RESUMEN
Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan-Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late-stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Ciclo Celular , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , División Celular , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Neoplasias Pulmonares/genética , Regulación hacia Arriba/genéticaRESUMEN
Adrenocortical carcinoma (ACC) is a malignant carcinoma with an extremely poor prognosis, and its pathogenesis remains to be understood to date, necessitating further investigation. This study aims to discover biomarkers and potential therapeutic agents for ACC through bioinformatics, enhancing clinical diagnosis and treatment strategies. Differentially expressed genes (DEGs) between ACC and normal adrenal cortex were screened out from the GSE19750 and GSE90713 datasets available in the GEO database. An online Venn diagram tool was utilized to identify the common DEGs between the two datasets. The identified DEGs were subjected to functional assessment, pathway enrichment, and identification of hub genes by performing the protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The differences in the expressions of hub genes between ACC and normal adrenal cortex were validated at the GEPIA2 website, and the association of these genes with the overall patient survival was also assessed. Finally, on the QuartataWeb website, drugs related to the identified hub genes were determined. A total of 114 DEGs, 10 hub genes, and 69 known drugs that could interact with these genes were identified. The GO and KEGG analyses revealed a close association of the identified DEGs with cellular signal transduction. The 10 hub genes identified were overexpressed in ACC, in addition to being significantly associated with adverse prognosis in ACC. Three genes and the associated known drugs were identified as potential targets for ACC treatment.
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Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Biología Computacional , Regulación Neoplásica de la Expresión Génica , Mapas de Interacción de Proteínas , Humanos , Carcinoma Corticosuprarrenal/genética , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/patología , Neoplasias de la Corteza Suprarrenal/genética , Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Neoplasias de la Corteza Suprarrenal/patología , Mapas de Interacción de Proteínas/genética , Redes Reguladoras de Genes , Perfilación de la Expresión Génica , Ontología de Genes , Bases de Datos Genéticas , Biomarcadores de Tumor/genética , PronósticoRESUMEN
AIMS: To estimate the effects of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) on proteinuria and oxidative stress expression in type 2 diabetes patients. MATERIALS AND METHODS: 68 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according urinary albumin-to-creatinine ratio (UACR), including T2DM with non-albuminuria group (UACR < 30 mg/g), T2DM with microalbuminuria group (30 ≤ UACR ≤ 300 mg/g), T2DM with macroalbuminuria group (UACR>300 mg/g). They all received SGLT2 inhibitors (SGLT2i) treatment for 12 weeks. The expression of advanced glycation end products (AGEs) in plasma and 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine were measured as indications of oxidative stress. The 24-hour urine samples were collected to measure the concentration of proteinuria and 8-OHdG before and after 12 weeks SGLT2i treatment. Plasma renin activity (PRA), angiotensin II (Ang II) and Aldosterone (ALD) were measured to evaluate renin angiotensin aldosterone system (RASS) levels. RESULTS: After 12 weeks SGLT2 inhibitors treatment, the median values of 24-hour proteinuria decreased in macroalbuminuria compared to baseline (970 vs. 821 mg/d, P = 0.006). The median values of AGEs and 8-OHdG decreased in microalbuminuria and macroalbuminuria groups when compared to baseline, AGEs (777 vs. 136 ug/ml, P = 0.003) and (755 vs. 210 ug/ml, P = 0.001), 8-OHdG (8.00 vs. 1.88 ng/ml, P = 0.001) and (11.18 vs. 1.90 ng/ml, P < 0.001), respectively. Partial correlations showed that 8-OHdG were relevant to the baseline 24-h proteinuria (r = 0.389, p = 0.001), the reduction of OHdG (Δ8-OHdG) were positively correlated with the decrease of 24-h proteinuria (Δ24-h proteinuria) after 12 weeks of SGLT2i treatment (r = 0.283, P = 0.031). There was no significant correlation between 24-h proteinuria and AGEs in baseline (r = -0.059, p = 0.640) as well as between ΔAGEs and Δ24-h proteinuria (r = 0.022, p = 0.872) after12 weeks of SGLT2i treatment in T2DM patients. CONCLUSIONS: SGLT2i may reduce proteinuria in diabetic nephropathy patients, potentially by inhibiting renal oxidative stress, but not through the AGEs pathway and does not induce RAAS activation. TRIAL REGISTRATION: This clinical trial was registered on 15/10/2019, in ClinicalTrials.gov, and the registry number is NCT04127084.
RESUMEN
BACKGROUND: White matter lesions (WMLs) are increasingly linked to the pathological process of chronic vascular dementia (VaD). An effective crocins fraction extracted from Gardenia Fructus, GJ-4, has been shown to improve cognitive function in several Alzheimer's disease models and VaD models. OBJECTIVES: To explore the potential mechanisms of GJ-4 on WMLs in a chronic VaD mouse model. METHODS: The chronic VaD mouse model was established, and WMLs were characterized by cerebral blood flow (CBF), behavioral tests, LFB staining, and immunohistochemistry. The anti-oxidative effect of GJ-4 was validated by examining biochemical parameters (SOD, MDA, and GSH) and the Keap1-Nrf2/HO-1 pathway. The impact of GJ-4 on lipid metabolism in WM was further investigated through lipidomic analysis. RESULTS: GJ-4 significantly attenuated cognitive impairments and improved the CBF of BCAS (bilateral common carotid artery stenosis)-induced mice. Mechanism research showed that GJ-4 could enhance cognition by promoting the repair of WMLs by inhibiting oxidative stress. Furthermore, GJ-4 treatment significantly reduced chronic cerebral hypoperfusion (CCH)-induced WMLs via improving lipid metabolism disorder in the WM. CONCLUSION: This research has provided valuable insights into the significance of WMLs in CCH-induced VaD and underscored the potential of GJ-4 as a therapeutic agent for improving cognitive function by targeting WMLs. These findings suggest that GJ-4 is a promising candidate for the treatment of VaD.
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Disfunción Cognitiva , Demencia Vascular , Modelos Animales de Enfermedad , Fármacos Neuroprotectores , Estrés Oxidativo , Sustancia Blanca , Animales , Demencia Vascular/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Masculino , Sustancia Blanca/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratones , Gardenia/química , Ratones Endogámicos C57BL , Carotenoides/farmacología , Carotenoides/uso terapéutico , Circulación Cerebrovascular/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Extractos Vegetales/farmacologíaRESUMEN
Background: Left ventricular ejection fraction (LVEF) is an indicator of heart failure, and it is controversial whether patients with reduced preoperative left ventricular ejection fraction can benefit from heart valve surgery. We aimed to assess the differences in clinical characteristics after surgery in patients with different grades of reduced preoperative LVEF to guide clinical management. Methods: A total of 100 heart valve disease patients with low LVEF (≤50%) who had undergone valve surgery in the Department of Cardiology. The patients were divided into three groups according to their LVEF measured by echocardiography before surgery, with LVEF ≤40% as group A, 40%< LVEF ≤45% as group B, and 45%< LVEF ≤50% as group C. Clinical characteristics such as postoperative LVEF values, oxygenation index, liver function and inflammatory index, intra-aortic balloon pump (IABP) utilization rate, and mortality were compared among the three groups of patients. Results: There was no statistically significant difference in the preoperative baseline data between the three groups of patients (P>0.05). The clinical outcomes of patients in group A (n=28) were similar to those of patients in groups B (n=39) and C (n=33) (P>0.05). The vasoactive-inotropic score (VIS), postoperative ventilator use time, length of stay in the care unit, IABP use rate, and mortality rate on the first postoperative day were higher in group A. By comparing the preoperative and postoperative (within 48 hours and 3 months after surgery) cardiac echocardiograms of the three groups, we learned that LVEF increased, LV end-systolic internal diameter and LV end-diastolic internal diameter decreased, and ventricular remodeling improved after surgery compared with the preoperative period (P<0.05). The postoperative improvement was more obvious in group A than in groups B and C. Three months after surgery, LVEF increased to 55%, the LV end-systolic internal diameter decreased to 39 mm, and the LV end-diastolic internal diameter decreased to about 55 mm in each group (P>0.05). Conclusions: Patients with heart valve disease and low LVEF should be actively treated with heart valve surgery, which can significantly improve the patient's left ventricular reverse remodeling and cardiac function, thereby facilitating survival.
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BACKGROUND: The objective of this study was to investigate changes in coagulation activation and platelet activation after transcatheter closure of atrial septal defect (ASD) by determining the levels of specific markers over time to provide insight into preventing postprocedural embolism. HYPOTHESIS: We hypothesis that the activation status of coagulation and the platelet would be changed after the closure of ASD. METHODS: Forty consecutive patients who underwent transcatheter closure of ASD with the Lifetech ASD occluder (Lifetech Scientific, Shenzhen, China) were included in this prospective study. The serum level of prothrombin fragment 1 + 2 (F1 + 2) and expressions of P-selectin (CD62P) and platelet glycoprotein IIb/IIIa receptor (CD41a) on the surface of platelets were evaluated at baseline and at 1 day, 1 month, and 3 months after the closure. RESULTS: The median F1 + 2 level was 0.96 nmol/L. This increased to a maximal value of 1.43 nmol/L at 1 day after closure, but gradually returned to the baseline level at 1 month after closure and remained there at 3 months after closure (medians were 0.98 nmol/L and 1.08 nmol/L, respectively). Platelet surface expression of CD62P and CD41a decreased at 1 day, 1 month, and 3 months after closure. For CD62P, average expressions were 8.21% +/- 2.11%, 6.28% +/- 1.72%, 5.29% +/- 1.52%, and 4.41% +/- 1.11%, respectively, for baseline and 1 day, 1 month, and 3 months after closure. For CD41a, average expressions were 79.37% +/- 14.14%, 71.98% +/- 13.77, 56.69% +/- 13.05%, and 54.88% +/- 11.62%, respectively. CONCLUSIONS: Transcatheter closure of ASD with the Lifetech ASD occluder was associated with significantly increased coagulation activation and decreased platelet activation. No evidence supporting the use of aspirin to prevent thrombus formation after closure was found.