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1.
BMC Cancer ; 24(1): 404, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561648

RESUMO

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.


Assuntos
Radiômica , Neoplasias Gástricas , Humanos , Estudos de Coortes , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Estudos Retrospectivos , Instabilidade de Microssatélites , Imunoterapia , Tomografia Computadorizada por Raios X , Imunoglobulinas
2.
Int J Antimicrob Agents ; 62(3): 106907, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37385564

RESUMO

Salmonella enterica is a food-borne pathogen that poses a severe threat to both poultry production and human health. Antibiotics are critical for the initial treatment of bacterial infections. However, the overuse and misuse of antibiotics results in the rapid evolution of antibiotic-resistant bacteria, and the discovery and development of new antibiotics are declining. Therefore, understanding antibiotic resistance mechanisms and developing novel control measures are essential. In the present study, GC-MS-based metabolomics analysis was performed to determine the metabolic profile of gentamicin sensitive (SE-S) and resistant (SE-R) S. enterica. Fructose was identified as a crucial biomarker. Further analysis demonstrated a global depressed central carbon metabolism and energy metabolism in SE-R. The decrease in the pyruvate cycle reduces the production of NADH and ATP, causing a decrease in membrane potential, which contributes to gentamicin resistance. Exogenous fructose potentiated the effectiveness of gentamicin in killing SE-R by promoting the pyruvate cycle, NADH, ATP and membrane potential, thereby increasing gentamicin intake. Further, fructose plus gentamicin improved the survival rate of chicken infected with gentamicin-resistant Salmonella in vivo. Given that metabolite structures are conserved across species, fructose identified from bacteria could be used as a biomarker for breeding disease-resistant phenotypes in chicken. Therefore, a novel strategy is proposed for fighting against antibiotic-resistant S. enterica, including exploring molecules suppressed by antibiotics and providing a new approach to find pathogen targets for disease resistance in chicken breeding.


Assuntos
Antibacterianos , Salmonella enteritidis , Animais , Humanos , Antibacterianos/farmacologia , Gentamicinas/farmacologia , NAD , Galinhas/microbiologia , Metabolômica , Trifosfato de Adenosina
3.
Sex Med Rev ; 10(4): 754-763, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35246405

RESUMO

INTRODUCTION: In Erectile dysfunction (ED) patients, phosphodiesterase type 5 (PDE5) inhibitors are considered as the first-line therapy. However, 30-50% of ED patients fail to follow this therapeutic option because of adverse events, lack of efficacy, or drug costs. Antioxidant supplementation is widely applied in clinical practice and viewed as a potential therapeutic option for ED. Therefore, it is attractive to assess the effect of antioxidants supplementation on ED patients. OBJECTIVES: To evaluate the effects of antioxidants supplementation on ED. METHODS: Published randomized controlled trials of antioxidants in ED were searched in the PubMed, Embase, and Cochrane Library databases from inception to October 3, 2021. Meta-analyses were carried out using a random-effects model. The results were presented as standard mean differences (SMDs) with their 95% confidence intervals (CIs). RESULTS: Eighteen studies with 1,331 ED patients were included in the study. Compared with placebo, antioxidants alone treatment showed a statistical increase in International Index of Erectile Function (IIEF) score (SMD = 1.93; 95% CI: 0.15, 3.72; P = .034). Compared with placebo, antioxidants compound treatment elicited a significant increase in IIEF score (SMD = 2.74; 95% CI: 1.67, 3.81; P < .001) as well as sexual satisfaction score (SMD = 1.61; 95% CI: 0.63, 2.59; P = .001). Compared with the PDE5 inhibitors alone, combination of PDE5 inhibitors and antioxidants showed a significant increase in IIEF score (SMD = 1.1; 95% CI: 0.51, 1.68; P < .001) and sexual satisfaction score (SMD = 1.28; 95% CI: 0.06, 2.51; P = .04). CONCLUSION: This study found that the effect of antioxidant alone treatment on ED may be limited. However, antioxidant compound treatment, as well as combination of PDE5 inhibitors and antioxidants, were associated with improved ED, and can be considered as an accessary therapeutic option for ED. Su L, Yang Z, Qu H, et al. Effect of Antioxidants Supplementation on Erectile Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Sex Med Rev 2022;10:754-763.


Assuntos
Disfunção Erétil , Antioxidantes/uso terapêutico , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Suplementos Nutricionais , Disfunção Erétil/etiologia , Humanos , Masculino , Inibidores da Fosfodiesterase 5/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Sex Med Rev ; 10(4): 754-763, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37051969

RESUMO

INTRODUCTION: In Erectile dysfunction (ED) patients, phosphodiesterase type 5 (PDE5) inhibitors are considered as the first-line therapy. However, 30-50% of ED patients fail to follow this therapeutic option because of adverse events, lack of efficacy, or drug costs. Antioxidant supplementation is widely applied in clinical practice and viewed as a potential therapeutic option for ED. Therefore, it is attractive to assess the effect of antioxidants supplementation on ED patients. OBJECTIVES: To evaluate the effects of antioxidants supplementation on ED. METHODS: Published randomized controlled trials of antioxidants in ED were searched in the PubMed, Embase, and Cochrane Library databases from inception to October 3, 2021. Meta-analyses were carried out using a random-effects model. The results were presented as standard mean differences (SMDs) with their 95% confidence intervals (CIs). RESULTS: Eighteen studies with 1,331 ED patients were included in the study. Compared with placebo, antioxidants alone treatment showed a statistical increase in International Index of Erectile Function (IIEF) score (SMD = 1.93; 95% CI: 0.15, 3.72; P = .034). Compared with placebo, antioxidants compound treatment elicited a significant increase in IIEF score (SMD = 2.74; 95% CI: 1.67, 3.81; P < .001) as well as sexual satisfaction score (SMD = 1.61; 95% CI: 0.63, 2.59; P = .001). Compared with the PDE5 inhibitors alone, combination of PDE5 inhibitors and antioxidants showed a significant increase in IIEF score (SMD = 1.1; 95% CI: 0.51, 1.68; P < .001) and sexual satisfaction score (SMD = 1.28; 95% CI: 0.06, 2.51; P = .04). CONCLUSION: This study found that the effect of antioxidant alone treatment on ED may be limited. However, antioxidant compound treatment, as well as combination of PDE5 inhibitors and antioxidants, were associated with improved ED, and can be considered as an accessary therapeutic option for ED.


Assuntos
Disfunção Erétil , Masculino , Humanos , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Antioxidantes/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Suplementos Nutricionais
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