Changes in the expression levels of CB1 and GLP-1R mRNAs and microRNAs 33a and 122 in the liver of type 2 diabetic rats treated with ghrelin

coskun, zeynep mine/0000-0003-4791-6537; Bolkent, Sema/0000-0001-8463-5561WOS: 000484212400001PubMed: 31468622The aim of the study is to clarify the effect of ghrelin treatment on the messenger RNA (mRNA) expression of the cannabinoid receptor 1 (Cnr1/CB1) and glucagon-like peptide 1 receptor (Glp1r/GLP-1R) as well as microRNAs (miR)-122 and miR-33a in the liver of rats with type 2 diabetes mellitus (T2DM). Adult Sprague-Dawley rats were divided into three groups: control (n = 7), T2DM (n = 7), and treatment (n = 7). Control animals received tap water. T2DM was induced by feeding 10% fructose in drinking water for 2 weeks followed by a single injection of streptozotocin (40 mg/kg, intraperitoneally [IP]). in the treatment group, diabetic rats were injected ghrelin (25 mu g/kg, IP) for 14 days. Serum lipid profiles were evaluated, and mRNA expression levels of Cnr1 and Glp1r in the liver were detected using quantitative real-time polymerase chain reaction (RT-qPCR). in addition, miR-122 and miR-33a levels were measured using RT-qPCR. Serum triglycerides, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol significantly increased in the T2DM group compared with control rats but ghrelin treatment showed no effect on serum lipid levels. the mRNA expression levels of Cnr1 and Glp1r decreased in the T2DM group compared with the control group. These reductions were significantly increased in the T2DM group treated with ghrelin. Furthermore, the increase in miR-33a expression level was reduced in the treatment group compared to rats with T2DM. Our findings suggested that ghrelin treatment may alter the mRNA expression levels of CB1 and GLP-1R in the liver of rats with T2DM. the mRNA levels of Cnr1 and Glp1r may inversely correlate with the expression level of miR-33a but not miR-122

Cytotoxic and apoptotic effects of ethanolic propolis extract on C6 glioma cells

coskun, zeynep mine/0000-0003-4791-6537WOS: 000513379500001PubMed: 32061154Propolis is a natural resinous substance obtained from beehives, and emerging evidence supports that it has antitumor, antiinflammatory, antioxidant, and antimicrobial activities. the aim of the study is to examine the cytotoxic, antioxidant, and apoptotic features of ethanolic propolis extract (PE) on C6 glioma cells. the cells were treated with ethanolic PE at various concentrations for 24 hours, after which the total antioxidant status (TAS) and total oxidant status; malondialdehyde, protein carbonyl, 8-hydroxy-2 '-deoxyguanosine, and glutathione (GSH) levels; Cu/Zn-superoxide dismutase (Cu/Zn-SOD) activity; and apoptotic markers were measured. Ethanolic PE at 100, 250, and 500 mu g/mL concentrations showed optimal activity on C6 glioma cells. TAS and GSH levels were significantly increased in C6 glioma cells treated with 100 and 500 mu g/mL PE compared to control cells (P < .05). Similarly, the activity of Cu/Zn-SOD was higher in C6 glioma cells treated with 250 or 500 mu g/mL ethanolic PE compared to control cells (P < .05), as was the caspase-3 mRNA expression level. the highest levels of caspase-8 and -9 expression were in C6 glioma cells treated with 500 mu g/mL PE. Collectively, our results indicate that ethanolic PE has cytotoxic and apoptotic effects on C6 glioma cells. Furthermore, it may provide a protective role in the antioxidant defense system. PE shows potential for development as a natural antioxidant and apoptotic agent for the treatment of brain tumors

Screening of Antimicrobial Activity and Cytotoxic Effects of Two Cladonia Species

WOS: 000323864600004PubMed ID: 23923615The present study explores the antimicrobial activity and cytotoxic effects in culture assays of two fruticose soil lichens, Cladonia rangiformis Hoffm. and Cladonia convoluta (Lamkey) Cout., to contribute to possible pharmacological uses of lichens. In vitro antimicrobial activities of methanol and chloroform extracts against two Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli), two Gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus), and the yeast Candida albicans were examined using the paper disc method and through determination of minimal inhibitory concentrations (MICs). The data showed the presence of antibiotic substances in the chloroform and the methanol extracts of the lichen species. The chloroform extracts exhibited more significant antimicrobial activity than the methanol extracts. However, a higher antifungal activity was noted in the methanol extract of C. rangiformis. The maximum antimicrobial activity was recorded for the chloroform extract of C. convoluta against E. coli. The cytotoxic effects of the lichen extracts on human breast cancer MCF-7 cells were evaluated by the trypan blue assay yielding IC50 values of ca. 173 and 167 mu g/ml for the extracts from C. rangiformis and C. convoluta, respectively.Research Fund of Marmara University [FEN-A-200611-0208]We thank Prof. Dr. Engin Ozhatay (the Manager of The Marmara University Research Centre for Native Flora and Fishery Products of Turkey) for providing accommodation and transport during collection of lichen material. This study is part of a research project supported by The Research Fund of Marmara University with the project number FEN-A-200611-0208

A patient with a novel homozygous missense mutation in FTO and concomitant nonsense mutation in CETP

The fat mass and obesity associated (FTO) gene has previously been associated with a variety of diseases and conditions, notably obesity, acute coronary syndrome and metabolic syndrome. Reports describing mutations in FTO as well as in FTO animal models have further demonstrated a role for FTO in the development of the brain and other organs. Here, we describe a patient born of consanguineous union who presented with microcephaly, developmental delay, behavioral abnormalities, dysmorphic facial features, hypotonia and other various phenotypic abnormalities. Whole-exome sequencing revealed a novel homozygous missense mutation in FTO and a nonsense mutation in the cholesteryl ester transfer protein (CETP). Exome copy number variation analysis revealed no disease-causing large duplications or deletions within coding regions. Patient's, her parents' and non-related control' fibroblasts were analyzed for morphologic defects, abnormal proliferation, apoptosis and transcriptome profile. We have shown that FTO is located in the nucleus of cells from each tested sample. Western blot analysis demonstrated no changes in patient FTO. Quantitative (qPCR) analysis revealed slightly decreased levels of FTO expression in patient cells compared with controls. No morphological or proliferation differences between the patient and control fibroblasts were observed. There is still much to be learned about the molecular mechanisms by which mutations in FTO contribute to such severe phenotypes

Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis

Background. Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis

Integrated genomic characterization of IDH1-mutant glioma malignant progression

Gliomas represent approximately 30% of all central nervous system tumors and 80% of malignant brain tumors(1). To understand the molecular mechanisms underlying the malignant progression of low-grade gliomas with mutations in IDH1 (encoding isocitrate dehydrogenase 1), we studied paired tumor samples from 41 patients, comparing higher-grade, progressed samples to their lower-grade counterparts. Integrated genomic analyses, including whole-exome sequencing and copy number, gene expression and DNA methylation profiling, demonstrated nonlinear clonal expansion of the original tumors and identified oncogenic pathways driving progression. These include activation of the MYC and RTK-RAS-PI3K pathways and upregulation of the FOXM1- and E2F2-mediated cell cycle transitions, as well as epigenetic silencing of developmental transcription factor genes bound by Polycomb repressive complex 2 in human embryonic stem cells. Our results not only provide mechanistic insight into the genetic and epigenetic mechanisms driving glioma progression but also identify inhibition of the bromodomain and extraterminal (BET) family as a potential therapeutic approach

Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas

Youngblood MW, Erson-Omay Z, Li C, et al. Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas. Nature Communications . 2023;14(1): 6279.Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO. In this study, we find 35.6% of meningiomas that lack previously known drivers acquired various types of somatic structural variations affecting chromosomes 2q35 and 7q36.3. These cases exhibit ectopic expression of Hedgehog ligands, IHH and SHH, respectively, resulting in Hedgehog signaling activation. Recurrent tandem duplications involving IHH permit de novo chromatin interactions between super-enhancers within DIRC3 and a locus containing IHH. Our work expands the landscape of meningioma molecular drivers and demonstrates enhancer hijacking of Hedgehog ligands as a route to activate this pathway in neoplasia. Hedgehog signalling is known to be linked to oncogenic proliferation. Here, the authors identify structural events as a mechanism of Hedgehog activation in over one-third of driver unknown meningiomas