Spontaneous cerebrospinal fluid rhinorrhea in a patient with Pallister–Hall syndrome

Pallister-Hall syndrome (PHS) is extremely rare autosomal dominant disorder with typical clinical features such as presence of polydactyly, hypothalamic hamartoma, bifid epiglottis, anal, renal, genitourinary and pulmonary abnormalities, mainly located in the midline of the body. Spontaneous cerebrospinal fluid (CSF) rhinorrhea is also a rare condition, and it is used to describe nasal discharge of CSF unrelated to previous trauma, localized tumour, surgery, or previous radiation therapy. The exact cause is not yet fully understood. We report a case of adult female patient previously diagnosed with PHS and late onset of spontaneous nasal liquorrhea, due to defect in the anterior skull base. Although it can be incidental finding, we believe that described defect in the body midline can be another presentation of congenital craniofacial abnormality which are common in PHS

EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells

Introduction: Beta cell dysfunction by loss of beta cell identity, dedifferentiation, and the presence of polyhormonal cells are main characteristics of diabetes. The straightforward strategy for curing diabetes implies reestablishment of pancreatic beta cell function by beta cell replacement therapy. Aristaless-related homeobox (Arx) gene encodes protein which plays an important role in the development of pancreatic alpha cells and is a main target for changing alpha cell identity. Results: In this study we used CRISPR/dCas9-based epigenetic tools for targeted hypermethylation of Arx gene promoter and its subsequent suppression in mouse pancreatic αTC1-6 cell line. Bisulfite sequencing and methylation profiling revealed that the dCas9-Dnmt3a3L-KRAB single chain fusion constructs (EpiCRISPR) was the most efficient. Epigenetic silencing of Arx expression was accompanied by an increase in transcription of the insulin gene (Ins2) mRNA on 5th and 7th post-transfection day, quantified by both RT-qPCR and RNA-seq. Insulin production and secretion was determined by immunocytochemistry and ELISA assay, respectively. Eventually, we were able to induce switch of approximately 1% of transiently transfected cells which were able to produce 35% more insulin than Mock transfected alpha cells. Conclusion: In conclusion, we successfully triggered a direct, transient switch of pancreatic alpha to insulin-producing cells opening a future research on promising therapeutic avenue for diabetes management. 1 Introductio

Winter diet composition of the golden jackal (Canis aureus L., 1758) in Serbia

The winter diet composition of golden jackals was determined by analysing the stomach contents of 248 specimens collected between December and February 2005-2009 at six localities in Serbia. The average weight of stomach contents was 189.9 +/- 137.3 g. At all localities, livestock carcasses were the primary food category (frequency 56.1\%, biomass 77.7\%). The secondary food category consisted of small mammals taken as live prey (frequency 20.7\%, biomass 5.2\%). Other food categories were present less frequently (roe deer, wild boar, hare, and birds), and rarely (plant material, dogs, carnivores, lizards, and inedible inorganic material). No statistically significant differences were found in diet between jackals from different localities. The only difference was found between yearlings and adults with regard to the consumed biomass (\%B). The analysis of the winter diet of golden jackals in Serbia indicates that the species has opportunistic feeding habits consisting primarily of easily accessible food sources. (C) 2013 Deutsche Gesellschaft fur Saugetierkunde. Published by Elsevier GmbH. All rights reserved.Ministry of Education, Science and Technological Development of the Republic of Serbia {[}TR 31009

Metabolically healthy obesity: is there a link with polyunsaturated fatty acid intake and status?

The aim of this study was to compare dietary intake and status of polyunsaturated fatty acids (PUFA) in plasma and erythrocyte phospholipids metabolically healthy and unhealthy, and obese and nonobese persons. Metabolic health status in 171 participants was defined according to criteria for metabolic syndrome. Obese and nonobese metabolically unhealthy persons (MUHO and MUHNO) had higher energy intake of n-6 PUFA (7.82 ± 1.03 and 7.49 ± 0.86) and lower intake of n-3 PUFA (0.60 ± 0.12 and 0.62 ± 0.11) compared to obese and nonobese metabolically healthy persons (MHO and MHNO) (5.92 ± 0.63 and 5.72 ± 0.67; 1.20 ± 0.07 and 1.22 ± 0.09, respectively) and a higher n-6/n-3 PUFA ratio. The plasma level of n-6 PUFA was lower in the MUHO and MUHNO groups (38.49 ± 3.71 and 38.53 ± 2.19) compared to MHNO (40.90 ± 2.43), while n-3 PUFA status was lower in obese than in nonobese persons (3.58 ± 0.79 and 3.50 ± 1.02 vs. 4.21 ± 0.80 and 4.06 ± 1.15). The MHO group had a higher eicosapentaenoic/arachidonic acid ratio and estimated desaturase (SCD16, D6D) and elongase activity in plasma phospholipids compared to MHNO. The low intake of n-3 PUFA is directly associated with metabolic risk factors. These results indicated that obesity is closely associated with low levels of n-3 PUFA in plasma phospholipids, suggesting that dietary modifications including n-3 PUFA supplementation appear to be suitable therapeutic strategy in obese persons.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Nutrition and Physical Activity as Modulators of Osteosarcopenic Adiposity: A Scoping Review and Recommendations for Future Research

Osteosarcopenic adiposity (OSA) syndrome denotes the confluence of bone, muscle, and adipose tissue deterioration. Being a complex entity, numerous uncertainties about OSA still exist, despite the extensive research on the topic. Our objectives were to evaluate human studies addressing dietary intake/nutritional status and the quantity/types of physical activity related to OSA. The search in PubMed, Scopus, and Web of Science databases was conducted to examine relevant articles published from inception to the end of December 2022, utilizing the MeSH strings in the search strategy. Only studies published in English and conducted in humans (≥18 years) without chronic conditions (cancers, kidney/liver disease) or pregnancy were used. Book chapters, abstracts-only, and studies in which participants did not have all three body composition components measured to identify OSA or when body composition components could not be related to the independent/exposure variables were excluded. A total of n = 1020 articles were retrieved from all three databases and eight more from the reference lists. After the exclusion of duplicates and other unsuitable articles, n = 23 studies were evaluated. Among those, eleven were from epidemiological or cross-sectional studies relating nutrients/dietary intake or nutritional status with OSA. Another four examined the relationship between serum biomarkers (vitamin D and ferritin) with OSA, while eight articles presented the results of the interventional studies with resistance training. Overall, higher protein, calcium, potassium, and vitamins D and C intakes emerged as nutrients positively modifying OSA, along with a diet higher in fruits and low-fat dairy foods. Higher serum vitamin D and ferritin were respectively positively and negatively related to OSA. Resistance training was a safe intervention yielding several beneficial outcomes for the OSA syndrome in older women

Calorie-Restricted Mediterranean and Low-Fat Diets Affect Fatty Acid Status in Individuals with Nonalcoholic Fatty Liver Disease

Lifestyle modifications are the main support of nonalcoholic fatty liver disease (NAFLD) therapy. Weight loss is one of the primary goals in NAFLD, but the effects of different calorie-restricted diets remain unclear. Thus, we evaluated the effects of two calorie-restricted diets—the Mediterranean diet (Med diet) and low-fat diet—on liver status, cardiometabolic markers, and fatty acid profiles in patients with NAFLD. Twenty-four overweight/moderately obese men were randomly assigned to consume one of these diets. Lipid levels, glucose, insulin, liver enzymes, steatosis, and fatty acid profiles of serum and erythrocytes phospholipids were assessed. After 3 months, all participants had a significant weight loss (>9%), with improvements in waist circumference, body fat %, index of visceral adiposity (VAI), lipid accumulation product, fatty liver (FLI), and hepatic steatosis (HSI) index (p < 0.001). Both diets significantly lowered triglycerides, total and LDL-cholesterol, liver enzymes, fasting glucose, insulin, and HOMA-IR index. Fatty acid profiles were enhanced after both diets, with a significantly decreased n-6/n-3 ratio. Participants on the Med diet had higher levels of HDL-cholesterol and monounsaturated and n-3 docosahexaenoic acids in serum phospholipids and lower levels of saturated fatty acids, triglycerides, TG/HDL ratio, and FLI when compared to participants on the low-fat diet. Our results indicate that dietary patterns and calorie restriction represent central therapeutic issues in the improvement of obesity-related cardiometabolic alterations that are involved in the mechanism of hepatic steatosis. The Med diet may contribute to disease treatment even more than the low-fat diet since it leads to decreased saturated and increased monounsaturated and n-3 polyunsaturated fatty acid status and improved FLI in NAFLD patients

Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats

A Western-style diet, rich in fat and simple sugars, is the main risk factor for a significant number of chronic diseases and disorders, as well as for a progression of metabolic syndrome (MetS). One of the key mechanisms involved in MetS development is increased oxidative stress caused by the accumulation of body fat. Some dietary polyphenols have shown a protective role in preventing oxidative-stress-induced damage. We investigated the difference in the oxidative response of plasma, liver, and visceral adipose tissue in rats fed with a high-fat high-fructose (HFF) diet for ten weeks, and the effectiveness of polyphenol-rich juices (black currant (BC) and cornelian cherry (CC)) in HFF-diet-induced oxidative stress prevention. The most prominent impact of the HFF diet on redox parameters was recorded in the liver, whereas adipose tissue showed the most potent protection mechanisms against oxidative stress. Consumption of both juices decreased advanced oxidation protein product (AOPP) level in plasma, increased paraoxonase1 (PON1) activity in the liver, and significantly decreased total oxidative status (TOS) in adipose tissue. BC exerted stronger antioxidative potential than CC and decreased the superoxide anion radical (O2•−) level in the liver. It also reduced TOS, total antioxidative status (TAS), and malondialdehyde (MDA) concentration in adipose tissue. The multiple linear regression analysis has shown that the best predictors of MetS development, estimated through the increase in visceral adiposity, were superoxide dismutase (SOD), AOPP, TOS, and TAS. The consumption of polyphenol-rich juices may provide a convenient approach for the systemic reduction of oxidative stress parameters

Development of resistance to antiglioma agents in rat C6 cells caused collateral sensitivity to doxorubicin

Chemoresistance is a severe limitation to glioblastoma (GBM) therapy and there is a strong need to understand the underlying mechanisms that determine its response to different chemotherapeutics. Therefore, we induced resistance in C6 rat glioma cell line, which considerably resembles the characteristics of human GBM. The resistant phenotype was developed by 3-bis (2-chloroethyl)-1-nitrosourea (BCNU), one of the most commonly used therapeutic drug in the course of GBM treatment. After confirmation of the cross-resistance to cisplatin (CPt) and temozolomide (TMZ) in newly established RC6 cell line, we examined cell death induction and DNA damage by these drugs. Resistance to apoptosis and deficiency in forming DNA double-strand breaks was followed by significant decrease in the mRNA expression of pro-apoptotic and anti-apoptotic genes. The development of drug resistance was associated with significant increase in reactive oxygen species (ROS) and decrease in oxidized to reduced gluthatione ratio in RC6 cell line indicating a reduced level of oxidative stress. The mRNA expression levels of manganese superoxid dismutase (MnSOD), inducible nitric oxide synthase (iNOS) and gluthatione peroxidase (GPx) were increased while hypoxia-inducible factor 1-alpha (HIF-1 alpha) was decreased in RC6 compared to C6 cells. This was in line with obtained changes in ROS content and increased antioxidative capacity of RC6 cells. Importantly, RC6 cells demonstrated collateral sensitivity to doxorubicin (DOX). The analysis of this phenomenon revealed increased accumulation of DOX in RC6 cells due to their adaptation to high ROS content and acidification of cytoplasm. In conclusion, newly established RC6 rat glioma cell line could be used as a starting material for the development of allogenic animal model and preclinical evaluation of new antiglioma agents. Collateral sensitivity to DOX obtained after BCNU treatment may prompt new studies aimed to find efficient delivery of DOX to the glioma site in brain. (C) 2015 Elsevier Inc. All rights reserved.Ministry of Education, Science and Technological Development of Serbia {[}III 41031, III 41025

Synergistic effect of Fenton oxidation and adsorption process in treatment of azo printing dye: DSD optimization and reaction mechanism interpretation

The main challenges to overcome within the Fenton process are the acidic pH as an optimal reaction condition, sludge formation in neutral pH medium and high toxicity of treated printing wastewater due to the generation of contaminating by-products. This research discusses catalytic activity of homogeneous (FeSO4/H2O2) and heterogeneous (Fe2(MoO4)3/H2O2) Fenton processes in treatment of Yellow azo printing dye in synthetic aqueous solution and real printing effluent, with an integration of adsorption on functionalized biochar synthesized from wild plum kernels. The definitive screening design (DSD), was used to design the experiment. Independent variables were initial dye concentration (20 - 180 mg L-1), iron concentration (0.75 - 60 mg L-1), pH (2 - 10) and hydrogen peroxide concentration (1 - 11 mM). Higher decolorization efficiency of 79% was obtained within homogeneous Fenton treatment of printing wastewater, in comparison to heterogeneous Fenton treatment (54%), after a reaction time of 60 min. Same trend of mineralisation degree was established: COD removal was 59% and 33% for homogeneous and heterogeneous Fenton process, respectively. The application of adsorption treatment has achieved significant advantages in terms of toxicity reduction (95%) and decolorization efficiency (90% of TOC removal and 22% of dye removal) of treated samples, even at neutral pH medium. Degradation mechanisms within Fenton and adsorption processes were proposed based on the qualitative gas chromatography/mass spectrometry analysis, physico-chemical properties of dye degradation products and functionalized biochar. Overall, the homogeneous Fenton/adsorption combined process can be potentially used as treatment to remove azo dyes from contaminated water.</p