The role of next-generation sequencing in the examination of signaling genes in Brca1/2-negative breast cancer cases.

INTRODUCTION: Breast cancer is the most prevalent malignancy in women worldwide. Although pathogenic variants in the BRCA1/2 genes are responsible for the majority of hereditary breast cancer cases, a substantial proportion of patients are negative for pathogenic variations in these genes. In cancers, the signal transduction pathways of the cell are usually affected first. Therefore, this study aimed to detect and classified genetic variations in non-BRCA signaling genes and investigate the underlying genetic causes of susceptibility to breast cancer. METHODS: Ninety-six patients without pathogenic variants in the BRCA1/2 genes who met the inclusion criteria were enrolled in the study, and 34 genes were analyzed using next-generation sequencing (NGS) for genetic analysis. RESULTS: Based on the ClinVar database or American College of Medical Genetics criteria, a total of 55 variants of 16 genes were detected in 43 (44.8%) of the 96 patients included in the study. The pathogenic variants were found in the TP53, CHEK2, and RET genes, whereas the likely pathogenic variants were found in the FGFR1, FGFR3, EGFR, and NOTCH1 genes. CONCLUSION: The examination of signaling genes in patients who met the established criteria for hereditary breast cancer but were negative for BRCA1/2 pathogenic variants provided additional information for approximately 8% of the families. The results of the present study suggest that NGS is a powerful tool for investigating the underlying genetic causes of occurrence and progression of breast cancer.

Shared Biological Pathways and Processes in Patients with Intellectual Disability: A Multicenter Study.

BACKGROUND: Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses. METHODS: In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RESULTS: Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage-gated ion channel activity/voltage-gated channel activity, respectively. CONCLUSION: Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients.

Differentially expressed miRNAs associated with generalized aggressive periodontitis.

OBJECTIVE: This study aimed to investigate miRNA expression profiles in individuals with periodontitis which is a chronic inflammatory condition affecting the integrity of the periodontal attachment. miRNAs play a crucial role in gene regulation through various mechanisms, making them potential diagnostic markers and therapeutic targets for various diseases. MATERIALS AND METHODS: A total of 25 individuals with aggressive periodontitis and 25 controls were included in the study. Gingival tissues were collected for miRNA isolation and cDNA synthesis. miRNAs associated with periodontitis, including hsa-miR-185-5p, hsa-miR-17, hs-miR-146a, hs-miR-146b, hs-miR-155, hs-miR-203, hs-miR-205, hs-miR-223, and hsa-miR-21-3p, were analyzed using a combination of miRTarBase database analysis and literature mining was performed. Real-time PCR was used to assess the expression patterns of the target miRNAs, and the data were analyzed using the REST program. RESULTS: The study revealed upregulated expression levels of hsa-miR-223-3p, hsa-miR-203b-5p, hsa-miR-146a-5p, hsa-miR-146b-5p, and hsa-miR-155-5p in individuals with periodontitis. Conversely, downregulated expression was observed for hsa-miR-185-5p, hsa-miR-21-3p, and hsa-miR-17-3p. CONCLUSION: The findings suggest significant differences in the expression of specific miRNAs associated with inflammation in periodontitis. MZB1 acts as a hormone-regulated adipokine/pro-inflammatory cytokine, driving chronic inflammation and influencing cellular expansion. Predominantly expressed in marginal zone and B1 B cells, specialized subsets that respond rapidly to infections, MZB1 impacts immune protein synthesis and immune cell maturation, notably targeting microRNA-185 to potentially impede T cell development. Further research is needed to elucidate the functional significance and potential implications of these miRNAs. CLINICAL RELEVANCE: miRNAs regulate the expression of target genes by finely tuning protein expression levels. The current findings provide compelling evidence of notable variations in the expression levels of specific miRNAs associated with inflammation in individuals affected by periodontitis; hence, miRNAs hold promise as potential therapeutic targets for periodontitis.

The diagnostic importance of pathogenic variants and variant coexistence determined by NGS-based liquid biopsy approach in patients with lung adenocarcinoma.

BACKROUND: Identification of driver mutations and rapid detection of genetic changes in lung cancer are critical in the management of the disease. Genetic structures of tumor tissues tend to change constantly and the possibility of emergence of new pathogenic variants that will create resistance to treatment. Liquid biopsy analysis has been one of the most effective approaches used to monitor and identify individual genetic changes. METHODS: In this study, TP53, EGFR, MET, ALK, PIK3CA, MAP2K, ERBB2 and ROS genes in cf DNA samples of 324 patients with lung adenocarcinoma were screened for genetic variations by NGS method. Analysis of the data showed that there were a total of 755 variations in 324 patients. RESULTS: Pathogenic and possibly pathogenic variations were identified in 178 patients (54.9%) on TP53, 118 (36.4%) on EGFR, 55 (17.0%) on MET, 46 (14.2%) on ALK, 39 (12.0%) on MAP2K, 6 (1.9%) on ERBB2 and in 2 (0,6%) patients ROS genes. The detailed variant data of the genes included in the study were compared with the patients' stage status, metastasis status, smoking, age distribution and life span data, and the presence of possible significant relationships and candidate biomarkers for the molecular pathogenesis of the disease were investigated. CONCLUSION: As a result of data analysis, genetic changes associated with metastasis and adenocarcinoma formation were identified. It has been shown that variations identified in TP53, PIK3CA, MAP2K1 and EGFR genes can play critical roles in the pathogenesis and development of the disease.

Haplotype Analysis of Vitamin D Receptor (VDR) Gene in Breast Cancer Patients.

BACKGROUND: The aim of the study was to evaluate the role of well-characterized vitamin D receptor (VDR) gene polymorphisms, BsmI (rs 1544410), ApaI (rs 7975232), TaqI (rs 731236), and FokI (rs 10735810) and their haplotypes in the pathogenesis of breast cancer in Turkish women. METHODS: The subjects consisted of women including 331 breast cancer patients and 345 healthy controls. After conventional DNA isolation genotyping was done by a PCR-RFLP method, haplotype analysis was performed using Haploview 4.2. RESULTS: Haplotype analysis in different combinations revealed that frequencies of Fbt, fbt, bAt, and bt haplotypes are significantly higher in breast cancer patients than controls (χ2 = 6.862, p = 0.0088; χ2 = 4.176, p = 0.041; χ2 = 4.184, p = 0.0408; χ2 = 8.409, p = 0.0037 respectively). However, no statistically significant difference between genotypes of cases and controls were found when analyzed separately. CONCLUSIONS: All these data support the hypothesis that it is crucial to evaluate VDR gene polymorphism by haplotype analysis in order to understand how changes in VDR sequence influence the function of the VDR gene and how this variability affects the risk of breast cancer.

Exenatide Alters Gene Expression of Neural Cell Adhesion Molecule (NCAM), Intercellular Cell Adhesion Molecule (ICAM), and Vascular Cell Adhesion Molecule (VCAM) in the Hippocampus of Type 2 Diabetic Model Mice.

BACKGROUND Glucagon-like peptide-1 (GLP-1), a potent and selective agonist for the GLP-1 receptor, ameliorates the symptoms of diabetes through stimulation of insulin secretion. Exenatide is a potent and selective agonist for the GLP-1 receptor. Cell adhesion molecules are members of the immunoglobulin superfamily and are involved in synaptic rearrangements in the mature brain. MATERIAL AND METHODS The present study demonstrated the effects of exenatide treatment (0.1 µg/kg, subcutaneously, twice daily for 2 weeks) on the gene expression levels of cell adhesion molecules, neural cell adhesion molecule (NCAM), intercellular cell adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) in the brain tissue of diabetic BALB/c male mice by real-time quantitative polymerase chain reaction (PCR). Diabetes was induced by streptozotocin/nicotinamide (STZ-NA) injection to male mice. RESULTS The results of this study revealed that hippocampal gene expression of NCAM, ICAM, and VCAM were found to be up-regulated in STZ-NA-induced diabetic mice compared to those of controls. A significant decrease in the gene expression levels of NCAM, ICAM, and VCAM were determined after 2 weeks of exenatide administration. CONCLUSIONS Cell adhesion molecules may be involved in the molecular mechanism of diabetes. Exenatide has a strong beneficial action in managing diabetes induced by STZ/NA by altering gene expression of NCAM, ICAM, and VCAM.

Validation of reported genetic risk factors for periodontitis in a large-scale replication study.

AIM: Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP). MATERIAL AND METHODS: We analysed 23 genes in 600 German AgP patients and 1441 controls on the Illumina custom genotyping array Immunochip. We tested a suggestive association in a Dutch and German/Austrian AgP case-control sample, and a German chronic periodontitis (CP) case-control sample using Sequenom iPlex assays. We additionally tested the common known risk variant rs1333048 of the gene ANRIL for its association in a Turkish and Italian population. RESULTS: None of the analysed genes gave statistical evidence for association. Upon covariate adjustment for smoking and gender, in the pooled German-Austrian AgP sample, IL10 SNP rs6667202 was associated with p = 0.016, OR = 0.77 (95% CI = 0.6-0.95), and in the Dutch AgP sample, adjacent IL10 SNP rs61815643 was associated with p = 0.0009, OR = 2.31 (95% CI = 1.4-3.8). At rs61815643, binding of the transcription factor PPARG was predicted. ANRIL rs1333048 was associated in the Turkish sample (pallelic = 0.026, OR = 1.67 [95% CI = 1.11-2.60]). CONCLUSIONS: Previous candidate genes carry no susceptibility factors for AgP. Association of IL-10 rs61815643 with AgP is suggested. ANRIL is associated with periodontitis across different populations.

Unique variant of Adams-Oliver syndrome with dilated cardiomyopathy and heart block.

Reported herein is the case of a 2-year-old boy with Adams-Oliver syndrome who presented with dilated cardiomyopathy and complete atrioventricular block. The patient had aplasia cutis congenita with partial aplasia of the skull bones, and terminal transverse limb malformations characteristic of the disease. Although congenital cardiac malformations may be associated with the syndrome, dilated cardiomyopathy has not been previously reported to be associated with the syndrome.

High Throughput FISH Analysis: A New, Sensitive Option For Evaluation of Hematological Malignancies.

OBJECTIVE: The aim of this study was to determine the efficiency of the high throughput FISH analysis (HTFA) method for detecting genetic alterations in hematological malignancies, which is a new bacterial artificial chromosome array-based approach. MATERIALS AND METHODS: We performed a HTFA study of bone marrow aspiration and peripheral blood samples of 77 cases (n=19 myelodysplastic syndrome, n=17 acute lymphoblastic leukemia, n=9 chronic myeloid leukemia, n=32 acute myeloid leukemia) with hematological malignancies during the periods of initial diagnosis, treatment, and/or follow-up. RESULTS: Both numerical and structural abnormalities were detected by HTFA. We observed aberrations in 88% of our acute lymphoblastic leukemia patients, 25% of acute myeloid leukemia patients, and 31% of myelodysplastic syndrome patients. In chronic myeloid leukemia cases, aberration was not detected by HTFA. CONCLUSION: Our results showed that HTFA, combined with other methods, will gradually take a place in the routine diagnosis of hematologic malignancies. CONFLICT OF INTEREST: None declared.

Microsurgical anatomy of membranous layers of the pituitary gland and the expression of extracellular matrix collagenous proteins.

BACKGROUND: There are several reports about the microanatomical and histological features of sellar and parasellar membranous structures and clinical studies about MMP proteinase as a predictive factor. However, studies on collagen contents of sellar and parasellar membranous structures are limited. We demonstrated the membranous structures surrounding the pituitary gland and defined extracellular matrix (ECM) collagenous proteins, collagen I-IV expression patterns of sellar and parasellar connective tissues. METHODS: The study was carried out on ten fresh postmortem human bodies at the Forensic Medicine Institution. Cavernous sinuses were resected with sellar structures and were stored at -80°C liquid nitrogen tanks. Medial wall of the cavernous sinus, pituitary capsule and pituitary tissue samples were obtained for RT-PCR. Opposite side specimens were used for histological and immune staining studies. Collagens I-IV were studied by immunohistochemical and reverse transcription polymerase chain reaction (RT-PCR) methods. FINDINGS: The pituitary capsule and medial wall were identified as two different structures. The fibrous membrane, as the third membrane, was identified as staying whole in eight of ten specimens. Increased type IV collagen was determined in the pituitary gland, medial wall and pituitary capsule, respectively, in both RT-PCR and immunhistochemical studies. Immunhistochemical studies revealed that collagen I was strongly expressed in both the medial wall and pituitary gland. CONCLUSION: Increased type IV collagen was detected especially in pituitary tissue, the medial wall and the pituitary capsule by immune staining and RT-PCR. Type IV collagen was considered to be an important factor in the progression of adenoma and invasion.

Unbalanced 3;22 translocation with 22q11 and 3p deletion syndrome.

This report describes a 25-day-old Turkish boy with unbalanced 3;22 translocation that includes the 22q11.2 deletion and 3p25 deletion syndrome. The karyotype was 45, XY,der(3)t(3;22)(p25;q11),-22. Although no immunological dysfunction could be demonstrated, the boy presented some manifestations of DiGeorge anomaly (DGA), which has been associated with monosomy for the same region of chromosome 22, velocardiofacial syndrome (VCFS), and the 3p deletion syndrome. Clinical features include short stature, hypertelorism, low set ears, cleft lip with cleft palate, short neck, truncus arteriosus, micropenis, clubfoot, over riding toes on right foot, four digits on left foot and growth delay. In addition he had feeding difficulties, respiratory infections, and developmental delay. Fluorescence in situ hybridization (FISH) studies confirmed loss of the proximal DiGeorge chromosomal region (DGCR). Array CGH analysis showed the deletion sites on chromosomes 3 and 22. This report documents a rare chromosomal aberration that causes the 22q11 and 3p deletion syndrome simultaneously.

Two four-marker haplotypes on 7q36.1 region indicate that the potassium channel gene HERG1 (KCNH2, Kv11.1) is related to schizophrenia: a case control study.

BACKGROUND: The pathobiology of schizophrenia is still unclear. Its current treatment mainly depends on antipsychotic drugs. A leading adverse effect of these medications is the acquired long QT syndrome, which results from the blockade of cardiac HERG1 channels (human ether-a-go-go-related gene potassium channels 1) by antipsychotic agents. The HERG1 channel is encoded by HERG1 (KCNH2, Kv11.1) gene and is most highly expressed in heart and brain. Genetic variations in HERG1 predispose to acquired long QT syndrome. We hypothesized that the blockade of HERG1 channels by antipsychotics might also be significant for their therapeutic mode of action, indicating a novel mechanism in the pathogenesis of schizophrenia. METHODS: We genotyped four single nucleotide polymorphisms (SNPs) in 7q36.1 region (two SNPs, rs1805123 and rs3800779, located on HERG1, and two SNPs, rs885684 and rs956642, at the 3'-downstream intergenic region) and then performed single SNP and haplotype association analyses in 84 patients with schizophrenia and 74 healthy controls after the exclusion of individuals having prolonged or shortened QT interval on electrocardiogram. RESULTS: Our analyses revealed that both genotype and allele frequencies of rs3800779 (c.307+585G>T) were significantly different between populations (P = 0.023 and P = 0.018, respectively). We also identified that two previously undescribed four-marker haplotypes which are nearly allelic opposite of each other and located in chr7:150225599-150302147bp position encompassing HERG1 were either overrepresented (A-A-A-T, the at-risk haplotype, P = 0.0007) or underrepresented (C-A-C-G, the protective haplotype, P = 0.005) in patients compared to controls. CONCLUSIONS: Our results indicate that the potassium channel gene HERG1 is related to schizophrenia. Our findings may also implicate the whole family of HERG channels (HERG1, HERG2 and HERG3) in the pathogenesis of psychosis and its treatment.

I405V and TaqIB polymorphisms of the cholesteryl ester transfer protein and their relation to serum lipid and lipoprotein levels in a Turkish population.

Cholesteryl ester transfer protein (CETP) plays a central role in high-density lipoprotein (HDL) metabolism. Genetic polymorphisms of the CETP gene can influence levels of serum lipoproteins. It has been reported that mean HDL-cholesterol (HDL-C) concentrations are low in Turkish population. Thus, we investigated the frequencies of the common I405V and TaqIB polymorphisms of the CETP gene and their relation to serum lipid and lipoprotein levels in a Turkish population. The variant allele frequencies of I405V and TaqIB polymorphisms of the CETP gene were found to be 0.38 and 0.46, respectively and similar to some of the European populations. Subjects for the VV genotype of I405V polymorphism had higher HDL-C levels than did II subjects. The covariance analysis showed that gender and triglyceride (TG) levels have an effect on the association of HDL-C and I405V polymorphism. In conclusion, our results indicate that I405V polymorphism may affect the HDL-C levels in Turkish population. The association of this polymorphism and HDL-C levels could be modified by other factors, such as gender and TG levels.

HOXA-10 gene expression in ectopic and eutopic endometrium tissues: Does it differ between fertile and infertile women with endometriosis?

OBJECTIVE: To compare HOXA-10 gene expression in eutopic endometrium samples, between fertile and infertile endometriosis patients and the fertile control cases, and in endometrium and endometrioma specimens, between severe and moderate endometriosis cases. STUDY DESIGN: Prospective clinical study included women without infertility and endometriosis (Group 1); women without infertility but with endometrioma (Group 2); and infertile women with endometrioma (Group 3). In addition, the Group 2 and 3 cohort were assessed based on the findings obtained during laparoscopy, based on the (rAFS) scoring, as women with a rAFS score of 16-40 were evaluated in Group A, whereas those with rAFS score above 40 were considered in Group B. HOXA-10 gene expression was evaluated in both secretory endometrium tissue and endometrioma specimens. RESULTS: Eutopic endometrium samples from group 2 (reference gene = 0,680 vs. target gene = 0,362) and group 3 (reference gene = 0,641 vs. target gene = 0,183) patients revealed a 1,871-fold and 3,509-fold decrease in HOXA-10 gene expression, respectively, as compared to group 1. Endometrial HOXA-10 gene expression was 1,778-fold down-regulated in group 3 women (reference gene = 1,510 vs. target gene = 0,850), when compared to group 2. Both eutopic endometrium and endometrioma tissue samples from severe endometriosis patients revealed 1,259-fold (reference gene = 1,523 vs. target gene = 1,210) and 1,338-fold (reference gene = 1,274 vs. target gene = 0,952), down-regulation in HOXA-10 gene expressions, respectively, as compared to moderate cases. CONCLUSION: Endometrial HOXA-10 gene expression in women with endometriosis is significantly down-regulated than in those without endometriosis. Endometriosis patients with infertility have significantly lower levels of endometrial HOXA-10 gene expression than endometriosis without infertility; thus decreased expression of this gene may, directly or indirectly, be related with the endometriosis-associated infertility. Severe endometriosis cases express, in their both endometrium and endometrioma tissues, significantly lower levels of HOXA-10 gene than moderate endometriosis cases.

Molecular signatures of chronic periodontitis in gingiva: A genomic and proteomic analysis.

BACKGROUND: To elucidate molecular signatures of chronic periodontitis (CP) using gingival tissue samples through omics-based whole-genome transcriptomic and whole protein profiling. METHODS: Gingival tissues from 18 CP and 25 controls were analyzed using gene expression microarrays to identify gene expression patterns and the proteins isolated from these samples were subjected to comparative proteomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The data from transcriptomics and proteomics were integrated to reveal common shared genes and proteins. RESULTS: The most upregulated genes in CP compared with controls were found as MZB1, BMS1P20, IGLL1/IGLL5, TNFRSF17, ALDH1A1, KIAA0125, MMP7, PRL, MGC16025, ADAM11, and the most upregulated proteins in CP compared with controls were BPI, ITGAM, CAP37, PCM1, MMP-9, MZB1, UGTT1, PLG, RAB1B, HSP90B1. Functions of the identified genes were involved cell death/survival, DNA replication, recombination/repair, gene expression, organismal development, cell-to-cell signaling/interaction, cellular development, cellular growth/proliferation, cellular assembly/organization, cellular function/maintenance, cellular movement, B-cell development, and identified proteins were involved in protein folding, response to stress, single-organism catabolic process, regulation of peptidase activity, and negative regulation of cell death. The integration and validation analysis of the transcriptomics and proteomics data revealed two common shared genes and proteins, MZB1 and ECH1. CONCLUSION: Integrative data from transcriptomics and proteomics revealed MZB1 as a potent candidate for chronic periodontitis.

TP53, EGFR and PIK3CA gene variations observed as prominent biomarkers in breast and lung cancer by plasma cell-free DNA genomic testing.

Use of plasma cell-free DNA genomic testing, also know as liquid biopsy, reveals information for early detection and monitoring of solid tumors. Our study reports the analysis of 113 lung and 18 breast cancer patients using commercially available platforms. Lung and breast cancer panel hotspot regions on the genes were investigated. There was a significant increase in isolation efficiency with very fresh blood samples of at least 15 millilitres which were processed in minutes. TP53 gene variations were detected in both types of tumors. Additionally, associations were found for EGFR variations in lung tumors and PIK3CA variations in breast tumors. Mutation assessment of these three genes are recommended as useful biomarkers for predictive studies, to follow up tumor growth and for personalized treatment. Mutations observed in this study warrant further investigation for follow up studies and may justify expression studies. However, in our subsequent studies, we intensify our tumor profiling strategy with other methods. However in terms of true personalized medicine,future plans would include repeating these studies with ctDNA size analysis and methylation analysis of the non-coding region in the individual tumors.

Association of MDR1 (C3435T) polymorphism and resistance to carbamazepine in epileptic patients from Turkey.

BACKGROUND AND AIMS: We investigated the prevalence of this multidrug resistance 1 gene (MDR1) polymorphism in drug-responsive versus drug-resistant epilepsy patients treated with carbamazepine (CBZ), which is a substrate of this protein. METHODS: We genotyped the C3435T variant of MDR1 in 97 patients treated with CBZ monotherapy who had been on stable doses for more than 1 month. Our control group included 174 healthy individuals. Plasma CBZ concentrations were also measured using fluorescence polarization immunoassay. RESULTS: We could not demonstrate any statistically significant relationship with the genotypes among drug-resistant patients (n = 44). The frequency of the homozygous mutant (TT) genotype was 15% in drug-responsive patients, 11.3% in drug-resistant patients and 25.8% in the control group. We also did not observe any significant correlation between the presence of a specific allele and CBZ plasma level/dose index. CONCLUSION: Our study did not support any significant association between the MDR1 (C3435T) polymorphism and resistance to CBZ in epilepsy patients from Turkey.

Exenatide upregulates gene expression of glucagon-like peptide-1 receptor and nerve growth factor in streptozotocin/nicotinamide-induced diabetic mice.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has modulating effects on insulin release. GLP-1 and receptors for GLP-1 are widely expressed throughout the body including the brain. The expression of GLP-1 receptors is very specific to large neurons in hippocampus, neocortex, and cerebellum. GLP-1 receptor stimulation enhances glucose-dependent insulin secretion and lowers blood glucose in type 2 diabetes mellitus. Studies on adipobiology of neurotrophins have focused on nerve growth factor (NGF) as an example of adipose-derived neurotrophins. Compromised trophic factor signaling may underlie neurodegenerative diseases ranging from Alzheimer's disease to diabetic neuropathies. Exenatide, a potent and selective agonist for the GLP-1 receptor, is currently approved for the treatment of type 2 diabetes mellitus. The aim of this study was to assess the effect of chronic exenatide treatment on the hippocampal gene expression levels of GLP-1 receptor and NGF in diabetic mice. The effects of chronic exenatide treatment (0.1 µg/kg, s.c., twice daily for 2 weeks) on GLP-1 receptor and NGF gene expression levels in the hippocampus of streptozotocin/nicotinamide (STZ-NA)-induced diabetic mice were assessed by quantitative real-time polymerase chain reaction (RT-PCR). The results of this study revealed that hippocampal gene expression of GLP-1 receptor and NGF were downregulated in diabetic mice. Importantly, a significant increase in the gene expression level of GLP-1 receptor and NGF was determined after 2 weeks of exenatide administration. Increased gene expression level of GLP-1 receptor and NGF may underlie the beneficial action of exenatide in STZ/NA-induced diabetes.

Gene-Expression Profiles in Generalized Aggressive Periodontitis: A Gene Network-Based Microarray Analysis.

BACKGROUND: In this study, molecular biomarkers that play a role in the development of generalized aggressive periodontitis (GAgP) are investigated using gingival tissue samples through omics-based whole-genome transcriptomics while using healthy individuals as background controls. METHODS: Gingival tissue biopsies from 23 patients with GAgP and 25 healthy individuals were analyzed using gene-expression microarrays with network and pathway analyses to identify gene-expression patterns. To substantiate the results of the microarray studies, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to assess the messenger RNA (mRNA) expression of MZB1 and DSC1. The microarrays and qRT-PCR resulted in similar gene-expression changes, confirming the reliability of the microarray results at the mRNA level. RESULTS: As a result of the gene-expression microarray studies, four significant gene networks were identified. The most upregulated genes were found as MZB1, TNFRSF17, PNOC, FCRL5, LAX1, BMS1P20, IGLL5, MMP7, SPAG4, and MEI1; the most downregulated genes were found as LOR, LAMB4, AADACL2, MAPT, ARG1, NPR3, AADAC, DSC1, LRRC4, and CHP2. CONCLUSIONS: Functions of the identified genes that were involved in gene networks were cellular development, cell growth and proliferation, cellular movement, cell-cell signaling and interaction, humoral immune response, protein synthesis, cell death and survival, cell population and organization, organismal injury and abnormalities, molecular transport, and small-molecule biochemistry. The data suggest new networks that have important functions as humoral immune response and organismal injury/abnormalities. Future analyses may facilitate proteomic profiling analyses to identify gene-expression patterns related to clinical outcome.

Deregulated Levels of the NF-κB1, NF-κB2, and Rel Genes in Ukrainian Patients with Leukemia and Lymphoma in the Post-Chernobyl Period.

OBJECTIVE: Nuclear factor kappa B (NF-κB) is an important transcription factor in cancer and NF-κB activation has been seen in angiogenesis, tumor progression, and metastasis. Relationships between specific NF-κB gene networks, leukemogenesis, and radiation exposure are still unknown. Our aim was to study the expression levels of the NF-κB1, NF-κB2, and Rel genes in hematological malignancies in the post-Chernobyl period. MATERIALS AND METHODS: We analyzed gene expression levels of NF-κB1, NF-κB2, and Rel in 49 B-cell chronic lymphocytic leukemia, 8 B-cell non-Hodgkin's lymphoma, 3 acute myeloid leukemia, 3 chronic myeloid leukemia, 2 hairy cell leukemia, 2 myelodysplastic syndrome, and 2 T-cell large granular lymphocytic leukemia patients using real-time polymerase chain reaction. RESULTS: Expression levels of NF-κB1, NF-κB2, and Rel genes were found to be deregulated. CONCLUSION: These results could be accepted as specific gene traces to radiation-induced leukemia or as potential candidates for new diagnostic biomarker studies. Larger experiments and non-exposed control malignant cell populations are needed to clarify these suggestions.