INTRODUCTION: Angiogenesis-associated disease conditions are often treated with anti-angiogenic therapy. Many of the anti-angiogenic agents approved as adjuvant cancer therapy target the vascular endothelial growth factor (VEGF) axis, as VEGF signaling is regarded as the primary angiogenesis promoter. These drugs are expected to enhance immunity, antagonizing the immunosuppressive functions of VEGF, and to control angiogenesis. Despite a mechanistic rationale that strongly supports their benefits, anti-VEGF agents have shown limited success rates in most cases, along with an association with hypertensive side effects. This article briefly reviews the approved anti-VEGF agents and offers a possible explanation for their limitations.

METHODS: PubMed and Scopus databases were searched with the corresponding keywords (such as anti-VEGF), and the relevant knowledge was collected. The included studies were limited to these, which report indications, responses, and side effects. In addition to the review, HuH7 and HEK293T cells were subjected to chemical induction of hypoxia by means of treatment with cobalt chloride (CoCl₂). This treatment induced hypoxia inducible factor 1 alpha (HIF-1) under normoxic conditions. Target protein levels were then assessed with immunoblotting to confrm the review results.
RESULTS: The results support the fact that both VEGF and endothelin-1 (ET-1) levels are elevated in response to hypoxia.
Consequently, the modulation of the proangiogenic and vasodilatory effects of the VEGF axis by anti-VEGF agents is anticipated to have an incomplete impact on angiogenesis, while resulting in hypertensive complications due to the ongoing proangiogenic activity and unopposed vasoconstrictive efects of endothelin-1.
DISCUSSION AND CONCLUSION: Given the uncertainty regarding the capacity of anti-VEGF therapy to concurrently inhibit ET-1, the dual antagonism of VEGF and ET-1 appears to be the preferred approach for effective management of angiogenesis-related pathologies. Additional studies are necessary to validate this conclusion.

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. Urokinase-type plasminogen activator (uPA), which is encoded by the PLAU gene, is a serine protease involved in the degradation of the extracellular matrix. Increasing evidence indicates that PLAU is overexpressed in various cancers and is associated with poor prognosis, making it a potential biomarker for cancer. However, its potential role in HCC remains unclear. Therefore, this study aimed to investigate the role of PLAU and related microRNAs in HCC using multiple bioinformatics tools.
METHODS: PLAU expression was evaluated using the TNMplot and GEPIA2 databases. Promoter methylation levels were assessed through UALCAN. Survival analysis (overall survival (OS) and recurrence-free survival (RFS) rates), was conducted using the Kaplan-Meier Plotter. Protein-protein interaction networks were examined with STRING. Target miRNAs were identified using TargetScan 8.0. Differential expression, survival analysis, and coexpression of miRNAs were investigated using ENCORI.
RESULTS: PLAU expression was signifcantly upregulated in liver hepatocellular carcinoma (LIHC) compared to normal tissues (p<0.05). Promoter methylation level of PLAU was significantly increased (hypermethylation) in LIHC tissues (p=5.43×10–¹²). Elevated PLAU expression was not associated with OS (p=0.16) and RFS (p=0.28) rates. hsa-miR-181a-5p, hsa-miR-181b-5p, hsa-miR-181c-5p, and hsa-miR-181d-5p were positively correlated with PLAU in LIHC tissue (p<0.05). The hsa-miR-181a-5p and hsa-miR-181b-5p were up-regulated in LIHC (p<0.05).
DISCUSSION AND CONCLUSION: In conclusion, our study highlights the potential role of PLAU and its related miRNAs (hsa-miR-181a-5p and hsa-miR-181b-5p) in HCC. However, elevated PLAU expression did not correlate with survival rates, indicating its involvement in tumor development but no prognostic signifcance. Further applicable studies are needed on this subject.

INTRODUCTION: The microtubule-associated protein tau, responsible for stabilizing microtubules, plays a role in the pathology of neurodegenerative diseases called tauopathies, including Alzheimer's disease. In Alzheimer's disease, neurofibrillary tangle formation is observed as a result of tau hyperphosphorylation. Although it is known that tau protein plays a role in many cellular processes, all of its functions have not yet been elucidated. The inverse relationship between Alzheimer's disease and cancer has been a topic of research that has attracted attention in recent years. In addition, the role of tau protein in cancer has also gained importance with the determination of its direct relationship with DNA. In particular, the negative correlation between Alzheimer's disease and cancer points to two extremes of a common mechanism. Discovering a common molecule or pathway will allow understanding the cause of both diseases and developing treatments.
METHODS: In this study, we obtained a cell model that mimics cancer metabolism by creating aerobic glycolysis-like conditions with glucose repression in S. pombe cells heterologously expressing human tau protein. We examined tau protein expression and phosphorylation (S262, S396 and S404) and various cellular processes (glucose metabolism, stress response, ER stress, autophagy, 20S proteosome activity, intracellular oxidation) at the molecular level in model cells.
RESULTS: Under aerobic glycolysis-like conditions, we observed an approximately 2-fold increase in tau protein expression. In addition to this increase, we determined that the amount of phosphorylation at S396 residue of tau protein was decreased, while phosphorylation at S262 and S404 residues was increased.
DISCUSSION AND CONCLUSION: These fndings suggest a potential divergence in tau regulation under altered metabolic conditions, warranting further investigation.

INTRODUCTION: Mitochondrial gene networks constitute a fundamental subsystem of cellular homeostasis, integrating bioenergetic, metabolic, and signaling functions. In cancer, the rewiring of these networks represents a critical mechanism of metabolic adaptation, enabling tumor cells to sustain growth and survival under diverse microenvironmental constraints. To systematically characterize these alterations, we analyzed transcriptomic data from The Cancer Genome Atlas (TCGA) with a specific focus on mitochondrial genes, aiming to uncover cancer-type-specific patterns of differential expression and their potential biological implications.
METHODS: Transcriptomic data from The Cancer Genome Atlas (TCGA) were analysed to identify diferential expression patterns in mitochondrial genes. Weighted Gene Coexpression Network Analysis (WGCNA) was applied to detect coexpressed gene modules. The biological relevance of these modules was assessed through functional enrichment analysis and survival modelling using Cox regression and Kaplan–Meier estimations. Dimensionality reduction techniques including PCA and UMAP were used to evaluate module-driven clustering patterns across cancer types.
RESULTS: Seven mitochondrial gene modules were identifed, six of which demonstrated signifcant associations with specific cancer types. Modules ME2, ME4, ME5, ME6, and ME7 were associated with improved overall survival, while ME3 correlated with poorer prognosis. Functional enrichment analyses revealed distinct mitochondrial processes including oxidative phosphorylation, apoptosis, fatty acid β-oxidation, and ketone body metabolism. Dimensionality reduction analyses supported the presence of module-specifc expression patterns with cancer-type-dependent clustering.
DISCUSSION AND CONCLUSION: The observed cancer-type-specific expression and prognostic associations of mitochondrial gene networks reflect their central involvement in the metabolic flexibility of tumors. By underscoring the clinical and biological significance of mitochondrial subsystems, these findings suggest that they may serve not only as prognostic markers but also as promising targets for therapeutic modulation.

INTRODUCTION: The aim was to investigate the efects of cinnamon on the kidney tissue serum endoplasmic reticulum (ER) stress marker, reticulone (RTN)1A, receptor for advanced glycation end products (RAGE) and the lipid peroxidation indicator, malondialdehyde (MDA) in an experimental diabetes mellitus (DM) rat model.
METHODS: Twenty-eight male Wistar Albino rats (six months old and weighing 350–400 g) were divided equally into four groups: 1) Control group - citrate buffer (0.2 M, pH 4.4; ip); 2) Cinnamon group - cinnamon (600 mg/kg/day, orogastric tube); 3) DM group -STZ (35 mg/kg, ip); and 4) DM + cinnamon group; Cinnamon and STZ were given at the same doses and route as in Groups 2 and 3, respectively. At the end of the 12-week experiment period, serum, urine and kidney tissue samples were taken from all groups. Serum RTN 1A, RAGE, MDA, urea, blood urea nitrogen (BUN), creatinine levels andkidney tissue RTN 1A, RAGE and MDA levels were measured.
RESULTS: Our biochemical results showed that there was a statistically signifcant decrease in RAGE and MDA levels in the DM + cinnamon group compared to the DM group (p<0.05). In addition, the decrease in serum urea, BUN, and creatinine levels in the DM + cinnamon group was also remarkable (p<0.05). Althought histologically no widespread necrosis was observed, cortical interstitial vascular dilatation was observed in DM+cinnamon group.
DISCUSSION AND CONCLUSION: Cinnamon was efective in reducing markers of oxidative stress and ER stress including RAGE and MDA, in kidney tissue in an animal model of diabetic nephropathy.

INTRODUCTION: Crimean-congo hemorrhagic fever (CCHF) is a viral disease characterized by thrombocytopenia and systemic inflammation. In this study, we evaluated the role of platelet-normalizing biomarkers as diagnostic and prognostic indicators of CCHF.
METHODS: This study included 60 patients with CCHF and 30 age-/sex-matched healthy controls. Biochemical parameters, including aspartate aminotransferase, alanine aminotransferase (ALT), gamma-glutamyl transferase, alkaline phosphatase, C-reactive protein and interleukin-6 (IL-6) levels were measured using photometric or electrochemiluminescence methods (Roche Cobas 8000, c702 and e801). Coagulation parameters’ levels; activated partial thromboplastin time, international normalized ratio, fibrinogen, and D-dimer were determined using Roche Cobas t511. These parameters were expressed as ratios to platelet count (Plt). Comparisons were performed between the CCHF cohort and control group. Subgroup analyses evaluated associations with intensive care unit (ICU) admission and mortality risk.
RESULTS: Statistically signifcant diferences were observed between CCHF patients and healthy controls in all parameters (p<0.05). Patients admitted to the ICU or those who did not survive exhibited a significant increase in all platelet-normalized ratios (p<0.05), except ALT/Plt. ROC analysis revealed that IL-6/Plt (AUC=0.998, cut-off>0.018, sensitivity=98.3%, specificity=100%) and D-dimer/Plt (AUC=0.992, cut-off>0.002, sensitivity=95%, specificity=96.7%) had the highest diagnostic accuracy for CCHF. Furthermore, IL-6/Plt and D-dimer/Plt ratios also showed high predictive accuracy for predicting the need for ICU admission and mortality risk.
DISCUSSION AND CONCLUSION: Platelet-normalized biomarkers, particularly IL-6/Plt and D-dimer/Plt, demonstrate strong diagnostic and prognostic potential for CCHF. Their inclusion in clinical protocols could improve early detection, risk assessment and treatment decisions for CCHF patients.

INTRODUCTION: This study aimed to evaluate the analytical performances of N-terminal pro-B-type natriuretic peptide (NT-proBNP), which has not been investigated before, and activated partial thromboplastin time (aPTT), which has been the subject of little research, using the six sigma methodology and to calculate the quality goal index values of low-performing parameters. It was aimed to evaluate the analytical process with three methods by presenting this performance with Operation specifcation charts, which have been done in few other studies.
METHODS: Three consecutive months of internal quality control data obtained from NT-proBNP and aPTT tests, twice daily, and data obtained from a monthly external quality control program were used. Sigma values were calculated using the calculation of Sigma=(Total allowable error-bias)/(Coefficient of variation) and shown with Operation specifi-cation charts (OPSpecs). Quality goal index (QGI) was calculated for those with sigma <6.
RESULTS: The sigma values for levels 1 and 2 of the NT-proBNP test were calculated as 5.06 and 5.65, and the perfor-mance status was determined as very good. The sigma values for levels 1 and 2 of the aPTT test were calculated as 4.28 and 3.56, respectively, and this was evaluated as moderate and good performance. The Quality goal index values (QGI) for levels 1 and 2 of the NT-proBNP test were calculated as 0.11 and 0.12, respectively. The Quality goal index (QGI) values for levels 1 and 2 of the aPTT test were calculated as 0.90 and 0.75, respectively.
DISCUSSION AND CONCLUSION: Both tests had moderate, good and very good performance. It is of great importance to increase quality standards in laboratory tests. In this direction, continuous improvement-oriented initiatives should be implemented to make analytical processes more competent.

INTRODUCTION: In this study, we aimed to establish reliable reference intervals (RIs) for free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) in our population using the Beckman Coulter UniCel DxI 800.
METHODS: We followed the Clinical Laboratory Standards Institute (CLSI) C28-A3 guidelines to calculate RIs through both direct (DRM) and indirect methods (IDM) and compared them with the RIs provided by Beckman Coulter UniCel DxI 800 Access® immunoassay system. High sensitive (h)TSH reagent used for TSH analyses. For DM, we excluded anti thyroid peroxidase (anti-TPO) or antithyroglobulin (anti-TG) positive samples, outliers, and samples with insufficient serum, resulting in final sample sizes of 420 for TSH, 411 for fT4, and 407 for fT3. For IDM, anti-TPO or anti-TG-positive samples, repeated samples, and outliers were excluded, resulting in fnal sample sizes of 2874 for TSH, 2072 for fT4, and 1163 for fT3.
RESULTS: Our study included 450 participants (225 females, 225 males) over the age of eighteen for DRM and utilized
data from the Laboratory Information System (LIS) between March 1, 2018, and February 28, 2020, for IDM. After excluding certain samples and outliers, the final sample sizes were determined. The reference intervals (RIs) for TSH, fT4, and fT3 were 0.42-4.18 mIU/L, 0.41-4.45 mIU/L, 0.57–1.08 ng/dL, 0.63–1.14 ng/dL, 2.62–4.01 pg/mL, and 2.72- 4.41 pg/mL for DRM and IDM, respectively.
DISCUSSION AND CONCLUSION: In conclusion, the RI that we will use for thyroid hormones in our laboratory is diferent from that provided by the manufacturer.

INTRODUCTION: We aimed to compare the analytical performance of the Access Vitamin B12 assay with the new B12 II calibrator to the current Access and Abbott assays and determined the method-specifc reference interval.
METHODS: The new B12 II was assessed for imprecision, accuracy, analytical sensitivity, linearity, and carryover. Bland-Altman, Passing Bablok, and concordance correlation coefficient (CCC) analyses were performed on 650 samples. Vitamin B12 tests were performed using the UniCel DxI 800 (Beckman Coulter, USA), and Alinity i System (Abbott Laboratories,
Abbott Park, IL, USA) analyzers.
RESULTS: The Access new B12 II assay demonstrated acceptable analytical performance; however, its reference range (138-787 pg/mL) was lower than the manufacturer’s recommendation. The Access Vitamin B12 assay showed significant negative differences of 45.8% and 37.0% relative to the Abbott and new B12 II assays, respectively, while the new B12 II assay showed a smaller difference of 9.4% against Abbott. Significant proportional and constant errors were observed between Access and new B12 II (slope: 0.780, intercept: -21.95) and Access and Abbott (slope: 0.707, intercept: -18.95). Abbott and new B12 II demonstrated lower proportional and constant errors (slope: 0.902, intercept: 6.388). Concordance analysis indicated poor agreement of the Access assay with both Abbott and new B12 II (CCC: 0.806, 0.879), whereas Abbott and new B12 II demonstrated substantial agreement (CCC: 0.958).

DISCUSSION AND CONCLUSION: The new B12 II assay demonstrated appropriate analytical performance and improved consistency with the Abbott assay. The reference interval we established differed from the manufacturer’s suggested range, highlighting the importance of determining population-based reference intervals.