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1.
Chem Biodivers ; : e202400792, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738487

RESUMO

In the current work, grifolin was obtained from the twigs and leaves of Daphne genkwa for the first time and displayed significant growth inhibition against human lung carcinoma A549 cells. Subsequent in vitro antitumor evaluation revealed that grifolin could induce remarkable cell apoptosis and G0/G1 phase arrest, as well as block cell migration and invasion. In addition, grifolin also disrupted cellular energy metabolism by inducing reactive oxygen species, reducing adenosine triphosphate and mitochondrial membrane potential, and damaging DNA synthesis. Further RNA-seq analysis demonstrated that treatment of grifolin on A549 cells led to gene enrichment in MAPK, PI3K/Akt and NF-κB signaling pathways, all of which were inhibited by grifolin according to immunoblotting experiments. Further mechanistical studies disclosed that the expression of a key upstream protein KRAS was also blocked, and the cell death triggered by grifolin could be rescued by a RAS activator ML-099. Moreover, pretreatment of ML-099 on A549 cells could reverse the grifolin-induced downregulation of key proteins in the three aforementioned pathways. These findings indicate that grifolin could induce cell death in A549 cell line by inhibiting KRAS-mediated multiple signaling pathways.

2.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731870

RESUMO

Transcranial magneto-acoustic stimulation (TMAS), which is characterized by high spatiotemporal resolution and high penetrability, is a non-invasive neuromodulation technology based on the magnetic-acoustic coupling effect. To reveal the effects of TMAS treatment on amyloid-beta (Aß) plaque and synaptic plasticity in Alzheimer's disease, we conducted a comparative analysis of TMAS and transcranial ultrasound stimulation (TUS) based on acoustic effects in 5xFAD mice and BV2 microglia cells. We found that the TMAS-TUS treatment effectively reduced amyloid plaque loads and plaque-associated neurotoxicity. Additionally, TMAS-TUS treatment ameliorated impairments in long-term memory formation and long-term potentiation. Moreover, TMAS-TUS treatment stimulated microglial proliferation and migration while enhancing the phagocytosis and clearance of Aß. In 5xFAD mice with induced microglial exhaustion, TMAS-TUS treatment-mediated Aß plaque reduction, synaptic rehabilitation improvement, and the increase in phospho-AKT levels were diminished. Overall, our study highlights that stimulation of hippocampal microglia by TMAS treatment can induce anti-cognitive impairment effects via PI3K-AKT signaling, providing hope for the development of new strategies for an adjuvant therapy for Alzheimer's disease.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Microglia , Placa Amiloide , Animais , Microglia/metabolismo , Camundongos , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Estimulação Magnética Transcraniana/métodos , Estimulação Acústica , Camundongos Transgênicos , Modelos Animais de Doenças , Sinapses/metabolismo , Hipocampo/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Plasticidade Neuronal , Potenciação de Longa Duração , Transdução de Sinais
3.
Bioorg Chem ; 140: 106803, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37659144

RESUMO

Phytochemical investigation into the leaves and branches of Daphne genkwa afforded 25 meroterpenoids (1-16) including nine pairs of enantiomers (1a/1b-8a/8b and 12a/12b), among which 20 compounds have been reported in the present work for the first time. The structures with absolute configurations of the new molecules (excluding 10-13) were established via comprehensive spectroscopic analyses especially electronic circular dichroism (ECD) and Mosher's methods. A preliminary in vitro cell viability assay revealed remarkable cytotoxicities of selective compounds against A549 (lung), Hela (cervical), MDA-MB231 (breast) and MCF-7 (breast) cancer cells, and compound 8a showed the best inhibitory activity with IC50 values in the range of 3.12-4.67 µM toward the four cell lines. Subsequent in vitro antitumor evaluation of 8a disclosed that it could inhibit the proliferation and metastasis, as well as induce significant apoptosis and cycle arrest, of A549 cells. Further mechanistic investigations revealed that 8a could exert its antitumor activity via inhibiting the PI3K/Akt/mTOR signaling pathway.


Assuntos
Daphne , Humanos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Células A549 , Serina-Treonina Quinases TOR , Células HeLa , Transdução de Sinais
4.
Otolaryngol Head Neck Surg ; 168(6): 1453-1462, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36939469

RESUMO

OBJECTIVE: To compare the survival outcomes of early-stage oropharyngeal cancer (OPC) patients treated with upfront surgery versus definitive radiotherapy (RT). STUDY DESIGN: Retrospective observational study. SETTING: Publicly available database. METHODS: A total of 1877 patients with T1-2N0-1M0 OPC were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine-Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. RESULTS: In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 2.29; 95% confidence interval [CI], 1.42-3.68; p = .001) and noncancer mortality (adjusted SHR, 2.74; 95% CI, 1.50-5.02; p = .001). In the HPV-positive cohort, definitive RT and upfront surgery could achieve similar cancer-specific and noncancer survival outcomes. CONCLUSION: Upfront surgery is associated with lower cancer-specific and noncancer mortality in HPV-negative early-stage OPC patients. However, in the setting of HPV-positive early-stage OPC with better prognosis, the 2 treatment modalities have similar efficacy in terms of cancer-specific and noncancer survival outcomes. In the future, carefully designed prospective clinical trials are needed to confirm our findings.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/complicações , Estudos Prospectivos , Prognóstico , Medição de Risco , Neoplasias de Cabeça e Pescoço/complicações
5.
Nat Commun ; 13(1): 6485, 2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36309528

RESUMO

Bound states in the continuum (BICs) in photonic crystals describe the originally leaky Bloch modes that can become bounded when their radiation fields carry topological polarization singularities. However, topological polarization singularities do not carry energy to far field, which limits radiation efficiencies of BICs for light emitting applications. Here, we demonstrate a topological polarization singular laser which has a topological polarization singular channel in the second Brillouin zone and a paired linearly polarized radiation channel in the first Brillouin zone. The presence of the singular channel enables the lasing mode with a higher quality factor than other modes for single mode lasing. In the meanwhile, the presence of the radiation channel secures the lasing mode with high radiation efficiency. The demonstrated topological polarization singular laser operates at room temperature with an external quantum efficiency exceeding 24%. Our work presents a new paradigm in eigenmode engineering for mode selection, exotic field manipulation and lasing.

6.
Front Immunol ; 13: 952059, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045683

RESUMO

Background: PD-1/PD-L1 blockade is a promising immunotherapeutic strategy with the potential to improve the outcomes of various cancers. However, there is a critically unmet need for effective biomarkers of response to PD-1/PD-L1 blockade. Materials and methods: Potential biomarkers of response to PD-1/PD-L1 blockade were obtained from the Cancer Treatment Response gene signature Database (CTR-DB). A comprehensive pan-cancer analysis was done on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Correlations between gene expression and infiltration by immune cells were assessed using TIMER, EPIC, MCPcounter, xCell, CIBERSORT, and quanTIseq. Immunophenoscore (IPS) was used to assess the potential application of the biomarkers to all TCGA tumors. Results: Analysis of CTR-DB data identified CD69 and SBK1 as potential biomarkers of response to PD-1/PD-L1 blockade. Correlation analysis revealed that in various TCGA cancer datasets, CD69 expression level correlated positively with most immune checkpoints and tumor-infiltrating immune cells, while SBK1 expression level correlated negatively with infiltrating immune cells. IPS analysis demonstrated the ability of CD69 and SBK1 to predict PD-1/PD-L1 blockade responses in various cancers. Conclusion: CD69 and SBK1 are potential predictors of response to cancer immunotherapy using PD-1/PD-L1 blockade. These biomarkers may guide treatment decisions, leading to precise treatment and minimizing the waste of medical resources.


Assuntos
Neoplasias Pulmonares , Melanoma , Antígeno B7-H1/genética , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Pulmonares/patologia , Melanoma/tratamento farmacológico , Receptor de Morte Celular Programada 1
7.
J Voice ; 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36127214

RESUMO

PURPOSE: This study was performed to introduce a modified procedure involving a combination of bilateral vocal fold mucosal flaps and microsurgical sutures for the management of anterior glottic webs and to study its efficacy in decreasing the recurrence rate and improving voice quality. METHODS: We retrospectively reviewed 102 patients with anterior glottic webs who underwent surgical treatment by a carbon dioxide laser incision with or without microsurgical suturing in our hospital from May 2014 to April 2021. We focused on the reoperation rate and the voice outcomes based on the 30-item Voice Handicap Index. RESULTS: This study included 102 patients with anterior glottic webs, which were caused by papilloma excision and endoscopic laryngocarcinoma resection in 97 (95.1%) of the 102 patients; less common causes were infection and traumatic injury. All incisions were performed along the midline with a carbon dioxide laser under microscopy and a self-retaining laryngoscope; 37 (36.3%) patients underwent microsurgical suturing and 65 (63.7%) patients did not. The microsuture group had a lower reoperation rate (χ2= 7.069, P = 0.0078) and higher voice quality (t = 2.054, P = 0.0462) than the non-microsuture group. CONCLUSIONS: We introduced a modified procedure that can both decrease the recurrence rate and improve the voice quality in patients with anterior glottic webs. Hence, this combination therapy involving bilateral vocal fold mucosal flaps and microsurgical sutures is worthy of clinical application and promotion.

8.
Inorg Chem ; 61(19): 7484-7496, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35511935

RESUMO

Due to the inherent thermodynamic stability and kinetic inertness of CO2, heterogeneous catalytic conversion of CO2 to cyclic carbonates often requires harsh operating conditions, high temperature and high pressure, and the addition of cocatalysts. Therefore, the development of efficient heterogeneous catalysts under cocatalyst-free and mild conditions for CO2 conversion has always been a challenge. Herein, an infrequent tetracoordinated Cd-MOF was synthesized and used to catalyze CO2 cycloaddition reactions efficiently without the addition of any cocatalyst, and its catalytic mechanism was systematically investigated through a series of experiments, including fluorescence analysis, X-ray photoelectron spectroscopy, microcalorimetry, and density functional theory (DFT) calculation. Cd-MOF features a 3D supermolecule structure with 1D 11.6 × 7.7 Å2 channels, and the abundant Lewis acid/base and I- sites located in the confined channel boost efficient CO2 conversion with a maximum yield of 98.2% and a turnover number value of 1080.11 at 60 °C and 0.5 MPa, far surpassing most pristine MOF-based catalytic systems. A combined experimental and DFT calculation demonstrates that the exposed Cd(II) Lewis acid sites rapidly participate in coordination to activate the epoxides, and the resulting large steric hindrance facilitates leaving of the coordinated iodide ions in a reversibly dynamic fashion convenient for the rate-determining step ring-opening as a strong nucleophile. Such a pristine MOF catalyst with self-independent catalytic ring-opening overcomes the complicated operation limitation of the traditional cocatalyst-free MOF systems based on encapsulating/postmodifying cocatalysts, providing a whole new strategy for the development of simple, green, and efficient heterogeneous catalysts for CO2 cycloaddition.

9.
Arch Pharm Res ; 45(5): 328-339, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35478401

RESUMO

One new clerodane-type furanoditerpenoid tinosinoid A (1) and nine new nor-clerodane analogs tinosinoids B-J (2-10) have been isolated from the stems of Tinospora sinensis. The structures of the new compounds with absolute configurations have been elucidated by spectroscopic means, including MS, NMR and ECD techniques, as well as chemical correlation. Compound 1 is a rare sulfur-containing clerodane diterpenoid incorporating a 2-mercaptoethanol unit via a thioether bond, while compounds 4/5 and 9 represent two pairs of unusual equilibrium regioisomers through an interesting intramolecular transesterification. Our bioassays established that 1 and 8 displayed moderate antiproliferative effects against two human tumor cell lines, and 9 and 10 showed significant α-glucosidase inhibitory activities. A kinetics study revealed that compound 10 was a noncompetitive α-glucosidase inhibitor, and its possible binding mode to the enzyme was further probed by molecular docking experiments.


Assuntos
Diterpenos Clerodânicos , Tinospora , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Tinospora/química
10.
Front Cell Dev Biol ; 9: 727762, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527677

RESUMO

OBJECTIVE: To investigate the role of ferroptosis, an iron-dependent form of non-apoptotic cell death, in the head and neck squamous cell carcinoma (HNSCC) immune microenvironment. MATERIALS AND METHODS: A list of ferroptosis-related genes was obtained from the FerrDb database. Gene expression data were acquired from the cancer genome atlas (TCGA) and analyzed using the R language. Protein-protein interaction analysis was conducted using STRING and GeneMANIA. The correlations between gene expression levels and a patient's survival were analyzed using GEPIA, the Kaplan-Meier estimate, and a multivariate Cox proportional hazards model. The expression results were verified using Oncomine and Human Protein Atlas data. We used the TIMER, GEPIA2, GEPIA2021, and TIMER2 databases to investigate the relationships between gene expression and infiltrating immune cells. RESULTS: Analysis of differentially expressed genes (DEGs) identified nine each ferroptosis drivers and ferroptosis suppressors, among which four genes correlated with survival as follows: two drivers (SOCS1, CDKN2A) associated with better survival and two suppressors (FTH1, CAV1) associated with poorer survival. Multivariate Cox survival analysis identified SOCS1 and FTH1 as independent prognostic factors for HNSCC, and their higher expression levels were verified using Oncomine and HPA data. The results acquired using TIMER, GEPIA2, GEPIA2021, and TIMER2 data revealed that the driver SOCS1 and the suppressor FTH1 independently correlated with M1 and M2 macrophage infiltration. CONCLUSIONS: The ferroptosis driver SOCS1 and suppressor FTH1 are independent prognostic factors and that correlate with M1 and M2 macrophage infiltration in HNSCC. Targeting ferroptosis-immunomodulation may serve as a strategy to enhance the activity of immunotherapy.

11.
Sci Rep ; 11(1): 14294, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253828

RESUMO

Both electrical properties and biomarkers of biological tissues can be used to distinguish between normal and diseased tissues, and the correlations between them are critical for clinical applications of conductivity (σ) and permittivity (ε); however, these correlations remain unknown. This study aimed to investigate potential correlations between electrical characteristics and biomarkers of breast cancer cells (BCC). Changes in σ and ε of different components in suspensions of normal cells and BCC were analyzed in the range of 200 kHz-5 MHz. Pearson's correlation coefficient heatmap was used to investigate the correlation between σ and ε of the cell suspensions at different stages and biomarkers of cell growth and microenvironment. σ and ε of the cell suspensions closely resembled those of tissues. Further, the correlations between Na+/H+ exchanger 1 and ε and σ of cell suspensions were extremely significant among all biomarkers (pε < 0.001; pσ < 0.001). There were significant positive correlations between cell proliferation biomarkers and ε and σ of cell suspensions (pε/σ < 0.05). The microenvironment may be crucial in the testing of cellular electrical properties. ε and σ are potential parameters to characterize the development of breast cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/fisiologia , Feminino , Humanos
12.
Cancer Cell Int ; 21(1): 281, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34044823

RESUMO

BACKGROUND: Systematic profiling studies have implicated regulators of pre-mRNA splicing as important disease determinants in gastric cancer (GC), but the underlying mechanisms have remained elusive. Here we focused on hnRNPA2B1 splicing factor-dependent mechanisms governing GC development. METHODS: The expression of hnRNPA2B1 was analyzed among the Cancer Genome Atlas (TCGA) datasets of GC and validated at mRNA level. The function of hnRNPA2B1 in GC cells was analyzed and its downstream gene was identified using RNA immunoprecipitation. Further, effect of hnRNPA2B1 on BIRC5 alternative splicing was investigated. RESULTS: We show that overexpression of hnRNPA2B1 in GC is correlated with poor survival, and hnRNPA2B1 is required for maintaining GC malignant phenotype by promoting cell proliferation, inhibiting cell apoptosis and increasing cell metastasis. Mechanistically, hnRNPA2B1 co-expressed with several core spliceosome components and controls alternative splicing of anti-apoptotic factor BIRC5. BIRC5 isoform 202 (BIRC5-202) played the oncogenic function in GC cells, and overexpression of the BIRC5-202 transcript partly rescued the decrease in cisplatin resistance induced by downregulation of hnRNPA2B1. CONCLUSIONS: We demonstrate that hnRNPA2B1 regulates BIRC5 splicing and might act as a therapeutic target of chemo-resistant GC cells.

13.
Aging (Albany NY) ; 13(8): 11491-11506, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33864445

RESUMO

Ferritin is the most important iron storage form and is known to influence tumor immunity. We previously showed that expression of ferritin light chain (FTL) and ferritin heavy chain (FTH1) subunits is increased in head and neck squamous cell carcinoma (HNSC). Here, we analyzed solid tumor datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases to investigate correlations between FTL and FTH1 expressions and (i) patient survival, using univariate, multivariate, Kaplan-Meier and Receiver Operator Characteristic analysis; and (ii) tumor-infiltrating immune cell subsets, using the bioinformatics tools Estimation of Stomal and Immune cells in Malignant Tumor tissues, Microenvironment Cell Population-counter, Tumor Immune Estimation Resource, and Tumor Immunology Miner. We found that FTL and FTH1 are upregulated and downregulated, respectively, in most of the human cancers analyzed. Tumor FTL levels were associated with prognosis in patients with lower grade glioma (LGG), whereas FTH1 levels were associated with prognosis in patients with liver hepatocellular carcinoma, HNSC, LGG, and kidney renal papillary cell carcinoma. In many cancers, FTL and FTH1 levels was significantly positively correlated with tumor infiltration by tumor-associated macrophages and T regulatory cells. These results suggest an important role for FTL and FTH1 in regulating tumor immunity to solid cancers.


Assuntos
Apoferritinas/genética , Biomarcadores Tumorais/genética , Ferritinas/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias/imunologia , Oxirredutases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Conjuntos de Dados como Assunto , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/patologia , Prognóstico , Linfócitos T Reguladores/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/imunologia , Adulto Jovem
14.
J Appl Toxicol ; 41(11): 1826-1838, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33759202

RESUMO

2-isopropyl-N,2,3-trimethylbutyramide (WS-23) is a well-known artificial synthesis cooling agent widely used in foods, medicines, and tobaccos. As a commonly cooling agent in e-cigarette liquids, WS-23 has led to concerns about the inhalation toxicity with the prosperous of e-cigarettes in recent years. Thus, the aim of this study is to assess the acute and subacute inhalation toxicity of WS-23 in Sprague-Dawley (SD) rats according to the Organization for Economic Cooperation and Development (OECD) guidelines. In the acute toxicity study, there was no mortality and behavioral signs of toxicity at the limit test dose level (340.0 mg/m3 ) in the exposure period and the following 14-day observation period. In the subacute inhalation toxicity study, there was no significant difference observed in the body weights, feed consumption, and relative organ weights. Haematological, serum biochemical, urine, and bronchoalveolar lavage fluid (BALF) analysis revealed the non-adverse effects after 28-day repeated WS-23 inhalation (342.85 mg/m3 ), accompanied by slight changes in few parameters which returned to normal during the 28-day recovery period. The histopathologic examination also did not show any differences in vital organs. In conclusion, the maximum tolerated dose for WS-23 acute inhalation is not less than 340.0 mg/m3 , and the No Observed Adverse Effect Level (NOAEL) of WS-23 subacute inhalation was determined to be over 342.85 mg/m3 .


Assuntos
Amidas/toxicidade , Exposição por Inalação , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Organismos Livres de Patógenos Específicos , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda
15.
Int J Otolaryngol ; 2020: 2373549, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32508926

RESUMO

OBJECTIVE: Studies on factors affecting pharyngocutaneous fistulas (PCFs) and PCF repair methods have been widely reported. However, the healing phases of PCF are unclear, and their elucidation could guide clinical treatment. METHODS: Clinical stages of the PCF healing process were identified by a retrospective study of 39 patients with head and neck cancer who developed a PCF. RESULTS: Different conservative treatments were performed in turn according to three defined stages of the PCF healing process: stage I (drainage and debriding period), stage II (pressure dressing period), and stage III (healing period). A 7-day course of antibiotic therapy was only performed in stage I in 23 patients. The PCF was cured in 30 (76.9%) of 39 patients; the remaining 9 patients underwent subsequent surgical interventions for PCF healing. CONCLUSION: The three stages of PCF healing have a certain reference value in guiding clinical treatments. Moreover, antibiotics should be used in stage I when signs of infection are present, but they should not be used in all three phases of conservative treatment.

16.
Cancer Cell Int ; 19: 335, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31857793

RESUMO

BACKGROUND: The high prevalence of alternative splicing among genes implies the importance of genomic complexity in regulating normal physiological processes and diseases such as gastric cancer (GC). The standard form of stem cell marker CD44 (CD44S) and its alternatives with additional exons are reported to play important roles in multiple types of tumors, but the regulation mechanism of CD44 alternative splicing is not fully understood. METHODS: Here the expression of hnRNPK was analyzed among the Cancer Genome Atlas (TCGA) cohort of GC. The function of hnRNPK in GC cells was analyzed and its downstream targeted gene was identified by chromatin immunoprecipitation and dual luciferase report assay. Finally, effect of hnRNPK and its downstream splicing regulator on CD44 alternative splicing was investigated. RESULTS: The expression of hnRNPK was significantly increased in GC and its upregulation was associated with tumor stage and metastasis. Loss-of-function studies found that hnRNPK could promote GC cell proliferation, migration, and invasion. The upregulation of hnRNPK activates the expression of the splicing regulator SRSF1 by binding to the first motif upstream the start codon (- 65 to - 77 site), thereby increasing splicing activity and expression of an oncogenic CD44 isoform, CD44E (has additional variant exons 8 to 10, CD44v8-v10). CONCLUSION: These findings revealed the importance of the hnRNPK-SRSF1-CD44E axis in promoting gastric tumorigenesis.

17.
Med Biol Eng Comput ; 57(5): 1059-1067, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30569398

RESUMO

Magneto-acoustic imaging is a novel functional imaging method to electrical characteristics of tissue. It provides valuable tools for diagnosing early stage tumor and monitoring bioelectrical current. Common single short-pulse excitation limits SNR due to the short-pulse duration and low power of magneto-acoustic signal. In this study, we propose M-sequence-coded excitation and pulse compression approach to improve SNR of magneto-acoustic imaging. Simulations on the magneto-acoustic signal under different bit lengths M-sequence-coded excitation are performed. Experiments on the samples made of pork and graphite slices are done to validate the proposed coded excitation method. The SNR and sidelobe levels were investigated. The results showed when 7, 15, 31, 63, 127 bits M-sequence-coded excitations were applied onto the samples, SNR was improved by 17.4 dB, 24.2 dB, 30.6 dB, 37.6 dB, and 40.1 dB, respectively. For a similar SNR improvement, the total used time under coded excitation can be shortened to 9.4% under the single pulse excitation. The result indicates the M-sequence-coded excitation approach is effective to improve the magneto-acoustic signal SNR and shorten the imaging time. Graphical abstract SNR of the magneto-acoustic signal is significantly improved by the coded excitation than the pulse excitation, the reconstructed image of the front and back boundary of the pork can be seen clearly under the 7, 15, 31, 63, 127 bit M-sequence-coded excitations.


Assuntos
Acústica , Processamento de Imagem Assistida por Computador/métodos , Processamento de Sinais Assistido por Computador , Simulação por Computador , Compressão de Dados , Campos Eletromagnéticos , Análise de Elementos Finitos , Grafite , Carne Vermelha , Razão Sinal-Ruído
18.
Chin Med J (Engl) ; 130(15): 1816-1823, 2017 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-28748855

RESUMO

BACKGROUND: Foreign bodies within the sinuses, orbit, and skull base (FBSOS) are rare; hence, diagnosis and management guidelines are lacking. Endoscopic sinus surgery (ESS) removal is preferred because of the less invasiveness and minimal morbidity. This study was designed to summarize clinical experience with ESS management of FBSOS. METHODS: We retrospectively reviewed clinical manifestations, imaging findings, treatment, and outcomes in consecutive patients with ESS removal of FBSOS between 2004 and 2015 at a tertiary academic medical center. The Chi-square test was performed to compare the infection rate between wooden and nonwooden FBSOS. RESULTS: There were 23 male and five female patients, with median age of 11 years. FBSOS were located within the sinuses (86%), orbit (75%), and skull base/intracranial region (46%). Wooden FBSOS had a significantly higher risk of infection (78%) compared with nonwooden FBSOS (5%, P < 0.05). Contrast-enhanced computed tomography (CT) plus three-dimensional reconstruction was sensitive in all cases. Twenty-seven (96%) FBSOS were removed by ESS alone, while 1 (4%) FBSOS was removed using the combined ESS and lateral cervical approach. Four of the nine intracranial penetrating FBSOS patients had intraoperative cerebrospinal fluid (CSF) leak and received endoscopic CSF leak repair. Twelve (43%) patients suffered complications (meningitis, diplopia, and vision loss). CONCLUSIONS: ESS is a minimally invasive, safe, and promising surgical approach for FBSOS removal. Contrast-enhanced CT is effective in preoperative diagnosis and intraoperative guidance. Wooden FBSOS had higher risk of infection, thus antibiotics are recommended.


Assuntos
Corpos Estranhos/cirurgia , Órbita/cirurgia , Base do Crânio/cirurgia , Adolescente , Adulto , Pré-Escolar , Endoscópios , Feminino , Humanos , Masculino , Estudos Retrospectivos
19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 32(4): 717-24, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26710438

RESUMO

Functional imaging method of biological electrical characteristics based on magneto-acoustic effect gives valuable information of tissue in early tumor diagnosis, therein time and frequency characteristics analysis of magneto-acoustic signal is important in image reconstruction. This paper proposes wave summing method based on Green function solution for acoustic source of magneto-acoustic effect. Simulations and analysis under quasi 1D transmission condition are carried out to time and frequency characteristics of magneto-acoustic signal of models with different thickness. Simulation results of magneto-acoustic signal were verified through experiments. Results of the simulation with different thickness showed that time-frequency characteristics of magneto-acoustic signal reflected thickness of sample. Thin sample, which is less than one wavelength of pulse, and thick sample, which is larger than one wavelength, showed different summed waveform and frequency characteristics, due to difference of summing thickness. Experimental results verified theoretical analysis and simulation results. This research has laid a foundation for acoustic source and conductivity reconstruction to the medium with different thickness in magneto-acoustic imaging.


Assuntos
Acústica , Diagnóstico por Imagem , Simulação por Computador , Eletricidade , Fenômenos Eletrofisiológicos , Humanos , Magnetismo , Modelos Teóricos
20.
J Exp Clin Cancer Res ; 34: 79, 2015 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-26253106

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) have recently emerged as important regulators in governing fundamental biological processes, and many of which are likely to have functional roles in tumorigenesis. Maternally expressed gene 3 (MEG3) gene encodes a lncRNA whose expression is lost in an expanding list of primary human tumors and tumor cell lines, however its biological role and regulatory mechanism in gastric cancer (GC) development and progression are poorly defined. METHODS: Quantitative RT-PCR analysis was used to determine whether aberrant MEG3 expression was associated with GC patients pTNM stage and pM state. Furthermore, the effect of ectopic expression of MEG3 on cell proliferation, migration, invasion and cell apoptosis was assessed by using CCK-8, wound healing, transwell invasion assays and flow cytometric analysis, respectively, in GC cell lines HGC-27 and MGC-803. Moreover, the competing endogenous RNA (ceRNA) activity of MEG3 on miR-181a was investigated via luciferase reporter assay and immunoblot analysis. RESULTS: MEG3 is decreased in GC patients and cell lines, and its expression was associated with metastatic GC. Furthermore, ectopic expression of MEG3 in HGC-27 and MGC-803 cells inhibited cell proliferation, migration, invasion, and promoted cell apoptosis, which might be due to MEG3 sequestering oncogenic miR-181 s in GC cells. Furthermore, MEG3 could up-regulated Bcl-2 via its competing endogenous RNA (ceRNA) activity on miR-181a. CONCLUSIONS: These findings suggest that lncRNA MEG3, a ceRNA of miR-181 s, could regulate gastric carcinogenesis and may serve as a potential target for antineoplastic therapies.


Assuntos
Transformação Celular Neoplásica/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Apoptose , Proliferação de Células , Progressão da Doença , Humanos , MicroRNAs/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/metabolismo , Transfecção
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