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1.
Opt Express ; 32(9): 16333-16350, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38859263

RESUMEN

Compressed ultrafast photography (CUP) is a computational imaging technology capable of capturing transient scenes in picosecond scale with a sequence depth of hundreds of frames. Since the inverse problem of CUP is an ill-posed problem, it is challenging to further improve the reconstruction quality under the condition of high noise level and compression ratio. In addition, there are many articles adding an external charge-coupled device (CCD) camera to the CUP system to form the time-unsheared view because the added constraint can improve the reconstruction quality of images. However, since the images are collected by different cameras, slight affine transformation may have great impacts on the reconstruction quality. Here, we propose an algorithm that combines the time-unsheared image constraint CUP system with unsupervised neural networks. Image registration network is also introduced into the network framework to learn the affine transformation parameters of input images. The proposed algorithm effectively utilizes the implicit image prior in the neural network as well as the extra hardware prior information brought by the time-unsheared view. Combined with image registration network, this joint learning model enables our proposed algorithm to further improve the quality of reconstructed images without training datasets. The simulation and experiment results demonstrate the application prospect of our algorithm in ultrafast event capture.

2.
Sensors (Basel) ; 24(12)2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38931519

RESUMEN

The domain of gamma-ray imaging necessitates technological advancements to surmount the challenge of energy-selective imaging. Conventional systems are constrained in their dynamic focus on specific energy ranges, a capability imperative for differentiating gamma-ray emissions from diverse sources. This investigation introduces an innovative imaging system predicated on the detection of recoil electrons, addressing the demand for adjustable energy selectivity. Our methodology encompasses the design of a gamma-ray imaging system that leverages recoil electron detection to execute energy-selective imaging. The system's efficacy was investigated experimentally, with emphasis on the adaptability of the energy selection window. The experimental outcomes underscore the system's adeptness at modulating the energy selection window, adeptly discriminating gamma rays across a stipulated energy spectrum. The results corroborate the system's adaptability, with an adjustable energy resolution that coincides with theoretical projections and satisfies the established criteria. This study affirms the viability and merits of utilizing recoil electrons for tunable energy-selective gamma-ray imaging. The system's conceptualization and empirical validation represent a notable progress in gamma-ray imaging technology, with prospective applications extending from medical imaging to astrophysics. This research sets a solid foundation for subsequent inquiries and advancements in this domain.

3.
Int J Biol Sci ; 20(8): 3008-3027, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38904013

RESUMEN

SET domain containing 7(SETD7), a member of histone methyltransferases, is abnormally expressed in multiple tumor types. However, the biological function and underlying molecular mechanism of SETD7 in clear cell renal cell carcinoma (ccRCC) remain unclear. Here, we explored the biological effects of SETD7-TAF7-CCNA2 axis on proliferation and metastasis in ccRCC. We identified both SETD7 and TAF7 were up-regulated and significantly promoted the proliferation and migration of ccRCC cells. Concurrently, there was a significant positive correlation between the expression of SETD7 and TAF7, and the two were colocalized in the nucleus. Mechanistically, SETD7 methylates TAF7 at K5 and K300 sites, resulting in the deubiquitination and stabilization of TAF7. Furthermore, re-expression of TAF7 could partially restore SETD7 knockdown inhibited ccRCC cells proliferation and migration. In addition, TAF7 transcriptionally activated to drive the expression of cyclin A2 (CCNA2). And more importantly, the methylation of TAF7 at K5 and K300 sites exhibited higher transcriptional activity of CCNA2, which promotes formation and progression of ccRCC. Our findings reveal a unique mechanism that SETD7 mediated TAF7 methylation in regulating transcriptional activation of CCNA2 in ccRCC progression and provide a basis for developing effective therapeutic strategies by targeting members of SETD7-TAF7-CCNA2 axis.


Asunto(s)
Carcinoma de Células Renales , Movimiento Celular , Proliferación Celular , N-Metiltransferasa de Histona-Lisina , Neoplasias Renales , Humanos , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Proliferación Celular/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Movimiento Celular/genética , Neoplasias Renales/metabolismo , Neoplasias Renales/genética , Neoplasias Renales/patología , Línea Celular Tumoral , Factores Asociados con la Proteína de Unión a TATA/metabolismo , Factores Asociados con la Proteína de Unión a TATA/genética , Metilación , Factor de Transcripción TFIID/metabolismo , Factor de Transcripción TFIID/genética , Regulación Neoplásica de la Expresión Génica
4.
Opt Express ; 32(4): 6567-6574, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38439356

RESUMEN

This paper present a novel, integrated compressed ultrafast photography system for comprehensive measurement of the aluminium planar wire array Z-Pinch evolution process. The system incorporates a large array streak camera and embedded encoding to improve the signal-to-noise ratio. Based on the "QiangGuang-I" pulsed power facility, we recorded the complete continuous 2D implosion process of planar wire array Z-Pinch for the first time. Our results contribute valuable understanding of imploding plasma instabilities and offer direction for the optimization of Z-Pinch facilities.

5.
J Cancer ; 15(8): 2193-2205, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38495485

RESUMEN

With the development of guidance technology and ablation equipment, ablative procedures have emerged as important loco-regional alternatives to surgical resection for recurrent hepatocellular carcinoma (rHCC) patients. Currently, ablation modalities used in clinical practice mainly include radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation (LA), cryoablation (CRA), high-intensity focused ultrasound (HIFU), and irreversible electroporation (IRE). Accumulated comparative data of ablation versus surgical resection reveal noninferior responses and outcomes but superior adverse effects. Moreover, studies demonstrate that ablation may serve as an excellent procedure for rHCC given its exact minimal invasiveness and immune modulation. We focus on the current status of ablation in clinical practice for rHCC and discuss new research in the field, including ablation combined with these other modalities, such as targeted therapy and immunotherapy.

6.
Cell Death Discov ; 9(1): 152, 2023 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-37156838

RESUMEN

Epidemiological studies have demonstrated that the use of antidepressants is associated with a decreased risk of colorectal cancer (CRC); however, the mechanisms behind this association are yet unknown. Adrenergic system contributes to the stress-related tumor progression, with norepinephrine (NE) mainly secreted from adrenergic nerve fibers. Norepinephrine serotonin reuptake inhibitors are successfully used antidepressants. This study demonstrates that a widely used antidepressant venlafaxine (VEN) antagonizes NE-promoted colon cancer in vivo and in vitro. Bioinformatic analysis suggested that NE transporter (NET, SLC6A2), a target of VEN, was closely associated with the prognosis of clinical patients with CRC. In addition, the knockdown of NET antagonized the effect of NE. The NET-protein phosphatase 2 scaffold subunit alpha/phosphorylated Akt/vascular endothelial growth factor pathway partially mediates the antagonizing effect of VEN on NE's actions in colon cancer cells. These were also confirmed by in vivo experiments. Our findings revealed for the first time that, in addition to its primary function as a transporter, NET also promotes NE-enhanced colon cancer cell proliferation, tumor angiogenesis, and tumor growth. This provides direct experimental and mechanistic evidence for the use of antidepressant VEN in the treatment of CRC and a therapeutic potential for repurposing existing drugs as an anti-cancer approach to improve the prognosis of patients with CRC.

8.
Cell Cycle ; 22(3): 269-275, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36101480

RESUMEN

SET domain containing lysine methyltransferase 7 (SETD7) belongs to the protein lysine methyltransferase family and can catalyze the monomethylation of histone H3K4, which plays a vital role in the regulation of cell cycle, cell differentiation, DNA damage response and chromatin remodeling through K/R-S/T-K (K is lysine residue) sites and the recognition of substrates mediated by SET, i-SET, and n-SET domains and electrostatic action. SETD7 also can regulate the transcription of several genes including ß-catenin, Cullin l and lin-28 homolog A (LIN28A), etc. In addition, the abnormal expression of SETD7 can promote the proliferation, migration, invasion of tumor cells, predict the poor prognosis of tumor patients, and may be a potential target for tumor therapy. This paper reviews the structure of SETD7, its role in tumor genesis and development, and the current research progress of relevant targeted drugs to explore its regulatory mechanism in tumor genesis and development and the prospect of targeted therapy.


Asunto(s)
Transformación Celular Neoplásica , N-Metiltransferasa de Histona-Lisina , Humanos , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/metabolismo , Dominios PR-SET
9.
Rev Sci Instrum ; 93(11): 113551, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-36461445

RESUMEN

Neutron and x-ray imaging are essential ways to diagnose a pulsed radiation source. The three-dimensional (3D) intensity distribution reconstructed from two-dimensional (2D) radiation images can significantly promote research regarding the generation and variation mechanisms of pulsed radiation sources. Only a few (≤5) projected images at one moment are available due to the difficulty in building imaging systems for high-radiation-intensity and short-pulsed sources. The reconstruction of a 3D source with a minimal number of 2D images is an ill-posed problem that leads to severe structural distortions and artifacts of the image reconstructed by conventional algorithms. In this paper, we present an iterative method to reconstruct a 3D source using spherical harmonic decomposition. Our algorithm improves the representation ability of spherical harmonic decomposition for 3D sources by enlarging the order of the expansion, which is limited in current analytical reconstruction algorithms. Prior knowledge of the source can be included to obtain a reasonable solution. Numerical simulations demonstrate that the reconstructed image quality of the iterative algorithm is better than that of the analytical algorithm. The iterative method can suppress the effect of noise in the integral projection image and has better robustness and adaptability than the analytical method.

10.
World J Gastrointest Oncol ; 14(7): 1252-1264, 2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-36051096

RESUMEN

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed and treated in advanced tumor stages with poor prognosis. More effective screening programs and novel therapeutic means are urgently needed. Recent studies have regarded tight junction protein claudin 18.2 (CLDN18.2) as a candidate target for cancer treatment, and zolbetuximab (formerly known as IMAB362) has been developed against CLDN18.2. However, there are few data reported thus far related to the clinicopathological characteristics of CLDN18.2 expression for PDAC. AIM: To investigate the expression of CLDN18.2 in PDAC patients and subsequently propose a new target for the treatment of PDAC. METHODS: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, and European Genome-phenome Archive databases were first employed to analyze the CLDN18 gene expression in normal pancreatic tissue compared to that in pancreatic cancer tissue. Second, we analyzed the expression of CLDN18.2 in 93 primary PDACs, 86 para-cancer tissues, and 13 normal pancreatic tissues by immunohistochemistry. Immunostained tissues were assessed applying the histoscore. subsequently, they fell into two groups according to the expression state of CLDN18.2. Furthermore, the correlations between CLDN18.2 expression and diverse clinicopathological characteristics, including survival, were investigated. RESULTS: The gene expression of CLDN18 was statistically higher (P < 0.01) in pancreatic tumors than in normal tissues. However, there was no significant correlation between CLDN18 expression and survival in pancreatic cancer patients. CLDN18.2 was expressed in 88 (94.6%) of the reported PDACs. Among these tumors, 50 (56.8%) cases showed strong immunostaining. The para-cancer tissues were positive in 81 (94.2%) cases, among which 32 (39.5%) of cases were characterized for strong staining intensities. Normal pancreatic tissue was identified solely via weak immunostaining. Finally, CLDN18.2 expression significantly correlated with lymph node metastasis, distant metastasis, nerve invasion, stage, and survival of PDAC patients, while there was no correlation between CLDN18.2 expression and localization, tumor size, patient age and sex, nor any other clinicopathological characteristic. CONCLUSION: CLDN18.2 expression is frequently increased in PDAC patients. Thus, it may act as a potential therapeutic target for zolbetuximab in PDAC.

11.
Pathol Res Pract ; 236: 153966, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35679753

RESUMEN

OBJECTIVE: The sesquiterpene lactone costunolide (CTL) has attracted much attention due to its antitumor effect on a variety of malignant tumors. However, the effect of CTL on hypopharyngeal squamous cell carcinoma (HSCC) remains unclear. This study aimed to examine the effects of this sesquiterpene lactone on HSCC FaDu cells. METHODS: The FaDu cell line was treated with CTL and/or cisplatin. CCK-8 was used to examine cell viability. Annexin-FITC/PI and Hoechst 33258 staining were used to measure apoptosis. Reactive oxygen species (ROS) were analysed by MitoSOX Red staining. Protein expression was examined by Western blotting. RESULTS: CTL (0, 2, 4, 6, 8, 10, 20, 30, and 40 µM) dose-dependently induced cytotoxicity in FaDu cells. CTL increased ROS production and induced apoptosis in FaDu cells. Moreover, CTL synergized with cisplatin to induce apoptosis in FaDu cells. In addition, the caspase inhibitor Z-DEVD-FMK attenuated CTL-induced apoptosis. Western blot analysis showed that CTL increased the expression levels of cleaved caspase-3 and Bax and decreased the expression levels of Bcl-2, phospho-AKT and phospho-NF-κB. CONCLUSION: In conclusion, these data demonstrate that CTL induced apoptosis and enhanced cisplatin-induced cytotoxicity in HSCC FaDu cells.


Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias Hipofaríngeas , Sesquiterpenos , Apoptosis , Línea Celular Tumoral , Cisplatino/farmacología , Humanos , Neoplasias Hipofaríngeas/tratamiento farmacológico , Neoplasias Hipofaríngeas/metabolismo , Neoplasias Hipofaríngeas/patología , Lactonas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sesquiterpenos/farmacología , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico
12.
Opt Express ; 30(9): 14645-14650, 2022 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-35473203

RESUMEN

A single-shot imaging system with multiple frames has been developed, which can record sequential multiple frames by delaying multiple optical images with fiber bundles and then capturing the images with a single intensified camera. The observed optical object is imaged through four lenses onto the end faces of four sets of fiber bundles. These fiber bundles with different lengths can provide different delays for delivering optical images, which determine the inter-frame separation times. The optical images exported from the fiber bundles are captured with a single intensified CMOS camera simultaneously. This imaging system has been applied for investigating the dynamic x-ray spot of the rod-pinch diode via a combination of scintillators, which are used to convert x-ray images to optical images. Four sequential x-ray images in a single shot have been obtained, which show the dynamic development of the rod-pinch x-ray spot. The results experimentally reveal the dynamics of the electrons flow bombarding the rod, which roughly agrees with the theoretical modeling of the rod-pinch diode.

13.
Int J Biol Sci ; 18(6): 2527-2539, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35414793

RESUMEN

Background: Colorectal cancer (CRC) is one of the most common malignant tumors with high rates of recurrence and mortality. Thymine DNA glycosylase (TDG) is a key molecule in the base excision repair pathway. Recently, increasing attention has been paid to the role of TDG in tumor development. However, the specific functions of TDG in CRC remain unclear. Methods: The biological functions of TDG and DNA methyltransferase 3 alpha (DNMT3A) in CRC were evaluated using migration and invasion assays, respectively. A tumor metastasis assay was performed in nude mice to determine the in vivo role of TDG. The interaction between TDG and DNMT3A was determined via co-immunoprecipitation (Co-IP). Chromatin immunoprecipitation analysis (ChIP) was used to predict the DNA-binding site of DNMT3A. We also performed methylation-specific PCR (MSP) to detect changes in TIMP2 methylation. Results: TDG inhibited the migration and invasion of human colon cancer cells both in vitro and in vivo. TDG promoted the ubiquitination and degradation of DNMT3A by binding to it. Its interference with siDNMT3A also inhibits the migration and invasion of human colon cancer cells. Furthermore, the ChIP, MSP, and rescue experiments results confirmed that TDG accelerated the degradation of DNMT3A and significantly regulated the transcription and expression of TIMP2, thereby affecting the migration and invasion of human colon cancer cells. Conclusion: Our findings reveal that TDG inhibits the migration and invasion of human colon cancer cells through the DNMT3A-TIMP2 axis, which may be a potential therapeutic strategy for the development and treatment of CRC.


Asunto(s)
Neoplasias del Colon , Timina ADN Glicosilasa , Animales , Neoplasias del Colon/genética , ADN/metabolismo , Metilación de ADN/genética , ADN Metiltransferasa 3A , Humanos , Ratones , Ratones Desnudos , Timina ADN Glicosilasa/genética , Timina ADN Glicosilasa/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/genética , Inhibidor Tisular de Metaloproteinasa-2/metabolismo
14.
Sci Rep ; 12(1): 93, 2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34997105

RESUMEN

The stomach is the main digestive organ in humans. Patients with gastric cancer often develop digestive problems, which result in poor nutrition. Nutritional status is closely related to postoperative complications and quality of life (QoL) in patients with gastric cancer. The controlling nutritional status (CONUT) score is a novel tool to evaluate the nutritional status of patients. However, the relationship of the CONUT score with postoperative complications, QoL, and psychological status in patients with gastric cancer has not been investigated. The present follow-up study was conducted in 106 patients who underwent radical gastrectomy in our hospital between 2014 and 2019. The CONUT score, postoperative complications, psychological status, postoperative QoL scores, and overall survival (OS) of patients with gastric cancer were collected, and the relationship between them was analyzed. A significant correlation was observed between the CONUT score and postoperative complications of gastric cancer (P < 0.001), especially anastomotic leakage (P = 0.037). The multivariate regression analysis exhibited that the CONUT score (P = 0.002) is an independent risk factor for postoperative complications. The CONUT score was correlated with the state anxiety questionnaire (S-AI) for evaluating psychological status (P = 0.032). However, further regression analysis exhibited that the CONUT score was not an independent risk factor for psychological status. Additionally, the CONUT score was associated with postoperative QoL. The multivariate regression analysis exhibited that the CONUT score was an independent risk factor for the global QoL (P = 0.048). Moreover, the efficiency of CONUT score, prognostic nutrition index, and serum albumin in evaluating complications, psychological status, and QoL was compared, and CONUT score was found to outperform the other measures (Area Under Curve, AUC = 0.7368). Furthermore, patients with high CONUT scores exhibited shorter OS than patients with low CONUT scores (P = 0.005). Additionally, the postoperative complications (HR 0.43, 95% CI 0.21-0.92, P = 0.028), pathological stage (HR 2.26, 95% CI 1.26-4.06, P = 0.006), and global QoL (HR 15.24, 95% CI 3.22-72.06, P = 0.001) were associated with OS. The CONUT score can be used to assess the nutritional status of patients undergoing gastric cancer surgery and is associated with the incidence of postoperative complications and QoL.


Asunto(s)
Gastrectomía , Desnutrición/diagnóstico , Evaluación Nutricional , Estado Nutricional , Neoplasias Gástricas/cirugía , Fuga Anastomótica/etiología , Biomarcadores/sangre , Colesterol/sangre , Femenino , Gastrectomía/efectos adversos , Gastrectomía/mortalidad , Humanos , Recuento de Linfocitos , Masculino , Desnutrición/etiología , Desnutrición/mortalidad , Desnutrición/fisiopatología , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Calidad de Vida , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Albúmina Sérica Humana/análisis , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Factores de Tiempo , Resultado del Tratamiento
15.
Front Nutr ; 8: 654194, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34490317

RESUMEN

Background: The optimal treatment of cancer-related malnutrition remains unknown. A single-center prospective cohort study was performed to compare the efficacy of megestrol acetate (MA) combined with oral nutrition supplement (ONS) and MA alone for the treatment of lung cancer-related malnutrition. Methods: 76 eligible patients were prospectively enrolled in two arms, Arm 1 patients (n = 40, 52.6%) received MA 160 mg/d, and Arm 2 patients (n = 36, 47.4%) received MA 160 mg/d combined with ONS 55.8 g/t.i.d, all orally. All patients received anticancer therapy. Treatment duration was 3 months. The primary endpoints were improvements in body mass index (BMI) and Eastern Cooperative Oncology Group (ECOG) score. Secondary endpoints were assessed by appetite, mid-upper arm circumference (MAC), serum pre-albumin levels, and serum albumin levels. Results: Baseline levels were comparable between Arm 1 and Arm 2 patients. Compared with Arm 1, primary endpoints (BMI, P = 0.018; ECOG, P = 0.022) and secondary endpoints (MAC, P = 0.025; serum pre-albumin, P = 0.043; and serum albumin, P = 0.034) were improved significantly after treatment in Arm 2. While toxicity was negligible and comparable between Arm 1 and Arm 2. Conclusion: MA combined with ONS may be an effective and safe treatment option for lung cancer-related malnutrition patients. Clinical Trial Registration:www.clinicaltrials.gov, identifier ChiCTR2100049007.

16.
Cell Biol Int ; 44(10): 2075-2085, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32652867

RESUMEN

DNA-binding protein A (dbpA) is reported to be upregulated in many cancers and associated with tumor progress. The present study aimed to investigate the role of dbpA in 5-fluorouracil (5-FU)-resistant and oxaliplatin (L-OHP)-resistant colorectal cancer (CRC) cells. We found that 5-FU and L-OPH treatment promoted the expression of dbpA. Enhanced dbpA promoted the drug resistance of SW620 cells to 5-FU and L-OHP. DbpA knockdown inhibited cell proliferation, induced cell apoptosis, and cell cycle arrested in SW620/5-FU and SW620/L-OHP cells. Besides, dbpA short hairpin RNA (shRNA) enhanced the cytotoxicity of 5-FU and L-OHP to SW620/5-FU and SW620/L-OHP cells. Meanwhile, dbpA shRNA inhibited the activation of the Wnt/ß-catenin pathway that induced by 5-FU stimulation in SW620/5-FU cells. Activation of the Wnt/ß-catenin pathway or overexpression of checkpoint kinase 1 (Chk1) abrogated the promoting effect of dbpA downregulation on 5-FU sensitivity of CRC cells. Importantly, downregulation of dbpA suppressed tumor growth and promoted CRC cells sensitivity to 5-FU in vivo. Our study indicated that the knockdown of dbpA enhanced the sensitivity of CRC cells to 5-FU via Wnt/ß-catenin/Chk1 pathway, and DbpA may be a potential therapeutic target to sensitize drug resistance CRC to 5-FU and L-OHP.


Asunto(s)
Apoptosis/efectos de los fármacos , Proteínas Potenciadoras de Unión a CCAAT/fisiología , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas de Choque Térmico/fisiología , Animales , Línea Celular Tumoral , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Vía de Señalización Wnt/efectos de los fármacos
17.
Mol Oncol ; 14(5): 1059-1073, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32118353

RESUMEN

The adrenergic system contributes to the stress-induced onset and progression of cancer. Adrenergic fibers are the primary source of norepinephrine (NE). The underlying mechanisms involved in NE-induced colon cancer remain to be understood. In this study, we describe the function and regulatory network of NE in the progression of colon cancer. We demonstrate that NE-induced phosphorylation of cAMP response element-binding protein 1 (CREB1) promotes proliferation, migration, and invasion of human colon cancer cells. The downstream effector of NE, CREB1, bound to the promoter of miR-373 and transcriptionally activated its expression. miR-373 expression was shown to be necessary for NE-induced cell proliferation, invasion, and tumor growth. We confirmed that proliferation and invasion of colon cancer cells are regulated in vitro and in vivo by miR-373 through targeting of the tumor suppressors TIMP2 and APC. Our data suggest that NE promotes colon cancer cell proliferation and metastasis by activating the CREB1-miR-373 axis. The study of this novel signaling axis may provide mechanistic insights into the neural regulation of colon cancer and help in the design of future clinical studies on stress biology in colorectal cancer.


Asunto(s)
Carcinogénesis/efectos de los fármacos , Carcinogénesis/genética , Neoplasias del Colon/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , MicroARNs/metabolismo , Norepinefrina/farmacología , Proteína de la Poliposis Adenomatosa del Colon/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica , Norepinefrina/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
18.
Front Psychol ; 10: 2270, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31636595

RESUMEN

Considerable research has shown that children with dyslexia have deficits in visual spatial attention orientation. Additionally, self-referential processing makes self-related information play a unique role in the individual visual spatial attention orientation. However, it is unclear whether such self-referential processing impacts the visual spatial attention orientation of children with dyslexia. Therefore, we manipulated the reference task systematically in the cue-target paradigm and investigated the modulation effect of self-referential processing on visual spatial attention of children with dyslexia. In the self-referential processing condition, we observed that children with dyslexia demonstrated stable cue effects in the visual spatial attention orientation tasks when the Stimulus Onset Asynchronies (SOAs) were set to 100 ms, while other-referential processing weakened the cue effects of the visual spatial attention orientation of children with dyslexia. With cue effect as the index, we also observed that the self-referential processing had a significant larger regulatory effect at the early stage of visual spatial attention orientation, as compared with other-referential processing. These differences have a high-ranked consistency between children with dyslexia and typically developing reader. The results suggested that self-referential processing can regulate the visual spatial attention deficits of children with dyslexia.

19.
Am J Pathol ; 189(11): 2233-2245, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31430464

RESUMEN

Little is known about the role of the spleen in mediating systemic inflammatory responses in severe acute pancreatitis (SAP). We investigated the role played by the spleen in rats after SAP induction. Splenectomy was performed at designated time points after SAP induction. Pancreatic tissue and serum samples were collected and subjected to histologic, immunohistochemical, and immunologic analyses. After SAP induction, the splenic immune response was enhanced during SAP progression, as shown by the increased diameter of the splenic periarterial lymphatic sheath and the thickness of the splenic marginal zone. Rats with splenectomy developed acute pancreatitis more slowly than rats without splenectomy. In addition, pancreatic tissues of rats with splenectomy contained lower levels of serum amylase, tumor necrosis factor-α, and IL-6 and exhibited less acinar cell death, leukocyte infiltration, and interstitial edema than those of rats without splenectomy. Compared with splenectomy alone, cotreatment with splenectomy and the administration of splenic cells originating from a rat with SAP 12 hours after induction increased systemic inflammation in SAP rats. Splenic factors exacerbated SAP-associated liver and lung injury and accentuated intestinal mucosal barrier dysfunction. Splenectomy altered the serum cytokine profile in rats with SAP. In a rat model of SAP, the spleen exacerbated the systematic inflammatory responses and injury to multiple organs, indicating a new role for the spleen in SAP.


Asunto(s)
Pancreatitis/complicaciones , Pancreatitis/patología , Bazo/fisiología , Síndrome de Respuesta Inflamatoria Sistémica/patología , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Mediadores de Inflamación/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad , Bazo/inmunología , Bazo/metabolismo , Esplenectomía , Síndrome de Respuesta Inflamatoria Sistémica/etiología
20.
Proteomics Clin Appl ; 13(5): e1900048, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31207145

RESUMEN

PURPOSE: Early diagnosis is crucial to improve outcomes for pancreatic cancer patients (PC). The present study is designed to identify differently expressed peptides involved in PC as potential biomarkers. EXPERIMENTAL DESIGN: The serum proteome of 22 PC patients, 12 pancreatitis patients (PP), and 45 healthy controls (HC) are analyzed using magnetic bead-based weak cation exchange (MB-WCX) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Next, a supervised neural network (SNN) algorithm model is established by ClinProTools and the candidate biomarker identified using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Finally, the candidate biomarker is validated in tissue samples. RESULTS: The SNN algorithm model discriminates PC from HC with 92.97% sensitivity and 94.55% specificity. Seventy-six differentially expressed peptides are identified, seven of which are significantly different among PC, PP, and HC (p < 0.05). Only one peak (m/z: 1466.99) tends to be upregulated in samples from HC, PP, and PC, which is identified as region of RNA-binding motif protein 6 (RBM6). In subsequent tissue analysis, it is verified that RBM6 expression is significantly higher in PC tissues than paracancerous tissue. CONCLUSIONS AND CLINICAL RELEVANCE: The results indicate that RBM6 might serve as a candidate diagnostic biomarker for PC. CLINICAL RELEVANCE: Methods used in this study could generate serum peptidome profiles of PC, PP, and HC, and present an approach to identify potential biomarkers for diagnosis of this malignancy.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias Pancreáticas/sangre , Proteómica , Proteínas de Unión al ARN/sangre , Detección Precoz del Cáncer , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo
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