Integrated biomarkers of oxidative stress NLRP3 inflammasome and kynurenine pathway reflect disease severity and diagnostic discrimination in depression
Serum levels of kynurenine, NLRP3, and 8-OHdG are all markedly increased in depression and together offer helpful diagnostic data, implying potential utility as complementary biological markers for diagnosing depression and describing its underlying pathophysiology, notwithstanding their modest relationships with symptom severity.
Abstract
Depression is associated with dysregulation of oxidative stress and inflammatory pathways. Serum biomarkers such as 8-hydroxy-2′-deoxyguanosine (8-OHdG), NLRP3, and kynurenine may reflect these pathological processes and relate to disease severity. This study evaluated the clinical relevance of these biomarkers in patients with depression and their association with symptom severity. A total of 50 patients with depression and 50 healthy controls were assessed. Serum levels of 8-OHdG, NLRP3, and kynurenine were measured. Depression severity was evaluated using the Hamilton Depression Rating Scale (HAM-D) and Patient Health Questionnaire-9 (PHQ-9). Correlations, multiple linear regression, and multivariate logistic regression. Bonferroni and Benjamini–Hochberg corrections were applied. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. Patients with depression exhibited significantly higher levels of 8-OHdG, NLRP3, and kynurenine (all p < 0.05). Among the evaluated biomarkers, only 8-OHdG demonstrated a weak inverse correlation with PHQ-9 scores and a positive correlation with disease duration, whereas no significant associations were observed for other markers. In multivariable regression analyses, 8-OHdG showed nominal association with PHQ-9 scores; however, this relationship did not remain significant after correction for multiple comparisons. Multivariate logistic regression demonstrated independent associations of all three biomarkers with depression status without evidence of significant multicollinearity. ROC analysis showed moderate diagnostic performance for individual biomarkers, while the combined biomarker model achieved superior discrimination between patients and controls (AUC = 0.857). Serum levels of kynurenine, NLRP3, and 8-OHdG are all markedly increased in depression and together offer helpful diagnostic data. These indicators’ combined performance implies potential utility as complementary biological markers for diagnosing depression and describing its underlying pathophysiology, notwithstanding their modest relationships with symptom severity. Larger prospective trials are necessary for additional validation.
Although gastrointestinal disorders (GI) present with a diverse array of clinical symptoms, they are fundamentally linked by an underlying biological crosstalk between oxidative stress and chronic inflammation, making it exceptionally difficult to predict disease trajectory or tailor effective treatments. The study aimed to identify and validate a panel of serum- or tissue-based biomarkers that specifically correlate with the severity of inflammation and oxidative stress in patients with different GI diagnoses. This case-control study, conducted from September to December 2025, investigated inflammatory and oxidative stress biomarkers in 128 participants (88 GI patients and 40 healthy controls) at the Hospital of Digestive Diseases in Al-Najaf Al-Ashraf, Iraq. All participants underwent upper gastrointestinal endoscopy, with demographic and clinical data systematically collected. The determination of serum interleukin-6 (IL-6), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and malondialdehyde (MDA) via ELISA, alongside comprehensive biochemical profiling and Helicobacter pylori assessment. Results indicated that GI patients showed significantly higher glucose, TG, NLR, IL-6, MDA, and 8-OHdG levels and decreased hemoglobin and HDL compared to controls (p < 0.05). Specific GI disease subgroups, notably Crohn's disease and ulcerative colitis, demonstrated pronounced elevations in inflammatory and oxidative stress markers. Linear regression highlighted significant associations of 8-OHdG with various clinical and biochemical parameters. Furthermore, multinomial logistic regression identified IL-6 as a significant predictor for Crohn's disease (odds ratio [OR] = 1.34, p = 0.046), while IL-6 (OR = 1.37, p = 0.023), 8-OHdG (OR = 1.01, p = 0.024), and Nes-1 (OR = 0.61, p = 0.007) were predictive for ulcerative colitis. ROC analysis revealed excellent diagnostic performance for IL-6 (AUC = 0.96) and MDA (AUC = 0.89) in distinguishing GI patients from healthy controls. These findings emphasise the vital function of inflammatory and oxidative stress pathways in GI pathologies and suggest these biomarkers hold promise for diagnostic and prognostic applications.
I. Sharba, S. Mohammed, Jinan Mohammed Zahid· Al-Kufa University Journal f...· 0 citations
(1) Fibromyalgia syndrome (FMS) is a chronic pain disorder with a multifactorial pathogenesis involving neuroinflammation, oxidative stress, and immune dysfunction. This study aimed to evaluate serum biomarkers related to purinergic signaling, inflammasome activation, pyroptosis, and oxidative stress in patients with FMS. (2) Methods: A total of 93 patients with FMS and 93 age- and sex-matched healthy controls were enrolled. Serum levels of pannexin-1 (PANX1), purinergic receptor P2X7 (P2RX7), NLRP3, caspase-1 (CASP1), interleukin-1β (IL-1β), interleukin-18 (IL-18), gasdermin D (GSDMD), and gasdermin E (GSDME) were measured using enzyme-linked immunosorbent assays (ELISA). (3) Results: Total antioxidant status (TAS) and total oxidant status (TOS) were determined. Patients with FMS exhibited significantly increased serum CASP1, GSDME, PANX1, P2RX7, and total oxidative stress (TOS) levels, whereas GSDMD, NLRP3, IL-18, and TAS levels were significantly decreased compared with controls (all p < 0.05). No significant differences were observed in IL-1β levels. Receiver operating characteristic analysis demonstrated exploratory discriminatory performance within this case–control cohort for CASP1 and TAS (AUC = 0.898), followed by TOS (AUC = 0.849) and P2RX7 (AUC = 0.757). (4) Conclusions: These findings indicate alterations in circulating biomarkers related to purinergic signaling, inflammasome-associated pathways, pyroptosis-related proteins, and oxidative stress in patients with FMS. These alterations may contribute to the pathophysiology of FMS and provide a foundation for future mechanistic studies investigating their potential as biomarkers and therapeutic targets.
E. Hayta, Tuğba Ağbektaş, Gonca Kabak et al.· International Journal of Mol...· 0 citations
Background and Objectives: Oxidative stress and chronic inflammation are closely interconnected processes involved in colorectal cancer (CRC) development and progression. However, the relationships between oxidative stress biomarkers, emerging hematological inflammatory indices, clinicopathological characteristics, and survival outcomes remain insufficiently characterized. This study evaluated circulating levels of 8-epi-prostaglandin F2α (8-epi-PGF2α), malondialdehyde (MDA), and superoxide dismutase 1 (SOD1), together with conventional and novel inflammatory indices, including the mean corpuscular volume-to-lymphocyte ratio (MCVL) and cumulative inflammatory index (IIC), in patients with CRC. Materials and Methods: This prospective observational study included 140 patients with histologically confirmed CRC and 40 healthy controls. Serum concentrations of 8-epi-PGF2α, MDA, and SOD1 were measured by ELISA, and hematological inflammatory indices were calculated from complete blood counts. Associations with clinicopathological characteristics were evaluated using non-parametric analyses with correction for multiple testing where appropriate. Spearman correlations with false discovery rate correction were used to assess oxidative–inflammatory associations. Prognostic analyses included 24-month time-dependent receiver operating characteristic (ROC) analysis accounting for censoring, Kaplan–Meier analysis, and Cox proportional hazards regression for overall survival (OS) and progression-free survival (PFS). Results: CRC patients exhibited significantly higher serum levels of 8-epi-PGF2α (p = 0.016), MDA (p < 0.001), and SOD1 (p < 0.001) than controls. Oxidative stress biomarkers differed significantly across TNM stage, nodal status, and histological grade, although the observed patterns were not uniformly progressive with disease stage. After false discovery rate correction, MDA retained significant correlations with multiple hematological inflammatory parameters, whereas SOD1 showed a more restricted correlation profile and 8-epi-PGF2α showed no significant correlations. At 24 months, MDA demonstrated the highest time-dependent discrimination for OS (AUC = 0.920; bootstrap 95% CI: 0.834–0.978), whereas its discrimination for PFS was modest (AUC = 0.636; bootstrap 95% CI: 0.487–0.773). High MDA, defined by the internally derived 24-month threshold, was associated with shorter PFS after adjustment for age, sex, and TNM stage (HR = 2.49, 95% CI: 1.29–4.80; p = 0.006) and, separately, metastatic status (HR = 2.40, 95% CI: 1.22–4.72; p = 0.011). However, when modeled continuously, MDA was no longer significantly associated with PFS after multivariable adjustment. Conclusions: CRC was associated with increased circulating oxidative stress biomarkers, with MDA showing the most consistent relationships with systemic inflammatory parameters and survival outcomes. Its prognostic association with PFS was dependent on the modeling approach, while its high discrimination for 24-month OS should be interpreted cautiously because of the limited number and metastatic restriction of death events. These findings identify MDA as a promising candidate oxidative–inflammatory marker warranting external validation rather than an independently established prognostic biomarker.
R. Marinescu, Daniela Marinescu, A. Ciurea et al.· Medicina· 0 citations
Oxidative stress and systemic inflammation are considered key mechanisms linking obstructive sleep apnea (OSA) to cardiovascular disease. This study aimed to investigate the relationships among oxidative stress, nitrosative stress, inflammatory biomarkers, and echocardiographic alterations in OSA. This cross-sectional observational study included 72 adults with OSA, classified according to disease severity as mild, moderate, or severe. Clinical characteristics and echocardiographic parameters were assessed. Oxidative stress biomarkers—malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), nitric oxide (NO), oxidative stress index (OSI), and paraoxonase-1 (PON1); the nitrosative stress marker 3-nitrotyrosine (3-NT), inflammatory biomarkers—interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α); and N-terminal pro-B-type natriuretic peptide (NT-proBNP)—were determined using spectrophotometric and ELISA methods. Correlation and regression analyses were performed to evaluate associations between oxidative stress and inflammation. No significant differences in echocardiographic parameters, oxidative stress biomarkers, inflammatory markers, or NT-proBNP concentrations were observed across OSA severity categories (all p > 0.05). Patients with diabetes mellitus exhibited larger left and right atrial diameters and higher pulmonary artery systolic pressure values compared with non-diabetic patients (all p < 0.05). Significant positive correlations were identified between IL-6 and MDA (ρ = 0.364, p = 0.002), TOS (ρ = 0.259, p = 0.029), and OSI (ρ = 0.257, p = 0.030). The nitrosative stress marker 3-NT was also positively correlated with MDA, TOS, and OSI (all p < 0.05). In multivariable regression analyses adjusted for age, body mass index, and diabetes mellitus, MDA remained independently associated with IL-6 concentrations (B = 1.776, 95% CI 0.110–3.442, standardized β = 0.271, p = 0.037). Similarly, OSI remained independently associated with IL-6 (B = 0.043, 95% CI 0.003–0.083, standardized β = 0.277, p = 0.034). OSA severity was not associated with significant differences in oxidative stress, inflammatory, or echocardiographic parameters. However, oxidative stress biomarkers were strongly interrelated and remained significantly associated with IL-6 concentrations, suggesting a potential link between oxidative stress and systemic inflammation in patients with OSA. These findings support further investigation of oxidative stress pathways as biomarkers of disease-related biological activity in OSA.
Crina Veronica Zinveliu (Bercian), D. Măgureanu, R. Pop et al.· International Journal of Mol...· 0 citations
BACKGROUND
Aberrations in neuro-immune, metabolic, and oxidative stress (NIMETOX) pathways are implicated in major depressive disorder (MDD). First-episode simple dysmood disorder (FE-SDMD) without metabolic syndrome offers a unique model to investigate early lipid alterations using a systems biology approach.
METHODS
Plasma samples were collected from 88 university students (44 FE-SDMD, 44 healthy controls). Participants underwent psychiatric assessments, including adverse childhood experiences (ACEs), negative life events (NLEs), depression, anxiety, suicidal behaviors, and insomnia. Untargeted lipid profiling was performed using LC-QTOF-MS, while indices of oxidative and nitrosative stress (ONS) and lecithin-cholesterol acyltransferase (LCAT) activity were assessed. Data was analyzed using machine learning approaches with recursive feature elimination and cross-validation.
RESULTS
FE-SDMD was characterized by increased ceramides (CER), diacylglycerides (DAG), triacylglycerides (TG), sphingomyelins (SM), bis-monoacylglycerol phosphates (BMP), cholestone, and fatty-acyl amino acids (FAAA). DAG, CER, and BMP were the strongest predictors of depression severity and physiosomatic symptoms, whereas cholestone, CER, and SM predicted suicidal behaviors. These lipid modules, together with lowered LCAT and increased ONS, explained substantial variance in depression severity (46.4%), physiosomatic symptoms (42.4%), cognitive-affective symptoms (37.9%), suicidal behaviors (30.1%), insomnia (32%), and anxiety (19.5%). ACEs and NLEs were strongly associated with CER (p < 0.001), DAG (p < 0.01), and cholestone (p < 0.01), revealing coordinated lipidomic networks within a systems biology framework.
CONCLUSION
Early-stage MDD is characterized by lipid dysregulations, which are linked to psychosocial stress exposure, oxidative stress and attenuated reverse cholesterol transport. These lipid modules identify biologically functional pathways associated with early disease and may inform the development of future therapeutic strategies.
V. Sirivatanapa, Pannipa Janta, A. Almulla et al.· Journal of Affective Disorde...· 0 citations
The research showed that the GM and their predicted metabolic pathways in patients with MDD were closely related to cognitive function and peripheral blood indicators, and that differences in these factors may manifest as oxidative stress and inflammation.
He-hua Li, Baoyuan Zhu, Yuanyuan Huang et al.· Frontiers in Microbiology· 0 citations