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OBJECTIVE: The purpose of this study was to investigate the diagnostic value of circ_0013958 in acute myocardial infarction (AMI) patients and its influence on the prognosis of AMI patients. METHODS: The GSE160717 dataset was downloaded from the NCBI database and differentially expressed genes were analyzed between the control group and the AMI group. The up-regulated genes included circ_0013958. The expression of circ_0013958 in both groups was further verified by RT-qPCR. The Receiver Operating Characteristic curve was used to evaluate the diagnostic value of circ_0013958 in AMI. Pearson correlation analysis was used to examine the correlation between circ_0013958 levles and biochemical indicators. Binary logistic regression was used to analyze the risk factors affecting the occurrence of AMI. Prognostic analysis was performed using COX regression analysis and the Kaplan-Meier Curve. RESULTS: Compared to the control group, the level of circ_0013958 in AMI patients increased. Circ_0013958 can effectively distinguish AMI patients from non-AMI patients. Circ_0013958 levels were positively correlated with cTnI, LDH, CRP and TC levels. The elevated level of circ_0013958 was an independent risk factor for the occurrence of AMI. Higher circ_0013958 levels were also associated with the occurrence of major adverse cardiac events (MACEs) in AMI patients. Additionally, elevated circ_0013958 levels reduced the survival probability of AMI patients. CONCLUSION: Circ_0013958 levels were up-regulated in AMI patients. It can be used as a diagnosis biomarker for AMI. The level of circ_0013958 was correlated with the disease severity and was an independent risk factor for the occurrence of AMI. Elevated circ_0013958 levels were associated with poor prognosis in AMI patients.
Asunto(s)
Infarto del Miocardio , ARN Circular , Humanos , Infarto del Miocardio/genética , Pronóstico , Masculino , Femenino , ARN Circular/genética , Persona de Mediana Edad , Curva ROC , Anciano , Factores de Riesgo , Biomarcadores/sangre , Biomarcadores/metabolismoRESUMEN
Background: Ischemic heart disease (IHD) is a major global health concern, and its burden among young adults aged 25-49 years remains underexplored. This study aims to provide a comprehensive assessment of the global burden and trends of IHD over the past 30 years (1990-2019) among this age group, as well as to analyze the health inequalities related to socioeconomic development. Methods: Data from Global Burden of Disease Study 2019 (GBD 2019) were utilized to analyze the prevalence, mortality, and disability-adjusted life years (DALYs) rate of IHD among young adults globally. Joinpoint regression analysis was applied to examine the trends over the study period. Health inequality analysis was performed to investigate the disparities in IHD burden related to the Socio-Demographic Index (SDI) of countries. Results: According to GBD 2019 data, in 2019, the global numbers of young adults with IHD cases, deaths, and DALYs were 18,050,671 (95% UI, 15,551,940-21,254,746), 597,137 (548,250-647,778), and 28,692,968 (26,397,448-31,178,464), respectively, accounting for 9.15%, 6.53%, and 15.7% of the total global cases. Over the past 30 years, the mortality [AAPC = -0.4%, 95% CI (-0.7% to -0.1%)] and DALYs rate [AAPC = -0.3%, 95% CI (-0.6% to -0.1%)] of IHD among young adults decreased, while the prevalence rate [AAPC = 0.4%, 95% CI (0.4%-0.4%)] and YLDs rate [AAPC = 0.4%, 95% CI (0.3%-0.4%)] increased. Furthermore, countries with lower levels of socio-demographic index (SDI) disproportionately bore a higher burden of IHD among young adults. The inequality slope index for young adult IHD shifted from -56.6 [95% CI (-480.4-370.2)] in 1990 to -583.0 [95% CI (-996.8 to -169.2)] in 2019, and the concentration index moved from -8.2 [95% CI (-8.5 to -7.9)] in 1990 to -13.2 [95% CI (-13.9 to -12.4)] in 2019. Conclusions: While the mortality and DALYs rate of IHD among global young adults have decreased over the past 30 years, the degree of inequality related to SDI among countries has continued to increase. Decision-makers in various countries should allocate resources wisely and implement effective strategies to improve the burden of young adults IHD globally and address the health inequalities associated with it.
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Cisplatin yields significant efficacy and is generally used as a frontline therapy for non-small cell lung cancer (NSCLC). However, acquired resistance strongly limits its application. Here, we identified that a novel histone deacetylase (HDAC) inhibitor S11, with P-glycoprotein inhibitory activity, could obviously suppress cell growth in cisplatin-resistant NSCLC cell lines. In addition, S11 could increase the expression of Ac-H4 and p21, which confirmed its HDAC inhibitory action, suppress colony formation, and block cell migration of cisplatin-resistant NSCLC cells. Notably, co-treatment with S11 and cisplatin exhibited synergistically inhibitory efficacy in cisplatin-resistant NSCLC cells. Gene microarray data showed that OAZ1 was downregulated in resistant cells but upregulated after S11 treatment. Further study indicated that knockdown of OAZ1 by siRNA resulted in the decrease of sensitivity of resistant cells to cisplatin treatment and contributed to the increase of resistant cell migration. Additionally, ChIP assay data demonstrated that HDAC inhibitor S11 could increase the accumulation of Ac-H4 in OAZ1 promoter region, suggesting the direct regulation of OAZ1 by HDAC. Importantly, the combination of S11 and cisplatin overcome resistance through inhibiting HDAC activity and subsequently increasing the OAZ1 expression in preclinical model. Moreover, we observed that positive expression of HDAC1 was associated with the downregulation of OAZ1 in NSCLC patients with platinum-based treatment, and predicted drug resistance and poor prognosis. In summary, we demonstrated a role of HDAC/OAZ1 axis in cisplatin-resistant NSCLC and identified a promising compound to overcome cisplatin resistance.
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Resistencia a Antineoplásicos/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Proteínas/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Sitios de Unión , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Cisplatino/uso terapéutico , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/uso terapéutico , Histona Desacetilasas/química , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Simulación del Acoplamiento Molecular , Regiones Promotoras Genéticas , Proteínas/antagonistas & inhibidores , Proteínas/genética , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
A series of novel N-hydroxypropenamides containing adamantane moiety were identified and most of them exhibited HDAC inhibitory activity and could reverse the resistance of cisplatin in NSCLC cell lines. In this process, molecular docking was employed to verify the rationality of designing, subsequently, target compounds were synthesized and conducted to enzyme- and cell-based biological evaluation. Most of synthesized compounds could inhibit HDAC activity with the IC50 values lower than 50â¯nM and result in the increase of Ac-H4 and p21 in A549 cells. Importantly, we assessed the reversal effect of those compounds and found several compounds display an anti-resistant effect in lung cancer cells, especially compound 8f. As compared to belinostat and cisplatin, compound 8f showed improved inhibitory activity against A549/CDDP cell lines with IC50 value of 5.76⯵M, and far lower resistance index of 1.24. Moreover, the structure-activity relationships of these compounds were summarized and compound 8f could serve as a research tool for identifying the mechanism of reversing resistance and a template for designing novel compounds to reverse cisplatin resistance.