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1.
BMC Nephrol ; 24(1): 45, 2023 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-36849937

RESUMO

BACKGROUND: Accurate diagnosis and assessment of hematuria is crucial for the early detection of chronic kidney disease(CKD). As instability of urinary RBC count (URBC) often results with clinical uncertainty, therefore new urinary indexes are demanded to improve the accuracy of diagnosis of hematuria. In this study, we aimed to investigate the benefit of applying new complex indicators based on random urine red blood cell counts confirmed in hematuric kidney diseases. METHODS: All patients enrolled underwent renal biopsy, and their clinical information was collected. Urinary and blood biomedical indexes were implemented with red blood cell counts to derive complex indicators. Patients were divided into two groups (hematuria-dominant renal histologic lesions and non-hematuria-dominant renal histologic lesions) based on their renal pathological manifestations. The target index was determined by comparing the predictive capabilities of the candidate parameters for hematuric kidney diseases. Hematuria stratification was divided into four categories based on the scale of complex indicators and distributional features. The practicality of the new complex indicators was demonstrated by fitting candidate parameters to models comprising demographic information. RESULTS: A total of 1,066 cases (678 hematuria-dominant renal histologic lesions) were included in this study, with a mean age of 44.9 ± 15 years. In differentiating hematuria-dominant renal histologic lesion from the non-hematuria-dominant renal histologic lesion, the AUC value of "The ratio of the random URBC to 24-h albumin excretion" was 0.76, higher than the standard approach of Lg (URBC) [AUC = 0.744] (95% Confidence interval (CI) 0.712 ~ 0.776). The odds ratio of hematuria-dominant renal histologic lesion (Type I) increased from Q2 (3.81, 95% CI 2.66 ~ 5.50) to Q4 (14.17, 95% CI 9.09 ~ 22.72). The predictive model, composed of stratification of new composite indexes, basic demographic characteristics, and biochemical parameters, performed best with AUC value of 0.869 (95% CI 0.856-0.905). CONCLUSION: The new urinary complex indicators improved the diagnostic accuracy of hematuria and may serve as a useful parameter for screening hematuric kidney diseases.


Assuntos
Líquidos Corporais , Insuficiência Renal Crônica , Humanos , Adulto , Pessoa de Meia-Idade , Tomada de Decisão Clínica , Incerteza , Hematúria/diagnóstico , Rim , Insuficiência Renal Crônica/diagnóstico
2.
Int J Nanomedicine ; 17: 1593-1608, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35411142

RESUMO

Background: Dendritic cell (DC) targeted antigen delivery is a promising strategy to enhance vaccine efficacy and delivery of therapeutics. Self-assembling peptide-based nanoparticles and virus-like particles (VLPs) have attracted extensive interest as non-replicating vectors for nanovaccine design, based on their unique properties, including molecular specificity, biodegradability and biocompatibility. DCs are specialized antigen-presenting cells involved in antigen capture, processing, and presentation to initiate adaptive immune responses. Using DC-specific ligands for targeted delivery of antigens to DCs may be utilized as a promising strategy to drive efficient and strong immune responses. Methods: In this study, several candidates for DC-binding peptides (DCbps) were individually integrated into C-terminal of porcine circovirus type 2 (PCV2) Cap, a viral protein that could self-assemble into icosahedral VLPs with 60 subunits. The immunostimulatory adjuvant activity of DC-targeted VLPs was further evaluated in a vaccine model of PCV2 Cap. Results: With transmission electron microscopy (TEM), E. coli expressed Cap-DCbp fusion proteins were observed self-assembled into highly ordered VLPs. Further, in dynamic light scattering (DLS) analysis, chimeric VLPs exhibited similar particle size uniformity and narrow size distribution as compared to wild type Cap VLPs. With a distinctly higher targeting efficiency, DCbp3 integrated Cap VLPs (Cap-DCbp3) displayed enhanced antigen uptake and increased elicitation of antigen presentation-related factors in BM-DCs. Mice subcutaneously immunized with Cap-DCbp3 VLPs exhibited significantly higher levels of Cap-specific antibodies, neutralizing antibodies and intracellular cytokines than those with other DCbp integrated or wild type Cap VLPs without any DCbp. Interestingly, Cap-DCbp3 VLPs vaccine induces robust cellular immune response profile, including the efficient production of IFN-γ, IL-2 and IL-10. Meanwhile, the improved proliferation index in lymphocytes with Cap-DCbp3 was also detected as compared to other VLPs. Conclusion: This study described the potential of DC-binding peptides for further improved antigen delivery and vaccine efficacy, explainning nanovaccine optimization in relation to a range of emerging and circulating infectious pathogens.


Assuntos
Proteínas do Capsídeo , Circovirus , Animais , Antivirais/metabolismo , Proteínas do Capsídeo/química , Circovirus/genética , Células Dendríticas/metabolismo , Escherichia coli/metabolismo , Camundongos , Peptídeos/metabolismo , Suínos
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