RESUMEN
Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.
Asunto(s)
Microbioma Gastrointestinal , Lipopolisacáridos , FN-kappa B , Prevotella , Transducción de Señal , Calcificación Vascular , Animales , Humanos , Masculino , Ratas , Heces/microbiología , Inflamasomas/metabolismo , Lipopolisacáridos/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Osteogénesis/efectos de los fármacos , Prevotella/metabolismo , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/microbiología , Insuficiencia Renal Crónica/patología , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Calcificación Vascular/metabolismo , Calcificación Vascular/microbiología , Calcificación Vascular/patologíaRESUMEN
The human IgG molecules were labeled with 13 nm gold nanoparticles and the complex of the gold-labeled human IgG molecules was immobilized on a silicon surface modified by 3-aminopropyltriethoxysilane and glutaraldehyde. The method increases not only the tightness but also the surface coverage for immobilization of the complex and retains protein configuration well on the silicon surface. The self-assembled complex surface was observed by AFM. The complex aggregated on the silicon surface and the "island" monolayer of the complex was obtained. Meanwhile the SERS spectrum of the complex self-assembled "island" monolayer on silicon surface was presented. In the present paper, the gold labeled human IgG molecules were self-assembled on the silicon surface, SERS spectra of protein were obtained and as SERS active substrates were provided for the study of the protein molecules.
Asunto(s)
Inmunoglobulina G/química , Oro/química , Humanos , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Microscopía de Fuerza Atómica , Unión Proteica , Espectrometría Raman , Propiedades de SuperficieRESUMEN
OBJECTIVE: To study the relationship of per-capita tobacco consumption and lung cancer mortality in Henan province, and to provide evidence for policy development on tobacco control and reduction of lung cancer mortality. METHODS: Data regarding lung cancer mortality and per-capita tobacco consumption among household residents from 1992 to 2011, was collected from published almanacs in Henan and Henan Tumor Institutes. Trend Method was used to analyze the development of lung cancer in Henan province and the trend of per-capita tobacco consumption of residents in the household. 'Spearman rank correlation' was used to analyze the correlation between per-capita tobacco consumption of residents in the household from 1992 to 2001 and the lung cancer mortality rates from 2002 to 2011, with the lag time unite as 10 years in this study. Cure Estimation was used to fit the model regarding the relationship between per-capita tobacco consumption of residents in the household and lung cancer. RESULTS: Lung cancer mortality among those permanent residents in Henan province increased from 14.75/100 000 in 1992 to 27.00/100 000 in 2011, with an increase of 83.05%. Both the trend of per-capita tobacco consumption among the permanent residents and the lung cancer mortality were uprising, with the tobacco consumption showing a lag effect to the lung cancer mortality. Correlation coefficient between the per-capita tobacco consumption of residents in the household from 1992 to 2001 and the lung cancer mortality from 2002 to 2011 was rs = 0.770, P = 0.009 < 0.05, with statistically significant difference. Along with the uprising trend of lung cancer mortality, the per-capita tobacco consumption of residents in the household was also parallelly rising with the equation of relevance between per-capita tobacco consumption of residents in the household in Henna province and lung cancer as y = 2.60 x(0.46) (F = 576.483) and the R(2) was 0.667. CONCLUSION: Per-capita tobacco consumption of residents in the household in Henan province appeared a factor that influencing the lung cancer mortality and an association between the per-capita tobacco consumption of residents in the household and lung cancer was noticed. Tobacco consumption had a lag trend to the mortality of lung cancer.
Asunto(s)
Neoplasias Pulmonares/mortalidad , Uso de Tabaco/epidemiología , China/epidemiología , Humanos , Neoplasias Pulmonares/epidemiología , Análisis de RegresiónAsunto(s)
Ablación por Catéter/métodos , Hematoma/cirugía , Trombosis/cirugía , Anciano , Femenino , HumanosRESUMEN
BACKGROUND: CCN family, comprising six members (Cyr61, CTGF, Nov, WISP-1, WISP-2, WISP-3), is involved in the stimulation of cell proliferation, migration, adhesion, angiogenesis, and tumorigenesis. Several studies have shown that expression of Cyr61, CTGF, and WISP-1 affects the tumorigenic potential of lung cancer cells in vitro. However, the correlation of expression of CCN family proteins and clinical features of lung cancer remains unknown. METHODOLOGY AND PRINCIPAL FINDINGS: In the present work, we quantified the mRNA levels of Cyr61, CTGF, and WISP-1 in samples from 60 primary lung cancers and their matched normal lung tissues by quantitative real-time PCR assay. Downregulation of the Cyr61 and CTGF genes and upregulation of the WISP-1 gene were found in primary lung cancers compared to the paired normal lung tissues. Immunohistochemistry analysis also disclosed a similar expression pattern of Cyr61, CTGF, and WISP-1 protein in paired lung cancer tissues. Statistical analysis revealed significant associations between expression of either Cyr61 or CTGF with tumor stage, tumor histology, metastasis, smoking, and family history at diagnosis. A significant correlation also existed between WISP-1 expression with tumor histology, and patient age. Moreover, expression levels of Cyr61 and CTGF correlated with survival of the lung-cancer patients. CONCLUSIONS: Our results suggest that Cyr61, CTGF, and WISP-1 might be implicated in the development and progression of primary lung cancers, and their levels might serve as valuable prognostic markers, as well as potential targets for therapeutic intervention.