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1.
Mol Med ; 27(1): 142, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732131

RESUMO

BACKGROUND: Cardiotoxicity is a common complication following anthracycline chemotherapy and represents one of the serious adverse reactions affecting life, which severely limits the effective use of anthracyclines in cancer therapy. Although some genes have been investigated by individual studies, the comprehensive analysis of key genes and molecular regulatory network in anthracyclines-induced cardiotoxicity (AIC) is lacking but urgently needed. METHODS: The present study integrating several transcription profiling datasets aimed to identify key genes associated with AIC by weighted correlation network analysis (WGCNA) and differentially expressed analysis (DEA) and also constructed miRNA-transcription factor-gene regulatory network. A total of three transcription profiling datasets involving 47 samples comprising 41 rat heart tissues and 6 human induced pluripotent stem cell-derived cardiomyocytes (hiPSCMs) samples were enrolled. RESULTS: The WGCNA and DEA with E-MTAB-1168 identified 14 common genes affected by doxorubicin administrated by 4 weeks or 6 weeks. Functional and signal enrichment analyses revealed that these genes were mainly enriched in the regulation of heart contraction, muscle contraction, heart process, and oxytocin signaling pathway. Ten (Ryr2, Casq1, Fcgr2b, Postn, Tceal5, Ccn2, Tnfrsf12a, Mybpc2, Ankrd23, Scn3b) of the 14 genes were verified by another gene expression profile GSE154603. Importantly, three key genes (Ryr2, Tnfrsf12a, Scn3b) were further validated in a hiPSCMs-based in-vitro model. Additionally, the miRNA-transcription factor-gene regulatory revealed several top-ranked transcription factors including Tcf12, Ctcf, Spdef, Ebf1, Sp1, Rcor1 and miRNAs including miR-124-3p, miR-195-5p, miR-146a-5p, miR-17-5p, miR-15b-5p, miR-424-5p which may be involved in the regulation of genes associated with AIC. CONCLUSIONS: Collectively, the current study suggested the important role of the key genes, oxytocin signaling pathway, and the miRNA-transcription factor-gene regulatory network in elucidating the molecular mechanism of AIC.

2.
DNA Cell Biol ; 40(10): 1251-1260, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34491823

RESUMO

Microsatellite instability (MSI) is emerging as a promising subtype related to immunotherapy in gastric cancer (GC). However, the underlying mechanism between MSI and microsatellite stability (MSS) remains unclear. In this study, we conducted a weighted gene co-expression network analysis and found that the expression of heterogeneous nuclear ribonucleoprotein L (HNRNPL) was significantly increased in MSI GC compared with MSS GC. This finding was further validated in public GC cohorts and commercialized human GC tissue microarray. The significant negative correlation with the expression of mismatch repair protein mutL homolog 1 (MLH1) may be one of the potential mechanisms for the upregulation of HNRNPL expression in MSI GC (R = -0.689, p = 8.59e-11). In addition, HNRNPL expression was markedly upregulated in GC tissues compared with adjacent normal tissues. High HNRNPL expression also predicted a poor prognosis in GC patients. Finally, gene set enrichment analysis revealed that high HNRNPL MSI GC samples were highly positive associated with the biological functions of inflammation and cell proliferation, such as interferon gamma response, MYC targets, E2F targets, and G2/M checkpoints. In conclusion, HNRNPL could be a new MSI-associated prognostic biomarker in GC and could be a new target for the MSI GC treatment.


Assuntos
Biomarcadores Tumorais/genética , Instabilidade Genômica , Repetições de Microssatélites , Ribonucleoproteínas/genética , Neoplasias Gástricas/genética , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Ribonucleoproteínas/metabolismo , Neoplasias Gástricas/patologia , Regulação para Cima
3.
Arch Gynecol Obstet ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34324029

RESUMO

BACKGROUND: Breast cancer is an aggressive tumor, which poses a heavy burden to human health. Circular RNAs have been involved in the pathogenesis of breast cancer. This study aims to investigate whether circ_0008673 mediates breast cancer malignant progression by microRNA-153-3p (miR-153-3p)/cofilin 2 (CFL2) pathway. METHODS: The RNA levels of circ_0008673, miR-153-3p and CFL2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of CFL2, E-cadherin and N-cadherin was determined by western blot analysis. Cell proliferation was demonstrated through cell counting kit-8 and cell colony-formation assays. Cell apoptosis was detected by flow cytometry analysis. Cell migratory and invasive capacities were determined by transwell assay. The associated relationship between miR-153-3p and circ_0008673 or CFL2 was predicted by online databases, and testified by dual-luciferase reporter and RNA immunoprecipitation assays. In vivo assay was employed to demonstrate the effects of circ_0008673 silencing on tumor formation in vivo. RESULTS: Circ_0008673 and CFL2 expressions were upregulated, while miR-153-3p expression was downregulated in breast cancer tissues and cells compared with adjacent normal breast tissues and cells, respectively. Circ_0008673 overexpression promoted cell proliferation, migration and invasion, and repressed cell apoptosis, while circ_0008673 silencing had opposite effects. Additionally, circ_0008673 served as a sponge of miR-153-3p. And circ_0008673 was proved to regulate breast cancer cell malignancy by sponging miR-153-3p. MiR-153-3p was found to modulate breast cancer cell carcinogenesis via targeting CFL2. Furthermore, circ_0008673 silencing repressed tumor growth in vivo. CONCLUSION: Circ_0008673 promoted breast cancer progression by upregulating CFL2 expression through sponging miR-153-3p. This study provides a theoretical basis for researching circRNA-directed treatment of breast cancer.

4.
Front Pharmacol ; 12: 638993, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935728

RESUMO

Anthraquinones are bioactive natural products, some of which are active components in medicinal medicines, especially Chinese medicines. These compounds exert actions including purgation, anti-inflammation, immunoregulation, antihyperlipidemia, and anticancer effects. This study aimed to review the pharmacokinetics (PKs) of anthraquinones, which are importantly associated with their pharmacological and toxicological effects. Anthraquinones are absorbed mainly in intestines. The absorption rates of free anthraquinones are faster than those of their conjugated glycosides because of the higher liposolubility. A fluctuation in blood concentration and two absorption peaks of anthraquinones may result from the hepato-intestinal circulation, reabsorption, and transformation. Anthraquinones are widely distributed throughout the body, mainly in blood-flow rich organs and tissues, such as blood, intestines, stomach, liver, lung, kidney, and fat. The metabolic pathways of anthraquinones are hydrolysis, glycuronidation, sulfation, methylation/demethylation, hydroxylation/dehydroxylation, oxidation/reduction (hydrogenation), acetylation and esterification by intestinal flora and liver metabolic enzymes, among which hydrolysis, glycuronidation and sulfation are dominant. Of note, anthraquinones can be transformed into each other. The main excretion routes for anthraquinones are the kidney, recta, and gallbladder. Conclusion: Some anthraquinones and their glycosides, such as aloe-emodin, chrysophanol, emodin, physcion, rhein and sennosides, have attracted the most PK research interest due to their more biological activities and/or detectability. Anthraquinones are mainly absorbed in the intestines and are mostly distributed in blood flow-rich tissues and organs. Transformation into another anthraquinone may increase the blood concentration of the latter, leading to an increased pharmacological and/or toxicological effect. Drug-drug interactions influencing PK may provide insights into drug compatibility theory to enhance or reduce pharmacological/toxicological effects in Chinese medicine formulae and deserve deep investigation.

5.
Neuroscience ; 455: 79-88, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33285236

RESUMO

The rat auditory cortex is divided anatomically into several areas, but little is known about the functional differences in information processing among these areas. Three tonotopically organized core fields, namely, the primary (A1), anterior (AAF), and ventral (VAF) auditory fields, as well as one non-tonotopically organized belt field, the dorsal belt (DB), were identified based on their response properties. Compared to neurons in A1, AAF and VAF, units in the DB exhibited little or no response to pure tones but strong responses to white noise. The few DB neurons responded to pure tones with thresholds greater than 60 dB SPL, which was significantly higher than the thresholds of neurons in the core regions. In response to white noise, units in DB showed significantly longer latency and lower peak response, as well as longer response duration, than those in the core regions. Responses to repeated white noise were also examined. In contrast to neurons in A1, AAF and VAF, DB neurons could not follow repeated stimulation at a 300 ms inter-stimulus interval (ISI) and showed a significant steeper ISI tuning curve slope when the ISI was increased from 300 ms to 4.8 s. These results indicate that the DB processes auditory information on broader spectral and longer temporal scales than the core regions, reflecting a distinct role in the hierarchical cortical pathway.


Assuntos
Estimulação Acústica , Córtex Auditivo , Vias Auditivas , Mapeamento Encefálico , Animais , Neurônios , Ratos , Vigília
7.
Dose Response ; 18(2): 1559325820917824, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32284703

RESUMO

Objective: The prognostic value of C-reactive protein to albumin ratio (CAR) has been identified in several cancers but not in extranodal natural killer T-cell lymphoma (ENKTL) as yet. We aimed to evaluate the prognostic value of CAR in ENKTL. Methods: A retrospective study with 246 patients with ENKTL was performed to determine the prognostic value of pretreatment CAR and examine the prognostic performance of CAR incorporating with International Prognostic Index (IPI) or natural killer/T-cell lymphoma prognostic index (NKPI) by nomogram. Results: The Cox regression analyses showed that high CAR (>0.3) independently predicted unfavorable progression-free survival (PFS, P = .011) and overall survival (OS, P = .012). In the stratification analysis, the CAR was able to separate patients into different prognoses regarding both OS and PFS in Ann Arbor stage I+II as well as III+IV, IPI score 0 to 1, and NKPI score 1 to 2 subgroups (all P < .05). Additionally, the predictive accuracy of the IPI-based nomogram incorporating CAR, albumin to globulin ratio (AGR), and IPI for OS and PFS appeared to be lower than the NKPI-based nomogram incorporating CAR, age, AGR, extranodal site, and NKPI. Conclusion: Pretreatment CAR is a simple and easily accessible parameter for independently predicting OS and PFS in patients with ENKTL.

8.
J Immunother Cancer ; 8(1)2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32152220

RESUMO

BACKGROUND: Interferon-α (IFN-α) plays a pivotal role in host antitumor immunity, and the evasion of IFN-α signaling pathway can lead to IFN-α resistance during the treatment of cancer. Although the interplay between IFN-α and tumor cells has been extensively investigated in differentiated tumor cells, much less attention has been directed to tumor-repopulating cells (TRCs). METHODS: Three-dimentional soft fibrin matrix was used to select and grow highly malignant and tumorigenic melanoma TRCs. The regulation of integrin ß3 (ITGB3)-c-SRC-STAT signaling pathway in melanoma TRCs was investigated both in vitro and in vivo. The relevant mRNA and protein expression levels were analyzed by qRT-PCR and western blot analysis. Immunoprecipitation and chromatin immunoprecipitation (ChIP) followed by qPCR (ChIP-qPCR) assays were performed to detect protein-protein and protein-DNA interactions. The clinical impacts of retinoic acid inducible gene-I (RIG-I) were assessed in melanoma datasets obtained from The Cancer Genome Atlas and Gene Expression Omnibus profiles. RESULTS: IFN-α-induced apoptosis was decreased in melanoma TRCs. Compared with conventional flask-cultured cells, IFN-α-mediated STAT1 activation was diminished in melanoma TRCs. Decreased expression of RIG-I in melanoma TRCs led to diminished activation of STAT1 via enhancing the interaction between Src homology region 2 domain-containing phosphatase-1 and STAT1. In addition, low expression levels of RIG-I correlated with poor prognosis in patients with melanoma. STAT3 was highly phosphorylated in TRCs and knockdown of STAT3 reversed the downregulation of RIG-I in TRCs. Knockdown of STAT3 resulted in STAT1 activation and increased expression of the pro-apoptosis genes in IFN-α-treated TRCs. Combined treatment of STAT3 inhibitor and IFN-α increased the apoptosis rate of TRCs. Disruption of ITGB3/c-SRC/STAT3 signaling pathway significantly elevated the efficiency of IFN-α-induced apoptosis of TRCs. CONCLUSIONS: In melanoma TRCs, ITGB3-c-SRC-STAT3 pathway caused RIG-I repression and then affect STAT1 activation to cause resistance to IFN-α-induced apoptosis. RIG-I is a prognostic marker in patients with melanoma. Combination of STAT3 inhibitor and IFN-α could enhance the efficacy of melanoma treatment. Our findings may provide a new concept of combinatorial treatment for future immunotherapy.


Assuntos
Proteína DEAD-box 58/metabolismo , Integrina beta3/metabolismo , Interferon-alfa/farmacologia , Melanoma Experimental/tratamento farmacológico , Melanoma/tratamento farmacológico , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proteína DEAD-box 58/antagonistas & inibidores , Proteína DEAD-box 58/genética , Regulação para Baixo , Feminino , Células Hep G2 , Humanos , Fatores Imunológicos/farmacologia , Melanoma/imunologia , Melanoma/metabolismo , Melanoma/patologia , Melanoma Experimental/imunologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Prognóstico , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais , Taxa de Sobrevida
9.
Brain Struct Funct ; 224(5): 1753-1766, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31004193

RESUMO

Using oddball stimulus with pure tones, researchers have extensively investigated stimulus-specific adaptation (SSA), which has been regarded as a method of novelty detection, from the inferior colliculus (IC) to the auditory cortex (AC). However, until now, it is not clear whether SSA is preserved for natural sounds or whether it exists for spatial cues in the AC. Moreover, it is also unclear whether SSA integrates different types of cues within a single modality such as sound location and sound identity. Here, we addressed these issues using two natural sounds presented at two different locations while simultaneously performing extracellular recordings in the AC of awake rats. Our data showed that SSA was present in the AC for the natural sounds, the pure tones, and the spatial locations in the neuronal population. We also found that the AC response to a double deviant stimulus (a deviant sound at a deviant location) was stronger than that to a single (either a deviant sound or the same sound at a deviant location); this finding suggests that detecting unexpected events benefits from the integration of different cues within the same modality.


Assuntos
Estimulação Acústica , Adaptação Fisiológica/fisiologia , Córtex Auditivo/fisiologia , Ruído , Vigília/fisiologia , Estimulação Acústica/métodos , Animais , Percepção Auditiva/fisiologia , Potenciais Evocados Auditivos/fisiologia , Colículos Inferiores/fisiologia , Masculino , Neurônios/fisiologia , Ratos Wistar
10.
Redox Biol ; 20: 451-457, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30439686

RESUMO

Metabolic reprogramming is a feature of cancer cells and crucial for tumor growth and metastasis. Interferon-γ (IFNγ) is a cytokine that plays a pivotal role in host antitumor immunity. However, little is known about the roles of metabolic reprogramming in immune responses. Here, we show that colon cancer cells reprogram metabolism to coordinate proper cellular responses to IFNγ by downregulating mitochondrial pyruvate carrier (MPC)1 and 2 via STAT3 signaling. Forced overexpression of MPC promote the production of reactive oxygen species and enhance the apoptosis induced by IFNγ in colon cancer cells. Moreover, inhibiting STAT3 sensitize the antitumor efficacy of IFN-γ against colon cancer cells. Our findings present a previously unrecognized mechanism that colon cancer manipulate to resist IFNγ mediated antitumor immunity that have implications for targeting a unique aspect of this disease.


Assuntos
Neoplasias do Colo/metabolismo , Interferon gama/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Piruvatos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Transporte Biológico , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos , Mitocôndrias/genética , Modelos Biológicos , Oxirredução , Pró-Proteína Convertase 1/genética , Pró-Proteína Convertase 1/metabolismo , Pró-Proteína Convertase 2/genética , Pró-Proteína Convertase 2/metabolismo
11.
Biosens Bioelectron ; 129: 216-223, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30297172

RESUMO

Parkinson's disease caused by lack of dopamine in brain is a common neurodegenerative disorder. The traditional treatment is to replenish levodopa since it could pass through blood brain barrier and form dopamine. However, its accumulation can cause patients' movement disorders and uncontrollable emotion. Therefore, it is critical to control the levodopa dosage accuracy to improve the curative effect in clinical. In this study, a smartphone-based electrochemical detection system was developed for rapid monitoring of levodopa. The system involved a disposable sensor, a hand-held electrochemical detector, and a smartphone with designed application. Single-wall carbon nanotubes and gold nanoparticles modified screen-printed electrodes were used to convert and amplify the electrochemical current signals upon presence of levodopa molecules. The electrochemical detectors were used to generate electrochemical excitation signals and detect the resultant currents. Smartphone was connected to the detector, which was used to control the detector, calculate data, and plot graph in real-time. The smartphone-based differential pulse amperometry system was demonstrated to monitor levodopa at concentrations as low as 0.5 µM in human serum. Furthermore, it has also been verified to be able to distinguish levodopa from other representative substances in the body. Therefore, its performance was more sensitive and rapid than electrochemical workstation. With these advantages, the system can be used in the field of point-of-care testing (POCT) to detect levodopa and provide the possibility to solve clinical demand for levodopa detection.


Assuntos
Antiparkinsonianos/sangue , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , Ouro/química , Levodopa/sangue , Nanopartículas Metálicas/química , Nanotubos de Carbono/química , Monitoramento de Medicamentos/instrumentação , Eletrodos , Desenho de Equipamento , Humanos , Limite de Detecção , Modelos Moleculares , Doença de Parkinson/tratamento farmacológico , Smartphone
12.
J Exp Clin Cancer Res ; 37(1): 259, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30373678

RESUMO

BACKGROUND: Lysosome-associated agents have been implicated as possible chemo-sensitizers and immune regulators for cancer chemotherapy. We investigated the potential roles and mechanisms of hydroxychloroquine (HCQ) in combination with chemotherapy in lung cancer treatment. METHODS: The effects of combined treatment on non-small cell lung cancer (NSCLC) were investigated using cell viability assays and animal models. The influence of HCQ on lysosomal pH was evaluated by lysosomal sensors and confocal microscopy. The effects of HCQ on the tumour immune microenvironment were analysed by flow cytometry. RESULTS: HCQ elevates the lysosomal pH of cancer cells to inactivate P-gp while increasing drug release from the lysosome into the nucleus. Furthermore, single HCQ therapy inhibits lung cancer by inducing macrophage-modulated anti-tumour CD8+ T cell immunity. Moreover, HCQ could promote the transition of M2 tumour-associated macrophages (TAMs) into M1-like macrophages, leading to CD8+ T cell infiltration into the tumour microenvironment. CONCLUSIONS: HCQ exerts anti-NSCLC cells effects by reversing the drug sequestration in lysosomes and enhancing the CD8+ T cell immune response. These findings suggest that HCQ could act as a promising chemo-sensitizer and immune regulator for lung cancer chemotherapy in the clinic.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Células A549 , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Hidroxicloroquina/farmacologia , Neoplasias Pulmonares/patologia , Lisossomos/química , Lisossomos/efeitos dos fármacos , Macrófagos/patologia , Camundongos , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Neuroscience ; 392: 13-24, 2018 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-30248436

RESUMO

Recent electrophysiological studies in animals using oddball stimuli have demonstrated that neurons along the auditory pathway from the inferior colliculus to the auditory cortex (AC) have a strong response to rarely presented stimuli. This phenomenon is termed stimulus-specific adaptation (SSA), which is regarded as novelty detection. However, in the medial geniculate body (MGB), it is not clear whether SSA is frequency dependent or if neurons in the MGB are sensitive to the regularity of the stimuli. In this present study, we analyzed the relationship between stimulus frequency and SSA, as well as explored regularity sensitivity using extracellular recordings in the MGBs of rats with regular and irregular oddball stimuli. It was found MGB neurons exhibited strong SSA when the pure-tone stimulus of the oddball stimulus deviated far from the characteristic frequency, even in the ventral region of the MGB, suggesting that the MGB may contribute to SSA in the primary AC. Moreover, we found the neuronal population in the MGB was sensitive to high-order sound structure, where deviant responses were smaller and standard responses were stronger for irregular oddball stimuli. We conclude that regularity detection occurs in the MGB, but in a manner distinct from the AC.


Assuntos
Adaptação Fisiológica , Percepção Auditiva/fisiologia , Corpos Geniculados/fisiologia , Neurônios/fisiologia , Estimulação Acústica , Potenciais de Ação , Animais , Feminino , Masculino , Ratos Wistar
14.
Biosens Bioelectron ; 119: 55-62, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30098467

RESUMO

Ascorbic acid, dopamine, and uric acid are important electroactive biomolecules for health monitoring and they coexist in serum or urine. Their quantitative determination by electrochemistry could provide the accurate reference for diseases diagnosis and treatment. However, the traditional electrochemical workstations are too large for on-field inspection. Hence, the design of handheld electrochemical system for the detection of biomolecules is significant for point-of-care testing (POCT). In this paper, a smartphone-based integrated voltammetry system using modified electrode was developed for simultaneous detection of biomolecules. The system contained a disposable sensor, a coin-size detector, and a smartphone equipped with application program. Screen-printed electrodes were used as sensors for the detection, on which reduced graphene oxide and gold nanoparticles were electrochemically deposited by the system. The detector was used with voltammetric methods, in which excitation voltage was applied on the sensors and subsequent current responses were detected. The smartphone is the core component to communicate with the detector, calculate data, and plot voltammograms in real-time. Then, the system was applied to detect standard solutions of the biomolecules and their mixtures as examples. The results showed that the peak currents of each substance increased with higher concentration and the method allowed the discrimination of the different potentials of the studied species. Finally, the practical applications of the system were tested through detections of the biomolecules in artificial urine. The results exhibited that the system could be used to detect electrochemical activity of biomolecules with linear, high sensitivity, and specific responses in point-of-care testing.


Assuntos
Ácido Ascórbico , Técnicas Biossensoriais/métodos , Análise Química do Sangue/métodos , Dopamina , Smartphone , Ácido Úrico , Urinálise/métodos , Ácido Ascórbico/análise , Ácido Ascórbico/sangue , Ácido Ascórbico/urina , Técnicas Biossensoriais/instrumentação , Análise Química do Sangue/instrumentação , Dopamina/análise , Dopamina/sangue , Dopamina/urina , Técnicas Eletroquímicas , Eletrodos , Ouro/química , Grafite/química , Humanos , Nanopartículas Metálicas , Ácido Úrico/análise , Ácido Úrico/sangue , Ácido Úrico/urina , Urinálise/instrumentação
15.
Neuroscience ; 365: 1-11, 2017 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-28942322

RESUMO

The capacity to identify unanticipated abnormal cues in a natural scene is vital for animal survival. Stimulus-specific adaptation (SSA) has been considered the neuronal correlate for deviance detection. There have been comprehensive assessments of SSA in the frequency domain along the ascending auditory pathway, but only little attention given to deviance detection in the spatial domain. We found that thalamic reticular nucleus (TRN) neurons exhibited stronger responses to a tone when it was presented rarely as opposed to frequently at a certain spatial location. Subsequently, we engaged signal detection theory to directly gauge neuronal spatial discriminability and found that discrimination of deviant locations was considerably higher than standard locations. The variability in neuronal spatial discriminability among the TRN population was directly related to response difference (RD) but not variance; meanwhile, further analyses attributed higher spatial sensitivity at deviant locations to larger RD. Astonishingly, a significant correlation was found between the amount of adaptation and deviant discriminability. Collectively, our results suggest that adaptation facilitates rare location discrimination by sharpening the response gap between two locations.


Assuntos
Adaptação Fisiológica/fisiologia , Vias Auditivas/fisiologia , Discriminação Psicológica/fisiologia , Percepção Espacial/fisiologia , Núcleos Talâmicos/fisiologia , Estimulação Acústica , Potenciais de Ação/fisiologia , Animais , Percepção Auditiva , Feminino , Masculino , Neurônios/fisiologia , Curva ROC , Ratos , Ratos Wistar , Núcleos Talâmicos/citologia
16.
Biochem Biophys Res Commun ; 491(1): 104-111, 2017 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-28709865

RESUMO

PURPOSE: The present study was to evaluate the prognostic value of protein expression of Pofut1 and Notch1 signaling in breast cancer. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded 314 breast specimens including 174 infiltrating ductal carcinoma(IDC), 50 ductal carcinoma in situ(DCIS) and 90 adjacent normal tissue(ANT) were immunohistochemically examined to evaluate the protein expression of Pofut1, activated Notch1(N1IC) and Slug on specimens. Survival analysis was performed by Kaplan-Meier method and Cox's proportional-hazards model. A online database was computationally used to further explore the prognostic role of Pofut1 and Notch1 mRNA expression by Kaplan-Meier Plotter. RESULTS: Pofut1, Slug and N1IC expression were significantly increased in IDC compared to ANT(all p < 0.05). High expression of Pofut1, Slug and N1IC were associated with tumor aggressiveness including lymph node metastasis (LNM: p = 0.005 for Pofut1, p < 0.001 for N1IC, p = 0.017 for Slug), advanced stage(p = 0.039 for Pofut1, p = 0.025 for N1IC) and higher histological grade(p = 0.001 for N1IC). Additionally, high expression of Pofut1 was found to be significantly associated with high expressions of N1IC and Slug in IDC(r = 0.244, p = 0.001; r = 0.374, p < 0.001, respectively), similar correlation was also observed between high N1IC and Slug expression(r = 0.496, p < 0.001). Moreover, Kaplan-Meier and Cox's regression analysis indicated the significant prognostic value of elevated Pofut1, N1IC, Slug expressions, positive LNM and advanced tumor stage for the prediction of a shorter disease-free survival (DFS) and overall survival(OS). The web-based analysis also suggested a significant association of high Pofut1 and Notch1 mRNA expression with worse survival outcome. CONCLUSION: Our findings suggested that overexpression of Pofut1 and activated Notch1 signaling may be associated with a poor prognosis in breast cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Fucosiltransferases/metabolismo , Receptor Notch1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Taxa de Sobrevida , Regulação para Cima
17.
Phys Rev Lett ; 118(1): 017201, 2017 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-28106442

RESUMO

A key property of many-body localized Hamiltonians is the area law entanglement of even highly excited eigenstates. Matrix product states (MPS) can be used to efficiently represent low entanglement (area law) wave functions in one dimension. An important application of MPS is the widely used density matrix renormalization group (DMRG) algorithm for finding ground states of one-dimensional Hamiltonians. Here, we develop two algorithms, the shift-and-invert MPS (SIMPS) and excited state DMRG which find highly excited eigenstates of many-body localized Hamiltonians. Excited state DMRG uses a modified sweeping procedure to identify eigenstates, whereas SIMPS applies the inverse of the shifted Hamiltonian to a MPS multiple times to project out the targeted eigenstate. To demonstrate the power of these methods, we verify the breakdown of the eigenstate thermalization hypothesis in the many-body localized phase of the random field Heisenberg model, show the saturation of entanglement in the many-body localized phase, and generate local excitations.

18.
Elife ; 62017 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-28075326

RESUMO

Sensory signals undergo substantial recoding when neural activity is relayed from sensors through pre-thalamic and thalamic nuclei to cortex. To explore how temporal dynamics and directional tuning are sculpted in hierarchical vestibular circuits, we compared responses of macaque otolith afferents with neurons in the vestibular and cerebellar nuclei, as well as five cortical areas, to identical three-dimensional translational motion. We demonstrate a remarkable spatio-temporal transformation: otolith afferents carry spatially aligned cosine-tuned translational acceleration and jerk signals. In contrast, brainstem and cerebellar neurons exhibit non-linear, mixed selectivity for translational velocity, acceleration, jerk and position. Furthermore, these components often show dissimilar spatial tuning. Moderate further transformation of translation signals occurs in the cortex, such that similar spatio-temporal properties are found in multiple cortical areas. These results suggest that the first synapse represents a key processing element in vestibular pathways, robustly shaping how self-motion is represented in central vestibular circuits and cortical areas.


Assuntos
Núcleos Cerebelares/fisiologia , Córtex Cerebral/fisiologia , Percepção Espacial/fisiologia , Núcleos Talâmicos/fisiologia , Percepção do Tempo/fisiologia , Vestíbulo do Labirinto/fisiologia , Potenciais de Ação/fisiologia , Vias Aferentes/anatomia & histologia , Vias Aferentes/fisiologia , Animais , Mapeamento Encefálico , Núcleos Cerebelares/anatomia & histologia , Córtex Cerebral/anatomia & histologia , Eletrodos Implantados , Macaca mulatta , Neurônios Aferentes/citologia , Neurônios Aferentes/fisiologia , Técnicas Estereotáxicas , Transmissão Sináptica/fisiologia , Núcleos Talâmicos/anatomia & histologia , Vestíbulo do Labirinto/anatomia & histologia
19.
Onco Targets Ther ; 9: 2049-56, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27103831

RESUMO

BACKGROUND: Previous studies have investigated the associations between the common polymorphisms in FAS/FASL genes and lung cancer risk; however, the results remain inconsistent and inconclusive. Hence, we performed a meta-analysis to reassess the relationships between FAS rs2234767 and FASL rs763110 polymorphisms and the risk of lung cancer. METHODS: Eligible studies retrieved by an electronic search were pooled to calculate the strength of the associations using the odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: A total of 13 case-control studies involving 39,736 subjects (9,237 cases and 10,838 controls on FAS rs2234767 and 8,957 cases and 10,704 controls on FASL rs763110) were included in the meta-analysis. The results showed a significant association between FAS rs2234767 polymorphism and increased risk of lung cancer (A vs G: OR =1.07, 95% CI =1.01-1.13; AA vs GG: OR =1.23, 95% CI =1.06-1.43; AA vs GA + GG: OR =1.24, 95% CI =1.08-1.43). Similar association was also observed in Asian population (AA vs GA + GG: OR =1.30, 95% CI =1.01-1.67) and in the studies with large sample size (A vs G: OR =1.07, 95% CI =1.00-1.14; AA vs GG: OR =1.30, 95% CI =1.07-1.58). However, no significant association between FASL rs763110 polymorphism and lung cancer risk was found other than in the Asian population (CC vs TC + TT: OR =1.35, 95% CI =1.01-1.80). CONCLUSION: The meta-analysis indicated that FAS rs2234767 polymorphism was significantly associated with an increased risk of lung cancer and FASL rs763110 polymorphism may not contribute to susceptibility to lung cancer other than in Asian population.

20.
Oncotarget ; 7(23): 35437-45, 2016 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-27105507

RESUMO

The purpose of this study is to summarize the currently available evidence regarding the concerned issue by performing a comprehensive meta-analysis. Relevant publications reporting the association of metformin use with survival of lung cancer patients with diabetes were electronically searched to identify eligible studies. The meta-analysis was performed with hazard ratios (HRs) and 95% confidence intervals (95% CIs) as effect measures for disease-free survival(DFS) and overall survival(OS) estimates. A total of 17 individual studies from 10 publications were included in the meta-analysis. Overall, the results revealed a significant association of metformin use with a better survival of lung cancer patients with diabetes(for DFS: HR = 0.65, 95%CI = 0.52-0.83; for OS: HR = 0.78, 95%CI = 0.64-0.93). The subgroup analyses showed similar association in Asian region(for DFS:HR = 0.69, 95%CI = 0.59-0.80; for OS: HR = 0.55, 95%CI = 0.46-0.67) but not in Western region. Such association was also presented in small cell lung cancer (for DFS: HR = 0.54, 95%CI = 0.38-0.77; for OS: HR = 0.52, 95%CI = 0.39-0.69) and in non-small cell lung cancer(for DFS: HR = 0.70, 95%CI = 0.51-0.96; for OS: HR = 0.75, 95%CI = 0.58- 0.97). Analyses stratified by treatment strategy showed a reduction in the risk of cancer-related mortality in patients receiving chemotherapy(for DFS: HR = 0.71, 95%CI = 0.64-0.83; for OS: HR = 0.58, 95%CI = 0.47-0.71) but not in patients receiving chemoradiotherapy. The meta-analysis demonstrated that metformin use was significantly associated with a favorable survival outcome of lung cancer patients with diabetes.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Neoplasias Pulmonares/complicações , Metformina/uso terapêutico , Complicações do Diabetes , Humanos , Neoplasias Pulmonares/mortalidade
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