Ayşegül Çört

Spleen tyrosine kinase is a non-receptor tyrosine kinase that couples receptor engagement to cellular survival, immune responses, and tissue injury. This narrative review compares its biology in malignancies and sepsis to examine how cellular compartment, receptor architecture, activation state, and signaling duration alter the meaning of a common signaling hub. A structured narrative search of PubMed/MEDLINE, Scopus, and Web of Science covered English-language publications from January 2000 to August 2026, supplemented by older seminal studies. In several hematological malignancies, sustained receptor signaling or oncogenic cooperation supports malignant-cell persistence; solid tumors show both tumor-promoting and tumor-suppressive functions. In sepsis, dynamically changing immune and vascular responses link spleen tyrosine kinase to pathogen recognition, inflammatory and oxidative responses, endothelial dysfunction, and organ injury. Oncology includes mechanistic studies, human cohorts, and early clinical therapeutic trials, whereas sepsis evidence remains predominantly experimental, with limited human observational and ex vivo validation. Transcript abundance, total protein, and phosphorylation are distinct biomarker endpoints whose interpretation requires identification of the cellular source and sampling context. Kinase inhibitors have shown clinical activity in selected malignancies and protection in experimental sepsis, but these findings do not establish a validated predictive biomarker or clinical efficacy in sepsis. Translation requires disease-specific validation, standardized cellular assessment, and attention to treatment timing and preservation of host defense.

Objective This case–control study compared urinary concentrations of parabens and phthalate metabolites between adolescents with attention-deficit/hyperactivity disorder (ADHD) and healthy peers and examined whether product-use behaviors accounted for observed exposure differences.Methods Adolescents aged 12–17 years with clinically diagnosed ADHD (n=39) and age- and sex-matched healthy controls (n=41) were recruited. Urinary concentrations of seven parabens and ten phthalate metabolites were quantified using validated high-performance liquid chromatography and gas chromatography–mass spectrometry protocols. ADHD symptoms were assessed using Conners Parent and Adolescent Rating Scales. Group comparisons were conducted using t-tests with effect sizes (Cohen’s d). Multivariable logistic regression, factorial analysis of covariance (ANCOVA) models (reporting partial η²), and multiple mediation analyses were performed, adjusting for household income, parental education, and body mass index.Results Differences in the urinary concentrations of several parabens and phthalate metabolites were observed between adolescents with ADHD and controls. However, detection frequencies varied across analytes, and findings for compounds with low detection frequency should be interpreted with caution. In multivariable logistic regression, an association between dimethyl phthalate and ADHD status was observed (odds ratio=6.13; 95% confidence interval, 1.10–34.34), with improved model discrimination (Δχ²=17.2, p=0.002; area under the receiver operating characteristic curve, 0.856→0.921); however, this finding should be interpreted with caution given its low detection frequency. In ANCOVA models adjusting for product-use behaviors, group differences remained significant only for dimethyl phthalate (F(1, 71)=7.97, p=0.006, η²=0.099); however, this finding should likewise be interpreted with caution due to its low detection frequency. Mediation analyses indicated that recent personal care product use did not substantially mediate the association between ADHD status and chemical exposure levels.Conclusion Adolescents with ADHD showed differences in internal exposure to selected parabens and phthalate metabolites. These findings should be interpreted with caution, particularly for analytes with low detection frequency. Overall, these findings suggest that exposure differences may reflect behavior-linked vulnerability patterns during adolescence rather than short-term cosmetic use alone. Longitudinal studies are needed to clarify temporal and causal pathways.

Purpose: Recent studies have shown promising outcomes in the utilization of natural, non-toxic polyphenols with fat-burning properties to combat obesity. The aim of this study was to investigate the changes in the gene expression profile of hypertrophic 3T3-L1 adipocytes in response to Verbascoside (VB) treatment and the mRNA levels of 5' AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPAR-γ), hormone-sensitive lipase (HSL), and lipid droplet-associated protein (perilipin1, PLIN1), which play an important role in fat metabolism. Materials and methods: For this purpose, 3T3-L1 preadipocytes were differentiated and hypertrophied. Triglyceride accumulation in the cells was evaluated using Oil Red O staining. The hypertrophic 3T3-L1 cells were incubated with VB for 48 h. Results: Microarray analysis at the end of this period showed that VB increased the mRNA levels of many proteins involved in lipolysis processes, but did not change the expression of PPARγ, AMPK, HSL and PLIN1. Therefore, we confirmed by RT-PCR that PPARγ, AMPK, HSL, and PLIN1 expression levels were altered by VB treatment. Our results showed that VB treatment caused a significant increase in the expression of genes involved in lipolytic processes compared to the control. Conclusion: The findings of this study suggest that VB may play an active role through important intracellular proteins involved in lipolytic processes.

Purpose: S-sulfocysteine (SSC), a toxic byproduct of sulfur-containing amino acid metabolism, accumulates in conditions such as molybdenum cofactor deficiency (MoCD) and isolated sulfite oxidase deficiency (iSOD), leading to severe neurodegeneration. Despite evidence of SSC's neurotoxicity, the apoptotic mechanisms it triggers remain unclear, particularly in different brain regions. This study aimed to investigate the region-specific apoptotic pathways induced by SSC in hippocampal HT-22 and primary cortical neurons, focusing on caspase-dependent and -independent mechanisms. Materials and methods: Neuronal cells were treated with increasing doses of SSC, and cell viability, glutathione (GSH) levels, and apoptosis-related proteins (AIF, calpain, cytochrome c, caspase-3) were assessed using CCK-8 assay, GSH enzymatic assay, and ELISA. The protective effects of specific inhibitors targeting AIF, calpain, and cytochrome c were also evaluated. Results: SSC reduced cell viability in both neuronal types with half-maximal lethal dose (LD50) values of 150 μM (HT-22) and 155 μM (cortical neurons). In both models, SSC elevated AIF and calpain levels, whereas cytochrome c and caspase-3 were significantly increased only in cortical neurons. GSH levels initially rose at 2–8 hours and declined by 16 hours. Inhibitors of AIF, calpain, and cytochrome c partially restored viability, with combined administration offering the most robust protection. Conclusion: SSC induces both caspase-independent and caspase-dependent apoptosis in a region-specific manner: HT-22 cells predominantly activate AIF and calpain, while cortical neurons engage additional cytochrome c and caspase-3 pathways. These findings suggest distinct molecular vulnerabilities and offer potential targets for therapeutic intervention in sulfite-related neurodegenerative diseases.

Purpose: The present study evaluates the levels of oxidative stress and DNA damage in patients diagnosed with acute myeloid leukemia (AML; newly diagnosed patients and patients in remission) compared to healthy controls. Materials and methods: A total of 96 participants were enrolled into this study in three groups: 32 newly diagnosed AML patients, 32 patients in remission, and 32 age- and sex-matched healthy individuals. Various laboratory analyses were conducted to measure biochemical parameters, total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and DNA damage using the comet assay. Results: We showed that while TOS levels did not differ significantly between the groups, both the newly diagnosed and remission groups exhibited higher OSI levels compared to controls. TAS levels were notably lower in the remission group, suggesting decreased antioxidant capacity. The comet assay demonstrated significantly elevated DNA damage in the newly diagnosed AML group, followed by the remission group, relative to healthy controls. These findings highlight an increased oxidative stress burden and genotoxicity in AML patients, which may contribute to disease pathophysiology. Furthermore, the results suggest that the oxidative stress and DNA damage are more pronounced in newly diagnosed patients compared to those in remission. Conclusion: The study showed that the oxidative stress and DNA damage observed in AML patients, particularly at diagnosis, could play a role in the progression and recurrence of the disease, suggesting potential prognostic value for oxidative stress markers in AML management.

Purpose: Metabolic syndrome (MetS) is a health condition characterized by obesity, insulin resistance, dyslipidemia and type 2 diabetes (T2DM). This study aimed to assess the effects of quercetin, a natural flavonoid on MetS induced by fructose in Sprague Dawley rats. Materials and methods: The rats, aged 8-10 weeks, were divided into 4 groups: control (C) group, metabolic syndrome (MetS) group, control+quercetin (C+Q) group, and metabolic syndrome+quercetin (MetS+Q) group. The MetS groups received a 20% fructose solution in drinking water for a duration of 10 weeks. For the last 4 weeks of the study, rats in the Q groups were administered 50 mg/kg/body weight quercetin. After 10 weeks, serum samples were tested using ELISA for Triglycerides (TG), High-Density Lipoprotein (HDL), fasting insulin, resistin, (Interleukin 6) IL6, Tumor Necrosis Factor-alpha (TNF-α), leptin, C-Reactive Protein (CRP) and, adiponectin (ADP). The body weights, Lee index and HOMA-IR scores were also measured. Results: Fructose-fed rats showed significant increases in body weight, Lee index, HOMA-IR scores and, fasting insulin with significant decrease in HDL compared to controls. In MetS group, ADP levels were significantly lower compared to control group. In MetS+Q group, there was a tendency for reduced levels of resistin, IL-6, and leptin compared to the untreated MetS group. Conclusion: These findings suggest that quercetin may be beneficial in managing MetS, though further research is needed to explore its mechanisms and effectiveness.

Purpose: Chronic lymphocytic leukemia (CLL) is the most seen type of leukemia in adults. There are few biomarkes that are used for better understanding how oxidative stress is involved in the pathophysiology of hematologic malignency.We aimed to oxidative stress, DNA damage and erythrocyte membrane lipid profile in CLL patients in this study. The study is included 38 CLL patients and 38 age-sex matched controls. Materials and method: Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), DNA damage examination with Comet assay, serum 8-OHdG measurement and gas chromatographic analysis were performed between the case and control groups. Results: It was observed that TOS and OSI values were higher in the case group than in the control group (p=0.014 and p=0.022, respectively). DNA damage measured by Comet method was found to be increased in the case group (p0.05). Conclusion: It has been shown that CLL patients had higher oxidant capasity as consequence. Oxidative stress and DNA damage are increased in CLL patients in this study. It is early to evaulate on erythrocyte membrane lipid profile in CLL patients. However, the study can be ligthed the way future studies on the subject.

Introduction: Despite the numerous studies demonstrating gut microbiota dysbiosis in obese subjects, there is no data on the association between obesity and gastric microbiota. The aim of this study was to address this gap in literature by comparing the composition of gastric microbiota in obese patients and a control group which included normal weight volunteers diagnosed with functional dyspepsia (FD). Methodology: A total of 19 obese patients, and 18 normal weight subjects with FD and normal endoscopy results were included in the study. The gastric tissue samples were collected from participants in both groups by bariatric surgery and endoscopy, respectively, and profiled using 16S ribosomal RNA gene sequencing. Results: There was no significant difference in the α-diversity scores, while distinct gastric microbial compositions were detected in both groups. Significantly lower levels of Bacteroidetes and Fusobacteria, and higher Firmicutes/Bacteroidetes ratio were recorded in the obese patients. A total of 15 bacterial genera exhibited significant difference in gastric abundance with Prevotella_7, Veillonella, Cupriavidus, and Acinetobacter, present in frequencies higher than 3% in at least one subject group. Conclusions: Our study suggests a significant association between obesity and gastric microbiome composition. Future studies with larger sample size and gastric samples from subjects without any gastrointestinal complications are required to confirm our conclusions.

Osteocytes play an important role as regulators of both osteoclasts and osteoblasts, and some proteins that are secreted from them play a role in bone remodeling and modeling. LPS affects bone structure because it is an inflammatory factor, despite verbascoside’s potential for bone preservation and healing. Osteocytes may also be involved in the control of the bone’s response to immunological changes in inflammatory situations. MLO-Y4 cells were cultured in either supplemented -MEM alone with a low serum to inhibit cell growth or media with LPS (10 ng/mL) and/or verbascoside (50 g/mL) to show the LPS effect. In our research, LPS treatment increased RANKL levels while decreasing OPG and RUNX2 expression. Treatment with verbascoside reduced RANKL expression. In our work, verbascoside increased the expression of OPG and RUNX2. In MLO-Y4 cells exposed to verbascoside, SOD, CAT, and GSH activities as well as the expression levels of bone mineralization proteins like PHEX, RUNX2, and OPG were all elevated.

Background: Src family tyrosine kinases play a potential role in Bcr-Abl-induced leukemogenesis. Src kinase inhibitors are reported as selective inhibitors of chronic myeloid leukemia. Objective: Since Src kinase inhibitors have an inhibitive effect on chronic myeloid leukemia, indole derivatives (C-1, C-2, C-3) previously found as potent inhibitors of Src kinase were tested against chronic myeloid leukemia in this study. Methods: Cell viability of K562 and R/K562 cells, antiproliferative and antioxidant effects, and inhibition profiles of Bcr-Abl kinase of indole derivatives were determined compared to dasatinib and imatinib. Results: The results showed that compounds affected cell proliferation and decreased the levels of Bcr/Abl. These results confirmed that the antileukemic activity of compounds was related to Bcr/Abl expression. Docking studies also presented that compounds are inhibitors of both Src and Abl kinases. Calculation of drug-like properties showed that compounds could be potential drug candidates. Conclusion: Among indole-2-on derivatives, previously identified as Src kinase inhibitors, C-2 has been discovered to be a strong anticancer drug that is active against susceptible and resistant K562 cell lines and induces apoptosis.