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Povzetek: Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition often accompanied by gastrointestinal (GI) symptoms. Inflammatory proteins in stool have been proposed as potential biomarkers, but evidence remains inconsistent. We compared fecal levels of a1-antitrypsin (A1AT), immunoglobulin A (IgA), and calprotectin (Cal) in 57 children with ASD and 57 biological siblings without ASD. Sibling designs are now preferred to disentangle ASD-specific biology from shared environmental and microbiome factors. Participants were carefully screened to exclude recent antibiotic use, digestive problems, gastrointestinal infections, and abnormal dietary patterns, thereby controlling for major factors known to influence gut inflammatory markers. Methods: Stool samples were thawed, freeze-dried, and proteins extracted using ammonium bicarbonate buffer with sodium deoxycholate. After BCA quantification, samples were reduced, alkylated, spiked with stable isotope– labelled peptides, and digested with trypsin. Peptides were purified and analyzed by UHPLC–MS/MS (Agilent 6495A) in dynamic SRM mode. Quantification used internal standards and normalization to total protein. Ratios of IgA1/IgA2 and S100A8/S100A9 were calculated. ASD severity was evaluated using the Childhood Autism Rating Scale (CARS). Results: Children with ASD showed trends toward higher IgA and calprotectin and lower a1-antitrypsin compared with siblings, but differences were not statistically significant. Subgroup analysis suggested different distribution patterns in moderate versus severe ASD, including higher IgA in the moderate group and altered S100A8/S100A9 ratio in the severe group. These subgroup findings were exploratory, derived from critically underpowered post-hoc analyses (severe subgroup: n = 11 pairs, ~18% power for medium effects), and should be considered hypothesis-generating only, pending validation in adequately powered pre-registered studies. Conclusions: The results are consistent with recent meta-analyses reporting no consistent evidence of gut inflammation in ASD. Larger, sex-matched studies with full assay validation are needed to clarify the role of stool proteins in ASD.
Ključne besede: autism, inflammation, protein biomarkers
Objavljeno v DiRROS: 16.04.2026; Ogledov: 35; Prenosov: 20
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Povzetek: Porphyrins are intermediates in heme biosynthesis and have been proposed as biomarkers of metabolic dysfunction and environmental exposure in autism spectrum disorder (ASD). This study aimed to evaluate urinary porphyrin fractions and trace element ratios in children with ASD compared to neurotypical controls. Urinary porphyrins were quantified using high-performance liquid chromatography (HPLC), and trace elements were measured via inductively coupled plasma mass spectrometry (ICP-MS) normalized to urinary creatinine. Trace element ratios (e.g., Zn/Cu, Se/Pb) were calculated. Statistical comparisons were made using the Mann–Whitney U-test. Children with ASD showed significantly elevated urinary levels of coproporphyrin (median: 1.94 µg/g creatinine vs. 1.32 in controls; p = 0.02) and pentacarboxyporphyrin (0.86 vs. 0.57; p = 0.01), and reduced hexacarboxyporphyrin (0.12 vs. 0.23; p = 0.03). Lead (Pb) levels were significantly higher in ASD (median: 1.96 µg/g creatinine vs. 0.82; p = 0.004), while mercury (Hg) was not significantly different. Several trace element ratios differed significantly: Zn/Cu (ASD 41.9 vs. controls 49.1; p = 0.021), Se/Pb (12.9 vs. 25.7; p = 0.002), Cu/Se (0.49 vs. 0.38; p = 0.008), and Zn/Pb (19.5 vs. 44.8; p = 0.002). The Hg/Se ratio did not differ significantly.: Children with ASD demonstrate altered porphyrin profiles and trace element imbalances, including increased Pb and disrupted Zn/Cu and Se/Pb ratios, indicating oxidative stress and impaired detoxification. Combined assessment of porphyrins and trace element ratios may provide valuable non-invasive biomarkers for environmental and metabolic disturbances in ASD.
Ključne besede: autism spectrum disorder, porphyrins, lead, heme biosynthesis, environmental toxicants, biomarkers, trace elements, ICP-MS
Objavljeno v DiRROS: 14.04.2026; Ogledov: 71; Prenosov: 36
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Povzetek: Autism spectrum disorder (ASD) is increasingly associated with microbial and metabolic disturbances, including the altered production of gut-derived uremic toxins. We investigated urinary concentrations of five representative uremic toxins—indoxyl sulfate (IS), p-cresyl sulfate (PCS), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)—in 161 children with ASD and 71 healthy controls. Toxins were measured using LC-MS/MS and were normalized to creatinine. Subgroup analyses were performed by sex, age group (2–5.9 vs. 6–17 years), and autism severity based on the Childhood Autism Rating Scale (CARS). In addition to individual concentrations, we calculated the total toxin burden, proportional contributions, and functional ratios (IS/PCS, PCS/TMAO, and IS/ADMA). While individual toxin levels did not differ significantly between groups, stratified analyses revealed that PCS was higher in girls and in severe cases of ASD, whereas IS and TMAO were reduced in younger and more severely affected children. The functional ratios shifted consistently with severity—IS/PCS declined from 1.69 in controls to 0.99 in severe cases of ASD, while PCS/TMAO increased from 12.2 to 20.5. These patterns suggest a phenolic-dominant microbial signature and an altered host–microbial metabolic balance in ASD. Functional toxin profiling may offer a more sensitive approach to characterizing metabolic disturbances in ASD than concentration analysis alone.
Ključne besede: autism spectrum disorder, uremic toxins, p-cresyl sulfate, indoxyl sulfate, metabolomics, urinary biomarkers, gut microbiota, TMAO, ADMA
Objavljeno v DiRROS: 14.04.2026; Ogledov: 74; Prenosov: 39
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Povzetek: Background: Although total 25-hydroxyvitamin D (25(OH)D) measurements may not accurately reflect functional vitamin D status, vitamin D deficiency is common in hepatocellular carcinoma (HCC). The contribution of altered vitamin D-binding protein (VDBP) and albumin to impaired bioavailability is poorly characterized in liver cancer. Methods: We measured total, free, and bioavailable 25(OH)D, VDBP, and albumin in 46 HCC patients and 87 healthy controls during winter and summer. Correlations with Child–Pugh score, Barcelona Clinic Liver Cancer (BCLC) stage, and disease aetiology were evaluated. Results: HCC patients exhibited significantly lower VDBP (177.3 ± 237.0 vs. 239.9 ± 141.9 mg/L, p < 0.001) and albumin (35.9 ± 5.4 vs. 48.0 ± 3.9 g/L, p < 0.001) compared to winter controls. Total 25(OH)D was lower in HCC (39.3 ± 22.1 nmol/L) versus summer controls (75.0 ± 22.8 nmol/L, p < 0.001) but comparable to winter controls (p = 0.061). HCC patients lacked seasonal variation in vitamin D fractions, unlike the controls. VDBP negatively correlated with free (ρ = −0.606, p < 0.001) and bioavailable 25(OH)D (ρ = −0.541, p < 0.001). Child–Pugh score correlated positively with BCLC stage (ρ = 0.378, p = 0.012) and inversely with albumin (ρ = −0.565, p < 0.001). Conclusions: Free and bioavailable vitamin D are profoundly compromised in HCC, reflecting impaired hepatic synthetic function and systemic inflammation. These fractions may serve as novel metabolic biomarkers superior to total 25(OH)D for assessing vitamin D deficiency and guiding individualized supplementation strategies in patients with liver cancer.
Ključne besede: hepatocellular carcinoma, vitamin D metabolism, 25-hydroxyvitamin D, free vitamin D, bioavailable vitamin D, vitamin D-binding protein, albumin, Child-Pugh score, BCLC staging, biomarkers
Objavljeno v DiRROS: 08.04.2026; Ogledov: 78; Prenosov: 54
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Povzetek: Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis in which inflammation plays a central pathogenic role. Endovascular revascularisation may transiently amplify inflammation due to vascular injury, but successful restoration of perfusion could reduce inflammatory burden over time. This prospective, observational, single-centre pilot study aimed to characterise the temporal dynamics of inflammatory biomarkers during the first three months following endovascular revascularisation of the lower limbs. Consecutive patients with PAD who underwent successful percutaneous femoropopliteal revascularisation at the Department of Vascular Diseases, University Medical Centre Ljubljana, Slovenia, between January 2022 and January 2024 were enrolled. Venous blood was obtained one hour before the procedure, one day afterwards, and again approximately three months later. Concentrations of high-sensitivity C-reactive protein (hsCRP), interleukins (IL-6, IL-8, IL-10), and tumour necrosis factor-alpha (TNFα) were measured. Temporal changes in biomarker levels were analysed using Friedman and Wilcoxon signed-rank tests where appropriate. Clinical outcomes were evaluated at three months and one year post-procedure and were further verified through patient telephone interviews. The observed outcomes were worsening of PAD symptoms, newly diagnosed angina pectoris, myocardial infarction, stroke, transient ischaemic attack (TIA), or death. Twenty-eight patients (median age 69 years) completed all blood samplings. IL-6 concentrations increased significantly one day after revascularisation and decreased below preprocedural levels at three months, with significant differences observed across all time points (p < 0.001). IL-10 and TNFα decreased significantly between the postprocedural and three-month measurements (p = 0.012 and p = 0.016, respectively), but not below preprocedural levels. No significant changes were observed in hsCRP or IL-8. Over a median follow-up of 732 days, 9 patients experienced worsening PAD symptoms in the treated limb, 2 developed new-onset PAD symptoms in the contralateral limb, and 1 was newly diagnosed with angina pectoris. No myocardial infarction, stroke, TIA, or death occurred. To conclude, endovascular femoropopliteal revascularisation induces distinct short-term inflammatory responses, with IL-6 showing the most pronounced peri-procedural dynamics. The observed reductions in some inflammatory biomarker levels at three months suggest that restored limb perfusion may modulate systemic inflammation. Larger studies are warranted to clarify the prognostic relevance of these biomarkers.
Ključne besede: peripheral arterial disease, biomarkers, inflammation, endovascular revascularisation, intermittent claudication, atherosclerosis
Objavljeno v DiRROS: 09.03.2026; Ogledov: 171; Prenosov: 111
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