A novel gene selection method for gene expression data for the task of cancer type classification.

Cancer is a poligenetic disease with each cancer type having a different mutation profile. Genomic data can be utilized to detect these profiles and to diagnose and differentiate cancer types. Variant calling provide mutation information. Gene expression data reveal the altered cell behaviour. The combination of the mutation and expression information can lead to accurate discrimination of different cancer types. In this study, we utilized and transferred the information of existing mutations for a novel gene selection method for gene expression data. We tested the proposed method in order to diagnose and differentiate cancer types. It is a disease specific method as both the mutations and expressions are filtered according to the selected cancer types. Our experiment results show that the proposed gene selection method leads to similar or improved performance metrics compared to classical feature selection methods and curated gene sets.

Statistical representation models for mutation information within genomic data.

BACKGROUND: As DNA sequencing technologies are improving and getting cheaper, genomic data can be utilized for diagnosis of many diseases such as cancer. Human raw genome data is huge in size for computational systems. Therefore, there is a need for a compact and accurate representation of the valuable information in DNA. The occurrence of complex genetic disorders often results from multiple gene mutations. The effect of each mutation is not equal for the development of a disease. Inspired from the field of information retrieval, we propose using the term frequency (tf) and BM25 term weighting measures with the inverse document frequency (idf) and relevance frequency (rf) measures to weight genes based on their mutations. The underlying assumption is that the more mutations a gene has in patients with a certain disease and the less mutations it has in other patients, the more discriminative that gene is. RESULTS: We evaluated the proposed representations on the task of cancer type classification. We applied various machine learning techniques using the tf-idf and tf-rf schemes and their BM25 versions. Our results show that the BM25-tf-rf representation leads to improved classification accuracy and f-score values compared to the other representations. The highest accuracy (76.44%) and f-score (76.95%) are achieved with the BM25-tf-rf based data representation. CONCLUSIONS: As a result of our experiments, the BM25-tf-rf scheme and the proposed neural network model is shown to be the best performing classification system for our case study of cancer type classification. This system is further utilized for causal gene analysis. Examples from the most effective genes that are used for decision making are found to be in the literature as target or causal genes.

The neuroprotective effects of 2-APB in rats with experimentally- -induced severe acute pancreatitis.

AIM: The objective of this study was to determine the neuroprotective effects of 2-aminoethyl diphenyl-borinate (2-APB) on the brains of rats with experimentally-induced severe acute pancreatitis. MATERIALS AND METHODS: Thirty Spraque-Dawley male rats with an average weight of 200-250 grams were randomly divided into three groups. Group 1: Sham group, Group 2: Severe acute pancreatitis group, Group 3: Treatment group with severe acute pancreatitis, given 2 mg/kg 2-APB before pancreatitis onset. In Groups 2 and 3, severe acute pancreatitis was induced by intraperitoneal administration of 1.5 g/kg L-arginine with a 1-hour interval. Tumor necrosis factor-α, interleukin 6, pancreatic amylase were all measured. Brain tissue samples were evaluated histopathologically. TUNEL staining method was used to visualize apoptotic cells. RESULTS: In Group 3, it was determined that the density of TUNEL-positive cells in the cerebral cortex has decreased, while the number of Bcl-2-positive cells had increased. In Group 3, it was observed that glial aggregation areas were diminished and histopathological changes were decreased as compared to Group 2. In Group 2, on the other hand, it was observed that in areas with glial cell aggregation, the density of TUNEL-positive glial cells had increased, while Bcl-2-positive cell reaction has been feeble. CONCLUSIONS: It was observed that 2-APB decreases neuronal apoptosis and glial cell aggregation (Tab. 2, Fig. 3, Ref. 21).

Coagulation parameters and platelet function analysis in patients with acromegaly.

OBJECTIVE: Acromegaly is associated with increased cardiovascular morbidity and mortality. The data about the evaluation of coagulation and fibrinolysis in acromegalic patients are very limited and to our knowledge, platelet function analysis has never been investigated. So, we aimed to investigate the levels of protein C, protein S, fibrinogen, antithrombin 3 and platelet function analysis in patients with acromegaly. METHODS: Thirty-nine patients with active acromegaly and 35 healthy subjects were included in the study. Plasma glucose and lipid profile, fibrinogen levels, GH and IGF-1 levels and protein C, protein S and antithrombin III activities were measured in all study subjects. Also, platelet function analysis was evaluated with collagen/ADP and collagen-epinephrine-closure times. RESULTS: Demographic characteristics of the patient and the control were similar. As expected, fasting blood glucose levels and serum GH and IGF-1 levels were significantly higher in the patient group compared with the control group (pglc: 0.002, pGH: 0.006, pIGF-1: 0.001, respectively). But lipid parameters were similar between the two groups. While serum fibrinogen and antithrombin III levels were found to be significantly higher in acromegaly group (p fibrinogen: 0.005 and pantithrombin III: 0.001), protein S and protein C activity values were significantly lower in the patient group (p protein S: 0.001, p protein C: 0.001). Also significantly enhanced platelet function (measured by collagen/ADP- and collagen/epinephrine-closure times) was demonstrated in acromegaly (p col-ADP: 0.002, p col-epinephrine: 0.002). The results did not change, when we excluded six patients with type 2 diabetes in the acromegaly group. There was a negative correlation between serum GH levels and protein S (r: -0.25, p: 0.04)) and protein C (r: -0.26, p: 0.04) values. Likewise, there was a negative correlation between IGF-1 levels and protein C values (r: -0.39, p: 0.002), protein S values (r: -0.39, p: 0.001), collagen/ADP-closure times (r: -0.28, p: 0.02) and collagen/epinephrine-closure times (r:-0.26, p: 0.04). Also, we observed a positive correlation between IGF-1 levels and fibrinogen levels (r: 0.31, p: 0.01). CONCLUSION: Acromegaly was found to be associated with increased tendency to coagulation and enhanced platelet activity. This hypercoagulable state might increase the risk for cardiovascular and cerebrovascular events in acromegaly.

Melatonin Modulates the Immune System Response and Inflammation in Diabetic Rats Experimentally-Induced by Alloxan.

Diabetes mellitus (DM) is a metabolic disease, which causes an increase in the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß), and also proliferation of monocyte chemotactic protein. In the present study, the potential effects of melatonin on proinflammatory cytokines, hematological values, and lymphoid tissues were investigated in diabetic rats. In the study, 36 male rats were randomly divided into 4 groups as follows: Control, Mel (melatonin), DM, and DM-Mel. For 15 days, an isotonic saline solution was given to the Control and DM groups; melatonin was administered to the Mel and DM-Mel groups intraperitoneally. At the end of the study, all animals were sacrificed by drawing the blood from their hearts under deep anesthesia. Samples of the spleen, thymus, and lymph nodes were fixed in 10% formaldehyde for histologic analysis. Increases in proinflammatory serum cytokine concentrations, mast cells, and total white blood cell counts as well as tissue destruction in the lymphoid organs were determined in the DM group via biochemical, hematological, and histologic analyses. However, the findings for the DM-Mel group revealed decreases in serum IL-1ß concentration and mast cell densities, and destructions in lymphoid tissues by the melatonin administration. The present study suggests that melatonin treatment may control immune system regulation and inhibit the production of proinflammatory cytokines and tissue mast cell accumulation by preventing the destruction of lymphoid organs in the diabetic process.

Assessment of the biocompatibility of mineral trioxide aggregate, bioaggregate, and biodentine in the subcutaneous tissue of rats.

OBJECTIVE: The objective of this study was to evaluate the tissue inflammation caused by three endodontic repair materials. MATERIALS AND METHODS: The materials included micro mega-mineral trioxide aggregate (MM-MTA), bioaggregate (BA), and biodentine (BD), which were implanted into the subcutaneous tissue of rats. The tissue samples for histological examination were prepared. The infiltration of lymphocytes and macrophages into the tissue was examined to assess the inflammatory response. RESULTS: Lymphocyte infiltration: A significant increase was detected in the MM-MTA and BA groups on the 7th and 14th days as compared with the control (7th day P=0.0001, 14th day P=0.0176). There was no difference between the groups on the 45th day (P=0.1730). Lymphocyte infiltration had decreased over time in all groups. Macrophage infiltration: There was a significant increase by the 7th day in the test groups as compared to the control group (P=0.007). However, there was no difference between the experimental groups on the 14th (P=0.2708) and 45th (P=0.1291) days. CONCLUSION: While MM-MTA and BA showed a similar biocompatibility, BD was more biocompatible than MM-MTA and BA in the 1 st week of the experiment. However, there was no difference between the materials at the end of the 45th day. MM-MTA, BA, and BD can be considered suitable endodontic repair materials.

Association of collagen type I alpha 1 gene polymorphism with inguinal hernia.

PURPOSE: A positive family history is an important risk factor for inguinal hernia development, suggesting a genetic trait for hernia disease. However, gene mutations responsible for abdominal wall hernia formation in humans have not yet been studied. We aimed to evaluate whether the functional Sp1 binding site polymorphism within intron 1 of the collagen type I, alpha 1 (COL1A1) gene was associated specifically with inguinal hernia disease. METHODS: 85 participants with surgically diagnosed inguinal hernia disease, and 82 physically active controls without any history of connective tissue disease and hernia were recruited for this case-control genetic association study. Polymerase chain reaction and restriction fragment length polymorphism and agarose gel electrophoresis techniques were used to detect these polymorphisms. RESULTS: Significantly, more patients gave a positive family history for an inguinal hernia compared to healthy controls (OR 3.646, 95 % CI 1.375-9.670, P = 0.006). COL1A1 Sp1 SNP (rs 1800012) was identified. Results demostrated statistically significant deviation from HWE for cases (P = 0.007), but not for the controls (P = 0.276). Our results revealed an increased frequency of COL1A1 Sp1 Ss genotype in inguinal hernia patients (OR 3.593, 95 % CI 1.867-6.915, P = 0.000). CONCLUSIONS: This results suggest that polymorphism of the COL1A1 Sp1 binding site is associated with an increased risk for developing inguinal hernias. So, rs 1800012 locus is a potential candidate region for susceptibility in molecular mechanism of inguinal hernia pathophysiology.

Effects of melatonin on islet neogenesis and beta cell apoptosis in streptozotocin-induced diabetic rats: an immunohistochemical study.

This investigation was carried out to explore the antidiabetic, antiapoptotic and neogenetic effects of melatonin (MLT) in streptozotocin-induced diabetic rats. Sixty-four male rats were assigned randomly to one of four groups for periods of 21 and 42 d as follows; i) control, ii) MLT, iii) diabetic (DM), and iv) DM + MLT. Immunohistochemical methods were used -with pancreatic tissue to determine the intensity of insulin, caspase-3 and Bcl-x(L) immune reactivities, and new islet formation. In untreated DM rats, BW loss, increased plasma glucose and MLT concentrations, as well as cytoplasmic degranulation and vacuolization were observed. We also observed a marked increase in the number of apoptotic caspase-3 positive cells and a few insulin- positive cells, but not antiapoptotic Bcl-x(L) positive cells. Observations in the DM + MLT-treated group revealed a high intensity of insulin- and antiapoptotic Bcl-x(L) immune reactivities at 21 and 42 d. Moreover, data indicated that MLT may cause beta cell proliferation and that new small islets originate from cells associated with ductal epithelium and from centroacinar cells by day 21. These data indicate that; i) MLT treatment may stimulate neogenesis in the pancreas of diabetic rats, and ii) MLT's antiapoptotic action may increase beta cell differentiation and caspase-3 inactivation or Bcl-x(L) activation.

The effect of royal jelly on CD3(+), CD5(+), CD45(+) T-cell and CD68(+) cell distribution in the colon of rats with acetic acid-induced colitis.

BACKGROUND: Traditional medicines and health supplements have historically been used to treat many illnesses but most of them have not been evaluated objectively to prove their efficacy. We have been investigating the effects of royal jelly (RJ) supplements on acetic acid-induced colitis on the distribution of CD3(+), CD5(+), CD45(+) T-cell and CD68(+) cells in rats. METHODS: The rats were divided into four equal groups: control group, royal jelly-treated (RJ - 150mgkg(-1) body weight), acetic acid-treated (colitis) and acetic acid-treated (colitis)+royal jelly (CRJ - 150mgkg(-1) body weight). Colitis was induced by intracolonic instillation of 4% acetic acid; the control group received physiological saline (10mLkg(-1)). Colon samples were obtained under deep anaesthesia from animals in four groups. Tissues were fixed in 10% formalin neutral buffer solution for 24h and embedded in paraffin. RESULTS: The proliferative response of CD3(+) and CD45(+) T cells stimulated with colitis was affected by colitis treated with RJ. No differences were found in CD5(+) T cells and CD68(+) macrophages in the colitis treated with RJ. CONCLUSIONS: This study has shown that RJ has anti-inflammatory and cell regeneration effect in the colon of rats with acetic acid induced colitis.

The role of allopurinol on oxidative stress in experimental hyperthyroidism.

AIM: During hyperthyroidism, production of free oxygen radicals derives, where xanthine oxidase may also play an important role. Allopurinol, a xanthine oxidase inhibitor, has a significant effect on thyrotoxicosis-related oxidative stress. However, the relationship between thyroid hormones, oxidative stress parameters and allopurinol remains to be explored. METHODS: Forty-two Wistar albino rats were divided into three groups. Rats in group A served as negative controls, while group B had untreated thyrotoxicosis and group C received allopurinol. Hyperthyroidism was induced by daily 0.2 mg/kg L-thyroxine intraperitoneally in groups B and C; 40 mg/kg allopurinol were given daily intraperitoneally. Efficacy of the treatment was assessed after 72 h and 21 days, by measuring serum xanthine oxidase (XO), malondialdehyde (MDA), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx) and nitric oxide derivates (NO*x). RESULTS: In both time periods, serum XO, MDA, GSH and NO*x levels were significantly increased after thyroid hormone induction (p<0.05). Levels of XO, MDA and NO*x decreased with allopurinol treatment (p<0.05). There was a remarkable decrease in triiodothyronine levels in group C after 72 h (p<0.05), and in both triiodothyronine and thyroxine levels in group C after 21 days (p<0.05). There was no difference between groups B and C in means of serum GSH, GR and GPx levels (p>0.05). CONCLUSIONS: This study suggests an association between allopurinol and the biosynthesis of thyroid hormones. Allopurinol prevents the hyperthyroid state, which is mediated predominantly by triiodothyronine and not by XO. This issue has to be questioned in further studies where allopurinol is administered in control subjects.

Immunohistochemical studies on the splenic lobe of the pancreas in young Japanese quails (Coturnix c. japonica).

The splenic lobe (Lobus splenicus) of the pancreas of young meat-type quails (Coturnix c. japonica) was examined by immunohistochemical and light microscopic methods. The endocrine cells are mainly grouped as alpha, beta and mixed islets. A large region consisting of alpha cells is located in the central region of the splenic lobe whereas numerous beta islets are detected in the periphery of the splenic lobe. Alpha islets are in the majority composed of toluidine blue positive A cells and a few toluidine blue negative D and / or avian pancreatic polypeptide (APP) endocrine cells. Beta islets contain only a few toluidine blue negative B and a few D cells. Immunohistochemical staining of the splenic lobe reveal in the centre of beta islets numerous insulin immunoreactive cells and scarcely in alpha islets, exocrine tissue and / or among acinar cells. Somatostatin immune-reactive cells form a circular layer in the periphery of beta islets whereas these cells are uniformly distributed throughout the alpha islet parenchyma and exocrine tissue. In conclusion, the morphology but also the endo- and exocrine functions of the splenic lobe of quails are similar to observations in other avian species such as chicken, duck, goose and pigeon.

Ultrastructure of pancreatic alpha and beta cells in young quails (Coturnix coturnix japonica) fed aflatoxin.

The present investigation was undertaken to assess the effects of aflatoxin (AF) containing diets on alpha and beta cells of the endocrine pancreas in young quails by means of light and electron microscopy. A total of thirty quails were divided into 3 groups, each comprising 10 animals. Total AF was incorporated into the diet of these groups, at dosages of 0 (control, group 1), 2.5 (group 2), and 5.0 (group 3) mg AF/kg feed. The chicks were housed in electrically heated battery cages and exposed to light for 24 h from hatching to 3 weeks of age. Quails consumed the diets and water ad libitum. Electron microscopic examinations demonstrated degranulation of alpha cells, decrease in the size and number of secreting granules, and increase in the number of free ribosomes and polisomes in the animals of group 2 and 3. In beta cells, the numbers of free ribosomes and polisomes decreased, whereas the number of mature granules increased in the animals of group 3. Mononuclear cell infiltrates were observed in the periphery of capillaries and around endocrine islets in the experimental groups. Furthermore, capillaries of the animals in group 2 and 3 were dilated at all sides of both alpha and beta islets. According to the results of this study, the addition of aflatoxin to the diets of quails at dosage of 2.5 and 5 mg AF/kg leads to significant changes in pancreatic alpha and beta cells. These changes may exhibit adverse effect on the metabolism of carbohydrates in poultry.

Effects of increasing zinc supplementation in drinking water on growth and thyroid gland function and histology in broiler chicks.

The aim of the study was to examine the effects of increasing zinc supplementation on growth, feed efficiency and thyroid function and histology in broiler chicks. Sixty new born male broiler chicks were randomly allotted into one of four treatment groups and fed for 60 d. Zinc (Zn) was added into drinking water at the levels of 0, 125, 500, and 1000 mg Zn/L. Body weight gain were significantly higher and feed efficiency were significantly lower in chicks supplemented with 125 mg Zn/L compared with chicks supplemented with 500 or 1000 mg Zn/L at the end of the experiment. Serum Zn concentration linearly increased with the increasing level of Zn intake. Serum triiodothyronine and thyroxine levels and the diameters of follicles of thyroid gland were significantly reduced with high levels (500 and 1000 mg Zn/L) of Zn intake at the end of the experiment. It was concluded that chick receiving 1000 mg Zn/L as ZnSO4.7H2O in drinking water showed signs of Zn toxicity.

An experimental study on the effect of collagen shields and therapeutic contact lenses on corneal wound healing.

We evaluated the effects of collagen shields and therapeutic contact lenses on corneal wound healing in rabbits. A corneal wound was created by mechanical removal of the central 6-mm zone of the corneal epithelium and basement membrane in 30 eyes of 15 rabbits. The animals were divided into three groups: five rabbits in the first group were treated with a collagen shield in one eye and a therapeutic lens in the other eye. In the remaining two groups, either a collagen shield or a therapeutic lens was applied in one eye and the other eye served as the control. The radius and area of the wound were measured at 0, 6, 24, and 48 h after wounding. Linear regression analysis revealed a significant reduction in the wound area with time in all groups. The healing rate was found to be 0.52 +/- 0.08 mm2/h in the collagen shield, 0.54 +/- 0.05 mm2/h in the therapeutic lens, and 0.43 +/- 0.06 mm2/h in the control group. Comparison of the study groups by Bonferroni modification of analysis of variance revealed no statistically significant difference between the collagen shield and the therapeutic lens group at any time (p > 0.05), whereas a significantly larger wound size was observed in the control group compared with the treatment groups at all times studied (p < 0.05 at 6 h; p < 0.001 at 24 and 48 h). In conclusion, our results indicate that both collagen shields and therapeutic lenses enhance wound healing in rabbit eyes.