Combination of dapagliflozin and pioglitazone lacks superiority against monotherapy in streptozotocin-induced nephropathy.

Oxidative stress and apoptosis are highly engaged in development of diabetic nephropathy (DN). In monotherapy, dapagliflozin and pioglitazone positively modulate target organ damage even independently of their hypoglycaemic effect. This study evaluated whether a simultaneous PPARγ activation and SGLT cotransporter inhibition offer superior protection against DN-related oxidative and apoptotic processes in a T1DM rat model.

Correlating plasma protein profiles with symptomatology and treatment response in acute phase and early remission of major depressive disorder.

Objectives: This study aimed to explore the relationship between plasma proteome and the clinical features of Major Depressive Disorder (MDD) during treatment of acute episode.

Methods: In this longitudinal observational study, 26 patients hospitalized for moderate to severe MDD were analyzed. The study utilized Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) alongside clinical metrics, including symptomatology derived from the Montgomery-Åsberg Depression Rating Scale (MADRS).

Adding SGLT2 Cotransporter Inhibitor to PPARγ Activator Does Not Provide an Additive Effect in the Management of Diabetes-Induced Vascular Dysfunction.

Introduction: Endothelial dysfunction (ED) plays a key role in the pathogenesis of diabetic vascular complications. In monotherapy, dapagliflozin (Dapa) as well as pioglitazone (Pio) prevent the progression of target organ damage in both type 1 (T1DM) and type 2 diabetes. We investigated whether the simultaneous PPAR-γ activation and SGLT2 cotransporter inhibition significantly alleviate ED-related pathological processes and thus normalize vascular response in experimental T1DM.

Rapid changes of mRNA expressions of cardiac ion channels affected by Torsadogenic drugs influence susceptibility of rat hearts to arrhythmias induced by Beta-Adrenergic stimulation.

Drug-induced long QT syndrome (LQTS) and Torsades de Pointes (TdP) are serious concerns in drug development. Although rats are a useful scientific tool, their hearts, unlike larger species, usually do not respond to torsadogenic drugs. Consequently, their resistance to drug-induced arrhythmias is poorly understood.

Pioglitazone Alters Ace/Ace 2 Balance to Favour Ace2 Independently Of Glycaemia Levels in Diabetic Rat Heart.

The activation of the renin-angiotensin system (RAS) contributes to the pathogenesis of cardiac damage during diabetes. In the present study, we investigated the role of pioglitazone, dapagliflozin and their combination on RAS components in streptozotocin-induced diabetic cardiomyopathy in Wistar rats. Blood glucose, serum lipids, and ACE (angiotensin-converting enzyme), ACE2 levels were determined.

Peripheral Inflammatory Markers in Subtypes and Core Features of Depression: A Systematized Review.

Introduction: The aim of this work was to summarize relationships between two subtypes of major depressive disorder (melancholic and atypical) and four core features of depression that reflect the domains identified consistently in previous studies of major depressive disorder endophenotypes (exaggerated reactivity to negative information, altered reward processing, cognitive control deficits, and somatic symptoms) on the one hand and selected peripheral inflammatory markers (C-reactive protein [CRP], cytokines, and adipokines) on the other.

Methods: A systematized review was conducted. The database used for searching articles was PubMed (MEDLINE).

Knockout of MITOGEN-ACTIVATED PROTEIN KINASE 3 causes barley root resistance against Fusarium graminearum.

The roles of mitogen-activated protein kinases (MAPKs) in plant-fungal pathogenic interactions are poorly understood in crops. Here, microscopic, phenotypic, proteomic, and biochemical analyses revealed that roots of independent transcription activator-like effector nuclease (TALEN)-based knockout lines of barley (Hordeum vulgare L.) MAPK 3 (HvMPK3 KO) were resistant against Fusarium graminearum infection.

Osteocalcin levels decrease during the treatment of an acute depressive episode.

Objectives: Osteocalcin is a protein secreted by osteoblasts with a versatile endocrine role. Several domains in which it plays a role-stress response, monoamine synthesis, and cognitive functioning-are implicated also in the pathophysiology of major depressive disorder. In search of possible objective biomarkers of depression, the aim of the study was to assess the relationship between osteocalcin and depressive symptoms during the treatment of depressive episode.

Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage.

Overweight and obesity have been linked with increased intake of sugar-sweetened beverages. On the other hand, physical activity has been known to lead to weight loss. Therefore, we hypothesized that exercise might influence the population in fecal microbiota as their changed abundance is often associated with shifts in the physical activity and diet.

Analysis of necroptosis and its association with pyroptosis in organ damage in experimental pulmonary arterial hypertension.

In this study, a role of cell loss due to necroptosis and its linkage with pyroptosis in organ damage under the conditions of pulmonary arterial hypertension (PAH) was examined. Monocrotaline (MCT) was used to induce PAH in Wistar rats, and depending on the severity of the disease progression, they were further divided into two subgroups: MCT group-sacrificed 4 weeks after MCT administration and ptMCT group-prematurely sacrificed due to rapid deterioration in vital functions (on Day 24,11 ± 0,7). The elevation of respiratory rate and right ventricular (RV) hypertrophy were more evident in ptMCT group, while the heart rate and cardiac haemodynamic stress markers were comparably higher in both diseased groups.

Proapoptotic and antiapoptotic stimuli alternation in myocardial infarction experimental model.

Myocardial infarction is a life-threatening complication of the coronary artery disease - the leading cause of premature death worldwide. The severity of this condition is the result of cellular death following the myocardial ischaemia, which occurs via several mechanism including apoptosis. For the research of this condition, animal models are often employed.

Pioglitazone restores phosphorylation of downregulated caveolin-1 in right ventricle of monocrotaline-induced pulmonary hypertension.

Background: Caveolin-1 (cav-1) plays a role in pulmonary arterial hypertension (PAH). Monocrotaline (MCT)-induced PAH is characterized by a loss of cav-1 in pulmonary arteries; however, less is known regarding its role in the hypertrophied right ventricle (RV). We aimed to characterize the role of cav-1 and Hsp90 in the RV of MCT-induced PAH and their impact on endothelial nitric oxide synthase (eNOS).

Aortic butyrylcholinesterase is reduced in spontaneously hypertensive rats.

Despite the fact that vessels have sparse cholinergic innervation, acetylcholine (ACh), the primary neurotransmitter of parasympathetic nervous system, has been commonly used in physiological experiments to assess vascular function. ACh is hydrolyzed by two cholinesterases (ChE), namely acetylcholin-esterase and butyrylcholinesterase (BChE). However, little is known about these enzymes in blood vessels.

CRISPR/Cas9-Induced Loss-of-Function Mutation in the Barley Gene Causes Abnormal Embryo Development Leading to Severely Reduced Grain Germination and Seedling Shootless Phenotype.

The diverse roles of mitogen-activated protein kinases (MAPKs, MPKs) in plant development could be efficiently revealed by reverse genetic studies. In knockout mutants complete the life cycle; however, ~40% of their embryos show defects in the development leading to abnormal phenotypes of seeds and seedlings' roots. Contrary to the , the rice () is an essential gene as transfer DNA (T-DNA) insertion and CRISPR/Cas9 induced loss-of-function mutations in the cause early embryo arrest.

TALEN-Based Knock-Out Attenuates Proteome and Root Hair Phenotypic Responses to flg22 in Barley.

Mitogen activated protein kinases (MAPKs) integrate elicitor perception with both early and late responses associated with plant defense and innate immunity. Much of the existing knowledge on the role of plant MAPKs in defense mechanisms against microbes stems from extensive research in the model plant . In the present study, we investigated the involvement of barley () MPK3 in response to flagellin peptide flg22, a well-known bacterial elicitor.

Hematocrit-Related Alterations of Circulating microRNA-21 Levels in Heart Failure Patients with Reduced Ejection Fraction: A Preliminary Study.

Circulating microRNA-21 (miR-21) has been utilized as a diagnostic tool in the assessment of heart failure (HF). Blood constitution may be altered when HF occurs and miR-21 may affect hematopoiesis. Sample hemolysis may influence the determination of circulating miRNAs, challenging the diagnostic use of miRNAs.

Dapagliflozin elevates plasma high-density lipoprotein levels and influences visceral fat gene expression in streptozotocin-induced diabetes mellitus.

Objectives: Dapagliflozin (Dapa) could potentially be used to treat type 1 diabetes mellitus. We tested the hypothesis that it would influence blood lipid levels and visceral fat accumulation in a rodent diabetic model.

Methods: We used three groups of male Wistar rats: Controls, streptozotocin (STZ)-treated rats and STZ-treated orally with Dapa (STZ+Dapa), 10 mg/kg/day for six weeks.

Isolated downregulation of HCN2 in ventricles of rats with streptozotocin-induced diabetic cardiomyopathy.

Background: In spite of disrupted repolarization of diabetic heart, some studies report less tendency of diabetic heart to develop ventricular arrhythmias suggesting effective compensatory mechanism. We hypothesized that myocardial alterations in HCN2 and HCN4 channels occur under hyperglycaemia.

Methods: Diabetes was induced in rats using a single injection of streptozotocin (STZ; 55 mg/kg body weight, i.

Altered serum levels of neprilysin in heart failure patients with reduced ejection fraction.

Objective: In addition to the recent success of neprilysin inhibition in treatment of heart failure, elevated soluble neprilysin (sNEP) in circulation has been suggested to be a prognostic biomarker in heart failure with a reduced ejection fraction (HFrEF). However, the diagnostic performance of sNEP is nebulous and its levels in HFrEF have not been compared with controls. For the purpose of this study, we determined the role of sNEP levels as a biomarker in routine ambulatory care of HFrEF patients, when compared to the control subjects.

The tyrosine kinase inhibitor crizotinib influences blood glucose and mRNA expression of GLUT4 and PPARs in the heart of rats with experimental diabetes.

Tyrosine kinases inhibitors (TKIs) may alter glycaemia and may be cardiotoxic with importance in the diabetic heart. We investigated the effect of multi-TKI crizotinib after short-term administration on metabolic modulators of the heart of diabetic rats. Experimental diabetes mellitus (DM) was induced by streptozotocin (STZ; 80 mg·kg, i.

Impact of improving eating habits and rosmarinic acid supplementation on rat vascular and neuronal system in the metabolic syndrome model.

Decreasing high fat and high carbohydrate intake, together with the administration of natural bioactive drugs, is assumed to have a protective effect in the prevention and amelioration of the metabolic syndrome (MetS). The aim of the study was to evaluate effects of diet improvement and/or a phenolic compound (rosmarinic acid; RA) administration (100 mg/kg per d) on metabolic as well as functional changes of vessels and hippocampus caused by the MetS-like conditions. The MetS-like conditions were induced by a high-fat-fructose diet (HFFD) in Prague hereditary hypertriacylglycerolaemic (HTG) rats.

Complementary Superresolution Visualization of Composite Plant Microtubule Organization and Dynamics.

Microtubule bundling is an essential mechanism underlying the biased organization of interphase and mitotic microtubular systems of eukaryotes in ordered arrays. Microtubule bundle formation can be exemplified in plants, where the formation of parallel microtubule systems in the cell cortex or the spindle midzone is largely owing to the microtubule crosslinking activity of a family of microtubule associated proteins, designated as MAP65s. Among the nine members of this family in , MAP65-1 and MAP65-2 are ubiquitous and functionally redundant.

Disease severity-related alterations of cardiac microRNAs in experimental pulmonary hypertension.

Right ventricular (RV) failure is the primary cause of death in pulmonary arterial hypertension (PAH). We hypothesized that heart-relevant microRNAs, that is myomiRs (miR-1, miR-133a, miR-208, miR-499) and miR-214, can have a role in the right ventricle in the development of PAH. To mimic PAH, male Wistar rats were injected with monocrotaline (MCT, 60 mg/kg, s.

YODA-HSP90 Module Regulates Phosphorylation-Dependent Inactivation of SPEECHLESS to Control Stomatal Development under Acute Heat Stress in Arabidopsis.

Stomatal ontogenesis, patterning, and function are hallmarks of environmental plant adaptation, especially to conditions limiting plant growth, such as elevated temperatures and reduced water availability. The specification and distribution of a stomatal cell lineage and its terminal differentiation into guard cells require a master regulatory protein phosphorylation cascade involving the YODA mitogen-activated protein kinase kinase kinase. YODA signaling results in the activation of MITOGEN-ACTIVATED PROTEIN KINASEs (MPK3 and MPK6), which regulate transcription factors, including SPEECHLESS (SPCH).

Effects of inorganic nitrate in a rat model of monocrotaline-induced pulmonary arterial hypertension.

The nitrate-nitrite-nitric oxide (NO) pathway represents an alternative source of NO generation, which is independent of NO synthase and potentiated by hypoxia. Augmentation of this pathway by dietary nitrate has proven favourable effects in several cardiovascular disease models. However, less is known regarding its potential value in pulmonary arterial hypertension (PAH).