Circular RNAs and Its Biological Functions in Health and Disease

Circular RNAs (circRNAs) belong to the family of long noncoding RNAs (lncRNA) that, unlike linear RNAs, are characterized by a covalently closed circular RNA structure lacking 5′ cap and 3′ poly-adenylated tails. circRNAs have a role in epigenetic regulation of downstream targets. circRNAs play a crucial role in regulating gene and protein expressions by acting as a microRNA (miRNA) sponge and RNA binding protein (RBP) sponge and interact with proteins to affect cell behavior. circRNA expression profiles differ between physiological and pathological states. Moreover, the expression patterns of circRNAs exhibit differences in a tissue-specific manner. Although investigations on circRNAs have been exploding nowadays, yet only a limited number of circRNAs are identified. Furthermore, further researches are needed to shed light on their functions and targets. Therefore, circRNAs are becoming vital as potential biomarkers that may be used for the diagnosis and treatment of diseases. In this chapter, we review the current advancement of cirRNAs with regard to their biogenesis, biological functions, gene regulatory mechanisms, and implications in human diseases and summarize the recent studies on circRNAs as potential diagnostic and prognostic biomarkers based on existing knowledge

Expression of iNOS, COX-2 and VEGF in canine mammary tumours and non-neoplastic mammary glands: Association with clinicopathological features and tumour grade

The aim of the present study was to investigate the relationship between the expression of iNOS, COX-2 and VEGF mRNA levels and malignancy degree in canine malignant mammary tumours. Thirty-five bitches presented with the complaint of mammary masses, aged 6–10 years and representing different breeds, were used. The expressions of iNOS, COX-2 and VEGF mRNA levels were significantly higher in both benign and malignant tumours than in the adjacent nonneoplastic mammary glands (P < 0.05). The iNOS, COX-2 and VEGF mRNA expression levels of grade 2 tumours were higher than those of grade 1 tumours; however, the highest expression levels were detected in grade 3 tumours. Thus, increased iNOS, COX-2 and VEGF gene mRNA levels were found to be related with the histological grade of malignancy in dogs with mammary tumours

PHENOXODIOL SENSITIZES METASTATIC COLORECTAL CANCER CELLS TO 5-FLUOROURACIL-AND OXALIPLATIN-INDUCED APOPTOSIS THROUGH INTRINSIC PATHWAY

Colorectal cancer (CRC) is one of the most common types of cancer seen in the world. 5-Fluorouracil (5-Fu) plus Oxaliplatin (1-OHP) remains the backbone of CRC chemotherapeutics, but with limited success. Phenoxodiol (Pxd) is an isoflavone analog with antitumor activity against various types of cancers, and sensitizes chemoresistant cancer cells to chemotherapeutics including platinum and taxanes. This study was, therefore, undertaken to examine whether Pxd pre-treatment with conventional chemotherapeutic agent(s) 5-Fu and 1-OHP co-administration be a therapeutic strategy for CRC. Cell viability and cytotoxicity were evaluated using dimethyl-thiazolyl diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase assays. The percentage of apoptotic and necrotic cells were determined by fluorescence microscopy analysis. Besides, active Caspase-3 levels by ELISA and relative mRNA levels of Caspase 3 (CASP3), CASP8 and CASP9 genes were determined by quantitative real-time PCR (qPCR) analysis. The pre-treatment of Pxd followed by 5-Fu and 1-OHP co-administration was more effective at inhibiting cell viability than either chemotherapeutic agents treatment alone. When compared to 5 -Fu with 1-OHP alone treatment, Pxd pre-treatment overwhelmingly increased apoptotic Caspase-3 activity levels in CRC cells. Moreover, qPCR analyses showed that CASP3 and CASP9 mRNA levels significantly increased after pretreatment with Pxd followed by 5-Fu and 1-OHP treatments, compared to 5-Fu with 1-OHP alone. Our results suggested that Pxd enhanced the in vitro antitumor activity of 5-Fu and 1-OHP. Our study also suggested that Pxd may be a potential candidate agent in advanced CRC and inclusion of Pxd to the conventional chemotherapeutic agent(s) could be an effective therapeutic strategy for CRC

Serum Concentrations of Anti-Mullerian Hormone and its Expression in the Remnant Ovarian Tissue of Rats with Experimentally Induced Ovarian Remnant Syndrome

Anti-Mullerian hormone (AMH) is synthesised in the Sertoli cells of the testes and granulosa cells of the ovary. As the ovaries seem to be the primary source of AMH, it may be used for determination of the presence or absence of ovaries or ovarian remnants in mammalians. The purpose of the present study was to compare the serum AMH concentration of rats with experimentally induced ovarian remnant syndrome and the expression of AMH in the ovarian tissue removed during ovariohysterectomy and remnant ovarian tissue. A total of eighteen Sprague Dawley rats were used in the study. Group I consisted of 6 rats that were gone through ovarian remnant syndrome (ORS) experimentally, group II consisted of 6 rats in which both ovaries were removed and group III consisted of 6 rats that were sham-operated. Median laparotomy was performed in the all groups under general anaesthesia. AMH mRNA expression was determined using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). AMH mRNA expression levels in group I were decreased on day 30 after surgery when compared to day 0 (P>0.05). Mean concentration of serum AMH on day 10 after surgery in group I, II and III were found 2.27 +/- 0.52 ng/ml, <0.312 ng/ml and 3.96 +/- 0.53 ng/ml, respectively (P<0.05). In conclusion, this finding suggests that evaluation of serum AMH concentration could be an useful method to determine the presence or absence of ovaries or ovarian remnants in the rat

HDAC inhibitors, MS-275 and salermide, potentiates the anticancer effect of EF24 in human pancreatic cancer cells.

Histone deacetylases (HDACs) play a major role in the regulation of chromatin structure and gene expression by changing acetylation status of histone and non-histone proteins. MS-275 (entinostat, MS) is a well-known benzamide-based HDACI and Salermide (SAL), a reverse amide compound HDACI, have antiproliferative effects on several human cancer cells. In this study, we aimed to investigate the effects of HDACIs (MS and SAL) alone and/or combined use with EF24 (EF), a novel synthetic curcumin analog, on human pancreatic cancer cell line (BxPC-3). In vitro, BxPC-3 cells were exposed to varying concentrations of MS, SAL with or without EF, and their effects on cell viability, acetylated Histone H3 and H4 levels, cytotoxicity, and cleaved caspase 3 levels, and cell cycle distribution were measured. The viability of BxPC-3 cells decreased significantly after treatment with EF, MS and SAL treatments. MS and SAL treatment increased the acetylation of histone H3 and H4 in a dose dependent manner. MS and SAL alone or combined with EF were increased the number of cells in G1 phase. In addition, treatment with agents significantly decreased the ratio of cell in G2/M phase. There were significant dose-dependent increases at cleaved Caspase 3 levels after MS treatment but not after SAL treatment. Our results showed that HDAC inhibitors (MS and SAL), when combined with EF, may effectively reduce pancreatic cancer cell (BxPC-3) progression and stop the cell cycle at G1 phase. Further molecular analyses are needed to understand the fundamental molecular consequences of HDAC inhibition in pancreas cancer cells

Melatonin Modulates NMDA-Receptor 2B/Calpain-1/ Caspase-12 Pathways in Rat Brain After Long Time Exposure to GSM Radiation.

To investigate the potential protective effects of melatonin on the chronic radiation emitted by third generation mobile phones on the brain

Association of rs10757274 and rs2383206 Polymorphisms on 9p21 locus with Coronary Artery Disease in Turkish Population

Background and Objectives: Genetic predisposition is an important risk factor for coronary artery disease (CAD). In this study, we aimed to evaluate the impact of rs10757274 and rs2383206 polymorphisms in chromosome 9p21 on presence and severity of CAD in a Turkish population. Subjects and Methods: A total of 646 patients who underwent coronary angiography were included in this study. Coronary vessel score and Gensini score were calculated to assess the angiographic severity of CAD. Alleles of AA, AG, and GG were determined for rs10757274 (polymorphism-1) and rs2383206 (polymorphism-2) polymorphisms located in chromosome 9p21 from the blood samples. Results: There was a significant difference between the alleles in polymorphism-1 in the presence of coronary artery disease (38.9\% in AA, 48.0\% in GG and 56.4\% in AG, p=0.017). However, there was no difference between the alleles in polymorphism-2. According to vessel scores, there was a significant difference between the alleles in polymorphism-1 (AA 0.71 +/- 1.04, GG 0.88 +/- 1.07, AG 1.06 +/- 1.12, p=0.018). In polymorphism-2, vessel scores did not show a difference between the alleles. In polymorphism-1, there was a significant difference in Gensini score (p=0.041). Gensini scores did not differ between the alleles in polymorphism-2 (p>0.05 for all). In multivariate analyses, none of the alleles was an independent factor for presence of CAD. Conclusion: The presence of rs10757274 polymorphism including AG allele in chromosome 9p21 was related to CAD. However, this relationship was not independent of other cardiovascular risk factors

HDAC INHIBITORS, MS-275 AND SALERMIDE, POTENTIATES THE ANTICANCER EFFECT OF EF24 IN HUMAN PANCREATIC CANCER CELLS

Histone deacetylases (HDACs) play a major role in the regulation of chromatin structure and gene expression by changing acetylation status of histone and non-histone proteins. MS-275 (entinostat, MS) is a well-known benzamide-based HDACI and Salermide (SAL), a reverse amide compound HDACI, have antiproliferative effects on several human cancer cells. In this study, we aimed to investigate the effects of HDACIs (MS and SAL) alone and/or combined use with EF24 (EF), a novel synthetic curcumin analog, on human pancreatic cancer cell line (BxPC-3). In vitro, BxPC-3 cells were exposed to varying concentrations of MS, SAL with or without EF, and their effects on cell viability, acetylated Histone H3 and H4 levels, cytotoxicity, and cleaved caspase 3 levels, and cell cycle distribution were measured. The viability of BxPC-3 cells decreased significantly after treatment with EF, MS and SAL treatments. MS and SAL treatment increased the acetylation of histone H3 and H4 in a dose dependent manner. MS and SAL alone or combined with EF were increased the number of cells in G1 phase. In addition, treatment with agents significantly decreased the ratio of cell in G2/M phase. There were significant dose-dependent increases at cleaved Caspase 3 levels after MS treatment but not after SAL treatment. Our results showed that HDAC inhibitors (MS and SAL), when combined with EF, may effectively reduce pancreatic cancer cell (BxPC-3) progression and stop the cell cycle at G1 phase. Further molecular analyses are needed to understand the fundamental molecular consequences of HDAC inhibition in pancreas cancer cells