Plasma Fetuin-B Levels are Associated with Nervous Symptoms and Conduction Velocity in Patients with Painful DPNLin, Wang, Gu
et alDiabetes Metab Syndr Obes (2025) 18, 785-793
Abstract: To assess the plasma concentrations of the novel hepatokine fetuin-B in individuals with type 2 diabetes with or without diabetic peripheral neuropathy (DPN), and to evaluate the relationship among fetuin-B levels, nervous function, and metabolic parameters.A total of 333 participants were recruited and divided into three groups: DPN, painful DPN (pDPN), and non-DPN. Metabolic parameters, peripheral neuropathy-associated indices, and general biochemical parameters were also measured.Compared with the non-DPN group, general parameters, including age, SBP, BUN, Cr, and ALT, were significantly higher in the DPN and pDPN groups, and FPG, HbA1c, TC, TG, LDL, BUN, Cr, and UA levels were higher in the pDPN group. The neuropathy symptom score (NSS), neuropathy disability score (NDS), and Douleur Neuropathique en 4 Questions (DN4) were highest in the pDPN group, followed by the DPN group, and lowest in the non-DPN group. Moreover, fetuin B levels showed the same trends as peripheral neuropathy indices. Additionally, oxidative stress markers showed a decrease in total antioxidant capacity (TAC) and an increase in malondialdehyde (MDA) across all groups, with the most pronounced changes observed in pDPN patients. Bivariate correlation analysis showed that fetuin B levels were positively correlated with FPG, TC, LDL, NSS, NDS, DN4, and MDA levels, and negatively associated with TAC after adjusting for age and sex. Furthermore, nerve conduction velocity, including MLT, MRT, SRS, and SLT, showed decreasing trends among tertiles of fetuin B levels.The current study suggests that circulating fetuin-B levels may be associated with the progression of pDPN and highlights the effects of hepatokine-mediated liver-to-peripheral nervous system crosstalk in DPN.© 2025 Lin et al.
Epithelial FETUB-mediated the inhibition of NEP activity aggravates asthmaSun, Hua, Fu
et alInt Immunopharmacol (2025) 152, 114397
Abstract: Neuropeptide accumulation exacerbates asthma, with reduced neprilysin (NEP) activity implicated. However, this regulatory mechanism remains unexplored.To identify and characterize epithelial-derived modulators of NEP activity and their role in asthma pathogenesis.Bioinformatics and molecular docking identified fetuin B (FETUB) as a NEP inhibitor. FETUB expression in human lung tissue was assessed by immunohistochemistry, and its levels in exhaled breath condensate (EBC) and serum were quantified by ELISA. Functional assays and a lung-specific FETUB knockdown mouse model using Adeno-associated virus (AAV) vector confirmed its role in NEP inhibition and asthma pathogenesis.Bioinformatic analysis, protein binding assays, and fluorescence substrate degradation experiments confirmed that FETUB is an inhibitor of NEP. Serum FETUB levels were elevated in asthmatics and positively correlated with serum IgE, eosinophil counts. Similarly, in asthmatic EBC, FETUB levels were significantly higher than in healthy controls and negatively correlated with asthma control test, FEV1 and FEV1%pred. The expression of FETUB was elevated in asthma lung tissue and primarily localized to airway epithelial cells. Combined bioinformatics and experimental data indicated that IL-13 as a key inducer of epithelial FETUB expression. Lung-specific FETUB knockdown restored NEP activity, reduced neuropeptides CGRP and SP, and improved airway inflammation and hyperresponsiveness in asthma.The findings suggest that epithelial-derived FETUB exacerbates airway inflammation and hyperresponsiveness in asthma through the inhibition of NEP activity and the resultant accumulation of CGRP and SP.Copyright © 2025 Elsevier B.V. All rights reserved.
Proteomic Analysis of Human Follicular Fluid-Derived Exosomes Reveals That Insufficient Folliculogenesis in Aging Women is Associated With InfertilityLiu, Zhou, Zan
et alMol Cell Proteomics (2025) 24 (4), 100930
Abstract: Although the risk of female infertility increases with advancing age, the underlying mechanisms remain unknown. Exosomes in follicular fluid are suggested to regulate folliculogenesis and influence oocyte quality, potentially playing a critical role in age-related infertility. Elucidating their content could enhance the understanding of the molecular mechanisms associated with female aging-induced infertility. In this study, we explored the proteomic profiles of exosomes derived from human follicular fluid to identify protein signatures associated with infertility in both young and aging women. Despite the lack of significant differences in the morphology and particle size of follicular fluid-derived exosomes between the two groups, proteomic analysis revealed a distinct pattern of differentially expressed proteins (DEPs). DEPs associated with B-cell activation, pathogen invasion, and disrupted metabolic processes were significantly more highly expressed in the aging group than in the young group, indicating their involvement in age-related infertility. In vivo experiments demonstrated that the application of exosomes, particularly those derived from young female group, facilitated the successful maturation of follicles. Key exosomal proteins, including ENO1, HSP90B1, fetuin-B, C7, and APOC4, were found to be associated with follicular maturation. Furthermore, the PI3K/AKT signaling pathway, which is known to be related to folliculogenesis, was activated by the application of exosomes in aging female mice. This study provides novel insights into the aging-associated protein signatures of follicular fluid-derived exosomes and their potential role in infertility. These findings suggest that aging-related protein signatures in exosomes could contribute to the treatment of age-related infertility.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Hepatokines and their role in cardiohepatic interactions in heart failureShouman, Najmeddine, Sinno
et alEur J Pharmacol (2025) 992, 177356
Abstract: Heart failure is one of the leading causes of death and disease worldwide. It is a condition that affects multiple systems within the body. There is a large body of evidence supporting that the liver is a major organ involved in the pathogenesis of heart failure. Cardiac hepatopathy and cirrhotic cardiomyopathy are two conditions that are associated with poor clinical outcomes in patients with heart failure. Despite the extensive proposed explanations of the mechanisms entailing heart failure, there remains a gap in the role of proteins and metabolic regulators produced by hepatocytes and their effect on the development, progression, and prognosis of heart failure, including adverse cardiac remodeling, fibrosis, cardiac cachexia, and renal dysfunction associated with heart failure. The aim of this review is to identify the major hepatokines being studied (adropin, fetuin-A, fetuin-B, FGF-21, selenoprotein P and α1-microglobulin) as modulators of metabolic homeostasis and cardiac dysfunction in heart failure. Research suggests that these factors play a role in modulating oxidative stress, fibrosis, apoptosis, inflammatory responses, immune cell activation, mitochondrial dysfunction, and cellular migration. The exact role of each of these hepatokines is under on-going research and requires more investigations for future clinical use.Copyright © 2025 Elsevier B.V. All rights reserved.
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