RESUMO
Numerous studies on perceptual training exist, however, most have focused on the precision of temporal audiovisual perception, while fewer have concentrated on ability promotion for audiovisual integration (AVI). To investigate these issues, continuous 5-day audiovisual perceptual training was applied, during which electroencephalography was performed in response to auditory-only (A), visual-only (V) and audiovisual (AV) stimuli before and after training. The results showed that the perceptual sensitivity was greater for training group than for control group and was greater in the posttest than in the pretest. The response to the AV stimulus was significantly faster in the posttest than in the pretest for the older training group but was significantly greater for A and V stimuli for the younger training group. Electroencephalography analysis found higher P3 AVI amplitudes [AV-(A + V)] in the posttest than in the pretest for training group, which were subsequently reflected by an increased alpha (8-12 Hz) oscillatory response and strengthened global functional connectivity (weighted phase lag index). Furthermore, these facilitations were greater for older training groups than for younger training groups. These results confirm the age-related compensatory mechanism for AVI may be strengthened as audiovisual perceptual training progresses, providing an effective candidate for cognitive intervention in older adults.
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Estimulação Acústica , Ritmo alfa , Percepção Auditiva , Estimulação Luminosa , Percepção Visual , Humanos , Masculino , Feminino , Percepção Visual/fisiologia , Percepção Auditiva/fisiologia , Idoso , Ritmo alfa/fisiologia , Estimulação Luminosa/métodos , Eletroencefalografia , Pessoa de Meia-Idade , Envelhecimento/fisiologia , Adulto Jovem , Encéfalo/fisiologia , AdultoRESUMO
Thin endometrium has been widely recognized as a critical cause of infertility, recurrent pregnancy loss, and placental abnormalities; however, access to effective treatment is a formidable challenge due to the rudimentary understanding of the pathogenesis of thin endometrium. Here, we profiled the transcriptomes of human endometrial cells at single-cell resolution to characterize cell types, their communications, and the underlying mechanism of endometrial growth in normal and thin endometrium during the proliferative phase. Stromal cells were the most abundant cell type in the endometrium, with a subpopulation of proliferating stromal cells whose cell cycle signaling pathways were compromised in thin endometrium. Both single-cell RNA sequencing and experimental verification revealed cellular senescence in the stroma and epithelium accompanied by collagen overdeposition around blood vessels. Moreover, decreased numbers of macrophages and natural killer cells further exacerbated endometrial thinness. In addition, our results uncovered aberrant SEMA3, EGF, PTN, and TWEAK signaling pathways as causes for the insufficient proliferation of the endometrium. Together, these data provide insight into therapeutic strategies for endometrial regeneration and growth to treat thin endometrium.
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Endométrio/metabolismo , Endométrio/patologia , Endométrio/fisiologia , Proteínas de Transporte/metabolismo , Citocina TWEAK/metabolismo , Citocinas/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Células Epiteliais/metabolismo , Epitélio , Feminino , Expressão Gênica/genética , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/fisiopatologia , Semaforina-3A/genética , Semaforina-3A/metabolismo , Transdução de Sinais/genética , Análise de Célula Única , Células Estromais/metabolismo , Transcriptoma/genéticaRESUMO
The lattice parameter of platinum-based intermetallic compounds (IMCs), which correlates with the intrinsic activity of the oxygen reduction reaction (ORR), can be modulated by crystal phase engineering. However, the controlled preparation of IMCs with unconventional crystal structures remains highly challenging. Here, we demonstrate the synthesis of carbon-supported PtCu-based IMC catalysts with an unconventional L10 structure by a composition-regulated strategy. Experiment and machine learning reveal that the thermodynamically favorable structure changes from L11 to L10 when slight Cu atoms are substituted with Co. Benefiting from crystal-phase-induced strain enhancement, the prepared L10-type PtCu0.8Co0.2 catalyst exhibits much-enhanced mass and specific activities of 1.82 A mgPt-1 and 3.27 mA cmPt-2, which are 1.91 and 1.73 times higher than those of the L11-type PtCu catalyst, respectively. Our work highlights the important role of crystal phase in determining the surface strain of IMCs, and opens a promising avenue for the rational preparation of IMCs with different crystal phases by doping.
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Plasma proteins are considered the most informative source of biomarkers for disease diagnosis and monitoring. Mass spectrometry (MS)-based proteomics has been applied to identify biomarkers in plasma, but the complexity of the plasma proteome and the extremely large dynamic range of protein abundances in plasma make the clinical application of plasma proteomics highly challenging. We designed and synthesized zeolite-based nanoparticles to deplete high-abundance plasma proteins. The resulting novel plasma proteomic assay can measure approximately 3000 plasma proteins in a 45 min chromatographic gradient. Compared to those in neat and depleted plasma, the plasma proteins identified by our assay exhibited distinct biological profiles, as validated in several public datasets. A pilot investigation of the proteomic profile of a hepatocellular carcinoma (HCC) cohort identified 15 promising protein features, highlighting the diagnostic value of the plasma proteome in distinguishing individuals with and without HCC. Furthermore, this assay can be easily integrated with all current downstream protein profiling methods and potentially extended to other biofluids. In conclusion, we established a robust and efficient plasma proteomic assay with unprecedented identification depth, paving the way for the translation of plasma proteomics into clinical applications.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Zeolitas , Humanos , Carcinoma Hepatocelular/diagnóstico , Proteoma , Proteômica/métodos , Neoplasias Hepáticas/diagnóstico , Biomarcadores/análise , Proteínas Sanguíneas/análiseRESUMO
OBJECTIVE: Moyamoya disease (MMD) is a rare and progressive stenosis of cerebral arteries characterized by abnormally proliferative vasculopathy. Current studies have demonstrated that Neuregulin 1 (NRG1) plays a key role in angiogenesis-related disorders. Thus, the aim of our study is to investigate the serum NRG1 levels and their clinical correlations in MMD patients. METHODS: In this study, thirty adult patients with MMD and age-gender matched healthy controls were enrolled from our hospital between July 2020 and April 2022. Peripheral blood samples were collected at baseline, and clinical data were obtained from the electronic medical record system. Serum NRG1 concentrations were measured by enzyme-linked immunosorbent assay. Sanger sequencing was applied to detect the RNF213 p.R4810K mutation. RESULTS: The serum NRG1 levels were significantly higher in MMD patients compared to controls (14.48 ± 10.81 vs.7.54 ± 6.35mmol/L, p < 0.001). No statistical difference in baseline clinical characteristics was found between both groups. Correlation analyses showed that NRG1 levels were positively associated with Suzuki staging (r = 0.4137, p = 0.023) while not related to other clinical features (reduced cerebral blood flow, posterior cerebral artery involvement, bilateral or unilateral steno-occlusive changes). Furthermore, subgroup analysis revealed that MMD patients with the RNF213 p.R4810K mutation presented with significantly higher NRG1 levels than those without the mutation (9.60 ± 0.929 vs. 25.89 ± 4.338 mmol/L, p = 0.001). CONCLUSIONS: Our study suggests that increased serum NRG1 levels may constitute a characteristic feature of MMD, indicating a potential positive correlation with disease progression and the presence of the RNF213 mutation. This positions NRG1 as a potentially crucial target for further studies aimed at comprehending the pathogenesis of MMD.
Assuntos
Doença de Moyamoya , Adulto , Humanos , Adenosina Trifosfatases/genética , Biomarcadores , Estudos de Casos e Controles , China , Progressão da Doença , Predisposição Genética para Doença , Doença de Moyamoya/diagnóstico , Doença de Moyamoya/genética , Neuregulina-1/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
BACKGROUND: Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) engraftment is a promising therapy for acute ischemic stroke (AIS). However, the harsh ischemic microenvironment limits the therapeutic efficacy of hUC-MSC therapy. Curcumin is an anti-inflammatory agent that could improve inflammatory microenvironment. However, whether it enhances the neuroprotective efficacy of hUC-MSC transplantation is still unknown. In the present study, we investigated the therapeutic efficacy and the possible mechanism of combined curcumin and hUC-MSC treatment in AIS. METHODS: Middle cerebral artery occlusion (MCAO) mice and oxygen glucose deprivation (OGD) microglia were administrated hUC-MSCs with or without curcumin. Neurological deficits assessment, brain water content and TTC were used to assess the therapeutic effects of combined treatment. To elucidate the mechanism, MCAO mice and OGD microglia were treated with AKT inhibitor MK2206, GSK3ß activator sodium nitroprusside (SNP), GSK3ß inhibitor TDZD-8 and Nrf2 gene knockout were used. Immunofluorescence, flow cytometric analysis, WB and RT-PCR were used to evaluate the microglia polarization and the expression of typical oxidative mediators, inflammatory cytokines and the AKT/GSK-3ß/ß-TrCP/Nrf2 pathway protein. RESULTS: Compared with the solo hUC-MSC-grafted or curcumin groups, combined curcumin-hUC-MSC therapy significantly improved the functional performance outcomes, diminished the infarct volumes and the cerebral edema. The combined treatment promoted anti-inflammatory microglia polarization via Nrf2 pathway and decreased the expression of ROS, oxidative mediators and pro-inflammatory cytokines, while elevating the expression of the anti-inflammatory cytokines. Nrf2 knockout abolished the antioxidant stress and anti-inflammation effects mediated with combined treatment. Moreover, the combined treatment enhanced the phosphorylation of AKT and GSK3ß, inhibited the ß-TrCP nucleus translocation, accompanied with Nrf2 activation in the nucleus. AKT inhibitor MK2206 activated GSK3ß and ß-TrCP and suppressed Nrf2 phosphorylation in nucleus, whereas MK2206 with the GSK3ß inhibitor TDZD-8 reversed these phenomena. Furthermore, combined treatment followed by GSK3ß inhibition with TDZD-8 restricted ß-TrCP nucleus accumulation, which facilitated Nrf2 expression. CONCLUSIONS: We have demonstrated that combined curcumin-hUC-MSC therapy exerts anti-inflammation and antioxidant stress efficacy mediated by anti-inflammatory microglia polarization via AKT/GSK-3ß/ß-TrCP/Nrf2 axis and an improved neurological function after AIS.
Assuntos
Curcumina , AVC Isquêmico , Transplante de Células-Tronco Mesenquimais , Humanos , Camundongos , Animais , Glicogênio Sintase Quinase 3 beta , Proteínas Proto-Oncogênicas c-akt , Proteínas Contendo Repetições de beta-Transducina , Fator 2 Relacionado a NF-E2 , Antioxidantes , Infarto da Artéria Cerebral Média , Citocinas , Cordão Umbilical , Anti-Inflamatórios/farmacologiaRESUMO
BACKGROUND: Thin endometrium (TE) is a challenging clinical issue in the reproductive medicine characterized by inadequate endometrial thickness, poor response to estrogen and no effective treatments currently. At present, the precise pathogenesis of thin endometria remains to be elucidated. We aimed to explore the related molecular mechanism of TE by comparing the transcriptome profiles of late-proliferative phase endometria between TE and matched controls. METHODS: We performed a bulk RNA-Seq (RNA-sequencing) of endometrial tissues in the late-proliferative phase in 7 TE and 7 matched controls for the first time. Differential gene expression analysis, gene ontology enrichment analysis and protein-protein interactions (PPIs) network analysis were performed. Immunohistochemistry was used for molecular expression and localization in endometria. Human endometrial stromal cells (HESCs) were isolated and cultured for verifying the functions of hub gene. RESULTS: Integrative data mining of our RNA-seq data in endometria revealed that most genes related to cell division and cell cycle were significantly inhibited, while inflammation activation, immune response and reactive oxygen species associated genes were upregulated in TE. PBK was identified as a hub of PPIs network, and its expression level was decreased by 2.43-fold in endometria of TE patients, particularly reduced in the stromal cells, which was paralleled by the decreased expression of Ki67. In vitro experiments showed that the depletion of PBK reduced the proliferation of HESCs by 50% and increased the apoptosis of HESCs by 1 time, meanwhile PBK expression was inhibited by oxidative stress (reduced by 76.2%), hypoxia (reduced by 51.9%) and inflammatory factors (reduced by approximately 50%). These results suggested that the insufficient expression of PBK was involved in the poor endometrial thickness in TE. CONCLUSIONS: The endometrial transcriptome in late-proliferative phase showed suppressed cell proliferation in women with thin endometria and decreased expression of PBK in human endometrial stromal cells (HESCs), to which inflammation and reactive oxygen species contributed.
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Proliferação de Células/genética , Endométrio/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Adulto , Estudos de Casos e Controles , Células Cultivadas , Regulação para Baixo/genética , Endométrio/metabolismo , Feminino , Humanos , Tamanho do Órgão/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA-Seq , Análise de Sequência de RNA , Células Estromais/metabolismo , Células Estromais/patologia , TranscriptomaRESUMO
BACKGROUND: Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) plays an important role in mediating inflammatory responses during ischemic stroke. Bile acid receptor Takeda-G-protein-receptor-5 (TGR5) has been identified as an important component in regulating brain inflammatory responses. In this study, we investigated the mechanism of TGR5 in alleviating neuroinflammation after middle cerebral artery occlusion (MCAO). METHODS: Sprague-Dawley rats were subjected to MCAO and TGR5 agonist INT777 was administered intranasally 1 h after MCAO. Small interfering RNAs (siRNA) targeting TGR5 and Pellino3 were administered through intracerebroventricular injection 48 h before MCAO. Infarct volumes and neurologic scores were evaluated, and ELISA, flow cytometry, immunofluorescence staining, immunoblotting, and co-immunoprecipitation were used for the evaluations. RESULTS: Endogenous TGR5 and Pellino3 levels increased after MCAO. TGR5 activation by INT777 significantly decreased pro-inflammatory cytokine, cleaved caspase-8, and NLRP3 levels, thereby reducing brain infarctions; both short- and long-term neurobehavioral assessments showed improvements. Ischemic damage induced the interaction of TGR5 with Pellino3. Knockdown of either TGR5 or Pellino3 increased the accumulation of cleaved caspase-8 and NLRP3, aggravated cerebral impairments, and abolished the anti-inflammatory effects of INT777 after MCAO. CONCLUSIONS: TGR5 activation attenuated brain injury by inhibiting neuroinflammation after MCAO, which could be mediated by Pellino3 inhibition of caspase-8/NLRP3.
Assuntos
Caspase 8/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Mediadores da Inflamação/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Administração Intranasal , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ácidos Cólicos/administração & dosagem , Infarto da Artéria Cerebral Média/prevenção & controle , Mediadores da Inflamação/antagonistas & inibidores , Injeções Intraventriculares , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , RNA Interferente Pequeno/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/agonistas , Ubiquitina-Proteína Ligases/antagonistas & inibidoresRESUMO
Intrauterine adhesions (IUAs), the leading cause of uterine infertility, are characterized by endometrial fibrosis. The management of IUA is challenging because the pathogenesis of the disease largely unknown. In this study, we demonstrate that the mRNA and protein levels of high mobility group AT-hook 2 (HMGA2) were increased by nearly 3-fold (P < 0.0001) and 5-fold (P = 0.0095) in the endometrial epithelial cells (EECs) of IUA patients (n = 18) compared to controls. In vivo and in vitro models of endometrial fibrosis also confirmed the overexpression of HMGA2 in EECs. In vitro cell experiments indicated that overexpression of HMGA2 promoted the epithelial-mesenchymal transition (EMT) while knockdown of HMGA2 reversed transforming growth factor-ß-induced EMT. A dual luciferase assay confirmed let-7d microRNA downregulated HMGA2 and repressed the pro-EMT effect of HMGA2 in vitro and in vivo. Therefore, our data reveal that HMGA2 promotes IUA formation and suggest that let-7d can depress HMGA2 and may be a clinical targeting strategy in IUA.
Assuntos
Endométrio/metabolismo , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Proteína HMGA2/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Doenças Uterinas/metabolismo , Adulto , Animais , Estudos de Casos e Controles , Linhagem Celular , Modelos Animais de Doenças , Endométrio/patologia , Células Epiteliais/patologia , Feminino , Fibrose , Regulação da Expressão Gênica , Proteína HMGA2/genética , Humanos , Camundongos Endogâmicos BALB C , Oligonucleotídeos/genética , Oligonucleotídeos/metabolismo , Transdução de Sinais , Aderências Teciduais , Doenças Uterinas/genética , Doenças Uterinas/patologia , Adulto JovemRESUMO
Previous studies have shown that exogenous attention decreases audiovisual integration (AVI); however, whether the interaction between exogenous attention and AVI is influenced by cue-target onset asynchrony (CTOA) remains unclear. To clarify this matter, twenty participants were recruited to perform an auditory/visual discrimination task, and they were instructed to respond to the target stimuli as rapidly and accurately as possible. The analysis of the mean response times showed an effective cueing effect under all cued conditions and significant response facilitation for all audiovisual stimuli. A further comparison of the differences between the probability of audiovisual cumulative distributive functions (CDFs) and race model CDFs showed that the AVI latency was shortened under the cued condition relative to that under the no-cue condition, and there was a significant break point when the CTOA was 200 ms, with a decrease in the AVI upon going from 100 to 200 ms and an increase upon going from 200 to 400 ms. These results indicated different mechanisms for the interaction between exogenous attention and the AVI under the shorter and longer CTOA conditions and further suggested that there may be a temporal window in which the AVI effect is mainly affected by exogenous attention, but the interaction might be interfered with by endogenous attention when exceeding the temporal window.
Assuntos
Atenção/fisiologia , Percepção Auditiva/fisiologia , Discriminação Psicológica/fisiologia , Percepção Visual/fisiologia , Adulto , Sinais (Psicologia) , Feminino , Humanos , Masculino , Estimulação Luminosa , Tempo de Reação/fisiologia , Adulto JovemRESUMO
BACKGROUND: It is difficult to distinguish benign pulmonary nodules (PNs) from malignant PNs by conventional examination. Therefore, novel biomarkers that can identify the nature of PNs are needed. Exosomes have recently been identified as an attractive alternative approach since tumor-specific molecules can be found in exosomes isolated from biological fluids. METHODS: Plasma exosomes were extracted via the exoEasy reagent method. The major proteins from plasma exosomes in patients with PNs were identified via labelfree analysis and screened for differentially expressed proteins. A GO classification analysis and KEGG pathway analysis were performed on plasma exosomal protein from patients with benign and malignant PNs. RESULTS: Western blot confirmed that protein expression of CD63 and CD9 could be detected in the exosome extract. Via a search of the human Uniprot database, 736 plasma exosome proteins from patients with PNs were detected using high-confidence peptides. There were 33 differentially expressed proteins in the benign and malignant PNs. Of these, 12 proteins were only expressed in the benign PNs group, while 9 proteins were only expressed in the malignant PNs group. We further obtained important information on signaling pathways and nodal proteins related to differential benign and malignant PNs via bioinformatic analysis methods such as GO, KEGG, and String. CONCLUSIONS: This study provides a new perspective on the identification of novel detection strategies for benign and malignant PNs. We hope our findings can provide clues for the identification of benign and malignant PNs.
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BACKGROUND/AIMS: To investigate the clinical effects of the combination therapy with Bushen Formula (BSF) plus enticavir (ETV) on chronic hepatitis B (CHB) patients with suboptimal response to ETV and explore the regulatory mechanisms of BSF on B cells-mediated humoral immunity. METHODS: Sixty-four HBeAg-positive CHB patients with suboptimal response to ETV were enrolled, and were randomly assigned into control group (C-Group, placebo combined with ETV for 12 months) or treatment group (T-Group, BSF combined with ETV for 12 months). Serum samples from 57 treatment-naïve CHB patients and 15 healthy controls were collected. Serum HBV DNA levels were evaluated by real-time PCR. Characteristics of peripheral blood B-cell subtypes were analyzed by flow cytometry. Serum HBV markers and B cell-activating factor (BAFF) levels were detected by ELISA. Chinese medicine symptom complex score was evaluated and recorded. RESULTS: After treatment, the rates of patients with a reduction of HBsAg > 0.5 log10 IU/ml or 1.0 log10 IU/ml and the rates of HBeAg clearance in T-Group were all higher than those in C-group, with no significant intergroup difference. Only in T-Group, Chinese medicine symptom complex score and the frequency of total B cells were significantly decreased, and the frequencies of Bm1, CD24+CD27-switched B cells and plasma cells were markedly increased after treatment compared with those before treatment. Compared with healthy controls, serum BAFF levels in treatment-naïve CHB patients were increased, and there was a significant positive correlation between serum BAFF and HBsAg levels. However, serum BAFF levels did not differ after treatment in T-Group and C-Group. CONCLUSIONS: The combination therapy with BSF plus ETV promotes the reduction of HBsAg level and the clearance of HBeAg in CHB patients with partial response to ETV through regulating the differentiation of B-cell subsets.
Assuntos
Antivirais/farmacologia , Diferenciação Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Antivirais/uso terapêutico , Linfócitos B/citologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Estudos de Casos e Controles , DNA Viral/sangue , DNA Viral/metabolismo , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
MicroRNA-186-5p (miR-186-5p) is upregulated and exhibits as a crucial oncogene in various human tumors. However, the functions and underlying mechanisms of this microRNA on colorectal cancer remain largely unknown. Here, we report that miR-186-5p share a lower expression in colorectal cancer cell lines (HT116, H29, SW620 and LoVo) than in normal colonic epithelial cell line NCM460. MiR-186-5p overexpression inhibits proliferation, metastasis and epithelial-to-mesenchymal transition (EMT) of colorectal cancer cell line LoVo. Zinc Finger E-Box Binding Homeobox 1 (ZEB1), an EMT related marker, is predicted as a target of miR-186-5p. Luciferase reporter assay, qRT-PCR and western blot analysis showed that miR-186-5p directly targeted the 3'-untranslated regions (3'UTR) of ZEB1 messenger RNA. Further functional experiments indicated that overexpression of miR-186-5p suppress the proliferation and metastasis ability of LoVo, which was consistent with the inhibitory effects by knockdown of ZEB1. Additionally, overexpression of ZEB1 could significantly reverse the miR-186-5p mimics initiated suppression impact of proliferation, metastasis and EMT on LoVo. In summary, miRNA-186-5p affects the proliferation, metastasis and EMT process of colorectal cancer cell by inhibition of ZEB1. Hence, it may serve as a promising therapeutic target for colorectal cancer.
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Proliferação de Células/fisiologia , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/fisiologia , MicroRNAs/fisiologia , Regulação para Cima , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Regulação para Baixo , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Metástase Neoplásica , RNA Mensageiro/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genéticaRESUMO
BACKGROUND: Cervicocephalic artery dissection (CAD) is an important etiology of stroke in the youth. Findings from recent studies suggest it a "group of disease entities" with different underlying etiologies, presentations and prognosis, necessitating an integral study including various types of CAD to get a better understanding of this disease. In addition, Chinese patients with CAD are likely to carry different features from their western counterparts, which remains uncertain yet. Chinese Cervicocephalic Artery Dissection Study (CCADS) therefore aims at exploring the epidemiology, risk factors, clinical/radiological features, diagnosis and prognosis of CAD in Chinese patients. METHODS/DESIGN: CCADS is a multicenter prospective cohort study enrolling patients age ≥ 18 years with recent (<14 days after onset) CAD. Baseline clinical data, laboratory tests and imaging studies are performed within 3 days after admission, and follow-ups will be conducted through face-to-face interviews at discharge, 3 months, 6 months and 12 months after admission, when the modified Rankin Scale (mRS), cerebrovascular events, medication compliance, CAD evolution and so on are evaluated. Additional blood samples will also be collected at baseline, 3 and 12 months follow-up. The primary outcome is radiographic evolution of CAD; secondary outcomes include cerebrovascular events, major bleeding complications, all-cause mortality and functional independence. DISCUSSION: Through the integration of information on epidemiology, risk factors, clinical/radiological features and prognosis of various types of CAD in Chinese population, combined with the application of advanced imaging techniques, collection of potential blood biomarkers, and assessment of novel treatment strategies. CCADS will provide thorough information on CAD - the major cause of stroke in the youth, and play a role in prevention and treatment determination in the future.
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Dissecção Aórtica/complicações , Dissecção Aórtica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Adolescente , Idoso , Artérias/patologia , Povo Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Projetos de Pesquisa , Fatores de RiscoRESUMO
PURPOSE: Spinal solitary fibrous tumor/hemangiopericytoma (SFT/HPC), a rare mesenchymal tumor that arises from pericytes of Zimmerman, comprises only 0.08% of all primary bone tumors and 0.1% of primary malignant bone tumor and rarely occurs in the spine. We attempt to correlate the clinical factors and different treatment options with the recurrence rate and overall survival of SFT/HPC over time. METHODS: A retrospective study of 20 patients with spinal osseous SFT/HPCs who were surgically treated in our center between 2003 and 2015 was performed. Kaplan-Meier curves and log-rank tests were used to compare the survival probability or recurrence-free probability between groups, and P values < 0.05 were considered statistically significant. RESULTS: Three surgical management strategies, including subtotal resection, piecemeal total resection, and total en bloc spondylectomy (TES) were applied. Postoperative radiotherapy was carried out in 14 cases. The mean follow-up period was 38.3 (median 35, range 7-93) months, and 6 patients passed away with the mean follow-up time of 47.7 (median 41, range 24-77) months. Relapse was detected in 9 patients (45%) with the mean time from surgery to recurrence being 36.6 (median 28, range 12-73) months. Our results indicate that grade III is an adverse prognostic factor for both recurrence and over survival (OS) for spinal osseous SFT/HPC, while total resection, especially TES, is a positive prognostic factor. CONCLUSIONS: Spinal osseous SFT/HPC is a challenging clinical entity given its high local recurrence rate. Surgical management plays a crucial role in the whole treatment of spinal SFT/HPCs and total excision, especially TES, should be strived for whenever possible. Postoperative radiotherapy is recommended to lower the recurrent rate. This study also confirms that pathology grade III is an adverse prognostic factor for spinal osseous SFT/HPCs.
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Hemangiopericitoma/cirurgia , Procedimentos Ortopédicos/métodos , Tumores Fibrosos Solitários/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adolescente , Adulto , Criança , Feminino , Seguimentos , Hemangiopericitoma/mortalidade , Hemangiopericitoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Procedimentos Ortopédicos/efeitos adversos , Prognóstico , Estudos Retrospectivos , Tumores Fibrosos Solitários/mortalidade , Tumores Fibrosos Solitários/patologia , Neoplasias da Coluna Vertebral/mortalidade , Neoplasias da Coluna Vertebral/patologia , Coluna Vertebral/patologia , Coluna Vertebral/cirurgia , Análise de Sobrevida , Adulto JovemRESUMO
Certain viruses use microRNAs to regulate the expression of their own genes, host genes, or both. A number of microRNAs expressed by herpes simplex virus type 2 have been confirmed by previous studies. However, whether these microRNAs play a role in the metastasis of lung cancers and how these viral microRNAs precisely regulated the tumor biological process in lung cancer bone metastasis remain obscure. We recently identified the high expression of an acutely and latently expressed viral microRNA, Hsv2-miR-H9-5p, encoded by herpes simplex virus type 2 latency-associated transcript through microarray and quantitative polymerase chain reaction analyses which compared the expression of microRNAs in bone metastasis from lung cancer with primary lung cancers. We now reported that Hsv2-miR-H9-5p was highly expressed in bone metastasis and closely associated with pathological and metastatic processes of lung cancers. The functions of Hsv2-miR-H9-5p were determined by overexpression which results in an increase in survival, migration, and invasion of lung cancer cells in vitro. We determined that Hsv2-miR-H9-5p directly targeted SOCS2 mechanistically by dual-luciferase reporter assay. Then, we investigated the functions of SOCS2 in the progress of lung cancers. Reduction of SOCS2 dosage by hsv2-miR-H9-5p induced increased migration and invasion of lung cancer cells. Overexpression of SOCS2 inverted these phenotypes generated by hsv2-miR-H9-5p, indicating the potential roles of SOCS2 in Hsv2-miR-H9-5p-driven metastasis in lung cancers. The results highlighted that Hsv2-miR-H9-5p regulated and contributed to bone metastasis of lung cancers. We proposed that Hsv2-miR-H9-5p could be used as a potential target in lung cancer therapy.
Assuntos
Neoplasias Ósseas/genética , Herpesvirus Humano 2/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas Supressoras da Sinalização de Citocina/biossíntese , Idoso , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Neoplasias Ósseas/virologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Herpesvirus Humano 2/patogenicidade , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/virologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas Supressoras da Sinalização de Citocina/genéticaRESUMO
BACKGROUND: Primary spinal osseous tumors are rare, yet they represent a difficult treatment paradigm because of the complexities of tumor resection and significant resistance to chemotherapy and radiation therapy. The geographic distribution of primary spinal osseous tumors throughout the world appears to be quite variable, with a very low incidence reported in Asian countries. METHODS: Data on 1209 cases of primary spinal osseous malignant and benign tumor cases diagnosed during the 20-year period of 1995 through 2015 in eastern China were analyzed. RESULTS: In 780 cases (64.5%), the lesion was benign and in 429 (35.5%) was malignant. The commonest primary malignant tumors were chordoma (9.8% of all cases) followed by plasma cell myeloma (8.5% of all cases). The most common benign tumor was hemangioma (28.1% of all cases) followed by giant cell tumor of bone (15.7% of all cases) and osteoblastoma (4.4% of all cases). The benign tumors affected men in 33.8% of cases and women in 30.7% of cases, the malignant tumors affected men in 23.7% of cases and women in 11.8%. The mean age (mean ± SD) in the benign group was 34.7 ± 19.8 years and in the malignant group was 47.4 ± 16.5 years. Related symptoms were pain (54.4%), radiculopathy (12.9%), cord compression (9.2%), mass (5.7%), pathological fracture (4.7%), deformity (2.1%), and weight loss (1.9%). The anatomical locations included almost every vertebra of the spine. The thoracic spine (38.1%) was the most common location of the tumors, followed by the cervical spine (27.4%) and lumbar spine (18.4%). CONCLUSIONS: Compared with other similar series reported in the literature from the other countries, our results obtained in a developing country were different in some degree. This large series of primary spinal osseous tumors may reflect fairly well their real incidence and provide a sufficiently detailed perspective on epidemiologic studies of primary spinal osseous tumors in eastern China.
Assuntos
Vértebras Cervicais/patologia , Cordoma/epidemiologia , Hemangioma/epidemiologia , Neoplasias da Coluna Vertebral/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Adulto JovemRESUMO
B7-H1 binding to programmed death-1 may deliver a coinhibitory signal to T cells that is involved in the regulation of T-cell activation and tolerance. B7-H1 plays a key role in dysfunction of dendritic cells (DCs) during chronic HBV infection, but the expression mechanism of B7-H1 remains unclear. One hundred and twenty-nine patients with chronic HBV infection were categorized into either the immune tolerance phase (HBV-IT), the immune clearance phase (HBV-IC), or the inactive carrier phase (HBV-IA). Twenty healthy volunteers were enrolled as controls. Another 16 patients with HBeAg-positive chronic Hepatitis B were enrolled, and entecavir was administrated at 0.5 mg per day for 6 months. The B7-H1 expression level on peripheral DCs was tested by flow cytometry. In vitro, expression levels of B7-H1 and signaling molecules on monocyte-derived DC (MO-DC) induced by recombinant hepatitis B virus C antigen (rhHBcAg) were examined by RT-PCR, flow cytometry, and western blotting, and the apoptosis rate was tested by flow cytometry. The percentages of peripheral DCs and myeloid DCs (mDCs) were decreased and B7-H1 levels were increased in patients compared with controls. Serum HBV-DNA levels were positively correlated with B7-H1 levels on mDCs in patients with HBV-IT. B7-H1 levels on peripheral DCs from patients with chronic hepatitis B decreased after antiviral therapy. In vitro studies demonstrated that the B7-H1 level on MO-DC was upregulated by rhHBcAg, which resulted from the activation of PI3K-AKT, ERK, and P38 signaling pathways, and the percentage of MO-DC was downregulated by rhHBcAg. In addition, rhHBcAg promoted the apoptosis of MO-DC. The data suggest that HBcAg induced B7-H1 upregulation by activating AKT, ERK, and P38 signaling pathways, which inhibited the clearance of HBV-DNA and the reduction of DCs contributed to immune tolerance, which may correlate with apoptosis.
Assuntos
Antígeno B7-H1/metabolismo , Células Dendríticas/metabolismo , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Hepatite B Crônica/metabolismo , Sistema de Sinalização das MAP Quinases , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Antivirais/uso terapêutico , Apoptose , Estudos de Casos e Controles , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adulto JovemRESUMO
Giant cell tumor of bone(GCTB) is a special bone tumor for it consists of various cell types, and its biological characteristics is different from common benign or malignant neoplasm. In the present study, we report the biological features of a primary Asian GCTB cell line named GCTB28. We analyzed extensive properties of the GCTB28 cells including morphological observations, growth, cell cycle, karyotype, proliferation, proteins expression, surface biomarker verification, and tumorigenicity in nude mice. We found that the stromal cells of GCTB were endowed with self-renewal capacity and played dominant roles in GCTB development. Moreover, we confirmed that GCTB cells can be CD33(-)CD14(-) phenotype which was not in accord with previous study. This study provides an in vitro model system to investigate pathogenic mechanisms and molecular characteristics of GCTB and also provides a useful tool for researching the therapeutic targeting of GCTB.
Assuntos
Neoplasias Ósseas/patologia , Tumor de Células Gigantes do Osso/patologia , Coluna Vertebral/patologia , Adulto , Animais , Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Carcinogênese/genética , Carcinogênese/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Tumor de Células Gigantes do Osso/genética , Humanos , Receptores de Lipopolissacarídeos/genética , Masculino , Camundongos , Camundongos Nus , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Células Estromais/patologiaRESUMO
MicroRNAs play important roles in the development of cancers. Although miR-92b has been reported to promote the tumorigenesis of some cancers, its role in osteosarcoma remains unknown. In the present study, we focused on the expression, function and mechanisms of miR-92b in osteosarcoma development. The miRNA miR-92b was up-regulated in osteosarcoma cell lines and tissues; miR-92b up-regulation correlated with poor prognosis in osteosarcoma. Overexpression of miR-92b promoted osteosarcoma cell proliferation, migration and invasion, which was abrogated by miR-92b inhibition. Reversion-inducing, cysteine-rich protein with kazal motifs (RECK) was identified as the direct and functional target of miR-92b in osteosarcoma. Importantly, restoring RECK expression abrogated increases in cell growth, motility and invasiveness induced by miR-92b RECK was down-regulated in osteosarcoma tissues, and its expression level negatively correlated with miR-92b Collectively, our results indicate that miR-92b acts as an oncogenic miRNA and may be a therapeutic target in osteosarcoma.