Pyruvate kinase deficiency in 29 Turkish patients with two novel intronic variants.

Pyruvate kinase (PK) is a key enzyme of anaerobic glycolysis. The genetic heterogeneity of PK deficiency (PKD) is high, and over 400 unique variants have been identified. Twenty-nine patients who had been diagnosed as PKD genetically in seven distinct paediatric haematology departments were evaluated. Fifteen of 23 patients (65.2%) had low PK levels. The PK:hexokinase ratio had 100% sensitivity for PKD diagnosis, superior to PK enzyme assay. Two novel intronic variants (c.695-1G>A and c.694+43C>T) have been described. PKD should be suspected in patients with chronic non-spherocytic haemolytic anaemia, even if enzyme levels are falsely normal. Total PKLR gene sequencing is necessary for the characterization of patients with PKD and for genetic counselling.

Comparison of dietary inflammatory index and total antioxidant capacities of familial Mediterranean fever and healthy adolescents.

BACKGROUND: Although it is known that consumed nutrition affects inflammatory load, and total antioxidant capacity (TAC) is affected by inflammatory diseases and consumed nutrients, these conditions have not been adequately investigated in adolescents with familial Mediterranean fever (FMF). Therefore, this study aimed to compare the dietary inflammatory index (DII), TAC and total oxidant capacity (TOC) of adolescents with FMF and healthy adolescents. METHODS: This case-controlled study consisted of 180 adolescents (aged 10-19) divided into FMF (n = 135) and control (n = 45 healthy) groups. Study data were collected face-to-face using a survey on demographic characteristics, anthropometric measurements, biochemical biomarkers and 3-day dietary recall to calculate DII scores. RESULTS: FMF group had lower DII score than controls (2.12 ± 0.78 vs. 2.33 ± 1.06, p < 0.05). In addition, they had higher C-reactive protein (CRP), TOC (p < 0.05) and oxidative stress index (OSI) (p = 0.51) than the control group. On the contrary, the control group had significantly higher tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) values (p < 0.05). There was a positive correlation between DII scores and TNF-α in the FMF group (p < 0.05). The control group had significantly higher energy, protein, medium-chain fatty acids (MCT) and saturated fatty acids (SFA) intake than FMF (p < 0.05). On the contrary, the FMF group had significantly higher vitamin A and D, niacin and zinc intake (p < 0.05). CONCLUSION: The results showed that adolescents with FMF had lower DII and higher OSI than healthy adolescents. It may be beneficial for adolescents with FMF to consume a diet containing anti-inflammatory nutrients to maintain normal growth and development and to prevent symptoms and complications of the disease.

The study of Tau and phospho Tau protein levels in attention deficit and hyperactivity disorder

Background/aim: Attention deficit and hyperactivity disorder (ADHD) is a widespread neurodevelopmental disorder that begins in childhood and has negative consequences throughout adult life. The etiology and pathogenesis of ADHD are still unclear. Tau protein is a soluble microtubule-related protein expressed by neurons and localized in the cytoplasm as well as axons. Tau protein provides stability of microtubule in two ways: phosphorylation and isoforms. The excessive phosphorylation of Tau separates the protein from the microtubule, thus making it unstable. In this study, we aimed to investigate whether there is a relationship between serum Tau protein and phospho Tau (p-Tau181) levels and ADHD occurrence. Materials and methods: This study included 26 male children aged 7­12 years with newly diagnosed ADHD, who had previously not used any medication for ADHD, and 26 male healthy children. Serum Tau and p-Tau181 concentrations were performed by enzyme- linked immunosorbent assay (ELISA). Results: In patients, the Tau levels were not significantly different from those of the controls; the p-Tau181 levels were significantly higher than those of the controls. Conclusion: We concluded that high p-Tau181 might be associated with the progression of ADHD and cognitive changes in ADHD.

The study of sirtuins in breast cancer patients before and after radiotherapy

Background/aim: Targeting the new and unique proteins is an important medical strategy for treating breast cancer. It is quite important to find out proteins that have a role in the development of cancer. Sirtuins (SIRT) are well related in different physiological activities and connected with cancer. We aimed to determine the effect of radiotherapy on SIRT1 and SIRT2, which have not been yet been clarified as a tumor suppressor or promoter. Materials and methods: Twenty-two women with nonmetastatic breast cancer enrolled in the study. Blood samples were taken before and after radiotherapy, soluble SIRT1 and SIRT2 levels were determined with ELISA kits. Results: There was no difference in SIRT1 levels before and after radiotherapy (p = 0.548). SIRT2 levels were significantly found to be decreased after radiotherapy (p = 0.042). There was a strong and positive correlation before radiotherapy (p < 0.001), and a moderate and positive correlation after radiotherapy (p = 0.007) between SIRT1 and SIRT2. Conclusion: These results suggest that SIRT2 may provide a new strategy for follow-up of breast cancer treatment. Additionally, by emphasizing the importance of SIRT2 in breast cancer, it opens ways to provide grounds for the development of the next generation of SIRT2-specific radiotracers. Finally, the most important thing, in fact, the positive correlation between SIRT1 and SIRT2 both before and after radiotherapy, appears to be clear evidence suggesting more oncogenic roles of sirtuins.

Serum vitamin D concentration is inversely associated with matrix metalloproteinase-9 level in periodontal diseases.

BACKGROUND: The aim of this study was to investigate the potential association between vitamin D deficiency and matrix metalloproteinase-9 (MMP-9) levels in gingival crevicular fluid (GCF) across various periodontal health and disease statuses. METHODS: A total of 200 volunteers were divided into two groups according to serum vitamin D concentration (25(OH)D < 10 ng/mL and 25(OH)D ≥ 10 ng/mL). Periodontal health status was determined based on a full-mouth periodontal examination and radiographic evaluation. Participants in both groups were categorized according to periodontal diagnoses, encompassing periodontal health, gingivitis, and periodontitis. Following sampling, the MMP-9 levels in GCF were determined by the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The GCF MMP-9 levels were found to be higher in individuals with serum 25(OH)D < 10 ng/mL, in both the healthy and gingivitis and periodontitis groups, compared to those with 25(OH)D ≥ 10 ng/mL. Nevertheless, a statistically significant distinction was observed exclusively within the gingivitis and periodontitis groups. Correlation analysis and robust regression analyses provided additional evidence supporting the predictive role of periodontal disease status and vitamin D concentration in local MMP-9 levels. These associations remained significant after adjusting for age and sex in robust regression analysis (p = 0.002). Furthermore, the inclusion of periodontal clinical parameters in the regression analysis revealed notable associations of clinical attachment loss with local MMP-9 levels, along with periodontal disease status and serum vitamin D concentration (p < 0.001). CONCLUSION: The findings of our study suggest a potential mechanistic relationship between serum vitamin D levels and periodontitis. PLAIN LANGUAGE SUMMARY: Vitamin D deficiency is a widespread issue globally due to urban living, less outdoor time, seasonal changes, aging, and sunscreen use, leading to inadequate sun exposure. Low vitamin D levels are linked to several health problems, including hypertension, diabetes, heart diseases, and periodontal diseases, which affect the gums and bones around teeth and can cause tooth loss if untreated. Although the link between vitamin D and periodontal disease is unclear, it may involve the enzyme matrix metalloproteinase-9 (MMP-9). Our study examined 200 people, dividing them into two groups based on vitamin D levels. We assessed their gum health and measured MMP-9 levels in their gingival crevicular fluid, a liquid that seeps out from the tiny space between gums and teeth. We found that people with lower vitamin D levels had higher MMP-9 levels, especially those with gum disease. Our analysis showed that both vitamin D levels and gum health significantly impact MMP-9 levels, with gum health being the more influential factor. Maintaining good gum health and adequate vitamin D levels is crucial for managing MMP-9, an enzyme critical for tissue remodeling during healing and inflammation. However, excessive MMP may rapidly destroy periodontal tissues.

Serum GAS6, sAXL, IL-10, NO, and BCL-2 levels are decreased in patients with Behçet's disease.

PURPOSE: Behçet's disease (BD) is an autoimmune chronic systemic inflammatory disease characterized by a versatile clinical spectrum. Growth arrest specific protein 6 (GAS6)/soluble AXL (sAXL) signaling pathway draws attention in the resolution of inflammation, and its deficiency is associated with chronic inflammatory, autoimmune diseases, as well as clearance of apoptotic cells by phagocytes - efferocytosis. In this study, it was aimed to investigate whether GAS6/sAXL, interleukin (IL)-10, nitric oxide (NO), and BCL-2 levels were associated with inflammation and efferocytosis contributes to the pathogenesis of BD. METHODS: A total of 37 Behçet patients with ocular involvement and 30 healthy control subjects were included in this study. GAS6, sAXL, IL-10, NO, and BCL-2 levels were quantified using enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Serum GAS6, sAXL, IL-10, NO, and BCL-2 levels were significantly lower in patients with BD compared to the controls (P < 0.005, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). In correlation analysis, research parameters decreased in patients with BD was significantly correlated with each other: GAS6-IL-10 (r = 0.585, P < 0.001), GAS6-BCL-2 (r = 0.541, P < 0.001), sAXL-BCL-2 (r = 0.696, P < 0.001), IL-10-NO (r = 0.717, P < 0.001), IL-10-BCL-2 (r = 0.759, P < 0.001), and NO-BCL-2 (r = 0.541, P < 0.001). CONCLUSION: In conclusion, decreased serum BCL-2 level may be an indicator of increased apoptosis in these patients and decreased levels of GAS6/sAXL, IL-10, and NO may indicate insufficient clearance of apoptotic bodies released as a result of increased apoptosis in BD patients.

If AFP is elevated, where is cancer? The case report on hereditary persistence of Alpha-fetoprotein.

Alpha-fetoprotein (AFP) is expressed by tumors with a high mitotic index such as hepatocellular carcinoma and germ cell tumors, therefore it is used as a tumor biomarker. Interestingly, although there is no underlying cause, elevated AFP has been reported in some genetically predisposed individuals. This is a very rare and benign condition called "hereditary persistence of AFP (HPAFP)" and an inherited in an autosomal dominant manner. To our knowledge, only 28 families have been reported to date. Some of the reported cases received inappropriate treatments such as chemotherapy and surgery. The possibility of HPAFP should be kept in mind in patients with high AFP in the absence of radiological evidence of hepatocellular carcinoma or germ cell tumor to avoid harmful procedures. It can be easily confirmed by analyzing AFP levels in other family members. We report a case of HPAFP with surprisingly higher AFP levels than previously reported cases and this is the first case reported from Turkey.

New Avenues to Explore in SARS-CoV-2 Infection: Both TRIM25 and TRIM56 Positively Correlate with VEGF, GAS6, and sAXL in COVID-19 Patients.

The ongoing COVID-19 pandemic poses a significant threat to human health. Many hypotheses regarding pathogenesis have been proposed and are being tried to be clarified by experimental and clinical studies. This study aimed to reveal the roles of the innate immune system modulator GAS6/sAXL pathway, endothelial dysfunction markers vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α, and antiviral effective TRIM25 and TRIM56 proteins in pathogenesis of COVID-19. The study included 55 patients with COVID-19 and 25 healthy individuals. The serum levels of GAS6, sAXL, VEGF, HIF-1α, TRIM25, and TRIM56 were measured using commercial ELISA kits and differences between COVID-19 patients and healthy controls, and the relationship to severity and prognosis were evaluated. GAS6, sAXL, TRIM56, and VEGF were found to be higher, while TRIM25 was lower in patients. There were strong positive correlations between GAS6, sAXL, TRIM25, TRIM56, and VEGF. None of the research parameters other than HIF-1α was associated with severity or prognosis. However, HIF-1α was positively correlated with APACHE II. We speculate that the antiviral effective TRIM25 and TRIM56 proteins, as well as the GAS6/sAXL pathway, act together as a defense mechanism in COVID-19. We hope that our study will contribute to further studies to elucidate the molecular mechanism associated with TRIM56, TRIM25, GAS6, sAXL, and VEGF in COVID-19 patients.

Comparison of treatments with the Forsus fatigue resistant device in relation to skeletal maturity: a cephalometric and magnetic resonance imaging study.

INTRODUCTION: The aim of this study was to compare the dentoskeletal changes and alterations of mandibular condyle-disc-fossa relationships in subjects at the peak and the end of the pubertal growth period treated with the Forsus fatigue resistant device (3M Unitek, Monrovia, Calif). METHODS: The sample consisted of 29 subjects with Class II Division 1 malocclusions who were classified according to their hand-wrist radiographs. Fifteen patients were at or just before the peak phase of pubertal growth (peak pubertal group). Fourteen patients were near the end of the pubertal growth period (late pubertal group). The study was conducted by using lateral cephalometric radiographs and magnetic resonance images obtained at the beginning and at the end of the application of the Forsus fatigue resistant device. The treatment period was 9 months. RESULTS: The Wilcoxon signed rank test was used to evaluate differences within groups. The changes observed in both groups were compared by using the Mann-Whitney U test. There were statistically significant group differences in mandibular length and ramus length, with significant increases of these parameters in the peak pubertal group (P <0.05). No significant differences were observed between the groups concerning dental parameters (P >0.05), with the exception of mandibular molar vertical movements, which were significantly greater in the peak pubertal group (P <0.05). Analysis of the magnetic resonance images showed no positional changes of the mandibular condyle in relation to the glenoid fossa in either group (P >0.05). Although the articular disc was positioned more anteriorly in the peak pubertal group compared with its pretreatment position (P <0.05), the position of the disc was still within the physiologic range. No significant intergroup difference was observed for disc-condyle relationship (P >0.05). CONCLUSIONS: The Forsus fatigue resistant device did not appear to cause significant increases in mandibular dimensions in subjects in late puberty. According to the magnetic resonance image findings, Forsus treatment is not a risk factor for the development of temporomandibular dysfunction in subjects with no signs and clinical symptoms of dysfunction.

Macrolipasemia secondary to colon cancer chemotherapy: a case report.

We reported macrolipasemia in a colon cancer patient during the chemotherapy period without any evidence of pancreatitis. A 52-year-old man formerly treated for papillary thyroid carcinoma had elevated a carcinoembryonic antigen (CEA) concentration in the latest control and was diagnosed with colon cancer. Xelox chemotherapy (oxaliplatin and capecitabine) protocol was planned for six months. Interestingly, the lipase activities gradually increased from 30 U/L to 434 U/L, and exceeded three times the upper limit of the reference range (13-60 U/L). There were no symptoms of pancreatitis, and the abdominal computed tomography (CT) scan was also normal. Polyethylene glycol (PEG) recovery % values of serum samples gradually decreased and were 27% in the recent sample before the end of chemotherapy. Interestingly, the serum lipase activity fell a month after chemotherapy, and PEG recovery % increased (39%). We considered the following possibilities: (1) macrolipasemia due to chemotherapy drugs, (2) macrolipasemia due to antibodies against chemotherapy drugs.

In vitro activity of plant extracts against biofilm-producing food-related bacteria.

The identification of effective antimicrobial agents also active on biofilms is a topic of crucial importance in food and industrial environment. For that purpose methanol extracts of Turkish plants, Ficus carica L., Juglans regia L., Olea europaea L., Punica granatum L. and Rhus coriaria L., were investigated. Among the extracts, P. granatum L. and R. coriaria L. showed the best antibacterial activity with minimum inhibitory concentrations (MIC) of 78-625µg/ml for Listeria monocytogenes and Staphylococcus aureus and 312-1250µg/ml for Escherichia coli and Pseudomonas aeruginosa. SubMICs produced a significant biofilm inhibition equal to 80-60% for L. monocytogenes and 90-80% for S. aureus. The extracts showed also the highest polyphenol content and the strongest antioxidant activity. Bioassay-guided and HPLC procedures demonstrated the presence of apigenin 4'-O-ß-glucoside in P. granatum L. and myricetrin and quercitrin in R. coriaria L. Antigenotoxicity of plant extracts was also observed The present findings promote the value-adding of P. granatum L. and R. coriaria L. leaves as natural antimicrobial/antioxidant agents for control of food-related bacterial biofilms.

Evaluation of oil content and fatty acid composition of five endemic Bupleurum species growing in the Central Anatolia region of Turkey.

The fatty acid composition of five endemic Bupleurum (Apiaceae) species was analysed by GC technique for their nutritional value. The amount of oil content of the species varied from 3.77% to 7.03%. Twenty-one fatty acids were identified in the oils. The fatty acid composition of the studied species contained oleic, palmitic and linoleic acids as the major components. Oleic acid ranged from 8.81% to 68.30%, while the levels of palmitic acid were found to be between 12.47% and 47.85%. Bupleurum lycaonicum, Bupleurum sulphureum and Bupleurum heldreichii are very good sources of oleic acid. The remaining species were characterised as containing the highest level of palmitic acid. In this study, the total saturated fatty acids ranged between 15.02 and 65.20%, while total monounsaturated fatty acids were between 18.10 and 70.65%. The total polyunsaturated fatty acid accounted for 13.47-35.20% of the studied fatty acids. Therefore, we can conclude that Bupleurum oils have a significant nutritional value.