Screening of polymorphisms in the folate pathway in Turkish pediatric Acute Lymphoblastic Leukemia patients

Background and aim: Folate metabolic pathway plays a significant role in leukemogenesis because of its necessity for nucleotide synthesis and DNA methylation. Folate deficiency causes DNA damage. Thus polymorphisms of folate-related genes may affect the susceptibility to childhood Acute Lymphoblastic Leukemia (ALL). MTHFR (Methylenetetrahydrofolate Reductase), DHFR (Dihydrofolate reductase), CBS (Cystathionine b-synthase) and TYMS (Thymidylate Synthase) have an important role in folate pathway because their activated variants modulate synthesis of DNA and levels of folate. In this study, we aimed to investigate whether polymorphisms in genes related to folate metabolic pathway influence the risk to childhood ALL.Subject and methods: The patient groups who were diagnosed with childhood ALL at Losante Pediatric Hematology-Oncology Hospital and healthy control groups were included in the study. MTHFR 677 CT, MTHFR 1298 A-C, CBS 844ins68, DHFR 19-bp and TYMS 1494del6 polymorphisms were screened. Genotyping of these polymorphisms was performed by Restriction Fragment Length Polymorphism (RFLP) analysis and Real Time Polymerase chain Reaction (Real Time-PCR).Results: In total, we have screened 5 polymorphisms in the studied genes. The results were compared between childhood ALL patients and healthy groups. Genotype frequencies of MTHFR 677 C-T, MTHFR 1298 A-C, CBS 844ins68 and DHFR 19-bp del were similar for childhood ALL patients and healthy groups. However, statistical results showed that TYMS 1494del6 may be associated with ALL pathogenesis (p < 0.001).Conclusion: We showed that TYMS polymorphism (rs2853542) may be associated with ALL pathogenesis. In addition, our results demonstrated that MTHFR, DHFR and CBS do not affect development of leukemia. Our study displays also importance as it is the first screening results to identify association with the studied polymorphisms in Turkish patients with childhood ALL and determination of the frequency in Turkish population

Ringtones : the next napster? / Mazlina Mahali and Mohd Izan Helmi Mohamed Aslar

Ringtones is an essential part of a mobile phone. There are many types of ringtones, from the traditional monotones to the latest true tones. The users seem to be excited with the ringtones more than ever as now they can use their favourite songs as their ringtones. However, a question arises here? Does ringtones amount to infringement of copyright of the original songs? This research is meant to answer that question and other questions with regards to the issue of ringtones. Ringtones amount to infringement of copyright of the original songs if it been obtained without the consent of the original authors or the copyright owners. So, in case of infringement, who should then be held liable for the infringement? There are numbers of parties that should be held liable for the infringement, namely the users, the service providers and the distributors. The researchers are of the opinion that all the three parties above are liable in case of infringement by ringtones. There are also other parties that had been discussed on the aspect of liability, but the researchers are of the opinion that these parties are not liable. They are the publishing house or the producers, and the Music Authors Copyright Protection (MACP). The researchers also come out with some suggestions in order to overcome any issues with regards of ringtones

Highly selective and real-time detection of 5-hydroxymethylcytosine in genomic DNA using a carbon nitride-modified gold transducer-based electrochemical sensor

Cancer biomarkers are crucial indicators of cancer status and progression that aid in early detection and more effective treatment of the disease. The loss of 5-hydroxymethylcytosine (5hmC), an oxidation product of 5-methylcytosine (5mC), is a recurrent epigenetic biomarker across various types of cancers. Therefore, accurately quantifying 5hmC holds great potential for various clinical applications. However, distinguishing 5hmC from 5mC using conventional methods is challenging. In this study, we developed a rapid and highly selective electrochemical sensor for label-free detection of 5hmC-enriched DNAs using a graphitic carbon nitride (g-C3N4)-modified gold transducer. Two-dimensional g-C3N4 sheets were synthesized via direct pyrolysis of urea under ambient or nitrogen atmospheres and drop-cast onto the gold electrode. Subsequently, 5hmC-containing DNAs were immobilized onto g-C3N4 via hydrogen bonding between the ???OH of 5hmC and the -NH2 of g-C3N4. The developed sensor demonstrated high sensitivity, selectivity, remarkable reproducibility, and stability, with a low oxidation potential (0.23 V) and an extremely low limit of detection (0.316 pM) for 5hmC. The sensor was also tested for its applicability to real samples using primary liver samples from mouse models, in which 5hmC levels were diminished due to either Tet gene knockout or hepatocellular carcinogenesis. The sensor effectively detected reduced genomic 5hmCs in TET-deficient livers and hepatocellular carcinomas compared to controls. Thus, this novel sensing strategy has the potential to develop clinically applicable sensors for early cancer diagnosis and prognosis evaluation by rapidly quantifying genomic 5hmC

Detection of TET2, KRAS and CBL variants by Next Generation Sequencing and analysis of their correlation with JAK2 and FLT3 in childhood AML

Background: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder in terms of cytogenetic and molecular aberrations. Ten-Eleven-Translocation 2 (TET2), Kirsten rat sarcoma viral oncogene homolog (KRAS), and Casitas B-cell lymphoma (CBL) have an important role pathogenesis of acute myeloid leukemia (AML) and their activated mutations confer proliferative and survival signals. Aim: In this study, we aimed to find possible genetic markers for molecular analysis in childhood AML by screening hot-spot exons of TET2, KRAS, and CBL using Next Generation Sequencing (NGS) analysis. In addition, association between found variants and mutations of Januse Kinase-2 (JAK2) and Fms-Related Tyrosine Kinase (FLT3) were analyzed which are important prognostic risk factors for AML. Methods: Eight patients who were diagnosed with pediatric AML at Losante Pediatric Hematology–Oncology Hospital were included to the study. Hot-spot exons of TET2, KRAS and CBL genes were screened using the NGS method. Furthermore, FLT3-Internal Tandem Duplicate (FLT3-ITD) and JAK2-V617F were analyzed by Real Time Polymerase chain Reaction (Real Time-PCR). Results: In total, we identified 20 variants in studied genes by NGS. In our patient group, 16 variants in the TET2 (seven novel, seven missense and two silent), two variants in the KRAS (one missense and one intronic) and two variants in the CBL (two novel) were found. All of AML patients were found negative for JAK V617 F. Three of the eight patients (37.5%) showed mutations of both FLT3-ITD and TET2, KRAS, CBL. Conclusion: We found novel mutations for TET2, KRAS, and CBL. The detected variants in this article seem to be the first screening results of genes studied by NGS in childhood AML patients. Our results also showed some degree of association between FLT3-ITD and TET2, KRAS, CBL mutations

Screening of Variations in CD22 Gene in Children with B-Precursor Acute Lymphoblastic Leukemia.

Background: CD22 is expressed on the surface of B-cell lineage cells from the early progenitor stage of pro-B cell until terminal differentiation to mature B cells. It plays a role in signal transduction and as a regulator of B-cell receptor signaling in B-cell development. Objectives: We aimed to screen exons 9-14 of the CD22 gene, which is a mutational hot spot region in B-precursor acute lymphoblastic leukemia (pre-B ALL) patients, to find possible genetic variants that could play role in the pathogenesis of pre-B ALL in Turkish children. Methods: This study included 109 Turkish children with pre-B ALL who were diagnosed at Losante Hospital for Children with Leukemia. Genomic DNA was extracted from both peripheral blood and bone marrow leukocytes. Gene amplification was performed with PCR, and all samples were screened for the variants by single strand conformation polymorphism. Samples showing band shifts were sequenced on an automated sequencer. Results: In our patient group a total of 9 variants were identified in the CD22 gene by sequencing: a novel variant in intron 10 (T2199G); a missense variant in exon 12; 5 intronic variants between exon 12 and intron 13; a novel intronic variant (C2424T); and a synonymous in exon 13. Thirteen of 109 children (11.9%) carried the T2199G novel intronic variant located in intron 10, and 17 of 109 children (15.6%) carried the C2424T novel intronic variant. Conclusion: Novel variants in the CD22 gene in children with pre-B ALL in Turkey that are not present, in the Human Gene Mutation Database or NCBI SNP database, were found

Tomato Powder Modulates NF-κB, mTOR, and Nrf2 Pathways during Aging in Healthy Rats

Purpose. In the present study, we aimed to investigate the effects of tomato powder (TP) on glucose and lipid metabolism, as well as oxidative stress and the NF-κB, mTOR, and Nrf2 pathways during the aging process in healthy rats. Methods and Results. Male Wistar rats were randomly assigned to four groups as follows: (i) Control group 1 (n=15, 3-week old): rats were fed standard diet for 7 weeks; (ii) TP group 1 (n=15, 3-week old): rats were fed standard diet supplemented with TP for 7 weeks; (iii) Control group 2 (n=15, 8-week old): rats were fed standard diet for 69 weeks; and (iv) TP group 2 (8-week old): rats were fed standard diet supplemented with TP for 69 weeks. TP supplementation significantly reduced the hyperglycemia, hypertriglyceridemia, and hypercholesterolemia and improved liver function and kidney function in 77-week old rats compared with the control animals (P<0.05). In addition, TP significantly decreased the serum and liver MDA levels (P<0.003 and P<0.001, respectively) while increasing the activities of liver SOD (P<0.001), CAT (P<0.008), and GPx (P<0.01) compared with the control groups in both 10-week-old and 77-week-old rats (P<0.05). Age-related increases in phosphorylation of NF-κBp65, mTOR, 4E-BP1, and P70S6K were observed in livers of 77-week-old rats compared to those of 10-week-old rats (P<0.001). TP supplementation decreased the expression of NF-κBp65 and activation of mTOR, 4E-BP1, and P70S6K in livers of 77-week-old rats compared to the control animals. Moreover, TP supplementation significantly elevated Nrf2 expression in livers of both 10-week-old and 77-week-old rats (P<0.05). Conclusion. TP ameliorates age-associated inflammation and oxidative stress through the inhibition of NF-κBp65, mTOR pathways, and Nrf2 activation may explain the observed improvement in glucose and lipid metabolism as well as the improved liver and kidney functions

Rare pediatric malignant tumors: Single center experience

WOS: 000361247201338