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1.
Aging Clin Exp Res ; 35(12): 3023-3031, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37923935

RESUMEN

BACKGROUND: Observational studies have suggested an association between white blood cells (WBCs) and frailty, but considering the susceptibility to reverse causality and confounding, the causal direction and magnitude of this association remain ambiguous. Our aim was to investigate the causal effect of WBCs on frailty by means of a Mendelian randomization (MR) analysis. METHODS: Based on the genome-wide association study (GWAS) summary statistics data provided by the European Bioinformatics Institute (EBI), we carried out a two-sample MR study. We applied the genetically predicted independent WBCs from GWAS as a measure of exposure data. The Rockwood Frailty Index (FI) was used as outcome measure, which was derived from a meta-analysis from GWAS in UK Biobank European ancestry participants and Swedish TwinGene participants. Our study applied inverse variance weighted (IVW), weighted median, Mendelian randomization-Egger (MR-Egger) and outlier test (MR-PRESSO) methods to explore relationships between various WBCs and frailty. RESULTS: In our study, a possible causal relationship between eosinophil levels and frailty was demonstrated by two-sample MR analysis. Eosinophils were associated with FI (beta:0.0609; 95% CI 0.0382, 0.0836; P = 1.38E-07). Our results suggest that as the level of eosinophils increases, so does the risk of frailty. No meaningful causal relationship between neutrophils, lymphocytes, monocytes or basophils and FI was found in the MR results (P > 0.05). CONCLUSIONS: According to this MR study, higher eosinophil counts are related to an increased risk of frailty. To validate these findings and investigate the mechanisms underlying these connections, future studies are warranted.


Asunto(s)
Fragilidad , Humanos , Fragilidad/genética , Estudio de Asociación del Genoma Completo , Leucocitos , Monocitos , Predisposición Genética a la Enfermedad
2.
Aging Clin Exp Res ; 34(10): 2465-2471, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35962897

RESUMEN

BACKGROUND: Sarcopenia is an age-associated decline in muscle mass that negatively affects the metabolic rate, strength, and function of the body and ultimately leads to a decrease in quality of life. Insulin-like growth factor 1 (IGF-1) is a modulator of muscle mass and muscle function. There is evidence that IGF-1 is related to the appendicular skeletal muscle mass index (ASMI) and grip strength. The aim of this study was to explore the relationship between serum IGF-1 levels and sarcopenia in older people. METHODS: In this cross-sectional survey of 984 people older than 60 years old, we used the 2019 criteria of the Asian Working Group for Sarcopenia (AWGS) to define sarcopenia. We collected demographic variables, measured ASMI and grip strength, and detected serum IGF-1 data. The levels of serum IGF-1 were separated into quintiles (Q1-Q5). RESULTS: Adjusted for age, education level, smoking, number of diseases and BMI, the multivariable linear regression analysis revealed that serum IGF-1 levels were related to ASMI in elderly men (coefficient = 0.03, 95% CI = 0.02-0.05, P < 0.001) but were not related to their grip strength. There was no significant relationship between serum IGF-1 levels and ASMI or grip strength in elderly women. The multivariable log-binomial regression analysis showed that higher serum IGF-1 levels were associated with a lower prevalence of sarcopenia in elderly men (prevalence ratio (PR) = 0.99, 95% CI = 0.98-1.00, P < 0.05) but not in elderly women. CONCLUSION: Serum IGF-1 levels were highly correlated with sarcopenia in older men. Further studies are needed to further explore the possible reasons for the observed difference between genders. Serum IGF-1 might predict sarcopenia prevalence in elderly men.


Asunto(s)
Sarcopenia , Femenino , Humanos , Masculino , Anciano , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Estudios Transversales , Factor I del Crecimiento Similar a la Insulina/metabolismo , Calidad de Vida , Fuerza de la Mano , Músculo Esquelético/fisiología
3.
Eur J Pharmacol ; 890: 173654, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33068589

RESUMEN

Tobacco smoke is the major risk factor for developing chronic obstructive pulmonary disease (COPD). Viral infection is a major cause of COPD exacerbation, which lacks effective drug treatments. In the present study, to mimic the pathogenesis of COPD, we employed a TLR3 ligand [Poly (I:C), PIC] to mimic viral infection to determine whether it enhances the effects of cigarette smoke (CS)-induced airway inflammation and remodeling. Our results showed that PIC enhanced the effects of cigarette smoke extract (CSE)-induced inflammatory cytokine IL-1ß, TNF-α and IL-8 mRNA expression and remodeling factor E-cadherin, α-SMA and TGF-ß1 mRNA expression with TLR3 upregulation and EGFR phosphorylation in pulmonary epithelial NCI-H292 cells. These responses were inhibited by a TLR3/dsRNA complex inhibitor (TLR3i) or a tyrosine kinase inhibitor icotinib (Ico). Similarly, in the PIC-enhanced CS-induced airway inflammation and remodeling mouse model, treatment with TLR3i or Ico reduced the mRNA and protein expression of the inflammatory cytokines IL-1ß and TNF-α and keratinocyte chemoattractant (KC) and the remodeling factors α-SMA, TGF-ß1, MMP-9 and MUC5AC, while increasing E-cadherin mRNA and protein expression. Furthermore, we found that TLRi and Ico can attenuate the airway hyperreactivity induced by PIC, which is enhanced by CS. Finally, PIC enhanced the effects of CS on TLR3 upregulation and EGFR phosphorylation and significantly increased Erk1/2 and P38 phosphorylation, whereas TLR3i and Ico markedly suppressed TLR3 upregulation and EGFR, Erk1/2 and P38 phosphorylation in the model. Our findings suggest that TLR3/EGFR may be a potential target for the treatment of airway inflammation and remodeling in COPD.


Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Fumar Cigarrillos/efectos adversos , Neumonía/prevención & control , Poli I-C/toxicidad , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptor Toll-Like 3/antagonistas & inhibidores , Animales , Línea Celular , Receptores ErbB/metabolismo , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Ratones , Ratones Endogámicos ICR , Neumonía/inducido químicamente , Neumonía/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/patología , Receptor Toll-Like 3/metabolismo
4.
Zhonghua Jie He He Hu Xi Za Zhi ; 31(4): 268-71, 2008 Apr.
Artículo en Chino | MEDLINE | ID: mdl-18846963

RESUMEN

OBJECTIVE: To improve the recognition of thoracic involvement of Castleman' s disease. METHODS: Ten patients with thoracic involvement of Castleman' s disease were retrospectively studied by review of the clinical manifestations, radiology, pathology, differential diagnosis, therapy and prognosis. RESULTS: The 10 patients were all females. Five of the patients, aged from 29 to 49 years, presented with multicentric lesions, manifested by interstitial pneumonia and mediastinal lymphadenopathy on radiology, as well as extrathoracic involvement including peripheral lymphadenopathy, and multiple organ impairment. The pathology was the plasma cell type. Treatment with corticosteroids and chemotherapy achieved partial remission in 4 cases, but 1 died of cardiac and respiratory failure. Localized lesions were found in the other 5 patients, aged from 13 to 49 years. No specific manifestations were revealed in these patients. The major radiological sign was right mediastinal masses, 6-9 cm in diameter, uniformly enhanced by contrast radiology. The pathology revealed vascular hyaline degeneration. Early surgical resection achieved good prognosis. The 5 patients were all alive. CONCLUSIONS: Diagnosis of thoracic involvement of Castleman' s disease is not easy. Early, repeated and multiple biopsy of lymph nodes is recommended, especially when the disease is multicentric or when the lymph nodes are massive. Synchronous enhancement with the vessels on contrast radiology is suggestive of the diagnosis.


Asunto(s)
Enfermedad de Castleman/diagnóstico , Tórax/patología , Adulto , Enfermedad de Castleman/patología , Diagnóstico Diferencial , Femenino , Humanos , Ganglios Linfáticos/patología , Persona de Mediana Edad
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