Evaluation of the protective and therapeutic effects of extra virgin olive oil rich in phenol in experimental model of neonatal necrotizing enterocolitis by clinical disease score, inflammation, apoptosis, and oxidative stress markers.

BACKGROUND AND AIM: Necrotizing Enterocolitis (NEC) is an inflammation-associated ischemic necrosis of the intestine. To investigate the effects of extra virgin olive oil (EVOO) on inflammation, oxidative stress, apoptosis, and histological changes in NEC-induced newborn rats. MATERIALS AND METHODS: 24 rats were randomly divided into three groups: control, NEC and NEC + EVOO. NEC induction was performed using hypoxia-hyperoxia, formula feeding, and cold stress. The NEC + EVOO group received 2 ml/kg EVOO with high phenolic content by gavage twice a day for 3 days. 3 cm of bowel including terminal ileum, cecum, and proximal colon was excised. RESULTS: Weight gain and clinical disease scores were significantly higher in the NEC + EVOO group than in the NEC group (p < 0.001). EVOO treatment caused significant decreases in IL1ß, IL6 levels (p = 0.016, p = 0.029 respectively) and EGF, MDA levels (p = 0.032, p = 0.013 respectively) compared to NEC group. Significant decreases were observed in IL6 gene expression in the NEC + EVOO group compared to the NEC group (p = 0.002). In the group NEC + EVOO, the number of Caspase-3 positive cells was found to be significantly reduced (p < 0.001) and histopathological examination revealed minimal changes and significantly lower histopathological scores (p < 0.001). CONCLUSION: Phenol-rich EVOO prevents intestinal damage caused by NEC by inhibiting inflammation, oxidative stress, apoptosis.

Germline landscape of BRCAs by 7-site collaborations as a BRCA consortium in Turkey.

BRCA1/2 mutations play a significant role in cancer pathogenesis and predisposition particularly in breast, ovarian and prostate cancers. Thus, germline analysis of BRCA1 and BRCA2 is essential for clinical management strategies aiming at the identification of recurrent and novel mutations that could be used as a first screening approach. We analyzed germline variants of BRCA1/2 genes for 2168 individuals who had cancer diagnosis or high risk assessment due to BRCAs related cancers, referred to 10 health care centers distributed across 7 regions covering the Turkish landscape. Overall, 68 and 157 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-two novel variants were reported from both genes while BRCA2 showed higher mutational heterogeneity. We herein report the collective data as BRCA Turkish consortium that confirm the molecular heterogeneity in BRCAs among Turkish population, and also as the first study presenting the both geographical, demographical and gene based landscape of all recurrent and novel mutations which some might be a founder effect in comparison to global databases. This wider perspective leads to the most accurate variant interpretations which pave the way for the more precise and efficient management affecting the clinical and molecular aspects.

Evaluation of the protective effects of morin against acrylamide-induced lung toxicity by biomarkers of oxidative stress, inflammation, apoptosis, and autophagy.

Acrylamide (ACR) has genotoxic, neurotoxic, and carcinogenic effects. From past to present, various plants or their products have been used for therapeutic purposes such as morin. It was aimed to detect possible protective effects of morin vs ACR-induced lung toxicity. The rats, treated with ACR alone or with morin for 10 consecutive days, were included in the study. A broad variety of biomarkers related to oxidative stress, apoptosis, autophagy, and inflammatory responses were evaluated. ACR increased malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), nuclear factor kappa-B (NF-κB), Beclin-1, IL-1ß, bcl-2 associated X protein (Bax), caspase-3, light chain 3-A (LC3-A), and light chain 3-B (LC3-B) levels but reduced mammalian target of rapamycin (mTOR), b-cell lymphoma-2 (Bcl-2), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione (GSH) in lung tissues. The morin had effects on the level of these molecules in a way that is opposite to ACR. While ACR-induced oxidative stress, apoptotic, autophagic, inflammatory responses, and may cause pulmonary dysfunction, the morin reduced ACR-induced lung damage. PRACTICAL APPLICATIONS: ACR is a toxic chemical produced by frying, baking, roasting, or grilling foods with high starch content and has genotoxic, neurotoxic, and carcinogenic effects. As an antioxidant compound, the morin is obtained from plants or their products. It was aimed to detect possible protective effects of morin against ACR-induced lung toxicity. It was detected that ACR-induced oxidative stress, apoptotic, autophagic, inflammatory responses, and may cause pulmonary dysfunction, but the morin reduced ACR-induced lung damage.

White-Sutton syndrome with hot water epilepsy and coexistence of SHOX gene variations.

The purpose of this study is to reveal the effect on the clinical phenotype of variants detected at family examination of a case of combined pogo transposable element derived with zinc finger domain (POGZ) gene, tubulin folding cofactor E (TBCE) gene, and short stature homeobox (SHOX) gene variation. A Turkish non-consanguineous family consisting of five members was investigated. Whole exome sequence analysis and chromosomal microarray analysis (CMA) were performed for a 2-year-old male patient (the proband) with global developmental delay, hypotonia, dysmorphia, and hot water epilepsy. Targeted sequence and chromosomal microarray analyses were performed for each family member. A heterozygous c.3908_3911delTCTG/p.V1303fs*6 variant was detected in the POGZ gene and a heterozygous c.626 T > G(p.L209X) variant in the TBCE gene in the proband. In addition, a gain of 0.1 MB was detected in the Xp22.33(602488-733497) × 3/Yp11.32(552488-683497) × 3 region at CMA. The SHOX (312865) gene defined in Online Mendelian Inheritance in Man is located in this region. While the proband's father and brother had heterozygous variations only in the TBCE gene, neither TBCE nor POGZ mutations were detected in the mother or sister. A gain in Xp22.33(419224-883640) × 3 was detected in the mother at CMA. Except for short stature and Madelung deformity, no phenotypical findings were detected in the mother. Other family members were also phenotypically normal. The family screening confirmed that dysmorphic findings and global developmental delay in the proband resulted from the variation in the POGZ gene, while short stature was caused by the gain in the Xp22.33(602488-733497) × 3/Yp11.32(552488-683497) × 3 region. In addition, the pathogenic POGZ gene variation in our patient may be a possible cause of hot water epilepsy. Heterozygous variation in the TBCE gene was clinically insignificant. Hot water epilepsy has not previously been reported in the rare patients with POGZ gene mutation. Additionally, in contrast to the previous literature, the proband exhibited no features of autism. It should also be remembered that posterior fossa abnormalities are frequently seen in these patients. We think that this case and family review involving POGZ and SHOX gene mutations will make a useful contribution to the existing literature.

Combination of Novel c.3484G> T/p.Glu162Ter Variant in ABCB11 and c.208G> A/p.Asp70Asn Variant in ATP8B1 Are Associated with Severe Symptoms in Progressive Family Intrahepatic Cholestasis.

Progressive family intrahepatic cholestasis (PFIC) is an autosomal recessive disease that causes chronic cholestasis. It is associated with pathogenic variants in genes that encode proteins involved in bile secretion to canaliculus from hepatocytes. In this study, we present a 16-year-old boy who presented with severe pruritus and cholestatic jaundice. All possible infectious etiologies were negative. A liver biopsy was consistent with intrahepatic cholestasis and portal fibrosis. DNA was isolated from a peripheral blood sample, and whole exome sequencing was performed. A novel c.3484G > T/p.Glu162Ter variant in the ABCB11 gene and a c.208G> A/p.Asp70Asn variant in the ATP8B1 gene were detected. Despite traditional treatment, the patient's recurrent severe symptoms did not improve. The patient was referred for a liver transplantation. This novel c.3484G > T/p.Glu162Ter variant is associated with a severe and recurrent presentation, and the two compound variants could explain the severity of PFIC.

Novel mutation identified in the DDB2 gene in patients with xeroderma pigmentosum group-E.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare photosensitive syndrome, which is divided into eight complementation groups (XP-A to XP-G and XPV) and characterized by skin cancers diagnosed at early age. A family of seven members (age range between 5 and 47 years) with carriers of the novel nonsense mutation that causes XP-E type were included in the current study. METHODS: DNA was isolated from peripheral blood samples of the proband, and cancer predisposition genes were sequenced with next-generation sequencing. The demographic features and the laboratory, clinical, and histopathological findings of patients were evaluated. RESULTS: In the proband, squamous cell carcinoma was first diagnosed in the right-eye cornea at the age of 13 years and then in the left-eye cornea at the age of 15 years. Later, the patient was diagnosed with basosquamous cell carcinoma on the dorsum of the nose at the age of 18 years. After genetic analysis, a novel nonsense c.1063C>T(p.Arg355Ter) pathogenic variation that causes XP-E type was detected as homozygous in the DDB2 gene of the proband and her siblings, 11 and 5 years of age, and as heterozygous in her parents and a 22-year-old brother. CONCLUSION: Because of the occurrence of early termination codon, truncated nonfunctional proteins or proteins with deleterious loss or gain-of-function activities are synthesized in nonsense mutation. Thus, to avoid the development of pathological lesions, it is important that such patients with nonsense mutation stay away from agents that might cause DNA damage and develop an appropriate lifestyle according to this condition.

Does capsaicin have therapeutic benefits in human colon adenocarcinoma? Selection of the most reliable dose via AgNOR

Background/aim: To determine the effect of different doses of capsaicin on AgNOR protein synthesis in human colon adenocarcinoma derivate from colon cancer (Caco-2 cell). Materials and methods: In this experimental study, after the cultured of Caco-2 cell line, the cells are divided into 4 groups as control and different capsaicin exposed doses (25uµ, 50uµ, and 75uµ). Mean AgNOR number and total AgNOR area/nuclear area (TAA/NA) were calculated. Results: A significant differences were detected between control and capsaicin (50uµ) (P = 0.001), between control and capsaicin (75uµ) (P = 0.000), between capsaicin (25uµ) and capsaicin (50uµ) (P = 0.001) and between capsaicin (25uµ) and capsaicin (75uµ) (P = 0.000) for TAA/NA. Also, there were significant differences between control and capsaicin (50uµ) (P = 0.001), between control and capsaicin (75uµ) (P = 0.000), between capsaicin (25uµ) and capsaicin (50uµ) (P = 0.000) and between capsaicin (25uµ) and capsaicin (75uµ) (P = 0.000) for mean AgNOR number. Conclusion: A certain amount of capsaicin has a protective effect against colon adenocarcinoma and the dose concentrations are important for the most reliable treatment.

Association between survivin gene polymorphisms and the susceptibility to colon cancer development in the Turkish population.

BACKGROUND: Colon cancer is one of the most common cancers worldwide. Apoptosis is a necessary physiological process for cell elimination which is very important both cellular homeostasis and cell proliferation and differantiation. Dysregulation can lead to uncontrolled cell growth and tumor development. Survivin, a member of the IAP family, plays a key role in promotion of cell proliferation as well as inhibition of apoptosis in cancer cells. The aim of this study was to investigate whether specific genetic polymorphisms of survivin could be associated with colon cancer development and progression in a Turkish population. Our study is the first to our knowledge to investigate the relationship between colon cancer risk and survivin gene polymorphisms. MATERIALS AND METHODS: The relation between colon cancer and survivin -31 G/C (rs9904341), -241 C/T (rs17878467) and -625 C/G (rs8073069) polymorphism in promotor site of survivin gene associated with apoptosis was investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Individuals with -31C allele and CC genotype were found to have a higher risk of developing colon cancer (OR=13.4, p=0.01). The -241 CT genotype considerably increased the risk of colon cancer (OR=12.0, p=0.0001). However, there was no significant varaition of the survivin -625 C/G polymorphism among colon cancer patients and controls in our study. CONCLUSIONS: This study provides the first evidence that survivin -31 G/C and -241 C/T SNP significantly contribute to the risk of colon cancer in the Turkish population.

Evaluation of smoking habits among Turkish family physicians.

Smoking is still a major public health problem in Turkey. It was aimed to investigate smoking prevalence and habits among Turkish family physicians. Cross-sectional study among physicians working in primary care settings was established. A self-administered study survey was applied. The surveys of 1233 family physicians were analyzed. The study included 704 (57.1%) male and 529 (42.9%) female physicians. Mean age (SD) was 38.94 (7.01) years. The proportions of the current, the former and never smokers among family physicians were 34.1%, 14.7% and 51.3%, respectively. Mean age (SD) of smoking initiation was 21.73 (5.04) years. Mean duration (SD) of smoking use was 14.61 (7.29) years. Proportion of current smoker in male physicians was quite higher than in female counterparts (36.9% vs. 30.4%; p < 0.001). Mean age (SD) of smoking initiation in female was 21.42 (4.59) years, but in male was 22.33 (4.98) years (p = 0.36). In female physicians, mean age (SD) for quitting cigarette smoking was found higher than in male (35.85 (6.35) years vs. 33.09 (6.45) years; p = 0.004). No significant difference between nicotine dependence (mean score (SD) of 3.76 (2.48) vs. 3.65 (2.82); p > 0.05) and mean (SD) unit of cigarette a day (18.34(6.03) vs. 17.17 ± 6.79; p > 0.05) between genders was observed. The number of male physicians who started smoking before faculty was higher than female counterparts (15.5% vs. 8.6%; p = 0.023). In conclusion, the smoking prevalence among Turkish family physicians is considerably high.

Value of argyrophilic nucleolar organizing region protein determinations in nondiagnostic fine needle aspiration samples (due to insufficient cell groups) of thyroid nodules.

OBJECTIVE: To evaluate the diagnostic value of argyrophilic nucleolar organizing regions (AgNORs) in the nondiagnostic fine needle aspiration biopsy (NFNAB) specimens (due to insufficient cell groups) of cases with thyroid nodules. STUDY DESIGN: Thirty-five patients with NFNAB were included in the study. FNAB stained with Giemsa was faded using the McKee technique, then stained for AgNOR detection according to a specific protocol. One hundred nuclei per individual were evaluated to detect the AgNOR count/nucleus and total AgNOR area/ nuclear area (TNA/NA) of individual cells by using a computer program. RESULTS: The AgNOR values of patients with NFNAB were between 1.2-2.4% for AgNOR count/ nucleus and between 3.1-9.1%for TNA/NA. When the cutoff values were taken as > 3 for AgNOR count/nucleus and > 8 for TNA/NA, the sensitivity ratios were 100% and 97% for AgNOR count/nucleus and TNA/ NA for discriminating benign/malignant lesions. CONCLUSION: By using some cutoff values obtained from a modified AgNOR staining method, benign/malignant potential of thyroid aspirations with NFNAB may be estimated. (Anal Quant Cytopathol Histopathol

Detection and comparison of cut-off values for total AgNOR area/nuclear area and AgNOR number/nucleus in benign thyroid nodules and normal thyroid tissue.

Argyrophilic nucleolar organising region associated proteins (AgNORs) are of interest in a variety of diseases including thyroid disorders. We have investigated the cut-off values for AgNOR count and with a new approach, Total AgNOR area/nuclear area (TNORa/Na) proportions to discriminate thyrocytes obtained from benign thyroid nodules and normal thyroid tissue. Thirty patients whose fine needle aspiration (FNA) materials were compatible with a benign lesion (named as goiter group) and 30 controls (subjects with normal thyroid tissue) were included. In the control group, biopsy material was obtained from histologically normal thyroid gland operated on because FNA material was compatible with papillary thyroid carcinoma (PTC). These samples were stained for AgNOR and 100 nuclei per individual were examined. Both AgNOR values for individual cells and cut-off values were detected for each group. Patients with goiter had significantly (P<0.001) higher AgNOR count (2.1 ± 0.6%) and TNORa/Na (6.1 ± 1.5%) than the control groups (1.4 ± 0.2 and 3.0 ± 0.4, respectively). The cut-off values were <1.5 for AgNOR count and <3.8 for TNORa/Na in thyrocytes of the controls. This modified method is an easy and reliable method for discriminating various thyroid disorders, including the differentiation of benign thyroid nodules from malignant ones. It also helps to discriminate thyrocytes obtained from benign nodules from normal thyroid tissue, aiding accurate localisation of sampling in FNA material.

The evaluation of argyrophilic nucleolar organizing region proteins in fine-needle aspiration samples of thyroid.

Argyrophilic nucleolar organizing region associated proteins (AgNORs) have been shown to be of interest in a variety of different diseases including thyroid disorders. Our aim was to distinguish benign thyroid lesions from papillary thyroid carcinoma (PTC) via AgNOR count and with a new approach, via AgNOR surface area/total nuclear surface area (NORa/TNa) proportions in the nuclei on fine-needle aspiration (FNA) materials. Thirty patients (eight men and 22 women) whose FNA was compatible with benign lesion and 26 patients (eight men and 18 women) whose FNA was compatible with PTC were included in the study. Fine-needle aspiration materials were stained for AgNOR detection according to a specific protocol. One hundred nuclei per individual have been evaluated, and AgNOR number and NORa/TNa proportions of individual cells were measured and calculated by using a computer program. Patients with PTC had significantly (p<0.001) higher AgNOR count (4.6 ± 1.2%) than in the patients with benign lesions (2.0 ± 0.5%). Additionally, patients with PTC had significantly (p<0.001) higher NORa/TNa (13.4 ± 2.4) than in the patients with benign lesion (5.7 ± 1.0). Modified method of AgNOR staining is an easy and reliable method for evaluating proliferation activity of cells in malignant and benign thyroid lesions and it may contribute to routine cytopathology in inconclusive situations.