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Heparanase has been identified as a universal tumor-associated antigen, but heparanase epitope peptides are difficult to recognize. Therefore, it is necessary to explore novel strategies to ensure efficient delivery to antigen-presenting cells. Here, we established a novel immunotherapy model targeting antigens to dendritic cell (DC) receptors using a combination of heparanase CD4+ and CD8+ T-cell epitope peptides to achieve an efficient cytotoxic T-cell response, which was associated with strong activation of DCs. First, pegylated poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs) were used to encapsulate a combined heparanase CD4+ and CD8+ T-cell epitope alone or in combination with Toll-like receptor 3 and 7 ligands as a model antigen to enhance immunogenicity. The ligands were then targeted to DC cell-surface molecules using a DEC-205 antibody. The binding and internalization of these PLGA NPs and the activation of DCs, the T-cell response and the tumor-killing effect were assessed. The results showed that PLGA NPs encapsulating epitope peptides (mHpa399 + mHpa519) could be targeted to and internalized by DCs more efficiently, stimulating higher levels of IL-12 production, T-cell proliferation and IFN-γ production by T cells in vitro. Moreover, vaccination with DEC-205-targeted PLGA NPs encapsulating combined epitope peptides exhibited higher tumor-killing efficacy both in vitro and in vivo. In conclusion, delivery of PLGA NP vaccines targeting DEC-205 based on heparanase CD4+ and CD8+ T-cell epitopes are suitable immunogens for antitumor immunotherapy and have promising potential for clinical applications. [ABSTRACT FROM AUTHOR]

• An increase in the expression or activity of ALP suggests osteoblast differentiation. • ALP activity can be an important indicator of metabolic bone diseases. • A percentile curve for ALP activity per month in infants was created. • This curve is a reference for diseases related to abnormal ALP activity in infants. Alkaline phosphatase (ALP) is a ubiquitous enzyme in humans that can be used for diagnosing childhood diseases. Infants have the highest rapid growth rate and are susceptible to metabolic bone diseases. In infants, ALP activities exhibit significant month-wise variations, and authoritative standards are lacking. The present study aimed to provide a reference for the diagnosis of diseases related to abnormal ALP activities in infants. This study included 24,618 samples collected from infants aged 0–12 months from three medical centers in Chongqing, China. Samples of infants diagnosed with diseases that may affect ALP activity have been exclude. ALP activity was analyzed using an automatic biochemical analyzer. A percentile curve for ALP activity in male and female infants was constructed using MATLAB, and the skewness-median-coefficient of variation method was employed for curve fitting. ALP activity in male and female infants peaked at 0–4 months; the peak appeared at 1–2 months and declined gradually thereafter. After 4–5 months of age, the ALP activities declined further, with the lowest values observed at 11–12 months of age. A comparison between the data from this study and a those from a published German study indicates that Chinese infants exhibited peak ALP activity later and subsequent decline greater than German infants. A percentile curve was constructed for month-wise ALP activity in male and female infants, which could provide a reference for diagnosing diseases related to abnormal ALP activity in infants. [ABSTRACT FROM AUTHOR]

• There are no universally applicable reference intervals for alkaline phosphatase activity in children. • The reference values for adults are used for children in the clinical settings. • Biochemical indicator values should be established for the local populations. • Trends in pediatric alkaline phosphatase activity mimic the trends in height growth. • Percentile graphs depicting age-based trends in the enzyme's activity aid diagnosis. Alkaline phosphatase (ALP) serves as a biomarker for diagnosing several types of diseases in adults; nonetheless, its use is restricted in children because of changes in ALP activity during different physiological phases. The present study aimed to investigate ALP activity and its dynamics in children of different ages to establish the reference values for ALP activity in children. Total 167,625 samples of children aged 0–18 years were enrolled in this study. ALP activity was measured using the 4-nitrophenyl-1-phosphate disodium salt (4-NPP)–2-amino-2-methyl-1-propanol (AMP) method with an automatic biochemical analyzer. Patients with known diagnoses that may affect ALP activity were excluded. A percentile curve was plotted using MATLAB software, and the curve was fitted using the skewness–median–coefficient of variation (LMS) method. ALP activity reached the highest peak at 12–13 years of age and then gradually decreased to the lowest peak at 18–19 years of age in boys, whereas it reached the highest at 10–11 years and then gradually reduced to the lowest at 17–18 years in girls. Furthermore, the highest peak of ALP activity appeared substantially earlier in children of either sex in China than in those in Germany. We showed the dynamics of ALP activity in both boys and girls between the ages of 0 and 18 years in China and compared the difference in ALP activity between children in China and Germany. Our findings provide a reference for clinicians. [ABSTRACT FROM AUTHOR]

Due to the higher birth rate of preterm infants and improvements in their management, metabolic bone disease of prematurity (MBDP) has a high incidence and is attracting attention. However, clear indicators for the early diagnosis of MBDP are lacking. We aimed to explore simple and feasible early warning indicators for diagnosing MBDP. Our study collected case data of premature infants from two medical centers in Chongqing from January 2020 to February 2022. According to the inclusion and exclusion criteria, data from 136 cases were collected. The correlation between 14 variables in each case and the occurrence of MBDP was analyzed. According to area under the receiver operating characteristic curve (AUROC) analysis, the best cutoff value for each variable was determined. Potential predictors were selected, and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to establish the association of two models with MBDP, whose results were used to develop a diagnostic nomogram. Furthermore, a model decision curve was analyzed. Four predictors were selected from 14 clinical variables by LASSO regression, and Model I was established, including the following characteristics: height (>36 cm), head circumference (≤29.49 cm), total serum calcium (Ca) (>2.13 mmol/L), and alkaline phosphatase (ALP) (>344 U/L) levels. A single predictor, the ALP level (>344 U/L), was used to establish Model II. The AUROC values of the two models were 0.959 for Model I and 0.929 for Model II. In conclusion, in this study, two diagnostic models of MBDP were developed using four combinations of predictors and ALP as a single predictor. Both models showed good sensitivity and specificity for the early diagnosis of metabolic bone disease (MBD), and an ALP level of 344 U/L was defined as a simple and effective diagnostic threshold. In future studies, using larger samples, diagnostic threshold values of ALP for premature infants of different ages should be established, and internal and external validations are needed to improve the adaptability of the current model. • Metabolic bone disease of prematurity (MBDP) has high incidence recently. • No easy-to-measure biomarkers are available for MBDP. • We assessed 4 predictors in 2 models; both showed good sensitivity and specificity. • Alkaline phosphatase 344 U/L is a cutoff for an early warning of metabolic bone disease in premature infants. [ABSTRACT FROM AUTHOR]