Immunohistochemical and molecular evaluation of TUSC2 expression in breast cancer.

OBJECTIVE: Tumor suppressor candidate 2 has shown to be deleted in lung, colon, and bladder cancer types. In the present study, we aimed to investigate the expression of TUSC2 in breast cancer. MATERIALS AND METHODS: A total of thirty patients with breast cancer were included in the study. Normal and tumor tissue samples from fresh mastectomy materials were stored at -80 C until the number of cases was completed for gene expression analysis. Histopathological examination was carried out with routine hematoxylin & eosin method. TUSC2 staining was performed for immunohistochemical analysis. RESULTS: The tumors of thirteen patients were Luminal A, fourteen patients were Luminal B, one patient was cerbB2(+), and tumors of two patients were triple-negative. Ki67 proliferation index was less than 14% in fifteen cases and tumor size was less than 2 cm in seven cases. Lymphovascular invasion and lymph node metastasis were present in thirteen cases. Statistically, TUSC2 expression significantly decreased or was lost in breast tumor tissues compared to normal tissues (p < 0.0001). TUSC2 expression decreased as the Ki67 proliferation index increased (p = 0.0003), and TUSC2 expression decreased as tumor size increased (p = 0.0483). The loss or decrease in the TUSC2 expression was significant as the tumor grade increased (p = 0.3740). Gene expression analysis correlated with immunohistochemistry results. CONCLUSION: The results of the present study demonstrated a decrease or loss of TUSC2 expression in breast cancer tissue compared to normal tissue. A correlation was found between TUSC2 expression and Ki67 proliferation index and tumor size.

Changes of miR-139-5p, TGFB1, and COL1A1 in the placental tissue of cases with gestational diabetes mellitus.

There are structural changes in the placenta of cases with Gestational Diabetes Mellitus (GDM). TGF-ß and collagen pathways have crucial roles in tissue remodeling and TGF-ß1 and COL1A1 are important genes in these signalling respectively. Also, lncRNA NEAT1, and miRNA hsa-miR-139-5p and hsa-miR-129-5p have regulatory effects on TGF-ß1 and COL1A1. Here we aimed to assess their expressions in the placenta tissue of GDM cases. 30 patients with GDM and 30 healthy pregnant women participated in the study. Placental tissues taken during normal or cesarean delivery were used and total RNA was isolated from the tissues. mRNA levels were determined by qPCR and protein levels were determined by ELISA methods. An in silico analysis was done to elucidate the possible relation of TGF-ß1 and COL1A1 gene networks with GDM. We determined that NEAT1 and miR-129-5p expression levels did not differ between GDM and healthy control groups (p = 0.697 and 0.412, respectively). But, miR-139-5p mRNA level, TGFB1 and COL1A1 protein levels significantly differ between the GDM and control groups (p = 0.000, p = 0.000 and p = 0.001, respectively). The in silico analysis revealed that TGFB1 and COL1A1 genes network may have important role in the GDM with their variety of members and regulatory molecules NEAT1, hsa-miR-139-5p, and hsa-miR-129-5p can control their functions. The expression of TGFB1, COL1A1 and miR-139-5p is changed in placenta tissue of GDM cases and many genes in the interacting networks of TGFB1 and COL1A1 could contribute to the pathogenicity of GDM.

Molecular and in silico analyses of SYN III gene variants in autism spectrum disorder.

BACKGROUND: Defects in neurotransmission and synaptogenesis are noteworthy in the pathogenesis of ASD. Synapsin III (SYN III) is defined as a synaptic vesicle protein that plays an important role in synaptogenesis and regulation of neurotransmitter release and neurite outgrowth. Therefore, SYN III may associate with many neurodevelopmental diseases, including ASD. AIM: The aim of this study was to investigate whether the SYN III gene -631 C > G (rs133946) and -196 G > A (rs133945) polymorphisms are associated with susceptibility to ASD. METHODS: SYN III variants and the risk of ASD were investigated in 26 healthy children and 24 ASD children. SYN III gene variants were genotyped by PCR-RFLP methods. The differences in genotype and allele frequencies between the ASD and control groups were calculated using the chi-square (χ2). We analysed the SYN III gene using web-based tools. RESULTS: Our results suggest that the presence of the AA genotype of the SYN III -196 G > A (rs133945) polymorphism affects the characteristics and development of ASD in children (p = 0.012). SYN III -631 C > G (rs133946) polymorphism was not associated with ASD (p = 0.524). We have shown the prediction of gene-gene interaction that SYN III is co-expressed with 17 genes, physical interaction with 3 genes, and co-localization with 12 genes. The importance of different genes (SYN I, II, III, GABRD, NOS1AP, GNAO1) for ASD pathogenesis was revealed by GO analysis. CONCLUSION: Considering the role of SYN III and related genes, especially in the synaptic vesicle pathway and neurotransmission, its effect on ASD can be further investigated.

Evaluation of mTOR Activity in COPD Patients with Emphysema.

OBJECTIVE: To evaluate the function of the mammalian target of the rapamycin (mTOR) pathway in chronic obstructive pulmonary disease (COPD) patients with emphysema. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Pulmonology, Mugla Training and Research Hospital, Turkey, from January to March 2022. METHODOLOGY: Thirty COPD patients and thirty healthy volunteers were included. Demographic data, pack-year of cigarette, spirometric values, and emphysema percentage (calculated with CT scan) were recorded. mTOR, raptor, and deptor were measured with ELISA method. Statistical significance was accepted as p<0.05. RESULTS: The mean value of mTOR in the COPD group was 3.48±2.01 ng/ml and it was significantly higher than the control (1.51±0.44 ng/ml). The mTOR was positively correlated with MMRC, annual exacerbation rate, emphysema percentage, and pack/year of cigarette and negatively correlated with SpO2 and FEV1. The significant relationship was found with only emphysema (B=0.067, SE=0.020, 95% CI=0.027-0.107, p=0.002). The cut-off value of mTOR for COPD was found as 1.815 ng/ml (sensivity=77%). CONCLUSION: Overexpression of mTOR and its signalling proteins have a significant role in emphysema development. Reduction of mTOR expression/activity might be helpful to control dyspnea severity, number of exacerbations, loss of FEV1, and progression of emphysema. KEY WORDS: COPD, Emphysema, mTOR.

Vesicle trafficking with snares: a perspective for autism.

Vesicle-mediated membrane traffic is the mechanism fundamental to many biological events, especially the release of neurotransmitters. The main proteins of the mechanism that mediates membrane fusion in vesicle-mediated membrane traffic are N-ethylmaleimide sensitive factor (NSF) supplemental protein (SNAP) receptor (SNAREs) proteins. SNAREs are classified into vesicle-associated SNAREs (vesicle-SNAREs/v-SNAREs) and target membrane-associated SNAREs (target-SNARE/t-SNAREs). Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by many symptoms, especially complications in social communication and stereotypical behaviours. Defects in synaptogenesis and neurotransmission, oxidative stress, and developmental defects in the early stages of development are defined in the pathogenesis of the disease. SNARE proteins are on the basis of synaptogenesis and neurotransmission. Although the formation mechanisms and underlying causes of the SNARE complex are not fully understood, expression differences, polymorphisms, abnormal expressions or dysfunctions of the proteins that make up the SNARE complex have been associated with many neurodevelopmental diseases, including autism. Further understanding of SNARE mechanisms is crucial both for understanding ASD and for developing new treatments. In this review, the formation mechanisms of the SNARE complex and the roles of various factors involved in this process are explained. In addition, a brief evaluation of clinical and basic studies on the SNARE complex in autism spectrum disorders was made.

miR-181a-5p is a potential candidate epigenetic biomarker in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal degeneration. Abnormal expression of microRNAs (miRNAs) plays an important role in MS pathology. In this cohort study, differential expression of the four miRNAs (hsa-miR-155-5p, hsa-miR-9-5p, hsa-miR-181a-5p, and hsa-miR-125b-5p) was investigated in 69 individuals, including 39 MS patients (relapsing-remitting MS (RRMS), n = 27; secondary progressive MS (SPMS), n = 12) and 30 healthy controls. In silico analyses revealed possible genes and pathways specific to miRNAs. Peripheral blood miRNA expressions were detected by quantitative real-time PCR (qPCR). hsa-miR-181a-5p was downregulated and associated with increased MS risk (P = 0.012). The other three miRNAs were upregulated and not associated with MS (P < 0.05). The area under the curve (AUC) is 0.779. In silico analyses showed that hsa-miR-181a-5p may participate in MS pathology by targeting MAP2K1, CREB1, ATXN1, and ATXN3 genes in inflammation and neurodegeneration pathways. The circulatory hsa-miR-181a-5p can regulate target genes, reversing the mechanisms involved in MS pathologies such as protein uptake and processing, cell proliferation and survival, inflammation, and neurodegeneration. Thus, this miRNA could be used as an epigenomic-guided diagnostic tool and for therapeutic purpose.

Prodynorphin (PDYN) gene polymorphisms in Turkish patients with methamphetamine use disorder, changes in PDYN serum levels in withdrawal and the relationship between PDYN, temperament and depression.

Aim of the study is to compare prodynorphin (PDYN) rs1997794, rs1022563, rs6045819, rs2235749 polymorphisms in individuals with methamphetamine use disorder (MD) to that of healthy controls (HC), and to investigate the differences in serum PDYN levels in methamphetamine withdrawal. It is also aimed to explore the temperament characteristics and depression and their relationship with PDYN polymorphisms and PDYN serum levels in MD group. PDYN gene and serum levels were studied in 134 patients with MD and 97 HC. Patients with MD were administered Beck Depression Inventory (BDI) and Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A). For rs1022563 polymorphism, TT and CT genotype frequency and T allele frequency were significantly higher in the MD group than the frequencies in HC. It was found that rs2235749 polymorphism AA genotype was associated with increased risk of MD. PDYN rs1997794 CT genotypes had significantly higher scores of TEMPS-A irritable than CC genotypes and PDYN rs1022563 CC genotypes had significantly higher scores of TEMPS-A irritable than TT genotypes. PDYN levels among persons with MD were significantly higher than among the HC group when the withdrawal level increased and withdrawal symptoms improved. During the period in which the withdrawal level increased, there was a negative correlation between PDYN level and BDI and a positive relationship between PDYN level and TEMPS-A hyperthymic. It may be beneficial to screen temperament characteristics associated with increased risk of addiction in patients with MD and develop interventions based on temperament characteristics and the effects of PDYN.

In Vitro Effects of Propofol on Cytotoxic, Apoptotic and PI3K-Akt Signaling Pathway Genes on Brain Cancer Cells.

AIM: The study aimed to determine the cytotoxic and apoptotic effect of propofol on glioma cells. BACKGROUND: Propofol [2,6-diisopropylphenol] is a commonly used intravenous anesthetic. Propofol is known to have a mechanism of action on the PI3K-AKT pathway. OBJECTIVE: This study aimed to evaluate the effect of propofol on the proliferation and apoptosis of human glioma cells, as well as to investigate changes in expression levels of the PI3K-AKT signaling pathway genes. MATERIALS AND METHODS: The cytotoxic effect of propofol on the U-87 MG cell line was determined by WST-1 method. Annexin V-FITC and Mitoprobe JC-1 assay were used to measure apoptosis by flow cytometry. The expression levels of genes in the PI3K-AKT signaling pathway were investigated by qRT-PCR. RESULTS: We have shown that propofol induced apoptosis in U-87 MG cells by 17.1 fold compared to the untreated control. Furthermore, significant differences were found in the expression levels of the PI3K-AKT signaling pathway genes. CONCLUSION: As a result of our study, it was found that propofol caused differences in expression levels of PI3K-AKT signaling pathway genes and it was suggested that these differences may be related to apoptosis induction.

The role of Wnt pathway antagonists in early-stage lung adenocarcinoma.

PURPOSE: We aimed to examine the expression levels of the genes encoding adenomatous polyposis coli (APC) 1, APC-2, Dickkopf related protein (DKK)-1, DKK-3, secreted frizzled-related protein (SFRP)-2, SFRP-4, and SFRP-5, which play roles in the Wnt signaling pathway, in lung adenocarcinoma and adjacent normal lung tissues and to evaluate their relationships with clinicopathologic factors. MATERIALS AND METHODS: The expression levels of genes in formalin-fixed paraffin-embedded samples of tumor tissue and adjacent intact lung tissue from 57 patients who underwent surgery for lung adenocarcinoma between 2011 and 2018 were determined by real-time PCR analysis. RESULTS: The expression levels of the DKK-1 in tumor tissue, especially in stage I-II tumor tissue, were significantly suppressed compared to those in normal tissue (p < 0.025). Whereas DKK-1 expression was suppressed in the tumor tissue of patients with early-stage lung adenocarcinoma, expression of the SFRP-5 in these patients was significantly higher in tumor tissue than in normal tissue (p < 0.039). CONCLUSION: In our study, opposing regulation was found between the SFRP-5 and DKK-1, which are known to be extracellular antagonists of the Wnt signaling pathway. The SFRP-5 was found to have an oncogenic role in adenocarcinoma development. Studies of the opposing regulation between these genes in early-stage lung adenocarcinoma may shed light on the mechanisms associated with the development of carcinogenesis. The relationships or interactions of these genes may serve as potential therapeutic targets.

Exploration of Potential miRNA Biomarkers and Prediction for Ovarian Cancer Using Artificial Intelligence.

Ovarian cancer is the second most dangerous gynecologic cancer with a high mortality rate. The classification of gene expression data from high-dimensional and small-sample gene expression data is a challenging task. The discovery of miRNAs, a small non-coding RNA with 18-25 nucleotides in length that regulates gene expression, has revealed the existence of a new array for regulation of genes and has been reported as playing a serious role in cancer. By using LASSO and Elastic Net as embedded algorithms of feature selection techniques, the present study identified 10 miRNAs that were regulated in ovarian serum cancer samples compared to non-cancer samples in public available dataset GSE106817: hsa-miR-5100, hsa-miR-6800-5p, hsa-miR-1233-5p, hsa-miR-4532, hsa-miR-4783-3p, hsa-miR-4787-3p, hsa-miR-1228-5p, hsa-miR-1290, hsa-miR-3184-5p, and hsa-miR-320b. Further, we implemented state-of-the-art machine learning classifiers, such as logistic regression, random forest, artificial neural network, XGBoost, and decision trees to build clinical prediction models. Next, the diagnostic performance of these models with identified miRNAs was evaluated in the internal (GSE106817) and external validation dataset (GSE113486) by ROC analysis. The results showed that first four prediction models consistently yielded an AUC of 100%. Our findings provide significant evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer.

The role of adropin, salusin-α, netrin-1, and nesfatin-1 in endometriosis and their association with insulin resistance

Objective: The pathogenesis of endometriosis has not been clearly explained. Inflammatory factors of ectopic implantation and the growth of ectopic endometrial cells have been subjects of major interest. The number of studies evaluating salusin-α and nesfatin-1 markers in patients with endometriosis is limited. No studies have evaluated the levels of anti-inflammatory markers for adropin and netrin-1 in patients with endometriosis. This study investigates how some important inflammatory regulatory markers in the inflammatory process affect the pathogenesis of endometriosis and determines whether any relationship exists between serum levels of these parameters and endometriosis and insulin resistance. Materials and Methods: This prospective study included 73 patients with endometriosis diagnosed histopathologically after laparoscopic surgery and 75 healthy controls. Serum adropin, salusin-α, netrin-1, and nesfatin-1 levels and homeostatic model assessment of insulin resistance (HOMA-IR) values of the participants were measured. Results: The endometriosis group had significantly lower nesfatin-1 levels than the control group (3.0±0.53 vs 9.5±0.94, p=0.005). Between the patient and control groups, there was no difference regarding serum adropin, salusin-α, and netrin-1 levels (p=0.36, p=0.34, p=0.75, respectively). Nesfatin-1 had a significant positive correlation with adropin, salusin-α, and netrin-1 (r=0.563, p<0.01; r=0.738, p<0.01; r=0.700, p<0.01, respectively), but had a negative correlation with fasting blood glucose (r=-0.343, p<0.05). HOMA-IR values were comparable between both groups. Conclusion: The lower nesfatin-1 levels leading to increased inflammatory pathway activity in patients with endometriosis might play a role in endometriosis pathogenesis. Without causing systemic insulin resistance, decreased nesfatin-1 might contribute to endometriosis pathogenesis locally by leading to the reduced insulin susceptibility of endometriosis cells.

Gene variants and serum levels of synaptic vesicle and presynaptic plasma membrane proteins in alcohol dependence and their relationship with impulsivity and temperament

ABSTRACT Background: Exocytosis-related gene variants have been suggested to be associated with externalizing behaviors. Objective: This study aimed to examine VAMP2 26 bp Ins/Del, synaptotagmin XI (Syt11) rs3820594 and 33-bp promoter, Syntaxin 1A (Syn-1A) rs1569061 and SNAP-25 rs1051312 and rs3746544 polymorphisms, their serum levels and their relationship with impulsivity, temperament in individuals with alcohol dependence (AD) and healthy controls (HC). Methods: The study included 107 individuals with AD and 104 HCs. Single-nucleotide polymorphisms (SNPs) were studied with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and serum levels with ELISA. Michigan Alcohol Screening Test (MAST), Barratt Impulsiveness Scale-11 (BIS-11) and Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) were applied. Results: Syn-1A rs1569061 C allele polymorphism was significantly higher in AD group. Syn-1A rs1569061 C allele was associated with 1.5 times increased risk of AD. All serum levels were significantly higher in the HC group. There was a relationship between Syn-1A rs1569061 polymorphism and BIS-11 motor impulsiveness in the AD group; Syt11 rs3820594 polymorphism and BIS-11 total, TEMPS-A depressive, hyperthymia in the HC group. Discussion: In our study, gene variants and serum levels of synaptic vesicle and presynaptic plasma membrane proteins were related to AD, impulsivity and temperament.

SMAD2, SMAD3 and TGF-ß GENE expressions in women suffering from urge urinary incontinence and pelvic organ prolapse.

We evaluated the changes in the levels of TGF-ß and SMAD gene and protein expression in the uterosacral ligament (USL) of patients with concomitant pelvic organ prolapse (POP) and urgency urinary incontinence (UUI) to illuminate the pathophysiology of UUI. The TGF-ß pathway is involved in collagen synthesis and degradation. The Transforming Growth Family-ß (TGF-ß) superfamily has essential intracellular signaling components, such as newly identified SMAD family members. We evaluated the changes in the levels of TGF-ß and SMAD gene and protein expression in the USL of patients with concomitant pelvic organ prolapse (POP) and UUI. This study included 10 patients who had been diagnosed with POP and UUI in the study group and 14 asymptomatic women without complaints of POP and UUI in the control group. Biopsy samples were collected from bilateral USL tissues during vaginal or abdominal hysterectomy. Total RNA was extracted from USL tissue and analyzed by qPCR. The protein expression levels were also analyzed with ELISA. In UUI patients, SMAD3 and TGF-ß1 gene expression levels significantly decreased compared to the control patients (p = 0.008 and p = 0.006, respectively). SMAD2 mRNA levels did not differ between the study and control groups (p = 0.139). No differences was found in the levels of SMAD2, SMAD3, and TGF-ß1 protein expression between the two groups. The reduction in the gene and protein expression levels of SMAD3 and TGF-ß1 in women with UUI and lax uterosacral ligaments may indicate a causal link.Clinical trial registration: NCT04525105.

Identifying Potential miRNA Biomarkers for Gastric Cancer Diagnosis Using Machine Learning Variable Selection Approach.

Aim: This study aimed to accurately identification of potential miRNAs for gastric cancer (GC) diagnosis at the early stages of the disease. Methods: We used GSE106817 data with 2,566 miRNAs to train the machine learning models. We used the Boruta machine learning variable selection approach to identify the strong miRNAs associated with GC in the training sample. We then validated the prediction models in the independent sample GSE113486 data. Finally, an ontological analysis was done on identified miRNAs to eliciting the relevant relationships. Results: Of those 2,874 patients in the training the model, there were 115 (4%) patients with GC. Boruta identified 30 miRNAs as potential biomarkers for GC diagnosis and hsa-miR-1343-3p was at the highest ranking. All of the machine learning algorithms showed that using hsa-miR-1343-3p as a biomarker, GC can be predicted with very high precision (AUC; 100%, sensitivity; 100%, specificity; 100% ROC; 100%, Kappa; 100) using with the cut-off point of 8.2 for hsa-miR-1343-3p. Also, ontological analysis of 30 identified miRNAs approved their strong relationship with cancer associated genes and molecular events. Conclusion: The hsa-miR-1343-3p could be introduced as a valuable target for studies on the GC diagnosis using reliable biomarkers.

Assessment of COL1A1 and MMP9 expression in patients with dermatochalasis.

PURPOSE: Dermatochalasis is a clinical condition characterized by loss of elasticity of eyelid skin and soft tissue, which typically affects the elderly population. The aim of this study is to investigate the mRNA expression levels of collagen type 1 alpha 1 (COL1A1) and matrix metalloproteinase-9 (MMP9) genes in dermatochalasis tissue. METHODS: The study group consisted of 15 patients who underwent upper eyelid blepharoplasty and were above 40 years old. The patients in our control group were divided into two subgroups according to their ages. Fourteen patients who were under 40 years old and had anterior blepharoptosis surgery for blepharoptosis were designed as the young control group. Sixteen patients who were older than 40 years old and had anterior blepharoptosis surgery for blepharoptosis were designed as the old control group. The patients in the dermatochalasis group were also evaluated according to their smoking status. Surgical tissue specimens were analyzed for COL1A1 and MMP9 mRNA gene expression levels by using real-time polymerase chain reaction. RESULTS: COL1A1 and MMP9 mRNA gene expression levels were not statistically different between the groups (p = 0.247; p = 0.052, respectively). When compared in means of the smoking habit, smokers in the dermatochalasis group exhibited higher COL1A1 mRNA expression levels when compared to nonsmokers (p = 0.008). MMP9 gene expression levels of smokers exhibited almost statistically higher levels but at the limit when compared to nonsmokers (p = 0.05). CONCLUSIONS: This study represents a preliminary study to detect the tissue changes at a molecular level in dermatochalasis, which is known to be related to connective tissue pathology. Collagen and MMPs are essential components of the extracellular matrix, and smoking might affect their gene expression. Further prospective studies on these regulatory genes and encoded protein levels with a larger group of patients may provide particular contribution to explaining the pathophysiology of dermatochalasis.

The effect of FOXO gene family variants and global DNA metylation on RRMS disease.

Multiple sclerosis is a chronic disease that usually occurs with exacerbations and remissions in young adults, affects the central nervous system white matter in multiple localization, and is thought to be the result of complex interactions of genetic and environmental factors, the most common form is relapsing-remitting MS. Forkhead transcription factors O class (FOXO) are responsible for the regulation of various cellular processes including cell cycle, apoptosis, DNA repair, cellular resistance and metabolism. DNA methylation is such an epigenetic change and has been shown to be associated with almost any biological process. The aim of our study to show the relation between the genetic variants of FOXO3a (rs2253310 rs4966936) and FOXO1 (rs3900833, rs4581585) and global DNA methylation in RRMS. We analyzed DNA obtained from 79 RRMS patients and 104 healthy individuals by PCR-RFLP method for the detection of genetic variants. For the determination of global DNA methylation, results were obtained using ELISA method. The data were evaluated statistically. As a result of our analysis; global DNA methylation is higher in RRMS patients compared to control individuals and it can be effective on the disease. In addition, it has been determined that variants of FOXO3a (rs2253310, rs4966936) and FOXO1 (rs3900833), which have been genotyped, may be effective in disease pathogenesis. These results suggest that DNAmethylation and FOXO gene variants may be effective in neuronal loss in RRMS.

Effects of adipose and bone marrow-derived mesenchymal stem cells on vaginal atrophy in a rat menopause model.

BACKGROUND & OBJECTIVES: Vaginal atrophy is characterized by thinning of vaginal epithelial layers and decreased local blood flow. We aimed to evaluate the regenerative effects of Adipose derived mesenchymal stem cells (ADMSC) and Bone marrow derived mesenchymal stem cells (BMDSC) on vaginal atrophy in rat menopause model. MATERIALS AND METHODS: Rats were randomly divided into 4 (four) groups: sham, control, ADMSC, BMDSC. Vaginal epithelial thickness, structure of the lamina propria, blood vessels in the lamina propria, collagen deposition, and muscle structure were evaluated. Anti ER α, VEGF, VEGFR 1, Bax and bcl-2 antibodies were analyzed. Beta actin gene was used as endogenous control. Genetical differences among the groups were compared by using Kruskal Wallis and Mann Whitney U test. p < 0.05 was regarded as statistically significant. RESULTS: Epithelial thickness of ADMSC group was higher than control group, but less than sham group Epithelial thickness of BMDSC group was less than sham group. Lamina propria and muscle tissue of ADMSC and BMDSC groups were found to be similar to sham group. VEGFR-1, VEGF, Bax and ER-α staining levels were higher in ADMSC and BMDSC groups than control group. ADMSC group stained stronger with VEGFR-1 and VEGF than BMDSC group. Bcl-2 staining level was increased in ADMSC applied group. No statistically significant difference was detected in Bax and Bcl-2 genes and Bax-/Bcl-2 ratio. CONCLUSIONS: Although genetic expression might have ended and could not be significantly demonstrated, histological and immunohistochemical results favor ADMSC application in vaginal atrophy rather than BMDSC.

Diagnostic Value of MiR-125b as a Potential Biomarker for Stage I Lung Adenocarcinoma.

BACKGROUND: We aimed at exploring biological functions of differentially expressed miRNAs during carcinogenesis, to identify miRNAs dysegulations involved in DNA repair mechanisms, and to evaluate potential of miRNAs as prognostic and diagnostic biomarkers for early lung adenocarcinomas (LAC). METHODS: We obtained 21 LAC and paired adjacent normal formalin-fixed, paraffinembedded lung tissues from patients who underwent curative resection for stage I LAC. We compared expression levels of eight miRNAs involved in the DNA repair mechanism between LAC and adjacent tissues. RESULTS: Expressions of Hsa-miR-9-5p, hsa-miR-24-3p, hsa-miR-125a-3p, hsa-miR- 125b-5p, hsa-miR-155-5p, and hsa-let-7a-5p were significantly up-regulated in stage I LAC tissues compared with those in the adjacent tissues. In addition, expressions of hsa-mir-9-5p, hsa-mir-24-3p, hsa-mir-125a-3p, hsa-mir-125b-5p, and hsa-mir-155-5p were significantly up-regulated in stage Ia LAC tissues, whereas expressions of hsa-mir- 125a-3p and hsa-mir-125b-5p were significantly up-regulated in stage Ib LAC tissues. Receiver operating characteristic (ROC) analysis revealed that AUROC of hsa-mir-125b- 5p was 0.875 (P < 0.001). CONCLUSION: Expression of hsa-mir-125b-5p could be used to distinguish LAC from adjacent tissues. Our result suggests that hsa-mir125b-5p can be a prognostic and diagnostic biomarker for LAC.

Extracellular Matrix Protein 1 Gene Mutation in Turkish Patients with Lipoid Proteinosis.

BACKGROUND: Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis characterized by mucocutaneous lesions and hoarseness of voice that develop in early childhood. LP is caused by mutation in the extracellular matrix protein 1 (ECM1) gene, which is located on 1q21.2. AIMS: This study aimed to present the profile of ECM1 gene mutations and to identify possible novel mutations specific to Turkey. MATERIALS AND METHODS: The ECM1 gene mutations of 19 LP patients from five families were evaluated using DNA isolated from peripheral blood samples. All ten exons in the ECM1 gene region were amplified by polymerase chain reaction (PCR). The PCR products were analyzed using a DNA sequencing analyzer. The results of DNA sequencing were analyzed with bioinformatics methods. RESULTS: of the 19 LP patients evaluated in our study, we detected defects in exon 6 (c.507delT, 658T>G), exon 9 (157C>T, 727C>T), and exon 10 (c.93_94delGCinsTT) of the ECM1 gene. CONCLUSIONS: Our results indicate that defects in exons 6, 9, and 10 of the ECM1 gene were responsible for LP in our country. The identification of these pathogenic mutations is valuable because it facilitates early diagnosis and genetic counseling.

Novel SNARE Complex Polymorphisms Associated with Multiple Sclerosis: Signs of Synaptopathy in Multiple Sclerosis

Background: It is well known that axonal degeneration plays a role in disability in patients with multiple sclerosis, and synaptopathy has recently become an important issue. Aims: To investigate the possible roles of selected synaptic and presynaptic membrane protein genetic polymorphisms (VAMP2, SNAP-25, synaptotagmin, and syntaxin 1A) in patients with multiple sclerosis. Study Design: Case-control study. Methods: A total of 123 patients with multiple sclerosis and 192 healthy controls were included. The functional polymorphisms of specific SNARE complex proteins (VAMP2, synaptotagmin XI, syntaxin 1A, and SNAP-25) were analyzed by polymerase chain reaction. Results: Significant differences were detected in the genotype and allele distribution of 26-bp Ins/Del polymorphisms of VAMP2 between patients with multiple sclerosis and control subjects; Del/Del genotype and Del allele of VAMP2 were more frequent in patients with multiple sclerosis (p=0.011 and p=0.004, respectively). Similarly, Ddel polymorphism of SNAP-25 gene C/C genotype (p=0.059), syntaxin 1A T/C and C/C genotypes (p=0.005), and synaptotagmin XI gene C allele (p=0.001) were observed more frequently in patients with multiple sclerosis. CC, syntaxin rs1569061 1A gene for 33-bp promoter region TC haplotypes, and synaptotagmin XI gene were found to be associated with an increased risk for multiple sclerosis (p=0.012). Similarly, GC haplotype for rs3746544 of SNAP-25 gene and rs1051312 of SNAP-25 gene were associated with an increased risk for multiple sclerosis (p=0.022). Conclusion: Genetic polymorphisms of SNARE complex proteins, which have critical roles in synaptic structure and communication, may play a role in the development of multiple sclerosis.