Role of Glutamate Receptor-related Biomarkers in the Etiopathogenesis of ADHD.

Objective: : Pathways associated with glutamate receptors are known to play a role in the pathophysiology of attention-deficit hyperactivity disorder (ADHD). However, cyclin-dependent kinase 5 (CDK5), microtubule-associated protein-2 (MAP2), guanylate kinase-associated protein (GKAP), and postsynaptic density 95 (PSD95), all of which are biomarkers involved in neurodevelopmental processes closely related to glutamatergic pathways, have not previously been studied in patients with ADHD. The main purpose of this study was to evaluate the plasma levels of CDK5, MAP2, GKAP, and PSD95 in children with ADHD and investigate whether these markers have a role in the etiology of ADHD. Methods: : Ninety-six children with ADHD between 6 and 15 years of age and 72 healthy controls were included in the study. Five milliliters of blood samples were taken from all participants. The samples were stored at -80°C until analyzed by the enzyme-linked immunosorbent assay method. Results: : Statistically significantly lower CDK5 levels were observed in children with ADHD than in healthy controls (p = 0.037). The MAP2, GKAP, and PSD95 levels were found to be statistically significantly higher in the ADHD group than in healthy controls (p = 0.012, p = 0.009, and p = 0.024, respectively). According to binary regression analysis, CDK5 and MAP2 levels were found to be predictors of ADHD. Conclusion: : In conclusion, we found that a close relationship existed between ADHD and glutamatergic pathways, and low levels of CDK5 and high levels of MAP2 and GKAP played a role in the etiopathogenesis of ADHD.

Nerve growth factor and angiotensin converting enzyme 2 levels in children with neurodevelopmental disorders.

OBJECTIVE: Neurodevelopmental disorders (NDDs) are the most common psychiatric disorders in childhood, and there are many factors in their etiology. In recent years, many biomarkers have been studied to elucidate the etiology of these disorders. In this study, it was aimed to investigate the levels of nerve growth factor (NGF) and angiotensin converting enzyme 2 (ACE2) in attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID). METHODS: The study included 74 children with NDDs (the number of patients in ADHD, ASD and ID groups were 24, 25 and 25 respectively) and 30 healthy controls (HCs). Serum NGF and ACE2 levels were studied with ELISA kits, also complete blood count (CBC), levels of fasting glucose and serum lipids were assessed. RESULTS: ACE2 levels were found to be lower in NDD group than HCs in girls. In boys with ASD, triglyceride levels were significantly higher than other groups. Also a positive correlation was found between ACE2 and NGF levels when all sample assessed together. CONCLUSIONS: This study is a premise for investigating ACE2 and NGF in NDDs. The role of these markers in ADHD, ASD, ID and other NDDs and their associations with gender should be assessed by studies in which both larger sample groups and more disorders.

Comparison of Cardioplegic Solutions in Coronary Bypass Surgery Over Autophagy and Apoptosis Mechanisms. / Comparação de Soluções Cardioplégicas em Cirurgia de Revascularização Miocárdica sobre Mecanismos de Autofagia e Apoptose.

BACKGROUND: Coronary artery disease (CAD) due to myocardial ischemia causes permanent loss of heart tissue. OBJECTIVES: We aimed to demonstrate the possible damage to the myocardium at the molecular level through the mechanisms of autophagy and apoptosis in coronary bypass surgery patients. METHODS: One group was administered a Custodiol cardioplegia solution, and the other group was administered a Blood cardioplegia solution. Two myocardial samples were collected from each patient during the operation, just before cardiac arrest and after the aortic cross-clamp was released. The expressions of autophagy and apoptosis markers were evaluated. The level of statistical significance adopted was 5%. RESULTS: The expression of the BECLIN gene was significant in the myocardial tissues in the BC group (p=0.0078). CASPASE 3, 8, and 9 gene expression levels were significantly lower in the CC group. Postoperative TnT levels were significantly different between the groups (p=0.0072). CASPASE 8 and CASPASE 9 gene expressions were similar before and after aortic cross-clamping (p=0.8552, p=0.8891). In the CC group, CASPASE 3, CASPASE 8, and CASPASE 9 gene expression levels were not found to be significantly different in tissue samples taken after aortic cross-clamping (p=0.7354, p=0.0758, p=0.4128, respectively). CONCLUSIONS: With our findings, we believe that CC and BC solutions do not have a significant difference in terms of myocardial protection during bypass operations.

FUNDAMENTO: A doença arterial coronariana (DAC) devido à isquemia miocárdica causa perda permanente de tecido cardíaco. OBJETIVOS: Nosso objetivo foi demonstrar o possível dano ao miocárdio em nível molecular através dos mecanismos de autofagia e apoptose em pacientes submetidos à cirurgia de revascularização miocárdica. MÉTODOS: Um grupo recebeu uma solução de cardioplegia Custodiol e o outro grupo uma solução de cardioplegia sanguínea. Duas amostras miocárdicas foram coletadas de cada paciente durante a operação, imediatamente antes da parada cardíaca e após a liberação do pinçamento aórtico. Foram avaliadas as expressões de marcadores de autofagia e apoptose. O nível de significância estatística adotado foi de 5%. RESULTADOS: A expressão do gene BECLIN foi significativa nos tecidos miocárdicos do grupo CS (p=0,0078). Os níveis de expressão dos genes CASPASE 3, 8 e 9 foram significativamente menores no grupo CC. Os níveis pós-operatórios de TnT foram significativamente diferentes entre os grupos (p=0,0072). As expressões dos genes CASPASE 8 e CASPASE 9 foram semelhantes antes e depois do pinçamento aórtico (p=0,8552, p=0,8891). No grupo CC, os níveis de expressão gênica de CASPASE 3, CASPASE 8 e CASPASE 9 não foram significativamente diferentes em amostras de tecido coletadas após pinçamento aórtico (p=0,7354, p=0,0758, p=0,4128, respectivamente). CONCLUSÕES: Com nossos achados, acreditamos que as soluções CC e CS não apresentam diferença significativa em termos de proteção miocárdica durante as operações de by-pass.

Decreased levels of alpha synuclein in families with autism spectrum disorder and relationship between the disease severity.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorders that begin in early childhood. Mutations in α-synuclein (SNCA) gene have been shown to result in the accumulation of α-synuclein, which occurs in many neurodegenerative diseases. Our aim was to determine the changes in the expression profile and protein level of this gene by comparing the autistic children with their healthy siblings, their mothers and healthy controls in order to elucidate the possible contribution of the SNCA gene to the etiology of ASD. 50 autistic patients, their mothers, siblings and 25 healthy controls and their mothers were enrolled to determine SNCA gene expression and serum α-synuclein levels. It was determined that α-synuclein serum levels decreased in the autistic patients. Similarly, it was found that SNCA gene expression and serum α-synuclein levels were significantly decreased in the mothers of the patients. Significant negative correlation was observed between the SNCA gene and protein expression amounts in the 6-8 age of the patients. This family-based study is the first in the literature, with both gene expression and serum levels of α-synuclein. The relationship between ASD severity and α-synuclein level needs to be confirmed in larger-scale studies.

Overexpression of the PTEN Gene in Myocardial Tissues of Coronary Bypass Surgery Patients. / Superexpressão Gênica PTEN em Tecidos Miocárdicos de Pacientes de Cirurgia de Revascularização Miocárdica.

BACKGROUND: Coronary artery disease is a complex disorder that causes death worldwide. One of the genes involved in developing this disease may be PTEN. OBJECTIVES: This study aimed to investigate the PTEN gene and protein expression in tissue and blood samples taken from coronary bypass surgery patients. METHODS: Molecular studies were performed at Erciyes University Genome and Stem Cell Center (GENKOK). Right atrial appendage and blood samples were taken from the central vein of 22 coronary bypass surgery patients before starting and ending cardiopulmonary bypass. PTEN expression was determined using quantitative real-time PCR and western blot analysis. The significance level was accepted as p<0.05. RESULTS: There was no significant difference in the PTEN gene expression in blood samples taken before and after cardiopulmonary bypass. However, a substantial increase in both protein and gene expression levels of P-PTEN and PTEN was observed in the tissue samples. Myocardial expression of the PTEN gene was significantly increased at the end of the cardiopulmonary bypass. PTEN gene expression in the post-cardiopulmonary bypass period was increased when compared to the pre-bypass period, but it was insignificant when compared to healthy controls. CONCLUSION: This study first revealed the role of the PTEN gene by analyzing both mRNA and protein expression in coronary bypass patients, appearing in both myocardial tissue and blood samples. Increased levels of PTEN may be a marker in myocardial tissue for patients with coronary artery disease.

FUNDAMENTO: A doença arterial coronariana é um distúrbio complexo que causa morte em todo o mundo. Um dos genes envolvidos no desenvolvimento dessa doença pode ser o PTEN. OBJETIVOS: Nosso objetivo foi investigar a expressão gênica e proteica do PTEN em amostras de tecido e sangue retiradas de pacientes submetidos à cirurgia de revascularização miocárdica. MÉTODOS: Foram realizados estudos moleculares no Centro de estudos do genoma humano e células-tronco da Universidade Erciyes (GENKOK). Amostras do apêndice atrial direito e de sangue foram coletadas da veia central de 22 pacientes submetidos à cirurgia de revascularização miocárdica antes de iniciar e terminar a circulação extracorpórea. A expressão do PTEN foi determinada usando PCR quantitativo em tempo real e análise de Western Blot. O nível de significância aceito foi de p<0,05. RESULTADOS: Não houve diferença significativa na expressão gênica do PTEN em amostras de sangue coletadas antes e depois da circulação extracorpórea. Entretanto, foi observado um aumento substancial nos níveis de expressão gênica e proteica de P-PTEN e PTEN nas amostras de tecido. A expressão gênica miocárdica PTEN aumentou significativamente ao final da circulação extracorpórea. A expressão gênica do PTEN no período pós-circulação extracorpórea aumentou em comparação com o período pré-circulação extracorpórea, mas não foi um aumento significativo em comparação com sujeitos saudáveis do grupo de controle. CONCLUSÃO: Este estudo revelou pela primeira vez o papel do gene PTEN analisando a expressão de mRNA e de proteína em pacientes com revascularização miocárdica, que se manifesta tanto em tecido miocárdico quanto em amostras de sangue. O aumento dos níveis de PTEN pode ser um marcador no tecido miocárdico para pacientes com doença arterial coronariana.

Heterozygous Cc2d1a mice show sex-dependent changes in the Beclin-1/p62 ratio with impaired prefrontal cortex and hippocampal autophagy.

Autism Spectrum Disorders (ASD) are a group of neurodevelopmental disorders characterized by repetitive behaviors, lack of social interaction and communication. CC2D1A is identified in patients as an autism risk gene. Recently, we suggested that heterozygous Cc2d1a mice exhibit impaired autophagy in the hippocampus. We now report the analysis of autophagy markers (Lc3, Beclin and p62) in different regions hippocampus, prefrontal cortex, hypothalamus and cerebellum, with an overall decrease in autophagy and changes in Beclin-1/p62 ratio in the hippocampus. We observed sex-dependent variations in transcripts and protein expression levels. Moreover, our analyses suggest that alterations in autophagy initiated in Cc2d1a heterozygous parents are variably transmitted to offspring, even when the offspring's genotype is wild type. Aberration in the autophagy mechanism may indirectly contribute to induce synapse alteration in the ASD brain.

Partial changes in apoptotic pathways in hippocampus and hypothalamus of Cc2d1a heterozygous.

Alterations in the apoptosis pathway have been linked to changes in serotonin levels seen in autistic patients. Cc2d1a is a repressor of the HTR1A gene involved in the serotonin pathway. The hippocampus and hypothalamus of Cc2d1a ± mice were analyzed for the expression of apoptosis markers (caspase 3, 8 and 9). Gender differences were observed in the expression levels of the three caspases consistent with some altered activity in the open-field assay. The number of apoptotic cells was significantly increased. We concluded that apoptotic pathways are only partially affected in the pathogenesis of the Cc2d1a heterozygous mouse model. A) Apoptosis is suppressed because the cell does not receive a death signal, or the receptor cannot activate the caspase 8 pathway despite the death signal. B) Since Caspase 8 and Caspase 3 expression is downregulated in our mouse model, the mechanism of apoptosis is not activated.

Comparação de Soluções Cardioplégicas em Cirurgia de Revascularização Miocárdica sobre Mecanismos de Autofagia e Apoptose / Comparison of Cardioplegic Solutions in Coronary Bypass Surgery Over Autophagy and Apoptosis Mechanisms

Resumo Fundamento A doença arterial coronariana (DAC) devido à isquemia miocárdica causa perda permanente de tecido cardíaco. Objetivos Nosso objetivo foi demonstrar o possível dano ao miocárdio em nível molecular através dos mecanismos de autofagia e apoptose em pacientes submetidos à cirurgia de revascularização miocárdica. Métodos Um grupo recebeu uma solução de cardioplegia Custodiol e o outro grupo uma solução de cardioplegia sanguínea. Duas amostras miocárdicas foram coletadas de cada paciente durante a operação, imediatamente antes da parada cardíaca e após a liberação do pinçamento aórtico. Foram avaliadas as expressões de marcadores de autofagia e apoptose. O nível de significância estatística adotado foi de 5%. Resultados A expressão do gene BECLIN foi significativa nos tecidos miocárdicos do grupo CS (p=0,0078). Os níveis de expressão dos genes CASPASE 3, 8 e 9 foram significativamente menores no grupo CC. Os níveis pós-operatórios de TnT foram significativamente diferentes entre os grupos (p=0,0072). As expressões dos genes CASPASE 8 e CASPASE 9 foram semelhantes antes e depois do pinçamento aórtico (p=0,8552, p=0,8891). No grupo CC, os níveis de expressão gênica de CASPASE 3, CASPASE 8 e CASPASE 9 não foram significativamente diferentes em amostras de tecido coletadas após pinçamento aórtico (p=0,7354, p=0,0758, p=0,4128, respectivamente). Conclusões Com nossos achados, acreditamos que as soluções CC e CS não apresentam diferença significativa em termos de proteção miocárdica durante as operações de by-pass.

Abstract Background Coronary artery disease (CAD) due to myocardial ischemia causes permanent loss of heart tissue. Objectives We aimed to demonstrate the possible damage to the myocardium at the molecular level through the mechanisms of autophagy and apoptosis in coronary bypass surgery patients. Methods One group was administered a Custodiol cardioplegia solution, and the other group was administered a Blood cardioplegia solution. Two myocardial samples were collected from each patient during the operation, just before cardiac arrest and after the aortic cross-clamp was released. The expressions of autophagy and apoptosis markers were evaluated. The level of statistical significance adopted was 5%. Results The expression of the BECLIN gene was significant in the myocardial tissues in the BC group (p=0.0078). CASPASE 3, 8, and 9 gene expression levels were significantly lower in the CC group. Postoperative TnT levels were significantly different between the groups (p=0.0072). CASPASE 8 and CASPASE 9 gene expressions were similar before and after aortic cross-clamping (p=0.8552, p=0.8891). In the CC group, CASPASE 3, CASPASE 8, and CASPASE 9 gene expression levels were not found to be significantly different in tissue samples taken after aortic cross-clamping (p=0.7354, p=0.0758, p=0.4128, respectively). Conclusions With our findings, we believe that CC and BC solutions do not have a significant difference in terms of myocardial protection during bypass operations.

Superexpressão Gênica PTEN em Tecidos Miocárdicos de Pacientes de Cirurgia de Revascularização Miocárdica / Overexpression of the PTEN Gene in Myocardial Tissues of Coronary Bypass Surgery Patients

Resumo Fundamento: A doença arterial coronariana é um distúrbio complexo que causa morte em todo o mundo. Um dos genes envolvidos no desenvolvimento dessa doença pode ser o PTEN. Objetivos: Nosso objetivo foi investigar a expressão gênica e proteica do PTEN em amostras de tecido e sangue retiradas de pacientes submetidos à cirurgia de revascularização miocárdica. Métodos: Foram realizados estudos moleculares no Centro de estudos do genoma humano e células-tronco da Universidade Erciyes (GENKOK). Amostras do apêndice atrial direito e de sangue foram coletadas da veia central de 22 pacientes submetidos à cirurgia de revascularização miocárdica antes de iniciar e terminar a circulação extracorpórea. A expressão do PTEN foi determinada usando PCR quantitativo em tempo real e análise de Western Blot. O nível de significância aceito foi de p<0,05. Resultados: Não houve diferença significativa na expressão gênica do PTEN em amostras de sangue coletadas antes e depois da circulação extracorpórea. Entretanto, foi observado um aumento substancial nos níveis de expressão gênica e proteica de P-PTEN e PTEN nas amostras de tecido. A expressão gênica miocárdica PTEN aumentou significativamente ao final da circulação extracorpórea. A expressão gênica do PTEN no período pós-circulação extracorpórea aumentou em comparação com o período pré-circulação extracorpórea, mas não foi um aumento significativo em comparação com sujeitos saudáveis do grupo de controle. Conclusão: Este estudo revelou pela primeira vez o papel do gene PTEN analisando a expressão de mRNA e de proteína em pacientes com revascularização miocárdica, que se manifesta tanto em tecido miocárdico quanto em amostras de sangue. O aumento dos níveis de PTEN pode ser um marcador no tecido miocárdico para pacientes com doença arterial coronariana.

Abstract Background: Coronary artery disease is a complex disorder that causes death worldwide. One of the genes involved in developing this disease may be PTEN. Objectives: This study aimed to investigate the PTEN gene and protein expression in tissue and blood samples taken from coronary bypass surgery patients. Methods: Molecular studies were performed at Erciyes University Genome and Stem Cell Center (GENKOK). Right atrial appendage and blood samples were taken from the central vein of 22 coronary bypass surgery patients before starting and ending cardiopulmonary bypass. PTEN expression was determined using quantitative real-time PCR and western blot analysis. The significance level was accepted as p<0.05. Results: There was no significant difference in the PTEN gene expression in blood samples taken before and after cardiopulmonary bypass. However, a substantial increase in both protein and gene expression levels of P-PTEN and PTEN was observed in the tissue samples. Myocardial expression of the PTEN gene was significantly increased at the end of the cardiopulmonary bypass. PTEN gene expression in the post-cardiopulmonary bypass period was increased when compared to the pre-bypass period, but it was insignificant when compared to healthy controls. Conclusion: This study first revealed the role of the PTEN gene by analyzing both mRNA and protein expression in coronary bypass patients, appearing in both myocardial tissue and blood samples. Increased levels of PTEN may be a marker in myocardial tissue for patients with coronary artery disease.

Evaluation of the Rho-kinase gene expression and polymorphisms in adult patients with acute appendicitis: a differential impact of gender.

OBJECTIVE: Acute appendicitis represents one of the most common causes of acute intra-abdominal emergencies worldwide. In this case-control study, we aimed to investigate associations of Rho-kinase gene expression and polymorphisms with acute appendicitis in a Turkish population. We also aimed to study the effects of gender on these parameters. METHODS: A total of 93 unrelated patients with acute appendicitis and 93 healthy controls in the Department of Emergency Medicine, Erciyes University, between June 2019 and June 2021 were included in this study. Genomic DNA was isolated from peripheral leukocytes, and the LightCycler 480 II real-time polymerase chain reaction was utilized to detect Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 (Thr431Asn) polymorphisms. Quantitative real-time polymerase chain reaction was applied to determine Rho-kinase1 and Rho-kinase2 gene expressions. RESULTS: There was a marked increase in Rho-kinase1, but not in Rho-kinase2, mRNA expression, and this increase was evident only in male patients (p=0.0008). No significant differences were found in allele and genotype frequencies for Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 polymorphisms between the patients with acute appendicitis and the control group. CONCLUSIONS: Our data imply that Rho-kinase1 (rs35996865) and Rho-kinase2 (rs2230774) gene variants are not risk factors for the development of acute appendicitis in the Turkish population. However, increased mRNA expression of the Rho-kinase1 gene in males indicated that Rho-kinase1 is involved in the pathogenesis of acute appendicitis in a gender-specific way.

Evaluation of the Rho-kinase gene expression and polymorphisms in adult patients with acute appendicitis: a differential impact of gender

SUMMARY OBJECTIVE: Acute appendicitis represents one of the most common causes of acute intra-abdominal emergencies worldwide. In this case-control study, we aimed to investigate associations of Rho-kinase gene expression and polymorphisms with acute appendicitis in a Turkish population. We also aimed to study the effects of gender on these parameters. METHODS: A total of 93 unrelated patients with acute appendicitis and 93 healthy controls in the Department of Emergency Medicine, Erciyes University, between June 2019 and June 2021 were included in this study. Genomic DNA was isolated from peripheral leukocytes, and the LightCycler 480 II real-time polymerase chain reaction was utilized to detect Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 (Thr431Asn) polymorphisms. Quantitative real-time polymerase chain reaction was applied to determine Rho-kinase1 and Rho-kinase2 gene expressions. RESULTS: There was a marked increase in Rho-kinase1, but not in Rho-kinase2, mRNA expression, and this increase was evident only in male patients (p=0.0008). No significant differences were found in allele and genotype frequencies for Rho-kinase1 gene rs35996865 and Rho-kinase2 gene rs2230774 polymorphisms between the patients with acute appendicitis and the control group. CONCLUSIONS: Our data imply that Rho-kinase1 (rs35996865) and Rho-kinase2 (rs2230774) gene variants are not risk factors for the development of acute appendicitis in the Turkish population. However, increased mRNA expression of the Rho-kinase1 gene in males indicated that Rho-kinase1 is involved in the pathogenesis of acute appendicitis in a gender-specific way.

Evaluation of the rs35996865 polymorphism of the ROCK1 gene in sepsis.

OBJECTIVE: Sepsis is a complex and serious medical condition resulting from the activation of an innate host response to infections. The etiology of sepsis is complex and can be influenced by genetic susceptibility. The purpose of the present study was to investigate a possible association of Rho-kinase 1 (ROCK1) gene polymorphism with sepsis in a Turkish population. METHODS: The study group consisted of 100 unrelated patients with sepsis and 100 healthy controls. Genomic DNA was isolated from peripheral leukocytes from EDTA-containing blood using the QIAamp DNA Blood Mini Kit. ROCK1 gene rs35996865 and rs112130712 (Lys1054Arg) polymorphisms were analyzed in genomic DNA using the LightCycler 480 II real-time polymerase chain reaction. RESULTS: There were no significant differences in allele and genotype frequencies for ROCK1 gene rs35996865 polymorphism between the patients with sepsis and control group (p>0.05). Additionally, no association was detected between the rs35996865 polymorphism and mortality in the patient group. No polymorphism was detected with ROCK1 gene rs112130712 (Lys1054Arg) in our study groups. CONCLUSIONS: Our data showed that there is no marked association between the rs35996865 polymorphism and sepsis. Therefore, these results suggest that ROCK1 gene rs35996865 polymorphism is not risk factor for the development of sepsis in the Turkish population.

Evaluation of the rs35996865 polymorphism of the ROCK1 gene in sepsis

SUMMARY OBJECTIVE: Sepsis is a complex and serious medical condition resulting from the activation of an innate host response to infections. The etiology of sepsis is complex and can be influenced by genetic susceptibility. The purpose of the present study was to investigate a possible association of Rho-kinase 1 (ROCK1) gene polymorphism with sepsis in a Turkish population. METHODS: The study group consisted of 100 unrelated patients with sepsis and 100 healthy controls. Genomic DNA was isolated from peripheral leukocytes from EDTA-containing blood using the QIAamp DNA Blood Mini Kit. ROCK1 gene rs35996865 and rs112130712 (Lys1054Arg) polymorphisms were analyzed in genomic DNA using the LightCycler 480 II real-time polymerase chain reaction. RESULTS: There were no significant differences in allele and genotype frequencies for ROCK1 gene rs35996865 polymorphism between the patients with sepsis and control group (p>0.05). Additionally, no association was detected between the rs35996865 polymorphism and mortality in the patient group. No polymorphism was detected with ROCK1 gene rs112130712 (Lys1054Arg) in our study groups. CONCLUSIONS: Our data showed that there is no marked association between the rs35996865 polymorphism and sepsis. Therefore, these results suggest that ROCK1 gene rs35996865 polymorphism is not risk factor for the development of sepsis in the Turkish population.

Blood mRNA Expression Profiles of Autophagy, Apoptosis, and Hypoxia Markers on Blood Cardioplegia and Custodiol Cardioplegia Groups

Abstract Introduction: Blood cardioplegia (BC) and Custodiol cardioplegia (CC) have been used for a long time in open heart surgery and are highly effective solutions. The most controversial issue among these two is whether there is any difference between them regarding myocardial damage after ischemia surgery. In this study, autophagy, apoptosis, and hypoxia markers were investigated and that way we evaluated the differences between BC and CC patients. Methods: A total of 30 patients were included in this study, using two different cardioplegic solutions. Three different whole blood samples of the patients were taken from a central vein (preoperatively, immediately postoperatively, and one day after surgery). Total ribonucleic acid was extracted from these samples. Quantitative real-time polymerase chain reaction was performed, and changes in gene expression were determined by the 2-∆∆Ct method of relative quantification. Results: In the CC group, Beclin gene expression level was found to be higher and this difference was statistically significant (P=0.0024). Similarly, cysteine-aspartic acid protease (caspase) 9 and hypoxia-inducible factor 1α messenger ribonucleic acid (mRNA) gene expression level increased and were significantly different in the CC group. In the BC group, Beclin and microtubule-associated protein light chain 3 expressions were higher in the samples taken one day after surgery. Caspases 3 and 8 gene expressions were significantly different in the BC group. Conclusion: As a result of the analysis performed between the two cardioplegia groups, it has been shown that CC harms the myocardium more than BC at the level of mRNA expression of related markers.

MicroRNA profiling identifies Forkhead box transcription factor M1 (FOXM1) regulated miR-186 and miR-200b alterations in triple negative breast cancer.

Breast cancer (BC) is the most commonly diagnosed malignancy. MicroRNAs (miRNAs) play important roles in the tumorigenesis, metastasis and progression of BC. Forkhead Box M1 (FOXM1) oncogenic transcription factor is involved in events considered as hallmarks of cancer. However, the specific mechanism by which FOXM1 exerts its oncogenic effects remains unclear and little is known about its effects on the regulation of miRNA expression. We have found that FOXM1 is upregulated in breast cancer cells and that its expression is associated with shortened overall survival and poor prognosis in patients with BC. Using microarray technology, we assessed the expression profiles of 752 miRNAs in highly aggressive and metastatic triple negative breast cancer (TNBC) cells in response to FOXM1 knockdown and identified 13 differentialy expressed miRNAs (3 miRNAs upregulated and 10 miRNAs down-regulated). We validated the results of the miRNA expression profile in two different TNBC cells by performing qRT-PCR and identified that miR-186-5p and miR-200b-5p were consistently down- or up-regulated, respectively, after knockdown of FOXM1. We further performed KEGG pathway analysis and GO enrichment analysis for miR-186-5p and miR-200b-5p, and identified that these miRNAs are associated with cancer development and progression involving toll-like receptor signaling, cell cycle, AMPK, p53 and NF-kappa B signaling pathways. Taken together, our results suggest that increased FOXM1 expression is associated with poor patient survival and leads to induction of oncomiR miR-186-5p expression and tumor-suppressor inhibition miR-200b-5p, suggesting that the FOXM1/miRNA signaling pathway may contribute to poor patient prognosis and may be a potential therapeutic target in TNBC.

Variants in TNF and NOS3 (eNOS) genes associated with sepsis in adult patients.

BACKGROUND: Sepsis is a life-threatening condition caused by a dysregulated host response to infections and is a leading cause of death in hospitalized patients. The present study aimed to elucidate the possible association between sepsis and the tumor necrosis factor (TNF) gene -308G/A (rs1800629) polymorphism, as well as endothelial nitric oxide synthase (eNOS, NOS3) gene -786T/C (rs2070744), 4a/4b (27 bp-VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. METHODS: In total, 188 septic adult cases and 188 healthy controls were enrolled. Genomic DNAs from the controls and patients were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. RESULTS: There were significant associations between the G/G genotype and G allele of the TNF -308G/A (rs1800629) polymorphism in the sepsis group (p < 0.001). The presence of the T/C genotype (p = 0.002) and C allele (p = 0.001) of the -786T/C (rs2070744) was markedly associated with an increased risk of sepsis. However, no significant associations were found with 4a/4b (27 bp-VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Higher 4bGC and lower 4bTT haplotype frequencies were associated with sepsis. CONCLUSIONS: Our results strongly suggest that TNF gene (-308G/A, rs1800629) and NOS3 gene -786T/C (rs2070744) polymorphisms may modify individual susceptibility to sepsis in the Turkish population.

Blood mRNA Expression Profiles of Autophagy, Apoptosis, and Hypoxia Markers on Blood Cardioplegia and Custodiol Cardioplegia Groups.

INTRODUCTION: Blood cardioplegia (BC) and Custodiol cardioplegia (CC) have been used for a long time in open heart surgery and are highly effective solutions. The most controversial issue among these two is whether there is any difference between them regarding myocardial damage after ischemia surgery. In this study, autophagy, apoptosis, and hypoxia markers were investigated and that way we evaluated the differences between BC and CC patients. METHODS: A total of 30 patients were included in this study, using two different cardioplegic solutions. Three different whole blood samples of the patients were taken from a central vein (preoperatively, immediately postoperatively, and one day after surgery). Total ribonucleic acid was extracted from these samples. Quantitative real-time polymerase chain reaction was performed, and changes in gene expression were determined by the 2-∆∆Ct method of relative quantification. RESULTS: In the CC group, Beclin gene expression level was found to be higher and this difference was statistically significant (P=0.0024). Similarly, cysteine-aspartic acid protease (caspase) 9 and hypoxia-inducible factor 1α messenger ribonucleic acid (mRNA) gene expression level increased and were significantly different in the CC group. In the BC group, Beclin and microtubule-associated protein light chain 3 expressions were higher in the samples taken one day after surgery. Caspases 3 and 8 gene expressions were significantly different in the BC group. CONCLUSION: As a result of the analysis performed between the two cardioplegia groups, it has been shown that CC harms the myocardium more than BC at the level of mRNA expression of related markers.

Disregulation of Autophagy in the Transgenerational Cc2d1a Mouse Model of Autism.

Autism spectrum disorder (ASD) is a heterogeneously childhood neurodevelopmental disorder, believed to be under development of various genetic and environmental factors. Autophagy and related pathways have also been implicated in the etiology of ASD. We aimed to investigate autophagic markers by generating the transgenerational inheritance of ASD-like behaviors in the Cc2d1a animal model of ASD. Cc2d1a (+/-) mouse model of ASD was built in two different groups by following three generations. After behavior test, bilateral hippocampus was sliced. Western Blot assay and quantitative real-time polymerase chain reaction (QRT-PCR) were used for measurement of LC3 and Beclin-1 as key regulators of autophagy. All of the animal and laboratory studies were conducted in the Erciyes University Genome and Stem Cell Center (GENKOK). Significant LC3 and Beclin-1 mRNA expression levels were observed in mouse hippocampus between groups and generations. Western blot confirmed the changes of the proteins in the hippocampus. LC3 expressions were increased for females and decreased for males compared to the control group. Beclin-1 expression levels were found to be significantly decreased in males and females compared to controls. This study could help explain a new pathway of autophagy in ASD mouse models. Future animal studies need to investigate sex differences in mouse modeling autism-relevant genes like CC2D1A. We anticipate our results to be a starting point for more comprehensive autophagy studies in this mouse model of ASD.

Role of circulating microRNAs in acute appendicitis.

BACKGROUND: Acute appendicitis (AA) is a momentous, emergency, surgical pathology that has still been investigated for both etiopathogenetic unknowns and challenges in diagnosis. Presently, there is little information about the role of microRNAs (miRNAs), which have basic biological functions in the cell, can be a marker, and are associated with various pathologies, in patients with AA. The aim of this study was to investigate the expressions of some miRNAs in AA. METHODS: Overall, 41 miRNAs were screened in 48 individuals comprising 24 patients with AA and 24 healthy controls at Erciyes University Genome and Stem Cell Center (GENKOK). The obtained data were analyzed using appropriate statistical methods. RESULTS: miR-29c-3p was found to be increased 2-fold during the first 4-6 h in AA, and this increase was revealed to be statistically significant compared with healthy individuals. Similarly, expressions of let-7b-5p, let-7i-5p, miR-30a-5p, miR-29b-3p, and miR-23a-3p also increased approximately 2-fold in AA, although not statistically significant. No significant differences were found in the screening of the remaining 35 miRNAs in patients with AA. CONCLUSION: Although there is little information about the relationship between AA and miRNAs currently, miR-29c-3p was reported to increase in the acute period of AA in this study. With the current results, it can be argued that miR-29c-3p bears the potential to be a marker in patients with AA. The present study may also be a basic research for more extensive and necessary miRNAs screening in this field.