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The prenatal diagnosis of congenital heart disease (CHD) is important because of mortality risk. The onset of CHD varies, and depending on the malformation type, the risk of aneuploidy is changed. To identify possible genetic alterations in CHD, G-banding, chromosomal microarray or if needed DNA mutation analysis and direct sequence analysis should be planned.In present study, to identify genetic alterations, cell culture, karyotype analysis, and single nucleotide polymorphism, array analyses were conducted on a total 950 samples. Interventional prenatal genetic examination was performed on 23 (2, 4%, 23/950) fetal CHD cases. Chromosomal abnormalities were detected in 5 out of 23 cases (21, 7%). Detected chromosomal abnormalities were 10q23.2 deletion, trisomy 18, 8p22.3-p23.2 deletion, 8q21.3-q24.3 duplication, 11q24.2q24.5 (9 Mb) deletion, and 8p22p12 (16.8 Mb) deletion. Our study highlights the importance of genetic testing in CHD.

It is extremely important to understand the causes of autism spectrum disorder (ASD) which is a neurodevelopmental disease. Treatment and lifelong support of autism are also important to improve the patient's life quality. In this article, several findings were explained to understand the possible causes of ASD. We draw, outline, and describe ASD and its relation with the epigenetic mechanisms. Here, we discuss, several different factors leading to ASD such as environmental, epigenetic, and genetic factors.

Genetic and epigenetic factors have an important role during the development of osteoporosis. Receptor activator of nuclear factor-κ B (NF-κB) (RANK)/receptor activator of NF-κB ligand (RANKL) pathway is important for the bone remodeling, and NFATC1 and FOS are the downtargets of this pathway. Here, we report methylation status of NFATC1 and FOS genes in post- and premenopausal women. In this study, 30 premenopausal and 35 postmenopausal women were included. Methylation sensitive-high resolution melting (MS-HRM) analysis was used for identification of NFATC1 and FOS genes methylation. The NFATC1 gene was methylated in 11 of the 35 postmenopausal women, and the FOS gene was methylated in six of the postmenopausal women (p >0.005). Here, we found statistically significant association between unmethylation of the NFATC1 gene and postmenopausal status. This result explains the epigenetic regulation of osteoclasts during the menopausal transition, and for the first time, our results can be used for epigenetic explanation of postmenopausal osteoporosis in the literature. However, the limited number of studies in this field makes our results crucial. Our results showed great value of epigenetic profiles of postmenopausal women.

Multiple myeloma (MM) is one of the plasma cell-related hematological malignancies exceeding 10.0% of all marrow cells, and they make a paraprotein that is a marker of the disease. Myeloma is one of the most common types of hematological malignancies in humans. Genetic bio-markers have been used for prognostic markers in patients diagnosed with MM. The genetic and genomic changes have been identified using karyotyping, fluorescent in situ hybridization (FISH), next generation sequencing (NGS), specifically whole-genome sequencing or exome sequencing. Circulatory plasma cells, circulating free DNA (cfD-NA) and microRNAs (miRNAs) comprised in liquid biopsy are potentially used in diagnosis/prognosis of MM. In this study, we analyzed and compared results of karyo-typing, FISH and NGS in 35 MM cases. Diagnostic strategies are expanding rapidly and newly developed NGS-based testing may help the understanding of the complexities of genetic alterations in karyotypically normal cases.

The gut microbiota has an extremely important role within the body and it is necessary for the regulation of the metabolism of the host and also for the development of metabolic diseases such as obesity. Here, we show several different factors leading to obesity such as epigenetic changes and how they result in differences to occur in the gut microbiota, along with gut dysbiosis which is caused by disturbances in the microbiota homeostasis. Several studies have been explained in this paper, providing evidence in how these findings can actually decrease the susceptibility of obesity, whether it be by changing an individual's diet pattern or observing the epigenetic changes which are taking place. KEY POINTS: • The microbiota depends on an individual's diet, lifestyle, environment, genetics and epigenetic profile. • Changes of the gut microbiota can increase obesity susceptibility. • Non-coding RNA has an important role in the metabolic homeostasis in check so if a disturbance occurs it can lead to resistance to obesity.

Cancer can be identified as an uncontrolled growth and reproduction of cell. Accumulation of genetic aberrations (mutations of oncogenes and tumor-suppressor genes and epigenetic modifications) is one of the characteristics of cancer cell. Increasing number of studies highlighted importance of the epigenetic alterations in cancer treatment and prognosis. Now, cancer epigenetics have a huge importance for developing novel biomarkers and therapeutic target for cancer. In this review, we will provide a summary of the major epigenetic changes involved in cancer and preclinical results of epigenetic therapeutics.

Articular cartilage is a poorly cellularized, non-vascularized connective tissue that undergoes alterations due to trauma and osteoarthritis. Tissue engineering strategies involving the combination of cells, biomaterials and bioactive agents have been of interest notably for the repair of damaged articular cartilage. The aim of this study was to design Chitosan/Silk Fibroin/Egg Shell Membrane (CHI/SF/ESM) hydrogels and analyse the cell proliferation activity of human chondrocyte cells. The FTIR spectrophotometer, XRD analysis, ICP-MS, SEM analysis, swelling kinetics and biodegradation tests with protease enzyme, and antibacterial activity test with Escherichia coli, Candida albicans have been used for characterization of hydrogels. CHI/SF/ESM hydrogel structures, and chemical homogeneity of the ECM was well-reproduced. Human articular chondrocytes were seeded on hydrogels and cultured up to 2 weeks under the standard culture conditions. The attachment and cell growth of chondrocytes were examined by phase contrast microscopy and by MTT assay at 24 h, 72 h and 7 days. The hydrogel supported better adhesion, growth and differentiation of chondrocyte cells under standard culture conditions. The results obtained have suggested that, CHI/SF/ESM hydrogels can potentially function as a promising cartilage substitute for tissue engineering application.

Coronavirus disease 2019 (COVID-2019) started in Wuhan, China, in December 2019. Angiotensin-converting enzyme 2 (ACE2) receptor was one of the most important genes related to the entrance of the virus to the host. Until now, several variations have been identified in ACE2 and related transmembrane protease serine 2. Epigenetic modifications not only play an important role during the maintenance of genome and cellular homoeostasis but also for the etiopathophysiology of the virus infection. Studies showed methylation of ACE2 was changed to depend on host and age of the host during the viral infection.In this study, we provided an epigenetics point of view to the coronavirus infection. We highlight the importance of epigenetic modifications during viral replication and infection and their interaction with COVID-19 susceptibility and host viral response.

The early fusion of the cranial sutures was described as a craniosynostosis. The early diagnosis and management of craniosynostosis is very important. Environmental factors and genetic abnormalities plays a key role during the development of craniosynostosis. Syndromic craniosynostosis cases are related with autosomal dominant disorders but nearly half of the affected cases carry a new mutation. In this study, in order to identify the genetic etiology of craniosynostosis the authors analyzed 20 craniosynostosis patients by using conventional karyotype, aCGH, sanger sequencing, next generation sequencing (NGS) and Multiplex ligation-dependent probe amplification (MLPA) techniques. The authors identified mutations on FGFR2 and FGFR3 genes which were associated with Muenke syndrome, Crouzon syndrome and skeletal dysplasia syndromes. NGS applied all of the cases and 7 clinical variations in 5 different gene were detected in %20 of cases. In addition to these abnormalities; del(11)(q14.1q22.2), del(17)(q21.31), dup(22)(q13.31) and t(2;16)(q37;p13) have been identified in our cohort which are not previously detected in craniosynostosis cases. Our study demonstrates the importance of detailed genetic analysis for the diagnosis, progression and management of the craniosynostosis.

During menopausal transition, decreased level of estrogen brings a number of physiological problems and hormonal changes. In this study, promoter methylation of RANKL and FSHR genes were identified in 30 premenopausal and 35 postmenopausal women using methylation-specific high resolution melting (MS-HRM) analysis. The statistical analyses and their association with patient characteristics were performed by Pearson χ2 and Fisher’s exact test (p RANKL gene was detected in 16 postmenopausal cases, and 12 (75.0%) of the RANKL methylated cases had hot flashes (p = 0.024). The methylated FSHR gene was detected in 18 postmenopausal cases, and 13 (75.0%) of the methylated cases had hot flashes (p = 0.028). In vitro studies demonstrated the association between RANKL expression, FSH level and hot flashes in the mouse. Although lack of epigenetic studies in this field proves our results crucial and therefore, our results showed magnitude of epigenetic profiles of Turkish Cypriot post-menopausal women. This was the first study which has investigated the RANKL and FSHR methylation and their relationship with hot flashes in postmenopausal women.

Osteoporosis is a major health issue, especially in older women. The absence of estrogen is the main cause of menopausal osteoporosis. Estrogen and androgen hormones play major roles during the growth and development of the skeletal system, including preservation of bone structure. Estrogen plays an important role in the balance between the bone formation of osteoblasts and osteoclasts, which are associated with bone resorption. Several pathways have been shown to regulate bone formation and degradation. Estrogen and Ephrin-Eph pathways are among the most important molecular mechanisms that regulate bone reconstruction. Many different genes are involved in these pathways, and in some cases, these pathways may work together for the bone reconstruction and resorption. In this review, we evaluate the relationship between estrogen, RANKL, and EphirinB2, and we highlight the direct relation between osteoporosis and estrogen hormone. The identification of direct or indirect pathways of bone formation and degradation in pre- and postmenopausal women could be an important tool for the development of therapeutic strategies in postmenopausal women.

Scaffolds are important tools in tissue engineering and play a unique role in tissue regeneration and repair of damaged tissues. A variety of natural, synthetic, and composite scaffold types can be used in cartilage tissue engineering. The limited capability of cartilage to repair itself has always been a problem during recovery from damage. The success of cartilage regeneration is dependent on a couple of factors, but the basic properties of scaffolds are biocompatibility, degradability under physiological conditions, and structural support for cell attachment. In this review, we summarize the use of different scaffold types in cartilage regeneration.

Genetic and epigenetic factors have an important role during the development of osteoporosis. RANK/RANKL pathway is important for the bone remodeling and NFATC1 and c-FOS are the downtargets of this pathway. Here, we report methylation status of NFATC1 and C-FOS genes in post and premenopausal cases. In this study 30 pre-menopausal and 35 post-menopausal cases were included. MS-HRM was used for identification of NFATC1 and C-FOS metyhylation.NFATC1 were methylated in 11 of the 35 post-menopausal women and C-FOS were methylated in 6 of the postmenopausal women (p >0.005). Here, we found statistically significant association between unmethylation of NFATC1 and post-menopausal status. This result explains the epigenetic regulation of osteoclasts during the menopausal transition and our results can be used for epigenetic explanation of post-menopausal osteoporosis for the first time in the literature. Although the limited number of studies in this field makes our results crucial. Therefore, our results showed great value of epigenetic profile of post-menopausal women.

Obesity is a complex disorder that is influenced by genetic and environmental factors. DNA methylation is an epigenetic mechanism that is involved in development of obesity and its metabolic complications. The aim of this study was to investigate the association between the RANKL and c-Fos gene methylation on obesity with body mass index (BMI), lipid parameters, homeostasis model assessment of insulin resistance (HOMA-IR), plasma leptin, adiponectin and resistin levels. The study included 68 obese and 46 non-obese subjects. Anthropometric parameters, including body weight, body mass index, waist circumference, and waist-hip ratio, were assessed. Serum glucose, triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), plasma leptin, adiponectin and resistin levels were measured. Methylation status of RANKL and c-Fos gen were evaluated by MS-HRM. Statistically significant differences were observed between obese patients and the controls with respect to RANKL and c-Fos gene methylation status (p

RNA methylation, which was identified back in 1970s, has gained remarkable interest in recent years as it was shown to be a reversible modification involved in many cellular processes like mRNA and miRNA processing, mRNA localisation, translation suppression, or activation. These, in turn, affect important bioprocesses such as tissue development, sex determination, and DNA damage response. Important group of proteins are responsible for adding, recognizing, and removing the methyl group to and from the RNA molecules, which are referred as writers, readers, and erasers, respectively. If any of the processes is not strictly controlled, this can cause abnormalities in gene expression, which result in diseases including cancers such as lung, pancreas, glioblastoma, and breast cancer. Mechanisms of RNA methylation and its role in various cancer types and diagnostic methods for RNA methylation are discussed in this article.

Advanced diagnostic methods give an advantage for the identification of the abnormalities in myeloid malignancies. Various researchers have shown the potential importance of genetic tests both before the onset of the disease and during the remission. Large testing panels prevents false negative results in myeloid malignancies. But the important question is how the results of conventional cytogenetic and molecular cytogenetic techniques can be merged together with NGS technologies. In this paper, we drew an algorithm for evaluation of the myeloid malignancies. In order to evaluate genetic abnormalities, we performed cytogenetics, molecular cytogenetics and NGS testing in hematologic malignancies. In this study, we analyzed 100 patients who admitted to Medical Genetics Laboratory within different type of myeloid malignancies. We highlighted the possible diagnostic algorithm for cytogenetically normal cases. We applied NGS 141 gene panel for cytogenetically normal patients and we detected two or more pathogenic variations in 61 out of 100 patients (61%). The pathogenic variation detection rate of NGS varies in disease groups: AML were 85% and MDS were 23%. Here, we identified 24 novel variation out of total pathogenic variations in myeloid malignancies. A total 18 novel variation were identified in AML and 6 novel variation were identified in MDS. Despite of long turnaround time, conventional techniques are still golden standard for myeloid malignancies but sometimes cryptic gene fusions or complex abnormalities cannot be identified easily by conventional techniques. In these conditions, advanced technologies like NGS are highly recommended.

Patients with Turner syndrome are generally characterized by having short stature with no secondary sexual characteristics. Some abnormalities, such as webbed neck, renal malformations (>50%) and cardiac defects (10%) are less common. The intelligence of these patients is considered normal. Non-mosaic monosomy X is observed in approximately 45% of postnatal patients with Turner syndrome and the rest of the patients have structural abnormalities or mosaicism involving 46,X,i(Xq), 45,X/46,XX, 45,X and other variants. The phenotype of 45,X/46,X,+mar individuals varies by the genetic continent and degree of the mosaicism. The gene content of the marker chromosome is the most important when correlating the phenotype with the genotype. Here we present an 11-year-old female who was referred for evaluation of her short stature and learning disabilities. Conventional cytogenetic investigation showed a mosaic 45,X/46,X,+mar karyotype. Fluorescence in situ hybridization showed that the marker chromosome originated from the X chromosome within the androgen receptor (AR) and X-inactive specific transcript (XIST) genes. Therefore, it is possible that aberrant activation of the marker chromosome, compromising the AR and XIST genes, may modify the Turner syndrome phenotype.

Purpose To establish the frequency of IDH1 mutations and MGMT methylation in primary glioblastomas. Experimental design We screened primary glioblastoma multiforme (GBM) in a population-based study for IDH1 mutations and MGMT methylation and correlated them with clinical data. Results IDH1 mutations were detected in 5 of 40 primary glioblastomas (12,5%). Primary GBM patients carrying IDH1 mutations were significantly younger, mean age of 41 ± 5.06 years, than patients with wild-type IDH1, mean age of 57 ± 2,29 years, p = 0.011. The mean survival time of all GBM patients with and without IDH1 mutations was 19 months (5 cases) and 16 months (35 cases), respectively (p > 0,05). MGMT methylation was detected in 13 of the 40 patients (32,5%). MGMT-promoter methylation did not correlate with overall survival (OS; p > 0,05). Conclusion In summary, our study is the first study to investigate the IDH1 mutation status and MGMT methylation in primary GBMs in Turkish population and confirmed IDH1 mutation as a genetic marker for also primary GBMs. Our data are still insufficient for definite ascertainment; and our preliminary results suggest: IDH1 status shows an association with younger age and there is a lack of association between IDH1 mutation and survival time. Furthermore MGMT promoter methylation had no prognostic value and lower frequency in primary glioblastomas.

Human mesenchymal stem cells (hMSCs) have the ability to differentiate into several tissue types. Their use in cancer therapeutics or as therapeutic delivery vehicles has significant potential, particularly in their exosome/microvesicle-mediated tissue regeneration abilities. In this review, the potential use of hMSCs in cancer therapy is discussed.

Glioblastoma (GBM) is the most aggressive primary brain tumor, providing few effective therapeutic options, given the tumor heterogeneity and the accumulation of different genetic abnormalities that cause treatment failure. The many different genetic and epigenetic alterations present in GBM lead to modification of several major signaling pathways resulting in brain tumor growth, progression, and therapeutic resistance. Many functionally important mutations have been discovered, known as neutral passengers. IDH1/2, EZH2, and DNMT3A are the best known epigenetic modifiers in cancer. These mutations are important in determining disease prognosis such that the status of the MGMT gene is a direct target of chemotherapy. For these reasons, newly developed technologies are necessary to determine new candidate targets for targeted-therapy development in GBM. The determination of mutations will aid in this and in the discovery of combinations of targeted and conventional therapies to improve GBM treatment.

Glioblastoma multiforme (GBM) is divided into two distinct disease entities called primary and secondary GBM. The genetic and the epigenetic background of these tumors are highly variable. These tumors are not successfully treated because of their cellular heterogeneity and intrinsic ability of the tumor cells to invade healthy tissues. The fatal outcomes of these tumors promote researchers to find new markers associated with prognosis and treatment planning. A better understanding of stem-like cells and the genetic and the epigenetic background of GBM are necessary for designing new effective treatments and developing novel molecular strategies to target tumor cells and glioblastoma stem cells. In this review, we discuss the new therapeutic targets. Focusing on inhibiting the signaling pathways, which are associated with hypoxia-mediated maintenance of glioblastoma stem cells or the knockdown of the hypoxia-inducible factor 1-alpha (HIF1α), may help to the develop new target-specific treatments.

Glioblastoma (GBM) can be divided into two distinct disease entities according to the genetic and the epigenetic background of the tumor. Tumor location is associated with high variability in its genetic abnormalities. The treatment procedures for these tumors are often unsuccessful because of the cellular heterogeneity and intrinsic ability of the tumor cells to invade healthy tissues. The fatal outcomes of these tumors have encouraged researchers to find new markers associated with prognosis and treatment planning. In the present communication, we discuss hypoxia as a new therapeutic target of glioblastoma multiforme and the molecular and phenotypic effects of hypoxia on cancer cells. We focus on the inhibition of the signaling pathways, which is associated with the hypoxia-mediated maintenance of glioblastoma stem cells and the knockdown of the hypoxia-inducible factor 1-alpha (HIFlα). This discussion may contribute to the development of new specifically targeted treatments. Furthermore, we highlight the idea that hypoxia-inducible factors (HIFs) could be attractive molecular targets for GBM therapeutics.

Human mesenchymal stem cells (hMSCs) are multipotent non-hematopoietic precursor cells with the ability to differentiate into several tissue types. The use of hMSCs has gained significant importance in cancer therapies as well as a large number of degenerative disease therapies due to their homing abilities. However, these cells may undergo spontaneous transformation leading to them bypassing naturally built-in cell controls that could lead to senescence and carcinogenesis. Therefore, although MSCs have great potential for cancer therapy, they also risk the development of cancer, which provides them with double-faced characteristics for both cancer development and therapy. The potential use of hMSCs in therapeutics from the aspect of in vitro expansion of hMSCs and telomere dynamic is discussed.

Background: We screened RARβ methylation in primary glioblastoma multiforme (GBM) and the results were evaluated based on the clinical data and treatment type. Objective: The objective of this study was to find new areas for the usage of MS HRM applications in the determination of methylation levels in primary GBM samples and it shows the association of RARβ methylation with the clinical outcome. Methods: In our study, tumor samples were collected during surgical resection by the Department of Neurosurgery. The clinical and radiologic data was carefully reviewed, compared, and evaluated with the histological results. The methylation status of RARβ was determined by using MS-HRM. Results: RARβ gene methylation was detected in 24 out of 40 cases (60%), with different quantitative methylation levels. The mean survival time was 19 months form ethylated cases and 15 months for the non-methylated cases. The survival time of the patients who received treatment was 25 months and the survival time of the patients who received radiotherapy alone or where no treatment protocol applied was 15-20 months. Therefore, a significant difference in survival rates has been observed (P

Primary and secondary glioblastomas (GBMs) are two distinct diseases. The genetic and epigenetic background of these tumors is highly variable. The treatment procedure for these tumors is often unsuccessful because of the cellular heterogeneity and intrinsic ability of the tumor cells to invade healthy tissues. The fatal outcome of these tumors promotes researchers to find out new markers associated with the prognosis and treatment planning. In this communication, the role of glioblastoma stem cells in tumor progression and the malignant behavior of GBMs are summarized with attention to the signaling pathways and molecular regulators that are involved in maintaining the glioblastoma stem cell phenotype. A better understanding of these stem cell-like cells is necessary for designing new effective treatments and developing novel molecular strategies to target glioblastoma stem cells. We discuss hypoxia as a new therapeutic target for GBM. We focus on the inhibition of signaling pathways, which are associated with the hypoxia-mediated maintenance of glioblastoma stem cells, and the knockdown of hypoxia-inducible factors, which could be identified as attractive molecular target approaches for GBM therapeutics.