Antioxidative and cardioprotective effects of minocycline in ischemia/reperfusion injury in experimental model of hypertension.

Cardiovascular diseases remains leading cause of death and disabilities. Coronary artery occlusion and consequent ischemia leads to acute myocardial infarction, but restoration of blood flow, paradoxically, provokes further myocardial damage known as reperfusion injury. Minocycline is possessing anti-inflammatory and anti-apoptotic activity, immune-modulating and antioxidative properties besides its primary antibacterial effect. Recently it gained significant interest in preventing cardiac damage especially due to myocardial ischemia/reperfusion injury (MI/RI). The aim of this study was to assess the protective ability of pre-treatment and post-treatment of isolated hearts from healthy and spontaneously hypertensive rats with minocycline, on functional recovery and redox status after MI/RI using Langendorff technique. Using sensor in the left ventricle, the cardiodynamic parameters were recorded and in the samples of the coronary venous effluent oxidative stress biomarkers were analyzed. Minocycline was injected directly into the coronary vessels, in pre-treatment 5 min before global ischemia, and in post-treatment during the first 5 min of reperfusion. Changes in redox balance induced by minocycline were more prominent in post-treatment fashion of application. Cardioprotective effects of minocycline due to MI/RI are even more significant in hypertensive hearts. Minocycline showed significant cardioprotective effects, which was more pronounced in hypertensive compared to healthy hearts. Reduction of pro-oxidative biomarkers was more prominent in hypertensive hearts compared to the normotensive, especially if it is applied in the form of post-treatment. Minocycline could be important tool in reduction of heart damage induced by MI/RI due to its antioxidative potential, if these results are confirmed by clinical study.

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.

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.

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.

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.

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.

Improving the reporting quality of intervention trials addressing the inter-individual variability in response to the consumption of plant bioactives: quality index and recommendations.

PURPOSE: The quality of the study design and data reporting in human trials dealing with the inter-individual variability in response to the consumption of plant bioactives is, in general, low. There is a lack of recommendations supporting the scientific community on this topic. This study aimed at developing a quality index to assist the assessment of the reporting quality of intervention trials addressing the inter-individual variability in response to plant bioactive consumption. Recommendations for better designing and reporting studies were discussed. METHODS: The selection of the parameters used for the development of the quality index was carried out in agreement with the scientific community through a survey. Parameters were defined, grouped into categories, and scored for different quality levels. The applicability of the scoring system was tested in terms of consistency and effort, and its validity was assessed by comparison with a simultaneous evaluation by experts' criteria. RESULTS: The "POSITIVe quality index" included 11 reporting criteria grouped into four categories (Statistics, Reporting, Data presentation, and Individual data availability). It was supported by detailed definitions and guidance for their scoring. The quality index score was tested, and the index demonstrated to be valid, reliable, and responsive. CONCLUSIONS: The evaluation of the reporting quality of studies addressing inter-individual variability in response to plant bioactives highlighted the aspects requiring major improvements. Specific tools and recommendations favoring a complete and transparent reporting on inter-individual variability have been provided to support the scientific community on this field.

Systematic Review of Observational Studies with Dose-Response Meta-Analysis between Folate Intake and Status Biomarkers in Adults and the Elderly.

BACKGROUND: Dietary reference values for folate intake vary widely across Europe. METHODS: MEDLINE and Embase through November 2016 were searched for data on the association between folate intake and biomarkers (serum/plasma folate, red blood cell [RBC] folate, plasma homocysteine) from observational studies in healthy adults and elderly. The regression coefficient of biomarkers on intake (ß) was extracted from each study, and the overall and stratified pooled ß and SE (ß) were obtained by random effects meta-analysis on a double log scale. These dose-response estimates may be used to derive folate intake reference values. RESULTS: For every doubling in folate intake, the changes in serum/plasma folate, RBC folate and plasma homocysteine were +22, +21, and -16% respectively. The overall pooled regression coefficients were ß = 0.29 (95% CI 0.21-0.37) for serum/plasma folate (26 estimates from 17 studies), ß = 0.28 (95% CI 0.21-0.36) for RBC (13 estimates from 11 studies), and ß = -0.21 (95% CI -0.31 to -0.11) for plasma homocysteine (10 estimates from 6 studies). CONCLUSION: These estimates along with those from randomized controlled trials can be used for underpinning dietary recommendations for folate in adults and elderly.

The influence of food consumption and socio-economic factors on the relationship between zinc and iron intake and status in a healthy population.

OBJECTIVE: To examine Zn and Fe nutritional status of a healthy population by means of anthropometric, dietary and biochemical measurements and to investigate the relationship of usual Zn and Fe dietary intakes to Zn and Fe status. In addition, to examine the impact of food choices and socio-economic factors on Fe and Zn dietary intakes and status with the aim to identify groups at risk of dietary deficiency and suggest factors that may influence the status of these nutrients. DESIGN: Food consumption was assessed by 24 h recall questionnaires. Twenty biochemical parameters were measured, of which Hb, haematocrit, erythrocyte count and plasma concentrations of Fe and Zn were directly related to Fe and Zn nutrition. The prevalence of study participants with inadequate micronutrient intakes was calculated using the Estimated Average Requirement cut-point method. SETTING: Serbia, Europe. SUBJECTS: Apparently healthy adults (25-65 years of age). RESULTS: Mean daily Zn and Fe intakes were 9·1 mg and 11·6 mg for males and 7·3 mg and 9·4 mg for females, respectively. Five per cent of the study population had inadequate dietary Fe intake and 15-25 % had inadequate Zn intake. Lower Hb concentrations were measured in women with lower Zn intakes. No differences in Fe and Zn intakes and status among various socio-economic groups were observed, except for Fe intake between the low-income and affluent groups. CONCLUSIONS: Regular follow-ups are needed to ensure that potential deficiencies of Zn and Fe do get recognized and addressed in a timely manner.

Validity of an FFQ assessing the vitamin D intake of young Serbian women living in a region without food fortification: the method of triads model.

OBJECTIVE: The objective of the present study was to examine the external validity of an FFQ designed to estimate dietary vitamin D intake compared with a plasma biomarker and three repeated 24 h dietary recalls in women of reproductive age in Serbia, where there is no exposure to food fortified with vitamin D. The method of triads was applied. DESIGN: In a cross-sectional study, 422 women completed the Women and Reproductive Health FFQ (WRH-FFQ) during the winter months. From a representative subgroup (n 44), three 24 h dietary recalls and anthropometric parameters were collected as well as a fasting blood sample for vitamin D biomarker analyses. Correlation coefficients were calculated between each of the dietary methods. Validity coefficients, as a correlation between the measured and estimated 'true' exposure, were calculated using the method of triads. Bland-Altman plots were also constructed. SETTING: Three major universities in Serbia. SUBJECTS: Healthy young women (n 422) aged 18-35 years. RESULTS: The WRH-FFQ estimate of vitamin D intake for all participants was 4.0 (sd 3.3) µg/d and 3.1 (sd 2.3) µg/d for the subgroup. Bland-Altman plots for these intakes showed high agreement. Validity coefficients for the FFQ, 24 h recall and biomarker were ρ QI=0.847 (95% CI 0.564, 0.928), ρ RI=0.810 (95% CI 0.537, 0.997) and ρ BI=0.499 (95% CI 0.190, 0.840), while the correlation coefficients were 0.686, 0.422 and 0.404. CONCLUSIONS: The FFQ applied in the present study is a valid tool for assessing dietary vitamin D intake in women living in Serbia, a region without mandatory vitamin D food fortification.

Professional training in nutrition in Central and Eastern Europe: current status and opportunities for capacity development.

OBJECTIVE: To examine the availability of academic programmes in nutrition and identify nutrition training needs in Central and Eastern Europe (CEE). DESIGN: A questionnaire with close-ended and open-ended questions was distributed to the members of the United Nations University Standing Committee on Nutrition, Regional Network for Capacity Development in Nutrition in CEE (NCDN CEE). SETTING: Participants' responses to the questionnaire including the comments of their colleagues from home institutions were obtained in group discussions during NCDN CEE meetings in 2010-2013. SUBJECTS: Sixteen CEE countries' experts and their colleagues from home institutions involved in NCDN CEE activities 2007-2013. RESULTS: The responses were obtained from fourteen out of sixteen participating countries; five countries have established Bachelor, Master and PhD studies in nutrition (Croatia, Czech Republic, Poland, Slovak Republic and Slovenia), whereas in Latvia and Republic of Macedonia only Bachelor and Master studies are set up. Seven countries have no Bachelor, Master or PhD studies: Bosnia and Herzegovina, Bulgaria, Estonia, Lithuania, Montenegro, Romania and Serbia. Introduction to data analysis and Nutritional epidemiology are the most needed nutrition trainings that would increase working competence of nutritionists and nutrition-related professionals in CEE. CONCLUSIONS: Availability of academic programmes in nutrition in CEE countries is limited. Opportunities for improving the competence of existing and future nutrition-related professionals should be addressed at national and regional level; distance learning courses and creation of a regional centre for nutrition training were seen as opportunities for sustainable capacity development in nutrition in CEE.

Hepatic inflammation induced by high-fructose diet is associated with altered 11ßHSD1 expression in the liver of Wistar rats.

PURPOSE: High fructose consumption provokes metabolic perturbations that result in chronic low-grade inflammation and insulin resistance. Glucocorticoids, potent anti-inflammatory hormones, have important role in pathogenesis of diet-induced metabolic disturbances. The aim of this study was to examine the link between glucocorticoid metabolism and inflammation in the liver of fructose-fed rats. METHODS: Fructose-fed male Wistar rats consumed 60% fructose solution for 9 weeks. Glucocorticoid prereceptor metabolism and signaling were analyzed by measuring the level of 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1) and hexose-6-phosphate dehydrogenase expression, as well as via determination of intracellular corticosterone concentration, glucocorticoid receptor subcellular distribution and expression of its target gene, phosphoenolpyruvate carboxykinase. Nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNFα) and the level of inhibitory phosphorylation of insulin receptor substrate-1 (IRS-1) on Ser(307) were analyzed as markers of hepatic inflammation. The protein and/or mRNA levels of all examined molecules were assessed by Western blot and/or qPCR. RESULTS: Fructose-rich diet led to an enhancement of 11ßHSD1 protein level in the liver, without affecting intracellular level of corticosterone and downstream glucocorticoid signaling. On the other hand, proinflammatory state was achieved through NFκB activation and increased TNFα expression, while elevated level of inhibitory phosphorylation of IRS-1 was observed as an early hallmark of insulin resistance. CONCLUSION: High-fructose diet does not influence hepatic glucocorticoid signaling downstream of the receptor, permitting development of NFκB-driven inflammation. The alteration in 11ßHSD1 expression is most likely the consequence of enhanced inflammation, finally leading to disruption of insulin signaling in the rat liver.

Socio-economic determinants of micronutrient intake and status in Europe: a systematic review.

OBJECTIVE: To provide the evidence base for targeted nutrition policies to reduce the risk of micronutrient/diet-related diseases among disadvantaged populations in Europe, by focusing on: folate, vitamin B12, Fe, Zn and iodine for intake and status; and vitamin C, vitamin D, Ca, Se and Cu for intake. DESIGN: MEDLINE and Embase databases were searched to collect original studies that: (i) were published from 1990 to 2011; (ii) involved >100 subjects; (iii) had assessed dietary intake at the individual level; and/or (iv) included best practice biomarkers reflecting micronutrient status. We estimated relative differences in mean micronutrient intake and/or status between the lowest and highest socio-economic groups to: (i) evaluate variation in intake and status between socio-economic groups; and (ii) report on data availability. SETTING: Europe. SUBJECTS: Children, adults and elderly. RESULTS: Data from eighteen publications originating primarily from Western Europe showed that there is a positive association between indicators of socio-economic status and micronutrient intake and/or status. The largest differences were observed for intake of vitamin C in eleven out of twelve studies (5-47 %) and for vitamin D in total of four studies (4-31 %). CONCLUSIONS: The positive association observed between micronutrient intake and socio-economic status should complement existing evidence on socio-economic inequalities in diet-related diseases among disadvantaged populations in Europe. These findings could provide clues for further research and have implications for public health policy aimed at improving the intake of micronutrients and diet-related diseases.

Comparative Cardioprotective Effectiveness: NOACs vs. Nattokinase-Bridging Basic Research to Clinical Findings.

The use of non-vitamin K antagonist oral anticoagulants (NOACs) has brought a significant progress in the management of cardiovascular diseases, considered clinically superior to vitamin K antagonists (VKAs) particularly in the prevention and treatment of thromboembolic events. In addition, numerous advantages such as fixed dosing, lack of laboratory monitoring, and fewer food and drug-to-drug interactions make the use of NOACs superior to VKAs. While NOACs are synthetic drugs prescribed for specific conditions, nattokinase (NK) is a natural enzyme derived from food that has potential health benefits. Various experimental and clinical studies reported the positive effects of NK on the circulatory system, including the thinning of blood and the dissolution of blood clots. This enzyme showed not only fibrinolytic activity due to its ability to degrade fibrin, but also an affinity as a substrate for plasmin. Recent studies have shown that NK has additional cardioprotective effects, such as antihypertensive and anti-atherosclerotic effects. In this narrative review, we presented the cardioprotective properties of two different approaches that go beyond anticoagulation: NOACs and NK. By combining evidence from basic research with clinical findings, we aim to elucidate the comparative cardioprotective efficacy of these interventions and highlight their respective roles in modern cardiovascular care.

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.

Biochemical, pathohistological, radiographic and cardiological analysis reveals the possible association between apical periodontitis and cardiac function in diabetic rats.

OBJECTIVE: To evaluate the possible effects of apical periodontitis (AP) on cardiac function, structure, and oxidative stress (OS) in rats with diabetes mellitus type 2 (T2DM). DESIGN: Forty-eight (Wistar albino, male) rats were randomized into four groups: control healthy (CTRL), normoglycemic with AP (AP), T2DM, and T2DM with AP (T2DM+AP). T2DM was induced by streptozotocin and a high-fat diet. AP was induced by pulp exposure to the oral environment for 4 weeks and analyzed radiographically. In the blood samples insulin and glucose were established. In vivo, cardiac function was evaluated by echocardiography. Ex vivo cardiac function was assessed by the Langendorff technique. Heart tissue was analyzed pathophysiologically. OS was determined in cardiac tissue homogenate and coronary venous effluent, spectrophotometrically. RESULTS: Impaired glycoregulation was observed in the T2DM+AP group compared to the T2DM, AP, and CTRL groups. The T2DM+AP group was associated with disturbed echocardiography and cardiodynamic parameters. The levels of superoxide anion radical, nitrite, and index of lipid peroxidation were significantly increased, while the superoxide dismutase and catalase were significantly decreased in the T2DM+AP group compared to T2DM, AP, and CTRL groups. The radiographic AP area was significantly larger in the T2DM+AP compared to the AP group. CONCLUSION: AP was associated with increased glucose levels, impaired cardiac function, structure, and OS in diabetic rats. Diabetes was related to an increased radiographic AP area. The study may be a starting point for further research to clarify the effects of AP on cardiac function in various models of systemic diseases.

Protective Effect of Hyperprolactinemia on Oxidative Stress in Patients with Psychotic Disorder on Atypical Antipsychotics Risperidone and Paliperidone: A Cross-Sectional Study.

Several studies indicate the impact of antipsychotics like risperidone and paliperidone on oxidative stress parameters, yet data remain inconsistent. We investigated the link between these medications, hyperprolactinemia (HPRL), and oxidative stress. This study was conducted at the Psychiatry Clinic, University Clinical Center, Kragujevac, between November 2022 and August 2023. Inclusion criteria comprised diagnosed psychotic disorders from the ICD-10-based F20-F29 spectrum and clinical stability on risperidone/paliperidone for ≥12 weeks with no recent dose adjustments. Exclusion criteria included pregnancy, breastfeeding, relevant medical conditions, or co-therapy with prolactin-secreting drugs. Data encompassed drug choice, administration method, therapy duration, and daily dose. Prolactin (PRL) levels, oxidative stress parameters (TBARS, H2O2, O2-, NO2-), and antioxidant system (CAT, GSH, SOD) were assessed. Of 155 subjects, women exhibited significantly higher PRL levels (p < 0.001) and symptomatic HPRL (p < 0.001). Drug choice and regimen significantly influenced TBARS (p < 0.001), NO2- (p < 0.001), O2- (p = 0.002), CAT (p = 0.04), and GSH (p < 0.001) levels. NO2- levels were affected by drug dose (p = 0.038). TBARS (p < 0.001), O2- (p < 0.001), and SOD (p = 0.022) inversely correlated with PRL levels, suggesting PRL's protective role against oxidative stress. The female sex association with higher PRL levels implies additional factors influencing PRL's antioxidant role. Antipsychotic choice and dosage impact PRL and oxidative stress markers, necessitating further exploration.

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.