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1.
Rev Cardiovasc Med ; 22(1): 231-238, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33792267

RESUMO

Trimethylamine N-oxide (TMAO) is reported to accelerate atherosclerosis and the development of adverse cardiac outcomes. Relationship between coronary atherosclerotic burden and TMAO has been examined in stable coronary artery disease and ST-segment elevation myocardial infarction, but not in non-ST-segment elevation myocardial infarction (NSTEMI). We examined the association between TMAO and coronary atherosclerotic burden in NSTEMI. In this prospective cohort study, two groups including NSTEMI (n = 73) and age-sex matched Healthy (n = 35) individuals were enrolled between 2019 and 2020. Coronary atherosclerotic burden was stratified based on the number of diseased coronary vessels and clinical risk scores including SYNTAX and GENSINI. Fasting plasma TMAO was measured by isotope dilution high-performance liquid chromatography. The median plasma TMAO levels were significantly higher in the NSTEMI group than in the Healthy group, respectively (0.59 µM; interquartile range [IQR]: 0.43-0.78 versus 0.42 µM; IQR: 0.33-0.64; P = 0.006). Within the NSTEMI group, higher TMAO levels were observed in the multivessel disease (MVD) versus single vessel disease (P = 0.002), and intermediate-high risk (score ≥ 23) versus low risk (score < 23) of SYNTAX (P = 0.003) and GENSINI (P = 0.005). TMAO level remained an independent predictor of MVD (odds ratio [OR]: 5.94, P = 0.005), intermediate-high risk SYNTAX (OR: 3.61, P = 0.013) and GENSINI scores (OR: 4.60, P = 0.008) following adjustment for traditional risk factors. Receiver operating characteristic curve (AUC) analysis for TMAO predicted MVD (AUC: 0.73, 95% confidence interval [Cl]: 0.60-0.86, P = 0.002), intermediate-high SYNTAX score (AUC: 0.70, 95% Cl: 0.58-0.82, P = 0.003) and GENSINI score (AUC: 0.70, 95% Cl: 0.57-0.83, P = 0.005). In all, TMAO levels are independently associated with high coronary atherosclerotic burden in NSTEMI.


Assuntos
Aterosclerose , Infarto do Miocárdio sem Supradesnível do Segmento ST , Humanos , Metilaminas , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Estudos Prospectivos
2.
BMC Cancer ; 19(1): 1116, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729963

RESUMO

OBJECT: Glioma is a common malignant tumours in the central nervous system (CNS), that exhibits high morbidity, a low cure rate, and a high recurrence rate. Currently, immune cells are increasingly known to play roles in the suppression of tumourigenesis, progression and tumour growth in many tumours. Therefore, given this increasing evidence, we explored the levels of some immune cell genes for predicting the prognosis of patients with glioma. METHODS: We extracted glioma data from The Cancer Genome Atlas (TCGA). Using the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm, the relative proportions of 22 types of infiltrating immune cells were determined. In addition, the relationships between the scales of some immune cells and sex/age were also calculated by a series of analyses. A P-value was derived for the deconvolution of each sample, providing credibility for the data analysis (P < 0.05). All analyses were conducted using R version 3.5.2. Five-year overall survival (OS) also showed the effectiveness and prognostic value of each proportion of immune cells in glioma; a bar plot, correlation-based heatmap (corheatmap), and heatmap were used to represent the proportions of immune cells in each glioma sample. RESULTS: In total, 703 transcriptomes from a clinical dataset of glioma patients were drawn from the TCGA database. The relative proportions of 22 types of infiltrating immune cells are presented in a bar plot and heatmap. In addition, we identified the levels of immune cells related to prognosis in patients with glioma. Activated dendritic cells (DCs), eosinophils, activated mast cells, monocytes and activated natural killer (NK) cells were positively related to prognosis in the patients with glioma; however, resting NK cells, CD8+ T cells, T follicular helper cells, gamma delta T cells and M0 macrophages were negatively related to prognosis in the patients with glioma. Specifically, the proportions of several immune cells were significantly related to patient age and sex. Furthermore, the level of M0 macrophages was significant in regard to interactions with other immune cells, including monocytes and gamma delta T cells, in glioma tissues through sample data analysis. CONCLUSION: We performed a novel gene expression-based study of the levels of immune cell subtypes and prognosis in glioma, which has potential clinical prognostic value for patients with glioma.


Assuntos
Células Dendríticas/imunologia , Glioma/genética , Glioma/imunologia , Células Matadoras Naturais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/imunologia , Células Dendríticas/patologia , Feminino , Perfilação da Expressão Gênica/métodos , Glioma/patologia , Humanos , Células Matadoras Naturais/patologia , Linfócitos do Interstício Tumoral/patologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
3.
Asia Pac J Clin Oncol ; 20(2): 220-227, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36658674

RESUMO

PURPOSE: This study investigated the clinical risk factors for peripheral neuropathy induced by docetaxel and albumin-bound paclitaxel (AP) in patients with breast cancer. METHODS: This prospective observational study recruited 268 patients between March 2019 and December 2020. Patient information was obtained through the query system for laboratory test results, patient consultations, and scale evaluations. Neuropathic symptoms were followed up throughout and until 3 months after taxane chemotherapy. Univariate and multivariate analyses were used to find the risk factors for overall and moderate-severe taxane-induced peripheral neuropathy (TIPN). RESULTS: Cumulative dose (odds ratio [OR] = 3.533, 95% confidence interval [CI]: 1.797-6.944, p < 0.001), body mass index (BMI) (OR = 2.926, 95% CI: 1.621-5.281, p < 0.001), body surface area (BSA) (OR = 1.724, 95% CI: 1.011-2.941, p = 0.045), and hypocalcemia (OR = 4.899, 95% CI: 1.518-15.811, p = 0.008) all increased the risk of TIPN. Only cumulative dose (OR = 2.577, 95% CI: 1.161-5.719, p = 0.020) and BSA (OR = 2.040, 95% CI: 1.073-3.877, p = 0.030) were independent risk factors for moderate-severe TIPN. CONCLUSION: Cumulative dose, BMI, BSA, and hypocalcemia are all risk factors for overall TIPN, whereas cumulative dose and BSA are risk factors for moderate-severe TIPN. Patients with breast cancer who have high BMI, large BSA, hypocalcemia, and large cumulative dose may be at risk of TIPN, and intervention measures must be actively carried out for them.


Assuntos
Neoplasias da Mama , Hidrocarbonetos Aromáticos com Pontes , Hipocalcemia , Doenças do Sistema Nervoso Periférico , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Hipocalcemia/induzido quimicamente , Paclitaxel/efeitos adversos , Taxoides/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Fatores de Risco
4.
Front Pharmacol ; 14: 1268649, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38273827

RESUMO

Fungal infections have become clinically challenging owing to the emergence of drug resistance in invasive fungi and the rapid increase in the number of novel pathogens. The development of drug resistance further restricts the use of antifungal agents. Therefore, there is an urgent need to identify alternative treatments for Cryptococcus neoformans (C. neoformans). Disulfiram (DSF) has a good human safety profile and promising applications as an antiviral, antifungal, antiparasitic, and anticancer agent. However, the effect of DSF on Cryptococcus is yet to be thoroughly investigated. This study investigated the antifungal effects and the mechanism of action of DSF against C. neoformans to provide a new theoretical foundation for the treatment of Cryptococcal infections. In vitro studies demonstrated that DSF inhibited Cryptococcus growth at minimum inhibitory concentrations (MICs) ranging from 1.0 to 8.0 µg/mL. Combined antifungal effects have been observed for DSF with 5-fluorocytosine, amphotericin B, terbinafine, or ketoconazole. DSF exerts significant protective effects and synergistic effects combined with 5-FU for Galleria mellonella infected with C. neoformans. Mechanistic investigations showed that DSF dose-dependently inhibited melanin, urease, acetaldehyde dehydrogenase, capsule and biofilm viability of C. neoformans. Further studies indicated that DSF affected C. neoformans by interfering with multiple biological pathways, including replication, metabolism, membrane transport, and biological enzyme activity. Potentially essential targets of these pathways include acetaldehyde dehydrogenase, catalase, ATP-binding cassette transporter (ABC transporter), and iron-sulfur cluster transporter. These findings provide novel insights into the application of DSF and contribute to the understanding of its mechanisms of action in C. neoformans.

5.
Analyst ; 137(7): 1706-12, 2012 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-22349179

RESUMO

Water-soluble cupric oxide nanoparticles are fabricated via a quick-precipitation method and used as peroxidase mimetics for ultrasensitive detection of hydrogen peroxide and glucose. The water-soluble CuO nanoparticles show much higher catalytic activity than that of commercial CuO nanoparticles due to their higher affinity to hydrogen peroxide. In addition, the as-prepared CuO nanoparticles are stable over a wide range of pH and temperature. This excellent stability in the form of aqueous colloidal suspensions makes the application of the water-soluble CuO nanoparticles easier in aqueous systems. A colorimetric assay for hydrogen peroxide and glucose has been established based on the catalytic oxidation of phenol coupled with 4-amino-atipyrine by the action of hydrogen peroxide. This analytical platform not only confirms the intrinsic peroxidase-like activity of the water-soluble cupric oxide nanoparticles, but also shows its great potential applications in environmental chemistry, biotechnology and medicine.


Assuntos
Cobre/química , Glucose/análise , Peróxido de Hidrogênio/análise , Nanopartículas Metálicas/química , Peroxidase/química , Água/química , Colorimetria , Microscopia Eletrônica de Transmissão , Solubilidade , Difração de Raios X
6.
World J Gastroenterol ; 18(22): 2850-8, 2012 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-22719196

RESUMO

AIM: To investigate whether DNA-dependent activator of interferon-regulatory factors (DAI) inhibits hepatitis B virus (HBV) replication and what the mechanism is. METHODS: After the human hepatoma cell line Huh7 was cotransfected with DAI and HBV expressing plasmid, viral protein (HBV surface antigen and HBV e antigen) secretion was detected by enzyme-linked immunosorbent assay, and HBV RNA was analyzed by real-time polymerase chain reaction and Northern blotting, and viral DNA replicative intermediates were examined by Southern blotting. Interferon regulatory factor 3 (IRF3) phosphorylation and nuclear translocation were analyzed via Western blotting and immunofluorescence staining respectively. Nuclear factor-κB (NF-κB) activity induced by DAI was detected by immunofluorescence staining of P65 and dual luciferase reporter assay. Transwell co-culture experiment was performed in order to investigate whether the antiviral effects of DAI were dependent on the secreted cytokines. RESULTS: Viral protein secretion was significantly reduced by 57% (P < 0.05), and the level of total HBV RNA was reduced by 67% (P < 0.05). The viral core particle-associated DNA was also dramatically down-regulated in DAI-expressing Huh7 cells. Analysis of involved signaling pathways revealed that activation of NF-κB signaling was essential for DAI to elicit antiviral response in Huh7 cells. When the NF-κB signaling pathway was blocked by a NF-κB signaling suppressor (IκBα-SR), the anti-HBV activity of DAI was remarkably abrogated. The inhibitory effect of DAI was independent of IRF3 signaling and secreted cytokines. CONCLUSION: This study demonstrates that DAI can inhibit HBV replication and the inhibitory effect is associated with activation of NF-κB but independent of IRF3 and secreted cytokines.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatócitos/metabolismo , Hepatócitos/virologia , Replicação Viral , Northern Blotting , Southern Blotting , Western Blotting , Linhagem Celular Tumoral , Técnicas de Cocultura , Citocinas/metabolismo , DNA Viral/biossíntese , Proteínas de Ligação a DNA/genética , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Células HEK293 , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatócitos/imunologia , Humanos , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Imunidade Inata , Fator Regulador 3 de Interferon/metabolismo , Inibidor de NF-kappaB alfa , NF-kappa B/genética , NF-kappa B/metabolismo , RNA Viral/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Fatores de Tempo , Transfecção
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