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1.
Dev Dyn ; 252(5): 605-628, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36606464

RESUMEN

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP), a rare disease characterized by progressive heterotopic ossification of muscle and connective tissues, is caused by autosomal dominant activating mutations in the type I receptor, ACVR1/ALK2. The classic human FOP variant, ACVR1R206H , shows increased bone morphogenetic protein (BMP) signaling and activation by activins. RESULTS: Here, we performed in vivo functional characterization of human ACVR1R206H and orthologous zebrafish Acvr1lR203H using early embryonic zebrafish dorsoventral patterning as a phenotypic readout for receptor activity. Our results showed that human ACVR1R206H and zebrafish Acvr1lR203H exhibit functional differences in early embryonic zebrafish, and that human ACVR1R206H retained its signaling activity in the absence of a ligand-binding domain (LBD). We also showed, for the first time, that zebrafish Acvr2ba/Acvr2bb receptors are required for human ACVR1R206H signaling in early embryonic zebrafish. CONCLUSIONS: Together, these data provide new insight into ACVR1R206H signaling pathways that may facilitate the design of new and effective therapies for FOP patients.


Asunto(s)
Receptores de Activinas Tipo I , Embrión no Mamífero , Miositis Osificante , Osificación Heterotópica , Animales , Humanos , Receptores de Activinas Tipo I/genética , Mutación , Transducción de Señal , Pez Cebra , Embrión no Mamífero/metabolismo
2.
Crit Rev Eukaryot Gene Expr ; 33(2): 27-40, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36734855

RESUMEN

Non-small-cell lung cancer (NSCLC) is the major subtype of lung cancer, with a series of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and proteins involved in its pathogenesis. This study sought to investigate the functionality of lncRNA EPB41L4A antisense RNA 1 (lncRNA EPB41L4A-AS1) in the proliferation of NSCLC cells and provide a novel theoretical reference for NSCLC treatment. Levels of lncRNA EPB41L4A-AS1, miR-105-5p, and GTPase, IMAP family member 6 (GIMAP6) in tissues and cells were measured by RT-qPCR and the correlation between lncRNA EPB41L4A-AS1 and clinicopathological characteristics was analyzed. Cell proliferation was evaluated by cell counting kit-8 and colony formation assays. The subcellular localization of lncRNA EPB41L4A-AS1 was analyzed by the subcellular fractionation assay and the binding of miR-105-5p to lncRNA EPB41L4A-AS1 or GIMAP6 was analyzed by dual-luciferase and RNA pull-down assays. Functional rescue experiments were performed to analyze the role of miR-105-5p/GIMAP6 in NSCLC cell proliferation. lncRNA EPB41L4A-AS1 and GIMAP6 were downregulated while miR-105-5p was upregulated in NSCLC tissues and cells. lncRNA EPB41L4A-AS1 was correlated with tumor size and clinical staging and its overexpression reduced NSCLC cell proliferation. lncRNA EPB41L4A-AS1 was negatively correlated with miR-105-5p and positively correlated with GIMAP6 in NSCLC tissues, and lncRNA EPB41L4A-AS1 sponged miR-105-5p to promote GIMAP6 transcription in NSCLC cells. Overexpression of miR-105-5p or knockdown of GIMAP6 reversed the inhibition of lncRNA EPB41L4A-AS1 overexpression on NSCLC cell proliferation. lncRNA EPB41L4A-AS1 was downregulated in NSCLC and mitigated NSCLC cell proliferation through the miR-105-5p/GI-MAP6 axis.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Humanos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismo
3.
J Vasc Interv Radiol ; 34(1): 108-115, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36182001

RESUMEN

PURPOSE: To compare the efficacy, adverse reactions, quality of life, and patient satisfaction of percutaneous radiofrequency (RF) thoracic sympatholysis at different rib-based anatomic targets for primary palmar hyperhidrosis (PPHH). MATERIALS AND METHODS: Patients with PPHH were divided according to the target, namely, the upper edge (Group U) and lateral border (Group L) of the fourth rib; there were 30 patients (mean age, 24.9 years; women, 31, 51.7%) and 60 cases in each group. The Hyperhidrosis Disease Severity Scale (HDSS) and Dermatology Life Quality Index (DLQI) were assessed. RESULTS: From before RF sympatholysis to 12 months after, the proportion of patients with HDSS Grades III and IV (100%-26.7%) and the DLQI (19.78 ± 5.08 to 4.98 ± 4.18) decreased significantly (P < .001). At 3, 6, and 12 months after RF, the HDSS grades were better in Group L than in Group U (P = .005, .002, and .004). At 6 and 12 months after RF, the DLQI in Group L was lower than that in Group U (P = .012 and .016), and at 1, 6, and 12 months after RF, patient satisfaction was higher than that in Group U (P = .025, .014, and .009). Adverse events were mild; 8 patients (13.3%) demonstrated compensatory hyperhidrosis at 12 months after RF, and there was no difference between the 2 groups (P = .448); neuralgia and pneumothorax also did not differ (P = .522 and .643). CONCLUSIONS: RF sympatholysis targeting the lateral border of the fourth rib had higher efficacy, better quality of life, and higher patient satisfaction.


Asunto(s)
Hiperhidrosis , Calidad de Vida , Humanos , Femenino , Adulto Joven , Adulto , Resultado del Tratamiento , Estudios Retrospectivos , Simpaticolíticos , Satisfacción del Paciente , Hiperhidrosis/terapia , Hiperhidrosis/cirugía , Simpatectomía/efectos adversos
4.
Anim Biotechnol ; 34(9): 4580-4587, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36794322

RESUMEN

This study aimed to identify the target genes of IGFBP3(insulin growth factor binding protein)protein and to investigate its target genes effects on the proliferation and differentiation of Hu sheep skeletal muscle cells. IGFBP3 was an RNA-binding protein that regulates mRNA stability. Previous studies have reported that IGFBP3 promotes the proliferation of Hu sheep skeletal muscle cells and inhibits differentiation, but the downstream genes that bind to it have not been reported yet. We predicted the target genes of IGFBP3 through RNAct and sequencing data, and verified by qPCR and RIP(RNA Immunoprecipitation)experiments, and demonstrated GNAI2(G protein subunit alpha i2)as one of the target gene of IGFBP3. After interference with siRNA, we carried out qPCR, CCK8, EdU, and immunofluorescence experiments, and found that GNAI2 can promote the proliferation and inhibit differentiation of Hu sheep skeletal muscle cells. This study revealed the effects of GNAI2 and provided one of the regulatory mechanisms of IGFBP3 protein underlying sheep muscle development.


Asunto(s)
Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Fibras Musculares Esqueléticas , Animales , Ovinos/genética , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Fibras Musculares Esqueléticas/metabolismo , ARN Interferente Pequeño , Diferenciación Celular , Proliferación Celular/genética , Músculo Esquelético/metabolismo
5.
Anim Biotechnol ; 34(7): 2691-2700, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36001393

RESUMEN

This study aimed to understand the expression level of YAP1 in the skeletal muscle of Hu sheep and to reveal the regulatory mechanism of YAP1 on Hu sheep skeletal muscle satellite cells (SMSCs). Previous research by our group has found that YAP1 may affect the growth and development of Hu sheep skeletal muscle. In the present study, we found the expression of YAP1 in the skeletal muscle is higher than in other tissues of Hu sheep. Then, we detected the effect of YAP1 on proliferation and differentiation in Hu sheep SMSCs. According to the results of qPCR, CCK-8, EDU, and Western blot, compared to the group of negative control, overexpression of YAP1 promoted the proliferation and inhibited the differentiation of SMSCs according to the results of qPCR, CCK-8, EDU, Western blot, while the interference of YAP1 was on the contrary. Overall, our study suggests that YAP1 is an important functional molecule in the growth and development of skeletal muscle by regulating the proliferation and differentiation of SMSCs. These findings are of great use for understanding the roles of YAP1 in the skeletal muscle of Hu sheep.


Asunto(s)
Células Satélite del Músculo Esquelético , Animales , Diferenciación Celular , Proliferación Celular , Músculo Esquelético , Ovinos
6.
Curr Psychol ; 42(8): 6912-6932, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34226810

RESUMEN

Pro-environmental behavior (PEB) has always been a hot topic in academic and practical, and it is highly necessary to explore the research progress and development trend of PEB. Based on 1038 relevant literatures published and the Web of Science core database, this paper used citation analysis, co-word analysis and cluster analysis methods to systematically analyze the dynamic evolution process of PEB's research topics, knowledge base and subject areas. The results show that PEB research is currently in a period of rapid growth. And PEB research presents typical multidisciplinary characteristics, mainly focuses on Psychology-Education-Social, Economics-Economic-Political, Environmental-Toxicology-Nutrition and other disciplines. Then, this study also finds that the PEB research hotspots mainly concentrated in seven directions such as "Environmental cognition, emotion and motivation process", etc., which can be further classified into three horizontal levels and three vertical levels. This study will provide valuable theoretical and practical reference for the future research of PEB.

7.
BMC Health Serv Res ; 22(1): 1453, 2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36451145

RESUMEN

BACKGROUND: Mental health problems have become a public health problem that needs to be solved in China. However, medical resources for mental healthcare remain insufficient and unevenly distributed. The Chinese central government has taken many measures to address this issue over the last decade. This study aimed to evaluate the changes in equity in mental health bed allocation from 2011 to 2020. METHODS: The data of this study came from the China Health Statistical Yearbook (2012-2021) and the China National Administrative Division Information Platform. The annual growth rate was used to evaluate the time trends of mental health beds. The Lorenz curve, Gini coefficient and Theil index were used to assess equity in the demographic and geographical dimensions. The distribution of mental health beds was visualized on a map using geographic information system (GIS) software. RESULTS: The total number of mental health beds in China increased steadily from 2011 to 2020. At the national level, the Gini coefficient and Theil index all exhibited downward trends over time. The mental health bed allocation in terms of the demographic dimension was relatively equitable, with Gini values all less than 0.3; however, the Gini coefficients by geographical area were all more than 0.6, indicating inequity. Intraregional contribution rates were higher than interregional contribution rates, which were all above 60%. CONCLUSION: The overall distribution equity of mental health beds improved from 2011 to 2020. The equity of mental health beds in terms of population size is superior to that in terms of geographical area. Intraregional differences are the main source of inequity. In particular, differences within the western region need to be given attention. Thus, the findings from this study emphasize that the demographic and geographical distributions and all influencing factors should be considered when the government makes mental health resource allocation policies.


Asunto(s)
Política de Salud , Salud Mental , Humanos , China/epidemiología , Densidad de Población , Pueblo Asiatico
8.
Mar Drugs ; 20(3)2022 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-35323512

RESUMEN

Four new dimeric sorbicillinoids (1-3 and 5) and a new monomeric sorbicillinoid (4) as well as six known analogs (6-11) were purified from the fungal strain Hypocrea jecorina H8, which was obtained from mangrove sediment, and showed potent inhibitory activity against the tea pathogenic fungus Pestalotiopsis theae (P. theae). The planar structures of 1-5 were assigned by analyses of their UV, IR, HR-ESI-MS, and NMR spectroscopic data. All the compounds were evaluated for growth inhibition of tea pathogenic fungus P. theae. Compounds 5, 6, 8, 9, and 10 exhibited more potent inhibitory activities compared with the positive control hexaconazole with an ED50 of 24.25 ± 1.57 µg/mL. The ED50 values of compounds 5, 6, 8, 9, and 10 were 9.13 ± 1.25, 2.04 ± 1.24, 18.22 ± 1.29, 1.83 ± 1.37, and 4.68 ± 1.44 µg/mL, respectively. Additionally, the effects of these compounds on zebrafish embryo development were also evaluated. Except for compounds 5 and 8, which imparted toxic effects on zebrafish even at 0.625 µM, the other isolated compounds did not exhibit significant toxicity to zebrafish eggs, embryos, or larvae. Taken together, sorbicillinoid derivatives (6, 9, and 10) from H. jecorina H8 displayed low toxicity and high anti-tea pathogenic fungus potential.


Asunto(s)
Ascomicetos/efectos de los fármacos , Agentes de Control Biológico , Hypocreales/química , Policétidos , Animales , Ascomicetos/crecimiento & desarrollo , Agentes de Control Biológico/química , Agentes de Control Biológico/aislamiento & purificación , Agentes de Control Biológico/farmacología , Agentes de Control Biológico/toxicidad , Camellia sinensis/microbiología , Embrión no Mamífero , Estructura Molecular , Policétidos/química , Policétidos/aislamiento & purificación , Policétidos/farmacología , Policétidos/toxicidad , Pez Cebra
9.
BMC Anesthesiol ; 21(1): 308, 2021 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-34876004

RESUMEN

BACKGROUND: Pain control after hepatectomy is usually achieved by opioids. There are significant individual differences in the amount of opioids used after hepatectomy, and the metabolism of opioids is liver-dependent. The purpose of our study was to explore the possible risk factors for opioid consumption during the first 48 h after surgery. METHODS: In a retrospective study design involving 562 patients undergoing open or laparoscopic hepatectomy, all patients were treated with intravenous patient-controlled analgesia (IV-PCA) along with continuous and bolus doses of sufentanil for a duration of 48 h after surgery during the time period of August 2015 and February 2019. The primary endpoint was high sufentanil consumption 48 h after hepatectomy, and patients were divided into two groups: those with or without a high PCA sufentanil dosage depending on the third quartile (Q3). The secondary endpoint was the effect of a high PCA sufentanil dosage on various possible clinical risk factors. The relevant parameters were collected, and correlation and multivariate regression analyses were performed. RESULTS: The median operation time was 185 min (range, 115-250 min), and the median consumption of sufentanil 48 h after the operation was 91 µg (IQR, 64.00, 133.00). Factors related to the consumption of sufentanil at 48 h after hepatectomy included age, operation time, blood loss, intraoperative infusion (red blood cells and fresh-frozen plasma), pain during movement after surgery (day 1 and day 2), preoperative albumin, and postoperative blood urea nitrogen. Age (≤ 60 and > 60 years), extent of resection (minor hepatic resection and major hepatic resection), surgical approach (laparoscope and open) and operation time (min) were independent risk factors for sufentanil consumption at 48 h postoperatively. CONCLUSION: Age younger than 60 years, major hepatic resection, an open approach and a longer operation are factors more likely to cause patients to require higher doses of sufentanil after hepatectomy, and the early identification of such patients can increase the efficacy of perioperative pain management.


Asunto(s)
Analgesia Controlada por el Paciente/métodos , Analgésicos Opioides/uso terapéutico , Hepatectomía/métodos , Dolor Postoperatorio/tratamiento farmacológico , Sufentanilo/uso terapéutico , Factores de Edad , Anciano , Analgésicos Opioides/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Retrospectivos , Factores de Riesgo , Sufentanilo/administración & dosificación
10.
World J Surg Oncol ; 19(1): 260, 2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34465365

RESUMEN

OBJECTIVE: The study aimed to compare the Steroid 5 alpha-reductase 3 (SRD5A3) expression levels in breast cancer (BC) and normal tissues, to investigate the prognostic value of SRD5A3 mRNA expression in BC patients and to identify the SRD5A3-related signaling pathways using bioinformatics approaches. METHODS: We evaluated the expression levels of SRD5A3 and survival data in BC patients using different bioinformatic databases. Further, Cox regression analysis was conducted to predict the independent prognostic factors for BC. Moreover, the association of SRD5A3 with clinicopathological factors was measured through LinkedOmics database. And the potential role of SRD5A3 was determined by Gene Ontology and KEGG pathway enrichment analysis. Finally, protein network of SRD5A3 was constructed and genetic alterations were analyzed. RESULTS: Bioinformatic data indicated that both mRNA and protein expression levels of SRD5A3 were higher in BC group than those in the normal group (P < 0.05). Besides, BC patients with higher SRD5A3 mRNA expression levels had a lower overall survival (all P < 0.05). Cox regression analysis further demonstrated the independent prognostic value of SRD5A3 in BC (P = 0.015). SRD5A3 mRNA expression was significantly associated with N stage (P < 0.001), age (P < 0.05), and histologic subtype (P < 0.001) but had no significant relationship with other clinical characteristics (all P > 0.05). Moreover, the functional enrichment analysis revealed that the SRD5A3 was involved in metabolism-related pathways (all P < 0.05). CONCLUSIONS: SRD5A3 was highly expressed in BC tissues and high SRD5A3 expression was related to poorer prognosis. SRD5A3 serves as an oncogene and might function as a potential biomarker for prognosis and a therapeutic target for BC.


Asunto(s)
Neoplasias de la Mama , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/genética , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Biología Computacional , Femenino , Ontología de Genes , Humanos , Proteínas de la Membrana/genética , Pronóstico , ARN Mensajero/genética
11.
Biomed Chromatogr ; 35(4): e5020, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33159321

RESUMEN

Chronic inflammation pain is a debilitating disease, and its mechanism still remains poorly understood. This study attempted to illuminate the metabolic mechanism of chronic inflammation pain induced by complete Freund's adjuvant (CFA) injection, especially at spinal level. The chronic inflammation pain model was established by CFA administration. Behavioral testing including mechanical allodynia and thermal hyperalgesia was performed. Meanwhile, a liquid chromatography-mass spectrometry-based metabolomics approach was applied to analyze potential metabolic biomarkers. The orthogonal partial least squares discrimination analysis mode was employed for determining metabolic changes, and a western blot was performed to detect the protein expression change. The results showed that 27 metabolites showed obviously abnormal expression and seven metabolic pathways were significantly enriched, comprising aminoacyl-tRNA biosynthesis, arginine and proline metabolism, histidine metabolism, purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glutathione metabolism, and phenylalanine metabolism. Meanwhile, the results showed that the expression of arginase I and nitric oxide levels were elevated in the CFA group compared with the control group, while the argininosuccinate synthetase and argininosuccinatelyase proteins were not significantly different between the groups. These findings demonstrate that metabolic changes of the spinal cord may be implicated in neurotransmitter release and pain conductivity following CFA administration.


Asunto(s)
Adyuvante de Freund , Inflamación , Metaboloma/efectos de los fármacos , Metabolómica/métodos , Dolor , Animales , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Adyuvante de Freund/efectos adversos , Adyuvante de Freund/farmacología , Hiperalgesia , Inflamación/inducido químicamente , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Dolor/inducido químicamente , Dolor/metabolismo , Médula Espinal/química , Médula Espinal/metabolismo
12.
Sheng Li Xue Bao ; 71(6): 917-934, 2019 Dec 25.
Artículo en Zh | MEDLINE | ID: mdl-31879747

RESUMEN

Exosome is a kind of nanoscale-size extracellular vesicles secreted by the means of cell active stimulation with outer membrane structure of vacuoles corpuscle. It can carry and transfer a lot of biological molecules, such as DNA fragments, circular RNA (circRNA), messenger RNA (mRNA), microRNA (miRNA), functional proteins, transcription factors, etc., so as to achieve the goal of information transmission between cells. The relationship between exosomes and diabetes has received extensive attention in recent years. The exosomes play an important role in insulin sensitivity, glucose homeostasis and vascular endothelial function. This paper reviews the role of exosomes in the occurrence and development of diabetes and its complications, and discusses the role and prospect of exosomes as a target for diabetes treatment and its role in the diagnosis and treatment of diabetes.


Asunto(s)
Diabetes Mellitus , Exosomas , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/fisiopatología , Diabetes Mellitus/terapia , Exosomas/metabolismo , Humanos , Resistencia a la Insulina/fisiología , MicroARNs/metabolismo , ARN Mensajero/metabolismo
13.
Entropy (Basel) ; 21(5)2019 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-33267235

RESUMEN

Aimed at distinguishing different fault categories of severity of rolling bearings, a novel method based on feature space reconstruction and multiscale permutation entropy is proposed in the study. Firstly, the ensemble empirical mode decomposition algorithm (EEMD) was employed to adaptively decompose the vibration signal into multiple intrinsic mode functions (IMFs), and the representative IMFs which contained rich fault information were selected to reconstruct a feature vector space. Secondly, the multiscale permutation entropy (MPE) was used to calculate the complexity of reconstructed feature space. Finally, the value of multiscale permutation entropy was presented to a support vector machine for fault classification. The proposed diagnostic algorithm was applied to three groups of rolling bearing experiments. The experimental results indicate that the proposed method has better classification performance and robustness than other traditional methods.

14.
Entropy (Basel) ; 21(7)2019 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-33267394

RESUMEN

This study presents a comprehensive fault diagnosis method for rolling bearings. The method includes two parts: the fault detection and the fault classification. In the stage of fault detection, a threshold based on refined composite multiscale dispersion entropy (RCMDE) at a local maximum scale is defined to judge the health state of rolling bearings. If the bearing is in fault, a generalized multi-scale feature extraction method is developed to fully extract fault information by combining fast ensemble empirical mode decomposition (FEEMD) and RCMDE. Firstly, the fault vibration signals are decomposed into a set of intrinsic mode functions (IMFs) by FEEMD. Secondly, the RCMDE value of multiple IMFs is calculated to generate a candidate feature pool. Then, the maximum-relevance and minimum-redundancy (mRMR) approach is employed to select the sensitive features from the candidate feature pool to construct the final feature vectors, and the final feature vectors are fed into random forest (RF) classifier to identify different fault working conditions. Finally, experiments and comparative research are carried out to verify the performance of the proposed method. The results show that the proposed method can detect faults effectively. Meanwhile, it has a more robust and excellent ability to identify different fault types and severity compared with other conventional approaches.

15.
Biochem Biophys Res Commun ; 503(4): 2293-2300, 2018 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-29964012

RESUMEN

Cisplatin (CDDP)-based systematic chemotherapy remains the mainstay of treatment for muscle-invasive bladder cancer (MIBC). However, acquired resistance to CDDP, a multifactorial process governed by an array of signals acting at different levels, is the major problem in BC treatment. Here, we report for the first time that, expression of Paired-box gene 5 (PAX5), a B-cell essential transcription factor, was significantly induced in CDDP-resistant BC tissues and in experimentally-induced CDDP-resistant BC cells. Inhibition of PAX5 expression by shRNA treatment effectively improved CDDP sensitivity in BC cells, whereas overexpression of PAX5 potentiated CDDP resistance through supporting BC cell survival. Mechanistically, using luciferase reporter and chromatin immunoprecipitation assays, we identified prostaglandin-endoperoxide synthase 2 (PTGS2, also called COX2), a potent enzyme responsible for prostanoids formation and inflammatory response, as the direct down-stream target of PAX5. PAX5 exerted its oncogenic function during the pathogenesis of CDDP resistance via stimulation of PTGS2 transcription. These observations collectively suggest that dysregulation of PAX5/PTGS2 cascade plays a causal role in the induction of CDDP resistance and gene silencing approaches targeting this pathway may therefore provide a novel therapeutic strategy for overcoming CDDP resistance in BC.


Asunto(s)
Cisplatino/farmacología , Ciclooxigenasa 2/genética , Resistencia a Antineoplásicos/genética , Factor de Transcripción PAX5/genética , Activación Transcripcional , Neoplasias de la Vejiga Urinaria/patología , Humanos , Neoplasias de los Músculos/secundario , Invasividad Neoplásica , Transducción de Señal , Células Tumorales Cultivadas
16.
Infect Immun ; 84(9): 2627-38, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27354447

RESUMEN

Trypanosoma cruzi infection drives the expansion of remarkably focused CD8(+) T cell responses targeting epitopes encoded by variant trans-sialidase (TS) genes. Infection of C57BL/6 mice with T. cruzi results in up to 40% of all CD8(+) T cells committed to recognition of the dominant TSKB20 and subdominant TSKB18 TS epitopes. However, despite this enormous response, these mice fail to clear T. cruzi infection and subsequently develop chronic disease. One possible reason for the failure to cure T. cruzi infection is that immunodomination by these TS-specific T cells may interfere with alternative CD8(+) T cell responses more capable of complete parasite elimination. To address this possibility, we created transgenic mice that are centrally tolerant to these immunodominant epitopes. Mice expressing TSKB20, TSKB18, or both epitopes controlled T. cruzi infection and developed effector CD8(+) T cells that maintained an activated phenotype. Memory CD8(+) T cells from drug-cured TSKB-transgenic mice rapidly responded to secondary T. cruzi infection. In the absence of the response to TSKB20 and TSKB18, immunodominance did not shift to other known subdominant epitopes despite the capacity of these mice to expand epitope-specific T cells specific for the model antigen ovalbumin expressed by engineered parasites. Thus, CD8(+) T cell responses tightly and robustly focused on a few epitopes within variant TS antigens appear to neither contribute to, nor detract from, the ability to control T. cruzi infection. These data also indicate that the relative position of an epitope within a CD8(+) immunodominance hierarchy does not predict its importance in pathogen control.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Enfermedad de Chagas/inmunología , Glicoproteínas/inmunología , Inmunidad/inmunología , Epítopos Inmunodominantes/inmunología , Neuraminidasa/inmunología , Trypanosoma cruzi/inmunología , Animales , Enfermedad de Chagas/parasitología , Epítopos de Linfocito T/inmunología , Ratones , Ratones Endogámicos C57BL
17.
Tumour Biol ; 37(6): 7615-23, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26687647

RESUMEN

As the first member of glycylcycline bacteriostatic agents, tigecycline is approved as a novel expanded-spectrum antibiotic, which is clinically available. However, accumulating evidence indicated that tigecycline was provided with the potential application in cancer therapy. In this paper, tigecycline was shown to exert an anti-proliferative effect on neuroblastoma cell lines. Furthermore, it was found that tigecycline induced G1-phase cell cycle arrest instead of apoptosis by means of Akt pathway inhibition. In neuroblastoma cell lines, the Akt activator insulin-like growth factor-1 (hereafter referred to as IGF-1) reversed tigecycline-induced cell cycle arrest. Besides, tigecycline inhibited colony formation and suppressed neuroblastoma cells xenograft formation and growth. After tigecycline treatment in vivo, the Akt pathway inhibition was confirmed as well. Collectively, our data provided strong evidences that tigecycline inhibited neuroblastoma cells growth and proliferation through the Akt pathway inhibition in vitro and in vivo. In addition, these results were supported by previous studies concerning the application of tigecycline in human tumors treatment, suggesting that tigecycline might act as a potential candidate agent for neuroblastoma treatment.


Asunto(s)
Antibacterianos/farmacología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Minociclina/análogos & derivados , Neuroblastoma/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Biomarcadores de Tumor/metabolismo , Western Blotting , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Técnicas In Vitro , Factor I del Crecimiento Similar a la Insulina/metabolismo , Ratones , Ratones SCID , Minociclina/farmacología , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/metabolismo , Fosforilación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Tigeciclina , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
18.
J Tradit Chin Med ; 36(1): 107-12, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26946627

RESUMEN

OBJECTIVE: To investigate the changes in the neuronal microenvironment of the middle cerebral artery (MCA) territory induced by Jing-well points bloodletting acupuncture (WPBA) and to explore the neuroprotective mechanism of WPBA in stroke. METHODS: Adult male Sprague Dawley (n = 32) rats were randomly divided into four groups of eight animals each: WPBA-thalamus group (WT), WPBA-caudate nucleus group (WC), sham-control thalamus group (ST) and sham-control caudate nucleus group (SC). Animals in the WT and WC groups received 2 µL of the extracellular tracer gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) injected into the thalamus or caudate nucleus, respectively, and 12 Jing-well points in the distal ends of the rats' digits were used for WPBA. Although 2 µL of Gd-DTPA was injected into the thalamus or caudate nucleus, respectively, for animals in the two sham groups (ST and SC), no acupuncture or bloodletting was performed. Brain extracellular space and interstitial fluid flow parameters were measured using Gd-DTPA-enhanced magnetic resonance imaging. RESULTS: The brain interstitial fluid flow speed was decreased in the thalamus after WPBA, with a significantly lower Gd-DTPA clearance rate and longer half-life of Gd-DTPA in the thalamus of treated rats than those in sham-control rats [WPBA-treated rats' clearance rate, (7.47 ± 3.15) x 10(-5)/s (P.= 0.009); half-life, (1.52 ± 0.13) h, P = 0.000]. By contrast, no significant changes in brain extracellular space and interstitial fluid flow parameters were detected in the caudate nucleus after WPBA (P = 0.649). In addition, no differences in the morphology of the brain extracellular space or the final distribution of the traced brain interstitial fluid were demonstrated between the WT and WC groups (P = 0.631, P = 0.970, respectively). CONCLUSION: The WPBA decreased the speed of the local thalamic ISF flow in rats, which is assumed to be a beneficial protection by down-modulated the metabolic rate of the attacked neurons under stroke.


Asunto(s)
Puntos de Acupuntura , Venodisección , Líquido Extracelular/metabolismo , Accidente Cerebrovascular/terapia , Tálamo/metabolismo , Animales , Humanos , Masculino , Ratas , Ratas Sprague-Dawley , Accidente Cerebrovascular/metabolismo , Tálamo/irrigación sanguínea
19.
Angew Chem Int Ed Engl ; 55(11): 3667-71, 2016 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-26880151

RESUMEN

One-dimensional (1D) micro- and nanostructured electrode materials with controllable phase and composition are appealing materials for use in lithium-ion batteries with high energy and power densities, but they are challenging to prepare. Herein, a novel ethanol-water mediated co-precipitation method by a chimie douce route (synthesis conducted under mild conditions) has been exploited to selectively prepare an extensive series of manganese-based electrode materials, manifesting the considerable generalizability and efficacy of the method. Moreover, by simply tuning the mixed solvent and reagents, transition metal oxide bars with differing aspect ratios and compositions were prepared with an unprecedented uniformity. Application prospects are demonstrated by Li-rich 0.5 Li2 MnO3 ⋅0.5 LiNi1/3 Co1/3 Mn1/3 O2 bars, which demonstrate excellent reversible capacity and rate capability thanks to the steerable nature of the synthesis and material quality. This work opens a new route to 1D micro- and nanostructured materials by customizing the precipitating solvent to orchestrate the crystallization process.

20.
BMC Biotechnol ; 14: 32, 2014 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-24766767

RESUMEN

BACKGROUND: Researchers are looking for biomimetic mineralization of ena/mel to manage dental erosion. This study evaluated biomimetic mineralization of demineralized enamel induced by a synthetic and self-assembled oligopeptide amphiphile (OPA). RESULTS: The results showed that the OPA self-assembled into nano-fibres in the presence of calcium ions and in neutral acidity. The OPA was alternately immersed in calcium chloride and sodium hypophosphate solutions to evaluate its property of mineralization. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed nucleation and growth of amorphous calcium phosphate along the self-assembled OPA nano-fibres when it was repetitively exposed to solutions with calcium and phosphate ions. Energy dispersive spectrometry (EDS) confirmed that these nano-particles contained calcium and phosphate. Furthermore, electron diffraction pattern suggested that the nano-particles precipitated on OPA nano-fibres were comparable to amorphous calcium phosphate. Acid-etched human enamel slices were incubated at 37°C in metastable calcium phosphate solution with the OPA for biomimetic mineralization. SEM and X-ray diffraction indicated that the OPA induced the formation of hydroxyapatite crystals in organized bundles on etched enamel. TEM micrographs revealed there were 20-30 nm nano-amorphous calcium phosphate precipitates in the biomimetic mineralizing solution. The particles were found separately bound to the oligopeptide fibres. Biomimetic mineralization with or without the oligopeptide increased demineralized enamel microhardness. CONCLUSIONS: A novel OPA was successfully fabricated, which fostered the biomimetic mineralization of demineralized enamel. It is one of the primary steps towards the design and construction of novel biomaterial for future clinical therapy of dental erosion.


Asunto(s)
Biomimética , Esmalte Dental/metabolismo , Oligopéptidos/metabolismo , Materiales Biocompatibles/química , Materiales Biocompatibles/metabolismo , Fosfatos de Calcio/química , Fosfatos de Calcio/metabolismo , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Nanofibras/química , Oligopéptidos/química , Ácidos Fosfínicos/química
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