👤 Engin Köse

BackgroundEpigenetic dysregulation is increasingly recognized as a key mechanism in the development and progression of Alzheimer's disease (AD). Herpes simplex virus type 1 (HSV-1) infection has been proposed as a potential biological trigger that may accelerate neurodegeneration through epigenetic modifications. Among HSV-1 structural proteins, glycoprotein B (HSV-gB) may influence host-virus interactions affecting neuronal gene regulation.ObjectiveThis study aimed to investigate the contribution of HSV-gB to AD-related epigenetic alterations and to determine whether HSV-gB exposure exacerbates epigenetic dysregulation in two in vitro neuronal AD models.MethodsHuman SH-SY5Y neuroblastoma cells were used to establish two AD models: a differentiation-based aging model induced by retinoic acid and brain-derived neurotrophic factor (RA + BDNF), and an amyloid aggregation model induced by amyloid-β 1-42 (Aβ Show less

The main objective of this study is to non-invasively investigate the relationship between metacognitive beliefs and cortisol, the primary stress output of the hypothalamic-pituitary-adrenal (HPA) axis, as well as neurotrophic factors associated with neuroplasticity brain-derived neurotrophic factor and neuron-derived neurotrophic factor (BDNF and NDNF). Within this framework, the hypotheses that negative metacognitions would be associated with increased cortisol and decreased BDNF levels, and that cortisol might play a mediating role in this relationship, were tested. The study was designed in a cross-sectional model with 60 university students. Participants' metacognitive beliefs were measured using the Metacognitions Questionnaire-30 (MCQ-30). Salivary cortisol, BDNF, and NDNF levels were analyzed using the ELISA method. Pearson correlation and hierarchical multiple regression analyses were used for data analysis. The results showed a significant positive relationship between the total metacognition score and cortisol (r = 0.589, p < 0.01) and a strong negative relationship between cortisol and BDNF (r = -0.662, p < 0.01). Hierarchical regression analysis supported a partial mediation model, indicating that dysfunctional metacognitive beliefs have both a significant direct negative association with BDNF and an indirect association mediated by cortisol. In the final model, both metacognition (β = -0.298, p < 0.05) and cortisol (β = -0.281, p < 0.05) were significant factors associated with lower BDNF levels. NDNF showed a positive relationship with BDNF (r = 0.571) but not with other variables. These findings point to a psychobiological model where dysfunctional metacognitive beliefs are linked to suppressed neuroprotective mechanisms like BDNF, both directly and indirectly through HPA axis activation. The results shed light on the potential neurobiological mechanisms underlying the effectiveness of metacognitive therapies. Show less

Depression, a prevalent psychiatric disorder, exerts severe and debilitating impacts on an individual's mental and physical well-being, and it is considered a chronic mental illness. Chronic stress plays an important role in the pathophysiology of depression. Lactobacillus plantarum and Streptococcus thermophilus are psychobiotic bacteria and synthesize some neurotransmitters that play a role in the pathogenesis of depression. In this study, we aimed to investigate the therapeutic effects of Bactolac (Lactobacillus plantarum NBIMCC 8767  + Streptococcus thermophilus NBIMCC 8258) on chronic stress-induced depression in rats. Behavioral tests, including the sucrose preference test, elevated plus maze test, forced swim test, and three-chamber sociability test, were employed to assess depressive and anxiety-like behaviors. The expression level of the 5-HT1A, DRD1, ADRA-2A, GABA-A α1, CNR1, NR3C2, NOD1, NLRP3 and MC4R; BDNF levels, glial activity and intestinal permeability were determined in chronic stress-induced depression in rats. In conclusions, chronic stress decreased the expression levels of 5-HT1A, DRD1, ADRA-2A, GABA-A α1, CNR1, NR3C2, NOD1 and BDNF level; increased the expression levels of NLRP3 and MC4R, caused neurodegeneration and glial activity, ultimately led to depressive effects. Bactolac was effective in reducing depressive-like behaviors according to the results of behavioral tests. Bactolac treatment provided high neuronal survival rate increasing BDNF level, prevented the excessive release of pro-inflammatory cytokines by reducing the expression levels of NLRP3 and MC4R, therefore, prevented the excessive activation of the hypothalamus-pituitary-adrenal (HPA) axis and accordingly, reduced neurodegeneration and glial cell activation in depressed rats. We can suggest that Bactolac supplementation may be beneficial in coping with stress, alleviate the effects of chronic stress and help to protect mental health. Show less

APOB-related familial hypobetalipoproteinemia (APOB-FHBL), the most common form of primary hypobetalipoproteinemia, often leaves heterozygous patients asymptomatic. This study aims to provide updated insights into the complications observed in heterozygous and homozygous APOB-FHBL patients. A retrospective analysis was conducted on 15 patients (53.3% female) from 7 families diagnosed with FHBL and followed in a metabolic clinic. Demographic, laboratory, clinical, and genetic data were reviewed. Patients were followed for an average of 4.5 ± 4.1 years. The median levels were as follows: low-density lipoprotein cholesterol (LDL-C; 25.7 ± 10.5 mg/dL), apolipoprotein B (ApoB; 0.3 ± 0.1 g/L), aspartate aminotransferase (AST; 40.1 ± 22.5 U/L), alanine aminotransferase (ALT; 43.0 ± 38.3 U/L), and alpha feto-protein (1.3 ± 0.7 ng/mL). Elevated AST and ALT levels were observed in 20.0% and 26.7% of cases, respectively. Vitamin E deficiency was identified in 26.7%, vitamin A deficiency in 13.3%, and vitamin D insufficiency in 66.7% of cases. Liver ultrasonography revealed hepatosteatosis in 73.3% of patients. Additionally, the study identified 5 novel APOB gene variants. Among the families, 3 had members who died due to complications related to viral infections (COVID-19, hepatitis B virus) or hepatocellular carcinoma (HCC) resulting from chronic liver disease. Patients with elevated transaminase levels or hepatosteatosis should undergo a lipid profile assessment. LDL-C levels below 50 mg/dL require further evaluation, including ApoB and fat-soluble vitamin levels. Monoallelic APOB variants are linked to poor outcomes due to deficiencies in vitamins A, E, and D, as well as an increased risk of HCC. Early recognition and regular monitoring are essential for the effective management of APOB-FHBL patients. Show less