Autoimmunity-related LINC01934 and AP002954.4 lncRNA polymorphisms may be effective in pediatric celiac disease: a case-control study.

OBJECTIVE: Various studies have reported that certain long non-coding RNA levels are unusually low in the intestines of celiac disease patients, suggesting that this may be associated with the inflammation observed in celiac disease. Despite these studies, the research aimed at uncovering the potential role of long non-coding RNAs in the pathogenesis of autoimmune diseases like celiac disease remains insufficient. Therefore, in this study, we plan to assess long non-coding RNA polymorphisms associated with autoimmunity in children diagnosed with celiac disease according to the European Society for Paediatric Gastroenterology Hepatology and Nutrition criteria. METHODS: DNA was isolated from paraffin tissue samples of 88 pediatric celiac disease patients and 74 healthy pediatric individuals. Single-nucleotide polymorphism genotyping of five long non-coding RNA polymorphisms associated with autoimmunity (LINC01934-rs1018326, IL18RAP-rs917997, AP002954.4-rs10892258, UQCRC2P1-rs6441961, and HCG14 rs3135316) was conducted using the TaqMan single-nucleotide polymorphism genotyping assays with the LightCycler 480. RESULTS: In our study, the genotypic and allelic frequency distribution of LINC01934-rs1018326 and AP002954.4-rs10892258 polymorphisms was found to be statistically significant in the comparison between the two groups (p<0.05). According to the multiple genetic model analyses, the LINC01934-rs1018326 polymorphism was observed to confer a 1.14-fold risk in the recessive model and a 1.2-fold risk in the additive model for pediatric celiac disease. Similarly, the AP002954.4-rs10892258 polymorphism was found to pose a 1.40-fold risk in the dominant model and a 1.7-fold risk in the additive model. CONCLUSION: Our study results draw attention to the LINC01934-rs1018326 and AP002954.4-rs10892258 polymorphisms in celiac disease and suggest that these polymorphisms may be associated with inflammation in autoimmune diseases like celiac disease.

Link Between Obsessive-Compulsive Disorder and ApoE Gene Polymorphisms.

Objective: Many researchers have considered obsessive compulsive disorder (OCD) to be a neurodegenerative disease just like Alzheimer's disease (AD). The most studied gene in neurodegenerative diseases is apolipoprotein E (ApoE) gene, and ApoE ɛ4 allele in particular. Although a small number of studies have explored the relationship between ApoE gene polymorphisms and OCD, the link between age at onset of OCD, its subtypes and ApoE gene polymorphisms has not been revealed so far. For this purpose, in our study, the relationship of ApoE gene polymorphisms with age at onset of OCD and its subtypes has been investigated to reveal their neurodegenerative connections. Patients and Methods: ApoE gene polymorphisms of 64 OCD and 28 healthy cases were studied using a LightCycler480 real-time PCR platform. Results: A statistically significant difference was found between groups of patients with early- and late-onset OCD in terms of age (p = 0.03), educational level (p = 0.00) and marital status (p = 0.002). ApoE ɛ4ɛ4 genotype, the prevalence of which is below 2% in healthy individuals, was not detected in our control groups; however, it was identified in 5.1% of our OCD cases. Correlation analysis revealed the presence of a potentially significant link between the hoarding obsession and presence of the ɛ4ɛ4 genotype. A significant correlation was detected between the presence of the ɛ3ɛ3 allele, the symmetry obsession and associated ordering compulsion in patients with OCD (p<0.005). Conclusion: The ApoE gene polymorphism profile and age of onset in OCD patients may play critical roles in the development process of neurodegenerative characteristics of the disease. The small number of cases and the inability to perform brain imaging in patients to detect the neurodegenerative link in OCD are limitations of our study. In this respect, we suggest conduction of further studies with a greater number of patients who will also undergo brain imaging studies. In addition, OCD patients have other genes associated with neurodegenerative diseases that can be screened.

Antileukemic potential of Nile blue-mediated photodynamic therapy on HL60 human myeloid leukemia cells.

Background/aim: Photodynamic therapy (PDT) has received great attention over the past decade in the treatment of diseases such as leukemia which is a cancer of the blood and bone marrow cells that causes a significant number of deaths worldwide. In this study, it was aimed to investigate the effects of Nile blue-mediated PDT (NB-mediated PDT) on HL60 cells. Materials and methods: The effect of NB-mediated PDT on cell proliferation was evaluated with cell volume analysis using flow cytometry at 24 h. Cell apoptosis, ROS production, mitochondrial membrane potential, and cell cycle analysis were evaluated using annexin V-FITC, H2DCFDA, JC-1, and PI staining, respectively, by flow cytometry and fluorescence microscopy. The morphological and ultrastructural analyses were examined by Giemsa staining and SEM. CD11b staining is used to determine the differentiation of leukemia cells. Results: NB-mediated PDT induced an apoptotic response at 12.5 µM in HL60 cells. When Giemsa staining and SEM images were evaluated, apoptotic bodies, holes, and occasional folds were detected on the surfaces of cells in the NB-mediated PDT group. Conclusion: The NB-mediated PDT had no effect on the differentiation of leukemia cells, but this therapy affects the growth of HL60 cells in vitro, which may provide a new idea for removing leukemic cells from bone marrow intended for autologous transplant.

Relationship between villous atrophy and Wnt pathway gene expressions in pediatric celiac patients.

OBJECTIVE: Celiac disease is an autoimmune disease characterized by an abnormal immune response occurring in the small intestine linked to consumption of food containing gluten in individuals with a genetic predisposition. Dysregulation of Wnt signal transduction plays a role in the pathogenesis of many diseases including autoimmune diseases like celiac disease. In this study, the correlation of Wnt pathway gene expressions with each other and the correlation with clinical data were researched in pediatric celiac disease cases grouped according to the Marsh classification. METHODS: Gene expression levels of FZD8, DVL2, LRP5, RHOA, CCND2, CXADR, and NFATC1, which are involved in the Wnt pathway, were determined using quantitative real-time polymerase chain reaction in 40 celiac disease and 30 healthy individuals. RESULTS: All cases with the short height symptom were observed to be in Marsh 3b\3c groups (p=0.03). The gene expressions of DVL2, CCND2, and NFATC1 were high in the Marsh 3b group, and these genes showed positive correlation with each other (p=0.002). LRP5 and CXADR gene expressions were lower in the Marsh 3b group compared to other Marsh groups, and these genes showed a positive correlation with each other (p=0.003). CCND2 gene expression was associated with Marsh 3b group, diarrhea, and vomiting symptoms. DVL2 gene expression was correlated with Marsh 2 group and constipation symptom (p<0.05). CONCLUSION: Wnt signaling in the early stages of the disease of Marsh 1-2 involves high expression of LRP5 and CXADR genes, while expression of these two genes reduces, and DVL2, CCND2, and NFATC1 gene expressions clearly increase with a transduction variation observed from Marsh 3a stage when villous atrophy begins to form. It appears that the Wnt pathway may contribute to disease progression through expression changes.

Serotonin, ghrelin, and motilin gene/receptor/transporter polymorphisms in childhood functional constipation.

OBJECTIVE: Functional constipation is the most common form of constipation, and its exact aetiology is still unclear. However, it is known that deficiencies in hormonal factors cause constipation by changing physiological mechanisms. Motilin, ghrelin, serotonin acetylcholine, nitric oxide, and vasoactive intestinal polypeptide are factors that play a role in colon motility. There are a limited number of studies in the literature where hormone levels and gene polymorphisms of serotonin and motilin are examined. Our study aimed to investigate the role of motilin, ghrelin, and serotonin gene/receptor/transporter polymorphisms in constipation pathogenesis in patients diagnosed with functional constipation according to the Rome 4 criteria. METHODS: Sociodemographic data, symptom duration, accompanying findings, the presence of constipation in the family, Rome 4 criteria, and clinical findings according to Bristol scale of 200 cases (100 constipated patients and 100 healthy control) who applied to Istanbul Haseki Training and Research Hospital, Pediatric Gastroenterology Outpatient Clinic, between March and September 2019 (6-month period) were recorded. Polymorphisms of motilin-MLN (rs2281820), serotonin receptor-HTR3A (rs1062613), serotonin transporter-5-HTT (rs1042173), ghrelin-GHRL (rs27647), and ghrelin receptor-GHSR (rs572169) were detected by real-time PCR. RESULTS: There was no difference between the two groups in terms of sociodemographic characteristics. Notably, 40% of the constipated group had a family history of constipation. The number of patients who started to have constipation under 24 months was 78, and the number of patients who started to have constipation after 24 months was 22. There was no significant difference between constipation and control groups in terms of genotype and allele frequencies in MLN, HTR3A, 5-HTT, GHRL, and GHSR polymorphisms (p<0.05). Considering only the constipated group, the rates of gene polymorphism were similar among those with/without a positive family history of constipation, constipation onset age, those with/without fissures, those with/without skin tag, and those with type 1/type 2 stool types according to the Bristol stool scale. CONCLUSION: Our study results showed that gene polymorphisms of these three hormones may not be related to constipation in children.

Serotonin, ghrelin, and motilin gene/receptor/transporter polymorphisms in childhood functional constipation

SUMMARY OBJECTIVE: Functional constipation is the most common form of constipation, and its exact aetiology is still unclear. However, it is known that deficiencies in hormonal factors cause constipation by changing physiological mechanisms. Motilin, ghrelin, serotonin acetylcholine, nitric oxide, and vasoactive intestinal polypeptide are factors that play a role in colon motility. There are a limited number of studies in the literature where hormone levels and gene polymorphisms of serotonin and motilin are examined. Our study aimed to investigate the role of motilin, ghrelin, and serotonin gene/receptor/transporter polymorphisms in constipation pathogenesis in patients diagnosed with functional constipation according to the Rome 4 criteria. METHODS: Sociodemographic data, symptom duration, accompanying findings, the presence of constipation in the family, Rome 4 criteria, and clinical findings according to Bristol scale of 200 cases (100 constipated patients and 100 healthy control) who applied to Istanbul Haseki Training and Research Hospital, Pediatric Gastroenterology Outpatient Clinic, between March and September 2019 (6-month period) were recorded. Polymorphisms of motilin-MLN (rs2281820), serotonin receptor-HTR3A (rs1062613), serotonin transporter-5-HTT (rs1042173), ghrelin-GHRL (rs27647), and ghrelin receptor-GHSR (rs572169) were detected by real-time PCR. RESULTS: There was no difference between the two groups in terms of sociodemographic characteristics. Notably, 40% of the constipated group had a family history of constipation. The number of patients who started to have constipation under 24 months was 78, and the number of patients who started to have constipation after 24 months was 22. There was no significant difference between constipation and control groups in terms of genotype and allele frequencies in MLN, HTR3A, 5-HTT, GHRL, and GHSR polymorphisms (p<0.05). Considering only the constipated group, the rates of gene polymorphism were similar among those with/without a positive family history of constipation, constipation onset age, those with/without fissures, those with/without skin tag, and those with type 1/type 2 stool types according to the Bristol stool scale. CONCLUSION: Our study results showed that gene polymorphisms of these three hormones may not be related to constipation in children.

Relationship between villous atrophy and Wnt pathway gene expressions in pediatric celiac patients

SUMMARY OBJECTIVE: Celiac disease is an autoimmune disease characterized by an abnormal immune response occurring in the small intestine linked to consumption of food containing gluten in individuals with a genetic predisposition. Dysregulation of Wnt signal transduction plays a role in the pathogenesis of many diseases including autoimmune diseases like celiac disease. In this study, the correlation of Wnt pathway gene expressions with each other and the correlation with clinical data were researched in pediatric celiac disease cases grouped according to the Marsh classification. METHODS: Gene expression levels of FZD8, DVL2, LRP5, RHOA, CCND2, CXADR, and NFATC1, which are involved in the Wnt pathway, were determined using quantitative real-time polymerase chain reaction in 40 celiac disease and 30 healthy individuals. RESULTS: All cases with the short height symptom were observed to be in Marsh 3b/3c groups (p=0.03). The gene expressions of DVL2, CCND2, and NFATC1 were high in the Marsh 3b group, and these genes showed positive correlation with each other (p=0.002). LRP5 and CXADR gene expressions were lower in the Marsh 3b group compared to other Marsh groups, and these genes showed a positive correlation with each other (p=0.003). CCND2 gene expression was associated with Marsh 3b group, diarrhea, and vomiting symptoms. DVL2 gene expression was correlated with Marsh 2 group and constipation symptom (p<0.05). CONCLUSION: Wnt signaling in the early stages of the disease of Marsh 1-2 involves high expression of LRP5 and CXADR genes, while expression of these two genes reduces, and DVL2, CCND2, and NFATC1 gene expressions clearly increase with a transduction variation observed from Marsh 3a stage when villous atrophy begins to form. It appears that the Wnt pathway may contribute to disease progression through expression changes.

Flax Fibre Yarn Coated with Lignin from Renewable Sources for Composites.

The present experimental work analyses the potential of lignin as a matrix for materials made from renewable resources for composite components and the production of hybrid semi-finished products by coating a flax fibre yarn. Natural fibres, due to their low density, in combination with lignin can be a new renewable source for lightweight products. For this purpose, the extrusion process was adapted to lignin as a matrix material for bio-based composites and coating of natural fibre yarns. A commercial flax yarn is the basis for the lignin coating by extrusion. Subsequently, the coated flax yarn was characterised with regard to selected yarn properties. In order to produce composite plates, the lignin-coated flax yarn was used as warp yarn in a bidirectional fabric due to its insufficient flexibility transversely to the yarn axis. The commercial flax yarn was used as weft yarn to increase the fibre volume content. The tensile and flexural properties of the bio-based composite material were determined. There was a significant difference in the mechanical properties between the warp and weft directions. The results show that lignin can be used as matrix material for bio-based natural fibre composites and the coating of natural fibre yarns is an alternative to spun hybrid yarns.

Link between obsessive-compulsive disorder and polymorphisms in HDAC genes

Objective: Recently, epigenetic mechanisms related to histone modifications including histone deacetylation (HDAC) have been emphasized in psychiatric diseases. Few studies have investigated the relationship of HDAC gene variations to psychiatric diseases, but these gene variations have never been studied in obsessive-compulsive disorder (OCD). The present case-control study aimed to compare symptomatology with HDAC gene variations in patients with OCD. Methods: Illumina next-generation sequencing of six HDAC genes (HDAC2,3,4,9,10,11) was performed on DNA samples isolated from 200 Turkish subjects recruited from routine clinical practice. Twenty-seven single nucleotide polymorphism (SNPs) in six HDAC genes were scanned with the LightSNiP method. Results: New variants, all previously unreported in the literature, were identified in the HDAC4, HDAC10, and HDAC11 genes. When control and OCD patient groups were compared, a statistically significant difference was found in HDAC2 rs13212283, HDAC4 rs1063639, and HDAC10 rs1555048 in terms of genotype distribution (p < 0.05). In addition, in the OCD group, a statistically significant relationship was found between some obsessions/compulsions and HDAC2, HDAC3, and HDAC4 polymorphisms (p < 0.05). Conclusions: Our study shows that the HDAC2, HDAC3, HDAC4, and HDAC10 genes may play a role in the pathogenesis of OCD.

Development of Natural Fibre-Reinforced Semi-Finished Products with Bio-Based Matrix for Eco-Friendly Composites.

Increasing resource consumption and a growing amount of textile waste increase the importance of a circular economy and recycling in the fashion and apparel industry. Environmentally friendly bio-based composites made from cellulosic fibres obtained from textile waste, and polymers based on renewable raw materials present a possible solution. In this study, the development of textile semi-finished products based on medium-to-long cotton and flax fibres obtained from textile waste in combination with a bio-based thermoplastic matrix for lightweight applications is investigated. For the production of natural fibre-polylactide hybrid yarns, fibre slivers with improved fibre orientation and blending are produced. Subsequently, quasi-unidirectional woven fabrics are produced and consolidated into bio-based composites. Textile and mechanical properties of hybrid yarns as well as bio-composites are analysed with regard to the influence of fibre length, fibre distribution in the yarn, yarn structure and fibre volume content. The results show that the production of bio-based semi-finished products can be a potential way for upcycling textile waste.

Link between obsessive-compulsive disorder and polymorphisms in HDAC genes.

OBJECTIVE: Recently, epigenetic mechanisms related to histone modifications including histone deacetylation (HDAC) have been emphasized in psychiatric diseases. Few studies have investigated the relationship of HDAC gene variations to psychiatric diseases, but these gene variations have never been studied in obsessive-compulsive disorder (OCD). The present case-control study aimed to compare symptomatology with HDAC gene variations in patients with OCD. METHODS: Illumina next-generation sequencing of six HDAC genes (HDAC2,3,4,9,10,11) was performed on DNA samples isolated from 200 Turkish subjects recruited from routine clinical practice. Twenty-seven single nucleotide polymorphism (SNPs) in six HDAC genes were scanned with the LightSNiP method. RESULTS: New variants, all previously unreported in the literature, were identified in the HDAC4, HDAC10, and HDAC11 genes. When control and OCD patient groups were compared, a statistically significant difference was found in HDAC2 rs13212283, HDAC4 rs1063639, and HDAC10 rs1555048 in terms of genotype distribution (p < 0.05). In addition, in the OCD group, a statistically significant relationship was found between some obsessions/compulsions and HDAC2, HDAC3, and HDAC4 polymorphisms (p < 0.05). CONCLUSIONS: Our study shows that the HDAC2, HDAC3, HDAC4, and HDAC10 genes may play a role in the pathogenesis of OCD.

The role of microRNAs in corneal neovascularization and its relation to VEGF.

PURPOSE: This study aimed to investigate the changes in the level of miRNA associated with Vascular Endothelial Growth Factor (VEGF) in corneal neovascularization (CNV), to elucidate the process of CNV formation and, thus, to prepare the ground for further experimental, and clinical studies together with drug treatments. METHODS: Twelve male Wistar-Albino rats were randomly divided into two groups of six, and two corneas of each rat were used. In all groups, CNV was generated by silver nitrate sticks. At the end of the study, rats were sacrificed by cervical dislocation under ether anaesthesia, and then, their corneas were removed. The expression levels of VEGF and miRNA in corneas were determined by qRT-PCR array and qRT-PCR. Data analysis was performed using web-based software named PCR array data. RESULTS: When the corneal samples of rats with CNV were compared to those of the control rats, it was found that a statistically significant difference was present regarding the VEGF level (p < 0.05) with the fold-regulation value> 2. According to the under- and over-expression data in miRNA PCR Array findings of both groups, statistically significant differences were found regarding nine genes with Fold-regulation value <-2 and Fold-regulation value> 2 (p < 0.05). When the corneal samples of the rats with CNV were compared to those of the control rats, statistically significant over-expressions (Fold-regulation value> 2) of rno-miR-21_2, rno-miR-126_1 and rno-miR-150_1 genes were found (p = 0.002443, p = 0.030146, p = 0.000348, respectively). In the same comparison, rno-miR-184_1 gene showed statistically significant under-expression with a Fold-regulation value <-2 (p = 0.006428). Also, in the comparison of the two groups, the fold regulation value of the rno-miR-31_1 gene was found to be close to - g and statistically significantly under-expressed (p = 0.005082). CONCLUSION: The over-expressions of rno-miR-21_2, rno-miR-126_1, and rno-miR-150_1 genes, and the under-expression of rno-miR-184_1 gene were thought to could play roles in the formation process of CNV by regulation of VEGF-A and through modulation of angiogenesis.

Chronic tinnitus and BDNF/GDNF CpG promoter methylations: a case-control study.

Brain-derived neurotrophic factor (BDNF) and Glial-derived neurotrophic factor (GDNF) are neurotrophic factors that play key roles in the auditory pathway. While the relationship between serum levels and polymorphisms of BDNF/GDNF and chronic tinnitus is emphasized in the literature, there is no study showing the link between the promoter methylations of these genes and tinnitus. For this purpose, the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations was investigated to identify their role in the pathophysiology of tinnitus. In this case-control study, we examined the possible effects of BDNF/GDNF methylations in the blood samples of patients with tinnitus complaints for more than 3 months. Sixty tinnitus subjects between the ages of 18-55 and 50 healthy control subjects in the same age group who were free of any otorhinolaryngology and systemic disease were selected for examination. Methylation of total 12 CpG sites in BDNF and GDNF promoter regions were determined by the bisulfite-pyrosequencing method. Statistically significant differences were detected between BDNF CpG6 and GDNF CpG3-5-6 methylation ratios in the comparison of control group and the chronic tinnitus patients (P = 0.002, 0.0005, 0.00003, and 0.0029, respectively). To our knowledge, this is the first study in the literature investigating the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations. It is believed that the current results might be supported by investigating the relationships between BDNF/GDNF methylations and genotypes in future research using higher sample sizes.

Roles of 5,10-methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in early- and late-onset obsessive-compulsive disorder.

BACKGROUND: The C677T and A1298C mutations of 5,10-methylenetetrahydrofolate reductase (MTHFR) have been linked with conditions such as depression, bipolar disorder, and schizophrenia, but there are not clear the relationship between MTHFR polymorphisms and obsessive-compulsive disorder (OCD). AIM: The current study was planned to investigate the link between the MTHFR polymorphisms and OCD in patients to reveal any potential correlations that may be used as a novel marker in diagnosis of people who are in high-risk group of developing OCD. MATERIALS AND METHODS: Blood samples from 64 highly characterized symptomatic cases and 64 gender- and age-matched control participants were analyzed for MTHFR C677T and A1298C gene variants. The MTHFR gene polymorphisms were detected through real-time polymerase chain reaction, followed by melting curve analysis. The results were tested with analysis of variance test and the differences with P < 0.05 were reported as statistically significant. RESULTS: A statistically significant difference in age, education level, and marital status was found in the comparison of all groups in sociodemographic findings (P = 0.004, P = 0.001, and P = 0.001, respectively). A statistically significant difference was found in the comparison of the tic story of early- and late-onset OCD patients (P = 0.002). There was no significant difference in the genotype frequencies and allele distributions of MTHFR polymorphisms between the patients and controls (P > 0.05). CONCLUSION: The results suggest that MTHFR polymorphisms are unlikely to play a major role in the pathogenesis of OCD. Further studies are needed in biochemical data on folate metabolism to clarify the effect of the MTHFR polymorphisms in OCD pathophysiology.

Current updates on microRNAs as regulators of chemoresistance.

Resistance to chemotherapeutics including platinum agents, nucleoside analogues, topoisomerase and microtubule inhibitors is the most important problem in the treatment of many cancer. Several resistance mechanisms has been described for each group and researchers have been trying to develop new approaches to overcome chemoresistance. miRNAs are the regulators of gene transcription at the post-transcriptional level. Dysregulated miRNAs have been reported in cancer tumorigenesis, diagnosis and prognosis and they are promising new therapeutic approaches to improve diagnosis and predictions of outcomes and response to chemotherapy. In this article, we summarized the results from 2015 January to 2017 June which explore the roles of miRNAs in the development of the chemotherapy resistance.