Diminazene aceturate uses different pathways to induce relaxation in healthy and atherogenic blood vessels.

Diminazene aceturate (DIZE), a putative angiotensin-converting enzyme 2 (ACE2) activator, elicits relaxation in various animal models. This study aimed to determine the relaxing mechanisms in internal iliac arteries utilised by DIZE in healthy and atherogenic rabbit models. Studies were conducted on internal iliac artery rings retrieved from male New Zealand White rabbits fed a 4-week healthy control (n = 24) or atherogenic diet (n = 20).

Mas-related G protein-coupled receptor type D antagonism improves portal hypertension in cirrhotic rats.

Splanchnic vasodilatation contributes to the development and aggravation of portal hypertension (PHT). We previously demonstrated that in cirrhosis, angiotensin- mediates splanchnic vasodilatation through the Mas receptor (MasR). In this study, we investigated whether the recently characterized second receptor for angiotensin-(1-7), Mas-related G protein-coupled receptor type D (MrgD), contributes to splanchnic vasodilatation in cirrhotic and noncirrhotic PHT.

Mechanisms of Cisplatin-Induced Acute Kidney Injury: Pathological Mechanisms, Pharmacological Interventions, and Genetic Mitigations.

Administration of the chemotherapeutic agent cisplatin leads to acute kidney injury (AKI). Cisplatin-induced AKI (CIAKI) has a complex pathophysiological map, which has been linked to cellular uptake and efflux, apoptosis, vascular injury, oxidative and endoplasmic reticulum stress, and inflammation. Despite research efforts, pharmaceutical interventions, and clinical trials spanning over several decades, a consistent and stable pharmacological treatment option to reduce AKI in patients receiving cisplatin remains unavailable.

Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells?

The occurrence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVD-19), represents a catastrophic threat to global health. Protruding from the viral surface is a densely glycosylated spike (S) protein, which engages angiotensin-converting enzyme 2 (ACE2) to mediate host cell entry. However, studies have reported viral susceptibility in intra- and extrapulmonary immune and non-immune cells lacking ACE2, suggesting that the S protein may exploit additional receptors for infection.

The Anti-Inflammatory Effect of Taurine on Cardiovascular Disease.

Taurine is a non-protein amino acid that is expressed in the majority of animal tissues. With its unique sulfonic acid makeup, taurine influences cellular functions, including osmoregulation, antioxidation, ion movement modulation, and conjugation of bile acids. Taurine exerts anti-inflammatory effects that improve diabetes and has shown benefits to the cardiovascular system, possibly by inhibition of the renin angiotensin system.

Undercarboxylated osteocalcin has no adverse effect on endothelial function in rabbit aorta or human vascular cells.

Undercarboxylated osteocalcin (ucOC) improves glucose metabolism; however, its effects on endothelial cell function are unclear. We examined the biological effect of ucOC on endothelial function in animal models ex vivo and human cells in vitro. Isometric tension and immunohistochemistry techniques were used on the aorta of male New Zealand white rabbits and cell culture techniques were used on human aortic endothelial cells (HAECs) to assess the effect of ucOC in normal and high-glucose environments.

Flavonoids against the Warburg phenotype-concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism.

The Warburg effect is characterised by increased glucose uptake and lactate secretion in cancer cells resulting from metabolic transformation in tumour tissue. The corresponding molecular pathways switch from oxidative phosphorylation to aerobic glycolysis, due to changes in glucose degradation mechanisms known as the 'Warburg reprogramming' of cancer cells. Key glycolytic enzymes, glucose transporters and transcription factors involved in the Warburg transformation are frequently dysregulated during carcinogenesis considered as promising diagnostic and prognostic markers as well as treatment targets.

The Effect of an Atherogenic Diet and Acute Hyperglycaemia on Endothelial Function in Rabbits Is Artery Specific.

Hyperglycaemia has a toxic effect on blood vessels and promotes coronary artery disease. It is unclear whether the dysfunction caused by hyperglycaemia is blood vessel specific and whether the dysfunction is exacerbated following an atherogenic diet. Abdominal aorta, iliac, and mesenteric arteries were dissected from New Zealand White rabbits following either a 4-week normal or atherogenic diet ( = 6-12 per group).

Imipridone enhances vascular relaxation via FOXO1 pathway.

Cardiovascular complications are a side effect of cancer therapy, potentially through reduced blood vessel function. ONC201 (TIC10) is currently used in phase 2 clinical trials to treat high-grade gliomas. TIC10 is a phosphatidylinositol 3-kinase (PI3K)/AKT/extracellular signal-regulated kinase (ERK) inhibitor that induces apoptosis via upregulation of TNF-related apoptosis-inducing ligand, which via stimulation of FOXO and death receptor could increase eNOS upregulation.

Genoprotective activities of plant natural substances in cancer and chemopreventive strategies in the context of 3P medicine.

Severe durable changes may occur to the DNA structure caused by exogenous and endogenous risk factors initiating the process of carcinogenesis. By evidence, a large portion of malignancies have been demonstrated as being preventable. Moreover, the targeted prevention of cancer onset is possible, due to unique properties of plant bioactive compounds.

The Effect of Recombinant Undercarboxylated Osteocalcin on Endothelial Dysfunction.

Low circulating levels of undercarboxylated osteocalcin (ucOC) is associated with a higher risk of cardiovascular disease, yet whether ucOC has a direct effect on endothelium-dependent vasorelaxation, or in proximity to its postulated receptor, the class CG protein-coupled receptor (GPCR6A), in blood vessels remains unclear. Immunohistochemistry and proximity ligation assays were used to localize the presence of ucOC and GPRC6A and to determine the physical proximity (< 40 nm) in radial artery segments collected from patients undergoing coronary artery bypass surgery (n = 6) which exhibited calcification (determined by Von Kossa) and aorta from New Zealand white rabbits exhibiting atherosclerotic plaques. Endothelium-dependent vasorelaxation was assessed using cumulative doses of acetylcholine in vitro on abdominal aorta of rabbits fed a normal chow diet (n = 10) and a 4-week atherogenic diet (n = 9) pre-incubated with ucOC (10 ng/mL) or vehicle.

Melatonin May Increase Anticancer Potential of Pleiotropic Drugs.

Melatonin (N-acetyl-5-methoxytryptamine) is not only a pineal hormone, but also an ubiquitary molecule present in plants and part of our diet. Numerous preclinical and some clinical reports pointed to its multiple beneficial effects including oncostatic properties, and as such, it has become one of the most aspiring goals in cancer prevention/therapy. A link between cancer and inflammation and/or metabolic disorders has been well established and the therapy of these conditions with so-called pleiotropic drugs, which include non-steroidal anti-inflammatory drugs, statins and peroral antidiabetics, modulates a cancer risk too.

Potential Role for Osteocalcin in the Development of Atherosclerosis and Blood Vessel Disease.

There is increasing evidence for the involvement of the skeleton in the regulation of atherosclerotic vascular disease. Osteocalcin, an osteoblast derived protein, exists in two forms, carboxylated and undercarboxylated osteocalcin. Undercarboxylated osteocalcin has been linked to the regulation of metabolic functions, including glucose and lipid metabolism.

Transdermal Delivery of AT1 Receptor Antagonists Reduce Blood Pressure and Reveal a Vasodilatory Effect on Kidney Blood Vessels.

Background: The Renin Angiotensin System (RAS) is pharmacologically targeted to reduce blood pressure, and patient compliance to oral medications is a clinical issue. The mechanisms of action of angiotensin receptor blockers (ARBs) in reducing blood pressure are not well understood and are purported to be via a reduction of angiotensin II signaling.

Objective: We aimed to develop a transdermal delivery method for ARBs (losartan potassium and valsartan) and to determine if ARBs reveal a vasodilatory effect of the novel RAS peptide, alamandine.

Are plant-based functional foods better choice against cancer than single phytochemicals? A critical review of current breast cancer research.

Breast cancer is the most common malignancy in women worldwide. Over 90% of all breast cancer cases are of different 'sporadic' cell types, thus placing emphasis on the need for breast cancer prevention and new effective treatment strategies. In recent years, pre-clinical research provides growing evidence regarding the beneficial action of bioactive plant-derived substances - phytochemicals, on multiple cancer-related biological pathways.

Alamandine reverses hyperhomocysteinemia-induced vascular dysfunction via PKA-dependent mechanisms.

Introduction: Hyperhomocysteinemia (HHcy) impairs nitric oxide endothelium-dependent vasodilation, consequently leading to atherosclerosis, a risk factor for cardiovascular disease. Novel treatments for HHcy are necessary.

Aim: We tested the hypothesis that alamandine, a vasoactive peptide of the renin-angiotensin system (RAS), could reverse HHcy-induced vascular dysfunction through the MrgD receptor and that this is mediated by the protein kinase A (PKA) pathway.

Therapeutical strategies for anxiety and anxiety-like disorders using plant-derived natural compounds and plant extracts.

Anxiety and anxiety-like disorders describe many mental disorders, yet fear is a common overwhelming symptom often leading to depression. Currently two basic strategies are discussed to treat anxiety: pharmacotherapy or psychotherapy. In the pharmacotherapeutical clinical approach, several conventional synthetic anxiolytic drugs are being used with several adverse effects.

HS causes contraction and relaxation of major arteries of the rabbit.

Objective: Cardiovascular disease (CVD) caused by atherosclerosis remains a worldwide burden. Hydrogen sulfide is a promising new therapeutic avenue for the treatment of CVD, however reports show exogenous HS has both vasodilator and vasoconstrictor effects depending on organ examined, and in vitro studies in animal models which are not resistant to developing atherosclerosis are limited. We sought to determine if rabbit arteries constricted or dilated to hydrogen sulfide.

IRAP inhibition using HFI419 prevents moderate to severe acetylcholine mediated vasoconstriction in a rabbit model.

Coronary artery vasospasm (constriction) caused by reduced nitric oxide bioavailability leads to myocardial infarction. Reduced endothelial release of nitric oxide by the neurotransmitter acetylcholine, leads to paradoxical vasoconstriction as it binds to smooth muscle cell M3 receptors. Thus, inhibition of coronary artery vasospasm will improve clinical outcomes.

Angiotensin (1-7) and Alamandine: Similarities and differences.

A primary peptide of the renin angiotensin system (RAS), Angiotensin (Ang) II, is a vasoconstrictor and promotor of atherosclerosis. To counter this, the RAS also consists of peptides and receptors which increase nitric oxide release from the endothelium and decrease nicotinamide adenine dinucleotide phosphate oxidase-related superoxide production. Two peptides, Ang (1-7) and alamandine are vasodilators, by activating the nitric oxide pathway via different receptors in the endothelium.

Caffeine and cardiovascular diseases: critical review of current research.

Caffeine is a most widely consumed physiological stimulant worldwide, which is consumed via natural sources, such as coffee and tea, and now marketed sources such as energy drinks and other dietary supplements. This wide use has led to concerns regarding the safety of caffeine and its proposed beneficial role in alertness, performance and energy expenditure and side effects in the cardiovascular system. The question remains "Which dose is safe?", as the population does not appear to adhere to the strict guidelines listed on caffeine consumption.