Effect of GLP-1 Receptor Agonist on Ischemia Reperfusion Injury in Rats with Metabolic Syndrome.

Metabolic syndrome (MetS) represents an important factor that increases the risk of myocardial infarction, and more severe complications. Glucagon Like Peptide-1 Receptor Agonists (GLP-1RAs) exhibit cardioprotective potential, but their efficacy in MetS-related myocardial dysfunction has not been fully explored. Therefore, we aimed to assess the effects of exenatide and dulaglutide on heart function and redox balance in MetS-induced rats. Twenty-four Wistar albino rats with induced MetS were divided into three groups: MetS, exenatide-treated (5 µg/kg), dulaglutide-treated (0.6 mg/kg). After 6 weeks of treatment, in vivo heart function was assessed via echocardiography, while ex vivo function was evaluated using a Langendorff apparatus to simulate ischemia-reperfusion injury. Heart tissue samples were analyzed histologically, and oxidative stress biomarkers were measured spectrophotometrically from the coronary venous effluent. Both exenatide and dulaglutide significantly improved the ejection fraction by 3% and 7%, respectively, compared to the MetS group. Histological analyses corroborated these findings, revealing a reduction in the cross-sectional area of cardiomyocytes by 11% in the exenatide and 18% in the dulaglutide group, indicating reduced myocardial damage in GLP-1RA-treated rats. Our findings suggest strong cardioprotective potential of GLP-1RAs in MetS, with dulaglutide showing a slight advantage. Thus, both exenatide and dulaglutide are potentially promising targets for cardioprotection and reducing mortality in MetS patients.

Effects of Different Therapeutic Approaches on Redox Balance in Psoriatic Patients.

Given that oxidative stress represents an important etiological factor in the pathogenesis of psoriasis, the aim of this study was to assess the effects of different therapeutic approaches, methotrexate, secukinumab, and ustekinumab on systemic oxidative stress biomarkers in psoriatic patients. This study involved 78 psoriatic patients, divided into the group treated with methotrexate (23 patients), secukinumab (28 patients), and ustekinumab (27 patients), and 15 healthy controls. Oxidative stress biomarkers (index of lipid peroxidation measured as TBARS, nitrites (NO2-), superoxide anion radical (O2-), and hydrogen peroxide (H2O2)) and antioxidative defense system (superoxide dismutase (SOD) activity, catalase (CAT) activity, and reduced glutathione (GSH)) were determined spectrophotometrically from the blood before the initiation of therapy in 16th, 28th, and 52nd week. O2- and SOD showed the most prominent changes comparing the psoriatic patients and healthy controls. CAT activity was significantly lower in psoriatic patients, and methotrexate induced a further decline in CAT activity. Ustekinumab induced a significant increase in GSH level after 52 weeks of treatment, while methotrexate reduced GSH. All applied therapeutic options induced a reduction in PASI, BSA, DLQI, and EARP. Biological drugs exert more pronounced antioxidant effects compared to methotrexate, which is most clearly observed in the values of O2- and SOD.

Sacubitril/valsartan promotes white adipose tissue browning in rats with metabolic syndrome through activation of mTORC1.

In addition to their usual use in the treatment of cardiovascular disease, weak evidence is available for the potential of combined use of neprilysin inhibitor (sacubitril) and AT1 receptor antagonist (valsartan) to promote browning of white adipose tissue (WAT) in rats with metabolic syndrome (MetS). This study involved 32 male Wistar albino rats divided into four groups: CTRL-healthy control rats; ENT-healthy rats treated with sacubitril/valsartan; MS-rats with MetS; MS + ENT-rats with MetS treated with sacubitril/valsartan. After finishing the experimental protocol, different WAT depots were isolated for further analysis of molecular pathways. Molecular docking and molecular dynamics studies were used for in silico assessment of the binding affinity of sacubitril and valsartan towards subunits of mechanistic target of rapamycin complex 1 (mTORC1). Sacubitril/valsartan treatment markedly diminished morphological changes in adipose tissue, resulting in smaller lipid size and multilocular lipid droplet structure in WAT. We showed significantly higher protein expression of uncoupling protein-1 (UCP-1) and mTORC1 in WAT of MS + ENT rats, correlating with increased relative gene expression of browning-related markers in tissue of rats treated with sacubitril/valsartan compared with MS group of rats. In silico analysis showed that sacubitrilat and valsartan exhibited the highest binding affinity against mTOR and mLST8, forming stable complexes with these mTORC1 subunits. The observed results confirmed strong potential of combined sacubitril/valsartan treatment to increase browning markers expression in different WAT depots in MetS condition and to form permanent complexes with mTOR and mLST8 subunits over the time.

Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food.

The European Commission asked EFSA to update its 2011 risk assessment on polybrominated diphenyl ethers (PBDEs) in food, focusing on 10 congeners: BDE-28, -47, -49, -99, -100, -138, -153, -154, -183 and ­209. The CONTAM Panel concluded that the neurodevelopmental effects on behaviour and reproductive/developmental effects are the critical effects in rodent studies. For four congeners (BDE-47, -99, -153, -209) the Panel derived Reference Points, i.e. benchmark doses and corresponding lower 95% confidence limits (BMDLs), for endpoint-specific benchmark responses. Since repeated exposure to PBDEs results in accumulation of these chemicals in the body, the Panel estimated the body burden at the BMDL in rodents, and the chronic intake that would lead to the same body burden in humans. For the remaining six congeners no studies were available to identify Reference Points. The Panel concluded that there is scientific basis for inclusion of all 10 congeners in a common assessment group and performed a combined risk assessment. The Panel concluded that the combined margin of exposure (MOET) approach was the most appropriate risk metric and applied a tiered approach to the risk characterisation. Over 84,000 analytical results for the 10 congeners in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary Lower Bound exposure to PBDEs were meat and meat products and fish and seafood. Taking into account the uncertainties affecting the assessment, the Panel concluded that it is likely that current dietary exposure to PBDEs in the European population raises a health concern.

The Enhanced Effects of Swimming and Running Preconditioning in an Experimental Model of Myocardial Ischemia/Reperfusion Injury.

Background and Objectives: This study was conducted to examine the influence of different swimming and running protocols as forms of physiological preconditioning on an isolated rat heart's ischemia/reperfusion injury. Materials and Methods: This study was conducted on 60 male Wistar albino rats (6 weeks old, bw: 200 ± 20 g), divided into: CTRL group-a sedentary control group; sAeT-a group that underwent aerobic swimming conditioning using a swimming protocol for 8 weeks; sAnT-a group that underwent anaerobic swimming conditioning; rAeT-a group that underwent aerobic running conditioning; and rAnT-a group that underwent anaerobic running conditioning. After the preconditioning protocols, ex vivo estimating of myocardial function according to the Langendorff technique was performed. Results: The anaerobic running training decreased heart rate and the anaerobic swimming training reduced coronary flow, demonstrating the difference in the physiological heart response of aerobic/anaerobic physical training (p < 0.05). Heart rate was significantly reduced in both training swimming groups after a period of ischemia (p < 0.05). On the other hand, the anaerobic running protocol induced a significantly decreased heart rate in comparison with the aerobic running group and the sedentary group (p < 0.05). Conclusions: The data from this experimental study support many protective training effects, i.e., improved contractility, improved resting heart rate, and increased physical work capacity and exercise tolerance. Physical training in the form of anaerobic running induces greater heart preconditioning for reperfusion injury in comparison with anaerobic swimming training.

Variations of Redox Balance in Different Stages of Childhood Immune Thrombocytopenic Purpura.

BACKGROUND: Few previous studies indicated the role of oxidative stress in the pathogenesis of childhood idiopathic thrombocytopenic purpura (ITP), but there are little data regarding changes in redox balance in different forms of the disease, and changes after therapeutic procedures. We aimed to investigate the values of pro-oxidants and antioxidative capacity in various forms of ITP before and after the applying therapy. MATERIALS AND METHODS: The research included 102 children, classified into the following groups: (1) newly diagnosed ITP (ndITP), (2) persistent ITP, (3) chronic ITP (chITP), and (4) control groups: (A) healthy control and (B) previously experienced ITP-healthy children who had been suffering from ITP earlier. During the clinical assessment, a blood sample was taken from the patients, from which the value of pro-oxidants (index of lipid peroxidation measured as TBARS, nitrites [NO2 -], as measurement of nitric oxide [NO] production, superoxide anion radical [O2 -], and hydrogen peroxide [H2O2]) and the capacity of antioxidant protection (activity of superoxide dismutase and catalase, and quantity of reduced glutathione) were determined spectrophotometrically. RESULTS: Our results demonstrated that values of pro-oxidants, especially reflected through the TBARS and O2 -, were the highest in the ndITP and exacerbated chITP groups. Also, the activity of the endogenous antioxidative defense system was the lowest in these groups. Intravenous immunoglobulin therapy in the ndITP group exerted the most prominent effect on the redox balance. CONCLUSION: It can be concluded that severity and exacerbation of the ITP are closely related to the redox status.

Lady's Bedstraw as a Powerful Antioxidant for Attenuation of Doxorubicin-Induced Cardiotoxicity.

This study aimed to examine the effects of a 14-day treatment with lady's bedstraw methanol extract on doxorubicin-induced cardiotoxicity through functional, biochemical and histological examinations. We used 24 male Wistar albino rats divided into the following groups: control (CTRL), doxorubicin (DOX), and DOX + GVE (Galium verum extract). GVE was administered orally at a dose of 50 mg/kg per day for 14 days, while a single dose of doxorubicin was injected into the DOX groups. After accomplishing treatment with GVE, cardiac function was assessed, which determined the redox state. During the autoregulation protocol on the Langendorff apparatus, ex vivo cardiodynamic parameters were measured. Our results demonstrated that the consumption of GVE effectively suppressed the disturbed response of the heart to changes in perfusion pressures caused by administration of DOX. Intake of GVE was associated with a reduction in most of the measured prooxidants in comparison to the DOX group. Moreover, this extract was capable of increasing the activity of the antioxidant defense system. Morphometric analyses showed that rat hearts treated with DOX showed more pronounced degenerative changes and necrosis compared to the CTRL group. However, GVE pretreatment seems to be able to prevent the pathological injuries caused by DOX injection via decrease in oxidative stress and apoptosis.

High Fat Diet Exaggerate Metabolic and Reproductive PCOS Features by Promoting Oxidative Stress: An Improved EV Model in Rats.

Background and Objectives: Polycystic ovary syndrome (PCOS) is a frequent multifactorial endocrinopathy affecting women in the reproductive period, often associated with infertility and metabolic disorders. The use of animal models helps to better understand etiopathogenesis, enabling the examination of the effects of certain drugs in order to discover the best possible therapeutic approach. We tried to investigate the additional effect of estradiol-valerate (EV) and high-fat diet (HFD) in female rats to explore PCOS-related alterations with special focus on oxidative stress. Materials and Methods: Animals were divided into three groups: control group (CTRL, n = 6), estradiol-valerate group (EV, n = 6), and estradiol-valerate group on HFD (EV + HFD, n = 6). PCOS was induced by single subcutaneous injection of long-acting EV in a dose of 4 mg/per rat. We tried to improve the metabolic characteristics of the PCOS animal model by adding HFD, so the CTRL and EV group had a regular diet, while the EV + HFD group had HFD during the induction period of 60 days. Results: We observed alterations of anthropometric parameters and hormonal disturbances, along with estrus cycle impairment reassembly to obese-type PCOS phenotype. Moreover, glucose metabolism was impaired after addition of HFD to EV protocol, contrary to EV administered alone. Histological analysis confirmed more numerous cystic follicles after the combination of EV and HFD protocol. The alterations of oxidative stress markers could be related to and serve as the mechanistic base for development of PCOS-related endocrine, reproductive, and metabolic properties. Conclusions: The additive effect of EV and HFD was obvious in the majority of the parameters observed. Our study strongly demonstrated metabolic as well as reproductive properties of PCOS in rats.

Characterization, In Vitro Biological Activity and In Vivo Cardioprotective Properties of Trametes versicolor (L.:Fr.) Quél. Heteropolysaccharides in a Rat Model of Metabolic Syndrome.

The present study aimed to examine the biological activity and cardioprotective potential of Trametes versicolor heteropolysaccharides (TVH) in a rat model of metabolic syndrome (MetS). This study included 40 Wistar rats divided into 5 groups: CTRL-healthy non-treated rats; MetS-non-treated rats; and H-TV, M-TV and L-TV-rats with MetS treated with either 300, 200 or 100 mg/kg TVH per os for 4 weeks. After finishing the treatment, we conducted an oral glucose tolerance test (OGTT), hemodynamic measurements and the animals were sacrificed, hearts isolated and subjected to the Langendorff technique. Blood samples were used for the determination of oxidative stress parameters, lipid status and insulin levels. We showed that α-amylase inhibition was not the mode of TVH antidiabetic action, while TVH showed a moderate inhibition of pathogenic microorganisms' growth (MIC 8.00 mg·mL-1; MBC/MFC 16.00 mg·mL-1). H-TV and M-TV significantly reduced the level of prooxidants (O2-, H2O2, TBARS; p < 0.05), increased antioxidants activity (SOD, CAT, GSH; p < 0.05), reduced blood pressure (p < 0.05), improved glucose homeostasis in the OGTT test (p < 0.05), and ejection fraction (p < 0.05) and cardiac contractility (p < 0.05) compared to MetS (p < 0.05). Moreover, TVH treatment normalized the lipid status and decreased insulin levels compared to MetS rats (p < 0.05). The obtained results demonstrated that the TVH may be considered a useful agent for cardioprotection in MetS conditions.

Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen.

The objective of this study was to synthesize seven novel thiourea derivatives of naproxen (8-14), examine the anti-inflammatory activity of the newly synthesized compounds, investigate the cytotoxic potential of both sets of synthesized compounds (1-7 and 8-14), and select the most promising anti-inflammatory and antitumor drug candidates. The results of the in vivo anti-inflammatory study clearly showed that compounds 8 and 9 were capable of decreasing paw edema, as evident from a high percentage of inhibition (44.83% and 49.29%, respectively). In addition, the results of in vitro enzyme inhibition assays demonstrated that neither of the newly synthesized compounds reached 50% inhibition of 5-LOX at concentrations lower than 100 µM. In terms of antitumor potential, derivatives 3 and 8 exhibited strong cytotoxic effects on the HeLa cell line, suggesting the involvement of the extrinsic pathway of apoptosis. According to the overall results obtained for both sets of synthesized molecules, derivatives 4 and 8 can be underlined as molecules with the strongest anti-inflammatory activity, while derivatives 3 and 8 are the most promising cytotoxic agents.

Cooling down with Entresto. Can sacubitril/valsartan combination enhance browning more than coldness?

BACKGROUND: It is a growing importance to induce a new treatment approach to encourage weight loss but also to improve maintenance of lost weight. It has been shown that promotion of brown adipose tissue (BAT) function or acquisition of BAT characteristics in white adipose tissue (terms referred as "browning") can be protective against obesity. MAIN TEXT: Amongst numerous established environmental influences on BAT activity, cold exposure is the best interested technique due to its not only effects on of BAT depots in proliferation process but also de novo differentiation of precursor cells via ß-adrenergic receptor activation. A novel combination drug, sacubitril/valsartan, has been shown to be more efficient in reducing cardiovascular events and heart failure readmission compared to conventional therapy. Also, this combination of drugs increases the postprandial lipid oxidation contributing to energy expenditure, promotes lipolysis in adipocytes and reduces body weight. To date, there is no research examining potential of combined sacubitril/valsartan use to promote browning or mechanisms in the basis of this thermogenic process. CONCLUSION: Due to the pronounced effects of cold and sacubitril/valsartan treatment on function and metabolism of BAT, the primary goal of further research should focused on investigation of the synergistic effects of the sacubitril/valsartan treatment at low temperature environmental conditions.

Short-Term Administration of Lemon Balm Extract Ameliorates Myocardial Ischemia/Reperfusion Injury: Focus on Oxidative Stress.

We aimed to investigate the cardioprotective effects of ethanolic Melissa officinalis L. extract (ME) in the rat model of myocardial ischemia/reperfusion (I/R) injury. Thirty-two Wistar rats were randomly divided into a CTRL non-treated control group with myocardial I/R injury and three experimental groups of rats treated with 50, 100, or 200 mg/kg of ME for 7 days per os. Afterward, hearts were isolated, and cardiodynamic function was assessed via the Langendorff model of global 20 min ischemia and 30 min reperfusion. Oxidative stress parameters were determined spectrophotometrically from the samples of coronary venous effluent (O2-, H2O2, TBARS, and NO2-,) and heart tissue homogenate (TBARS, NO2-, SOD, and CAT). H/E and Picrosirius red staining were used to examine cardiac architecture and cardiac collagen content. ME improved cardiodynamic parameters and achieved to preserve cardiac architecture after I/R injury and to decrease fibrosis, especially in the ME200 group compared to CTRL. ME200 and ME100 markedly decreased prooxidants TBARS, O2-, and H2O2 while increasing NO2-. Hereby, we confirmed the ME`s ability to save the heart from I/R induced damage, even after short-term preconditioning in terms of preserving cardiodynamic alterations, cardiac architecture, fibrosis, and suppressing oxidative stress, especially in dose of 200 mg/kg.

Effects of Combined Allogenic Adipose Stem Cells and Hyperbaric Oxygenation Treatment on Pathogenesis of Osteoarthritis in Knee Joint Induced by Monoiodoacetate.

The beneficial effects of HBO in inflammatory processes make it an attractive type of treatment for chronic arthritis. In addition, the effects of combination therapy based on adipose stem cells and HBO on OA progression have not been fully investigated. The current study explored the efficacy of intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (ADMSCs) combined with hyperbaric oxygenation treatment (HBO) in a rat osteoarthritis (OA) model. The rat OA model was induced by intra-articular injection of monoiodoacetate (MIA) and 7 days after application of MIA rats were divided into five groups: healthy control (CTRL), osteoarthritis (OA), ADMSCs (ADS), the HBO+ADS21day and HBO+ADS28day groups. A single dose of 1 × 106 allogeneic ADMSCs suspended in sterile saline was injected into the knee joint alone or in combination with HBO treatment. Rats were sacrificed at 3 or 4 weeks after MIA injection. Treatment outcomes were evaluated by radiographic, morphological and histological analysis and by specific staining of articular cartilage. We also measured the level of inflammatory and pro/antioxidative markers. We confirmed that combined treatment of ADMSCs and HBO significantly improved the regeneration of cartilage in the knee joint. Rtg score of knee joint damage was significantly decreased in the HBO+ADS21day and HBO+ADS28day groups compared to the OA. However, the positive effect in the HBO+ADS28day group was greater than the HBO+ADS21day group. The articular cartilage was relatively normal in the HBO+ADS28day group, but moderate degeneration was observed in the HBO+ADS21day compared to the OA group. These findings are in line with the histopathological results. A significantly lower level of O2-. was observed in the HBO+ADS28day group but a higher NO level compared to the HBO+ADS21day group. Moreover, in the HBO+ADS28day group significantly higher concentrations of IL-10 were observed but there was no significant difference in proinflammatory cytokine in serum samples. These results indicate that a single intra-articular injection of allogeneic ADMSCs combined with HBO efficiently attenuated OA progression after 28 days with greater therapeutic effect compared to alone ADMSCs or after 3 weeks of combined treatment. Combined treatment might be an effective treatment for OA in humans.

Update of the risk assessment of hexabromocyclododecanes (HBCDDs) in food.

The European Commission asked EFSA to update its 2011 risk assessment on hexabromocyclododecanes (HBCDDs) in food. HBCDDs, predominantly mixtures of the stereoisomers α-, ß- and γ-HBCDD, were widely used additive flame retardants. Concern has been raised because of the occurrence of HBCDDs in the environment, food and in humans. Main targets for toxicity are neurodevelopment, the liver, thyroid hormone homeostasis and the reproductive and immune systems. The CONTAM Panel concluded that the neurodevelopmental effects on behaviour in mice can be considered the critical effects. Based on effects on spontaneous behaviour in mice, the Panel identified a lowest observed adverse effect level (LOAEL) of 0.9 mg/kg body weight (bw) as the Reference Point, corresponding to a body burden of 0.75 mg/kg bw. The chronic intake that would lead to the same body burden in humans was calculated to be 2.35 µg/kg bw per day. The derivation of a health-based guidance value (HBGV) was not considered appropriate. Instead, the margin of exposure (MOE) approach was applied to assess possible health concerns. Over 6,000 analytical results for HBCDDs in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary LB exposure to HBCDDs were fish meat, eggs, livestock meat and poultry. The CONTAM Panel concluded that the resulting MOE values support the conclusion that current dietary exposure to HBCDDs across European countries does not raise a health concern. An exception is breastfed infants with high milk consumption, for which the lowest MOE values may raise a health concern.

Implementation of Harmonized Food Consumption Data Collection in the Balkan Region According to the EFSA EU Menu Methodology Standards.

Initiatives in the Capacity Development in Nutrition Research in the Balkan region in the last decade have been toward the creation of contemporary, harmonized Research Infrastructure (RI) compliant with European standards. This study describes the process of creation and implementation of the European Food Safety Authority (EFSA) EU Menu methodology in the Balkan region during the EFSA support projects for food consumption data collection in four countries (Serbia, Montenegro, Bosnia and Herzegovina, and North Macedonia). This process entailed the application and improvement of an innovative tool, the DIET ASSESS and PLAN (DAP), a platform for standardized food consumption data collection and dietary intake assessment. DAP comprises computerized food consumption, anthropometric measurements, and physical activity questionnaires, validated food picture book, and FoodEx2 exposure hierarchy with sets of facet descriptors of the interest. It hosts the Balkan food platform with a Serbian food composition database (FCDB) and Regional FCDB, compliant with European Food Information Resource (EuroFIR™) standards. The implementation of the DAP platform in national dietary surveys conducted with the support of the EFSA EU Menu project in Balkan countries enabled harmonized food consumption data compilation and reporting. Application of the methodology entailed the development of study protocol and extensive education and training of study personnel. The entire data collection process was managed by internal and external survey coordinators. A pilot study was conducted to test the entire data collection and control process and was afterward used to make necessary improvements and adjustments to meet EU Menu requirements. Data collected are internationally comparable with food consumption data in other European countries within the framework of the EU Menu program. The existence of such data in the Balkan region will catalyze research activities in emerging topics, such as identification of dietary patterns, the establishment of national nutrient reference values and food-based dietary guidelines (not only in Serbia, but in the whole Balkan region), dietary exposure assessments, the endorsement and evaluation of new food legislations, the environmental and other effects of diet on the food system. The developed and implemented methodology underpins evidence-based policy-making processes lacking in the field of public health nutrition in the region.

Impact of COVID-19 confinement on eating behaviours across 16 European countries: The COVIDiet cross-national study.

We aimed to evaluate the changes in eating behaviours of the adult population across 16 European countries due to the COVID-19 confinement and to evaluate whether these changes were somehow related to the severity of the containment measures applied in each country. An anonymous online self-reported questionnaire on socio-demographic characteristics, validated 14-items Mediterranean diet (MedDiet) Adherence Screener (MEDAS) as a reference of a healthy diet, eating and lifestyle behaviours prior to and during the COVID-19 confinement was used to collect data. The study included an adult population residing in 16 European countries at the time of the survey. Aggregated Stringency Index (SI) score, based on data from the Oxford COVID-19 Government Response Tracker, was calculated for each country at the time the questionnaire was distributed (range: 0-100). A total of 36,185 participants completed the questionnaire (77.6% female, 75.2% with high educational level and 42.7% aged between 21 and 35 years). In comparison to pre-confinement, a significantly higher adherence to the MedDiet during the confinement was observed across all countries (overall MEDAS score prior to- and during confinement: 5.23 ± 2.06 vs. 6.15 ± 2.06; p < 0.001), with the largest increase seen in Greece and North Macedonia. The highest adherence to MedDiet during confinement was found in Spain and Portugal (7.18 ± 1.84 and 7.34 ± 1.95, respectively). Stricter contingency restrictions seemed to lead to a significantly higher increase in the adherence to the MedDiet. The findings from this cross-sectional study could be used to inform current diet-related public health guidelines to ensure optimal nutrition is followed among the population, which in turn would help to alleviate the current public health crisis.

Olive Leaf Polyphenols (OLPs) Stimulate GLUT4 Expression and Translocation in the Skeletal Muscle of Diabetic Rats.

Skeletal muscles are high-insulin tissues responsible for disposing of glucose via the highly regulated process of facilitated glucose transporter 4 (GLUT4). Impaired insulin action in diabetes, as well as disorders of GLUT4 vesicle trafficking in the muscle, are involved in defects in insulin-stimulated GLUT4 translocation. Since the Rab GTPases are the main regulators of vesicular membrane transport in exo- and endo-cytosis, in the present work, we studied the effect of olive leaf polyphenols (OLPs) on Rab8A, Rab13, and Rab14 proteins of the rat soleus muscle in a model of streptozotocin (SZT)-induced diabetes (DM) in a dose-dependent manner. Glucose, cholesterol, and triglyceride levels were determined in the blood, morphological changes of the muscle tissue were captured by hematoxylin and eosin histological staining, and expression of GLUT4, Rab8A, Rab13, and Rab14 proteins were analyzed in the rat soleus muscle by the immunofluorescence staining and immunoblotting. OLPs significantly reduced blood glucose level in all treated groups. Furthermore, significantly reduced blood triglycerides were found in the groups with the lowest and highest OLPs treatment. The dynamics of activation of Rab8A, Rab13, and Rab14 was OLPs dose-dependent and more effective at higher OLP doses. Thus, these results indicate a beneficial role of phenolic compounds from the olive leaf in the regulation of glucose homeostasis in the skeletal muscle.

Association of meal timing with dietary quality in a Serbian population sample.

BACKGROUND: The world-wide adoption of Western lifestyles and eating patterns is associated with adverse effects on nutrient intakes. Here we evaluated the relationships between timing of meals and diet quality in Serbia, a Balkan country with a traditional eating pattern that includes the largest meal of the day as a late lunch. METHODS: A dietary survey was done in the Republic of Serbia using a nationally-representative sample of 74 children and 260 non-pregnant adults. Nutrient intakes were calculated from two 24-h recalls. A Dietary Quality Score (DQS) enumerated how many European Union (EU) Science Hub recommendations were met for fruit and vegetables, fiber, saturated fat, sodium, and sugar. We evaluated whether the timing of dietary intakes is associated with DQS and body mass index. RESULTS: The dietary intakes of children ages 10-17 and adults were similar and were high in total fat intake, with an average of 40% of energy from fat. Mean fruit and vegetable intakes of 473 g/day in adults exceeded the minimal EU recommendation. The most worrisome aspects of the Serbian diet were high intakes of saturated fat, sugar and sodium. Lunch was the meal with the highest mean content of energy, followed by breakfast and dinner, and the average time for lunch was 15:15. Consumption of a higher percentage of calories before 16:00 in adults was associated with higher fruit and vegetable intakes and with higher DQS. The subgroup of adults consuming their largest meal after 20:00 had a lower mean age, more men, and a larger percentage was employed outside of the home. There were no associations of meal timing with BMI, but the prevalence of obesity in this population sample was only 13%. CONCLUSIONS: These results indicate that an earlier meal pattern, and especially consuming the largest meal of the day earlier in the day, was associated with better quality diets. Public health efforts are needed to preserve nutrient intakes as the population shifts away from the traditional Serbian eating pattern. Long-term, deterioration of nutrient intakes could contribute to the increasing rates of obesity that have been observed in Serbia and world-wide.

Chronic Stress Potentiates High Fructose-Induced Lipogenesis in Rat Liver and Kidney.

SCOPE: Intake of fructose-sweetened beverages and chronic stress (CS) both increase risk of cardiometabolic diseases. The aim is to investigate whether these factors synergistically perturb lipid metabolism in rat liver and kidney. METHODS AND RESULTS: Fractional de novo lipogenesis (fDNL), intrahepatic- and intrarenal-triglycerides (IHTG and IRTG), de novo palmitate (DNPalm) content, FA composition, VLDL-TGs kinetics, and key metabolic gene expression at the end of the feeding and non-feeding phases in rats exposed to standard chow diet, chow diet + CS, 20% liquid high-fructose supplementation (HFr), or HFr+CS are measured. HFr induces hypertriglyceridemia, up-regulates fructose-metabolism and gluconeogenic enzymes, increases IHTG and DNPalm content in IHTG and IRTG, and augments fDNL at the end of the feeding phase. These changes are diminished after the non-feeding phase. CS does not exert such effects, but when combined with HFr, it reduces IHTG and visceral adiposity, enhances lipogenic gene expression and fDNL, and increases VLDL-DNPalm secretion. CONCLUSION: Liquid high-fructose supplementation increases IHTG and VLDL-TG secretion after the feeding phase, the latter being the result of stimulated hepatic and renal DNL. Chronic stress potentiates the effects of high fructose on fDNL and export of newly synthesized VLDL-TGs, and decreases fructose-induced intrahepatic TG accumulation after the feeding phase.

Energy, macronutrients and dietary fibre intake among adults in North Macedonia.

OBJECTIVE: The present research aimed to estimate macronutrients intake among adults in North Macedonia and to identify their predominant food sources. METHODS: Within this cross-sectional study dietary data were collected using repeated 24h recall interviews. Nationwide, adults aged 18+ were recruited. Dietary data, anthropometric measures and socio-demographic characteristics were available for 496 participants. Nutrient intake was analyzed using the Balkan Food Composition Database and Diet Assess and Plan platform. Macedonian dietary guidelines were used for estimation of inadequacy. RESULTS: Significant differences in macronutrients intake are noticed between age groups within certain socio-demographic factors. Total sugar intake was significantly higher among young adult females comparing with those older than 25 years (p = 0.049). Young urban females have significantly higher fats intake than older participants (p = 0.038). Higher total daily energy, proteins, fats and carbohydrates intake (p = 0.033, p = 0.043, p = 0.032, p = 0.042, respectively) was noticed among young urban males when compared to older ones. Only dietary fibre intake was higher among older urban males (p = 0.030). Univariate linear regression models showed that obese participants had significantly higher relative proteins intake comparing with those having BMI within recommended range (p = 0.024, ß = 1.21). Relative carbohydrates intake was significantly lower among males (p = 0.018, ß = -2.077) and among highly educated participants (p = 0.018, ß = -4.304). Participants with tertiary education had higher relative fats intake (p = 0.012, ß = 4.213). CONCLUSION: Macronutrients intake of adults should be improved. There is higher intake of dietary fats and need for an increase of complex carbohydrates intake, particularly dietary fibre. Findings of this survey should be used in shaping, fine-tuning and implementing food and nutrition policies that will stimulate healthier diets for prevention of diet related non-communicable diseases.