RESUMEN

This article explored the relationship between anthropometric indices and hyperuricemia in Chinese adults. The ability of each anthropometric index to predict hyperuricemia was also compared in this article. This is a cross-sectional study containing 69,842 samples from 31 provinces and cities in China. Anthropometric indices included body mass index (BMI), waist circumference (WC), a body shape index (ABSI), body roundness index (BRI), waist-to-height ratio (WHtR), lipid accumulation product (LAP), visceral adiposity index (VAI), triglyceride-glucose index (TyG), waist circumference-triglyceride index (WTI), and weight-adjusted waist index (WWI). The survey data obtained were disaggregated and analyzed according to sex and age. BMI, WC, BRI, WHtR, LAP, VAI, TyG, WTI, and WWI were all significantly associated with hyperuricemia (P < 0.001). In the total population, WTI (AUC 0.7015, P < 0.001) had the highest predictive power, and WWI (AUC 0.5417, P < 0.001) had the lowest. In addition, after dividing the male and female populations, LAP (AUC 0.6571, P < 0.001 for men; AUC 0.7326, P < 0.001 for women) had the highest predictive power among both men and women. The ABSI (AUC 0.5189, P < 0.001 for men; AUC 0.5788, P < 0.001 for women) had the lowest predictive power among both men and women. BMI, WC, BRI, WHtR, LAP, VAI, TyG, and WTI were positively correlated with the risk of hyperuricemia and serum uric acid concentrations in both sexes. Among the general population, WTI had the highest predictive power. After dividing the population by sex, LAP had the highest predictive power in both men and women. Key Points • Anthropometric indices are highly correlated with hyperuricemia. Waist circumference-triglyceride index (WTI) is first found to be associated with hyperuricemia, and it has high predictive power. • The predictive power of anthropometric indices for hyperuricemia is more useful in women. • The restricted cubic splines visually shows the ratio of anthropometric indices to hyperuricemia ratio and the patient's serum uric acid concentration.

Asunto(s)

Hiperuricemia , Obesidad , Adulto , Humanos , Masculino , Femenino , Obesidad/complicaciones , Ácido Úrico , Factores de Riesgo , Hiperuricemia/epidemiología , Hiperuricemia/complicaciones , Estudios Transversales , Índice de Masa Corporal , Circunferencia de la Cintura , China/epidemiología , Triglicéridos

RESUMEN

Objective: The metabolic syndrome (MetS) is diagnosed upon the manifestation of ≥ 3 out of 5 specific components. The present study evaluated the epidemiological characteristics of the MetS components and their clustering condition among Chinese adults. Methods: 68383 participants aged 18-80 years from TIDE were scored on a six-point (0-5) MetS severity score (MSSS), which quantified their cumulative amount of MetS risk components. We evaluated the epidemiological characteristics of these components and their clustering conditions. Additionally, we examined the relation of age with the prevalence of different MSSSs or specific MetS components using restricted cubic splines. Results: Among 68383 participants, 26113 men and 24582 women had abnormal MetS components. There were significant differences in most epidemiological characteristics between the 6 MSSS groups. The top three prevalence of abnormal metabolic components were high systolic blood pressure (SBP) (9.41%, n=6568), high waist circumference (WC) (8.13%, n=6120), and the cooccurrence of high SBP and high WC (6.33%, n=4622). Participants were more likely to have all five MetS components when HDL-C was low. Restricted cubic splines showed that when the MSSS ≥3, the MetS prevalence of male peaked and that of the female population increased most rapidly at 40-60 age group. Conclusion: The 40-60 age group can be regarded as the high-risk period of MetS, and elderly women have a higher risk of multiple metabolic disorders than men. The top three clustering of abnormal metabolic components were high SBP, high WC, and their combination. Multiple components aggregation was more likely to occur when HDL-C decreased.

Asunto(s)

Síndrome Metabólico , Adulto , Anciano , Humanos , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Estudios Transversales , Prevalencia , China/epidemiología

RESUMEN

Background: The effect of iodine on papillary thyroid cancer (PTC) has been controversial for many years. Since urinary iodine is an effective indicator of iodine intake, some recent epidemiological studies have described the relationship between urinary iodine concentration (UIC) and PTC. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science for case-control studies about UIC and PTC published before September 2022. Results are presented as the overall odds ratio (OR) and 95% confidence intervals (CI). Results: According to the analysis of the included studies, excessive iodine intake (UIC≥300ug/L) was positively associated with the occurrence of PTC patients compared with healthy controls (OR4.05, 95%CI 1.64-10.02, P=0.002). Meanwhile, adequate iodine exposure (100≤UIC<200ug/L) may play a protective role in the occurrence of PTC compared with healthy individuals (OR 0.36, 95%CI 0.14-0.91, P=0.03) while the difference in the prevalence of insufficient iodine intake (UIC<100ug/L) and iodine above requirements (200≤UIC<300ug/L) among the two groups were not significant (deficiency: OR 0.38, 95%CI 0.13-1.16, P=0.09; above requirements: OR 0.92, 95%CI 0.40-2.10, P=0.84). After comparing the UIC levels of PTC patients with those of other thyroid diseases, we found that there was also no significant difference in the incidence of different levels of UIC in the two groups (excessive: OR 1.25, 95%CI 0.87-1.80, P=0.22; above requirements: OR 0.93, 95%CI 0.77-1.14, P=0.49; adequate: OR 0.96, 95%CI 0.78-1.17, P=0.67; deficiency: OR 1.02, 95%CI 0.86-1.22, P=0.80). The result of this meta-analysis also did not support the relationship between UIC and the BRAF mutation and lymph node metastasis (LNM) of PTC patients. Besides, we also found that studies on the relationship between urinary iodine and PTC may be influenced by the way UIC was measured. Conclusion: The 10 case-control included studies involved a total of 6,544 participants. The results of this meta-analysis showed excessive iodine intake, that is, UIC≥300ug/L was associated with the occurrence of PTC but not with BRAF mutation and LNM while adequate iodine intake (100≤UIC<200ug/L) may be one of the protective factors for PTC.

Asunto(s)

Yodo , Enfermedades de la Tiroides , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/epidemiología , Proteínas Proto-Oncogénicas B-raf , Enfermedades de la Tiroides/epidemiología , Metástasis Linfática , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/patología

RESUMEN

AMP-activated protein kinase (AMPK) functions as an energy sensor and is pivotal in maintaining cellular metabolic homeostasis. Numerous studies have shown that down-regulation of AMPK kinase activity or protein stability not only lead to abnormality of metabolism but also contribute to tumor development. However, whether transcription regulation of AMPK plays a critical role in cancer metastasis remains unknown. In this study, we demonstrate that AMPKα1 expression is down-regulated in advanced human breast cancer and is associated with poor clinical outcomes. Transcription of AMPKα1 is inhibited on activation of PI3K and HER2 through ΔNp63α. Ablation of AMPKα1 expression or inhibition of AMPK kinase activity leads to disruption of E-cadherin-mediated cell-cell adhesion in vitro and increased tumor metastasis in vivo. Furthermore, restoration of AMPKα1 expression significantly rescues PI3K/HER2-induced disruption of cell-cell adhesion, cell invasion, and cancer metastasis. Together, these results demonstrate that the transcription control is another layer of AMPK regulation and suggest a critical role for AMPK in regulating cell-cell adhesion and cancer metastasis.

Asunto(s)

Proteínas Quinasas Activadas por AMP/genética , Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Animales , Mama/patología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Adhesión Celular/efectos de los fármacos , Adhesión Celular/genética , Línea Celular Tumoral , Cromonas/farmacología , Supervivencia sin Enfermedad , Regulación hacia Abajo , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Lapatinib/farmacología , Ratones , Morfolinas/farmacología , Estadificación de Neoplasias , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Pronóstico , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/metabolismo , Análisis de Matrices Tisulares , Transcripción Genética/efectos de los fármacos , Activación Transcripcional , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

Cell⁻cell adhesion plays an important role in regulation of cell proliferation, migration, survival, and drug sensitivity. Metformin, a first line drug for type 2 diabetes, has been shown to possess anti-cancer activities. However, whether cell⁻cell adhesion affects metformin anti-cancer activity is unknown. In this study, Microscopic and FACS analyses showed that metformin induced cancer cell⁻cell adhesion exemplified by cell aggregation and anoikis under glucose restriction. Furthermore, western blot and QPCR analyses revealed that metformin dramatically upregulated integrin ß1 expression. Silencing of integrin ß1 significantly disrupted cell aggregation and reduced anoikis induced by metformin. Moreover, we showed that p53 family member ΔNp63α transcriptionally suppressed integrin ß1 expression and is responsible for metformin-mediated upregulation of integrin ß1. In summary, this study reveals a novel mechanism for metformin anticancer activity and demonstrates that cell⁻cell adhesion mediated by integrin ß1 plays a critical role in metformin-induced anoikis.

Asunto(s)

Glucosa/farmacología , Integrina beta1/genética , Integrina beta1/metabolismo , Metformina/farmacología , Neoplasias/metabolismo , Anoicis , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Silenciador del Gen , Células HEK293 , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Regulación hacia Arriba

RESUMEN

The development of intelligent drug delivery system that can efficiently deliver doxorubicin (DOX) to tumor site with controlled drug release performance and enhanced therapeutic efficacy is of great significance for cancer chemotherapy. In this report, a nano-prodrug system was prepared successfully by conjugating DOX to pH-sensitive amphiphilic diblock copolymer poly (ethylene glycol) methyl ether­b­poly (ß­amino esters) through acid-labile cis­aconityl moiety (mPEG-b-PAE-cis-DOX). The resultant complex copolymer-drug was able to self-assemble into polymeric micelles (PMs) in an aqueous solution at low concentration, and the critical micelle concentration (CMC) was 3.6 mg/L which was increased as decrease of pH value. H-nuclear magnetic resonance (1H NMR), Fourier transform infrared (FT-IR), dynamic light scattering (DLS), transition electron microscopy (TEM), and classic acid-base titration were combined to confirm and characterize the chemical structure of the copolymer/drug conjugates and the physicochemical properties of the prodrug system. The DOX loading capacity, drug delivery and therapeutic efficacy of the conjugates were evaluated in vitro and in vivo. Notably, the antitumor experiments in tumor-bearing mice demonstrated that the pH-responsive nano-prodrug system effectively enhanced the therapeutic efficacy in comparison to free drug. All above results suggested that pH-responsive prodrug system has the potential to be effective carrier for the DOX delivery and pH-triggered controlled release.

Asunto(s)

Doxorrubicina/química , Sistemas de Liberación de Medicamentos/métodos , Polímeros/química , Profármacos/química , Células A549 , Animales , Células Hep G2 , Humanos , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , Ratones , Micelas , Estructura Molecular , Células 3T3 NIH

RESUMEN

Activation of phosphatidylinositol 3 kinase (PI3K), Ras, and Her2 signaling plays a critical role in cancer development. Hotspot constitutive activating mutations in oncogenes, such as PIK3CA encoding the p110α catalytic subunit or RAS, as well as overexpression of Her2, are frequently found in human tumors and cancers. It has been well established that activation of these oncogenes profoundly promotes tumor metastasis, whereas decreased expression of ΔNp63α, the major protein isoform of the p53-related p63 expressed in epithelial cells, has been associated with cancer metastasis. In this study, we demonstrate that hotspot oncogenic mutations on PIK3CA and RAS, including p110αH1047R, K-RasG12V, and H-RasG12V, as well as activation of Her2, all led to suppression of ΔNp63α expression via Akt-fork-head transcription factor 3a (Akt-FOXO3a) signaling, resulting in increased cell motility and tumor metastasis. Expression of ΔNp63α effectively reversed p110αH1047R-, K-RasG12V-, H-RasG12V-, or Her2-induced cell motility in vitro and tumor metastasis in mouse models. We show that ΔNp63α was a direct FOXO3a transcriptional target and that expression of FOXO3a and ΔNp63α was correlated in human cancer biopsy samples. Together, these results demonstrate that ΔNp63α is a common inhibitory target of oncogenic PI3K, Ras, and Her2, and that ΔNp63α may function as a critical integrator of oncogenic signaling in cancer metastasis.

Asunto(s)

Fosfatidilinositol 3-Quinasa Clase I/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Animales , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Femenino , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Genes ras/genética , Humanos , Ratones , Mutación , Metástasis de la Neoplasia/genética , Fosfohidrolasa PTEN/genética , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Isoformas de Proteínas , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Transducción de Señal

RESUMEN

The blood glucose modifier metformin is used to treat type II diabetes and has also been shown to possess anticancer activities. Recent studies indicate that glucose deprivation can greatly enhance metformin-mediated inhibition of cell viability, but the molecular mechanism involved in this inhibition is unclear. In this study, we report that, under glucose deprivation, metformin inhibited expression of ΔNp63α, a p53 family member involved in cell adhesion pathways, resulting in disruption of cell matrix adhesion and subsequent apoptosis in human squamous carcinoma cells. We further show that metformin promoted ΔNp63α protein instability independent of AMP-activated protein kinase and that WWP1, an E3 ligase of ΔNp63α, was involved in metformin-mediated down-regulation of ΔNp63α levels. In addition, we demonstrate that a combination of metformin and the glycolysis inhibitor 2-deoxy-d-glucose significantly inhibited ΔNp63α expression and also suppressed xenographic tumor growth in vivo In summary, this study reveals a new mechanism for metformin-mediated anticancer activity and suggests a new strategy for treating human squamous cell carcinoma.

Asunto(s)

Carcinoma de Células Escamosas/tratamiento farmacológico , Metformina/farmacología , Factores de Transcripción/antagonistas & inhibidores , Proteínas Supresoras de Tumor/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP , Animales , Antineoplásicos/farmacología , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Desoxiglucosa/farmacología , Quimioterapia Combinada , Xenoinjertos , Humanos , Metformina/uso terapéutico , Ratones , Estabilidad Proteica/efectos de los fármacos

RESUMEN

The adaptor protein Mig-6 is a negative regulator of EGF signaling. It is shown that Mig-6 inhibits cell migration via direct interaction with the ErbB receptors, thereby inhibiting cross-phosphorylation or targeting the receptors for degradation. Mig-6 has also been shown to bind to and inhibit the Rho GTPase Cdc42 to suppress cytoskeletal rearrangement. However, the molecular mechanism(s) by which Mig-6 inhibits cell migration via Cdc42 is still not entirely clear. Here, we show that Mig-6 binding to Cdc42 is necessary and sufficient to inhibit EGF-induced filopodia formation and migration. This binding, mediated by four specific residues (I11, R12, M26, R30) in the Mig-6 CRIB domain, is essential for Mig-6 function. In addition, ectopic expression of Cdc42 reverses Mig-6 inhibition of cell migration. Mig-6 CRIB domain, alone, is sufficient to inhibit cell migration. Conversely, Mig-6 binding to EGFR is dispensable for Mig-6-mediated inhibition of cell migration. Moreover, we found that decreased Mig-6 expression correlates with cancer progression in breast and prostate cancers. Together, our results demonstrate that Mig-6 inhibition of Cdc42 signaling is critical in Mig-6 function to suppress cell migration and that dysregulation of this pathway may play a critical role in cancer development.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/metabolismo , Movimiento Celular , Factor de Crecimiento Epidérmico/farmacología , Regulación de la Expresión Génica , Proteínas Supresoras de Tumor/metabolismo , Proteína de Unión al GTP cdc42/metabolismo , Aminoácidos/química , Neoplasias de la Mama/metabolismo , Citoesqueleto/metabolismo , Progresión de la Enfermedad , Receptores ErbB/metabolismo , Femenino , Células HEK293 , Humanos , Masculino , Fosforilación , Neoplasias de la Próstata/metabolismo , Unión Proteica , Seudópodos/metabolismo , Interferencia de ARN , Transducción de Señal