INTRODUCTION: Objectives: Parkinson's disease (PD) is associated with systemic metabolic alterations; however, reproducibility and methodological standardization remain ongoing challenges in metabolomics research. This exploratory case–control study aimed to evaluate whether targeted plasma free amino acid profiling reveals statistically robust differences be-tween PD patients and healthy controls.
METHODS: Methods: Forty-three patients with PD and 43 age- and sex-matched healthy controls were included. Plasma free ami-no acids were quantified using a targeted triple quadrupole LC–MS/MS platform with Appendix 1 isotope-labeled inter-nal standards. Between-group comparisons were performed with appropriate statistical tests. False discovery rate (FDR) correction and effect size (Cohen’s d) calculations were applied. Compound-based KEGG pathway enrichment analysis was conducted using FDR-significant metabolites. ROC analyses were performed for signal strength assessment only.
RESULTS: Results: After FDR correction, alanine, arginine, aspartic acid, proline, taurine, threonine, and phenylalanine/tyro-sine-related ratios remained significant, with moderate-to-large effect sizes. Compound-based KEGG enrichment demonstrated significant clustering within interconnected amino acid metabolism pathways, including arginine and proline metabolism, taurine and hypotaurine metabolism, glycine, serine and threonine metabolism, and alanine, aspartate and glutamate metabolism (pathway-level FDR <0.05). Exploratory ROC analyses showed moderate signal strength for proline (AUC=0.794), taurine (AUC=0.792), and threonine (AUC=0.780).

DISCUSSION AND CONCLUSION: Conclusion: Targeted plasma amino acid profiling revealed coordinated systemic alterations in amino acid metabolism in PD within a statistically disciplined analytical framework. These findings reflect peripheral metabolic variation and should be interpreted as exploratory and hypothesis-generating. The study primarily contributes an analytically vali-dated and FDR-corrected dataset to the discussion on methodological rigor in PD metabolomics, rather than evidence of diagnostic or mechanistic inference. Validation in longitudinal, clinically well-characterized cohorts is required.

INTRODUCTION: Objectives: Insulin resistance is one of the main reasons responsible for the pathogenesis of Type 2 Diabetes Mellitus (T2DM). LEAP2 functions as an endogenous antagonist of the ghrelin receptor and is associated with insulin resistance. Irisin is a thermogenic myokine that causes energy expenditure by converting white adipose tissue into brown adipose tissue. Based on this information, we aimed to reveal the possible relationship between Leap2, irisin levels, and insulin resistance in newly diagnosed T2DM patients
METHODS: Methods: Our study consisted of 82 patients newly diagnosed with T2DM and 74 Healthy control groups who do not use any medication. Leap2 and irisin levels were measured using the enzyme-linked immunosorbent assay method.
RESULTS: Results: Compared to the control group, we found the serum irisin levels significantly lower in the diabetic group. LEAP2 levels were significantly higher in the diabetic group. In the patient group, we found a negative correlation between irisin levels and HOMA-IR and insulin levels and a positive correlation with HDL. On the contrary, we found a positive correlation between LEAP2 levels and HOMA-IR, insulin, and triglyceride levels.
DISCUSSION AND CONCLUSION: Conclusion: In patients with T2DM, LEAP2 levels are higher and irisin levels are lower than in healthy people. Various molecules have been the target of many studies on maintaining glucous homeostasis, and preventing and improving diabetes mellitus. Therefore, the role of adipomyokines in T2DM and insulin resistance should be further investigated. To our knowledge, this study will be the first report correlating T2DM, LEAP2, and irisin levels and HOMA-IR in humans.

INTRODUCTION: Psoriasis is a chronic inflammatory disease characterized by epidermal dysregulation and increased oxida-tive stress. This study investigated the protective effects of boric acid (BA) in HaCaT keratinocytes exposed to lipopoly-saccharide (LPS)-induced acute inflammatory redox stress using a simultaneous treatment protocol.
METHODS: HaCaT cells were assigned to control, LPS (10 µg/mL or 200 ng/mL), BA (20 or 100 µM), and simultaneous treatment (LPS + BA) groups. Cell viability was assessed by CCK-8 assay. Oxidative status was evaluated by malondi-aldehyde (MDA) and advanced oxidation protein products (AOPP), total sulfhydryl (TSH), and antioxidant parameters [superoxide dismutase (SOD) and catalase (CAT)]. Cell migration was analyzed by a wound healing assay.
RESULTS: LPS exposure did not cause overt cytotoxicity at 24 h but was associated with increased MDA and reduced CAT activity, indicating inflammatory oxidative stress. AOPP levels did not show a marked change under these acute conditions. Simultaneous BA administration maintained keratinocyte viability and attenuated LPS-associated lipid per-oxidation, while partially restoring antioxidant defenses and improving wound closure.
DISCUSSION AND CONCLUSION: BA modulates oxidative stress markers and supports antioxidant defense and migratory capacity in LPS-stimulated keratinocytes. These findings support BA as a candidate redox-modulating compound that warrants validation in immune-competent and in vivo models relevant to psoriasis.

INTRODUCTION: Multiple myeloma (MM) is characterized by clonal plasma cell proliferation and significant systemic im-pacts. This study aimed to evaluate the relationship between routine hemogram and biochemical parameters and disease severity markers (M-protein and β-2 microglobulin [β-2M]) to identify accessible clinical indicators of tumor load at the time of diagnosis.
METHODS: In this retrospective cross-sectional study, newly diagnosed, treatment-naive MM patients and healthy con-trols were analyzed. Statistical significance was set at a threshold (p<0.00125) using Bonferroni correction to prevent Type I errors. Multivariable logistic regression was performed to identify independent predictors of high M-protein load (≥3g/dL), and ROC analysis was used to determine the diagnostic performance of significant parameters.
RESULTS: MM patients exhibited significantly lower WBC, RBC, HCT, and PLT counts, and higher BUN and CRP levels compared to controls (p<0.001). β-2M showed significant correlations with several routine parameters; however, partial correlation and multivariable regression revealed that these associations were entirely dependent on renal function. Conversely, multivariable logistic regression identified RBC count (OR=0.383, p=0.026), eGFR, and age as significant in-dependent predictors of high M-protein load. Notably, each 1×10⁶/μL decline in RBC count was associated with a 161% increase in the risk of high disease severity. ROC analysis established an optimal RBC cut-off value of 3.73×10⁶/μL (AUC: 0.695, sensitivity: 64.1%, specificity: 69.6%) for predicting high tumor load.
DISCUSSION AND CONCLUSION: Routine laboratory data, particularly RBC count, serve as powerful indicators of MM severity at the time of initial diagnosis. Unlike β-2M, which is heavily influenced by renal status, RBC count is an independent predictor of monoclonal protein load. A baseline RBC level below 3.73×10⁶/μL should alert clinicians to a potentially high tumor load, facilitating rapid triage and treatment prioritization.

INTRODUCTION: Immunochemical fecal occult blood test has been commonly used for community-based colorectal cancer screening. There is a wide variety of fecal immunochemical test (FIT) products available in the market. However, there is limited performance information for many brands, making it essential to assess and compare the performance of these FITs. Therefore, this study aims to assess the level of agreement between eight FIT products with various cut-off values (two quantitative, six qualitative) and to evaluate the analytical performance of FITs through repeatability, interference, and stability analyses.
METHODS: This study was conducted using a total of 313 stool specimens of which 211 specimens were obtained from randomly selected patients without any dietary restrictions, and the remainder 101 specimens were spiked with hemo-globin. The fecal occult blood results from all brands were evaluated as positive or negative. The level of agreement of FITs were assessed. Repeatability, stability and interference studies of FITs were also carried out.
RESULTS: FITs were found to have fair to almost perfect agreement with kappa values ranging from 0.28 to 0.94 (all p<0.001) in the pairwise comparisons but statistically significant differences were found among most FITs by McNe-mar’s test with Bonferroni correction (adjusted α=0.0018). Repeatability and interference studies showed consistent results, but stability performance varied among FITs.
DISCUSSION AND CONCLUSION: This study showed that agreement and analytical performance among FITs vary, that statistically signifi-cant differences may be observed between some test pairs, and that agreement measures alone are not sufficient when considering test interchangeability. Test selection should be based on a comprehensive assessment that considers ana-lytical performance together with agreement results and the potential impact on laboratory and clinical management.

INTRODUCTION: Diabetic retinopathy (DR) is a major microvascular complication of diabetes characterized by vascular in-stability and oxidative stress. This study aimed to evaluate the serum levels of Fibulin-5, Selenium-Binding Protein-1 (SBP-1), and Vascular Endothelial Growth Factor-C (VEGF-C) across different clinical stages of DR and to investigate their independent pathophysiological associations.
METHODS: This cross-sectional study included 179 participants categorized into four groups: healthy controls (n=45), di-abetes mellitus (DM) without retinopathy (n=45), non-proliferative DR (NPDR) (n=45), and proliferative DR (PDR) (n=44). Serum levels were measured using ELISA. The strength of clinical associations was evaluated via ROC analysis, and independent relationships were assessed using multivariable logistic regression models adjusting for age and HbA1c.
RESULTS: Serum Fibulin-5 and SBP-1 levels were significantly elevated in the NPDR group compared to all other groups (p<0.001 for both). In multivariable regression, both Fibulin-5 (OR: 3.13, p=0.0004) and SBP-1 (OR: 1.63, p=0.004) main-tained a strong, independent association with the NPDR stage, distinct from systemic glycemic control. VEGF-C levels did not show significant differences among the groups (p=0.310).
DISCUSSION AND CONCLUSION: The stage-specific dramatic elevations of Fibulin-5 and SBP-1 in NPDR suggest a systemic reflection of a compensatory mechanism against early retinal microvascular injury and oxidative stress, which appears to diminish in the advanced PDR stage. These findings provide novel observational insights into the systemic dynamics of extracellu-lar matrix remodeling and redox stress in DR pathogenesis.

INTRODUCTION: This study aimed to investigate novel composite lipid indices, including the non-High Density Cholesterol/High Density Cholesterol ratio, Lipoprotein Combined Index, and Triglyceride-Glucose Index in adults with low vitamin B12 levels, alongside established markers such as Castelli Risk Index I, Castelli Risk Index II, and the Atherogenic Index of Plasma. By examining the relationship between vitamin B12 status and these indices, it aimed to clarify the role of low vitamin B12 levels in cardiometabolic risk.
METHODS: This retrospective study included 400 participants. Glucose and lipid levels were measured using fasting serum samples. Composite lipid parameter values were calculated according to methodologies described in the litera-ture. Results were compared between low vitamin B12 levels and control groups.
RESULTS: In this study, low vitamin B12 levels were found to be associated with low high-density lipoprotein cholesterol (p=0.035), high atherogenic plasma index (p=0.048), and high triglyceride-glucose index (p=0.043). In contrast, no sig-nificant differences were observed between the groups in terms of Castelli Risk Index I, Castelli Risk Index II, non-High Density Cholesterol/High Density Cholesterol ratio, or Lipoprotein Combined Index. The area under the ROC curve was found to be ± standard error of 0.557±0.029 [95% CI: 0.501–0.613] (p=0.048) for the Atherogenic Plasma Index and ± standard error of 0.557±0.029 [95% CI: 0.500–0.613] (p=0.049) for the Triglyceride-Glucose Index.
DISCUSSION AND CONCLUSION: In this study, B12 deficiency was associated with negative lipid indices. It is hypothesized that regular assessment of B12 levels and appropriate correction of deficiencies may help reduce cardiometabolic risk. Further pro-spective studies with comprehensive biomarkers are needed to clarify causality and clinical benefit.

INTRODUCTION: Theobromine has been reported to exhibit anti-inflammatory and antioxidant effects. However, its molec-ular impact on cancer-associated signaling pathways remains poorly understood. This research was undertaken to eval-uate the pro-apoptotic signaling effects of Theobromine on A549 lung cancer and Saos-2 osteosarcoma cells, focusing on modulation of the NF-κB signaling pathway.
METHODS: A549 and Saos-2 cells were exposed to Theobromine and the reference NF-κB inhibitor sulfasalazine at their IC₅₀ concentrations. Cell viability and IC₅₀ values were determined using the WST-1 assay. Apoptosis was quantified by An-nexin V-FITC/PI staining, and total and phosphorylated NF-κB and IKK protein levels were quantified by flow cytometry.
RESULTS: Data were analyzed using one-way analysis of variance (ANOVA). In A549 lung cancer cells, Theobromine sig-nificantly induced apoptosis (p<0.001 for late apoptotic cells). A significant reduction in both total and phosphorylated NF-κB and IKK protein levels was observed compared with controls (p<0.05 for p-NF-κB and IKK, p<0.001 for p-IKK). In Saos-2 osteosarcoma cells, similarly increased apoptotic cell populations were observed (p<0.001 for early and late apoptotic cells). The treatment also resulted in reduced total and phosphorylated NF-κB and IKK levels (p<0.05 for NF-κB, p<0.001 for p-NF-κB, p<0.01 for IKK, and p<0.0001 for p-IKK).
DISCUSSION AND CONCLUSION: This study provides the first evidence that Theobromine suppresses the NF-κB/IKK signaling pathway and promotes apoptosis in A549 and Saos-2 cancer cells. These findings suggest that Theobromine may act as a safe, natu-rally derived NF-κB modulator with potential applications as an adjuvant or chemopreventive agent in cancer therapy.