Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
Commun Biol ; 7(1): 613, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773248

RESUMEN

Understanding how to increase soybean yield is crucial for global food security. The genetic and epigenetic factors influencing seed size, a major crop yield determinant, are not fully understood. We explore the role of DNA demethylase GmDMEa in soybean seed size. Our research indicates that GmDMEa negatively correlates with soybean seed size. Using CRISPR-Cas9, we edited GmDMEa in the Dongnong soybean cultivar, known for small seeds. Modified plants had larger seeds and greater yields without altering plant architecture or seed nutrition. GmDMEa preferentially demethylates AT-rich transposable elements, thus activating genes and transcription factors associated with the abscisic acid pathway, which typically decreases seed size. Chromosomal substitution lines confirm that these modifications are inheritable, suggesting a stable epigenetic method to boost seed size in future breeding. Our findings provide insights into epigenetic seed size control and suggest a strategy for improving crop yields through the epigenetic regulation of crucial genes. This work implies that targeted epigenetic modification has practical agricultural applications, potentially enhancing food production without compromising crop quality.


Asunto(s)
Metilación de ADN , Elementos Transponibles de ADN , Glycine max , Semillas , Glycine max/genética , Semillas/genética , Semillas/crecimiento & desarrollo , Elementos Transponibles de ADN/genética , Epigénesis Genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética
2.
World Neurosurg ; 182: e270-e275, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38006935

RESUMEN

OBJECTIVE: Seizures are one of the complications that can occur after cranioplasty (CP). In some regions, titanium mesh remains the material of choice for CP. However, risk factors for seizures after titanium CP have been less studied. The purpose of this study was to identify potential risk factors for early seizures (≤7 days) and late seizures (>8 days) after titanium CP in a single institution. METHODS: A retrospective review was conducted of 241 consecutive patients who received titanium CP at the First Affiliated Hospital of Harbin Medical University from January 2016 to December 2020. Univariate and multivariable logistic regression analyses were performed to determine the independent risk factors for new-onset seizures after titanium CP. RESULTS: Fifteen patients (6.22%) experienced early post-CP seizures, and late post-CP seizures were observed in 81 patients (33.61%). A flaccid concave cranial defect (P = 0.042) was associated with early post-CP seizures, whereas hypertension (P < 0.001) was the only significant predictor for late seizures after titanium CP. CONCLUSIONS: Seizure is a common complication after titanium CP, especially in patients who do not receive prophylactic antiepileptic drugs before the procedure. Risk factors for new-onset seizures at different periods after titanium CP were found to be different. In addition, radiologic factors before titanium CP may play a role in early new-onset seizures after titanium CP and should not be ignored.


Asunto(s)
Craniectomía Descompresiva , Titanio , Humanos , Titanio/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Craniectomía Descompresiva/efectos adversos , Convulsiones/epidemiología , Convulsiones/etiología , Convulsiones/prevención & control , Factores de Riesgo , Cráneo/cirugía , Estudios Retrospectivos
3.
Plants (Basel) ; 12(24)2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38140462

RESUMEN

The plant rhizosphere underlies the crosstalk between plant and soil and has a crucial role in plant growth and development under various environments. We examined the effect of temperature rise on the rhizosphere environment of soybean roots to clarify the rhizosphere crosstalk between roots and soil in response to warm temperature rises in a global warming background. The in situ results of root enzyme activity revealed that soybean roots secrete ß-glucosidase, and enzyme spectrum imaging demonstrated different enzymatic activities under different temperature environments. The soil enzyme kinetics results showed that soil enzymatic activity increased with increasing temperature, and soybean rhizosphere soil enzymatic activity was higher than that of non-rhizosphere soil. Rhizosphere soil and non-rhizosphere soil showed that the dominant bacterial phylum in soybean rhizosphere soil was Acidobacteria, and the dominant bacterial genus was JG30-KF-AS9. Compared with non-rhizosphere soil, rhizosphere soil was more nutrient-rich, and root secretions provided abundant carbon sources and other nutrients for soil microorganisms in the rhizosphere. Rhizosphere microorganisms affect plant growth by influencing the decomposition of soil organic carbon. The organic carbon content of rhizosphere soil was higher than that of non-rhizosphere soil under high temperatures.

4.
Sci Rep ; 12(1): 22220, 2022 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-36564462

RESUMEN

To address the problem of low efficiency of recycling process waste by gas-solid two-phase flow of the shot blasting machine recycling device, a method and structure by increasing the negative pressure value and optimizing the outlet pipe position are proposed. Computational fluid dynamics (CFD), discrete element method (DEM) and discrete phase model (DPM) were used to study the waste recovery efficiency at different pressure outlet conditions and outlet pipe locations. The validity of the model was verified by velocity tests at the outlet and inlet compared with simulations. The effect of particle size and particle generation rate on solid particle recovery efficiency was further investigated by analyzing the flow field distribution of the recovery unit. The results show that the maximum velocity of the gas phase in the recovery device increases with the increase of the absolute value of the outlet pressure, when the outlet pressure is -6500 Pa, the maximum velocity is 67.59 m/s. When the absolute value of the outlet pressure is greater than 6000 Pa, a small amount of steel shot particles is discharged from the recovery bin under the action of the outlet pressure, resulting in the loss of steel shot particles. After the outlet pipe position optimization, the steel shot particle recovery efficiency increased by 10% and the waste particle recovery efficiency increased by 18.9%.

6.
Cancer Cell Int ; 21(1): 297, 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34098960

RESUMEN

BACKGROUND: Although many biomarkers have been reported for detecting glioma, the prognosis for the disease remains poor, and therefore, new biomarkers need to be identified. GNG5, which is part of the G-protein family, has been associated with different malignant tumors, though the role of GNG5 in glioma has not been studied. Therefore, we aimed to identify the relationship between GNG5 and glioma prognosis and identify a new biomarker for the diagnosis and treatment of gliomas. METHODS: We used data on more than a thousand gliomas from multiple databases and clinical data to determine the expression of GNG5 in glioma. Based on clinical data and CGGA database, we identified the correlation between GNG5 and multiple molecular and clinical features and prognosis using various analytical methods. Co-expression analysis and GSEA were performed to detect GNG5-related genes in glioma and possible signaling pathways involved. ESTIMATE, ssGSEA, and TIMER were used to detect the relationship between GNG5 and the immune microenvironment. Functional experiments were performed to explore the function of GNG5 in glioma cells. RESULTS: GNG5 is highly expressed in gliomas, and its expression level is positively correlated with pathological grade, histological type, age, and tumor recurrence and negatively correlated with isocitrate dehydrogenase mutation, 1p/19 co-deletion, and chemotherapy. Moreover, GNG5 as an independent risk factor was negatively correlated with the overall survival time. GSEA revealed the potential signaling pathways involved in GNG5 function in gliomas, including cell adhesion molecules signaling pathway. The ssGSEA, ESTIMATE, and TIMER based analysis indicated a correlation between GNG5 expression and various immune cells in glioma. In vivo and in vitro experiments showed that GNG5 could participate in glioma cell proliferation and migration. CONCLUSIONS: Based on the large data platform and the use of different databases to corroborate results obtained using various datasets, as well as in vitro and in vivo experiments, our study reveals for the first time that GNG5, as an oncogene, is overexpressed in gliomas and can inhibit the proliferation and migration of glioma cells and lead to poor prognosis of patients. Thus, GNG5 is a potential novel biomarker for the clinical diagnosis and treatment of gliomas.

7.
Mol Med ; 27(1): 52, 2021 05 29.
Artículo en Inglés | MEDLINE | ID: mdl-34051735

RESUMEN

BACKGROUND: XRCC2, a homologous recombination-related gene, has been reported to be associated with a variety of cancers. However, its role in glioma has not been reported. This study aimed to find out the role of XRCC2 in glioma and reveal in which glioma-specific biological processes is XRCC2 involved based on thousands of glioma samples, thereby, providing a new perspective in the treatment and prognostic evaluation of glioma. METHODS: The expression characteristics of XRCC2 in thousands of glioma samples from CGGA and TCGA databases were comprehensively analyzed. Wilcox or Kruskal test was used to analyze the expression pattern of XRCC2 in gliomas with different clinical and molecular features. The effect of XRCC2 on the prognosis of glioma patients was explored by Kaplan-Meier and Cox regression. Gene set enrichment analysis (GSEA) revealed the possible cellular mechanisms involved in XRCC2 in glioma. Connectivity map (CMap) was used to screen small molecule drugs targeting XRCC2 and the expression levels of XRCC2 were verified in glioma cells and tissues by RT-qPCR and immunohistochemical staining. RESULTS: We found the overexpression of XRCC2 in glioma. Moreover, the overexpressed XRCC2 was associated with a variety of clinical features related to prognosis. Cox and meta-analyses showed that XRCC2 is an independent risk factor for the poor prognosis of glioma. Furthermore, the results of GSEA indicated that overexpressed XRCC2 could promote malignant progression through involved signaling pathways, such as in the cell cycle. Finally, doxazosin, quinostatin, canavanine, and chrysin were identified to exert anti-glioma effects by targeting XRCC2. CONCLUSIONS: This study analyzed the expression pattern of XRCC2 in gliomas and its relationship with prognosis using multiple datasets. This is the first study to show that XRCC2, a novel oncogene, is significantly overexpressed in glioma and can lead to poor prognosis in glioma patients. XRCC2 could serve as a new biomarker for glioma diagnosis, treatment, and prognosis evaluation, thus bringing new insight into the management of glioma.


Asunto(s)
Biomarcadores de Tumor , Proteínas de Unión al ADN/genética , Expresión Génica , Glioma/genética , Glioma/mortalidad , Adulto , Anciano , Biología Computacional , Proteínas de Unión al ADN/metabolismo , Descubrimiento de Drogas , Femenino , Perfilación de la Expresión Génica , Glioma/diagnóstico , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Curva ROC , Factores de Riesgo , Transducción de Señal , Relación Estructura-Actividad
8.
J Mol Neurosci ; 71(9): 1951-1966, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33403589

RESUMEN

Hippocampal sclerosis (HS) is one of the most prevalent pathological types of temporal lobe epilepsy (TLE), and it significantly affects patient prognoses. The methylation of DNA plays an important role in the development of epilepsy. However, few studies have focused on HS subtypes to determine DNA methylation profiles in TLE. This study aimed to determine the pathogenesis of TLE from an epigenetic perspective in patients with TLE-HS type I (TLE-HSTI) and TLE without HS (TLE-nHS) using whole-genome bisulfite sequencing (WGBS). We defined 1171 hypermethylated and 2537 hypomethylated regions and found 632 differentially methylated genes (DMG) in the promoter region that were primarily involved in the regulation of various aspects of epilepsy development. Twelve DMG overlapped with differentially expressed genes (DEG) in the promoter region, and RT-qPCR findings revealed significant overexpression of the SBNO2, CBX3, RASAL3, and TMBIM4 genes in TLE-HSTI. We present the first systematic analysis of methylation profiles of TLE-HSTI and TLE-nHS from an epigenetic perspective using WGBS. Overall, our preliminary data highlight the underlying mechanism of TLE-HSTI, providing a new perspective for guiding treatment of TLE.


Asunto(s)
Metilación de ADN , Epilepsia del Lóbulo Temporal/genética , Hipocampo/patología , Adolescente , Adulto , Proteínas Cromosómicas no Histona/genética , Epigenoma , Epilepsia del Lóbulo Temporal/patología , Femenino , Humanos , Masculino , Proteínas de la Membrana/genética , Proteínas Represoras/genética , Esclerosis , Proteínas Activadoras de ras GTPasa/genética
9.
Nanoscale ; 12(21): 11556-11561, 2020 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-32432271

RESUMEN

Cadmium-free quantum dots (QDs) are attracting considerable research attention because of their low toxicity. However, the bandgap of most cadmium-free QDs avoids the pure-blue region, which leads to difficulty in realizing pure-blue quantum-dot light-emitting diodes (QLEDs). In this work, we successfully tuned the emission wavelength of ZnSe/ZnS quantum dots from the violet region (∼420 nm) to the pure-blue region (450-460 nm) by doping Te into the ZnSe core. The ZnSe:0.03Te/ZnSeS/ZnS QD sample with emission at 450 nm and a quantum yield of 30% was the most balanced formula. To overcome the energy gap between the hole-transfer layer and QD layers, a specific hole-transfer layer was developed for normal-structure QLEDs. A QLED with such a structure with ZnSe:0.03Te/ZnSeS/ZnS QDs achieved the pure-blue light emission at 455 nm, a low turn-on voltage of 4.4 V, and an external quantum efficiency of 0.33%. Overall, our cadmium-free QLED achieved pure-blue emission, revealing the potential of ZnSe-based pure-blue QLEDs for future displays.

10.
PeerJ ; 7: e7950, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31824753

RESUMEN

In eukaryotes, proteins encoded by the 14-3-3 genes are ubiquitously involved in the plant growth and development. The 14-3-3 gene family has been identified in several plants. In the present study, we identified 22 GmGF14 genes in the soybean genomic data. On the basis of the evolutionary analysis, they were clustered into ε and non-ε groups. The GmGF14s of two groups were highly conserved in motifs and gene structures. RNA-seq analysis suggested that GmGF14 genes were the major regulator of soybean morphogenesis. Moreover, the expression level of most GmGF14s changed obviously in multiple stress responses (drought, salt and cold), suggesting that they have the abilities of responding to multiple stresses. Taken together, this study shows that soybean 14-3-3s participate in plant growth and can response to various environmental stresses. These results provide important information for further understanding of the functions of 14-3-3 genes in soybean.

11.
PeerJ ; 7: e7509, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31497394

RESUMEN

BACKGROUND: VQ proteins, the plant-specific transcription factors, are involved in plant development and multiple stresses; however, only few articles systematic reported the VQ genes in soybean. METHODS: In total, we identified 75 GmVQ genes, which were classified into 7 groups (I-VII). Conserved domain analysis indicated that VQ gene family members all contain the VQ domains. VQ genes from the same evolutionary branches of soybean shared similar motifs and structures. Promoter analysis revealed that cis-elements related to stress responses, phytohormone responses and controlling physical as well as reproductive growth. Based on the RNA-seq and qRT-PCR analysis, GmVQ genes were showed expressing in nine tissues, suggesting their putative function in many aspects of plant growth and development as well as response to stress in Glycine max. RESULTS: This study aims to understand the roles of VQ genes in various development processes and their expression patterns in responses to stimuli. Our results provide basic information in identification and classification of GmVQ genes. Further experimental analysis will allows us to know the functions of GmVQs participation in plant growth and stress responses.

12.
Neurol Res ; 41(9): 780-790, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31092134

RESUMEN

Objectives-Elevated protein O-GlcNAcylation could benefit cell survival and promote organ functional recovery. Thiamet-G (O-GlcNAcase inhibitor) could upregulate protein O-GlcNAcylation level to improve dyskinesia in models of neurodegenerative diseases without any obvious detrimental side-effects. Therefore, we conducted this study to investigate the effects of protein O-GlcNAcylation upregulation by Thiamet-G on the spinal cord injury (SCI) in rats. Methods-We randomly assigned 74 rats to three groups: sham-operated group (Sham) with no lesion (n = 22), injured control group (SCI+SS) with saline solution (n = 26), and Thiamet-G treated group (SCI+Thiamet-G) (n = 26). We assessed Locomotor behavior using the Basso, Beattice, and Bresnahan (BBB) scale and evaluated histopathological alterations by morphometry and histochemistry. We also assessed potential inflammatory effects by microglia/macrophages immunohistochemistry, and potential apoptosis effects by caspase-3 western blot. Results-Thiamet-G treatment improved hindlimb motor functional recovery by inducing elevated protein O-GlcNAcylation, and mitigated the severity, reduced the lesion size and promoted the structural recovery of the injured spinal cord. Thiamet-G treatment also inhibited microglia/macrophages infiltration at the injury sites and the caspase-3 mediated apoptosis pathway. Discussion-We conclude that Thiamet-G induced elevated protein O-GlcNAcylation to ameliorate acute SCI, which could provide a potential novel therapeutic approach for SCI treatment.


Asunto(s)
Actividad Motora/efectos de los fármacos , Piranos/farmacología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Médula Espinal/patología , Tiazoles/farmacología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Microglía/efectos de los fármacos , Ratas Wistar , Recuperación de la Función/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/patología
13.
Cell Mol Neurobiol ; 39(3): 461-470, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30790096

RESUMEN

Temporal lobe epilepsy (TLE) is associated with neurodegeneration, often leading to hippocampal sclerosis (HS). Type 1 HS, which is characterized by severe neuronal loss and gliosis predominantly in regions CA1 and CA4, is the most common subtype and is associated with the best prognosis according to the ILAE classification system. MiRNAs participate in the biological processes underlying many nervous system diseases, including epilepsy. However, the miRNA expression profile of HS ILAE type 1 is not completely understood. A total of 14 patients were identified as having the ILAE subtype, as determined by NeuN immunohistochemistry (ILAE type 1 = 7; no-HS = 7). Next-generation sequencing and reverse transcription polymerase chain reaction technology were used to validate the dysregulated miRNAs. Bioinformatics analysis of the predicted target genes was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. In total, 1643 mature miRNAs were detected in this study, along with 5 miRNAs that were upregulated and 2 miRNAs that were downregulated in the type 1 group. Bioinformatics analysis showed that 1545 target genes were predicted using the miRDB and Targetscan databases and that these predicted genes showed enrichment in pathways associated with nucleic acid binding, intracellular and cellular macromolecule metabolic processes, and the PI3K-Akt signaling pathway. This study is the first to report the miRNA expression profile of HS ILAE type 1 compared with those of no-HS. These results provide new insights into the neuronal loss pathology of type 1 HS.


Asunto(s)
Epilepsia del Lóbulo Temporal/genética , Perfilación de la Expresión Génica , Hipocampo/patología , MicroARNs/genética , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Biología Computacional , Femenino , Humanos , Masculino , MicroARNs/metabolismo , Reproducibilidad de los Resultados , Esclerosis , Adulto Joven
14.
Inorg Chem ; 57(21): 13071-13074, 2018 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-30351076

RESUMEN

In this paper, we report a simple, rapid, and stable method for the continuous synthesis of highly stable Cs4PbBr6 perovskite microcrystals (MCs) using a microfluidic system. To demonstrate the potential application of Cs4PbBr6 MCs, the sample was fabricated with K2SiF6:Mn4+ phosphor onto InGaN blue chips as white-light-emitting diodes (LEDs). Our white-LED device achieved a high National Television Standards Committee value of 119% for backlight display, which indicated that the Cs4PbBr6 MC is a promising material for future applications.

15.
Epilepsy Res ; 144: 34-42, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29751355

RESUMEN

OBJECTIVE: Studies have shown that microRNAs play a role in the development of epilepsy by regulating downstream target messenger (m)RNA. The present study aims to determine the changes associated with microRNA-21-5p (miR-21-5p) during epileptogenesis in a kainic acid rat model, and to assess whether the PTEN-mTOR pathway is a target of miR-21-5p. METHOD: Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the quantitative expressions of miR-21-5p and PTEN, and Western blotting was used to test the activity of mTOR in the acute, latent, and chronic stages of epileptogenesis. The antagomir of miR-21-5p was injected into the intracerebroventricular space using a microsyringe. Neuronal death and epilepsy discharge were assessed by Nissl staining and electroencephalography (EEG), respectively. The Morris water maze (MWM) was used to assess the cognitive impairment in rats after status epilepticus (SE). RESULTS: Both miR-21-5p and mTOR were upregulated and PTEN was downregulated in rats during acute, latent, and chronic stages of epileptogenesis when compared with those of the control. After using antagomir miR-21-5p in vivo, miR-21-5p and mTOR decreased and the expression of PTEN increased compared with that in the SE model. The silencing of miR-21-5p diminished the number of abnormal spikes on EEG and decreased the number of neuron deletions on Nissl staining. The cognitive and memory impairment caused by epilepsy could also be improved after miR-21-5p knockdown in vivo. CONCLUSION: The results of the present study demonstrate that PTEN-mTOR is the target of miR-21-5p in a kainic acid model of epilepsy. The knockout of miR-21-5p decreases the neuronal damage in stages of epileptogenesis. The miR-21-5p/PTEN/mTOR axis may be a potential target for preventing and treating seizures and epileptic damage.


Asunto(s)
Anticonvulsivantes/uso terapéutico , MicroARNs/metabolismo , Fosfohidrolasa PTEN/metabolismo , Estado Epiléptico/tratamiento farmacológico , Serina-Treonina Quinasas TOR/metabolismo , Animales , Antagomirs/uso terapéutico , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/etiología , Modelos Animales de Enfermedad , Agonistas de Aminoácidos Excitadores/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Inyecciones Intraventriculares , Ácido Kaínico/toxicidad , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , MicroARNs/genética , Fosfohidrolasa PTEN/genética , Ratas , Ratas Wistar , Estadísticas no Paramétricas , Estado Epiléptico/inducido químicamente , Estado Epiléptico/complicaciones , Estado Epiléptico/patología , Serina-Treonina Quinasas TOR/genética , Factores de Tiempo
16.
Oncol Lett ; 14(3): 2933-2939, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28928831

RESUMEN

Glioblastoma multiforme (GBM), one of the most aggressive human malignant brain tumors, is induced by multiple complex pathological mechanisms. The main cause of mortality in patients with GBM is the invasion-metastasis cascade of tumor cells. The dysfunction of Parkinson protein 2 E3 ubiquitin protein ligase (PARK2) is closely linked with the development of certain human cancers. However, whether PARK2 is associated with metastasis in GBM remains unknown. The present study demonstrated that the metastasis and invasion of U87 cells were significantly repressed by PARK2 overexpression. Conversely, knockdown of PARK2 facilitated the metastasis and invasion of A172 cells. Furthermore, PARK2 downregulated zinc finger E-box-binding homeobox 1 (ZEB1) expression and mitigated epithelial-mesenchymal transition (EMT). Promoter effects of PARK2 knockdown on cell metastasis and EMT were antagonized by silencing ZEB1 expression. These results indicated that PARK2 participated in regulating the invasion-metastasis cascade of cancer cells by depressing ZEB1 expression and acting as a metastasis suppressor in GBM progression, providing a potential therapeutic approach for GBM treatment.

17.
Exp Ther Med ; 14(2): 1253-1259, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28810585

RESUMEN

Hsp70 regulates α-Synuclein (α-Syn) degeneration in Parkinson's disease (PD), indicating that Hsp70 promotion may be able to prevent or reverse α-Syn-induced toxicity in PD. Additionally, it has been demonstrated that glutamine (Gln) enhances Hsp70 expression. In the present study, Gln-induced Hsp70 promotion in pheochromocytoma was investigated with reverse transcription- quantitative polymerase chain reaction and western blotting methods. Then it was observed whether heat shock factor (HSF)-1 was required for this phenomenon with an RNA interference strategy. The regulatory role of Gln on α-Syn degeneration was also determined in the α-Syn-overexpressed PC12 [PC12 (α-Syn+)] cells, which were treated with or without the proteasomal inhibitor lactacystin (Lac). The results demonstrated that treatment with ≥10 mM Gln significantly increased Hsp70 mRNA and protein levels (P<0.05) and that this promotion was HSF-1-dependent, as HSF-1 knockout with HSF-1-specific small interfering RNA abrogated Hsp70 promotion in PC12 (α-Syn+) cells. Furthermore, Gln treatment markedly upregulated α-Syn degeneration in PC12 (α-Syn+) cells, which was significantly reduced (P<0.05) in the presence of Lac. Therefore, the present study suggests that Gln is able to induce the promotion of Hsp70 expression in PC12 cells in an HSF-1-dependent manner and that Gln-mediated Hsp70 promotion may increase α-Syn degradation even in the presence of proteasomal inhibitor. Thus, glutamine may be a potential therapeutic agent to prevent α-Syn aggregation in PD.

18.
Clin Cancer Res ; 23(21): 6640-6649, 2017 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-28790108

RESUMEN

Purpose: Glioma-initiating cells (GIC) are glioma stem-like cells that contribute to glioblastoma (GBM) development, recurrence, and resistance to chemotherapy and radiotherapy. They have recently become the focus of novel treatment strategies. Cyclophilin A (CypA) is a cytosolic protein that belongs to the peptidyl-prolyl isomerase (PPIase) family and the major intracellular target of the immunosuppressive drug cyclosporin A (CsA). In this study, we investigate the functions of CypA and its mechanism of action in GICs' development.Experimental Design: We analyzed differences in CypA expression between primary tumors and neurospheres from the GDS database, both before and after GIC differentiation. A series of experiments was conducted to investigate the role of CypA in GIC stemness, self-renewal, proliferation, radiotherapy resistance, and mechanism. We then designed glutathione S-transferase (GST) pulldown and coimmunoprecipitation assays to detect signaling activity.Results: In this study, we demonstrated that CypA promotes GIC stemness, self-renewal, proliferation, and radiotherapy resistance. Mechanistically, we found that CypA binds ß-catenin and is recruited to Wnt target gene promoters. By increasing the interaction between ß-catenin and TCF4, CypA enhances transcriptional activity.Conclusions: Our results demonstrate that CypA enhances GIC stemness, self-renewal, and radioresistance through Wnt/ß-catenin signaling. Due to its promotive effects on GICs, CypA is a potential target for future glioma therapy. Clin Cancer Res; 23(21); 6640-9. ©2017 AACR.


Asunto(s)
Ciclofilina A/administración & dosificación , Glioma/tratamiento farmacológico , Factor de Transcripción 4/genética , beta Catenina/genética , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Autorrenovación de las Células/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioma/genética , Glioma/patología , Glutatión Transferasa/genética , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Unión Proteica/efectos de los fármacos , Tolerancia a Radiación/genética , Factor de Transcripción 4/metabolismo , Vía de Señalización Wnt , beta Catenina/metabolismo
19.
Oncol Res ; 25(2): 187-194, 2017 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-28277190

RESUMEN

Glioma is a common type of malignant brain tumor characterized by aggressive metastasis capability. Recent evidence has suggested that noncoding RNAs, including microRNAs, have important functions in the pathophysiology of glioma development. In this study, we investigated the biological function of miR-422a in human glioma. We found that miR-422a was downregulated in glioma tissues. We also demonstrated that expression of miR-422a in glioma cells markedly suppressed cell proliferation, migration, and invasion. In addition, we identified insulin-like growth factor 1 (IGF1) and IGF1 receptor (IGF1R) as inhibitory targets of miR-422a in glioma cells. We established that the expression levels of miR-422a were negatively correlated with the expression levels of IGF1/IGF1R and the clinical parameters in glioma patients. An IGFR inhibitor, AG1024, completely blocked the activity of miR-442a on glioma cell proliferation and invasion, which further confirmed that miR-422a functions through IGF1 and IGF1R.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Marcación de Gen , Glioma/metabolismo , Factor I del Crecimiento Similar a la Insulina/biosíntesis , MicroARNs/biosíntesis , Receptores de Somatomedina/biosíntesis , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Marcación de Gen/métodos , Glioma/genética , Glioma/patología , Humanos , Factor I del Crecimiento Similar a la Insulina/antagonistas & inhibidores , Factor I del Crecimiento Similar a la Insulina/genética , MicroARNs/genética , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Receptor IGF Tipo 1 , Receptores de Somatomedina/antagonistas & inhibidores , Receptores de Somatomedina/genética
20.
Oncol Res ; 25(6): 1009-1019, 2017 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-28244850

RESUMEN

Pyroptosis is a type of proinflammatory programmed cell death mediated by caspase 1 activity and occurs in several types of eukaryotic tumor cells, including gliomas. MicroRNAs (miRNAs), small endogenous noncoding RNAs, have been demonstrated to be advantageous in glioma therapy. However, the question of whether miRNAs regulate pyroptosis in glioma remains unknown. The current study found that caspase 1 expression was substantially increased in both glioma tissues and glioma cell lines, U87 and T98G, while miR-214 expression was significantly downregulated. Luciferase reporter assay recognized caspase 1 as a target gene of miR-214. These findings demonstrate that miR-214 could inhibit cell proliferation and migration through the regulation of pyroptosis intermediated by caspase 1 in glioma U87 and T98G cells and may suggest a novel therapeutic for the intervention of glioma.


Asunto(s)
Neoplasias Encefálicas/patología , Caspasa 1/metabolismo , Glioma/patología , MicroARNs/genética , Piroptosis/genética , Neoplasias Encefálicas/genética , Caspasa 1/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Humanos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...