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1.
Biomed Pharmacother ; 123: 109811, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31924597

RESUMEN

Melatonin (Mel) has been shown to involve in many essential cell functions via modulating many signaling pathways. We for the first time investigated that Mel exerted anti-tumor activities in Hodgkin lymphoma (HL) via inhibiting cell proliferation and promoting cell apoptosis. Further study revealed that Mel treatment increased expression of LC3-II and decreased p62 proteins with the enhanced production of autolysosome, indicating it induced activation of autophagy. Nevertheless, Mel treatment together with autophagy inhibitors 3-MA or CQ exacerbated the damage effect of Mel in HL cells, which means autophagy plays a protective role in this process. Furthermore, we found Mel treatment increased the expression of G protein-coupled receptors MT2 and retinoic acid-related orphan receptors (RORs), eg. RORA, RORB and RORC. While RORC has the highest increase in Mel treated HL cells. In addition, RORC overexpression induced autophagy activation. Therefore, Mel showed tumor-suppressive role due to an increased level of RORC induced autophagy in HL.

2.
Int Immunopharmacol ; 80: 106116, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31978804

RESUMEN

The myocardial inflammatory response is a consequence of myocardial infarction (MI), which may deteriorate cardiac remodeling and lead to dysfunction in the heart post-MI. Dectin-1 is a c-type lectin, which has been shown to regulate innate immune responses to pathogens. However, the role of Dectin-1 in the heart diseases remains largely unknown. In this study, we aimed to investigate the effects of Dectin-1 on cardiac remodeling post-MI. We found that cardiac Dectin-1 mRNA and protein expressions were significantly elevated in C57BL/6 mice after MI. In vitro, hypoxia induced cardiomyocyte injury in parallel with increased Dectin-1 protein expression. Knockdown of Dectin-1 remarkably attenuated cardiomyocyte death under hypoxia and lipopolysaccharide (LPS) stimulation. In vivo administration of adeno-associated virus serotype 9 mediated silencing of Dectin-1, which significantly decreased cardiac fibrosis, dilatation, and improved cardiac function in the mice post-MI. At the molecular level, downregulation of Dectin-1 dramatically suppressed up-regulation of nuclear factor-κB (NF-κB), nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), and the inflammatory genes involved in fibrogenesis and cardiac remodeling after MI. Furthermore, treatment with BAY11-7082, an inhibitor of NF-κB, repressed the activation of NF-κB, and attenuated LPS induced elevation of NLRP3 and cell death in cardiomyocytes. Collectively, upregulation of Dectin-1 in cardiomyocytes post-MI contributes to cardiac remodeling and cardiac dysfunction at least partially by activating NF-κB and NLRP3. This study identified Dectin-1 as a promising therapeutic target for ischemic heart disease.

3.
Acta Pharmacol Sin ; 41(3): 319-326, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31645662

RESUMEN

Pyroptosis is a form of inflammatory cell death that could be driven by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation following myocardial infarction (MI). Emerging evidence suggests the therapeutic potential for ameliorating MI-induced myocardial damages by targeting NLRP3 and pyroptosis. In this study, we investigated the myocardial protection effect of a novel anthraquinone compound (4,5-dihydroxy-7-methyl-9,10-anthraquinone-2-ethyl succinate) named Kanglexin (KLX) in vivo and in vitro. Male C57BL/6 mice were pre-treated either with KLX (20, 40 mg· kg-1per day, intragastric gavage) or vehicle for 7 consecutive days prior to ligation of coronary artery to induce permanent MI. KLX administration dose-dependently reduced myocardial infarct size and lactate dehydrogenase release and improved cardiac function as compared to vehicle-treated mice 24 h after MI. We found that MI triggered NLRP3 inflammasome activation leading to conversion of interleukin-1ß (IL-1ß) and IL-18 into their active mature forms in the heart, which could expand the infarct size and drive cardiac dysfunction. We also showed that MI induced pyroptosis, as evidenced by increased DNA fragmentation, mitochondrial swelling, and cell membrane rupture, as well as increased levels of pyroptosis-related proteins, including gasdermin D, N-terminal GSDMD, and cleaved caspase-1. All these detrimental alterations were prevented by KLX. In hypoxia- or lipopolysaccharide (LPS)-treated neonatal mouse ventricular cardiomyocytes, we showed that KLX (10 µM) decreased the elevated levels of terminal deoxynucleotidyl transferase dUTP nick end labeling- and propidium iodide-positive cells, and pyroptosis-related proteins. We conclude that KLX prevents MI-induced cardiac damages and cardiac dysfunction at least partly through attenuating NLRP3 and subsequent cardiomyocyte pyroptosis, and it is worthy of more rigorous investigations for its potential for alleviating ischemic heart disease.

4.
Medicine (Baltimore) ; 98(50): e18213, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31852078

RESUMEN

We aimed to investigate the association between excess body mass index (BMI) and papillary thyroid cancer (PTC) in an operative population, and the impact of higher BMI on clinicopathological aggressiveness of PTC.Charts of 10,844 consecutive patients with thyroid nodules undergoing partial or total thyroidectomy between 1993 and 2015 were reviewed. Patients diagnosed with PTC were stratified in 4 groups: BMI < 18.5 (underweight), 18.5 ≤ BMI < 24 (normal-weight), 24 ≤ BMI < 28 (overweight) and BMI ≥ 28(obese). The impacts of high BMI on prevalence and clinicopathological parameters of PTC were retrospectively analyzed in both univariate and multivariate binary logistic regression analysis.For every 5-unit increase in body mass, the odds of risk-adjusted malignance increased by 36.6%. The individuals who were obese and overweight were associated with high risk of thyroid cancer [odds ratio (OR)= 1.982, P < .001; OR= 1.377, P < .001; respectively] compared to normal weight patients, and this positive association was found in both genders. Obesity was independent predictors for tumors larger than 1 cm (OR = 1.562, P < .001) and multifocality (OR = 1.616, P < .001). However, there was no difference in cervical lymph node (LN) metastasis among BMI groups. Crude analysis showed BMI was associated with advanced tumor-node-metastasis (TNM) stage (relative risk, approximately 1.23 per 5 BMI units, P < .001), but this association disappeared after adjusting for confounding factors.Obesity was significantly associated with the risk of PTC in a large, operative population. Higher BMI was significantly associated with larger tumor size and multifocal tumor.


Asunto(s)
Índice de Masa Corporal , Obesidad/complicaciones , Cáncer Papilar Tiroideo/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Tiroidectomía/métodos , Estudios de Casos y Controles , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Estudios Retrospectivos , Cáncer Papilar Tiroideo/etiología , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/etiología , Neoplasias de la Tiroides/cirugía
5.
BMJ Open ; 9(1): e023334, 2019 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-30782703

RESUMEN

OBJECTIVES: This study aims to summarise the features and trends of thyroid carcinoma in the past two decades in China. DESIGN, SETTING AND PARTICIPANTS: Clinical data obtained from 10 798 patients treated by thyroidectomy from 1994 to 2015 at the Department of General Surgery of the People's Liberation Army General Hospital, Beijing, China were retrospectively analysed. OUTCOME MEASURES: Incidence and histopathological features of thyroid cancer were compared and the risk factors for local lymph node metastasis analysed. RESULTS: Our data indicated a significant increase in the detection of thyroid cancer (from 16.8% to 69.8%, p<0.01). Among the 5235 thyroid cancer cases, papillary thyroid carcinoma (PTC) was the most common histotype, accounting for 95.1% of all malignancies over the 22-year period. Among the 4979 PTCs, micro-PTCs (mPTC) with the largest diameter ≤10 mm has gradually become the dominant form, and its percentage in PTCs has increased from 13.3% in the biennial period of 1994-1995 to 51.2% in 2010-2011. Furthermore, the size of the tumour has decreased significantly from 2.3±1.1 cm in 1994 to 1.2±0.9 cm in the largest diameter (p<0.01), while the average age at diagnosis and female dominance remained unchanged during the period. Logistic regression showed that tumour nodules>1 cm and male gender were the main risk factors for local lymph node metastasis (LNM), whereas patients over 45 years had lower risk. CONCLUSIONS: During the 22-year period, an increased detection of thyroid cancer, particularly mPTC, was found while the occurrence of LNM decreased. Our results suggest that the current preoperative diagnosis and risk stratification are adequate, supporting the published guidelines for the diagnosis of thyroid cancer.


Asunto(s)
Cáncer Papilar Tiroideo/epidemiología , Neoplasias de la Tiroides/epidemiología , Tiroidectomía/estadística & datos numéricos , Adulto , Factores de Edad , Beijing/epidemiología , Estudios Transversales , Bases de Datos Factuales , Humanos , Incidencia , Metástasis Linfática/patología , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía
6.
Diagn Cytopathol ; 47(3): 187-193, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30499203

RESUMEN

BACKGROUND: Thyroid nodules are very common. Ultrasound (US) and fine needle aspiration (FNA) are both integral in cancer screening. This study investigated the concordance between thyroid nodule sizes measured by US and gross pathologic examination and their relationship with malignancy. METHODS: A retrospective design was used to select consecutive patients with proven carcinoma of the thyroid. The number and maximum diameter of nodules, rates and types of malignancy, as well as predictors of malignancy were determined. RESULTS: The 10 944 patients examined had 15 283 thyroid nodules, 44.6% of which were malignant. Of the 4449 nodules sampled by FNA and the 8748 not sampled by FNA, 76.5% and 30.5% were malignant, respectively. The sensitivity, specificity, positive and negative predictive values (NPVs), and overall accuracy of FNA based on final pathology were 97.9%, 96.3%, 98.8%, 93.5%, and 97.5%, respectively. Nodule sizes determined by US were comparable with most nodules having either the same size range (n = 2959, 77.7%) or differing only by one size range (n = 770, 20.5%). CONCLUSIONS: Thyroid nodule size is inversely related to malignancy risk, as larger nodules have lower malignancy rates. Nodule size estimated by US shows relatively good correlation with final pathologic size. However, thyroid nodules should undergo FNA regardless of size. If the FNA is not benign, nodule size should influence therapeutic decision making.


Asunto(s)
Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , Adulto , Anciano , Biopsia con Aguja Fina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Ultrasonografía
7.
Mol Ther Nucleic Acids ; 19: 421-436, 2019 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-31896070

RESUMEN

Methyltransferase-like 3 (METTL3) is the main enzyme for N6-methyladenosine (m6A)-based methylation of RNAs and it has been implicated in many biological and pathophysiological processes. In this study, we aimed to explore the potential involvement of METTL3 in osteoblast differentiation and decipher the underlying cellular and molecular mechanisms. We demonstrated that METTL3 is downregulated in human osteoporosis and the ovariectomized (OVX) mouse model, as well as during the osteogenic differentiation. Silence of METTL3 by short interfering RNA (siRNA) decreased m6A methylation levels and inhibited osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and reduced bone mass, and similar effects were observed in METTL3+/- knockout mice. In contrast, adenovirus-mediated overexpression of METTL3 produced the opposite effects. In addition, METTL3 enhanced, whereas METTL3 silence or knockout suppressed, the m6A methylations of runt-related transcription factor 2 (RUNX2; a key transcription factor for osteoblast differentiation and bone formation) and precursor (pre-)miR-320. Moreover, downregulation of mature miR-320 rescued the decreased bone mass caused by METTL3 silence or METTL3+/- knockout. Therefore, METTL3-based m6A modification favors osteogenic differentiation of BMSCs through m6A-based direct and indirect regulation of RUNX2, and abnormal downregulation of METTL3 is likely one of the mechanisms underlying osteoporosis in patients and mice. Thus, METTL3 overexpression might be considered a new approach of replacement therapy for the treatment of human osteoporosis.

8.
Sci Rep ; 7(1): 15832, 2017 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-29158505

RESUMEN

The study aimed to investigate the gender-related differences of disease onset, age distribution, blood type, clinical characteristics, and malignant behaviors of differentiated thyroid carcinoma (DTC) in Chinese patients. A total of 7385 consecutive thyroid cancer patients who underwent thyroidectomy were retrospectively reviewed. 4087 (55.3%) were diagnosed as benign and the other (3298, 44.7%) were as malignant. DTC accounted for 97.6% in the malignant tumor. More single nodules turned out to be DTC in male compared to multiple nodules (46.9% vs. 40.4%, P = 0.004). The proportion increased along with the increase of year during 2000-2013, which was from 7.5% to 68.1% in males and from 16.2% to 66.7% in females. The level of preoperative TSH was significantly higher in patients with DTC compared to the patients with benign (1.97 vs. 1.57 mIU/L, P < 0.001). The proportion of thyroid cancer was dominated in blood type B and the lowest incidence in blood type A in male, the difference was not statistically significant. The results showed that age, nodule number, BMI and serum TSH were the related factors for DTC. More aggressive behaviors of DTC were observed in male patients, and more attention should be focused on the timely diagnosis and treatment of these patients.


Asunto(s)
Adenocarcinoma/epidemiología , Carcinoma/epidemiología , Neoplasias de la Tiroides/epidemiología , Adenocarcinoma/sangre , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Factores de Edad , Anciano , Tipificación y Pruebas Cruzadas Sanguíneas , Carcinoma/sangre , Carcinoma/patología , Carcinoma/cirugía , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Caracteres Sexuales , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Nódulo Tiroideo/patología , Nódulo Tiroideo/cirugía , Tiroidectomía , Tirotropina/sangre , Adulto Joven
9.
Am J Cardiol ; 118(8): 1233-1238, 2016 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-27561195

RESUMEN

There are few data comparing the patient characteristics and outcomes of heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced EF (HFrEF) in Asian cohorts. We aimed to evaluate the prevalence, clinical characteristics, and 1-year outcomes of a well-defined Southeast Asian HFpEF cohort in comparison to an HFrEF cohort. We conducted a retrospective observational study of 1,978 patients discharged from Changi General Hospital, Singapore with a primary diagnosis of HF from 2009 to 2013. About 29% of discharges had HFpEF. Patients with HFpEF were more likely to be women, older age, and have a higher prevalence of hypertension. There were no significant differences in the absolute rates of 30-day outcomes between the 2 groups. The absolute rate of death at 1 year was similar in HFrEF and HFpEF at 17% and 15%, respectively (p = 0.3). After multivariate adjustment, there was no difference in the outcomes of the 2 groups. Atrial fibrillation at baseline was a predictor of death or HF hospitalization in HFpEF but not HFrEF (interaction p = 0.003). In conclusion, in this study of a Southeast Asian population with well-defined HF, we found that the clinical profile of patients with HF was similar to that in the West and 30-day and 1-year mortality and morbidity were not significantly different between cohorts.


Asunto(s)
Insuficiencia Cardíaca/fisiopatología , Hospitalización/estadística & datos numéricos , Mortalidad , Volumen Sistólico , Anciano , Anciano de 80 o más Años , Asia Sudoriental , Grupo de Ascendencia Continental Asiática , Fibrilación Atrial/epidemiología , Causas de Muerte , Estudios de Cohortes , Comorbilidad , Ecocardiografía , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/epidemiología , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Pronóstico , Estudios Retrospectivos , Factores Sexuales , Singapur
10.
J Ment Health ; 20(6): 509-24, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21988230

RESUMEN

BACKGROUND: The ubiquitous nature of mobile phones and their increasing functionality make them an ideal medium for the delivery of large-scale public health information and interventions. While mobile phones have been used to this end in behavioural and physical health settings, their role in monitoring and managing mental health is in its infancy. AIMS: The purpose of this paper is (1) to provide an overview of the field of mobile mental health and (2) by way of illustration, describe an initial proof of concept study carried out to assess the potential utility and effectiveness of a newly developed mobile phone and web-based program in the management of mild-to-moderate stress, anxiety and depression. METHODS: Over 6 weeks, participants were given access to "myCompass": an interactive self-help program, which includes real-time self-monitoring with short message service prompts and brief online modules grounded in cognitive behavioural therapy. RESULTS: Preliminary analyses found that participants' symptoms of stress, anxiety, depression and overall psychological distress were significantly reduced after using myCompass. Improvements were also found in functional impairment and self-efficacy. CONCLUSIONS: These preliminary results support the feasibility of implementing mobile phone-based interventions with the potential of improving psychological wellbeing.


Asunto(s)
Teléfono Celular , Servicios de Salud Mental , Adulto , Ansiedad/terapia , Terapia Cognitivo-Conductual/métodos , Depresión/terapia , Femenino , Humanos , Internet , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/terapia , Cooperación del Paciente , Estrés Psicológico/terapia , Encuestas y Cuestionarios
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