Metabolites

Background/Objectives: This study examined urinary cholanoid profiles in a descriptive case series evaluated for suspected inborn errors of bile acid synthesis (IEBAS) or unexplained cholestasis. Methods: Urinary excretion of 66 bile acid metabolites was measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS), and concentrations were interpreted as semi-quantitative estimates. In addition, cholesterol, cholestanol, and 7-dehydrocholesterol were analyzed by gas chromatography–mass spectrometry (GC-MS). Results: Five patients had genetically confirmed IEBAS: 3β-hydroxy-Δ5-C27-steroid dehydrogenase (HSD3B7) deficiency in 2 patients and cerebrotendinous xanthomatosis (CTX) in 3 patients. Two patients were subsequently diagnosed with biliary atresia and progressive familial intrahepatic cholestasis type 1. Other patients remained without a definitive etiological diagnosis. Of the two patients with genetically confirmed HSD3B7 deficiency, patient 1 showed a predominance of 3β-hydroxy-Δ⁵ bile acids (63.9% of total urinary bile acids), including sulfated dihydroxy-, glycine-conjugated dihydroxy-, and trihydroxy-Δ⁵ species. Patient 2 had an atypical urinary bile acid profile, with the 3β-hydroxy-Δ⁵ fraction dominated by a monohydroxy species. CTX patients had profiles with a different bile acid group composition; hydroxylated bile acids were reported in 2 patients, whereas no numerical result was reported for 1 patient. The 3β-hydroxy-Δ⁵ bile acid levels in 1 CTX patient were within the observed control range. Two patients also had differential profiles for hydroxylated and 3β-hydroxy-Δ⁵ bile acids, which provided biochemical findings for further etiological evaluation. The species assigned to glycoursodeoxycholic acid predominated in the urinary profiles of the five patients receiving ursodeoxycholic acid. Conclusions: Urinary cholanoid profiling may provide complementary biochemical information alongside the available clinical and genetic findings in the evaluation of suspected IEBAS.

Exercise-induced fatigue refers to the reversible decline in neuromuscular function during physical activity, whose immune–metabolic regulatory mechanisms remain incompletely understood. Recent studies have revealed that B cells can regulate hepatic glutamate metabolism via secretion of transforming growth factor-β1 (TGF-β1), thereby influencing mitochondrial function in skeletal muscle, revealing a novel immune–metabolic pathway relevant to exercise-induced fatigue. This review synthesizes current evidence on immune regulation in exercise-induced fatigue, centering on the TGF-β1-driven glutamate axis linking the liver and skeletal muscle, cross-organ signaling, and hypotheses of central fatigue. We also discuss targeted interventions along this pathway to inform future basic research and clinical management of exercise-induced fatigue.

Background: Preeclampsia (PE) is a multisystem pregnancy disorder associated with endothelial dysfunction, inflammation, and coagulation abnormalities. This study evaluated the fibrinogen-to-albumin ratio (FAR), platelet-to-albumin ratio (PAR), and creatinine-to-albumin ratio (CrAR) in relation to preeclampsia severity. Methods: This single-center retrospective case–control study included 205 pregnant women: 104 healthy controls, 70 patients with non-severe PE, and 31 with severe PE. Clinical, obstetric, neonatal, and laboratory data were reviewed. Group comparisons, receiver operating characteristic (ROC) analysis, and logistic regression adjusted for maternal age, body mass index, and gestational age at sampling were performed. Results: Fibrinogen and FAR were significantly higher in severe than in non-severe PE. Fibrinogen showed an area under the curve of 0.685, with 67.7% sensitivity and 58.6% specificity at a cut-off of 5.05 g/L. FAR showed an area under the curve of 0.657, with 67.7% sensitivity and 64.3% specificity at a cut-off of 0.143. Both fibrinogen and FAR remained independently associated with severe PE after adjustment for maternal age, body mass index, and gestational age at sampling. FAR did not demonstrate superior discriminatory performance compared with fibrinogen alone. PAR did not differ significantly among groups, while CrAR was higher in preeclampsia than in controls but did not discriminate severe disease. Conclusions: Fibrinogen and FAR were associated with severe PE but demonstrated only modest discriminatory performance. FAR did not outperform fibrinogen alone, and its incremental value beyond fibrinogen remains uncertain. Therefore, these findings should be considered exploratory and do not support the use of FAR or fibrinogen as standalone tools for clinical screening, risk stratification, or decision-making. Further prospective, multicenter studies are needed to determine whether these markers provide clinically meaningful value within broader multimodal assessment models.