Ozgen Kilic-Erkek

Globally, obesity stands as a major public health crisis, intricately linked to diverse clinical sequelae such as diabetes mellitus, cardiovascular conditions, and malignancies.1 Pathophysiological...

Alternate‐day fasting (ADF) may exert age‐related anti‐inflammatory effects by modulating key metabolic and immune pathways. This study aimed to investigate the sex‐specific effects of ADF on inflammation in middle‐aged male and female rats and focused on the Toll‐like receptor 4 (TLR4) and leptin signaling pathways. A total of 32 rats (16 males, 16 females; 14 months old) were assigned to four groups ( n = 8): ad libitum‐fed and ADF groups for each sex. The ADF protocol consisted of 24‐h fasting every other day for 2 months. Serum and hypothalamic samples were analyzed via ELISA to measure triglyceride, total cholesterol, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), suppressor of cytokine signaling 3 (SOCS3), leptin, and ObRb levels. TLR4 gene expression in the brain and liver was assessed via qRT–PCR. Two months of ADF significantly reduced body weight and retroperitoneal fat mass compared with those of the control groups ( p < 0.001). Cumulative food intake and fasting glucose levels decreased in both sexes following ADF ( p < 0.001), and serum triglyceride, total cholesterol, TNF‐α, and IL‐6 levels ( p < 0.001) were significantly reduced. Hypothalamic SOCS3 and leptin levels decreased, whereas ObRb expression increased ( p < 0.05). Additionally, TLR4 gene expression was significantly downregulated in both tissues ( p < 0.001). These findings suggest that ADF is associated with reduced age‐related inflammation and alterations in the TLR4 and leptin signaling pathways. The observed downregulation of SOCS3 and upregulation of ObRb indicate enhanced leptin sensitivity, highlighting ADF as a promising strategy to counteract sex‐specific aging‐related inflammation and leptin resistance.

Objective: This study investigated the effects of alternate-day fasting (ADF), a nonpharmacological intervention, on inflammation, oxidative stress, and lipid metabolism in adult rats with experimental knee osteoarthritis (KOA), with a particular emphasis on serum leptin and SOCS3 levels, as well as cartilage histopathology. Methods: Twenty-four male Wistar rats (16-weeks old) were randomly assigned to four groups: C (control), OA, ADF, and OA+ADF. The KOA model was induced by intra-articular monosodium iodoacetate (MIA) injection. ADF was applied for 28 days (24-hour fasting/feeding cycles). Biochemical analyses included fasting blood glucose(FBG), lipid profile, leptin, SOCS3, tumor necrosis factor-alpha(TNF-α), interleukin-6 (IL-6), and total oxidant-antioxidant status (TOS-TAS) analyses. Histopathological evaluation was performed via hematoxylin&eosin and Masson’s trichrome staining. Results: Compared with the C group, the OA group presented increased body weight (BW), FBG, leptin, IL-6, TNF-α, and TOS and decreased TAS and SOCS3 levels (p<0.05). Compared with the C group, the ADF group presented no adverse metabolic effects and maintained normal glucose and cytokine levels. Notably, the OA+ADF group demonstrated significantly lower BW, FBG, leptin, IL-6, TNF-α, and TOS levels and significantly greater TAS and SOCS3 levels than the OA group did (p<0.05). Histologically, the OA+ADF group presented better cartilage preservation and fewer degenerative changes than did the OA group. Additionally, ADF modulated gastrocnemius muscle weight and improved metabolic parameters. Conclusion: ADF exerts protective effects in experimental OA by reducing systemic inflammation, regulating leptin-SOCS3 signaling, and mitigating oxidative stress. These findings suggest that ADF is a promising dietary strategy for modulating OA progression during aging.

Purpose: The purpose of this study was to ascertain how radioactive iodine therapy (RAIT). affected the DNA damage in the lymphocytes of differentiated thyroid cancer (DTC) patients. Materials and Methods: Our study included 21 DTC patients in total, with a mean age of 45.09±10.02 years. Six (28.6%) of the 21 patients had a low dose of RAIT (≤30 mCi), eleven (52.4%) received a moderate dose of ablation (31 to 100 mCi), and four (%19) received a high dose (>100 mCi). Before, one week, and six months following treatment, venous blood samples were obtained from each patient. DNA damage was evaluated using the COMET assay. For a quantitative analysis of DNA damage, a number of characteristics were assessed, including head length, tail length, head intensity, tail intensity, and tail moment. Results: Compared to before treatment (23.83±9.82), tail intensity levels were considerably lower after treatment (1st week and 6th months) (18.30±6.48 vs. 18.06±5.58). Following therapy (1st week and 6th months), the head intensity values were statistically substantially higher (81.69±6.48 vs. 81.93±5.58) than they were prior to treatment (76.16±9.82). Six months after therapy, the tail moment was lower than it was before treatment (5.24±2.51 vs. 8.04±3.86). Conclusion: Treatment has a beneficial effect on peripheral blood cells, as seen by the increase in head intensity and decrease in tail intensity and moment after treatment. By triggering repair mechanisms, RAIT may have activated protective effects on the DNA of lymphocytes.

We aimed to investigate and compare the effects of two different frequently utilized intermittent fasting (IF) protocols (8:16 and 5:2) applied for eight weeks on weight loss, metabolic indices, serum/liver sterol regulatory protein (SREBP) levels, and endoplasmic reticulum stress (ERS) markers in normal and high-fructose (HF) fed rats. Sixty male, Wistar rats were divided into six groups (n = 60): Control(C), 8:16 (8 h ad libitum and 16 h fasting), 5:2 (2 days food restriction followed by 5 days ad libitum-feeding), HF (high-fructose, 20% drinking water, eight weeks), 8:16 + HF, 5:2 + HF groups. IF protocols were applied for eight weeks. Serum and liver SREBP-1c, SREBP-2, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), cholesterol, triglyceride (TG), and serum protein kinase RNA-like endoplasmic reticulum kinase (PERK), protein glucose-regulated protein 78 (GRP78), and X-box binding protein 1 (XBP1) levels were determined by commercial kits. The body weight (BW) and visceral fat lowering effects of 5:2 diet was more prominent compared to 8:16 TRF. Both IF protocols decreased serum SREBP-2, ACC, TG, cholesterol levels (p < 0.05). HF induced weight gain and increment in serum glucose which was reversed by 8:16 IF. The weight loss effect of 5:2 IF was also more prominent in HF. Serum and liver SREBP-1c, SREBP-2, cholesterol, TG levels were higher in HF group than C (p < 0.05). Both IF regimens decreased serum and liver SREBP-1, SREBP-2, ACC, TG, cholestreol levels in rats subjected to HF diet (p < 0.05). Although IF regimens did not cause ERS; they reversed elevated ERS induced by HF diet. Both IF protocols have beneficial effects on both normal and HF consuming rats, being superior to each other on several parameters.

Background: This study aimed to investigate the effects of alternate-day fasting (ADF) on body weight (BW), fat distribution, and key molecular markers related to endoplasmic reticulum stress (ERS) and sterol regulatory element-binding protein-1(SREBP-1) in young (3-month-old) and middle-aged (16-month-old) rats. Methods: Thirty-two male Wistar rats were divided into four groups: Group1 (ad libitum(AL)-fed young rats), Group2 (ADF-young rats), Group3 (AL-fed middle-aged rats), and Group4 (ADF-middle-aged rats). ADF was implemented as a 24 h feeding period followed by 24 h of fasting for 28 days. Serum and liver samples were analyzed via ELISA for SREBP-1, protein kinase RNA-like ER kinase (PERK), activating transcription factor-6 (ATF6), and glucose-regulated protein 78 (GRP78) levels. Results: Compared with Group-1, Group-3 had significantly greater BW and retroperitoneal fat content (p = 0.001). ADF reduced BW in young rats (Group-2 vs. Group-1,p = 0.015) but not in middle-aged rats (Group-4 vs. Group-3,p = 0.073). ADF significantly reduced fat accumulation in middle-aged rats (Group-4 vs. Group-3 p = 0.001), although fat accumulation was greater in middle-aged rats than in young rats (p = 0.001). Serum and liver PERK,GRP78,ATF6, and SREBP-1 levels were significantly greater in AL-fed middle-aged rats (Group-3 vs. Group-1,p < 0.05), indicating that ERS and lipid dysregulation increase with age. ADF significantly reduced these markers in middle-aged rats (Group-4 vs. Group-3,p < 0.05), suggesting a protective effect. Additionally, ADF lowered serum and liver SREBP-1 levels in young rats (Group-2 vs. Group-1,p = 0.003), highlighting its role in lipid metabolism regulation. Conclusions: ADF appears to be a promising nonpharmacological approach for mitigating age-related metabolic and molecular disturbances. Further research is warranted to explore its long-term effects and translational potential in human aging. Graphical

Purpose: COVID-19 may have acute and chronic adverse effects on the cardiovascular system. Heat shock protein beta-7 (HSPB7) is a cardiovascular heat-shock protein, and tetranectin is a type-C calcium (Ca)-binding lectin. The present study was conducted to investigate the relationship between HSPB7, tetranectin, disease severity and myocardial injury in COVID-19. Materials and methods: This study included 26 COVID-19 patients and 26 age and sex-matched healthy controls. Demographic characteristics, routine hemograms, and biochemical parameters were recorded. COVID-19 patients were classified as having mild to moderate and severe COVID-19 using clinical and laboratory data. HSPB7 and tetranectin levels were measured using commercial ELISA kits. Results: C-reactive protein, fasting glucose, ferritin, neutrophil-to-lymphocyte, monocyte-to-lymphocyte, and platelet-to-lymphocyte ratios were significantly elevated, whereas calcium, and albumin were decreased in COVID-19 patients (p<0.05). Respiratory rate, D-dimer, and ferritin were higher while SO2 and lymphocyte counts were lower in severe COVID-19 patients (p<0.05). Serum HSPB7 levels were higher in COVID-19 patients vs healthy controls (p<0.01), whereas tetranectin concentration was lower (p<0.001). When the cases were evaluated according to the severity of the disease it was observed that, HSPB7 level was increased in patients with severe COVID-19 and tetranectin was decreased parallel to the severity of the disease (p<0.001 and p<0.001, respectively). HSPB7 concentration was positively correlated with ferritin (p=0.002). Tetranectin was negatively correlated with HSPB7, ferritin and troponin (p=0.041, p<0.01, and p=0.005, respectively). Conclusion: The consequence of the present study indicates tetranectin as a potential biomarker for an accurate and more comprehensive understanding severity of cardiac damage in COVID-19 patients.

Introduction: This study investigated the role of fibroblast growth factor 23 (FGF23)/Klotho in the mortality of patients hospitalized with coronavirus disease 2019 (COVID-19), excluding those with chronic kidney disease (CKD). Methodology: A prospective cross-sectional study was conducted from April 2021 to May 2022. Patients who tested positive for COVID-19 via polymerase chain reaction and were hospitalized, were classified into two groups (survivors and non-survivors) at the end of their hospital follow-up. Demographic data, clinical status, and prognosis were analyzed. Results: A total of 66 patients (age 58.8 ± 17.0 years, 60.6% male) were included. The mean age of non-survivors (67.2 ± 1 years) was significantly higher than the survivors (49.2 ± 1 years; p < 0.0001). FGF23 was significantly elevated in non-survivors (301 ± 20 pg/mL), compared to survivors (160 ± 36 pg/mL; p < 0.0001). Factors with significant differences (p < 0.001) between the two groups were investigated as independent mortality predictors using logistic regression analysis. FGF23 (p = 0.01), age (p = 0.045), and oxygen saturation at admission (p = 0.02) were independent predictors of mortality. High serum FGF23 levels were associated with COVID-19-related mortality; Klotho levels were lower (p = 0.028). Vitamin D was not significantly different between the groups. Conclusion: Elevated serum FGF23 and parathyroid hormone (PTH), and lower Klotho levels, were associated with COVID-19-related mortality in patients without CKD. There was no association with serum vitamin D levels. Further studies are required to establish the relationship between mortality and FGF23/Klotho, PTH, and vitamin D levels.