer cells to afatinib and decrease the ability of invasion. Of clinical significance, we found that SSP1 was upregulated in lung cancer tissues compared with adjacent normal tissues, and low level of SSP1 was strongly associated with better overall survival. Our results suggest that SPP1 enhanced the second-generation EGFR TKI resistance in lung cancer, and inhibiting SPP1 might be a therapeutic target to overcome afatinib resistance.


Asunto(s)
Afatinib/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Osteopontina/genética , Afatinib/efectos adversos , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/genética , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratones , Mutación/genética , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Osteopontina/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Inflammation ; 33(3): 189-99, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20066559

RESUMEN

Schwann cells proliferation is the main characterize of kinds PNS inflammation diseases. It has been well documented that cyclin D3 /CDK11(p58) complex inhibits cell function through multiple mechanisms, but the mechanism of cyclin D3/CDK11(p58) complex exerts its repressive role in the Schwann cells proliferation remains to be identified. In the present investigation, we demonstrated that the expression of CDK11(p58) were upregulated in the inflammation caused by LPS, a main part of bacteria. Cyclin D3 and the 58-kDa isoform of cyclin-dependent kinase 11 (CDK11(p58)) interacted with each other mainly in nuclear region, repressed Schwann cells proliferation and induced cell apoptosis. Overexpression of CDK11(p58) expression might enhance this process, while silence of cyclin D3 reverting it. This work demonstrates for the first time the role of cyclin D3/CDK11(p58) complex in repressing the Schwann cells proliferation and inducing its apoptosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Ciclina D3/metabolismo , Lipopolisacáridos/farmacología , Células de Schwann , Animales , Caspasa 3/metabolismo , División Celular/efectos de los fármacos , División Celular/fisiología , Línea Celular , Núcleo Celular/metabolismo , Técnica del Anticuerpo Fluorescente , Ratas , Células de Schwann/citología , Células de Schwann/efectos de los fármacos , Células de Schwann/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología
18.
J Neuroimmunol ; 218(1-2): 36-47, 2010 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-19942298

RESUMEN

In bacterial-induced peripheral nervous system (PNS) inflammation, Schwann cells (SCs) are activated, producing inducible nitric oxide synthase (iNOS), contributed to the pathogenesis of demyelinating disease, such as multiple sclerosis. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been shown to play a protective role in cellular inflammatory responses. Here we showed that LPS-induced iNOS biosynthesis was in a concentration and time-dependent manner. In LPS-treated primary SCs, retreatment with PPAR-gamma agonist remitted the increase of iNOS, p38 phosphorylation and TLR4, MyD88, augmented the expression of PPAR-gamma and localization in nuclear. Coadministration of GW 9662 reversed the effect of PPAR-gamma agonists. These results suggest that PPAR-gamma agonists, 15d-PGJ(2) and pioglitazone, had the anti-inflammatory effects.


Asunto(s)
Lipopolisacáridos/farmacología , Óxido Nítrico Sintasa de Tipo II/biosíntesis , PPAR gamma/agonistas , Células de Schwann/metabolismo , Transducción de Señal/fisiología , Anilidas/farmacología , Animales , Antiinflamatorios/farmacología , Western Blotting , Línea Celular , Regulación hacia Abajo , Inhibidores Enzimáticos/farmacología , Técnica del Anticuerpo Fluorescente , Factor 88 de Diferenciación Mieloide/biosíntesis , Factor 88 de Diferenciación Mieloide/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , PPAR gamma/efectos de los fármacos , Pioglitazona , Prostaglandina D2/análogos & derivados , Prostaglandina D2/farmacología , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Tiazolidinedionas/farmacología , Receptor Toll-Like 4/biosíntesis , Receptor Toll-Like 4/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
19.
Inflammation ; 32(5): 279-86, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19548074

RESUMEN

beta4 Galactosylation of glycoproteins is one of the most important post-translational modifications. Recent studies have demonstrated that aberrant galactosylation associates with some inflammation diseases. beta-1,4-galactosyltransferase-I (beta-1,4-GalT-I), which transfers galactose to the terminal N-acetylglucosamine of N- and O-linked glycans in a beta-1,4- linkage, considered to be the major galactosyltransferse among the seven members of the subfamily responsible for beta4 galactosylation. In the present study, we investigated the expression of beta-1,4-GalT-I in Schwann cells under Lipopolysaccharide (LPS) treatment. RT-PCR revealed that the beta-1,4-GalT-I mRNA was significant increased as early as 2 h after LPS stimulation. Immunofluorescence showed that beta-1,4-GalT-I was located in Golgi apparatus and membrane of Schwann cells. With the 1 microg/ml LPS treatment, expression levels of beta-1,4-GalT-I was much higher compared with control group. In addition, lectin blot indicated that the beta4 galactosylation of glycoproteins such as integrin alpha5 was enhanced, which may due to the induced beta-1,4-GalT-I expression. These results suggested that beta-1,4-GalT-I may play an important role in adhesion and migration of Schwann cells during inflammation.


Asunto(s)
Galactosiltransferasas/genética , Galactosiltransferasas/metabolismo , Lipopolisacáridos/farmacología , N-Acetil-Lactosamina Sintasa/genética , N-Acetil-Lactosamina Sintasa/metabolismo , Células de Schwann/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Animales , Línea Celular , Fluoresceína-5-Isotiocianato/metabolismo , Técnica del Anticuerpo Fluorescente Directa , Colorantes Fluorescentes/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/enzimología , Inflamación/patología , Lipopolisacáridos/metabolismo , Ratas
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