RESUMEN
Renal cell carcinoma (RCC) is a serious threat to people's health due to its rapid progression, and patients easily develop resistance to targeted therapy. The absent in melanoma 2 (AIM2) is a receptor protein that has recently been proposed to play an important role in various diseases. In this study, AIM2 was identified as a new biomarker of RCC and promoted RCC progression and sunitinib resistance in an inflammasome-independent manner. Mechanistically, AIM2 promoted FOXO3a phosphorylation and proteasome degradation, thereby reducing its transcriptional effect on ACSL4 and inhibiting ferroptosis. In summary, AIM2 promoted RCC progression and sunitinib resistance through FOXO3a-ACSL4 axis-regulated ferroptosis, which could provide new ideas and therapeutic targets for RCC diagnosis and treatment.
Asunto(s)
Carcinoma de Células Renales , Ferroptosis , Neoplasias Renales , Melanoma , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Sunitinib/farmacología , Sunitinib/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Ferroptosis/genética , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Proteínas de Unión al ADNRESUMEN
Fluid intelligence is arguably the defining feature of human cognition. Yet the nature of its relationship with the brain remains a contentious topic. Influential proposals drawing primarily on functional imaging data have implicated 'multiple demand' frontoparietal and more widely distributed cortical networks, but extant lesion-deficit studies with greater causal power are almost all small, methodologically constrained, and inconclusive. The task demands large samples of patients, comprehensive investigation of performance, fine-grained anatomical mapping, and robust lesion-deficit inference, yet to be brought to bear on it. We assessed 165 healthy controls and 227 frontal or non-frontal patients with unilateral brain lesions on the best-established test of fluid intelligence, Raven's Advanced Progressive Matrices, employing an array of lesion-deficit inferential models responsive to the potentially distributed nature of fluid intelligence. Non-parametric Bayesian stochastic block models were used to reveal the community structure of lesion deficit networks, disentangling functional from confounding pathological distributed effects. Impaired performance was confined to patients with frontal lesions [F(2,387) = 18.491; P < 0.001; frontal worse than non-frontal and healthy participants P < 0.01, P <0.001], more marked on the right than left [F(4,385) = 12.237; P < 0.001; right worse than left and healthy participants P < 0.01, P < 0.001]. Patients with non-frontal lesions were indistinguishable from controls and showed no modulation by laterality. Neither the presence nor the extent of multiple demand network involvement affected performance. Both conventional network-based statistics and non-parametric Bayesian stochastic block modelling heavily implicated the right frontal lobe. Crucially, this localization was confirmed on explicitly disentangling functional from pathology-driven effects within a layered stochastic block model, prominently highlighting a right frontal network involving middle and inferior frontal gyrus, pre- and post-central gyri, with a weak contribution from right superior parietal lobule. Similar results were obtained with standard lesion-deficit analyses. Our study represents the first large-scale investigation of the distributed neural substrates of fluid intelligence in the focally injured brain. Combining novel graph-based lesion-deficit mapping with detailed investigation of cognitive performance in a large sample of patients provides crucial information about the neural basis of intelligence. Our findings indicate that a set of predominantly right frontal regions, rather than a more widely distributed network, is critical to the high-level functions involved in fluid intelligence. Further they suggest that Raven's Advanced Progressive Matrices is a useful clinical index of fluid intelligence and a sensitive marker of right frontal lobe dysfunction.
Asunto(s)
Encéfalo , Inteligencia , Humanos , Teorema de Bayes , Encéfalo/diagnóstico por imagen , Cognición , Corteza Prefrontal , Lóbulo Frontal/diagnóstico por imagen , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética , Pruebas NeuropsicológicasRESUMEN
Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system. The mortality of advanced RCC remains high despite advances in systemic therapy of RCC. Considering the misdiagnosis of early-stage RCC, the identification of effective biomarkers is of great importance. Tissue inhibitor matrix metalloproteinase 1 (TIMP1), which belongs to TIMP gene family, is a natural inhibitor of the matrix metalloproteinases (MMPs). In this study, we found TIMP1 was significantly up-regulated in cell lines and RCC tissues. Kaplan-Meier analysis revealed that high expression of TIMP1 indicated a poor prognosis. Multivariate analysis further indicated that TIMP1 overexpression was an independent prognostic factor of RCC patients. Furthermore, knockdown of TIMP1 in vitro suppressed the proliferation, migration, and invasion of RCC cells, while upregulating TIMP1 accelerated the proliferation, migration, and invasion of RCC cells. In addition, we also found that TIMP1 prompted the progression of RCC via epithelial-to-mesenchymal transition (EMT) signaling pathway. In conclusion, the present results suggested that TIMP1 indicated poor prognosis of renal cell carcinoma and could serve as a potential diagnostic and prognostic biomarker for RCC.
RESUMEN
Background: Brain-derived neurotrophic factor (BDNF) is involved in the regulation of Alzheimer's disease (AD), but the mechanism is not clear. This study explores the possible mechanism of microRNA-206-3p (miR-206-3p) participating in the neuroprotective effect of AD mice by regulating BDNF. Methods: 36 SPF grade C57 mice were randomly divided into normal group, model group and miR-206-3p mimics group (intraperitoneal injection of 3 mm miR-206-3p mimics) (n=12). miR-206-3p mimics group was intervened by miR-206-3p mimics on the basis of AD model. The expression of miR-206-3p was detected by Real time quantitative polymerase chain reaction (qPCR). Zea-Longa score and water maze were used for behavioral detection, he was used to observe the morphology of neurons, and immunohistochemical Western blot was used to detect the expression of BDNF protein, and the targeting relationship between miR-206-3p and BDNF was analyzed. Results: Compared with the model group, the expression level of miR-206-3p in miR-206-3p mimics group was significantly higher (P<0.05). compared with the model group, the Zea-Longa score in miR-206-3p mimics group was significantly lower (P<0.05). The escape latency of miR-206-3p mimics group was significantly shorter than that of model group, and the number of crossing the original platform was significantly more than that of model group (P<0.05). The morphology of neurons in miR-206-3p mimics group was significantly better than that in model group; Immunohistochemistry and Western blot showed that the relative expression of miR-206-3p mimics BDNF protein was significantly increased compared with the model group (P<0.05). Compared with miR-206-3p control group, the luciferase activity at 3' end untranslated area (3' UTR) end of wild-type BDNF in miR-206-3p inhibition group decreased significantly (P<0.01). Conclusions: miR-206-3p exerts neuroprotective effects on AD mouse neurons by up-regulating BDNF.
RESUMEN
Spray drift buffers are often required on herbicide labels to prevent potential drift effects to nontarget plants. Buffers are typically derived by determining the distance at which predicted exposure from spray drift equals the ecotoxicology threshold for sensitive plant species determined in greenhouse tests. Field studies performed under realistic conditions have demonstrated, however, that this approach is far more conservative than necessary. In 2016, the US Environmental Protection Agency estimated that isoxaflutole (IFT), a herbicide used to control grass and broadleaf weeds, could adversely affect downwind nontarget dicot plants at distances of ≥304 m from the edge of the treated field due to spray drift. This prediction implies that a buffer of at least 304 m is required to protect nontarget plants. To refine the predicted buffer distance for IFT, we conducted a field study in which sensitive nontarget plants (lettuce and navy bean, two to four leaf stage) were placed at various distances downwind from previously harvested soybean fields sprayed with Balance® Flexx Herbicide. The test plants were then transported to a greenhouse for grow out following the standard vegetative vigor test protocol. There were three trials. One had vegetation in the downwind deposition area (i.e., test plants placed in mowed grass; typical exposure scenario) and two had bare ground deposition areas (worst-case exposure scenario). For both plant species in bare ground deposition areas, effects on shoot height and weight were observed at 1.52 m but not at downwind distances of ≥9.14 m from the edge of the treated area. No effects were observed at any distance for plants placed in the vegetated deposition area. The field study demonstrated that a buffer of 9.14 m protects nontarget terrestrial plants exposed to IFT via spray drift even under worst-case conditions. Integr Environ Assess Manag 2022;18:757-769. © 2021 Bayer. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Asunto(s)
Herbicidas , Ecotoxicología , Herbicidas/análisis , Herbicidas/toxicidad , Isoxazoles , PlantasRESUMEN
BACKGROUND: The key role of hypoxia-inducible factor 2alpha (HIF2α) in the process of renal cancer has been confirmed. In the field of tumour research, oxidative stress is also considered to be an important influencing factor. However, the relationship and biological benefits of oxidative stress and HIF2α in ccRCC remain unclear. This research attempts to explore the effect of oxidative stress on the cancer-promoting effect of HIF2α in ccRCC and reveal its mechanism of action. METHODS: The bioinformatics analysis for ccRCC is based on whole transcriptome sequencing and TCGA database. The detection of the expression level of related molecules is realised by western blot and PCR. The expression of Nucleoside diphosphate-linked moiety X-type motif 1 (NUDT1) was knocked down by lentiviral infection technology. The functional role of NUDT1 were further investigated by CCK8 assays, transwell assays and cell oxidative stress indicator detection. The exploration of related molecular mechanisms is realised by Luciferase assays and Chromatin immunoprecipitation (ChIP) assays. RESULTS: Molecular screening based on knockdown HIF2α sequencing data and oxidative stress related data sets showed that NUDT1 is considered to be an important molecule for the interaction of HIF2α with oxidative stress. Subsequent experimental results showed that NUDT1 can cooperate with HIF2α to promote the progression of ccRCC. And this biological effect was found to be caused by the oxidative stress regulated by NUDT1. Mechanistically, HIF2α transcription activates the expression of NUDT1, thereby inhibiting oxidative stress and promoting the progression of ccRCC. CONCLUSIONS: This research clarified a novel mechanism by which HIF2α stabilises sirtuin 3 (SIRT3) through direct transcriptional activation of NUDT1, thereby inhibiting oxidative stress to promote the development of ccRCC. It provided the possibility for the selection of new therapeutic targets for ccRCC and the study of combination medication regimens.
Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/efectos adversos , Carcinoma de Células Renales/genética , Enzimas Reparadoras del ADN/efectos de los fármacos , Estrés Oxidativo/genética , Monoéster Fosfórico Hidrolasas/efectos de los fármacos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Carcinoma de Células Renales/fisiopatología , Línea Celular Tumoral/metabolismo , Enzimas Reparadoras del ADN/genética , Humanos , Neoplasias , Estrés Oxidativo/efectos de los fármacos , Monoéster Fosfórico Hidrolasas/genéticaRESUMEN
Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the kidney. New and reliable biomarkers are in urgent need for ccRCC diagnosis and prognosis. The CENP family is overexpressed in many types of cancers, but its functions in ccRCC have not been fully clarified. In this paper, we found that several CENP family members were highly expressed in ccRCC tissues. Also, CENPA expression level was related to clinicopathological grade and prognosis by weighted gene co-expression network analysis (WGCNA). CENPA served as a representative CENP family member as a ccRCC biomarker. Further in vitro experiments verified that overexpression of CENPA promoted ccRCC proliferation and metastasis by accelerating the cell cycle and activating the Wnt/ß-catenin signaling pathway. The elevated ß-catenin led by CENPA overexpression translocated to nucleus for downstream effect. Functional recovery experiment confirmed that Wnt/ß-catenin pathway was essential for ccRCC progression and metastasis. Developing selective drugs targeting CENPA may be a promising direction for cancer treatment.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/genética , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/genética , Pronóstico , Vía de Señalización WntRESUMEN
The voluntary generation of non-overlearned responses is usually assessed with phonemic fluency. Like most frontal tasks, it draws upon different complex processes and systems whose precise nature is still incompletely understood. Many claimed aspects regarding the pattern of phonemic fluency performance and its underlying anatomy remain controversial. Major limitations of past investigations include small sample size, scant analysis of phonemic output and methodologically insufficient lesion analysis approaches. We investigated a large number of patients with focal unilateral right or left frontal (n = 110) or posterior (n = 100) or subcortical (n = 65) lesions imaged with magnetic resonance or computed tomography and compared their performance on the number of overall responses, words produced over time, extremely infrequent/unknown words and inappropriate words generated. We also employed, for the first time parcel-based lesion-symptom mapping, tract-wise statistical analysis as well as Bayesian multi-variate analysis based on meta-analytically defined functional region of interest, including their interactions. We found that left frontal damage was associated with greater impairment than right frontal or posterior damage on overall fluency performance, suggesting that phonemic fluency shows specificity to frontal lesions. We also found that subcorticals, similar to frontals, performed significantly worse than posteriors on overall performance suggesting that subcortical regions are also involved. However, only frontal effects were found for words produced over time, extremely infrequent/unknown and inappropriate words. Parcel-based lesion-symptom mapping analysis found that worse fluency performance was associated with damage to the posterior segment of the left frontal middle and superior gyrus, the left dorsal anterior cingulate gyrus and caudate nucleus. Tract-wise statistical analysis revealed that disconnections of left frontal tracts are critical. Bayesian multi-variate models of lesions and disconnectome maps implicated left middle and inferior frontal and left dorsomedial frontal regions. Our study suggests that a set of well localized left frontal areas together with subcortical regions and several left frontal tracts are critical for word generation. We speculate that a left lateralized network exists. It involves medial, frontal regions supporting the process of 'energization', which sustains activation for the duration of the task and middle and inferior frontal regions concerned with 'selection', required due to the competition produced by associated stored words, respectively. The methodology adopted represents a promising and empirically robust approach in furthering our understanding of the neurocognitive architecture underpinning executive processes.
RESUMEN
Cognitive and behavioural outcomes in stroke reflect the interaction between two complex anatomically-distributed patterns: the functional organization of the brain and the structural distribution of ischaemic injury. Conventional outcome models-for individual prediction or population-level inference-commonly ignore this complexity, discarding anatomical variation beyond simple characteristics such as lesion volume. This sets a hard limit on the maximum fidelity such models can achieve. High-dimensional methods can overcome this problem, but only at prohibitively large data scales. Drawing on one of the largest published collections of anatomically-registered imaging of acute stroke-N = 1333-here we use non-linear dimensionality reduction to derive a succinct latent representation of the anatomical patterns of ischaemic injury, agglomerated into 21 distinct intuitive categories. We compare the maximal predictive performance it enables against both simpler low-dimensional and more complex high-dimensional representations, employing multiple empirically-informed ground truth models of distributed structure-outcome relationships. We show our representation sets a substantially higher ceiling on predictive fidelity than conventional low-dimensional approaches, but lower than that achievable within a high-dimensional framework. Where descriptive simplicity is a necessity, such as within clinical care or research trials of modest size, the representation we propose arguably offers a favourable compromise of compactness and fidelity.
Asunto(s)
Accidente Cerebrovascular , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Humanos , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
Ferroptosis is a novel form of cell death and plays a role in various diseases, especially tumors. It has been reported that ferroptosis is involved in the growth and progression of clear cell renal cell carcinoma (ccRCC); however, the specific molecular mechanisms are still unclear. In this study, we constructed a four-gene signature (FeSig) of ferroptosis-related genes via Cox regression analysis. ROC and survival analyses indicated that FeSig had good diagnostic and prognostic value. Further analysis revealed that ferroptosis was associated with tumor immunity in ccRCC. Next, weighted gene co-expression network analysis was performed to identify the potential regulatory mechanisms. Combined with correlation and survival analyses, the TAZ/WNT10B axis was identified as a tumor immune-related regulatory pathway. In conclusion, these findings suggest that ferroptosis is correlated with tumor immunity. The TAZ/WNT10B axis may be a novel biomarker and therapeutic target for immunotherapy in ccRCC.
RESUMEN
Synthetic pyrethroids are frequently detected as trace contaminants in sediment and natural waters. Because of the importance of measuring both total and freely available concentrations for ecotoxicity evaluations, solid-phase microextraction (SPME) combined with gas chromatography-mass spectrometry using negative chemical ionization (NCI-GC-MS) was investigated as an analytical technique. Automated SPME-NCI-GC-MS quantification of freely dissolved (and thus potentially bioavailable) pyrethroids in aqueous samples containing dissolved organic matter (DOM) was successfully applied. The introduction of stable isotope-labeled pyrethroid calibration standards into the water sample allows for the simultaneous determination of total concentrations. Because pyrethroids adsorb rapidly to container walls (especially in calibration standard solutions without DOM) it was necessary to develop a technique to minimize the resulting time-dependent losses from calibration standard solutions in autosampler vials as they await analysis. A staggered preparation of these analytical calibration standards immediately prior to analysis was shown to ameliorate this problem. The developed method provides accurate and reproducible results for aqueous samples containing a range of dissolved organic matter concentrations (e.g., sediment pore water or sediment/water mixtures) and yields practical benefits in comparison to conventional analysis methods, such as reduced sample volume requirements, reduced solvent consumption, and fewer sample manipulations, and makes simultaneous measurements of freely dissolved/bioavailable pyrethroids and total pyrethroids possible.
Asunto(s)
Piretrinas/análisis , Contaminantes del Suelo/análisis , Contaminantes Químicos del Agua/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Sedimentos Geológicos/análisis , Límite de Detección , Estanques/análisis , Piretrinas/aislamiento & purificación , Contaminantes del Suelo/aislamiento & purificación , Microextracción en Fase Sólida/métodos , Contaminantes Químicos del Agua/aislamiento & purificaciónRESUMEN
Clear cell renal cell carcinoma (ccRCC) accounts for approximately 4/5 of all kidney cancers. Accumulation of minor changes in the cellular homeostasis may be one cause of ccRCC. Therefore, we downloaded the RNA sequencing and survival data of the kidney renal cell carcinoma (KIRC) cohort from the Cancer Genome Atlas (TCGA) database. After the univariate and multivariate Cox regression analyses, 19 kidney-specific differentially expressed genes (DEGs) were found. Solute Carrier Family 22 Member 12 (SLC22A12) resulted in an independent prognostic predictor for both overall survival (OS) and disease-free survival (DFS). SLC22A12 expression was lower in tumoral tissue compared to normal tissue. Moreover, patients in the SLC22A12 low expression group had a higher pathological stage and worse survival than the high expression group. Additionally, qRT-PCR assay, immunoblotting test (IBT), and immunohistochemical (IHC) analyses of cancer tissues/cells and the corresponding normal controls verified that SLC22A12 is downregulated in ccRCC. Receiver operator characteristic (ROC) curves showed that the low expression level of SLC22A12 could be a good diagnostic marker for ccRCC (AUC=0.7258; p <0.0001). Gene set enrichment analysis (GSEA) showed that SLC22A12 expression levels are related to metabolism, cell cycle, and tumor-related signaling pathways. GO and KEGG analyses revealed that SLC22A12 transports multiple organic compounds, ions, and hormones and participates in the extracellular structure organization. Furthermore, SLC22A12 over-expression in vitro inhibited the proliferation, migration, and invasion of renal cancer cells by regulating PI3K/Akt pathways. Such effects were reversed when knocking out SLC22A12. In summary, as a transporter for many vital metabolites, SLC22A12 may affect tumor cell survival through its impacts on the mentioned metabolites. In conclusion, this study uncovered that SLC22A12 is a promising prognostic and diagnostic biomarker for ccRCC.
RESUMEN
Clear cell renal cell carcinoma (ccRCC) is characterized by its insensitivity to chemoradiotherapy and lacks effective diagnostic and prognostic biomarkers. In this study, we focused on the role of m6A RNA methylation regulators for tumor immunity. Based on the expression of 20 m6A regulators, consensus clustering was performed to divide patients into cluster1/cluster2 and showed that there was a survival difference between the two clusters. Through cox regression analysis, five hub m6A regulators were screened to construct a risk model. Further analysis showed that the risk score was an independent prognostic factor. GSEA, GSVA, and KEGG analysis revealed that immune cell pathways played a critical role between the high risk group and low risk group. Combined with CIBERSORT and survival analysis, five hub tumor-infiltrating immune cells (TIICs) were identified for further study. Meanwhile, correlation analysis indicated that IGF2BP2 was positively associated with activated memory CD4 T cell and METTL14 was negatively correlated to the regulatory T cell. Therefore, IGF2BP2 and METTL14 were regarded as key genes. Further study verified that only METTL14 possessed good diagnostic and prognostic value. Then, GSEA exhibited that METTL14 was mainly enriched in chemokine related pathways. We also found that CCL5 was negatively correlated to METTL14 and might serve as a potential target of METTL14. In conclusion, these findings suggest that the METTL14/CCL5/Tregs axis is a potential signaling pathway for regulating tumor immunity, and might become novel therapeutic targets for ccRCC.
RESUMEN
Renal cell carcinoma (RCC) is the most frequent malignant tumor of the kidney. 30% of patients with RCC are diagnosed at an advanced stage. Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of RCC. Currently, advanced ccRCC lacks reliable diagnostic and prognostic markers. We explored the potential of SAA1 as a diagnostic and prognostic marker for advanced ccRCC. In this study, we mined and analyzed the public cancer databases (TCGA, UALCAN and GEPIA) to conclude that SAA1 was up-regulated at mRNA and protein levels in advanced ccRCC. We further found that hypomethylation of SAA1 promoter region was responsible for its high expression in ccRCC. Receiver operating characteristic curve (ROC) indicated that high SAA1 levels could distinguish advanced ccRCC patients from normal subjects (p < 0.0001). Kaplan-Meier curve analysis showed that high SAA1 levels predicted poor overall survival time (p < 0.0001) and poor disease-free survival time (p = 0.0003). Finally, the functional roles of SAA1 were examined using a si-SAA1 knockdown method in RCC cell lines. Our results suggest that SAA1 may possess the potential to serve as a diagnostic and prognostic biomarker for advanced ccRCC patients. Moreover, targeting SAA1 may represent as a novel therapeutic target for advanced ccRCC patients.
RESUMEN
Immunotherapy is a novel approach and has been used in various diseases, especially in cancers. Recently, immunotherapy has gradually been used to treat advanced clear cell renal cell carcinoma (ccRCC) or metastatic ccRCC. However, the efficacy of immunotherapy is not satisfying due to the influence of the tumor microenvironment. In this study, we mainly focused on the abundance and function of tumor-infiltrating immune cells (TIICs). Monocyte and TNM stage were identified as independent prognostic factors via CIBERSORT and Cox regression analysis. Then, ccRCC patients were divided into high risk/TNMhighMonocyteslow cluster and low risk/TNMlowMonocyteshigh cluster. Further differential gene analysis, protein-protein interaction (PPI) network, and survival analysis screened nine hub genes between the above two clusters. MMP9 and IGFBP1 were selected for further study through sample validation. Moreover, gene set enrichment analysis revealed that MMP9 and IGFBP1 were involved in tumor immune via mediating cell surface receptor signal pathway, cytokine production pathway, or monocyte signal pathway. In conclusion, these findings suggested that monocyte acted as a protective factor and MMP9/IGFBP1 played a vital role in tumor immune, which might become potential novel biomarkers and therapeutic targets for immunotherapy in ccRCC.
RESUMEN
OBJECTIVE: The Weigl Colour-Form Sorting Test is a brief, widely used test of executive function. So far, it is unknown whether this test is specific to frontal lobe damage. Our aim was to investigate Weigl performance in patients with focal, unilateral, left or right, frontal, or non-frontal lesions. METHOD: We retrospectively analysed data from patients with focal, unilateral, left or right, frontal (n = 37), or non-frontal (n = 46) lesions who had completed the Weigl. Pass/failure (two correct solutions/less than two correct solutions) and errors were analysed. RESULTS: A greater proportion of frontal patients failed the Weigl than non-frontal patients, which was highly significant (p < 0.001). In patients who failed the test, a significantly greater proportion of frontal patients provided the same solution twice. No significant differences in Weigl performance were found between patients with left versus right hemisphere lesions or left versus right frontal lesions. There was no significant correlation between performance on the Weigl and tests tapping fluid intelligence. CONCLUSIONS: The Weigl is specific to frontal lobe lesions and not underpinned by fluid intelligence. Both pass/failure on this test and error types are informative. Hence, the Weigl is suitable for assessing frontal lobe dysfunction.
Asunto(s)
Función Ejecutiva , Lóbulo Frontal , Color , Lóbulo Frontal/diagnóstico por imagen , Humanos , Pruebas Neuropsicológicas , Estudios RetrospectivosRESUMEN
RNA methylation accounts for over 60% of all RNA modifications, and N6-methyladenosine (m6A) is the most common modification on mRNA and lncRNA of human beings. It has been found that m6A modification occurs in microRNA, circRNA, rRNA, and tRNA, etc. The m6A modification plays an important role in regulating gene expression, and the abnormality of its regulatory mechanism refers to many human diseases, including cancers. Pitifully, as it stands there is a serious lack of knowledge of the extent to which the expression and function of m6A RNA methylation can influence prostate cancer (PC). Herein, we systematically analyzed the expression levels of 35 m6A RNA methylation regulators mentioned in literatures among prostate adenocarcinoma patients in the Cancer Genome Atlas (TCGA), finding that most of them expressed differently between cancer tissues and normal tissues with the significance of p < 0.05. Utilizing consensus clustering, we divided PC patients into two subgroups based on the differentially expressed m6A RNA methylation regulators with significantly different clinical outcomes. To appraise the discrepancy in total transcriptome between subgroups, the functional enrichment analysis was conducted for differential signaling pathways and cellular processes. Next, we selected five critical genes by the criteria that the regulators had a significant impact on prognosis of PC patients from TCGA through the last absolute shrinkage and selection operator (LASSO) Cox regression and obtained a risk score by weighted summation for prognosis prediction. The survival analysis curve and receiver operating characteristic (ROC) curve showed that this signature could excellently predict the prognosis of PC patients. The univariate and multivariate Cox regression analyses proved the independent prognostic value of the signature. In summary, our effort revealed the significance of m6A RNA methylation regulators in prostate cancer and determined a m6A gene expression classifier that well predicted the prognosis of prostate cancer.
RESUMEN
Patients with advanced renal cell carcinoma who are resistant to sunitinib currently have limited clinical options for treatment. Therefore, it is necessary to explore the biological basis of sunitinib resistance and to uncover new targets for the intervention of sunitinib resistance. In this study, we identified that LINC00160 was associated with sunitinib resistance in renal cell carcinoma. Resistant tumor cells highly expressed LINC00160 to recruit transcriptional factor TFAP2A, which bound to SAA1 promoter regions and activated its expression. On one hand, SAA1 linked to ABCB1 protein, which facilitated sunitinib cellular efflux and diminished drug accumulation. On the other hand, SAA1 stimulated JAK-STAT signaling pathways, which countered cellular survival inhibition from drug. All these regulatory networks were well organized and collaborated, thus promoting sunitinib resistance in renal cell carcinoma. LINC00160 mediates sunitinib resistance in renal cell carcinoma via SAA1 that is implicated in STAT3 activation and compound transportation, which offers an opportunity for targeted intervention and molecular therapies in the future.
RESUMEN
INTRODUCTION: The Brixton Spatial Anticipation Test is a widely used neuropsychological test, thought to assess executive functions and to be sensitive to frontal lobe lesions. Our aim was to investigate Brixton performance in patients with focal frontal or posterior lesions and healthy controls. METHOD: We compared performance on the Brixton in a sample of 24 frontal patients, 18 posterior patients and 22 healthy controls. Both overall performance (total number of errors) and error types were analyzed. RESULTS: We found no significant differences between frontal and posterior patients and healthy controls in overall Brixton performance. Moreover, our error analysis showed no difference between frontal patients, posterior patients and healthy controls. The only exception was that posterior patients had a greater tendency to guess and make more errors when following specific rules than healthy controls but this was no longer significant once fluid intelligence was controlled for. We also found no significant difference between the performance of patients with left lateral (n = 11), right lateral (n = 10) or superior medial (n = 18) frontal lesions and healthy controls. CONCLUSIONS: The Brixton test is not sensitive to frontal lobe dysfunction. It is likely that the test draws on a range of cognitive abilities not specific to frontal lobe lesions. Hence, caution should be taken when drawing conclusions about its neural substrates.