Gulten Tuncel

Objectives: Structural, molecular and immunohistochemical changes in the liver of rats after acute cadmium (Cd) exposure and the effects of carvacrol (Car) and thymoquinone (TQ) were studied in this research. Methods: Control, DMSO, Cd-treated (3.5 mg/kg by subcutane), Car (50 mg/kg gavage)-Cd treated, TQ (5 mg/kg by gavage)- Cd treated, carvacrol, and thymoquinone groups were formed.H&E and Masson’s Trichrome stainings were performed. Histological scoring was performed in liver. On the liver sections TNF-α, IL-6, and NF-kB immunostainings were carried out. Also sections of liver tissue were evaluated by electron microscopy. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and triglyceride (TG), oxidative stress parameters, MDA and GPx, were evaluated. Tnf-α, Nfkb1, IL6, mTor and Casp3 mRNA gene expression levels were examined using RT-PCR. The obtained data was statistically analyzed using GraphPad Prism software. Results: Treatment groups showed significant reduction in ALT and TG when compared to cadmium group.In the cadmium group, MDA levels increased significantly and GPX1 levels decreased compared to the control group. As a results of the microscopic studies, cellular and structural defects by cadmium were decreased in the presence of carvacrol and thymoquinone. NF-kB, TNF-α and IL-6 immunostained surface area increased in cadmium compared to the control group. Cd-Car and Cd+Thymoquinone alleviated these inflammatory expressions. In treatment groups, Nfkb1, Tnf-α, IL6, mTor, Casp3 expressions reduced compared to cadmium alone. Conclusions: The study results indicate that carvacrol and thymoquinone alleviate the toxic effects of liver tissue induced by cadmium.

West Nile Virus (WNV) infection represents a major global public health challenge. Even though most of the patients are asymptomatic, some cases progress to critical condition which may be fatal. Diagnosis traditionally relies on serological methods, but their limitations, including cross‐reactivity, highlight the need for alternative approaches. Here, we present the development and validation of a novel RT‐qPCR assay for precise and rapid detection of WNV RNA in urine, emerging as a promising specimen due to its noninvasive collection and high viral load. The assay demonstrates high efficiency and sensitivity, with a detection limit comparable to commercially available kits. This study highlights the importance of in‐house kit design as a diagnostic tool in regions affected by emerging tropical infections, such as WNV, exemplified Cyprus. It emphasizes the critical role of low‐cost, early detection with high sensitivity and specificity in infection control and surveillance efforts.

Background: Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by mutations in the PAH gene, resulting in deficient phenylalanine hydroxylase (PAH) enzyme activity and neurotoxic phenylalanine accumulation. Untreated PKU results in progressive neurodegeneration and severe intellectual disability. Neonatal screening has evolved from the Guthrie test to advanced techniques like HPLC, tandem mass spectrometry, and next‐generation sequencing (NGS) for molecular confirmation. This study aimed to develop a rapid, scalable PAH genetic assay using Oxford Nanopore Technologies (ONTs) to enhance neonatal screening in high‐prevalence regions like Türkiye, through accelerated, cost‐effective genetic diagnostics. Methods: An in‐house panel was designed, implemented, and benchmarked against results obtained from the Illumina sequencing platform. A cohort of 40 PKU patients, previously diagnosed using Illumina platform, was selected for this study. Gene‐specific primers were strategically designed to amplify exonic regions, untranslated segments, and exon–intron junctions of the PAH gene. Sequencing libraries were then prepared and processed using the MinION Mk1c instrument, with subsequent data analysis conducted through the Guppy software and complementary bioinformatics tools. Results: The findings showed complete agreement between the ONT and Illumina platforms, corroborating the high fidelity and reliability of the ONT‐based assay. All pathogenic variants previously identified through Illumina sequencing were accurately detected, albeit with varying observed allele frequencies. Notably, the most prevalent variants identified in the patient cohort were NC_000012.12(NM_000277.3):c.1066‐11G > A with a frequency of 37.5% and NC_000012.12(NM_000277.3):c.782G > A, at 15%. Conclusion: The ONT‐based single‐gene testing for PKU demonstrated complete concordance with Illumina sequencing, validating its accuracy and reliability. This method effectively detects pathogenic variants and offers a faster, cost‐effective solution for neonatal screening, particularly beneficial in high‐prevalence regions like Türkiye.

Objective: As an alternative to RT-qPCR assays used in the diagnosis SARS-CoV-2, antigen-detecting rapid diagnostic tests (Ag-RDTs) are available for the qualitative detection of SARS-CoV-2 in nasopharyngeal swab samples. The aim of this study was to assess the accuracy and reliability of Ag-RDTs as a diagnostic method of detecting SARS-CoV-2 positive cases within a given population. Methods: In first phase of this investigation, 357 nasopharyngeal swab samples were screened for SARS-CoV-2 using Ag-RDTs. For the purposes of this study RT-qPCR was then applied to the same 357 nasopharyngeal swab samples in order to compare the reliability of the two detection methods. In the second phase of this investigation, Ag-RDTs were applied to an additional 75 nasopharyngeal swab samples that were already known to be RT-qPCR positive. Results: In the first phase of this investigation, of the 357 samples screened using Ag-RDTs 14 samples were positive for SARS-CoV-2, in contrast, when RT-qPCR analysis was applied to the same 357 samples no SARS-CoV-2 samples were detected. Therefore, the false antigen positivity was determined to be at 3.9%. In the second phase of this investigation 75 RT-qPCR positive samples were re-evaluated with a rapid antigen test. Twenty-four of the 75 RT-qPCR positive sample were undetected. Conclusion: Solely relying on rapid antigen tests to detect SARS-CoV-2 infections in the community could consequently result in infectious individuals remaining in the population. The impact of false negative rapid test results can be reduced by implementing confirmatory RT-qPCR analysis particularly in symptomatic patients.

Aim: SARS-CoV-2 variants of concern (VOCs) carry signature mutations particularly in the spike protein. Most VOCs lineages that carry N501Y substitution have been reported to evade viral diagnostic...

Neonatal progeroid syndrome or Wiedemann–Rautenstrauch syndrome (WRS; MIM 264090) is a rare genetic disorder that has clinical symptoms including premature aging, lipodystrophy, and variable mental impairment. Until recently genetic background of the disease was unclear. However, recent studies have indicated that WRS patients have compound heterozygote variations in the POLR3A (RNA polymerase III subunit 3A; MIM 614258) gene that might be responsible for the disease phenotype. In this study we report a WRS patient that has compound heterozygote variations in the POLR3A gene. One of the reported variations in our patient, c.3568C>T, p.(Gln1190Ter), is a novel variation that was not reported before. The other variant, c.3337-11T>C, was previously shown in WRS patients in trans with other variations.

Background: The use of psychoactive substances is one of the most dangerous social problems worldwide. Nicotine dependence results from the interaction between neurobiological, environmental and genetic factors. Semtonin is a neurotransmitter that has a wide range of central nervous system activities. The serotonin transporter gene has been previously linked to psychological traits. Objective: A variable number of tandem repeats within the serotonin transporter-linked polymorphic gene region are believed to alter the transcriptional efficiency of the 5-HTT gene. Therefore, we aimed to investigate the association between this polymorphic site and smoking behavior in the Turkish Cypriot population. Methods: A total of 259 (100 smokers, 100 non-smokers and 59 ex-smokers) Turkish Cypriots were included in this population-based cross-sectional study. Genomic DNA was extracted from peripheral blood samples and the 5-HTTVNTR2 polymorphisms were determined by the PCR-RFLP. Results: The allelic frequency and genotype distribution results of this study showed a strong association (P<0.0001) between smokers and non-smokers. No statistical significance was found between non-smokers and ex-smokers. Conclusion: This is the first genetic epidemiology study to investigate the allelic frequencies of 5-HTTVNTR2 polymorphisms associated with smoking behavior in the Turkish Cypriot population. Based on the results of this study, genome-wide association studies should be designed for preventive medicine in this population.

BRCA1 is involved in double-strand DNA damage repair pathways, and mutations in the gene are associated with hereditary breast and ovarian cancers. With great help of the development of high-throughput DNA sequencing techniques numerous single-nucleotide polymorphisms (SNPs) and insertion deletion (Indel) mutations are detected on both coding and non-coding/regulatory regions of the BRCA1. Mutations may cause pathogenic or benign changes on the protein function or affect its expression. In the last decade, use of genetic screening tests to detect mutations on such genes has become greatly popular. However, it is very important to know the effect of the detected mutations, which is mostly possible by the use of predictive softwares, and also the related family history to be able to correctly analyse the screening results and to inform the patient. Therefore, use of in silico and in vitro techniques to score the pathogenicity of detected variants on genes like BRCA1 is now of great importance. Otherwise, results obtained from screening tests and family history cannot be analysed precisely.

Vitamin D is an important molecule to keep teeth, bones and muscles healthy. It is obtained from diet, supplements and primarily from exposure to sunlight. In recent years, vitamin D deficiency is recognised as a worldwide health problem, which results in disturbances in mineral metabolism and skeletal problems. Deficiency might be caused due to sedentary lifestyle, insufficient diet, age as well as some polymorphisms in the VDR gene. In this study the four most common VDR polymorphisms (rs1544410 (BsmI), rs731236 (TaqI), rs7975232 (ApaI) and rs2228570 (FokI)) are investigated in a cohort of Turkish Cypriots and aimed to detect any possible links between low serum vitamin D levels and these variants. The rs2228570 (FokI) variant but not others were shown to have a significant association with decreased serum vitamin D levels in the Turkish Cypriot population.