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Background: Hemodialysis patients exhibit a reduced response to vaccination and have different vaccine dose regimens. Vaccines induce antibodies and affect the inflammatory balance through antibody glycosylation and effector functions. Therefore, we aimed to analyze the antibody glycosylation profiles in hemodialysis patients who were vaccinated against severe acute respiratory syndrome coronavirus 2, infected with the virus, or both, and compare them with those of dialysis patients in a control group., Methods: Plasma samples from 112 hemodialysis patients were assigned to four groups: control, infected, vaccinated, and post-vaccine-infected. Paired plasma samples from 47 people with vaccination (vaccinees) were analyzed before and after the booster dose. The same analytical approach was applied to the four groups for a cross-sectional comparison., Results: Our study found that both vaccination and infection groups showed decreased fucosylation of IgG1, which is associated with a proinflammatory biosignature. However, vaccination also leads to increased galactosylation and bisection of IgG antibodies, which are associated with anti-inflammatory effects and the additional regulation of immune responses. In contrast, infection led to an additional decrease in the fucosylation of IgG2 and IgA, demonstrating a more intense proinflammatory biosignature than vaccination., Conclusions: Our findings emphasize the proinflammatory biosignature of afucosylation in both vaccination and infection groups. Additionally, we uncovered further regulated profiles related to galactosylation in vaccinees. These findings suggest that antibody investigation for vaccination or infection should not solely focus on neutralization but should also consider effector function-related glycosylation profiling. This comprehensive information can be valuable for fine-tuning vaccine development in the future., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Duchenne muscular dystrophy (DMD) is a lethal, progressive skeletal and cardiac myopathy. Cardiomyopathy is the leading cause of death in patients with DMD, but the molecular basis for heart failure is incompletely understood. As with humans, in the mdx mouse model of DMD, cardiac function is impaired after the onset of skeletal muscle pathology. Dysregulation of Klotho gene regulation in dystrophic skeletal muscles occurs at disease onset, affecting pathogenesis. Whether Klotho is protective against dystrophin-deficient cardiomyopathy is unknown. This study found that expression of a Klotho transgene prevented deficits in left ventricular ejection fraction and fractional shortening in mdx mice. Improvements in cardiac performance were associated with reductions in adverse cardiac remodeling, cardiac myocyte hypertrophy, and fibrosis. In addition, mdx mice expressed high concentrations of plasma fibroblast growth factor 23 (FGF23), and expression was increased locally in hearts. The cardioprotective effects of Klotho were not associated with differences in renal function or serum biochemistries, but transgene expression prevented increased expression of plasma FGF23 and cardiac Fgf23 mRNA expression. Cardiac reactive oxygen species, oxidative damage, mitochondrial damage, and apoptosis were reduced in transgenic hearts. Our findings also showed that FGF23 stimulates hypertrophic growth in dystrophic neonatal mouse ventricular myocytes in vitro, which was inhibited by co-stimulation with soluble Klotho. Taken together, these results show that Klotho prevented dystrophic cardiac remodeling and improved function., Competing Interests: Disclosures None declared., (Copyright © 2025. Published by Elsevier Inc.)

Objective: An increase in proximal tubule fluid phosphate concentration is caused by increased serum fibroblast growth factor-23 (FGF23) levels, which resulted in renal tubular damage in a mouse model of chronic kidney disease (CKD). However, few human studies have supported this concept. This study aimed to explore the association among estimated proximal tubule fluid phosphate concentration (ePTFp), serum FGF23 levels, and renal tubular damage biomarkers in middle-aged and older populations with mild decline in renal function., Methods: This cross-sectional study included 218 participants aged ≥45 with CKD stages G2-G4. Anthropometric measurements, blood tests, spot urine biomarkers, renal ultrasonography, cardiovascular assessment, smoking status, and medication usage were obtained in the morning in fasted states. The ePTFp was calculated using serum creatinine, urine phosphate, and creatinine concentrations. Urinary β2-microglobulin (β2-MG) and liver-type fatty acid-binding protein (L-FABP) levels were evaluated to assess renal tubular damage., Results: PTFp, serum FGF23, urinary β2-MG, and urinary L-FABP levels increased with CKD stage progression (stages G2, G3, and G4). However, serum and urine phosphate concentrations were comparable across the CKD stages. Univariate analysis revealed a stronger correlation of ePTFp with serum FGF23, urinary β2-MG, and urinary L-FABP levels than with the corresponding serum and urine phosphate concentrations. Multivariate analyses demonstrated that increased ePTFp was independently associated with elevated serum FGF23 and urinary β2-MG levels, even after adjusting for potential covariates, including the estimated glomerular filtration rate and urinary albumin-to-creatinine ratio., Conclusions: Our results are consistent with the concept in mouse model and suggest that increased ePTFp are associated with increased serum FGF23 levels and renal tubular damage during the early stages of CKD., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)