Regular exercise improves health, modulating the immune system and impacting inflammatory status. Immunoglobulin G (IgG) N-glycosylation reflects changes in inflammatory status; thus, we investigated the impact of regular exercise on overall inflammatory status by monitoring IgG N-glycosylation in a previously inactive, middle-aged, overweight and obese population (50.30 ± 9.23 years, BMI 30.57 ± 4.81). Study participants (N = 397) underwent one of three different exercise programs lasting three months with blood samples collected at baseline and at the end of intervention. After chromatographically profiling IgG N-glycans, linear mixed models with age and sex adjustment were used to investigate exercise effects on IgG glycosylation. Exercise intervention induced significant changes in IgG N-glycome composition. We observed an increase in agalactosylated, monogalctosylated, asialylated and core-fucosylated N-glycans (padj = 1.00 × 10−4, 2.41 × 10−25, 1.51 × 10−21 and 3.38 × 10−30, respectively) and a decrease in digalactosylated, mono- and di-sialylated N-glycans (padj = 4.93 × 10−12, 7.61 × 10−9 and 1.09 × 10−28, respectively). We also observed a significant increase in GP9 (glycan structure FA2[3]G1, β = 0.126, padj = 2.05 × 10−16), previously reported to have a protective cardiovascular role in women, highlighting the importance of regular exercise for cardiovascular health. Other alterations in IgG N-glycosylation reflect an increased pro-inflammatory IgG potential, expected in a previously inactive and overweight population, where metabolic remodeling is in the early stages due to exercise introduction.
Physical inactivity and obesity are growing concerns, negatively impacting the general population. Moderate physical activity is known to have a beneficial anti-inflammatory effect. N-glycosylation of immunoglobulin G (IgG) reflects changes in the inflammatory potential of IgG. In this study, GlycanAge index of biological age (GlycanAge), one of the first commercially used biomarkers of aging, was employed to assess effects of exercise intensity in three different groups of athletes: professional competing athletes, regularly moderate active individuals and newly involved recreational individuals, compared to the group of inactive individuals. GlycanAge was significantly lower in the active group compared to the inactive group (β = -7.437, p.adj = 7.85E-03), and nominally significant and increased in professional athletes compared to the active group (β = 7.546, p = 3.20E-02). Competing female athletes had significantly higher GlycanAge comparing to active females exercising moderately (β = 20.206, p.adj = 2.71E-02), while the latter had significantly lower GlycanAge when compared with the inactive counterparts (β = -9.762, p.adj = 4.68E-02). Regular, life-long moderate exercise has an anti-inflammatory effect in both female and male population, demonstrated by lower GlycanAge index, and it has great potential to mitigate growing issues related to obesity and a sedentary lifestyle, which are relentlessly increasing world-wide.
Malignant pleural mesothelioma (MPM) is an aggressive pleural tumor associated with asbestos exposure. Poor clinical outcome of MPM is often driven by late-stage diagnosis due to non-specific clinical presentation, similarity to pleural lesions (e.g., inflammatory changes, metastatic adenocarcinoma), and limitations of current diagnostic methods. We employed Fourier transform infrared (FTIR) spectroscopy combined with convolutional neural networks (CNNs) to analyze formalin-fixed paraffin-embedded (FFPE) pleural tissue samples from patients with MPM, metastatic adenocarcinoma, pleural inflammation, and normal (healthy) pleura. Glycan analysis of FFPE normal pleura and MPM was performed using ultra-high-performance liquid chromatography (UPLC) and mass spectrometry (MS). Our FTIR-spectral analysis uncovered a strong spectral fingerprint of MPM that was especially apparent in the region typical for C-O and C-C stretches as well as local symmetry region typical for deformation vibrations of CH2 and C-OH groups, all appearing in carbohydrates. Our orthogonal validation of these findings through a targeted glycomics approach using UPLC confirmed that the MPM N-glycome exhibits a distinct fingerprint that distinguishes it from normal pleural tissue. Through utilization of MS for identifying the exact structures of differentially expressed N-glycan peaks, we also identified two high-mannose N-glycan structures that show a specific biomarker potential for MPM and need to be examined in future studies.
Background/Objectives: Increased risk of developing tendinopathies in athlete population has led to investigations of several genes associated with tendon properties, suggesting some individuals have greater genetic predisposition for developing tendinopathies. The main purpose of this study was to investigate how the functional polymorphisms within the COL5A1, COL27A1 and TNC genes impact risk of developing tendinopathies in Croatian high-level athletes. Methods: For this case-control genetic study we have recruited sixty-three high-level athletes with diagnosed tendinopathies and ninety-two asymptomatic healthy controls, all being unrelated Caucasians. Participants were genotyped for three single nucleotide polymorphisms (SNP) within COL5A1, COL27A1 and TNC genes using the pyrosequencing method. Results: TNC rs2104772 TT (P=0.0089) and T-T-T haplotype (P=0.0234) constructed of rs12722, rs946053 and rs2104772 were significantly over-represented in cases versus controls, implicating predisposition for tendinopathies. COL27A1 rs946053 GG (P=0. 0118) and G-A-C haplotype (P=0.0424) constructed of rs12722, rs946053 and rs2104772 were significantly over-represented in controls implicating protective role. Conclusions: These results further support associations between functional polymorphisms within the COL27A1 and TNC genes and risk of tendinopathies in high-level athletes. Further research is needed to replicate these results in various populations and in larger cohorts.