Background: Including Chronic Myeloid Leukemia (CML) patients with deep molecular responses (MR4.5) and those with suboptimal responses provides valuable insights into treatment-associated metabolic changes. This study aimed to characterize the metabolomic alterations associated with CML and identify potential biomarkers for treatment response, particularly in patients achieving a deeper molecular response versus those with poorer responses. Methods: Plasma samples were collected from 51 chronic-phase CML patients and 24 healthy controls. CML patients were classified into two groups based on molecular responses: T1 (BCR-ABL1 IS ≤ 0.0032%) and T2 (BCR-ABL1 IS > 0.0032%, 1.5 included glutamate, hypoxanthine, and D-galactonic acid. In the T2 group, significant increases in malate and 5-aminoimidazole-4-carboxamide ribonucleotide were observed, reflecting disruptions in purine metabolism, the tricarboxylic acid cycle, and amino acid metabolism. The pathway enrichment analysis highlighted significant alterations in CML energy metabolism, nucleotide synthesis, and amino acid biosynthesis. Conclusions: CML patients exhibit pronounced metabolic changes, particularly in energy and nucleotide metabolism, which are linked to treatment response. These findings provide novel insights into CML biology and suggest potential biomarkers for monitoring treatment efficacy and predicting outcomes and therapeutic targets for improving treatment outcomes and overcoming tyrosine kinase inhibitor resistance.

Background: Platelet-rich plasma (PRP) is a widely used therapeutic product in musculoskeletal treatments due to its regenerative and anti-inflammatory properties. However, the lack of standardization in PRP preparation protocols hampers clinical consistency. Methods: In this study, the metabolic profiles of 10 different PRP types were compared using untargeted metabolomics via Q-TOF LC–MS. PRP-G and PRP-S were prepared from six donors to assess inter-individual variability, while the remaining types were obtained from a single donor to isolate the impact of preparation method alone. Multivariate analyses, VIP scores, and pathway enrichment analyses were conducted. Results: PRP formulations exhibited distinct metabolic differences associated with inflammatory signaling, redox homeostasis, steroid metabolism, energy production, and platelet activation. Samples from both single- and multi-donor groups showed high intra-group similarity, indicating that preparation method is a major determinant of PRP’s biochemical composition. Conclusion: Metabolomic profiling reveals that even minor differences in PRP preparation protocols can lead to significant biochemical changes that may affect therapeutic outcomes. This study highlights the need for standardized, indication-specific PRP products and underscores the value of metabolomic analysis in guiding optimal formulation selection in clinical practice.

Background/Objectives: The differential diagnosis between primary polycythemia vera (PV) and secondary polycythemia (SP) presents significant clinical challenges owing to substantial phenotypic overlap. This investigation utilized untargeted metabolomic approaches to elucidate disease-specific metabolic perturbations and evaluate the metabolic consequences of cytoreductive therapeutic interventions. Methods: Plasma specimens obtained from PV patients (n = 40) and SP patients (n = 25) underwent comprehensive metabolomic profiling utilizing liquid chromatography–mass spectrometry (LC-MS) platforms. Multivariate statistical analyses, including principal component analysis (PCA), were employed in conjunction with pathway enrichment analyses to characterize disease-associated metabolic dysregulation. Additionally, receiving treatment (tPV) (n = 25) and not receiving treatment (ntPV) (n = 15) PV patients were compared to assess therapeutic metabolic effects. Results: Comprehensive metabolomic analysis identified 67 significantly altered metabolites between PV and SP patients, with 36 upregulated and 31 downregulated in PV. Key upregulated metabolites in PV included thyrotropin-releasing hormone, 3-sulfinoalanine, nicotinic acid adenine dinucleotide, and protoporphyrin IX, while 4-hydroxyretinoic acid and deoxyuridine were notably downregulated. Pathway enrichment analysis revealed disruptions in taurine, glutamate, nicotinate, and cysteine metabolism in PV. ntPV patients exhibited higher glucose and octanoyl-CoA levels compared to treated patients, indicating the normalization of glucose and fatty acid metabolism with cytoreductive therapy. ntPV was also associated with altered B-vitamin metabolism, including decreased nicotinic acid adenine dinucleotide and increased nicotinamide ribotide levels. Cross-comparison analysis revealed overlapping pathway enrichment in glutamate metabolism, nicotinate and nicotinamide metabolism, and cysteine metabolism between both comparisons. Conclusions: This study demonstrates that PV and SP exhibit fundamentally distinct metabolic signatures, providing novel insights into disease pathogenesis and potential diagnostic biomarkers. The identification of oxidative stress signatures, disrupted energy metabolism, and altered B-vitamin cofactor pathways distinguishes PV from SP at the molecular level. Cytoreductive therapy significantly normalizes metabolic dysregulation, particularly glucose and nucleotide metabolism, validating current therapeutic approaches while revealing broader systemic treatment effects. The metabolic signatures identified, particularly the combination of deoxyuridine, thyrotropin-releasing hormone, and oxidative stress metabolites, may serve as complementary diagnostic tools to traditional morphological and molecular approaches. These findings advance our understanding of myeloproliferative neoplasm pathophysiology and provide a foundation for developing metabolically targeted therapeutic strategies and precision medicine approaches in PV management.

Background: Distinguishing between osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PsA) remains challenging despite different underlying mechanisms. Synovial fluid reflects metabolic changes within affected joints, yet comprehensive metabolomic comparisons across these conditions are limited. We aimed to identify disease-specific metabolic signatures in synovial fluid that could improve differential diagnosis and reveal therapeutic targets. Methods: We collected synovial fluid from 39 patients (20 OA, 5 RA, and 14 PsA) during routine knee arthrocentesis between January 2023 and February 2024. Following metabolite extraction, we performed untargeted metabolomic profiling using quadrupole time-of-flight liquid chromatography–mass spectrometry (Q-TOF LC/MS). Data underwent multivariate statistical analysis, including principal component analysis (PCA) and partial least squares–discriminant analysis (PLS-DA), to identify discriminatory metabolites. Results: While unsupervised analysis showed overlap between groups, supervised PLS-DA achieved clear metabolic separation. RA samples showed elevated itaconic acid, indicating inflammatory macrophage activation, and increased O-acetylserine, suggesting altered one-carbon metabolism. Hypoxanthine was decreased, which reflected severe metabolic stress. PsA exhibited the unique elevation of 4,4-dimethylcholestane and 2-oxoarginine. These metabolites have previously been unreported in this disease. OA demonstrated increased hippuric acid and indoleacetic acid, which are both gut microbiota products, supporting the gut–joint axis hypothesis. Conclusions: Each arthritis type displayed distinct metabolic fingerprints in synovial fluid. Candidate discriminatory metabolites, including gut-derived metabolites in OA and specific lipid alterations in PsA, open new diagnostic and therapeutic avenues. Given the limited RA sample size (n = 5), RA-related results should be viewed as exploratory and requiring validation in larger independent cohorts. These metabolites may, after rigorous validation in larger and independent cohorts, contribute to multi-metabolite biomarker panels for earlier diagnosis and to the rational design of targeted therapeutics addressing disease-specific metabolic disruptions.

Background The etiology of Parkinson’s disease (PD) is not well known and there is increasing evidence that oxidative stress also plays an important role in its pathogenesis. Salusins alpha (salusin-α) and beta (salusin-β) affect the central nervous system, vasculature, and kidneys to increase the inflammatory response in endothelial cells, stimulate oxidative stress, and increase monocyte–endothelial adhesion. Neuroinflammation and oxidative stress play roles in the etiopathogenesis of PD. Purpose To investigate whether salusin-α and -β are related to PD and whether they are correlated with the development of atherosclerosis, body mass index, disease duration, and the Parkinson’s Hoehn and Yahr stage. Results The low-density lipoprotein cholesterol (LDL-C), total cholesterol, and salusin-β levels were significantly lower and age was significantly higher in Parkinson patients compared to healthy controls (ρ < 0.005). We found a negative linear correlation between salusin-β and the Hoehn and Yahr stage (ρ < 0.001, r = –0.515) in the patients. Conclusions There was a relationship between salusin-β and PD and a correlation between the salusin-β levels and Parkinson’s stage. A possible underlying disease mechanism is an increase in oxidative stress and decrease in neuroprotective effects due to low salusin-β levels. Therefore, the effects of salusin-β in treating Parkinson disease should be evaluated. Further studies are needed to understand the effects of salusin-β treatment on preventing or slowing the course of PD.