Diabetes mellitus is associated with metabolic alterations, but amino-acid differences among patients with coronary artery disease (CAD) remain incompletely characterized. We screened 45 amino acids and related metabolites by diabetes status in an exploratory retrospective disease-restricted cohort (recorded diseased-vessel count ≥ 1; n = 33). Argininosuccinic acid was available for 26 patients. Comparisons used exact Wilcoxon tests, Cliff’s delta, and Benjamini–Hochberg correction. Estimated argininosuccinic acid concentrations were higher in diabetes (0.28 [0.21–0.34] vs. 0.15 [0.13–0.19] µmol/L; Cliff’s delta = 0.765; p < 0.001; q = 0.035), the only association surviving false-discovery-rate correction. All argininosuccinic acid estimates were extrapolated below the lowest calibrator and should be interpreted as semiquantitative. The diabetes coefficient remained positive in crude and age- and sex-adjusted HC3-robust models, but renal and influence analyses were imprecise. Argininosuccinic acid correlated inversely with eGFR (rho = −0.445; p = 0.023) and positively with creatinine (rho = 0.486; p = 0.012). The diabetes-by-CAD interaction was not significant (p = 0.183). These data suggest a hypothesis-generating association requiring validation with an appropriate calibration range and careful renal phenotyping.

Background/Objectives: Sodium–glucose cotransporter-2 inhibitors (SGLT2is) exert metabolic and renal effects extending beyond glycemic control, yet their relationship with circulating trace-element profiles remains poorly characterized. We investigated whether prevalent SGLT2i use was associated with differences in serum trace elements and targeted metabolites, with particular attention to renal function and the possibility of a shared multielement phenotype. Methods: In this exploratory cross-sectional study, serum trace elements and targeted amino acid metabolites were evaluated according to prevalent SGLT2i exposure. The principal clinical comparison comprised participants with diabetes mellitus (DM) receiving SGLT2i (n = 6) versus those not receiving SGLT2i (n = 10). Secondary analyses incorporated the broader three-group cohort. Because of the small exposed group and nonrandom treatment allocation, analyses were considered hypothesis-generating. Group comparisons were complemented by permutation testing, regression adjusted for recalculated uncapped 2021 CKD-EPI estimated glomerular filtration rate (eGFR), false-discovery-rate correction, inter-element correlation analysis, principal-component analysis, and influence diagnostics. Results: Among participants with DM, circulating Cu, Mg, Se, and Zn concentrations were lower in SGLT2i users, with concordant directions across complementary analyses. In the secondary analysis incorporating multiplicity correction across eight molecular outcomes, Cu (q = 0.015) and Se (q = 0.047) met the prespecified FDR threshold, whereas Mg and Zn did not (both q = 0.051). Exploratory principal-component analysis identified a first component explaining 70.8% of the variance across the four measured elements. PC1 was lower among SGLT2i-treated participants and remained associated with exposure after eGFR adjustment (β = −2.43, 95% CI −4.22 to −0.65; p = 0.008); however, this component represents statistical covariance only and should not be interpreted as evidence of a common biological mechanism or shared trace-element depletion. Conclusions: Prevalent SGLT2i use among participants with DM was associated with directionally lower circulating concentrations across several measured trace elements; however, after multiplicity correction, only Cu and Se met the prespecified FDR threshold, whereas Mg and Zn did not. The cross-sectional design, small exposed subgroup, clinical imbalance, and absence of pretreatment, dietary, urinary trace element, inflammatory, treatment duration, and adherence data preclude attribution of this pattern to SGLT2 inhibition. These findings should therefore be considered hypothesis-generating and warrant prospective validation with serial pre- and post-treatment measurements to determine whether the observed phenotype reflects pharmacological effects, treatment selection, the underlying clinical phenotype, or a combination of these factors.

Oxidative stress and inflammation are increasingly recognized as reciprocally reinforcing components of cardiovascular disease rather than independent pathological processes. Their interaction is organized through a network that includes mitochondrial dysfunction, NADPH oxidases (NOX), redox-sensitive NF-κB signaling, NLRP3 inflammasome activation, endothelial nitric oxide synthase (eNOS) uncoupling, and loss of nitric oxide bioavailability. Within this framework, phytochemicals are more appropriately viewed as modulators of endogenous redox–inflammatory signaling than as simple radical scavengers. This review critically examines the evidence linking major phytochemical classes to the Nrf2–NOX–ROS–NF-κB/NLRP3–eNOS/NO axis and evaluates how these mechanisms translate across cardiovascular phenotypes, with emphasis on mechanistic hierarchy, as simultaneous pathway changes may reflect propagation from limited upstream targets rather than direct multi-target activity. The review addresses disease-stage dependence, context-specific roles of Nrf2 and NOX isoforms, mitochondrial–NOX crosstalk, pyroptosis, endothelial dysfunction, and the translational importance of pharmacokinetics, formulation, microbial biotransformation, and drug interactions. Current evidence supports a shift from generalized antioxidant supplementation toward mechanism-matched intervention in biologically selected patients, with the greatest credibility achieved when the active molecular species, dominant mechanism, cardiovascular phenotype, disease stage, clinically relevant exposure, molecular target engagement, functional benefit, and clinical outcomes are evaluated within an integrated framework.

Background: ELAFIN (peptidase inhibitor 3, PI3) is an endogenous inhibitor of neutrophil elastase and proteinase 3, but its circulating profile in type 2 diabetes mellitus (T2DM) and cardiovascular disease remains poorly characterized. We investigated circulating ELAFIN in patients undergoing elective coronary angiography and explored its associations with metabolic, inflammatory, renal, cardiac, and angiographic phenotypes. Methods: Forty-three consecutive clinically stable patients undergoing elective coronary angiography, including nine with T2DM, were prospectively enrolled. Plasma ELAFIN was quantified by ELISA. Associations with clinical and laboratory variables were assessed using non-parametric comparisons, correlation analyses, and parsimonious multivariable regression. Discrimination analyses were considered exploratory. Results: Median ELAFIN was 5.03-fold higher in patients with T2DM than in those without T2DM (31.2 [28.3–36.2] vs. 6.2 [5.5–7.0] ng/mL; p < 0.001; Cliff’s δ = 0.85). The association remained pronounced after adjustment for age, sex, and renal function. ELAFIN was positively correlated with REG3A and creatinine, and inversely correlated with eGFR, whereas no significant associations were observed with angiographic coronary stenosis, LVEF, or NT-proBNP. Conclusions: Circulating ELAFIN was markedly elevated in T2DM and associated predominantly with renal and inflammatory characteristics rather than anatomical coronary disease or left ventricular dysfunction. Because oxidative stress and protease activity were not directly measured, their relationship with ELAFIN remains hypothesis-generating. These findings require validation in larger prospective cohorts.

Cleft lip and/or palate (CL/P) is associated with recurrent upper respiratory tract complications, yet the immunoregulatory mechanisms accompanying this defect remain insufficiently understood. This study aimed to characterize cellular and soluble parameters associated with PD-1, PD-L1, and CTLA-4 in children with CL/P and to analyze their associations with selected clinical and hematological characteristics. This single-center cross-sectional study included 32 children with CL/P and 16 healthy children as controls. Serum concentrations of sPD-1, sPD-L1, and sCTLA-4 were measured, and the percentages of cells expressing PD-1, PD-L1, and CTLA-4 within T-lymphocyte (CD3+ CD4+ and CD3+ CD8+) and B-lymphocyte (CD19+) populations were assessed using flow cytometry. We analyzed relationships between immunological and clinical parameters, as well as differences between subgroups by gender and mode of delivery. Children with CL/P exhibited significantly higher serum concentrations of sPD-1, sPD-L1, and sCTLA-4, as well as higher percentages of T and B lymphocytes expressing these immune checkpoint molecules, compared to the control group (p < 0.0001 in all cases). We observed significant associations among selected immune checkpoint-related parameters, including a positive correlation between sPD-1 and sCTLA-4 and an inverse correlation between the percentages of CD19+ PD-L1+ and CD19+ CTLA-4+ B lymphocytes. The markers clearly distinguished children with CL/P from healthy children in the study cohort; however, we found no consistent differences by gender or mode of delivery. Children with CL/P exhibited distinct cellular and soluble immune checkpoint-related profiles compared to the control group. However, given the limited sample size and the study’s cross-sectional design, these results should be considered preliminary and require confirmation in larger, independent cohorts.

Background/Objectives: Thoracolumbar burst fractures often require surgical stabilization. Although posterolateral fusion (PLF) has been traditionally used, percutaneous posterior fixation (PPF) without fusion has emerged as a less invasive alternative. However, comparative data specifically addressing PPF and PLF are limited. This study aimed to compare the radiological and perioperative outcomes of PPF and PLF for thoracolumbar burst fractures. Methods: This retrospective cohort study analyzed 61 patients with T11–L2 burst fractures (PPF, 28; PLF, 33). Radiological parameters included local and global sagittal alignment and vertebral height ratio. Fracture morphology was assessed using a structured grading system based on anterior height ratios. Perioperative variables were also assessed. Statistical significance was set at p < 0.05. Results: PPF demonstrated significant advantages in operative time (160.7 min vs. 205.8 min, p < 0.01) and blood loss (165 cc vs. 317 cc, p < 0.01), with a shorter hospitalization time. PPF achieved outcomes comparable to PLF in global alignment and anterior height restoration. The PLF group showed greater local kyphotic angle correction (−7.77° vs. −1.53°, p = 0.01), whereas the PPF group showed significantly higher postoperative posterior height ratio (p = 0.02). Changes in morphological grades, assessed using the anterior height ratio-based grading system, showed similar patterns of improvement in both groups. All implant removals were performed due to patient-reported discomfort. Conclusions: PPF yielded radiological outcomes comparable to PLF in the treatment of thoracolumbar burst fractures. The use of a morphological grading system provided a structured descriptive tool to evaluate surgical impact, though its utility remains exploratory and requires further validation.