Objectives Cigarette smoking remains a major contributor to preventable cardiovascular morbidity and mortality. While the Fagerstr & ouml;m Test for Nicotine Dependence (FTND) evaluates behavioral addiction, objective biochemical markers linking dependence severity to cardiovascular risk remain limited. This study investigated associations between serum nicotine metabolites, FTND, and Framingham Risk Score (FRS) in male smokers.Methods A cross-sectional study was performed in 104 male smokers aged 18-65 years. Nicotine dependence was assessed using the FTND. Serum nicotine, cotinine, norcotinine, and 3-hydroxycotinine levels were quantified by a validated LC-MS/MS method. Cardiovascular risk was estimated using the FRS, and correlations among metabolites, FTND scores, and smoking duration (pack-years) were analyzed.Results Nicotine metabolite concentrations across FTND dependence categories demonstrated increasing trends for cotinine and norcotinine. However, after adjustment for multiple comparisons using the Benjamini-Hochberg false discovery rate, only norcotinine levels differed significantly between FTND groups (q=0.030), with higher concentrations observed in individuals with greater dependence severity. Smoking duration expressed as pack-years showed a positive association with serum norcotinine concentrations, and this relationship remained statistically significant following FDR correction (r=0.327, q=0.008).Conclusions Norcotinine emerged as the most robust biochemical marker of nicotine dependence and cumulative tobacco exposure, linking behavioral addiction severity with long-term metabolic burden. The absence of associations between nicotine metabolites and FRS highlights the limited capacity of single time-point exposure markers to reflect multifactorial cardiovascular risk. These findings support the need for integrated behavioral and metabolic approaches in addiction assessment.

Accurate measurement of urine creatinine is essential for evaluating renal function. Although the Jaffe and enzymatic methods are routinely applied in clinical laboratories, various urinary compounds can interfere with these assays. This study investigated the effects of hemoglobin and protein positivity on creatinine measurement and partially validated a mass spectrometric (LC-MS/MS) procedure. Urine samples from 136 participants were categorized based on dipstick results into three groups: negative (n = 55), hemoglobin-positive (n = 51), and protein-positive (n = 30). Creatinine concentrations were measured using Jaffe and enzymatic methods on an Architect c16000 analyzer and by LC-MS/MS on an API 3200 system. The LC-MS/MS method demonstrated linearity between 3-350 mg/dL, intra- and inter-assay coefficients of variation of 3.2-3.8% and 1.9-2.9%, and bias values ranging from 1.1% to 18.2%. Correlations among LC-MS/MS, enzymatic, and Jaffe methods ranged from 0.981 to 0.998. Bland-Altman analysis showed mean absolute biases of 0.06 to 17.33 mg/dL (1.48-19.42%) in controls, 1.44 to 4.78 mg/dL (0.79-9.59%) in hemoglobin-positive samples, and 2.18 to 9.87 mg/dL (0.52-14.39%) in protein-positive samples. Regression analysis showed slopes closer to unity in hemoglobin- and protein-positive samples compared to controls, likely reflecting higher creatinine concentrations in these groups. Despite this apparent improvement, bias values increased, particularly in protein-positive samples. Both routine methods showed acceptable agreement with LC-MS/MS, while the enzymatic method demonstrated slightly closer agreement under these conditions. LC-MS/MS maintained highest analytical specificity. These findings highlight the importance of method selection for reliable interpretation of renal function, especially in patients presenting with hematuria or proteinuria.

BACKGROUND:Bruxism has garnered increasing attention in both clinical practice and scientific research, underscoring its significance for patient management and understanding of its pathophysiology. OBJECTIVE:This study aims to investigate the potential relationship between tryptophan metabolites and bruxism. METHODS:The patients were divided into bruxism and non-bruxism groups. The bruxism group was determined according to the bruxism and Diagnostic Criteria for Temporomandibular Disorders classifications. Patients who did not fit either classification were classified as a non-bruxism group. Demographic data of all patients, maximum clinical interincisal opening (IO), state and trait anxiety levels (STAI), perceived stress (PS) levels, Oral Health Impact Profile-14, and pain on palpation (PoP) were recorded. Laboratory findings included measurements of tryptophan and its metabolites. RESULTS:A total of 97 participants volunteered; 49 had non-bruxism, and 48 had bruxism. There were no differences between the two groups in demographic findings. In clinical findings, a difference was found between the two groups in PS (p = 0.048), IO (p < 0.01), STAI-S (p < 0.01), and PoP (p < 0.01). Regarding laboratory findings, lower kynurenine levels (p < 0.01) and higher quinolinic acid levels (p < 0.01) were found in patients in the bruxism group. CONCLUSIONS:The findings suggest a possible role of TRP metabolites in the pathophysiology of bruxism. In particular, alterations in quinolinic acid and kynurenine may provide insight into the metabolic mechanisms involved. However, these results should be interpreted with caution, and further studies are warranted to confirm and expand upon these associations. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05760482.

This study aimed to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the simultaneous quantification of pregabalin (PGB) and gabapentin (GBP) and to explore real-world pharmacokinetic variability. A bioanalytical LC-MS/MS method was validated using serum samples prepared by acetonitrile protein precipitation. Chromatographic separation was achieved on a C18 column with gradient elution and positive electrospray ionization. The validated method was applied to serum samples obtained from 65 patients, and associations between serum drug concentrations and clinical measures were evaluated. The assay demonstrated excellent linearity (R² > 0.998), acceptable precision and accuracy, recovery ranging from 96.9% to 101.5%, and matrix effects below 7%. Considerable inter-individual variability in serum concentrations was observed (PGB: median 700 ng/mL [IQR: 500-1000]; GBP: median 4500 ng/mL [IQR: 3200-5700]). No significant dose-concentration relationships were identified (PGB: ρ = 0.03; GBP: ρ = -0.08), and no significant associations were observed between serum concentrations and the clinical outcome measures assessed. In contrast, both drugs showed moderate inverse correlations with post-dose sampling interval (PGB: ρ = -0.46; GBP: ρ = -0.45). These findings indicate substantial pharmacokinetic variability of gabapentinoids under routine clinical conditions. Although no clear dose-concentration or exposure-response relationships were identified in this cohort, interpretation should be made cautiously because of non-standardized sampling conditions and the relatively narrow range of renal function among participants.

Background: Pediatric headache is a common neurological condition that adversely affects quality of life. Vitamin B12 is involved in homocysteine (Hcy) and methylmalonic acid (MMA) metabolism, and nitric oxide (NO) plays a role in neurovascular signaling. This study evaluated vitamin B12-related biomarkers and NO in pediatric migraine and tension-type headache (TTH). Methods: The study included 39 migraine, 42 TTH and 29 control. Vitamin B12 and folic acid were measured using the Roche Cobas e601, Hcy were measured with the Shimadzu LC-20 HPLC, MMA were measured by a modified LC-MS/MS method, NO were measured using the Griess method. Results: Hcy levels differed significantly between the migraine and control, as well as between the TTH and control (p<0.05). For MMA, a significant difference was observed between the TTH and control groups (p<0.05). Total nitrite and nitrate concentrations were significantly higher in patients than in controls(p<0.05). Conclusions: Although serum vitamin B12 concentrations did not show a significant difference, median MMA values were elevated in the patient groups. MMA is recognized as a biomarker of subclinical vitamin B12 deficiency, and because oxidative stress may impair the cellular function of vitamin B12, MMA measurement provides valuable information even when serum B12 levels remain within the normal range. Furthermore, endothelial damage induced by Hcy, together with chronic oxidative stress associated with the Hcy-NO pathway, may contribute to the pathogenesis of pediatric migraine and TTH. Consistent with this, the significantly higher levels of NO metabolites in patients compared with controls suggest that NO may play a role in the development of migraine and TTH in the pediatric population.

Background and Objectives: This study investigated whether capillary and intravenous sampling affect acylcarnitine and amino acid profile results analyzed by tandem mass spectrometry. Methods: The study included 120 patients either diagnosed with an inherited metabolic disease or undergoing evaluation for a suspected metabolic disorder at the Department of Pediatric Nutrition and Metabolism, Selçuk University Faculty of Medicine. Paired capillary and intravenous blood samples were collected simultaneously, applied to filter paper, and analyzed by LC-MS/MS to determine acylcarnitine and amino acid profiles. Results: Significant differences were observed between capillary and intravenous samples for several acylcarnitines, including C0, C2, C8, C8.1, C10, C10.1, C14.1, C16, and C18.1 (p < 0.05). In the amino acid profile, arginine, aspartic acid, citrulline, glutamic acid, glycine, leucine + isoleucine, methionine, tyrosine, and the methionine/phenylalanine ratio differed significantly between sampling methods (p < 0.05). Despite these differences, Cohen’s kappa analysis showed high agreement between capillary and venous samples for most parameters (78.3–100%) when categorized as low, normal, or high based on reference ranges. Additionally, no significant discrepancies were found in key diagnostic parameters among patients with specific inherited metabolic diseases. Conclusions: Although certain acylcarnitine and amino acid levels differed between capillary and intravenous samples, overall diagnostic agreement was high. However, since the study group did not include any patients with fatty acid oxidation disorders, a separate confirmatory study is needed for this condition. Larger multicenter studies involving more patients and a wider range of metabolic disorders are needed to better understand the clinical impact of sampling method on dried blood spot analyses.

ED refers to the persistent difficulty in attaining or sustaining a firm enough erection for satisfactory sexual performance. The kynurenine pathway (KP) of tryptophan metabolism is associated with reactive oxygen species production and inflammation and may be related to the pathophysiology of ED. This study aimed to analyze KP biomarker levels in ED patients and examine their potential connection to ED. 110 consecutive male patients diagnosed with ED and 60 age-matched healthy male volunteers were included. Serum KP metabolite levels were analysed using the liquid chromatography tandem mass spectrometry method (LC-MS/MS). Multivariate Firth penalized logistic regression was used to assess the independence of metabolite associations, adjusted for age, BMI, total testosterone, LH, FSH, prolactin and smoking status. Compared to the control group, ED patients showed significantly lower TRP (6,760 vs 10,600 ng/mL, p < 0.001) and KYNA levels (1.39 vs 2.19 ng/mL, p < 0.001), while KYN, 3-HK, 3-HAA and QA levels were significantly higher (p < 0.001 for all). In Firth penalized logistic regression adjusted for age, BMI, smoking status, total testosterone, LH, FSH and prolactin, all metabolite associations remained independently significant (e.g., 3-HK OR 13.44, 95

Aim: Chest pain a common complaint in the emergency department, often associated with serious cardiovascular conditions such as ischemic heart disease, pulmonary embolism, and aortic aneurysm. Rapid and accurate diagnosis is crucial. Asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, contributes to the pathogenesis of cardiovascular disease. Measuring serum ADMA and arginine levels may aid in distinguishing life-threatening conditions and in improving clinical decision-making. This study explores the diagnostic value of ADMA and arginine derivatives in patients presenting with chest pain, aiming to enhance early and effective medical intervention Materials and Methods: Blood samples were collected from each participant and analyzed for serum ADMA and arginine levels using liquid chromatography-mass spectrometry. Patients were classified based on potentially life-threatening versus benign causes of chest pain. Serum ADMA and arginine levels were compared between the patient and control groups. Results: A total of 219 participants were included in the study. For biochemical measurements, no significant differences were observed in levels of ADMA, symmetric dimethyl arginine, and NG-monomethyl-l-arginine, whereas arginine and the ratios differed significantly between groups. Conclusion: The findings offer new approaches to improve early diagnosis and treatment processes. It is anticipated that the results will determine whether the levels of ADMA and arginine can serve as clinically useful adjuncts in the management of chest pain. This could enable the rapid and accurate differentiation of potentially fatal causes, ultimately improving patient management and outcomes.

Autoimmune thyroid diseases (AITD) may lead to increased cardiovascular risk; however, the underlying mechanism for this is unclear. The aim of our study was to investigate serum asymmetric dimethylarginine (ADMA), vitamin B12, folic acid and homocysteine (HCY) levels in patients with and without AITD. A total of 180 individuals were enrolled in this study, encompassing 45 patients with Hashimoto's Thyroiditis (HT), 45 patients with Graves' disease (GD), 45 individuals with multinodular goiter (MNG) and 45 healthy controls who were admitted to Sel & ccedil;uk University Medical Faculty's Department of Endocrinology. All statistical analyses were conducted using the R Statistical Software (version 4.2.1). We found increased levels of HCY and ADMA, and decreased levels of folic acid in AITD compared to the control group (P = 0.021, P = 0.04 and P = 0.017, respectively). Vitamin B12 levels were similar between groups. HCY was negatively correlated with vitamin B12 and folic acid (r=-0.028, P = 0.002 and r=-0.368, P < 0.001, respectively). Our study revealed that a rise in ADMA and HCY levels in patients with AITD can provide insight into how AITD may contribute to endothelial dysfunction and cardiovascular risks.

Background: This study aims to identify predictive factors for pulmonary fibrosis development in COVID-19 patients by analyzing thorax CT (computed tomography) findings, serum prolidase activity, MMP-1, MMP-7, TGF-β values, laboratory findings, and demographic characteristics. Materials and methods: The investigation involved 68 patients, both male and female, aged 18 years and older, who were volunteers and had been diagnosed with confirmed COVID-19. The pulmonologist and the radiologist evaluated the thorax CT by consensus. Patients were evaluated in two categories, group 1 and group 2, based on the status of fibrotic changes, and 3-month fibrosis scores were calculated. Findings in both lungs were calculated and noted for the lobes, considering lobar spread. Correlations between quantitative parameters were assessed with Spearman’s rho correlation coefficient. Comparisons between independent samples were evaluated using either the independent sample t-test or the Mann–Whitney U test. We evaluated the relationship between categorical variables using the Pearson chi-square test and Fisher’s exact test. Results: Serum prolidase activity, MMP-1, MMP-7, and TGF-β biomarkers were not statistically significant among groups. LDH was found to be significantly high in the group with fibrotic changes. Additionally, the group with fibrotic changes also had higher levels of fibrinogen. The percentage of neutrophils, the severity of the disease, muscle–joint pain and fatigue symptoms, and the length of hospitalization stay were correlated with the total scores of fibrosis at the third month. In the group with fibrotic changes, the duration of muscle–joint pain and fatigue symptoms and the length of hospitalization were longer than in the other group. Conclusions: The group with fibrotic changes showed an increase in biomarkers. However, this increase did not reach a statistically significant level, suggesting that the third month may be an early period for these changes. The group with fibrotic changes showed high levels of LDH, one of the most important laboratory parameters of pulmonary fibrosis risk factors, along with fibrinogen, suggesting that these parameters are valuable in predicting pulmonary fibrosis. Patients with fibrotic changes can experience specific symptoms, commonly seen in COVID-19.

In obstructive sleep apnea syndrome (OSAS), changes in the levels of methylated arginine derivatives have been observed due to intermittent hypoxia. While intermittent hypoxia initially increases the activity of the enzyme dimethylarginine dimethylaminohydrolase (DDAH), thereby reducing the levels of methylated arginine derivatives, prolonged hypoxia can disrupt this mechanism and trigger vascular damage. Therefore, methylated arginine metabolites play a critical role in the pathophysiology of OSAS. This study investigates the relationship between the L-arginine-nitric oxide (NO) pathway and methylated arginine metabolites-asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and N-monomethyl-L-arginine (L-NMMA)-in newly diagnosed OSAS patients without comorbidities, aiming to evaluate their potential as diagnostic and prognostic biomarkers. This observational case-control study included a total of 122 participants, consisting of 31 healthy controls and 91 patients with OSAS. OSAS patients were stratified by disease severity into 30 mild, 30 moderate, and 31 severe cases. Serum levels of methylated arginine metabolites (ADMA, SDMA, and L-NMMA) and arginine were measured using mass spectrometry. The analyses were performed with an AB Sciex API 3200 triple quadrupole mass spectrometer (USA) equipped with an electrospray ionization (ESI) source operating in positive ion mode, coupled to a Shimadzu LC-20AD liquid chromatography system (Kyoto, Japan). Compared to the control group, OSAS patients showed statistically significant lower levels of ADMA, L-NMMA, arginine, and total methylated arginine load (TMAL) (P < .001). SDMA levels were similar across groups. In OSAS patients without comorbidities, a reduction in TMAL may suggest the activation of compensatory mechanisms in response to sleep-related intermittent hypoxia. This could reflect a shift in the arginine pathway towards enhanced nitric oxide synthesis to mitigate hypoxia-induced vasoconstriction through vasodilation. The reduced arginine levels are likely due to increased utilization, while diminished synthesis of methylated arginine derivatives (ADMA, L-NMMA) may result from this metabolic shift. These findings imply that decreased arginine and methylated arginine levels may serve as potential diagnostic markers and could aid in identifying candidates for polysomnography (PSG), which is both costly and time-consuming, thereby contributing to more efficient patient selection and reducing the overall clinical burden.

Objectives This study aims to examine the trends and distribution of research areas and methodologies in biochemistry theses over time by performing a bibliometric analysis in the CoHE database and comparing them with PubMed trends.Methods The study includes biochemistry theses from T & uuml;rkiye spanning 1969 to 2023, totalling 5,543 theses in the CoHe database. Also, the PubMed database is used to compare the world's and our country's scientific trends. Google Sheets, AppSheets and Python are used for data analysis. The study employed various bibliometric techniques like performance analysis, cluster analysis, science mapping and co-occurrence analysis.Results Although several diseases exhibited insignificant associations, pregnancy demonstrated a significant positive correlation between CoHE and PubMed trends (rho=0.455, p=0.0022). The noted negative associations for atherosclerosis (rho = -0.429, p=0.0041) and hypertension (rho = -0.470, p=0.0015) suggest that national trends in thesis production differ from international publication trends for these conditions. Furthermore, oxidant-antioxidant system studies at CoHe have held the first place for over 30 years, despite being decreasing after the 2000s and having a positive but statistically irrelevant connection with global trends (rho=0.100; p=0.873).Conclusions We propose that biochemistry studies should prioritise diseases such as atherosclerosis and osteoarthritis in parallel with the findings in our work, particularly considering increasing life expectancy. Moreover, placing increased focus on microbiota studies and the utilisation of animal models within research methodologies will be crucial for advancing our understanding in the field.

BACKGROUND.Type 2 Diabetes Mellitus (T2DM) is a primary public health concern globally, characterized by chronic hyperglycemia, insulin resistance, impaired beta-cell function. Endothelial dysfunction is a hallmark of diabetes and is exacerbated by hyperlipidemia. AIM.This study investigates the impact of hyperlipidemia on nitric oxide synthesis, arginine metabolism, and vascular health markers in T2DM. MATERIALS AND METHODS. A total of 120 participants were included in this cross-sectional, comparative study. Serum methylarginine derivatives (Asymmetric dimethyl arginine (ADMA), Symmetric dimethyl arginine (SDMA), L-N Mono-methylarginine (L-NMMA) and related metabolites (arginine, homoarginine, citrulline, ornithine) levels were measured in three groups: diabetes with hyperlipidemia (DM-HL), diabetes with normolipidemia (DM-NL), and healthy controls (HC) using API SCIEX 3200 LC-MS/MS methods. Statistical comparisons between groups were performed using IBM SPSS 26.0 to assess the influence of hyperlipidemia on these markers. RESULTS. ADMA and SDMA levels were significantly elevated in DM-HL group compared to DM-NL and HC (p=0.001, p=0.000 respectively), indicating increased endothelial dysfunction and potential dyslipidemia-induced renal or vascular impairment. Reduced arginine and homoarginine levels in diabetic groups suggest impaired nitric oxide synthesis and altered urea cycle function (p=0.013, p=0.000 respectively). Notably, the DM-HL group exhibited significantly higher L-NMMA levels (p=0.001). It disrupted metabolic ratios (e.g., SDMA/ADMA, arginine/ADMA, and homoarginine/ADMA), reflecting enhanced nitric oxide inhibition and reduced bioavailability. Hyperlipidemia significantly exacerbated these disruptions, as evidenced by altered citrulline/arginine and citrulline/ADMA ratios, underscoring its additive impact on endothelial dysfunction. CONCLUSIONS. Hyperlipidemia amplifies the adverse effects of diabetes on endothelial function by exacerbating nitric oxide inhibition, oxidative stress, and arginine metabolism dysregulation. Key biomarkers and metabolic ratios, particularly ADMA and SDMA-related indices, provide valuable insights into cardiovascular risk in this population.Therapeutic strategies targeting lipid management, arginine supplementation, and ADMA reduction could improve vascular health and mitigate cardiovascular complications in DM-HL.

Objectives This study aims to investigate the effect of smoking on the metabolism of kynurenine and thus contribute to the elucidation of the potential mechanism of cigarette smoking. Methods The study included 82 smokers and 63 nonsmokers who applied to the Family Medicine Polyclinic for routine check-ups. Sociodemographic data, routine laboratory results, Framingham risk scores (FRS), and Fagerstr & ouml;m Nicotine Dependence Test (FTND) were recorded. Serum tryptophan, kynurenine, kynurenic acid, 3-hydroxyanthranilic acid, 3-hydroxykynurenine, and quinolinic acid concentrations were measured with tandem mass spectrometry. Results Serum tryptophan levels (p=0.040) were statistically significantly lower in smokers, and the kynurenine/tryptophan ratio and serum kynurenine, kynurenic acid, quinolinic acid, 3-hydroxyanthranilic acid levels were higher (p<0.001). The correlation analysis in the smoker group showed a positive correlation between serum kynurenic acid levels and FTDN. The serum kynurenine levels were positively correlated with the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and FRS. There was a positive correlation between serum quinolinic acid levels and participants' systolic and diastolic blood pressures. Conclusions Our findings showed that tryptophan metabolism via the kynurenine pathway was induced in smokers.

Our knowledge about the possible effects of inflammatory factors, oxidative stress, and coagulation factors on the venous vessel wall in patients with chronic venous insufficiency (CVI) is limited. The role of L-Arginine and endogenous dimethylarginine in endothelial dysfunction may be essential in explaining the etiopathogenesis of venous insufficiency (VI). In this study, 35 patients diagnosed with CVI were included. Venous blood samples were collected from (A) the VI-operated leg during endovenous ablation, (B) the vena saphena magna (VSM) of a healthy leg, and (C) the antecubital vein. The L-Arginine and its metabolite levels were measured using API SCIEX 3200 LC-MS/MS methods. The statistical analysis was performed using IBM SPSS 27.0 and MedCalc 15.8. In intra-group comparison, Ornithine and LNMMA values were lower in the Leg with operated CVI compared to the Upper Extremity (p < 0.05). According to CEAP classification, healthy leg serum ornithine levels were lower in CEAP-3 compared to CEAP-2 (p < 0.05). Serum LNMMA levels in the upper extremity were higher in CEAP-3 compared to CEAP-2 (p < 0.05). Intra-group Comparison by CEAP Class, L-Arginine, and Ornithine values were lower in the CEAP-3 class operated CVI leg compared to the upper extremity (p < 0.05). The literature shows decreased circulating nitric oxide levels in patients with CVI. This study found that L-arginine and Ornithine levels were lower, especially in the operated CVI group. These findings suggest that changes in L-arginine and dimethylarginine levels may provide valuable information about the pathophysiology of venous insufficiency. Biomarkers can help monitor treatment responses and assess disease progression.

Analyzing the local pericardial fluid (PF) surrounding the heart can provide insights into the function of myocardial and pericardial epithelial cells. Kynurenine (KYN) metabolites have been associated with endothelial dysfunction and the progression of atherosclerosis. This study investigated the relationship between KYN pathway metabolites in serum and PF and the severity of coronary atherosclerosis, as assessed by the Syntax Score (SS). The study involved 101 patients (mean age: 60 years). Of the participants, 17% were female. KYN and its metabolite levels were measured using API SCIEX 3200 LC-MS/MS methods. Statistical analysis was performed using IBM SPSS 25.0. The mean serum levels of tryptophan (TRP), 3-hydroxykynurenine (3-HK), and 3-hydroxyanthranilic acid were significantly higher (p < 0.01) when compared to the mean PF levels. In the SS-low group, PF IDO activity was significantly higher than serum IDO activity (p = 0.040). In the SS-high group, PF IDO activity was significantly higher than serum IDO activity (p = 0.002). The mean 3-HK measurements showed significant differences between the SS groups (p < 0.05). In this study, higher IDO enzyme activity in the PF compared to systemic circulation suggests the presence of inflammatory activity in the pericardial endothelial cells. This research aimed to uncover the role of amino acid metabolism, which is poorly understood in atherosclerosis. Specifically, 3-HK, a metabolite from the KYN pathway, may contribute to the development of atherosclerosis. These findings indicate that localized kynurenine pathway activation in the PF may contribute to coronary atherosclerosis, highlighting its potential as a biomarker or therapeutic target.

OBJECTIVE: Lung cancer is one of the most prevalent malignancies worldwide, with 80-85% of cases diagnosed as non-small cell lung cancer (NSCLC). The majority of NSCLC patients present with advanced disease, contributing to high mortality and limited treatment options. Angiogenesis, a crucial process in cancer progression, is largely regulated by growth factors and cytokines. Vascular Endothelial Growth Factor (VEGF) is a key regulator of angiogenesis. Asymmetric Dimethyl Arginine (ADMA) inhibits endothelial nitric oxide synthase (eNOS), leading to reduced nitric oxide (NO) release and subsequent endothelial dysfunction. The aim of this study is to investigate the serum levels of ADMA, NO, VEGF and several tumor markers including Carcinoembryonic Antigen (CEA), Cancer Antigen 125 (CA 125), Neuron Specific Enolase (NSE), Lactate dehydrogenase (LDH) and Cyfra 21-1 in NSCLC patients to assess their potential role in early diagnosis, tumor invasion, and staging of the disease. METHODS: Our study consisted of 56 newly diagnosed NSCLC patients and 32 controls with similar demographic characteristics. Patients with chronic diseases and inflammatory disorders were excluded. Statistical analysis was conducted using R Statistical Software. RESULTS: In our study, compared to the control group, the serum VEGF, NO, ADMA, CA 125, CEA, Cyfra 21-1 and NSE levels were significantly higher in NSCLC group (p=0.001, p=0.013, p=0.041, p<0.001, p<0.001, p<0.001 and p=0.001, respectively). In the diagnosis of NSCLC, Cyfra 21-1 exhibited the highest diagnostic efficacy with a 71% sensitivity and 94% specificity. The combination of VEGF, CA125, and Cyfra 21-1 showed a 73% sensitivity and 100% specificity, while the combination of CA125, CEA, and Cyfra 21-1 achieved an 85% sensitivity and 91% specificity. CONCLUSION: Our study revealed that the serum concentrations of VEGF, NO, ADMA, CA125, Cyfra 21-1, CEA, and NSE were significantly elevated in patients with NSCLC compared to the control group, and that levels of Cyfra 21-1, LDH, and NSE increased with advancing TNM stage. The combination of markers distinguished NSCLC with high sensitivity and specificity. Further studies involving larger populations, including those with benign lung diseases, are needed to validate and expand upon our findings.

OBJECTIVE:The study investigates experimental brain trauma in rabbits, assessing levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and interleukin 6 (IL-6) in serum and cerebrospinal fluid (CSF) and compares these biomarkers among trauma groups. METHODS:Thirty rabbits were randomized to a control group (n=6) or to mild-, moderate-, and severe-trauma groups (n=8 each) created by dropping 200, 350, or 500 g weights, respectively, onto their skulls using a modified Marmarou impact acceleration model. CSF and venous blood samples were collected at 0, 12, and 24 hours after injury; UCH-1 L, GFAP, and IL-6 concentrations in CSF and serum were quantified by enzyme-linked immunosorbent assays, and group differences were analyzed with a Friedman test followed by Dunn-Bonferroni correction. RESULTS:Neither CSF nor serum concentration of GFAP, IL-6, or UCH-L1 differed from those of controls after mild trauma. Severe head trauma produced markedly higher GFAP and IL-6 concentrations in CSF compared with the control group (P<0.05), with both biomarkers peaking at 12 hours after injury. Serum UCH-L1 increased significantly in both moderate-trauma (peak at 12 hours) and severe-trauma groups (peak at 24 hours) compared with the control group (P<0.05), whereas no intergroup difference in CSF UCH-L1 levels was evident. CONCLUSION:Serum UCH-L1 differentiated moderate and severe trauma from controls in a rabbit model, whereas CSF GFAP and IL-6 levels reflected severe injury. Validation in larger preclinical and clinical studies is warranted.

Generalized anxiety disorder (GAD) is marked by excessive worry and cognitive difficulties, yet its neurometabolic mechanisms remain unclear. 41patients with GAD and 41 healthy controls (HC) were assessed using neuropsychological tests: Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT-A/B), Digit Span Test (DST), Verbal Fluency Test (VFT), Stroop Test, and State-Trait Anxiety Inventory (STAI). Blood samples were analyzed for kynurenine pathway metabolites including kynurenic acid (KYNA), quinolinic acid (QUIN), tryptophan (TRP), 3-hydroxykynurenine (3-HK), kynurenine (KYN), and 3-hydroxyanthranilic acid (3-HAA) via liquid chromatography–mass spectrometry (LC-MS). Patients with GAD performed significantly worse than healthy controls on executive function and attention tasks, including WCST (p = 0.014), TMT-A (p < 0.001), TMT-B (p = 0.015), and Stroop tests (p < 0.001). Patients with GAD showed elevated QUIN levels and reduced KYNA/QUIN ratios (p < 0.001), while HC group had higher 3-HK/KYN ratios (p = 0.008) than the patient group. Among anxiety measures, only state anxiety was positively correlated with KYN levels (r = 0.34, p = 0.032) in the patient group. Notably, a higher KYNA/QUIN ratio was independently associated with lower odds of GAD (p = 0.001; OR = 0.531), suggesting a potential neuroprotective role of this balance. Dysregulation in kynurenine pathway, particularly elevated neurotoxic QUIN and reduced KYNA/QUIN ratio, may lead to executive dysfunction in GAD. The KYNA/QUIN ratio emerges as a potential biomarker and therapeutic target in GAD.

Sepsis is a life-threatening condition driven by a dysregulated host immune response to infection, with cytokine overproduction contributing to organ dysfunction and high mortality. Levosimendan, a calcium sensitizer used in acute heart failure, has been proposed to exert anti-inflammatory effects, but information on its immunomodulatory effects in early sepsis remains scarce. This study aimed to investigate the dose- and time-dependent effects of levosimendan on cytokine profiles in a rat model of lipopolysaccharide (LPS)-induced sepsis. Thirty-two male Wistar albino rats were randomly assigned to four groups: sham, sepsis control, low-dose levosimendan (1 mg/kg), and high-dose levosimendan (2 mg/kg). Cytokine levels (TNF-α, IL-1β, IL-6, IL-8, IL-17, MCP-1) were measured at 5 and 10 h post-LPS administration. High-dose levosimendan significantly reduced TNF-α, IL-1β, IL-6, and MCP-1 levels by the 10th hour, accompanied by improved Murine Sepsis Scores. IL-17 and IL-6 showed biphasic responses, increasing initially and decreasing significantly later, particularly with high-dose treatment. IL-8 reduction was observed only in the high-dose group. These findings support levosimendan’s dose and time-dependent anti-inflammatory effects and suggest it may modulate both early and late-phase cytokines in sepsis. Further studies are warranted to clarify its potential role in clinical sepsis management.