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1.
Sheng Li Xue Bao ; 76(3): 438-446, 2024 Jun 25.
Artículo en Chino | MEDLINE | ID: mdl-38939938

RESUMEN

Oocyte maturation and early embryonic development are key steps in the reproductive physiology of female mammals, and any error in this process can adversely affect reproductive development. Recent studies have shown that epigenetic modifications of histones play important roles in the regulation of oocyte meiosis and quality assurance of early embryonic development. Histone deacetylase 11 (HDAC11) is the smallest known member of the histone deacetylases (HDACs) family, and inhibition of HDAC11 activity significantly suppresses the rate of oocyte maturation, as well as the development of 8-cell and blastocyst embryos at the embryonic stage. This paper focuses on recent progress on the important role of HDAC11 in the regulation of mammalian oocyte maturation and early embryonic development, hoping to gain insights into the key roles played by epitope-modifying proteins represented by HDAC11 in the regulation of mammalian reproduction and their molecular mechanisms.


Asunto(s)
Desarrollo Embrionario , Histona Desacetilasas , Oocitos , Animales , Oocitos/fisiología , Desarrollo Embrionario/fisiología , Histona Desacetilasas/metabolismo , Histona Desacetilasas/fisiología , Histona Desacetilasas/genética , Femenino , Humanos , Oogénesis/fisiología , Mamíferos/embriología , Meiosis/fisiología
2.
BMC Med Imaging ; 23(1): 119, 2023 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-37697237

RESUMEN

BACKGROUND: To investigate the diagnostic performance of parameters derived from monoexponential, biexponential, and stretched-exponential diffusion-weighted imaging models in differentiating tumour progression from pseudoprogression in glioblastoma patients. METHODS: Forty patients with pathologically confirmed glioblastoma exhibiting enhancing lesions after completion of chemoradiation therapy were enrolled in the study, which were then classified as tumour progression and pseudoprogression. All patients underwent conventional and multi-b diffusion-weighted MRI. The apparent diffusion coefficient (ADC) from a monoexponential model, the true diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f) from a biexponential model, and the distributed diffusion coefficient (DDC) and intravoxel heterogeneity index (α) from a stretched-exponential model were compared between tumour progression and pseudoprogression groups. Receiver operating characteristic curves (ROC) analysis was used to investigate the diagnostic performance of different DWI parameters. Interclass correlation coefficient (ICC) was used to evaluate the consistency of measurements. RESULTS: The values of ADC, D, DDC, and α values were lower in tumour progression patients than that in pseudoprogression patients (p < 0.05). The values of D* and f were higher in tumour progression patients than that in pseudoprogression patients (p < 0.05). Diagnostic accuracy for differentiating tumour progression from pseudoprogression was highest for α(AUC = 0.94) than that for ADC (AUC = 0.91), D (AUC = 0.92), D* (AUC = 0.81), f (AUC = 0.75), and DDC (AUC = 0.88). CONCLUSIONS: Multi-b DWI is a promising method for differentiating tumour progression from pseudoprogression with high diagnostic accuracy. In addition, the α derived from stretched-exponential model is the most promising DWI parameter for the prediction of tumour progression in glioblastoma patients.


Asunto(s)
Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/terapia , Imagen de Difusión por Resonancia Magnética , Quimioradioterapia , Curva ROC
3.
Cell Rep ; 42(10): 113170, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37738124

RESUMEN

Chronic stress and chronic pain are two major predisposing factors to trigger depression. Enhanced excitatory input to the lateral habenula (LHb) has been implicated in the pathophysiology of depression. However, the contribution of inhibitory transmission remains unclear. Here, we dissect an inhibitory projection from the sensory thalamic reticular nucleus (sTRN) to the LHb, which is activated by acute aversive stimuli. However, chronic restraint stress (CRS) weakens sTRN-LHb synaptic strength, and this synaptic attenuation is indispensable for CRS-induced LHb neural hyperactivity and depression onset. Moreover, artificially inhibiting the sTRN-LHb circuit induces depressive-like behaviors in healthy mice, while enhancing this circuit relieves depression induced by both chronic stress and chronic pain. Intriguingly, neither neuropathic pain nor comorbid mechanical hypersensitivity in chronic stress is affected by this pathway. Altogether, our study demonstrates an sTRN-LHb circuit in establishing and modulating depression, thus shedding light on potential therapeutic targets for preventing or managing depression.


Asunto(s)
Dolor Crónico , Habénula , Ratones , Animales , Depresión/metabolismo , Neuronas/metabolismo , Habénula/fisiología , Núcleos Talámicos
4.
Nat Commun ; 14(1): 5124, 2023 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-37612268

RESUMEN

Chronic pain causes both physical suffering and comorbid mental symptoms such as anhedonia. However, the neural circuits and molecular mechanisms underlying these maladaptive behaviors remain elusive. Here using a mouse model, we report a pathway from vesicular glutamate transporter 3 neurons in the dorsal raphe nucleus to dopamine neurons in the ventral tegmental area (VGluT3DRN→DAVTA) wherein population-level activity in response to innocuous mechanical stimuli and sucrose consumption is inhibited by chronic neuropathic pain. Mechanistically, neuropathic pain dampens VGluT3DRN → DAVTA glutamatergic transmission and DAVTA neural excitability. VGluT3DRN → DAVTA activation alleviates neuropathic pain and comorbid anhedonia-like behavior (CAB) by releasing glutamate, which subsequently promotes DA release in the nucleus accumbens medial shell (NAcMed) and produces analgesic and anti-anhedonia effects via D2 and D1 receptors, respectively. In addition, VGluT3DRN → DAVTA inhibition produces pain-like reflexive hypersensitivity and anhedonia-like behavior in intact mice. These findings reveal a crucial role for VGluT3DRN → DAVTA → D2/D1NAcMed pathway in establishing and modulating chronic pain and CAB.


Asunto(s)
Dolor Crónico , Neuralgia , Humanos , Área Tegmental Ventral , Núcleo Dorsal del Rafe , Anhedonia , Neuronas Dopaminérgicas , Ácido Glutámico
5.
Angew Chem Int Ed Engl ; 62(42): e202310794, 2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37596246

RESUMEN

Covalent organic frameworks (COFs) with structural designability and tunability of photophysical properties enable them to be a promising class of organic luminescent materials by incorporating well-designed fluorescent units directly into the periodic skeletons. The photophysical properties of COFs are mainly affected by the structural features, which determine the conjugation degree, charge delocalization ability, and exciton dynamics of COFs. To understand the relationship between COF structures and their photophysical properties, two COFs with the same pyrene chromophore units but different linkages (imine or vinylene) were designed and synthesized. Interestingly, different linkages endow COFs with huge differences in solid-state photoluminescence quantum yield (PLQY) for imine- and vinylene-linked pyrene-based COFs, which possess PLQY values of 0.34 % and 15.43 %, respectively. The femtosecond-transient absorption spectra and time-dependent density functional theory reveal the different charge-transfer pathways in imine- and vinylene-linked COFs, which influence the exciton relaxation way and fluorescence intensity. In addition, an effective white-light device was obtained by coating the vinylene-linked COF on a light-emitting diode strip.

6.
Angew Chem Int Ed Engl ; 62(36): e202308523, 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37370248

RESUMEN

Constructing a powerful photocatalytic system that can achieve the carbon dioxide (CO2 ) reduction half-reaction and the water (H2 O) oxidation half-reaction simultaneously is a very challenging but meaningful task. Herein, a porous material with a crystalline topological network, named viCOF-bpy-Re, was rationally synthesized by incorporating rhenium complexes as reductive sites and triazine ring structures as oxidative sites via robust -C=C- bond linkages. The charge-separation ability of viCOF-bpy-Re is promoted by low polarized π-bridges between rhenium complexes and triazine ring units, and the efficient charge-separation enables the photogenerated electron-hole pairs, followed by an intramolecular charge-transfer process, to form photogenerated electrons involved in CO2 reduction and photogenerated holes that participate in H2 O oxidation simultaneously. The viCOF-bpy-Re shows the highest catalytic photocatalytic carbon monoxide (CO) production rate (190.6 µmol g-1 h-1 with about 100 % selectivity) and oxygen (O2 ) evolution (90.2 µmol g-1 h-1 ) among all the porous catalysts in CO2 reduction with H2 O as sacrificial agents. Therefore, a powerful photocatalytic system was successfully achieved, and this catalytic system exhibited excellent stability in the catalysis process for 50 hours. The structure-function relationship was confirmed by femtosecond transient absorption spectroscopy and density functional theory calculations.

7.
Neuroradiology ; 65(2): 323-336, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36219250

RESUMEN

PURPOSE: To investigate the alterations of topological organization of the whole brain functional networks in hypertension patients with cognitive impairment (HTN-CI) and characterize its relationship with cognitive scores. METHODS: Fifty-seven hypertension patients with cognitive impairment and 59 hypertension patients with normal cognition (HTN-NC), and 49 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Graph theoretical analysis was used to investigate the altered topological organization of the functional brain networks. The global topological properties and nodal metrics were compared among the three groups. Network-based statistic (NBS) analysis was used to determine the connected subnetwork. The relationships between network metrics and cognitive scores were also characterized. RESULTS: HTN-CI patients exhibited significantly decreased global efficiency, lambda, and increased shortest path length when compared with HCs. In addition, both HTN-CI and HTN-NC groups exhibited altered nodal degree centrality and nodal efficiency in the right precentral gyrus. The disruptions of global network metrics (lambda, Lp) and the nodal metrics (degree centrality and nodal efficiency) in the right precentral gyrus were positively correlated with the MoCA scores in HTN-CI. NBS analysis demonstrated that decreased subnetwork connectivity was present both in the HTN-CI and HTN-NC groups, which were mainly involved in the default mode network, frontoparietal network, and cingulo-opercular network. CONCLUSION: This study demonstrated the alterations of topographical organization and subnetwork connectivity of functional brain networks in HTN-CI. In addition, the global and nodal network properties were correlated with cognitive scores, which may provide useful insights for the understanding of neuropsychological mechanisms underlying HTN-CI.


Asunto(s)
Disfunción Cognitiva , Hipertensión , Humanos , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/complicaciones , Mapeo Encefálico , Hipertensión/complicaciones
8.
J Korean Neurosurg Soc ; 64(3): 418-426, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33993690

RESUMEN

OBJECTIVE: A role of diffusion-weighted imaging (DWI) in the diagnosis of cerebral venous thrombosis (CVT) is not wellunderstood. This study evaluates the effectiveness of DWI in the diagnosis of CVT. METHODS: Literature search was conducted in electronic databases for the identification of studies which reported the outcomes of patients subjected to DWI for CVT diagnosis. Random-effects meta-analyses were performed to achieve overall estimates of important diagnostic efficiency indices including hyperintense signal rate, the sensitivity and specificity of DWI in diagnosing CVT, and the apparent diffusion coefficient (ADC) of DWI signal areas and surrounding tissue. RESULTS: Nineteen studies (443 patients with 856 CVTs; age 40 years [95% confidence interval (CI), 33 to 43]; 28% males [95% CI, 18 to 38]; symptom onset to DWI time 4.6 days [95% CI, 2.3 to 6.9]) were included. Hyperintense signals on DWI were detected in 40% (95% CI, 26 to 55) of the cases. The sensitivity of DWI for detecting CVT was 22% (95% CI, 11 to 34) but specificity was 98% (95% CI, 95 to 100). ADC values were quite heterogenous in DWI signal areas. However, generally the ADC values were lower in DWI signal areas than in surrounding normal areas (mean difference-0.33×10-3 mm2/s [95% CI, -0.44 to -0.23]; p<0.00001). CONCLUSION: DWI has a low sensitivity in detecting CVT and thus has a high risk of missing many CVT cases. However, because of its high specificity, it may have supporting and exploratory roles in CVT diagnosis.

9.
ACS Nano ; 15(1): 1291-1300, 2021 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-33373181

RESUMEN

Second-harmonic generation (SHG) in plasmonic nanostructures has been investigated for decades due to their wide applications in photonic circuit, quantum optics and biosensing. Development of large-scale, uniform, and efficient plasmonic nanostructure system with tunable modes is desirable for their feasible utilizations. Herein, we design an efficient inch-scale SHG source by a solution-processed method instead of traditional high-cost processes. By assembling the gold nanoparticles with the porous anodic alumina templates, multiresonance in both visible and near-infrared regions can be achieved in hexagonal plasmonic nanostructure arrays, which provide strong electric field enhancement at the gap region. Polarization-independence SHG radiation has been realized owing to the in-plane isotropic characteristic of assembled unit. The tilt-angle dependent and angle-resolved measurement showed that wide-angle nonlinear response is achieved in our device because of the gap geometry of ball-in-bowl nanostructure with nonlinear emission electric dipoles distributed on the concave surface, which makes it competitive in practical applications. Our progress not only makes it possible to produce uniform inch-scale nonlinear arrays through low-cost solution process; and also advances the understanding of the SHG radiation in plasmonic nanostructures.

10.
Neurochem Res ; 45(12): 2915-2925, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33125618

RESUMEN

Abnormally high expression of glial cell line-derived neurotrophic factor (GDNF) derived from glioma cells has essential impacts on gliomagenesis and development, but the molecular basis underlying increased GDNF expression in glioma cells remain unclear. This work aimed to study the molecular mechanisms that may explain the accumulation of GDNF in glioma. Firstly, we observed that cAMP response element-binding protein (CREB), known as an important transcription factor for binding of GDNF promoter region, was highly expressed with an apparent accumulation into the nucleus of glioma cells, which may contribute to the transcription of GDNF. Secondly, CUE domain-containing protein 2 (CUEDC2), a ubiquitin-regulated protein, could increase the amount of binding between the E3 ligase tripartite motif-containing 21 (TRIM21) and CREB and affect the CREB level. Like our previous study, it showed that there was a significantly down-regulation of CUEDC2 in glioma. Finally, our data suggest that GDNF expression is indirectly regulated by transcription factor ubiquitination. Indeed, down-regulation of CUEDC2, decreased the ubiquitination and degradation of CREB, which was associated to high levels of GDNF. Furthermore, abundant CREB involved in the binding to the GDNF promoter region contributes to GDNF high expression in glioma cells. Collectively, it was verified the GDNF expression was affected by CREB ubiquitination regulated by CUEDC2 level.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Glioma/metabolismo , Ubiquitinación/fisiología , Línea Celular Tumoral , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica/fisiología , Glioma/genética , Humanos
11.
J Int Med Res ; 48(6): 300060520933448, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32589072

RESUMEN

OBJECTIVE: To evaluate the hyperintense signal (HIS) performance on diffusion-weighted imaging (DWI) in diagnosing cerebral venous thrombosis (CVT). METHODS: Seventy-eight patients with CVT hospitalized from January 2004 to January 2015 were retrospectively studied alongside 78 controls without intracranial organic diseases. Diagnostic accuracy indices of HIS on DWI or T2-weighted imaging (T2WI) to diagnose CVT at different sites and states were analyzed. RESULTS: The overall sensitivity of HIS on DWI for the diagnosis of CVT was significantly lower than that of HIS on T2WI (34.6% vs. 79.5%). HIS on T2WI was more sensitive than HIS on DWI in detecting thrombosis, especially in the superior sagittal sinus and transverse sinus. HIS on DWI was inversely related to the time between disease onset and imaging. Compared with HIS on T2WI, combining HIS on DWI and T2WI did not increase the sensitivity for detecting CVT. HIS on DWI was not detected in the control group, but HIS on T2WI was detected in 26.3% of control individuals. The specificity of HIS on DWI for CVT was higher than that of HIS on T2WI (97.4% vs. 76.9%). CONCLUSION: HIS on DWI has a lower sensitivity, but a higher specificity, than HIS on T2WI for diagnosing CVT.


Asunto(s)
Imagen de Difusión por Resonancia Magnética , Trombosis de la Vena , Humanos , Imagen por Resonancia Magnética , Estudios Retrospectivos , Sensibilidad y Especificidad , Trombosis de la Vena/diagnóstico por imagen
12.
Gen Comp Endocrinol ; 291: 113237, 2020 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-31374285

RESUMEN

The molecular mechanism underlying myostatin (MSTN)-regulated metabolic cross-talk remains poorly understood. In this study, we performed comparative proteomic and phosphoproteomic analyses of gluteus muscle tissues from MSTN-/- transgenic cattle using a shotgun-based tandem mass tag (TMT) 6-plex labeling method to explore the signaling pathway of MSTN in metabolic cross-talk and cellular metabolism during muscle development. A total of 72 differentially expressed proteins (DEPs) and 36 differentially expressed phosphoproteins (DEPPs) were identified in MSTN-/- cattle compared to wild-type cattle. Bioinformatics analyses showed that MSTN knockout increased the activity of many key enzymes involved in fatty acid ß-oxidation and glycolysis processes in cattle. Furthermore, comprehensive pathway analyses and hypothesis-driven AMP-activated protein kinase (AMPK) activity assays suggested that MSTN knockout triggers the activation of AMPK signaling pathways to regulate glucose and lipid metabolism by increasing the AMP/ATP ratio. Our results shed new light on the potential regulatory mechanism of MSTN associated with metabolic cross-talk in muscle development, which can be used in animal breeding to improve meat production in livestock animals, and can also provide valuable insight into treatments for obesity and diabetes mellitus in humans.


Asunto(s)
Bovinos/metabolismo , Edición Génica , Glucosa/metabolismo , Metabolismo de los Lípidos , Músculo Esquelético/metabolismo , Miostatina/metabolismo , Proteómica , Adenilato Quinasa/metabolismo , Tejido Adiposo/metabolismo , Secuencia de Aminoácidos , Animales , Animales Modificados Genéticamente , Biología Computacional , Glucógeno/metabolismo , Péptidos/química , Péptidos/metabolismo , Fosfoproteínas/metabolismo , Fosforilación , Reproducibilidad de los Resultados , Transducción de Señal
13.
Small ; 15(38): e1902811, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31373758

RESUMEN

Tin diselenide (SnSe2 ) nanosheets as novel 2D layered materials have excellent optical properties with many promising application prospects, such as photoelectric detectors, nonlinear optics, infrared photoelectric devices, and ultrafast photonics. Among them, ultrafast photonics has attracted much attention due to its enormous advantages; for instance, extremely fast pulse, strong peak power, and narrow bandwidth. In this work, SnSe2 nanosheets are fabricated by using solvothermal treatment, and the characteristics of SnSe2 are systemically investigated. In addition, the solution of SnSe2 nanosheets is successfully prepared as a fiber-based saturable absorber by utilizing the evanescent field effect, which can bear a high pump power. 31st-order subpicosecond harmonic mode locking is generated in an Er-doped fiber laser, corresponding to the maximum repetition rate of 257.3 MHz and pulse duration of 887 fs. The results show that SnSe2 can be used as an excellent nonlinear photonic device in many fields, such as frequency comb, lasers, photodetectors, etc.

14.
BMC Neurol ; 19(1): 150, 2019 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-31277603

RESUMEN

BACKGROUND: Mechanical thrombectomy has been proven as a standard care for moderate to severe ischemic stroke with anterior large vessel occlusion (LVO); however, whether it is equally effective in mild ischemic stroke (MIS) is controversial. METHODS: In this retrospective study, a total of 177 Chinese patients presenting with MIS (NIHSS ≤8) and LVO between January 2014 and September 2017 from seven comprehensive stroke centers were identified. Odds of good outcome with endovascular thrombectomy versus medical treatment were obtained by logistic regression analysis and propensity-score matching method, and a meta-analysis pooled results from six studies (n = 733). RESULTS: Good outcome (mRS: 0-1) was 58.2% (46/79) in the thrombectomy and 46.9% (46/98) in the medical group, which showed no statistical significance before adjustment (P = 0.13; OR = 1.57, 95% CI: 0.86 to 2.86). The adjusted ORs of thrombectomy versus medical group were 3.23 (95% CI, 1.35 to 7.73; P = 0.008) by multivariable logistic analysis, 2.78 (1.12 to 6.89; P = 0.02) by propensity score matching analysis, and 3.20 (1.22 to 8.37; P = 0.01) by propensity score matching analysis with additional adjustments, respectively. Thrombectomy treatment did not result in excessive mortality or symptomatic intracranial hemorrhage after adjustments. The meta-analysis did not confirm the associations between good outcome and endovascular treatment. CONCLUSIONS: The current study indicates that endovascular thrombectomy is associated with good functional outcome in MIS patients with LVO, and without additional risk of symptomatic intracranial hemorrhage and mortality. Although the meta-analysis failed to demonstrate its superiority compared to medical treatment, randomized clinical trials are needed.


Asunto(s)
Isquemia Encefálica/cirugía , Procedimientos Endovasculares/estadística & datos numéricos , Accidente Cerebrovascular/cirugía , Trombectomía/estadística & datos numéricos , Anciano , Pueblo Asiatico , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Hemorragias Intracraneales , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos , Trombectomía/efectos adversos , Resultado del Tratamiento
15.
PLoS One ; 14(1): e0211501, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30695072

RESUMEN

Gliomas are the most common malignant tumors of the brain and are characteristic of severe migration and invasion. Glial cell line-derived neurotrophic factor (GDNF) promotes glioma development process. However, the regulatory mechanisms of promoting occurrence and development of glioma have not yet been clearly elucidated. In the present study, the mechanism by which GDNF promotes glioma cell migration and invasion through regulating the dispersion and location of the Golgi apparatus (GA) is described. Following GDNF treatment, a change in the volume and position of GA was observed. The stack area of the GA was enlarged and it was more concentrated near the nucleus. Golgin-160 and Golgi microtubule-associated protein 210 (GMAP210) were identified as target molecules regulating GA positioning. In the absence of either golgin-160 or GMAP210 using lentivirus, the migration and invasion of U251 cells were decreased, while it was increased following GDNF. It was also found that the GA was decreased in size and dispersed following golgin-160 or GMAP210 knockdown, as determined by GA green fluorescence assay. Once GDNF was added, the above phenomenon would be twisted, and the concentrated location and volume of the GA was restored. In combination, the present data suggested that the regulation of the position and size of the GA by golgin-160 and GMAP210 play an important role in U251 cell migration and invasion.


Asunto(s)
Autoantígenos/metabolismo , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Factor Neurotrófico Derivado de la Línea Celular Glial/farmacología , Glioma/patología , Proteínas de la Matriz de Golgi/metabolismo , Proteínas Nucleares/metabolismo , Autoantígenos/genética , Proliferación Celular , Proteínas del Citoesqueleto , Glioma/genética , Glioma/metabolismo , Aparato de Golgi/efectos de los fármacos , Aparato de Golgi/metabolismo , Aparato de Golgi/patología , Proteínas de la Matriz de Golgi/antagonistas & inhibidores , Proteínas de la Matriz de Golgi/genética , Humanos , Invasividad Neoplásica , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Nucleares/genética , Células Tumorales Cultivadas , Cicatrización de Heridas
16.
Int J Oncol ; 53(6): 2542-2554, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30272346

RESUMEN

Malignant astrocytoma (MA) is the most common and severe type of brain tumor. A greater understanding of the underlying mechanisms responsible for the development of MA would be beneficial for the development of targeted molecular therapies. In the present study, the upregulated differentially expressed genes (DEGs) in MA were obtained from the Gene Expression Omnibus database using R/Bioconductor software. DEGs in different World Health Organization classifications were compared using the Venny tool and 15 genes, including collagen type I α1 chain (COL1A1) and laminin subunit γ1 (LAMC1), were revealed to be involved in the malignant progression of MA. In addition, the upregulated DEGs in MA were evaluated using functional annotations of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes with the Database for Annotation, Visualization, and Integrated Discovery tool. The results indicated that invasion­associated enrichment was observed in 'extracellular matrix' (ECM), 'cell adhesion' and 'phosphoinositide 3­kinase­protein kinase B signaling pathway'. Subsequently, the analysis of the protein­protein interactions was performed using STRING and Cytoscape software, which revealed that the ECM component was the invasion­associated module and its corresponding genes included COL1A1, LAMC1 and fibronectin 1. Finally, survival Kaplan­Meier estimate was conducted using cBioportal online, which demonstrated that COL1A1 expression affected the survival of and recurrence in patients with MA. Moreover, the results of in vitro Transwell assay and western blot analysis revealed that the depleted levels of COL1A1 also decreased the expression of several proteins associated with cell invasion, including phosphorylated­signal transducer and activator of transcription 3, matrix metalloproteinase (MMP)­2, MMP­9 and nuclear factor­κB. On the whole, the present study identified the invasion­related target genes and the associated potential pathways in MA. The results indicated that COL1A1 may be a candidate biomarker for the prognosis and treatment of MA.


Asunto(s)
Astrocitoma/genética , Neoplasias Encefálicas/genética , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Regulación hacia Arriba , Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Cadena alfa 1 del Colágeno Tipo I , Bases de Datos Genéticas , Matriz Extracelular/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Invasividad Neoplásica , Pronóstico , Transducción de Señal , Análisis de Supervivencia
17.
Oncol Rep ; 40(1): 443-453, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29750313

RESUMEN

Glial cell line-derived neurotrophic factor (GDNF) is considered to be involved in the development of glioma. However, uncovering the underlying mechanism of the proliferation of glioma cells is a challenging work in progress. We have identified the binding of the precursor of N-cadherin (proN-cadherin) and GDNF on the cell membrane in previous studies. In the present study, we observed increased U251 Malignant glioma (U251MG) cell viability by exogenous GDNF (50 ng/ml). We also confirmed that the high expression of the proN-cadherin was stimulated by exogenous GDNF. Concurrently, we affirmed that lower expression of proN-cadherin correlated with reduced glioma cell viability. Additionally, we observed glioma cell U251MG viability as the phosphorylation level of FGFR1 at Y653 and Y654 was increased after exogenous GDNF treatment, which led to increased interaction between proN-cadherin and FGFR1 (pY653+Y654). Our experiments presented a new mechanism adopted by GDNF supporting glioma development and indicated a possible therapeutic potential via the inhibition of proN-cadherin/FGFR1 interaction.


Asunto(s)
Antígenos CD/genética , Cadherinas/genética , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Glioma/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Línea Celular Tumoral , Proliferación Celular/genética , Supervivencia Celular/genética , Regulación Neoplásica de la Expresión Génica , Glioma/patología , Humanos , Fosforilación , Transducción de Señal
18.
Int J Neurosci ; 128(4): 311-317, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28830290

RESUMEN

BACKGROUND: A loading dose of antiplatelets reduces in-stent thrombosis after stent implantation. However, whether it is safe in patients undergoing acute stenting after intravenous recombinant tissue plasminogen activator (rt-PA) is unclear. METHODS: A case series of acute ischemic stroke patients treated with intravenous rt-PA followed by emergent stenting were prospectively included in Jinling Hospital Stroke Unit. An emergent loading dose of antiplatelets (aspirin 300 mg and clopidogrel 300 mg) were administered to all patients through a nasogastric tube immediately before stenting. Clinical and angiographic outcomes were evaluated in these patients. RESULTS: A total of 12 patients were included. The median of NIHSS score on admission was 15 points (interquartile range 11-19). The median of time from stroke symptom onset to start IV rt-PA and stent placement was 172 min (interquartile range 123.75-189) and 311.5 min (interquartile range 285.5-349.5), respectively. All patients reached complete or partial recanalization (TICI ≥2a). One patient occurred hemorrhagic transformation at 24 h following the emergent loading dose of antiplatelets. A favorable outcome as defined by mRS ≤2 at 90 days was obtained in 58.3% (7/12) of all patients. CONCLUSION: Our finding preliminary suggested that an emergent loading dose of antiplatelets may be safe and feasible for acute stenting after IV rt-PA.


Asunto(s)
Isquemia Encefálica/etiología , Fibrinolíticos/administración & dosificación , Stents , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Activador de Tejido Plasminógeno/administración & dosificación , Administración Intravenosa , Anciano , Aspirina/uso terapéutico , Clopidogrel , Angiografía por Tomografía Computarizada , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/diagnóstico por imagen , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico , Tomógrafos Computarizados por Rayos X , Resultado del Tratamiento
19.
Gene ; 630: 35-43, 2017 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-28757453

RESUMEN

The proliferation and differentiation of skeletal muscle satellite cells is regulated by multiple regulatory factors including non-coding RNAs. It has been reported that miR-133b regulates myogenesis. In this study, we detected a novel lncRNA, lnc133b, which is completely complemented by mature miR-133b, indicating that lnc133b may regulate the expression of miR-133b by "sponge" miR-133b. A luciferase report assay confirmed that lnc133b interacts with miR-133b in regions complemented by miR-133b. We successfully constructed lnc133b gain/loss-of-function cell models by infecting LV-1nc133b and transfecting si-lnc133b into satellite cells. Results of quantitative real-time polymerase chain reaction (qRT-PCR) and 5-ethynyl-2'-deoxyuridine (EdU) assays showed that overexpression or inhibition of lnc133b could promote the proliferation or inhibition of satellite cell differentiation. The qRT-PCR results also showed that lnc133b negatively regulates miR-133b expression and a Western blot assay showed that lnc133b positively regulates IGF1R expression, indicating that the lnc133b/miR-133b/IGF1R axis is a potential pathway for promoting satellite cell proliferation and repressing their differentiation through the ceRNA mechanism. Building on the findings of previous reports, we constructed the lnc133b/miR-133b/FGFR1 & PP2AC pathway to improve the lnc133b regulation network regulating the proliferation and differentiation of satellite cells. The current study provides a new perspective for understanding the mechanism regulating satellite cell proliferation and differentiation through the interaction of miR-133b and lnc133b.


Asunto(s)
Diferenciación Celular , Proliferación Celular , MicroARNs/genética , ARN Largo no Codificante/genética , Células Satélite del Músculo Esquelético/metabolismo , Animales , Bovinos , Células Cultivadas , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Células Satélite del Músculo Esquelético/citología
20.
J Lipid Res ; 58(8): 1524-1535, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28626062

RESUMEN

The n-3 PUFAs have many beneficial effects on human health, including roles in immunity, neurodevelopment, and preventing cardiovascular disease. In this study, we established reliable model fat-1 transgenic cattle using transgenic technology and performed a systematic investigation to examine the function of n-3 PUFAs. Our results showed that expression of the fat-1 gene improved several biochemical parameters related to liver function and to plasma glucose and plasma lipid metabolism. Results of global gene and plasma protein expression analysis showed that 310 genes and 13 plasma proteins differed significantly in the blood of fat-1 transgenic cattle compared with WT cattle, reflecting their regulatory roles in the immune and cardiovascular systems. Finally, changes in the gut microflora were also noted in the fat-1 transgenic cattle, suggesting novel roles for n-3 PUFAs in the metabolism of glucose and lipids, as well as anti-stress properties. To the best of our knowledge, this is the first report using multiple parallel analyses to investigate the role of n-3 PUFAs using models such as fat-1 transgenic cattle. This study provides novel insights into the regulatory mechanism of fat-1 in the immune and cardiovascular systems, as well as its anti-stress role.


Asunto(s)
Ácido Graso Desaturasas/genética , Ácidos Grasos Omega-3/metabolismo , Animales , Animales Modificados Genéticamente , Bovinos , Microbioma Gastrointestinal , Dosificación de Gen , Perfilación de la Expresión Génica
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