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2.
J Fungi (Basel) ; 9(3)2023 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-36983499

RESUMEN

Plants cope with abiotic stress in several ways, including by collaborating with microorganisms. Epichloë, an endophytic fungus, has been shown to improve plant tolerance to extreme external environments. Hordeum bogdanii is a known salt-tolerant plant with the potential to improve alkaline lands. NHX1 plays a key role in the transport of ions in the cell and is overexpressed in plants with increased salt tolerance. However, the expression levels of HbNHX1 in Epichloë endophytic fungal symbionts in H. bogdanii have not been elucidated. We used Hordeum bogdanii (E+) with the endophytic fungi Epichloë bromicola and H. bogdanii (E-) without the endophytic fungi and compared the differences in the ion content and HbNHX1 expression between the shoots and roots of E+ and E- plants under alkaline stress. The absorption capacity of both K+ and Na+ of H. bogdanii with endophytic fungi was higher than that without endophytic fungi. In the absence of alkaline stress, endophytic fungi significantly reduced the Cl- content in the host H. bogdanii. Alkaline stress reduced SO42- content in H. bogdanii; however, compared with E-, endophytic fungi increased the content of SO42- in E+ plants. With an increase in the alkaline concentration, the expression of HbNHX1 in the roots of H. bogdanii with endophytic fungus exhibited an upward trend, whereas the expression in the shoots exhibited a downward trend first and then an upward trend. Under 100 mmol·L-1 mixed alkaline stress, the expression of HbNHX1 in E+ was significantly higher than that in E-, indicating that endophytic fungi could increase the Na+ region in vacuoles. The external environment affects the regulation of endophytic fungi in H. bogdanii and that endophytic fungi can play a key role in soil salinization. Therefore, the findings of this study will provide technical support and a theoretical basis for better utilization of endophytic fungi from H. bogdanii in saline land improvement.

5.
J Vis Exp ; (174)2021 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-34487114

RESUMEN

A combined regional homogeneity (ReHo) and functional connectivity (FC) method, a type of noninvasive functional magnetic resonance imaging (fMRI) method, has been used to evaluate synchronous neuronal activity changes in retinitis pigmentosa (RP). The purpose of this study is to describe our method for analysis of intra- and interregional synchronizations of changes in neuronal activity in RP patients. The advantages of the combined ReHo and FC method are that it is both noninvasive and sufficiently sensitive to investigate changes in cerebral synchronous neuronal activity changes in vivo. Here, 16 RP patients and 14 healthy controls closely matched in age, sex, and education underwent resting-state fMRI scans. Two sample t-tests were conducted to compare ReHo and FC across groups. Our results showed that visual network disconnection and reorganization of the retino-thalamocortical pathway and dorsal visual stream occurred in the RP patients. Here, we describe the details of this method, its use, and the impact of its key parameters in a step-by-step manner.


Asunto(s)
Imagen por Resonancia Magnética , Corteza Visual , Encéfalo , Mapeo Encefálico , Humanos , Corteza Visual/diagnóstico por imagen
6.
Biomed Res Int ; 2020: 1913805, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32685447

RESUMEN

Previous neuroimaging studies demonstrated that visual deprivation triggers significant crossmodal plasticity in the functional and structural architecture of the brain. However, prior neuroimaging studies focused on the static brain activity in blindness. It remains unknown whether alterations of dynamic intrinsic brain activity occur in late blindness (LB). This study investigated dynamic intrinsic brain activity changes in individuals with late blindness by assessing the dynamic amplitude of low-frequency fluctuations (dALFFs) using sliding-window analyses. Forty-one cases of late blindness (LB) (29 males and 12 females, mean age: 39.70 ± 12.66 years) and 48 sighted controls (SCs) (17 males and 31 females, mean age: 43.23 ± 13.40 years) closely matched in age, sex, and education level were enrolled in this study. The dALFF with sliding-window analyses was used to compare the difference in dynamic intrinsic brain activity between the two groups. Compared with SCs, individuals with LB exhibited significantly lower dALFF values in the bilateral lingual gyrus (LING)/calcarine (CAL) and left thalamus (THA). LB cases also showed considerably decreased dFC values between the bilateral LING/CAL and the left middle frontal gyrus (MFG) and between the left THA and the right LING/cerebelum_6 (CER) (two-tailed, voxel-level P < 0.01, Gaussian random field (GRF) correction, cluster-level P < 0.05). Our study demonstrated that LB individuals showed lower-temporal variability of dALFF in the visual cortices and thalamus, suggesting lower flexibility of visual thalamocortical activity, which might reflect impaired visual processing in LB individuals. These findings indicate that abnormal dynamic intrinsic brain activity might be involved in the neurophysiological mechanisms of LB.


Asunto(s)
Ceguera/fisiopatología , Mapeo Encefálico , Encéfalo/fisiopatología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Curva ROC , Reproducibilidad de los Resultados , Factores de Tiempo
7.
Curr Med Sci ; 40(3): 539-547, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32681257

RESUMEN

Yu Gan Long (YGL) is a Chinese traditional herbal formula which has been reported to attenuate liver fibrosis for many years and we have explored its anti-fibrotic mechanism through blocking transforming growth factor (TGF-ß) in the previous study. But the mechanisms associated with platelet-derived growth factor (PDGF)-BB remain obscure. In this study, we further investigated the mechanism of YGL reducing carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Our results showed that YGL suppressed CCl4-induced upregulation of collagen IV (Col IV), type HI precollagen (PCHI), hyaluronuc acid (HA) and laminin (LN), which are implicated in liver fibrosis. Also, YGL reduced the α-smooth muscle actin (α-SMA) expression, which acts as the indicator of liver fibrosis. Furthermore, YGL decreased the serum levels of hepatic stellate cell (HSC) mitogen PDGF-BB and inflammation cytokines, including TNF-α, IL-1ß, IL-6. Markers involved in liver fibrosis, such as Ras, p-Raf-1, p-ERK1/2, p-JNK, p-P38, p-PI3K, p-AKT, p-JAKl, p-STAT3 were downregulated significantly after treatment with YGL. Our results indicated that YGL ameliorated CCl4-induced liver fibrosis by reducing inflammation cytokines production, and suppressing Ras/ERK, PI3K/AKT, and JAK1/STAT3 signaling pathways, which provided further evidence towards elucidation of the anti-fibrotic mechanism of YGL.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Tetracloruro de Carbono/farmacología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Janus Quinasa 1/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Cirrosis Hepática/inducido químicamente , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Medicina Tradicional China/métodos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Transcripción STAT3/metabolismo
8.
Neural Plast ; 2020: 6872508, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32399026

RESUMEN

Diabetic retinopathy (DR) patients are at an increased risk of cognitive decline and dementia. There is accumulating evidence that specific functional and structural architecture changes in the brain are related to cognitive impairment in DR patients. However, little is known regarding whether the functional architecture of resting-state networks (RSNs) changes in DR patients. The purpose of this study was to investigate the intranetwork functional connectivity (FC) and functional network connectivity (FNC) of RSN changes in DR patients using independent component analysis (ICA). Thirty-four DR patients (18 men and 16 women; mean age, 53.53 ± 8.67 years) and 38 nondiabetic healthy controls (HCs) (15 men and 23 women; mean age, 48.63 ± 11.83 years), closely matched for age, sex, and education, underwent resting-state magnetic resonance imaging scans. ICA was applied to extract the nine RSNs. Then, two-sample t-tests were conducted to investigate different intranetwork FCs within nine RSNs between the two groups. The FNC toolbox was used to assess interactions among RSNs. Pearson correlation analysis was conducted to explore the relationship between intranetwork FCs and clinical variables in the DR group. A receiver operating characteristic (ROC) curve was conducted to assess the ability of the intranetwork FCs of RSNs in discriminating between the two groups. Compared to the HC group, DR patients showed significant decreased intranetwork FCs within the basal ganglia network (BGN), visual network (VN), ventral default mode network (vDMN), right executive control network (rECN), salience network (SN), left executive control network (lECN), auditory network (AN), and dorsal default mode network (dDMN). In addition, FNC analysis showed increased VN-BGN, VN-vDMN, VN-dDMN, vDMN-lECN, SN-BGN, lECN-dDMN, and AN-BGN FNCs in the DR group, relative to the HC group. Furthermore, altered intranetwork FCs of RSNs were significantly correlated with the glycosylated hemoglobin (HbA1c) level in DR patients. A ROC curve showed that these specific intranetwork FCs of RSNs discriminated between the two groups with a high degree of sensitivity and specificity. Our study highlighted that DR patients had widespread deficits in both low-level perceptual and higher-order cognitive networks. Our results offer important insights into the neural mechanisms of visual loss and cognitive decline in DR patients.


Asunto(s)
Encéfalo/fisiopatología , Retinopatía Diabética/fisiopatología , Adulto , Mapeo Encefálico , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiopatología , Curva ROC
10.
Neuropsychiatr Dis Treat ; 15: 2487-2502, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31695385

RESUMEN

OBJECTIVE: There is increasing neuroimaging evidence that type 2 diabetes patients with retinal microvascular complications show abnormal brain functional and structural architecture and are at an increased risk of cognitive decline and dementia. However, changes in the topological properties of the functional brain connectome in diabetic retinopathy (DR) patients remain unknown. The aim of this study was to explore the topological organization of the brain connectome in DR patients using graph theory approaches. METHODS: Thirty-five DR patients (18 males and 17 females) and 38 healthy controls (HCs) (18 males and 20 females), matched for age, sex, and education, underwent resting-state magnetic resonance imaging scans. Graph theory analysis was performed to investigate the topological properties of brain functional connectome at both global and nodal levels. RESULTS: Both DR and HC groups showed high-efficiency small-world network in their brain functional networks. Notably, the DR group showed reduction in the clustering coefficient (P=0.0572) and local efficiency (P=0.0151). Furthermore, the DR group showed reduced nodal centralities in the default-mode network (DMN) and increased nodal centralities in the visual network (VN) (P<0.01, Bonferroni-corrected). The DR group also showed abnormal functional connections among the VN, DMN, salience network (SN), and sensorimotor network (SMN). Altered network metrics and nodal centralities were significantly correlated with visual acuity and fasting blood glucose level in DR patients. CONCLUSION: DR patients showed abnormal topological organization of the human brain connectome. Specifically, the DR group showed reduction in the clustering coefficient and local efficiency, relative to HC group. Abnormal nodal centralities and functional disconnections were mainly located in the DMN, VN, SN, and SMN in DR patients. Furthermore, the disrupted topological attributes showed correlations with clinical variables. These findings offer important insight into the neural mechanism of visual loss and cognitive deficits in DR patients.

11.
Vision Res ; 159: 68-75, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30904614

RESUMEN

This study investigated changes in intra- and inter-regional functional connectivity (FC) in individuals with retinitis pigmentosa (RP) by using regional homogeneity (ReHo) and FC methods. Sixteen RP individuals and 14 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scans (fMRI). A combined ReHo and FC method was conducted to evaluate synchronization of brain activity. Compared with HCs, RP individuals had significantly lower ReHo values in the bilateral lingual gyrus/cerebellum posterior lobe (LGG/CPL). In FC analysis, the RP group showed decreased positive FC relative to the HC group, from bilateral LGG/CPL to bilateral LGG/cuneus (CUN) and to left postcentral gyrus (PosCG). In contrast, the RP group showed increased negative FC relative to the HC group, from bilateral LGG/CPL to bilateral thalamus, and decreased negative FC from bilateral LGG/CPL to right middle frontal gyrus (MFG), and to left inferior parietal lobule (IPL). Moreover, ReHo values of the bilateral LGG/CPL showed negative correlations with the duration of RP. FC values of the bilateral LGG/CPL-left IPL showed negative correlations with best-corrected visual acuity (BCVA) of the right eye and left eye in RP individuals. Our results reveal reduced synchronicity of neural activity changes in the primary visual area in RP individuals. Moreover, RP individuals showed intrinsic visual network disconnection and reorganization of the retino-thalamocortical pathway and dorsal visual stream, suggesting impaired visuospatial and stereoscopic vision.


Asunto(s)
Ceguera/fisiopatología , Retinitis Pigmentosa/fisiopatología , Corteza Visual/fisiopatología , Vías Visuales/fisiología , Adulto , Mapeo Encefálico/métodos , Estudios de Casos y Controles , Conectoma , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Agudeza Visual
12.
Neuroreport ; 30(4): 295-304, 2019 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-30763285

RESUMEN

Previous neuroimaging studies have shown that the long-term effects of peripheral vision loss lead to functional and morphological reorganization in visual cortices. However, it has not been determined whether whole-brain functional network centrality changes occur during peripheral vision loss. This study aimed to investigate functional network centrality and connectivity changes in individuals with peripheral vision loss because of retinitis pigmentosa (RP) by using voxel-wise degree centrality (DC) and seed-based resting-state functional connectivity (rsFC) methods. In total, 30 RP patients (18 men and 12 women, mean age: 38.77±14.44 years) and 30 healthy controls (HCs) (18 men and 12 women, mean age: 34.57±10.70 years) matched for age, sex, cognition, education, and visual expertise underwent resting-state magnetic resonance imaging scans. Graph theory-based network analysis was carried out to investigate DC between the two groups. A seed-based rsFC analysis was then carried out to further reveal the abnormal functional connectivity of the altered DC brain region. Pearson's correlation was used to analyze the relationships of DC and rsFC index with the clinical variables in RP patients: visual function (best-corrected visual acuity and visual field, VF) and optical coherence tomography testing (mean retinal nerve fiber layer). Compared with HCs, RP patients had significantly lower DC values in the bilateral cuneus/calcarine/precuneus (CUN/CAL/PreCUN) [Brodmann's area (BA) 17/18/19/30/31]. In addition, RP patients showed decreased rsFC index, relative to that of HCs, from bilateral CUN/CAL/PreCUN to bilateral lingual/cuneus/calcarine (LIG/CUN/CAL) (BA 18/19/30) and the bilateral postcentral gyrus/superior parietal lobule (BA 3/5/7/40). In contrast, RP patients showed increased rsFC index, relative to that of HCs, from bilateral CUN/CAL/PreCUN to bilateral thalamus/caudate (voxel-level P<0.01; Gaussian random-field correction, cluster-level P<0.05). Moreover, the course of RP showed a negative correlation with the mean DC values of the bilateral CUN/CAL/PreCUN (r=-0.480; P=0.007) and the mean FC values of the bilateral LIG/CUN/CAL (r=-0.484; P=0.007); the mean DC values of the bilateral CUN/CAL/PreCUN in RP showed a negative correlation with the right eye VF (r=-0.411; P=0.024) and left eye VF (r=-0.426; P=0.019). Our results showed that RP patients showed abnormal function network hubs in various brain regions related to visual, thalamocortical, and sensorimotor networks; these might reflect impaired top-down modulations, visual imagery, and visuomotor coordination in RP patients. Moreover, the DC index can be used as a biomarker to indicate the severity of visual loss in RP patients.


Asunto(s)
Encéfalo/fisiopatología , Vías Nerviosas/fisiopatología , Retinitis Pigmentosa/fisiopatología , Adulto , Mapeo Encefálico/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad
13.
J Cell Physiol ; 234(7): 10324-10335, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30417359

RESUMEN

Renal cancer is a common urogenital system malignance. Novel biomarkers could provide more and more critical information on tumor features and patients' prognosis. Here, we performed an integrated analysis on the discovery set and established a three-gene signature to predict the prognosis for clear cell renal cell carcinoma (ccRCC). By constructing a LASSO Cox regression model, a 3-messenger RNA (3-mRNA) signature was identified. Based on the 3-mRNA signature, we divided patients into high- and low-risk groups, and validated this by using three other data sets. In the discovery set, this signature could successfully distinguish between the high- and low-risk patients (hazard ratio (HR), 2.152; 95% confidence interval (CI),1.509-3.069; p < 0.0001). Analysis of internal and two external validation sets yielded consistent results (internal: HR, 2.824; 95% CI, 1.601-4.98; p < 0.001; GSE29609: HR, 3.002; 95% CI, 1.113-8.094; p = 0.031; E-MTAB-3267: HR, 2.357; 95% CI, 1.243-4.468; p = 0.006). Time-dependent receiver operating characteristic (ROC) analysis indicated that the area under the ROC curve at 5 years was 0.66 both in the discovery and internal validation set, while the two external validation sets also suggested good performance of the 3-mRNA signature. Besides that, a nomogram was built and the calibration plots and decision curve analysis indicated the good performance and clinical utility of the nomogram. In conclusion, this 3-mRNA classifier proved to be a useful tool for prognostic evaluation and could facilitate personalized management of ccRCC patients.


Asunto(s)
Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Anciano , Biomarcadores de Tumor/genética , Femenino , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Estimación de Kaplan-Meier , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , ARN Mensajero/genética , Curva ROC , Transcriptoma/genética
14.
Neuropsychiatr Dis Treat ; 14: 3317-3327, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30584305

RESUMEN

BACKGROUND: Previous studies demonstrated that early blindness is associated with abnormal intrinsic functional connectivity (FC) between the primary visual cortex (V1) and other sensory areas. However, the V1 pattern of spontaneous neural activity occurring in late blindness (LB) remains unknown. The purpose of this study was to investigate the intrinsic FC patterns of V1 in LB. MATERIALS AND METHODS: Thirty LB individuals (18 males and 12 females; mean age: 38.76±14.43 years) and 30 sighted controls (SCs) individuals (18 males and 12 females; mean age: 38.67±13.85 years) closely matched for age, sex, and education, underwent resting-state magnetic resonance imaging scans. Region of interest analysis was performed to extract the correlation coefficient matrix among each pair of Brodmann area (BA) 17 and FC between V1 and vision-related subcortical nuclei. RESULTS: Compared with SCs, LB individuals showed a decreased FC between the left V1 and the bilateral cuneus (CUN)/lingual gyrus (LGG)/calcarine (CAL) (BA 18/19/30) and left precentral gyrus (PreCG) and the postcentral gyrus (PostCG) (BA 2/3/4). Also, LB individuals showed a decreased FC between the right V1 and the bilateral CUN/LGG/CAL (BA 18/19/30) and the left PreCG and PostCG (BA 2/3/4/6) (voxel-level: P<0.01, cluster-level: P<0.05). Meanwhile, LB individuals showed a decreased FC between the left V1 and the right V1 and increased FC between the left V1 and the right superior colliculus, the right V1, and the left hippocampus (P<0.05). Moreover, a positive correlation was observed between the onset age of blindness and FC values in V1 to CUN/LGG/CAL in LB. CONCLUSION: Our results highlighted that LB induces a decreased FC between V1 and higher visual areas, motor cortices, and somatosensory cortices at rest. This might indicate that LB humans could present with impaired top-down modulations, visual imagery, and vision-motor function.

15.
Front Genet ; 9: 328, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30158955

RESUMEN

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. And currently, there are no specific diagnostic biomarkers for ACC. In our study, we aimed to screen biomarkers for disease diagnosis, progression and prognosis. We firstly used the microarray data from public database Gene Expression Omnibus database to construct a weighted gene co-expression network, and then to identify gene modules associated with clinical features of ACC. Though this algorithm, a significant module with R2 = 0.64 (P = 9 × 10-5) was identified. Co-expression network and protein-protein interaction network were performed for screen the candidate hub genes. Checked by The Cancer Genome Atlas (TCGA) database, another independent dataset GSE19750, and GEPIA database, using one-way ANOVA, Pearson's correlation, survival analysis, diagnostic capacity (ROC curve) and expression level revalidation, a total 12 real hub genes were identified. Gene ontology and KEGG pathway analysis of genes in the significant module revealed that the hub genes are significantly enriched in cell cycle regulation. Moreover, gene set enrichment analysis suggests that the samples with highly expressed hub genes are correlated with cell cycle. Taken together, our integrated analysis has identified 12 hub genes that are associated with the progression and prognosis of ACC; these hub genes might lead to poor outcomes by regulating the cell cycle.

16.
Neuroreport ; 29(15): 1323-1332, 2018 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-30113921

RESUMEN

The study aimed to determine alterations in intrinsic brain activity in retinitis pigmentosa (RP) individuals using the amplitude of low-frequency fluctuation (ALFF)/fractional amplitude of low-frequency fluctuation (fALFF) method. Sixteen RP individuals (10 men and six women) and 14 healthy controls (HCs) (six men and eight women) closely matched in age, sex, and education were enrolled in the study. The ALFF/fALFF method was applied to compare different intrinsic brain activities between the RP group and the HC group. The relationship between the mean ALFF/fALFF signal values of different brain regions and the visual measurements in RP group was analyzed by Pearson correlation. Compared with HCs, RP individuals had significantly lower ALFF values in the bilateral lingual gyrus (LIGG)/cerebellum posterior lobe [Brodmann area (BA) 17,18], but lower fALFF values in the bilateral LIGG/cerebellum anterior lobe (BA 17,18). Meanwhile, RP individuals had significantly higher ALFF in the bilateral precuneus cortex/middle cingulate cortex (BA 7,31), as well as higher fALFF values in the left superior/middle frontal gyrus (BA 9,10) and bilateral supplementary motor area (BA 6,8) (voxel-level P<0.01, cluster-level P<0.05). Moreover, the fALFF values of the bilateral LIGG/cerebellum anterior lobe showed positive relationships with the best-corrected visual acuity (BCVA)-oculus dexter (r=0.574, P=0.020) and BCVA-oculus sinister (r=0.570, P=0.021) in RP individuals; our results provide evidence that RP individuals may have impaired intrinsic brain activity in the primary visual area and the visuomotor coordination area that correlates with BCVA. Moreover, our findings indicate that reorganization of the dorsal visual stream and the parietoprefrontal pathway occurs in RP individuals.


Asunto(s)
Encéfalo/fisiopatología , Retinitis Pigmentosa/fisiopatología , Trastornos de la Visión/fisiopatología , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Descanso , Retinitis Pigmentosa/complicaciones , Retinitis Pigmentosa/diagnóstico por imagen , Trastornos de la Visión/diagnóstico por imagen , Trastornos de la Visión/etiología , Adulto Joven
17.
Front Physiol ; 9: 399, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29720944

RESUMEN

Clear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cancer whose prognostic is affected by the tumor progression associated with complex gene interactions. However, there is currently no available molecular markers associated with ccRCC progression and used or clinical application. In our study, microarray data of 101 ccRCC samples and 95 normal kidney samples were analyzed and 2,425 differentially expressed genes (DEGs) were screened. Weighted gene co-expression network analysis (WGCNA) was then conducted and 11 co-expressed gene modules were identified. Module preservation analysis revealed that two modules (red and black) were found to be most stable. In addition, Pearson's correlation analysis identified the module most relevant to pathological stage(patho-module) (r = 0.44, p = 3e-07). Functional enrichment analysis showed that biological processes of the patho-module focused on cell cycle and cell division related biological process and pathway. In addition, 29 network hub genes highly related to ccRCC progression were identified from the stage module. These 29 hub genes were subsequently validated using 2 other independent datasets including GSE53757 (n = 72) and TCGA (n = 530), and the results indicated that all hub genes were significantly positive correlated with the 4 stages of ccRCC progression. Kaplan-Meier survival curve showed that patients with higher expression of each hub gene had significantly lower overall survival rate and disease-free survival rate, indicating that all hub genes could act as prognosis and recurrence/progression biomarkers of ccRCC. In summary, we identified 29 molecular markers correlated with different pathological stages of ccRCC. They may have important clinical implications for improving risk stratification, therapeutic decision and prognosis prediction in ccRCC patients.

18.
Cancer Lett ; 414: 278-293, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29175458

RESUMEN

Transmembrane-4-L-Six-Family-1 (TM4SF1) is a member of the L6 family and functions as a signal transducer to regulate cell development, growth and motility. Here we show that TM4SF1 is strongly upregulated in human muscle invasive bladder cancer (MIBC) tissues, corroborating the bioinformatical results of transcriptome analysis. Moreover, tissue microarray (TMA) shows significant correlations (p < 0.05) between high expression of TM4SF1 and T stage, TNM stage, lymph node metastasis status and survival rate of MIBC patients, indicating a positive association between TM4SF1 expression and poorer prognosis. Furthermore, in vitro and in vivo studies indicate that the proliferation of human bladder cancer (BCa) cells is significantly suppressed by knockdown of TM4SF1 (p < 0.05). Functionally, the reduction of TM4SF1 could induce cell cycle arrest and apoptosis possibly via the upregulation of reactive oxygen species (ROS) in BCa cells. In addition, these observations could be recovered by treatment with GW9662 (antagonist of PPARγ) and resveratrol (activator of SIRT1). Taken together, our results suggest that high expression of TM4SF1 predicts poor prognosis of MIBC.


Asunto(s)
Antígenos de Superficie/genética , Apoptosis/genética , Ciclo Celular/genética , Proteínas de Neoplasias/genética , PPAR gamma/genética , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/genética , Neoplasias de la Vejiga Urinaria/genética , Anciano , Animales , Antígenos de Superficie/metabolismo , Línea Celular Tumoral , Retroalimentación Fisiológica , Femenino , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Ratones Endogámicos NOD , Ratones SCID , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , PPAR gamma/metabolismo , Interferencia de ARN , Tratamiento con ARN de Interferencia/métodos , Sirtuina 1/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/terapia , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
19.
J Cancer ; 8(12): 2282-2295, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28819432

RESUMEN

Holliday Junction Recognition Protein (HJURP) is a centromeric histone chaperone involving in de novo histone H3 variant CenH3 (CENP-A) recruitment. Our transcriptome and in vivo study revealed that HJURP is significantly upregulated in bladder cancer (BCa) tissues at both mRNA and protein levels. Knockdown of HJURP inhibited proliferation and viability of BCa cell lines revealed by CCK-8, colony formation and Ki-67-staining assays, and induced apoptosis and reactive oxygen species (ROS) production, as well as triggered cell cycle arrest at G0/G1 phase possibly via loss of CENP-A. Interestingly, in the HJURP-reduced BCa cells the levels of PPARγ and acetylated-p53 were increased, while the ratio of phosphorylated/total SIRT1 protein was decreased. Moreover, after treatment of the BCa cells using PPARγ antagonist (GW9662) and SIRT1 agonist (resveratrol, RSV) respectively, thee phenotypes of cell cycle arrest, increased ROS production and inhibited proliferation rate were all rescued. Taken together, our results suggested that HJURP might regulate proliferation and apoptosis via the PPARγ-SIRT1 negative feedback loop in BCa cells.

20.
Nat Prod Res ; 31(19): 2239-2244, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28287271

RESUMEN

A new catechin derivative named as sterilin A (1), and three known compounds, (+)-catechin (2), kaji-ichigoside F1 (3) and 2α,3α,19α-trihydroxyurs-12-en-28-oic acid-28-O-ß-D-xylopyranosyl-(1 â†’ 2)-ß-D-glucopyranoside (4), was isolated from the fresh fruits of Rosa sterilis. Their structures were elucidated by means of extensive spectroscopic analysis and by comparison with data reported in the literatures.


Asunto(s)
Catequina/análogos & derivados , Catequina/aislamiento & purificación , Rosa/química , Catequina/química , Frutas/química , Glucanos , Estructura Molecular , Análisis Espectral
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