Liraglutide Protects Cardiomyocytes against Isoprenaline-Induced Apoptosis in Experimental Takotsubo Syndrome.

Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy, characterized by an increased concentration of catecholamines, free radicals, and inflammatory cytokines, endothelial dysfunction, and increased apoptotic activity. High doses of isoprenaline are used in animal models to induce Takotsubo (TT)-like myocardial injury. The aim of the study was to investigate the antiapoptotic effects of liraglutide in experimental TTS and its role in the NF-κB pathway. Wistar rats were pretreated with liraglutide for 10 days, and on days 9 and 10, TT-like myocardial injury was induced with isoprenaline. After the sacrifice on day 11, hearts were isolated for histopathological and immunohistochemical analysis. Liraglutide reduced isoprenaline-induced cardiomyocyte apoptosis by decreasing cleaved caspase-3 (CC3), BCL-2-associated X protein (BAX), and NF-κB and increasing B-cell lymphoma/leukemia-2 (BCL-2). An increase in NF-κB in isoprenaline-treated rats was in positive correlation with proapoptotic markers (BAX and CC3) and in negative correlation with antiapoptotic marker BCL-2. Liraglutide increased BCL-2 and decreased NF-κB, BAX, and CC3, preserving the same correlations of NF-κB to apoptotic markers. It is concluded that liraglutide protects cardiomyocytes against isoprenaline-induced apoptosis in experimental TT-like myocardial injury through downregulation of the NF-κB pathway.

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.

Emerging Trends in Pathophysiology: Insights from the 9th International Congress of the International Society for Pathophysiology (ISP 2023).

This article provides a summary of the 9th International Congress of the International Society for Pathophysiology (ISP 2023) which took place in Belgrade, Serbia, from 4 to 6 July 2023. It describes the main trends and the most promising areas of research in current pathophysiology, including investigations of new pathogenic pathways, and the identification of cellular and molecular mechanisms, target molecules, genetic mechanisms, and new therapeutic strategies. The present article also highlights the research conducted by leading scientific teams and national pathophysiological societies from various countries that adds to our understanding of the pathogenesis of diseases and pathological processes.

Cardiorespiratory fitness mediates cortisol and lactate responses to winter and summer marches.

Background: The influence of homeostatically regulated physiological processes, including cardiorespiratory fitness (VO2max), on the response to physical stressors such as acclimatisation and marching, remains understudied. We aimed to investigate the effects of summer and winter acclimatisation and marching on cortisol levels and blood lactate, to gain insight into the role of these physiological processes in the stress response. Methods: Two groups of young Europeans, classified as poor (PCF; n=9) and good physical condition (GCF; n=21), based on a VO2MAX threshold of 40 mL O2/ kg/min, underwent 2-h March (6-7 km/h) in winter (5˚C) and summer (32˚C). Commercial tests, UniCel DxI Access Cortisol assay and EKF Biosen Clinic/GP assay were used for cortisol and lactate blood measurements (morning samples and those taken immediately after marches), respectively.

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.

Examining the Effects of Hyperbaric Oxygen Therapy on the Cardiovascular System and Oxidative Stress in Insulin-Treated and Non-Treated Diabetic Rats.

BACKGROUND: This study explored the effects of hyperbaric oxygen therapy (HBOT) on the cardiovascular system and oxidative stress in streptozotocin-induced diabetic rats. Wistar albino rats were divided into four groups: DM group (diabetic rats), DM+HBOT group (diabetic rats exposed to HBOT for 1 h daily, five days a week, at 2.8 atmosphere absolute (ATA) with 100% oxygen for two weeks), DM+INS group (diabetic rats treated with neutral protamine hagedorn (NPH) insulin at a dosage of 3-5 U/day), and DM+HBOT+INS group (diabetic rats treated with both NPH insulin and HBOT for two weeks). METHODS: Evaluations included glycemic control, oxidative stress parameters, and cardiac function measurements. RESULTS: NPH insulin treatment reduced blood glucose levels, although normoglycemia was not achieved. The DM+HBOT+INS group demonstrated the lowest pro-oxidative marker levels. NPH insulin treatment improved cardiac function, and combination therapy effectively restored cardiac function in diabetic animals. CONCLUSIONS: NPH insulin treatment reduced hyperglycemia and improved cardiac function in diabetic rats. The combined approach of NPH insulin and HBOT resulted in decreased pro-oxidative markers. These findings provide valuable insights for managing cardiovascular complications and oxidative stress in diabetes.

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.

The еffects of low mineral content water on microbiota, metabolic, and oxidative stress parameters in patients with type 2 diabetes mellitus.

Although scientific evidence has shown that natural mineral waters have potential beneficial metabolic effects, there is still very scarce data on their influence on type 2 diabetes mellitus (T2DM). The study was designed to investigate the effects of low mineral water from the "Sneznik-1/79″ source in Serbia on microbiota, metabolic, and oxidative stress parameters in patients with T2DM. In total, 60 patients with confirmed T2DM were included in the study, and they consumed "Sneznik-1/79″ water for 28 days. To examine the positive effects of "Sneznik-1/79″ water, we compared the results before and after the four weeks of "Sneznik-1/79″ water intake. Standard biochemical analyses were carried out, such as glucose level, lipid profile, and stool tests. The blood samples were collected to evaluate the effects of "Sneznik-1/79″ water on the redox status. At the end of the monitoring period, the total cholesterol concentration significantly dropped compared to the initial value. A significant improvement in intestinal peristalsis was observed, which was reflected in the fact that after four weeks, all patients established regular, daily bowel movements. Moreover, consumption of "Sneznik-1/79″ water eliminated the appearance of dysbiosis in 50% of patients. Additionally, the antioxidant capacity was improved by increasing the concentration of superoxide dismutase and reduced glutathione. The result of our study pointed out that the intake of "Sneznik-1/79″ water could be a promising adjuvant therapy for improving intestinal peristalsis as well as reducing the appearance of dysbiosis in T2DM patients.

Sacubitril/valsartan reverses cardiac structure and function in experimental model of hypertension-induced hypertrophic cardiomyopathy.

This study evaluated the effect of sacubtril/valsartan on cardiac remodeling, molecular and cellular adaptations in experimental (rat) model of hypertension-induced hypertrophic cardiomyopathy. Thirty Wistar Kyoto rats, 10 healthy (control) and 20 rats with confirmed hypertension-induced hypertrophic cardiomyopathy (HpCM), were used for this study. The HpCM group was further subdivided into untreated and sacubitril/valsartan-treated groups. Myocardial structure and function were assessed using echocardiography, Langendorff's isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Echocardiographic examinations revealed protective effects of sacubitril/valsartan by improving left ventricular internal diameter in systole and diastole and fractional shortening. Additionally, sacubitril/valsartan treatment decreased systolic and diastolic blood pressures in comparison with untreated hypertensive rats. Moreover, sacubitril/valsartan treatment reduced oxidative stress and apoptosis (reduced expression of Bax and Cas9 genes) compared to untreated rats. There was a regular histomorphology of cardiomyocytes, interstitium, and blood vessels in treated rats compared to untreated HpCM rats which expressed hypertrophic cardiomyocytes, with polymorphic nuclei, prominent nucleoli and moderately dilated interstitium. In experimental model of hypertension-induced hypertrophic cardiomyopathy, sacubitril/valsartan treatment led to improved cardiac structure, haemodynamic performance, and reduced oxidative stress and apoptosis. Sacubitril/valsartan thus presents as a potential therapeutic strategy resulted in hypertension-induced hypertrophic cardiomyopathy.

Effects of dandelion root on rat heart function and oxidative status.

This study aimed to examine the effects of dandelion root on rat heart function and oxidative status. At the beginning of the experimental protocol, Wistar albino rats were randomly classified into two groups (10 rats per group): 1. control group - animals that drank tap water; 2. experimental group - animals that drank dandelion root for four weeks. Every morning for four weeks, the animals received freshly boiled dandelion root in a volume of 250 ml. At the end of the dandelion administration, animals were sacrificed, and their hearts were isolated and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure between 40 - 120 cm H2O. The following myocardial function parameters were measured: maximum rate of left ventricular pressure development (dp/dt max), minimum rate of left ventricular pressure development (dp/dt min), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), heart rate (HR). In addition, the coronary flow (CF) was measured flowmetrically. Finally, blood samples were collected after sacrificing to determine oxidative stress biomarkers: nitrite (NO2-), superoxide anion radical (O2-), hydrogen peroxide (H2O2), the index of lipid peroxidation (TBARS), reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD). The present pioneer results indicated that dandelion root did not manifest a negative impact on functional aspects of isolated rat heart. In addition, dandelion consumption was not associated with promising results in terms of maintaining systemic redox balance.

The impact of different diuretics on regression of myocardial reperfusion injury in spontaneously hypertensive rats.

The study's objective was to ascertain the results of sub-chronic therapy of various diuretics on the ischemia/reperfusion dysfunction of the heart in hypertensive rats by a global ischemia in an isolated rat heart model. The research included 40 spontaneously hypertensive male rats (Wistar Kyoto strain, body mass 250 ± 30 g, 8 weeks old) grouped into four groups. The animals were treated for 4 weeks with 10 mg/kg of hydrochlorothiazide, indapamide, or spironolactone per os. After a period of sub-chronic treatment, we analyzed hemodynamic measurements, echocardiography, and myocardial function according to the Langendorff retrograde perfusion method. The hearts were subjected to 20 min of global ischemia and then reperfused for 30 min (I20:R30). Cardiovascular parameters that depict the left ventricle functions were continuously monitored, while flowmetry was used to determine coronary flow values. Markers of oxidative stress were estimated from coronary venous effluent using spectrophotometry. All three examined diuretics (hydrochlorothiazide, spironolactone, indapamide) lowered the production of the majority of the detected prooxidants, reducing myocardial oxidative damage. The cardiological examination of heart function in vivo demonstrated that treatment with indapamide and spironolactone mitigates left ventricular hypertrophy but without significant lowering of blood pressure or increment in ejection fraction. Additionally, monitoring of cardiac function ex vivo indicated the cardiodepressant effect of spironolactone in spontaneously hypertensive rats.

The effect of a 6-month walking program on biochemical parameters in sedentary adults with type 2 diabetes mellitus.

This study assessed the effect of a 6-month walking program on biochemical parameters in patients with type-2 diabetes mellitus. A group of 40 sedentary patients with type-2 diabetes volunteered to participate in this study. Plasma glucose, triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase, urea, creatinine, uric acid, C-reactive protein (CRP), and erythrocyte sedimentation rate were measured. Differences in outcome measures between pre- and post-intervention were assessed using paired t-test or Wilcoxon signed-rank test, with effect sizes interpreted separately for normally (µ2: small 0.01-0.06, moderate 0.061-0.14, and large >0.14) and non-normally distributed data (r: small = 0.1-0.3, moderate = 0.3-0.5, and large >0.5). Significant (p < 0.001) large decrease between the initial and final measurements was observed for glucose (r = 0.62), total cholesterol (µ2 = 0.88), triglycerides (r = 0.62), LDL (r = 0.61), AST (µ2 = 0.82), ALT (µ2 = 0.79), gamma-glutamyl transferase (µ2 = 0.79), urea (µ2 = 0.92), creatinine (r = 0.62), uric acid (r = 0.62), CRP (µ2 = 0.80), and erythrocyte sedimentation rate (µ2 = 0.58). On the other hand, significant (p < 0.001) large increase between the initial and final measurements was observed for HDL (r = 0.62). Supervised 6-month aerobic walking program is an effective strategy in (1) reducing hyperglycemia; (2) increasing HDL and reducing LDL, and triglycerides; (3) reducing plasma biomarkers of liver dysfunction, kidney dysfunction, and inflammation in type-2 diabetic patients.

Body Fat Evaluation in Male Athletes from Combat Sports by Comparing Anthropometric, Bioimpedance, and Dual-Energy X-Ray Absorptiometry Measurements.

Multiple anthropometric equations have been developed aiming to provide accurate and affordable assessment of body fat composition in male athletes. This study examined correlations of values obtained from seventeen different anthropometric equations to DXA as well as BIA and DXA values. Male athletes (n = 101) from three different combat sports, wrestling (n = 33), judo (n = 35), and kickboxing (n = 33), with an average age of 20.9 ± 4.2 were included. Body fat percentage was estimated using anthropometry, BIA, and DXA. Correlations between anthropometric methods and DXA, as well as BIA and DXA, were determined using Spearman's rank correlation. Sixteen out of seventeen estimates of body fat percentages using existing anthropometric equations showed strong positive correlation with the values derived from DXA measurements (r = 0.569 - 0.909). The highest correlation was observed using the equation derived by Yuhasz, r = 0.909, followed by the equations from Oliver et al., Evans et al., Faulkner, and Thorland et al. (r ≈ 0.9). Statistical analysis of body fat percentages from DXA and BIA measurements also showed high positive correlation (r = 0.710). Correlation of seventeen anthropometric equations with BIA and DXA methods revealed that equations by Yuhasz, Oliver et al., Evans et al., Faulkner, and Thorland et al. are suitable alternative for assessing body fat percentage among male athletes from combat sports, showing even stronger correlation than BIA method.

Anti-inflammatory and Antioxidant Effects of Melissa officinalis Extracts: A Comparative Study.

Melissa officinalis L. (MO), traditionally referred to as lemon balm, is one of the lemon-scent aromatic herbs widely used in traditional medicine due to its calming, sedative, and anti-arrhythmic effects. Furthermore, several studies have linked its therapeutic potential with its antioxidant properties. Here, we aimed to evaluate and compare the content of active components, antioxidant, and anti-inflammatory potential of three different MO extracts (MOEs), ethanolic macerate (E1), aqueous (E2), and ethanolic (E3), obtained under reflux and their effects on systemic redox status after acute per os administration in vivo post-carrageenan application. The HPLC analysis revealed that the most abundant constituent in all the three extracts was rosmarinic acid (RA), with higher content in E1 and E3 than in E2 (P < 0.05). The highest flavonoid content was found in the aqueous extract, especially quercetin (P < 0.05). For the carrageenan-induced paw edema model, dark agouti rats were used and divided into the groups: Control, indomethacin, E1, E2, and E3 subgrouped according to applied doses: 50, 100, and 200 mg/kg. Ethanolic macerate (E1200) and aqueous (E2100) MOE were shown to be anti-inflammatory agents in the carrageenan paw edema model, with the most prominent edema inhibition in the sixth hour post-carrageenan (63.89% and 69.44%, respectively, vs. 76.67% in the indomethacin group). All the three extracts reduced the production of pro-oxidants H2O2 and TBARS post-carrageenan and increased GSH levels compared to control (P < 0.05). These data imply the possible future usage of MOEs to prevent inflammatory and oxidative stress-related diseases.

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.

Guanidinoacetic acid provides superior cardioprotection to its combined use with betaine and (or) creatine in HIIT-trained rats.

This study aimed to determine how guanidinoacetic acid (GAA) or its combined administration with betaine (B) or creatine (C) influences the cardiac function, morphometric parameters, and redox status of rats subjected to high-intensity interval training (HIIT). This research was conducted on male Wistar albino rats exposed to HIIT for 4 weeks. The animals were randomly divided into five groups: HIIT, HIIT + GAA, HIIT + GAA + C, HIIT + GAA + B, and HIIT + GAA + C + B. After completing the training protocol, GAA (300 mg/kg), C (280 mg/kg), and B (300 mg/kg) were applied daily per os for 4 weeks. GAA supplementation in combination with HIIT significantly decreased the level of both systemic and cardiac prooxidants ( O 2 - , H2O2, NO 2 - , and thiobarbituric acid reactive substances) compared with nontreated HIIT (p < 0.05). Also, GAA treatment led to an increase in glutathione and superoxide dismutase levels. None of the treatment regimens altered cardiac function. A larger degree of cardiomyocyte hypertrophy was observed in the HIIT + GAA group, which was reflected through an increase of the cross-sectional area of 27% (p < 0.05) and that of the left ventricle wall thickness of 27% (p < 0.05). Since we showed that GAA in combination with HIIT may ameliorate oxidative stress and does not alter cardiac function, the present study is a basis for future research exploring the mechanisms of cardioprotection induced by this supplement in an HIIT scenario.

The Evaluation of Healing Properties of Galium verum-Based Oral Gel in Aphthous Stomatitis in Rats.

Although oral ulcers represent one of the most frequent oral mucosal diseases, the available treatment is not sufficient to provide complete ulcer recovery without side-effects. Therefore, the aim of our study was to prepare a mucoadhesive oral gel based on Galium verum ethanol extract (GVL gel) and reveal its healing effects in the model of aphthous stomatitis in rats. Rats with oral ulcers were divided into the following groups: control (untreated), gel base (ulcer was treated with the gel base, three times per day for 10 days), and GVL gel group (the ulcer was treated with GVL gel in the same way as the gel base). Animals from each group were sacrificed on days 0, 3, 6, and 10 for collecting blood and ulcer tissue samples. Healing properties of oral gel were determined by clinical evaluation, as well as biochemical and histopathological examinations. Our findings suggest a significant decrease in the ulcer size in GVL gel group, with healing effects achieved through the alleviation of oxidative stress, reduction in COX-2 immunopositivity, and increase in collagen content in buccal tissue. Significant ulcer repairing potential of GVL gel highlights this oral mucoadhesive gel as a promising tool for prevention and treatment of RAS.

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.

Dose-dependent effects of perfluorocarbon-based blood substitute on cardiac function in myocardial ischemia-reperfusion injury.

The main goal of this study was to investigate the cardioprotective properties in terms of effects on cardiodynamics of perfluorocarbon emulsion (PFE) in ex vivo-induced ischemia-reperfusion injury of an isolated rat heart. The first part of the study aimed to determine the dose of 10% perfluoroemulsion (PFE) that would show the best cardioprotective effect in rats on ex vivo-induced ischemia-reperfusion injury of an isolated rat heart. Depending on whether the animals received saline or PFE, the animals were divided into a control or experimental group. They were also grouped depending on the applied dose (8, 12, 16 ml/kg body weight) of saline or PFE. We observed the huge changes in almost all parameters in the PFE groups in comparison with IR group without any pre-treatment. Calculated in percent, dp/dt max was the most changed parameter in group treated with 8 mg/kg, while the dp/dt min, SLVP, DLVP, HR, and CF were the most changed in group treated with 16 mg/kg 10 h before ischemia. The effects of 10% PFE are more pronounced if there is a longer period of time from application to ischemia, i.e., immediate application of PFE before ischemia (1 h) gave the weakest effects on the change of cardiodynamics of isolated rat heart. Therefore, the future of PFE use is in new indications and application methods, and PFE can also be referred to as antihypoxic and antiischemic blood substitute with mild membranotropic effects.