The ex vivo effects of hypoxanthine-tricyclano, a synthetic adenosine analogue, on rat left and right atria.

Hypoxanthine-tricyclano is a synthetic adenosine analogue, in which adenine and ribose have been replaced by hypoxanthine and a morpholino-derived tricyclic moiety, respectively. We investigated whether hypoxanthine-tricyclano could influence atrial inotropy and/or chronotropy, two important functions regulated by the A1 receptor, the main adenosine receptor type of the supraventricular myocardium. Paced left atria and spontaneously beating right atria, isolated from male, 30-35 weeks old, Wistar rats, were used.

Exercise Types: Physical Activity Mitigates Cardiac Aging and Enhances Mitochondrial Function via PKG-STAT3-Opa1 Axis.

Although age-related deterioration of the cardiac function is a well-studied area of research, the interventions and their molecular pathways have not yet been fully identified. Since physical activity is a powerful preventive measure against cardiac aging, our study compared the effects of long-term voluntary and forced physical activity with a sedentary group, utilizing an aging rat model characterized by mitochondrial dysfunction that contributes to age-related cardiovascular diseases. Four experimental groups were created: (I) young controls (12-week-old); (II) 18-month-old aged sedentary rats; (III) aged group with free access to running wheels for 6 months; (IV) aged rats subjected to forced physical activity for 6 months.

From Nature to Treatment: The Impact of Pterostilbene on Mitigating Retinal Ischemia-Reperfusion Damage by Reducing Oxidative Stress, Inflammation, and Apoptosis.

Retinal ischemia-reperfusion (I/R) injury is a critical pathogenic mechanism in various eye diseases, and an effective therapeutic strategy remains unresolved. Natural derivatives have recently reemerged; therefore, in our present study, we examined the potential therapeutic effects of a stilbenoid that is chemically related to resveratrol. Pterostilbene, recognized for its anti-inflammatory, anti-carcinogenic, anti-diabetic, and neuroprotective properties, counteracts oxidative stress during I/R injury through various mechanisms.

Effects of voluntary and forced physical exercise on the retinal health of aging Wistar rats.

Aging is accompanied by an increased prevalence of degenerative conditions, including those affecting ocular health, which significantly impact quality of life and increase the burden on healthcare systems. Among these, retinal aging is of particular concern due to its direct link to vision impairment, a leading cause of disability in the elderly. Vision loss in the aging population is associated with heightened risks of cognitive decline, social isolation, and morbidity.

The influence of the way of regression on the results obtained by the receptorial responsiveness method (RRM), a procedure to estimate a change in the concentration of a pharmacological agonist near the receptor.

The receptorial responsiveness method (RRM) enables the estimation of a change in concentration of an (even degradable) agonist, near its receptor, curve fitting to (at least) two concentration-effect (E/c) curves of a stable agonist. One curve should be generated before this change, and the other afterwards, in the same system. It follows that RRM yields a surrogate parameter ("c") as the concentration of the stable agonist being equieffective with the change in concentration of the other agonist.

Assessing the Impact of Influenza Vaccination Timing on Experimental Arthritis: Effects on Disease Progression and Inflammatory Biomarkers.

Numerous studies have indicated a link between vaccines and the exacerbation of autoimmune diseases including rheumatoid arthritis (RA). However, there is no consensus in clinical practice regarding the optimal timing of immunization. Therefore, this study aimed to investigate the impact of the 3Fluart influenza vaccine on the complete Freund's adjuvant (CFA)-induced chronic arthritis rat model and to identify new biomarkers with clinical utility.

Electroretinographical Analysis of the Effect of BGP-15 in Eyedrops for Compensating Global Ischemia-Reperfusion in the Eyes of Sprague Dawley Rats.

Retinal vascular diseases and consequential metabolic disturbances in the eye are major concerns for healthcare systems all around the world. BGP-15, a drug candidate small-molecule [O-(3-piperidino-2-hydroxy-1-propyl) nicotinic amidoxime dihydrochloride], has been formerly demonstrated by our workgroup to be retinoprotective both in the short and long term. Based on these results, the present study was performed to investigate the efficacy of BGP in an eyedrop formulation containing sulfobutylether-β-cyclodextrin (SBECD), which is a solubility enhancer as well.

Therapeutic Aspects of Extract in a Rabbit Model of Atherosclerosis-Associated Diastolic Dysfunction.

This study evaluates the potential therapeutic effects of anthocyanin-rich (sour cherry) extract (PCE) on atherosclerosis-associated cardiac dysfunction, described by the impairment of the NO-PKG (nitric oxide-protein kinase G) pathway and the antioxidant capacity. Initially, a rabbit model of atherosclerotic cardiovascular disease was established by administering a cholesterol-rich diet, enabling the examination of the impact of 9 g/kg PCE on the pre-existing compromised cardiovascular condition. After that, the animals were divided into four groups for 12 weeks: the (1) untreated control group; (2) PCE-administered healthy rabbits; (3) hypercholesterolemic (HC) group kept on an atherogenic diet; and (4) PCE-treated HC group.

Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted Rats.

Multi-target drug candidate BGP-15 has shown cardioprotective and antiarrhythmic actions in diseased models. Here, we investigated the effects of BGP-15 on ECG and echocardiographic parameters, heart rate variability (HRV), and arrhythmia incidence in telemetry-implanted rats, under beta-adrenergic stimulation by isoproterenol (ISO). In total, 40 rats were implanted with radiotelemetry transmitters.

Examination of Preferences for COVID-19 Vaccines in Hungary Based on Their Properties-Examining the Impact of Pandemic Awareness with a Hybrid Choice Approach.

The COVID-19 pandemic has posed a huge challenge to the world in recent years. The development of vaccines that are as effective as possible and accessible to society offers a promising alternative for addressing the problems caused by this situation as soon as possible and to restore the pre-epidemic system. The present study investigated the preferences of residents in Hungary's second-largest city (Debrecen) for the COVID-19 vaccine.

The Novel Cardiac Myosin Activator Danicamtiv Improves Cardiac Systolic Function at the Expense of Diastolic Dysfunction In Vitro and In Vivo: Implications for Clinical Applications.

Recent cardiotropic drug developments have focused on cardiac myofilaments. Danicamtiv, the second direct myosin activator, has achieved encouraging results in preclinical and clinical studies, thus implicating its potential applicability in the treatment of heart failure with reduced ejection fraction (HFrEF). Here, we analyzed the inotropic effects of danicamtiv in detail.

The effect of a long-term treatment with cannabidiol-rich hemp extract oil on the adenosinergic system of the zucker diabetic fatty (ZDF) rat atrium.

Cannabidiol (CBD), the most extensively studied non-intoxicating phytocannabinoid, has been attracting a lot of interest worldwide owing to its numerous beneficial effects. The aim of this study was to explore the effect that CBD exerts on the adenosinergic system of paced left atria isolated from obese type Zucker Diabetic Fatty (ZDF) rats, maintained on diabetogenic rat chow, received 60 mg/kg/day CBD or vehicle gavage for 4 weeks. We found that N6-cyclopentyladenosine (CPA), a relatively stable and poorly transported A1 adenosine receptor agonist, elicited a significantly weaker response in the CBD-treated group than in the vehicle-treated one.

Corrigendum: Improved survival and retinal function of aging ZDF rats in long-term, uncontrolled diabetes by BGP-15 treatment.

[This corrects the article DOI: 10.3389/fphar.2021.

Therapeutic Properties of Ayahuasca Components in Ischemia/Reperfusion Injury of the Eye.

Ischemic eye diseases are major causes of vision impairment. Thus, potential retinoprotective effects of N'N-dimethyltryptamine (DMT) were investigated. To inhibit its rapid breakdown by monoamine-oxidase A (MAO-A) enzyme, DMT was co-administered with harmaline, a β-carboline in the Amazonian Ayahuasca brew.

Cardioprotective Role of BGP-15 in Ageing Zucker Diabetic Fatty Rat (ZDF) Model: Extended Mitochondrial Longevity.

Impaired mitochondrial function is associated with several metabolic diseases and health conditions, including insulin resistance and type 2 diabetes (T2DM), as well as ageing. The close relationship between the above-mentioned diseases and cardiovascular disease (CVD) (diabetic cardiomyopathy and age-related cardiovascular diseases) has long been known. Mitochondria have a crucial role: they are a primary source of energy produced in the form of ATP via fatty acid oxidation, tricarboxylic acid (TCA) cycle, and electron transport chain (ETC), and ATP synthase acts as a key regulator of cardiomyocyte survival.

Nicotinic-acid derivative BGP-15 improves diastolic function in a rabbit model of atherosclerotic cardiomyopathy.

Background And Purpose: The small molecule BGP-15 has been reported to alleviate symptoms of heart failure and improve muscle function in murine models. Here, we investigated the acute and chronic effects of BGP-15 in a rabbit model of atherosclerotic cardiomyopathy.

Experimental Approach: Rabbits were maintained on standard chow (control) or atherogenic diet (hypercholesterolemic) for 16 weeks.

Changes in the SARS-CoV-2 cellular receptor ACE2 levels in cardiovascular patients: a potential biomarker for the stratification of COVID-19 patients.

Angiotensin-converting enzyme 2 (ACE2) is essential for SARS-CoV-2 cellular entry. Here we studied the effects of common comorbidities in severe COVID-19 on ACE2 expression. ACE2 levels (by enzyme activity and ELISA measurements) were determined in human serum, heart and lung samples from patients with hypertension (n = 540), heart transplantation (289) and thoracic surgery (n = 49).

A Body of Circumstantial Evidence for the Irreversible Ectonucleotidase Inhibitory Action of FSCPX, an Agent Known as a Selective Irreversible A Adenosine Receptor Antagonist So Far.

In previous studies using isolated, paced guinea pig left atria, we observed that FSCPX, known as a selective A adenosine receptor antagonist, paradoxically increased the direct negative inotropic response to A adenosine receptor agonists (determined using concentration/effect (E/c) curves) if NBTI, a nucleoside transport inhibitor, was present. Based on mathematical modeling, we hypothesized that FSCPX blunted the cardiac interstitial adenosine accumulation in response to nucleoside transport blockade, probably by inhibiting CD39 and/or CD73, which are the two main enzymes of the interstitial adenosine production in the heart. The goal of the present study was to test this hypothesis.

BGP-15 Inhibits Hyperglycemia-Aggravated VSMC Calcification Induced by High Phosphate.

Vascular calcification associated with high plasma phosphate (Pi) level is a frequent complication of hyperglycemia, diabetes mellitus, and chronic kidney disease. BGP-15 is an emerging anti-diabetic drug candidate. This study was aimed to explore whether BGP-15 inhibits high Pi-induced calcification of human vascular smooth muscle cells (VSMCs) under normal glucose (NG) and high glucose (HG) conditions.

Improved Survival and Retinal Function of Aging ZDF Rats in Long-Term, Uncontrolled Diabetes by BGP-15 Treatment.

Retinal complications of diabetes often lead to deterioration or even loss of vision. This hastens discovery of pharmacological agents able to counterbalance diabetic retinopathy. BGP-15, an emerging small molecule agent, was formerly proven by our workgroup to be retinoprotective on nonobese diabetic animals, Goto-Kakizaki rats.

Compounds with Antiviral, Anti-Inflammatory and Anticancer Activity Identified in Wine from Hungary's Tokaj Region via High Resolution Mass Spectrometry and Bioinformatics Analyses.

(1) Background: Wine contains a variety of molecules with potential beneficial effects on human health. Our aim was to examine the wine components with high-resolution mass spectrometry including high-resolution tandem mass spectrometry in two wine types made from grapes with or without the fungus , or "noble rot". (2) For LC-MS/MS analysis, 12 wine samples (7 without and 5 with noble rotting) from 4 different wineries were used and wine components were identified and quantified.

SIRT1 Activation by L. (Horsetail) Modulates Insulin Sensitivity in Streptozotocin Induced Diabetic Rats.

Background: L., commonly known as field horsetail is a perennial fern of which extracts are rich sources of phenolic compounds, flavonoids, and phenolic acids. Activation of SIRT1 that was shown to be involved in well-known signal pathways of diabetic cardiomyopathy has a protective effect against oxidative stress, inflammatory processes, and apoptosis that are the basis of diseases such as obesity, diabetes mellitus, or cardiovascular diseases.

Negative Inotropic Effect of BGP-15 on the Human Right Atrial Myocardium.

Cardiovascular morbidity and mortality carry great socioeconomic burden worldwide that mandates the development of new, efficacious therapeutic agents with limited adverse effects. O-(3-piperidino-2-hydroxy-1-propyl) nicotinic acid amidoxime (BGP-15) is a known, well-tolerable drug candidate that exerts beneficial effects in several disease models. As BGP-15 has a significant structural similarity with propranolol, it arose that BGP-15 might also have a direct effect on the heart.

Retinoprotection by BGP-15, a Hydroximic Acid Derivative, in a Type II Diabetic Rat Model Compared to Glibenclamide, Metformin, and Pioglitazone.

High blood glucose and the consequential ischemia-reperfusion (I/R) injury damage vessels of the retina, deteriorating its function, which can be clearly visualized by electroretinography (ERG). The aim of the present study was to evaluate the possible retinoprotective effects of systemic BGP-15, an emerging drug candidate, in an insulin resistant animal model, the Goto-Kakizaki rat, and compare these results with well-known anti-diabetics such as glibenclamide, metformin, and pioglitazone, which even led to some novel conclusions about these well-known agents. Experiments were carried out on diseased animal model (Goto-Kakizaki rats).