The impact of developmental genes in non-syndromic cleft lip and/or palate

Non-syndromic cleft lip and/or palate (NSCL/P) is a congenital malformation with a prevalence of 1:700 births. It has a multifactorial etiology. Human craniofacial development takes place during the first 10 weeks of pregnancy. Normal craniofacial development arises from the convergence and fusion of the facial and palatal processes and involves interactions between genes that regulate cell growth, proliferation, differentiation, epithelial-to-mesenchymal transition, and apoptosis. Whole genome/exome analysis, and also genome-wide association studies give us to chance to identify the genetic factors which contribute to the development of NSCL/P. After detecting a cleft lip and/or palate on ultrasonography without associated anomalies, the patient should be evaluated in collaboration with a clinical geneticist, taking into account the many genes and environmental factors involved in NSCL/P etiopathogenesis, and a roadmap for possible genetic diagnosis should be drawn.

Impact of Matrix Metalloproteinases 2 and 9 and Tissue Inhibitor of Metalloproteinase 2 Gene Polymorphisms on Allograft Rejection in Pediatric Renal Transplant Recipients.

OBJECTIVES: Acute and chronic allograft rejection have been continuously an important obstacle in the follow-up of renal transplant recipients. During clinical management, several factors acting simultaneously result in acute rejection and chronic allograft nephropathy. Matrix metalloproteinases and tissue inhibitors of metalloproteinases are responsible for the organization of the extracellular matrix and play roles in cell proliferation and cellular invasion. Changes in matrix metalloproteinase expression levels have been reported to be associated with renal allograft rejection and interstitial fibrosis. In this study, we aimed to investigate functional polymorphisms of MMP2, MMP9, and TIMP2 genes in pediatric renal transplant recipients. MATERIALS AND METHODS: Our study included 68 kidney transplant recipients and 58 control patients. The kidney transplant recipient group was further divided into 2 subgroups: no graft rejection (n = 47) and graft rejection (n =21). MMP2 -735C >T (rs2285053), MMP2 -1306C >T (rs243865), MMP2 -1575G >A (rs243866), MMP9 c.-1562C >T (rs3918242), TIMP2 -418G >C (rs8179090), and TIMP2 303C > T (rs2277698) polymorphisms were analyzed with the use of polymerase chain reaction and restriction fragment-length polymorphism methods. Allele prevalence was compared with reference values of the control group, and Hardy-Weinberg equilibrium was tested. RESULTS: Mean ages were 16.7 ± 3.9 years for the study group and 14.8 ± 5.6 years for the control group. The mean follow-up time after transplant was 37.7 ± 7.9 months. We compared allele frequencies in the 2 groups and calculated a statistically significant difference in rs2285053, rs243865, rs243866, rs3918242, rs8179090, and rs2277698 polymorphism frequencies between the transplant recipients and control patients. When the transplant recipient group was compared in itself with regard to allograft rejection, all investigated polymorphisms except TIMP2 -418G >C (rs8179090) revealed a statistically significant difference between those with and without rejection (P < .05). CONCLUSIONS: Matrix metalloproteinases and their tissue inhibitors could be important predictive biological markers for the follow-up of kidney transplant recipients.

Associations between IL-1α, IL-1ß, TNFα, and IL-6 variations, and susceptibility to transposition of the great arteries.

BACKGROUND: To evaluate the relationship between IL-1α -889C/T (rs1800587), IL-1ß -511C > T (rs16944), TNFα -308G > A (rs1800629), TNFα -238G > A (rs361525), IL-6 -174G > C (rs1800795), and IL-6 -572G > C (rs1800796) polymorphisms and the susceptibility to transposition of the great arteries (TGA). METHODS: A prospective analysis was performed on mothers whose newborns were diagnosed as having TGA. For each case of TGA, a mother who gave birth to a healthy neonate in the same period was randomly selected for the control group. The sample size was calculated before planning the study with 80% power and 5% alpha. RESULTS: Twenty-seven mothers whose newborn had TGA anomalies (group 1) and 27 mothers whose newborn had no TGA (group 2) were included in the study. There were no significant differences between the groups in terms of maternal age, pregestational body mass index, gestational age at birth and infant sex (p > 0.05). The genotype and allele distributions of IL-1α -889C/T (rs1800587), IL-1ß -511C > T (rs16944), TNFα -308G > A (rs1800629), TNFα -238G > A (rs361525), IL-6 -174G > C (rs1800795) and IL-6 -572G > C (rs1800796) gene variants were not different between the two groups (p > 0.05). CONCLUSIONS: There was no relation between IL-1α, IL-1ß, IL-6, and TNFα promoter gene polymorphisms and TGA occurrence in our study group. TRIAL REGISTRATION: This present prospective case-control study was conducted in Baskent University Hospital, Ankara, Turkey, between May 2020 and November 2021. Ethical approval was obtained from the university's Clinical Research Ethics Commitee (No: KA20/211) in accordance with the Declaration of Helsinki.

Persistent Hyperinsulinemic Hypoglycemia with Pancreatic Teratoma in Infancy: A Case Report.

BACKGROUND Pediatric intraabdominal pancreatic teratomas have been rarely reported. This is the first case of severe hyperinsulinemic hypoglycemia in a 6-month-old infant secondary to an intraabdominal teratoma. The hypoglycemia resolved after surgical removal. CASE REPORT A 6-month-old infant was seen in a pediatric emergency department with complaints of lethargy and abnormal eye movements. She was diagnosed with hyperinsulinemic hypoglycemia and started on diazoxide. A CT and MRI of the abdomen revealed a 165×77×72 mm cyst with a 51×45×30 mm solid structure connecting to the wall of the cyst by a stalk, raising suspicion of a fetus in fetu. The mass had no connection to her pancreas. Following total excision of the intraabdominal mass, her hypoglycemia resolved. Histopathological examination showed immature fetal pancreatic tissue consistent with a mature teratoma. Whole exon sequencing of the infant's peripheral blood showed a negative mutation of ABCC8 and presence of heterozygous variations of HNF1ß and IRS1 genes. CONCLUSIONS This is the first case report of an infant with severe hyperinsulinemic hypoglycemia secondary to a pancreatic teratoma. The heterozygous variations of HNF1ß and IRS1 genes likely played a role in the embryogenesis, causing a pancreatic teratoma and hyperinsulinemic hypoglycemia.

The Role of Heredity and the Prevalence of Strabismus in Families with Accommodative, Partial Accommodative, and Infantile Esotropia

Objectives: To investigate the prevalence of strabismus in families of a proband with accommodative, partial accommodative, or infantile esotropia, and to evaluate the mode of inheritance and the role of consanguineous marriages in this prevalence. Materials and Methods: Families of probands with comitant strabismus were invited to participate in the study. The family members of 139 subjects with accommodative, 55 with partial accommodative, and 21 with infantile esotropia agreed to participate. Detailed family trees were constructed. The first- and second-degree relatives were invited for a complete ophthalmological examination, and 518 individuals from 168 families were evaluated. The role of consanguinity, the presence of tropia, phoria (≥8 PD), microtropia, and hypermetropia (≥3.00 D) among first- and second-degree relatives were analyzed. Results: A non-Mendelian pattern was found in 49 families (23%), an autosomal dominant pattern in 39 families (18%), and an autosomal recessive pattern in 6 families (3%). The prevalence of consanguineous marriages among parents of probands was 18.1%, 22.6%, and 14.3% in the accommodative, partial accommodative, and infantile esotropia groups, respectively (p=0.652). The prevalence of strabismus in first-degree relatives was 58.9%, 45.5%, and 38.1%, respectively (p=0.07). The prevalence of microtropia in probands' siblings was significantly higher in the accommodative esotropia group (p=0.034). Conclusion: Sporadic cases and non-Mendelian inheritance were more frequent than autosomal recessive inheritance. Autosomal recessive inheritance was found not to be frequent in consanguineous marriages. The prevalence of strabismus and microtropia was significantly higher in families of esotropia cases than in the general population.

No Interaction Between Childhood Maltreatment and Serotonin Transporter Gene in Recurrent Major Depressive Disorder: A Clinical Sample.

INTRODUCTION: There is inconsistent evidence of interaction between childhood adversities and a serotonin transporter promoter polymorphism (5-HTTLPR) in depression. It is hypothesized that genetic sensitivity to stress could be more specific to recurrent major depressive disorder (MDD). The aim of the study is to replicate a recent study which provided preliminary evidence of interaction between severity of childhood maltreatment and the 5-HTTLPR polymorphism in recurrent MDD. METHODS: Participants included a well-characterized clinical sample of 70 recurrent MDD cases and 67 never psychiatrically ill controls, aged 18 years or over. Socio-demographic and clinical information form, Composite International Diagnostic Interview (CIDI), Childhood Trauma Questionnaire (CTQ), Beck Depression Inventory (BDI) were applied to both groups, along with genotyping. RESULTS: There was no interaction between childhood maltreatment and the 5-HTTLPR in relation to recurrent MDD. All forms of childhood maltreatment were reported as more severe by cases than controls, and there was an independent association between maltreatment and recurrent MDD. CONCLUSION: The path forward to detect genetic risk loci for depression remains challenging. Taking childhood maltreatment history into account could lead to a richer understanding of differences in biological correlates, genetic underpinnings, and outcomes.

A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies.

Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient "MISTRG" mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients' dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample's genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research.

Vitamin D receptor gene TaqI single nucleotide polymorphism is not associated with lead levels in maternal and umbilical cord blood.

PURPOSE: We aimed to investigate the association of vitamin D receptor (VDR) gene TaqI single nucleotide polymorphism (SNPs) with serum lead (Pb) levels in maternal and umbilical cord blood. MATERIALS AND METHODS: Eighty-one patients who lived in Konya, Turkey for the last 3 years and had delivery at Baskent University Konya Hospital in 2016 were included in this study. Venous blood samples were drawn from each volunteer immediately before giving birth to determine the maternal Pb levels and VDR SNPs. Additionally, umbilical cord blood samples were collected from the umbilical vein into tube with EDTA as an anticoagulant immediately after birth to determine Pb levels of the fetus. RESULTS: The median level of Pb in the maternal blood was 29.00 (Interquartile Range (IQR) = 16.35) µg/L and the median Pb level in the cord blood was 22.50 (IQR = 9.75) µg/L. Blood Pb level of women living in the urban area was significantly higher than in those living in the rural area (Z = 2.118; p = .034). There was a very strong positive correlation between the Pb levels in the maternal blood and in the umbilical cord blood (ρ = 0.825, p < .001, respectively). Regarding VDR SNPs, "TT", "TC", and "CC" VDR TaqI genotypes were observed in 28 (34.6%), 45 (55.5%), and eight samples (9.9%), respectively. Pb levels in maternal and cord blood were higher in women with the "CC" VDR TaqI genotype; however, there was no statistically significant difference (p > .05). CONCLUSIONS: Although women with the "CC" VDR TaqI genotype had higher maternal and cord blood Pb levels, this was statistically insignificant and therefore, VDR TaqI SNPs did not significantly affect maternal and umbilical cord blood Pb levels.

The differences in the expression of fractalkine and its receptor in conditions of tonsillar hypertrophy and chronic tonsillitis.

OBJECTIVE: Fractalkine, member of chemokine family, is involved in many inflammatory processes in the human body. The aim of this study is to compare expression levels of fractalkine ligand and its receptor in chronic tonsillitis and hypertrophic tonsil samples. METHODS: The study was conducted at Baskent University Departments of Otorhinolaryngology and Medical Genetics. It is designed as a prospective, non-randomized, controlled clinical study. Total 97 samples, obtained from adenotonsillectomy due to chronic tonsillitis or tonsillar hypertrophy, were participated in the study. Fractalkine and its receptor expression levels were determined and comparison was made between the tissue groups. c.839C>T (T280M) polymorphism of fractalkine receptor was analyzed, then relationship between polymorphism and the expression level of fractalkine receptor was investigated. RESULTS: Fractalkine receptor expression was significantly higher in the hypertrophic tonsil group than chronic tonsillitis group (p<0.05). CONCLUSION: Fractalkine, member of chemokine family, and its receptor may play role in preventing chronic-recurrent tonsillitis.

Odontogenic effects of two calcium silicate-based biomaterials in human dental pulp cells.

BACKGROUND: The goal of treating exposed pulp with an appropriate pulp capping material is to promote the dentinogenic potential of the pulpal cells. There have been recent attempts to develop more effective pulp-capping materials. OBJECTIVES: The aim of this study was to evaluate the effect of newly developed calcium silicate-based material on odontogenic differentiation of primary human dental pulp cells (HDPCs), in comparison with a contemporary calcium silicate-based material. MATERIAL AND METHODS: Human dental pulp cells isolated from dental pulps were cultured in standard culture conditions in Dulbecco's Modified Eagle's Medium (DMEM) and then the effects of Micro-Mega mineral trioxide aggregate (MM-MTA) (Micro-Mega, Besançon, France) and ProRoot MTA (MTA) (Dentsply Sirona, Tulsa, USA) (positive control) were evaluated on HDPCs at 1, 7 and 14 days. Untreated cells were used as a negative control. Odontoblastic differentiation was assessed by alkaline phosphatase (ALP) activity. Runtrelated transcription factor 2 (RUNX2), alkaline phosphatase liver/bone/kidney (ALPL), bone morphogenetic protein 2 (BMP2), dentin sialophosphoprotein (DSPP), and Distal-less homeobox 3 (DLX3), as odontoblastic/ osteoblastic expression markers, were evaluated by semi-quantitative real-time polymerase chain reaction (RT-PCR) analysis. Calcium levels of culture media were also determined. RESULTS: The MM-MTA group significantly increased the expression of BMP2 compared with that of the MTA group at 3 different time periods (p < 0.05). The up-regulation of ALPL between day 1 and 14 and the up-regulation of DSPP between day 7 and 14 were significant in both groups (p < 0.05). Micro-Mega MTA and MTA exhibited similar messenger RNA (mRNA) expression levels of ALPL, DSPP, RUNX2, DLX3, and ALP activities, as well as calcium levels. CONCLUSIONS: Based on the cell responses observed in this study, MM-MTA might be used efficiently in dental pulp therapy as a potential alternative to MTA.

The Impact of Iron Overload in Acute Leukemia: Chronic Inflammation, But Not the Presence of Nontransferrin Bound Iron is a Determinant of Oxidative Stress.

In the literature, studies on the oxidant effects of nontransferrin bound iron [NTBI (eLPI assay)] during chemotherapy of acute lymphoblastic leukemia and acute myeloblastic leukemia are lacking. We established NTBI and oxidative stress determinants (OSD), iron parameters, high-sensitive C-reactive protein (hs-CRP) levels, liver tests, cumulative chemotherapeutic doses, and transfused blood in 36 children with acute leukemia throughout chemotherapy. These parameters were determined at the beginning and end of chemotherapy blocks (11 time points) and in 20 healthy children using enzyme-linked immunosorbent assay, and colorimetric and fluorometric enzymatic methods. In acute lymphoblastic leukemia, NTBI, OSD, and hs-CRP were higher than controls at 4/11, 7/11, and 9/11 time points (P<0.05). At 3 time points, NTBI and OSD concurrently increased. Ferritin, soluble transferrin receptor, serum iron, and transferrin saturation were higher than in controls at 5 to 11/11 time points (P<0.05). Those with NTBI had higher iron parameters than those without NTBI (P<0.05), but showed similar OSD, hs-CRP, liver enzymes, cumulative chemotherapeutics, and transfused blood (P>0.05). OSD did not correlate with NTBI, but correlated with hs-CRP. In conclusion, NTBI is a poor predictor of OSD in acute leukemia possibly because of the heterogeneity of NTBI and chronic inflammation. Further studies are needed to delineate the pathophysiology of these diseases.

Enhancement of vascular endothelial growth factor's angiogenic capacity by the therapeutic modulation of notch signalling improves tram flap survival in rats submitted to nicotine.

BACKGROUND: Smoke of cigarettes, and specifically nicotine, has been shown to diminish pedicled transverse rectus abdominis musculocutaneous (TRAM) flap survival. Considering that Notch signalling through its ligand Delta-like 4 (Dll4) functions as anti-angiogenic factor by inhibiting the pro-angiogenic effects of vascular endothelial growth factor (VEGF), it is hypothesised that inhibition of the Notch would promote angiogenesis and increase TRAM flap survival in rats submitted to nicotine. METHODS: Twenty rats were treated with nicotine for 28 days preoperatively. Thereafter, a pedicled TRAM flap was created in all animals. The Notch inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine-t-butyl-ester was administered in animals of the treatment group. Animals in the control group were given the same amount of solvent. Five days after the surgery, viable flap areas were determined. Skin samples were evaluated for VEGF and Dll4 mRNA levels. Immunohistochemical analysis was used for the assessment of endothelial Dll4 expression. Vascular density was determined histologically. Plasma levels of VEGF and Dll4 were measured. RESULTS: A significant improvement in TRAM flap surviving area was observed in the treatment group (53.50 ± 14.25%) compared with the controls (32.20 ± 9.15%). Immunohistochemical analysis revealed a significant increase in the number of Dll4 stained vessels in animals of the treatment group (9.2 ± 1.6) in comparison with the controls (5.7 ± 1.9). VEGF mRNA levels (0.22 ± 0.08) in the treatment group were significantly lower than those in the control group (0.36 ± 0.09). CONCLUSION: Notch inhibition significantly improved TRAM flap survival in animals exposed to nicotine by promoting VEGF-induced angiogenesis.

The Notch Signaling System Is Involved in the Regulation of Reparative Angiogenesis in the Zone of Stasis.

The Notch pathway ligand Delta-like 4 (Dll4) functions as an antiangiogenic factor, inhibiting vascular endothelial growth factor (VEGF)-induced angiogenesis. This function is documented in tumor and embryonic vasculature. However, its implication in burn wounds remains unexplored. Our objective was to explore the involvement of the Notch in the healing of zone of stasis burns. We hypothesized that anti-Dll4 therapy would prevent progressive necrosis in the stasis zone by promoting angiogenesis. Burns were created in 21 rats using the comb burn model. The Notch inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine-t-butyl-ester was administered in the treatment group. Controls were given the same amount of solvent. Seven days after the burn, skin samples were evaluated for VEGF and Dll4 gene expressions. Immunohistochemical analysis was used for the assessment of vascular density, endothelial Dll4 expression, and apoptosis count. Histologic grading of tissue damage was performed. Circulating levels of VEGF and Dll4 were determined. VEGF and Dll4 mRNA levels were found to be simultaneously induced after the burn. In the treatment group, a significant increase in the number of vessels was observed. However, gross evaluation documented an expansion of necrosis to the zone of stasis with marked activation of apoptosis. Histologic assessment showed that the resultant vascular overgrowth was accompanied by extensive edema and abundant infiltration of leukocytes. We provide evidence for the involvement of Notch in the regulation of angiogenesis in zone of stasis burns.

BRCA1 and BRCA2 sequence variations detected with next-generation sequencing in patients with premature ovarian insufficiency.

OBJECTIVE: Although the association between BRCA1 and BRCA2 gene mutations and breast and ovarian cancer is known, there is insufficient data about premature ovarian insufficiency (POI). However, several studies have reported that there might be a relationship between POI and BRCA1 and BRCA2 gene mutation. Therefore, in the present study, we aimed to investigate the role of BRCA1 and BRCA2 gene mutations in the etiology of POI in a Turkish population. MATERIAL AND METHODS: The cohort was classified into two groups: a study group, consisting of 56 individuals diagnosed with premature ovarian insufficiency (and who were younger than 40 years of age, had an antral follicle count <3-5, and FSH levels >12 IU/I), and a control group, consisting of 45 fertile individuals. A total of 101 individuals were analyzed by next-generation sequencing to detect BRCA1 and BRCA2 gene mutations. RESULTS: We detected four new variations (p.T1246N and p.R1835Q in BRCA1 and p.I3312V and IVS-7T>A in BRCA2) that had not been reported before. CONCLUSION: We did not find an association between the BRCA1 and BRCA2 gene mutations and premature ovarian insufficiency. However, larger, functional studies are needed to clarify the association.

FCN2 c.772G>T polymorphism is associated with chronic adenoiditis and/or tonsillitis, but not -4 A>G and -602 G>A.

OBJECTIVE: Ficolins are complement activating peptides that play a role in the initial host defense against infectious pathogens. In the present study, we investigated the relationship between single nucleotide polymorphisms (SNPs) in the ficolin 2 gene (FCN2) and chronic adenotonsillitis in pediatric cases. STUDY DESIGN: Case-control study. METHODS: A total of 101 pediatric patients diagnosed with chronic adenotonsillitis and 100 healthy children were enrolled in the study. Genotypes of FCN2 promoter SNPs - 602 G>A and -4 A>G, and the exonic SNP c.772G>T were determined by light SNP assay after realtime PCR analysis using genomic DNA samples obtained from peripheral blood samples of all participants. RESULTS: Of the 101 chronic tonsillitis patients, 38 were girls and 63 were boys; the mean age was 5.2 ± 2.3 years. The c.772G>T SNP frequency was significantly higher in chronic adenotonsillitis cases compared to the control group (p = 0.00); however, no significant difference was determined at positions -602 G>A or -4 A>G (p > 0.05). CONCLUSIONS: The FCN2 c.772G>T genotype appears to be associated with predisposition to chronic adenotonsillitis in the pediatric age group. This nucleotide change is likely to influence the level of gene expression and contribute to the development of disease.

Effect of Hereditary Hemochromatosis Gene H63D and C282Y Mutations on Iron Overload in Sickle Cell Disease Patients.

OBJECTIVE: Hemochromatosis is an autosomal recessive disease that is one of the most important reasons for iron overload. Sickle cell disease is a hemoglobinopathy that occurs as a result of a homozygous mutation in the hemoglobin gene. Erythrocyte transfusion is frequently used in the treatment of this disease. Iron overload as a result of transfusion is important in the mortality and morbidity of sickle cell anemia patients as well as in other hemoglobinopathies. In this study, the effect of hemochromatosis gene (HFE) p.H63D and p.C282Y mutations on transfusion-related cardiac and liver iron overload in sickle cell disease patients who carry homozygous hemoglobin S mutation has been investigated. MATERIALS AND METHODS: This is a prospective single-center cross-sectional study in patients with homozygous hemoglobin S mutation between the years 2008 and 2013. The patients were divided into two groups. The first group (group A, n=31) was receiving chelation therapy and the second group (group B, n=13) was not. Direct and indirect iron loads were analyzed by magnetic resonance imaging and biochemically, respectively. HFE gene mutations were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analyses were performed by independent samples t-test. RESULTS: p.H63D mutation was detected in 10 (32.3%) patients in group A and in only 1 patient (7.7%) in group B. When the 2 groups were compared for iron overload, iron deposition in the liver was significantly higher in group B (p=0.046). In addition, in group A, iron deposition was significantly higher in HFE mutation carriers compared to patients without the mutation (p=0.05). CONCLUSION: Results of this study showed that HFE gene mutations are important in iron deposition in the liver in patients with sickle cell disease.

Lack of association of matrix metalloproteinase-9 promoter gene polymorphism in obstructive sleep apnea syndrome.

PURPOSE: Obstructive sleep apnea syndrome (OSAS) is a public health problem. There is an effort to establish the genetic contributions to the development of OSAS. One is matrix metalloproteinases, extracellular matrix degrading enzymes related to systemic inflammation. However, the impact of matrix metalloproteinase-9 (MMP-9) genotypes on the development of OSAS is unknown. Our aim was to determine whether MMP-9 single nucleotide polymorphism (SNP) (MMP-9 -1562C > T) is related to susceptibility to OSAS. MATERIAL AND METHODS: A total of 106 patients with a history of sleep apnea and 88 controls without a history of sleep apnea were enrolled in this study. Genotypes were determined by restriction fragment length polymorphism analyses after polymerase chain reaction. RESULTS: Genotypes and allele frequencies of the MMP-9 -1562C > T SNP was not statistically different between the patient and control groups (p > 0.05). There was a statistical association between apnea-hypopnea index (AHI) and body mass index (BMI), and also between AHI and neck circumference (p < 0.001). There was no association among the genotypes and AHI, neck circumference, or BMI (p > 0.05). CONCLUSIONS: We found no association between MMP-9 -1562C > T SNP and OSAS. Studies to investigate the role of other polymorphisms and expression of MMP-9 gene will provide more information.

Retrieving relevant experiments: The case of microRNA microarrays.

Content-based retrieval of biological experiments in large public repositories is a recent challenge in computational biology and bioinformatics. The task is, in general, to search in a database using a query-by-example without any experimental meta-data annotation. Here, we consider a more specific problem that seeks a solution for retrieving relevant microRNA experiments from microarray repositories. A computational framework is proposed with this objective. The framework adapts a normal-uniform mixture model for identifying differentially expressed microRNAs in microarray profiling experiments. A rank-based thresholding scheme is offered to binarize real-valued experiment fingerprints based on differential expression. An effective similarity metric is introduced to compare categorical fingerprints, which in turn infers the relevance between two experiments. Two different views of experimental relevance are evaluated, one for disease association and another for embryonic germ layer, to discern the retrieval ability of the proposed model. To the best of our knowledge, the experiment retrieval task is investigated for the first time in the context of microRNA microarrays.

The Notch pathway is a critical regulator of angiogenesis in a skin model of ischemia.

The Notch pathway is definitely required for normal vascular development. Although the contribution of Notch in postnatal angiogenesis is the focus of intense investigation, the implication of Notch in reparative neovascularization in the skin remains unexplored. In this study, we investigated Notch changes using a skin model of ischemia. Thirty Sprague-Dawley rats were divided into two groups. In the surgery group (n = 24), a caudally based dorsal skin flap was raised and sutured back into its initial position. In the control group, no surgical procedure was performed. Tissue biopsies were obtained at different time intervals. Tissue specimens were assessed for Delta-like ligand 4 (DLL4) and vascular endothelial growth factor (VEGF) gene expression by real-time polymerase chain reaction (PCR). Immunohistochemical staining was used for detection of DLL4 in tissue materials. Quantitative assessment of skin flap microvasculature was made. Compared with normoperfused tissue, VEGF and DLL4 expressions increased significantly (p < 0.01). Immunohistochemical analysis revealed weak and patchy expression of DLL4 in microvascular endothelial cells of normoperfused tissues. Conversely, DLL4 expression was upregulated in capillary endothelial cells after ischemia. In conclusion, in this study we have shown that the Notch ligand DLL4 is upregulated in skin tissue after ischemia. A deeper understanding of these fundamental principles will aid in the development of new avenues for the treatment of blood vessel-related skin pathologies.

Chronic tonsillitis is not associated with beta defensin 1 gene polymorphisms in Turkish population.

BACKGROUND: Defensins are antimicrobial peptides expressed on mucosal surfaces. They function as part of the innate immune system. Palatine tonsils play important roles in innate immune system. However, our knowledge on the pathophysiology of chronic tonsils is limited. OBJECTIVE: The aim of this study was to investigate the association between beta defensin 1 gene single nucleotide polymorphisms and chronic tonsillitis. STUDY DESIGN: Prospective, non-randomized, controlled clinical study. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Eighty six patients with chronic tonsillitis and eighty controls without history of chronic tonsillitis were enrolled in this study. Genotypes were determined by restriction fragment length polymorphism analyses after polymerase chain reaction. RESULTS: Genotype and allele frequencies of the -20G/A (rs11362), -44C/G (rs1800972) and -52G/A (rs1799946) single nucleotide polymorphisms were not statistically different between patients and control groups (p>0.05). CONCLUSION: In this study, we found that DEFB1 gene -20G/A, -44C/G and -52G/A single nucleotide polymorphisms were not associated with chronic tonsillitis. Studies, which analyse other polymorphism of the beta defensin 1 gene in large case series, should be conducted to understand the role of DEFB1 gene on chronic tonsillitis.