Investigation of effects of olea europaea leaf, rubus fruticosus and nigella CV extracts on microrna expression levels on colon cancer cell lines

Kolorektal kanser, dünyada en yaygın görülen kanserlerden biridir. Son 30 yılda gelişen cerrahi ve görüntüleme tekniklerine rağmen kemoterapatiklerin tedavide yeterince etkin sonuçlar veremediği görülmektedir. Biyoaktif ajanlar olarak adlandırılan bitki özütleri, son yıllarda yeni tedavilerin geliştirilmesi açısından yoğun olarak araştırılmaktadır. Epigenetik mekanizmalar üzerinden etkili olduğu anlaşılan bitkisel özütlerin yeni kanser tedavi modellerinin geliştirilmesinde faydalı olacağı düşünülmektedir. Tüm bu sebepler ile mevcut tez çalışmasında kolorektal kanser hücrelerinde bitkisel özütlerin etkilerinin, önemli bir epigenetik mekanizma olan mikroRNA (miRNA) ekspresyon seviyelerindeki değişimler ile değerlendirilmesi amaçlanmıştır. Gerçekleştirilen çalışmada, Nigella sativa (çörekotu) tohum özütü (NTE), Olea europeae (zeytin) yaprağı özütü (OLE) ve Rubus fruticosus (böğürtlen) kök özütü (RKE)'nün iki kolorektal kanser hücre hattındaki (HT-29 ve LoVo) anti kanser etkisi hücre proliferasyonu ve invazyonu açısından araştırıldı ve olası anti kanser etkinin moleküler mekanizması miRNA ekspresyon seviyesinde çalışılarak epigenetik olarak değerlendirildi. WST-1 analizi sonuçlarına göre değerlendirilen bitki özütlerinin hücre proliferasyonunu anlamlı düzeyde azaltıcı etkisinin (p<0.05) olduğu belirlendi. RKE ve NTE'nin her iki hücre hattında da istatistiki olarak anlamlı seviyede (p<0.05), OLE'nin ise LoVo hücre hattında istatistiki anlamlılığa yakın seviyede (p=0.0641) hücrelerin migrasyon özelliğini inhibe ettiği görüldü. Bitki özütlerinin RT-PCR yöntemi ile miRNA ekspresyon profillerine etkisi değerlendirildiğinde RKE'nin her iki hücre hattında da miR-140 ekspresyon artışına (p<0.05), NTE ve OLE'nin ise HT-29 hücrelerinde miR-182a ekspresyonunda istatistiki olarak anlamlı seviyede (p<0.05) düşüşe neden olduğu belirlendi. Mevcut çalışmada, RKE, NTE ve OLE'nin kolorektal kanser hücrelerinde epigenetik mekanizmalar aracılığı ile hücre proliferasyonu ve migrasyonunu azaltıcı yönde etkiye sahip olduğu literatürde ilk kez ortaya koyulmuştur. İleri çalışmalar gerekmekle birlikte her üç bitki özütünün de kolorektal kanserde yeni tedavilerin araştırılmasına yönelik çalışmalar için potansiyel birer aday olabileceğini düşünmekteyizColorectal cancer one of the most common cancers in the World. Although surgical and screening techniques have been improved a lot in last 30 years, chemotherapeutics have not advanced sufficiently for a successful treatment. New treatments options for many disease by the help of plant extracts, which are called bioactive agents, have been searching intensively. Plant extracts, also effective on epigenetic mechanisms, are thought to be efficious for developing new cancer therapy approaches. Aim of this dissertation study is to evaluate changes in one of the important epigenetic mechanisms microRNA (miRNA) expression levels due to effects of plant extracts on the colorectal cell lines. In present study, Nigella sativa (black cumin) seed extract (NTE), Olea europeae (olive) leaf extract (OLE) and Rubus fruticosus (blackberry) root extract (RKE) are investigated in two colorectal cell lines (HT-29 and LoVo) for their anti-proliferative and migration properties in means of effects on microRNA expressions. Anti-proliferative effects of plant extract are evaluated by WST-1 assay and cell proliferation is reduced significantly (p<0.05). In cell migration analysis RKE and NTE reduced migration in both cell line significantly (p<0.05). Migration properties of LoVo cell line is found to be inhibited by OLE with nearly significant values (p<0.06). Real time-PCR method is used for investigation of expression differences in miRNA after extract treatment. Statistically significant increases are observed in miR-140 expressions in both cell lines after RKE treatment, and in HT-29 cell line miR-182a expression is again significantly reduced after both OLE and NTE treatments (p<0.05). Our data show that NTE, OLE, RKE have capability to inhibit colorectal cancer cell proliferation and migration by the means of epigenetic mechanisms for the first time in the literature. Although further studies should be conducted in this topic, all three plant extracts are thought to be potential candidates for future researches on new therapy options for colorectal cancer

Batı karadeniz bölgesinde obezite prevelansı: Melen çalışması

Purpose: The aim of our study was to determine the prevalence of obesity and abdominal obesity in the West Black Sea region of Turkey and to display the associated chronic diseases, especially Diabetes Mellitus (DM) in this population. Material and Method: We evaluated 2222 (1418 female, 804 male, mean age: 50) participants in Yigilca. The medical histories were recorded and physical examinations were done in all participants. Body weight categories were defined according to the body mass index (BMI) as follows: BMI 94 cm in males and >90 cm in females were accepted as the cut-off points for abdominal obesity. Results: The mean BMI of the participants was 30.6 in females and 27.5 in males. According to BMI, obesity prevalence was 53.1% in females and 26.9% in males. The mean obesity prevalence was 43.5% in general. Abdominal obesity prevalence was 63% in females, 46% in males and 57% in all participants. Obesity prevalence increased with age in both sexes. Especially 3/4 (75%) of females and 1/3 (33%) of males aged 50-59 years were obese. Postmenopausal females had very high (64%) obesity prevalence but the rate was %43 in premenopausal women. While DM prevalence was 12.6% according to patient history, DM prevalence increased to 18.8% by adding patients with fasting glucose >126 mg/dl. Discussion: Obesity, especially abdominal obesity and DM prevalence was found to be at exaggerated rates in both sexes being highest in postmenopausal females

Cystatin C Levels in Patients With Dipper and Nondipper Hypertension

WOS: 000301976100011PubMed: 22373662Objective: Subjects with nondipper hypertension carry a higher risk of cardiovascular events than their normotensive counterparts. The present study was designed to investigate cystatin C levels in patients with dipper and nondipper hypertension. Methods: Eighty-eight consecutive patients who had been treated with antihypertensive drugs for at least 6 months were included in the study. Dipping and nondipping patterns were detected with ambulatory blood pressure monitoring. Clinical, laboratory, and ambulatory blood pressure monitoring data of patient groups with nondipper and dipper hypertension were compared. Results: Patients in the nondipper group were older than those in the dipper group. Serum cystatin C level was higher in the patients in the nondipper group. Cystatin C was negatively correlated with the rate of systolic blood pressure fall at night (r = -0.41; P < 0.001). Linear regression analyses revealed that only cystatin C level was a significant correlate of nocturnal systolic blood pressure decrease. Logistic regression analyses also showed that cystatin C was an independent predictor of nondipping pattern (odds ratio, 3.586; 95% confidence interval, 1.432-8.98; P = 0.006]). Conclusion: The present study showed that cystatin C is higher in patients with nondipper hypertension patients

Asymmetric dimethylarginine levels in dipper and nondipper hypertensive patients

Amaç: Asimetrik dimetil arjinin (ADMA), nitrik oksit sentezinin endojen bir inhibitörü olup aynı zamanda endotel disfonksiyonunun bir göstergesidir. Non-dipper hipertansiyon (HT) tipine sahip hastalarda yapılan çalışmalarda endotel disfonksiyonun dolayısıyla hedef organ hasarının dipper HT tipi olan hastalardan daha fazla olduğu gösterilmiştir. Biz çalışmamızda bu iki grup arasında endotel fonksiyonu değişikliklerini ADMA seviyelerine bakarak karşılaştırdık. Gereç ve yöntem: Bu çalışmaya 6 ay içerisinde Düzce Üniversitesi Tıp Fakültesi iç hastalıkları ve kardiyoloji polikliniğine başvuran ve daha önceden esansiyel HT tanısı konulup medikal tedavi ile takip edilen 87 hasta dahil edildi. Hastalar ambulatuar kan basıncı ölçümü yapılarak dipper ve non-dipper olmak üzere iki gruba ayrıldı. Hastaların vucut kitle indeksi(VKİ), sistolik kan basıncı ve diyastolik kan basıncı, trigliserid, total kolesterol, düşük dansiteli lipoprotein(LDL) kolesterol, yüksek dansiteli lipoprotein(HDL) kolesterol ve ADMA ölçümleri yapıldı. Bulgular: Grupların yaş, VKİ ve lipid değerleri arasında istatistiksel olarak fark yoktu (p0.05). Dipper grubunda bakılan ADMA seviyeleri 1.290.17 ?mol/L, non-dipper grubunda ise 1.270.13 ?mol/L idi. Dipper ve non-dipper grupları arasında ADMA açısından anlamlı farlılık yoktu (p0.575). Sonuç: ADMA seviyeleri HT hastalarında bozulmuş endotel fonksiyonuna bağlı olarak yüksek olarak bulunur. Kan basıncının non-dipper tipinde endotel disfonksiyonu dipper tipi olanlara göre daha fazladır. Çalışmamızda iki tip arasında ADMA seviyelerinde farklılık bulunamamıştır.Objectives: Asymmetric Dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthesis and also is an indicator of endothelial dysfunction. Patients who have nondipper blood pressure pattern have been shown to exhibit more endothelial dysfunction than patients who has dipper blood pressure pattern. However, other endogenous markers, but not ADMA, are used to assess endothelial function in these studies. In our study, we used ADMA levels to compare differences in endothelial function between each groups. Materials and methods: This study includes 87 patients who admitted to Düzce University internal medicine and Cardiology outpatient clinics throughout 6 months and have been diagnosed previously as essential hypertension and followed with medical therapy. Patients were divided into two groups as non-dippers and dippers, using ambulatory blood pressure measurement. Patients&#8217; body mass index, Systolic blood pressure and diastolic blood pressure, triglycerides, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and ADMA levels were measured. Results: Age, BMI, and lipid values did not differ significantly between groups (p>0.05). Mean ADMA level was 1.29±0.13 in dippers, and that of non-dippers was 1.27±0.13&#956;mol/L. ADMA levels did not differ significantly between the non-dipper and dipper groups (p0.575). Conclusion: ADMA levels were found to be higher in hypertensive patients due to endothelial dysfunction. Endothelial dysfunction was more frequent in patients who had nondipper blood pressure pattern than patients who had dipper blood pressure pattern. In our study, ADMA levels did not differ significantly between two patterns

A Multicenter Study of Genotype Variation/Demographic Patterns in 2475 Individuals Including 1444 Cases With Breast Cancer in Turkey

Objective: Breast cancer (BC) is the most common cancer type in women and may be inherited, mostly in an autosomal dominant pattern. The clinical diagnosis of BC relies on the published diagnostic criteria, and analysis of two genes, BRCA1 and BRCA2, which are strongly associated with BC, are included in these criteria. The aim of this study was to compare BC index cases with non-BC individuals in terms of genotype and diagnostic features to investigate the genotype/demographic information association. Materials and Methods: Mutational analyses for the BRCA1/BRCA2 genes was performed in 2475 individuals between 2013-2022 from collaborative centers across Turkey, of whom 1444 with BC were designated as index cases. Results: Overall, mutations were identified in 17% (421/2475), while the percentage of mutation carriers in cases of BC was similar, 16.6% (239/1444). BRCA1/BRCA2 gene mutations were detected in 17.8% (131/737) of familial cases and 12% (78/549) of sporadic cases. Mutations in BRCA1 were found in 4.9%, whereas 12% were in BRCA2 (p<0.05). Meta-analyses were performed to compare these results with other studies of Mediterranean-region populations. Conclusion: Patients with BRCA2 mutations were significantly more common than those with BRCA1 mutations. In sporadic cases, there was a lower proportion with BRCA1/BRCA2 variants, as expected, and these results were consistent with the data of Mediterranean-region populations. However, the present study, because of the large sample size, revealed more robust findings than previous studies. These findings may be helpful in facilitating the clinical management of BC for both familial and non-familial cases

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

Analysis of ACE2 and TMPRSS2 coding variants as a risk factor for SARS-CoV-2 from 946 whole-exome sequencing data in the Turkish population

Heterogeneity in symptoms associated with COVID-19 in infected patients remains unclear. ACE2 and TMPRSS2 gene variants are considered possible risk factors for COVID-19. In this study, a retrospective comparative genome analysis of the ACE2 and TMPRSS2 variants from 946 whole-exome sequencing data was conducted. Allele frequencies of all variants were calculated and filtered to remove variants with allele frequencies lower than 0.003 and to prioritize functional coding variants. The majority of detected variants were intronic, only two ACE2 and three TMPRSS2 nonsynonymous variants were detected in the analyzed cohort. The main ACE2 variants that putatively have a protective or susceptibility effect on SARS-CoV-2 have not yet been determined in the Turkish population. The Turkish genetic makeup likely lacks any ACE2 variant that increases susceptibility to SARS-CoV-2 infection. TMPRSS2 rs75603675 and rs12329760 variants that were previously defined as common variants that have different allele frequencies among populations and may have a role in SARS-CoV-2 attachment to host cells were determined in the population. Overall, these data will contribute to the formation of a national variation database and may also contribute to further studies of ACE2 and TMPRSS2 in the Turkish population and differences in SARS-CoV-2 infection among other populations

Clinical and molecular evaluation of MEFV gene variants in the Turkish population: a study by the National Genetics Consortium

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease