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The venoarteriolar reflex (VAR) is described as a vasoconstriction occurring in response to an increase in venous transmural pressure. Its underlying mechanisms are still not clarified, particularly the neural pathway that supposedly evokes this reflex. In addition, recent studies have shown that the postural maneuvers that evoke VAR also produce a decrease in contralateral perfusion, which is also poorly understood. Our study aimed to explore the contralateral response to unilateral upper limb dependency and its underlying mechanisms. Fifteen young, healthy subjects (24.1 ± 5.8 y.o.) participated in this study after giving informed consent. While seated, subjects remained for 7 min with both arms at heart level (baseline), after which a random hand was placed 40 cm below the heart level for 5 min (dependency) before resuming the initial position for another 7 min (recovery). Skin perfusion was assessed bilaterally with photoplethysmography, and electrodermal activity (EDA) was assessed in the contralateral hand. During hand dependency, perfusion decreased significantly in both limbs, although it was more pronounced in the dependent limb, corroborating previous reports that unilateral limb dependency evokes a decrease in contralateral perfusion. Transient EDA peaks were detected in the first seconds of the dependency and recovery phases. These results support the participation of the sympathetic nervous system as a mechanism regulating contralateral perfusion during unilateral limb dependency. This sympathetic activation is probably attributed to the postural changes themselves and is likely not related to the VAR.

This paper reflects the results of research analyzing models of multi-attribute decision-making based on fuzzy preference relations. Questions of constructing the corresponding multi-attribute models to deal with quantitative information concomitantly with qualitative information based on experts’ knowledge are considered. Human preferences may be represented within the fuzzy preference relations and by applying diverse other preference formats. Considering this, so-called transformation functions reduce any preference format to fuzzy preference relations. This paper’s results can be applied independently or as part of a general approach to solving a wide class of problems with fuzzy coefficients, as well as within the framework of a general scheme of multi-criteria decision-making under conditions of uncertainty. The considered techniques for fuzzy preference modeling are directed at assessing, comparing, choosing, prioritizing, and/or ordering alternatives. These techniques have served to develop a computing system for multi-attribute decision-making. It has been implemented in the C# programming language, utilizing the “.NET” framework. The computing system allows one to represent decision-makers’ preferences in one of five preference formats. These formats and quantitative estimates are reduced to nonreciprocal fuzzy preference relations, providing homogeneous preference information for decision procedures. This paper’s results have a general character and were applied to analyze power engineering problems.

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(1) Background: Synthetic cannabinoids (SCs) are emerging drugs of abuse sold as ‘K2’, ‘K9’ or ‘Spice’. Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher addiction potential unrelated to the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). Moreover, early cases of intoxication and death related to SCs highlight the inherent danger that may accompany the use of these substances. However, there is limited knowledge of the toxicology of Spice ingredients. This systematic review intends to analyze the toxicity of SCs compounds in Spice/K2 drugs. (2) Methods: Studies analyzing synthetic cannabinoid toxicity and dependence were included in the present review. We searched the PubMed database of the US National Library of Medicine, Google Scholar, CompTox Chemicals, and Web of Science up to May 2022. (3) Results: Sixty-four articles reporting the effects of synthetic cannabinoids in humans were included in our review. Ten original papers and fifty-four case studies were also included. Fourteen studies reported death associated with synthetic cannabinoid use, with AB-CHMINACA and MDMB-CHMICA being the main reported SCs. Tachycardia and seizures were the most common toxicity symptoms. The prevalence of neuropsychiatric symptoms was higher in third-generation SCs. (4) Conclusion: SCs may exhibit higher toxicity than THC and longer-lasting effects. Their use may be harmful, especially in people with epilepsy and schizophrenia, because of the increased risk of the precipitation of psychiatric and neurologic disorders. Compared to other drugs, SCs have a higher potential to trigger a convulsive crisis, a decline in consciousness, and hemodynamic changes. Therefore, it is crucial to clarify their potential harms and increase the availability of toxicology data in both clinical and research settings.

Ginkgo biloba is the oldest living tree species in the world. Despite less than encouraging clinical results, extracts from its leaves are among the most used herbal preparations in the prevention and treatment of cardiovascular diseases. Most data on the efficacy of Ginkgo biloba on cardiovascular disease is from clinical studies, with few results from healthy subjects. This paper aims to provide a comprehensive review of the mechanisms underlying the known beneficial cardiovascular activities of Ginkgo biloba. It displays myocardial suppressant and vasorelaxant activities ex vivo, potentiating endothelial-dependent and -independent pathways. It improves perfusion in different vascular beds, namely ocular, cochlear, cutaneous, cerebral, and coronary. Although scarce, evidence suggests that Ginkgo biloba displays a heterogeneous effect on tissue perfusion which is dependent on the individual elimination pathways. It displays an acceptable safety profile, with most reported adverse reactions constituting rare occurrences. Collectively, Ginkgo biloba positively impacts cardiovascular physiology, improving hemodynamics and organ perfusion. In the future, better controlled clinical studies should be performed in order to identify the target populations who may benefit the most from pharmacotherapeutic interventions involving Ginkgo biloba.

Lemongrass (Cymbopogon citratus (DC) Stapf) is a herb commonly used in folk medicine for many purposes. However, its anti-hypertensive potential has not yet been thoroughly studied. This paper reviews the anti-hypertensive effects of both lemongrass and its main compound citral in in vitro, ex vivo, preclinical and clinical studies. Lemongrass essential oil contains terpenes and their derivatives, whereas extracts contain different classes of polyphenols. Both citral and lemongrass display vasorelaxant activity ex vivo, acting by the promotion of endothelial nitric oxide/prostanoids secretion together with the blockage of calcium channels in the vascular smooth muscle. Citral also displays a negative chronotrope effect, probably due to a centrally mediated enhancement of parasympathetic activity. In both healthy and hypertensive animals, the acute administration of lemongrass results in a decrease in blood pressure, sometimes accompanied by a compensatory increase in heart rate. Similarly, in healthy and hypertensive human subjects, the consumption of lemongrass tea decreases blood pressure. Additionally, a weak/moderate diuretic activity has also been reported in animals and humans, although the mechanisms of action remain elusive. Future preclinical studies are necessary to identify other compounds with anti-hypertensive activity and additional pharmacological pathways. Although well tolerated, the safety profile of lemongrass should be better characterized.

Microcirculation in vivo has been assessed using non-invasive technologies such as laser Doppler flowmetry (LDF). In contrast to chronic hyperglycemia, known to induce microvascular dysfunction, the effects of short-term elevations in blood glucose on microcirculation are controversial. We aimed to assess the impact of an oral glucose load (OGL) on the cutaneous microcirculation of healthy subjects, quantified by LDF and coupled with wavelet transform (WT) as an interpretation tool. On two separate occasions, sixteen subjects drank either a glucose solution (75 g in 250 mL water) or water (equal volume). LDF signals were obtained in two anatomical sites (forearm and finger pulp) before and after each load (pre-load and post-load, respectively), in resting conditions and during post-occlusive reactive hyperemia (PORH). The WT allowed decomposition of the LDF signals into their spectral components (cardiac, respiratory, myogenic, sympathetic, endothelial NO-dependent). The OGL blunted the PORH response in the forearm, which was not observed with the water load. Significant differences were found for the cardiac and sympathetic components in the glucose and water groups between the pre-load and post-load periods. These results suggest that an OGL induces a short-term subtle microvascular impairment, probably involving a modulation of the sympathetic nervous system.

(1) Background: Cardiovascular disease (CVD) is a major public health concern worldwide and a key cause of morbidity and mortality in developed countries. Accumulating evidence shows that several CVD forms are characterized by significant microcirculatory dysfunction, which may both cause and be caused by macrovascular disease, often preceding clinical manifestations by several years. Therefore, interest in exploring food supplements to prevent and restore microcirculation has grown. Given the continuous need to expand the available therapeutic arsenal for CVD, the food supplements market has recently grown and is expected to continue growing. (2) Methods: We provide an authoritative up-to-date comprehensive review of the impact of food supplementation on microcirculation by analyzing the European and American legal food supplements framework and the importance of food safety/food quality in this industry. We review the main literature about food bioactive compounds with a focus on microcirculation and some main food supplements with proven benefits. (3) Results: Despite a lack of scientific evidence, diet and microcirculatory function are clearly connected. The main food supplement examples in the literature with potential beneficial effects on microcirculation are: Ruscus aculeatus L., Centella asiatica L., Ginkgo biloba L., Salvia miltiorrhiza Bunge, Crataegus spp., Ginseng, Mangifera indica L., Aesculus hippocastanum L., Hamamelis virginiana L., and Vitis vinifera L. (4) Conclusions: Further clinical trials are necessary to better explore the effects of these food supplements.

Periodontal disease consists in highly prevalent wide-ranging inflammatory conditions that affect the supporting apparatus of teeth. Tobacco use is the most important risk factor for periodontal disease as it increases disease severity and periodontal surgery complications. Tobacco use is harmful for the vasculature by causing microvascular dysfunction, which is known to negatively affect periodontal disease. To the author’s knowledge this paper is the first comprehensive review on the mechanisms by which tobacco use affects oral microcirculation and impacts the pathophysiology of periodontal disease. In healthy subjects, acute nicotine administration or tobacco use (smoking/smokeless forms) increases the blood flow in the oral mucosa due to local irritation and increased blood pressure, which overcome neural- and endocrine-mediated vasoconstriction. Chronic tobacco smokers display an increased gingival microvascular density, which is attributed to an increased capillary recruitment, however, these microcirculatory units show higher tortuosity and lower caliber. These morphological changes, together with the repetitive vasoconstrictive insults, contribute to lower gingival perfusion in chronic smokers and do not completely regress upon smoking cessation. In periodontal disease there is considerable gingival inflammation and angiogenesis in non-smokers which, in chronic smokers, are considerably suppressed, in part due to local immune suppression and oxidative stress. Tobacco exposure, irrespective of the form of use, causes long-term microvascular dysfunction that increases the risk of complications due to the natural disease course or secondary therapeutic strategies.

The aim of this study is to investigate the underlying mechanisms of the venoarteriolar reflex (VAR) in type 2 diabetes mellitus (T2DM), with and without peripheral neuropathy. Laser Doppler flowmetry (LDF) recordings were performed on the medial malleus and dorsal foot skin, before and during leg dependency in healthy controls, in persons with obesity, in those with T2DM, in those with T2DM and subclinical neuropathy, and in those with T2DM and confirmed neuropathy. LDF recordings were analyzed with the wavelet transform to evaluate the mechanisms controlling the flowmotion (i.e., endothelial nitric oxide-independent and -dependent, neurogenic, myogenic, respiratory and cardiac mechanisms). Skin blood perfusion decreased throughout leg dependency at both sites. The decrease was blunted in persons with confirmed neuropathy compared to those with T2DM alone and the controls. During leg dependency, total spectral power increased in all groups compared to rest. The relative contribution of the endothelial bands increased and of the myogenic band decreased, without differences between groups. Neurogenic contribution decreased in controls, in persons with obesity and in those with T2DM, whereas it increased in subclinical- and confirmed neuropathy. In conclusion, this study provides evidence that confirmed diabetic neuropathy alters the VAR through the neurogenic response to leg dependency.

Owing to its chemical richness, propolis has a myriad of therapeutic properties. To the authors’ knowledge, this is the first comprehensive review paper on propolis to focus exclusively on its major effects for cardiovascular health. The propolis compound varieties with the most promising therapeutic benefits and their respective physiological mechanisms will be discussed. Propolis displays an anti-atherosclerotic activity, attained through modulation of the plasma lipid profile and through stabilization of the fatty plaque by inhibiting macrophage apoptosis, vascular smooth muscle proliferation and metalloproteinase activity. The antihypertensive effects of propolis probably arise through the combination of several mechanisms, including the suppression of catecholamine synthesis, stimulation of endothelium-dependent vasorelaxation and vascular anti-inflammatory activity. The anti-hemostatic activity of propolis is attributed to the inhibition of platelet plug formation and antifibrinolytic activity. By inhibiting the secretion of proangiogenic factors, propolis suppresses endothelial cell migration and tubulogenesis, exerting antiangiogenic activity. The antioxidant and anti-inflammatory activities are responsible for protection against vascular endothelial and cardiomyocyte dysfunction, mostly by the prevention of oxidative stress. Among the reviewed propolis varieties, the Brazilian green and red varieties show the largest number of beneficial activities. Further research, especially preclinical, should be conducted to assess the cardiovascular benefits of the given varieties with different compositions.

Isoflavones are phytoestrogen compounds with important biological activities, including improvement of cardiovascular health. This activity is most evident in populations with a high isoflavone dietary intake, essentially from soybean-based products. The major isoflavones known to display the most important cardiovascular effects are genistein, daidzein, glycitein, formononetin, and biochanin A, although the closely related metabolite equol is also relevant. Most clinical studies have been focused on the impact of dietary intake or supplementation with mixtures of compounds, with only a few addressing the effect of isolated compounds. This paper reviews the main actions of isolated isoflavones on the vasculature, with particular focus given to their effect on the determinants of blood pressure regulation. Isoflavones exert vasorelaxation due to a multitude of pathways in different vascular beds. They can act in the endothelium to potentiate the release of NO and endothelium-derived hyperpolarization factors. In the vascular smooth muscle, isoflavones modulate calcium and potassium channels, leading to hyperpolarization and relaxation. Some of these effects are influenced by the binding of isoflavones to estrogen receptors and to the inhibition of specific kinase enzymes. The vasorelaxation effects of isoflavones are mostly obtained with plasma concentrations in the micromolar range, which are only attained through supplementation. This paper highlights isolated isoflavones as potentially suitable alternatives to soy-based foodstuffs and supplements and which could enlarge the current therapeutic arsenal. Nonetheless, more studies are needed to better establish their safety profile and elect the most useful applications.

Mints have been among the most widely used herbs for medicinal purposes since ancient civilizations. They are still presently used for numerous purposes, including non-medicinal, which makes them economically relevant herbs. Information regarding the medical and scientific uses given to mints throughout history are vastly scattered and/or incomplete. The aim of this paper is to provide an extensive descriptive overview of the medical uses given to these herbs, highlighting both the authors in medical culture responsible for their dissemination, as well as their major galenic formulations. Databases on medical science, reference textbooks on medical history, botanics (aromatic herbs), and pharmacognosy were consulted. The use of mints remotes to Classical Antiquity, with major contributions from Pliny the Elder. In the Middle Ages, the increased knowledge surrounding mints came from Byzantine physicians, while, in the Modern Age, technological developments allowed the production of mint-based products which have become part of elaborate galenic formulas employed by an increasing number of physicians, as well as have also stimulated both scientific and artistic interests alike. In present-day medicine, several mints and mint-based products are being researched as potential therapeutic alternatives for many diseases, while also being vastly employed in food and cosmetic industries.

A variety of animal models exist for the study of cardiovascular function using many approaches from surgically induced ischemia to genetic manipulation. A murine physiological model was recently proposed for the non-invasive study of peripheral circulation and was strengthened by the wavelet transform analysis (WA) of laser Doppler flowmetry (LDF) signals. WA allows the extraction of cardiac, respiratory, sympathetic, endothelial, and myogenic components from the raw LDF signal. The present study was designed to evaluate the discernment capacity of the model through an analysis of the short-term effects of the well-known hypotensive cardiovascular drug, atenolol. Six male C57/BL6 mice (16 weeks old) were included in the study, with each animal serving as its own control. Following anesthesia with ketamine-xylazine, skin perfusions were continuously assessed in both hindlimbs by LDF during baseline and after two sequential atenolol administrations (2.5 and 5.0 mg/kg, as commonly prescribed). Expected atenolol-induced hypotension was present, associated with a significantly increased heart rate and peripheral perfusion with both dosages. Through the application of WA to the LDF signal, we could detail the mechanisms of the atenolol-induced peripheral perfusion modulation: an immediate amplitude decrease of the cardiac LDF spectrum with an amplitude increase of the sympathetic component (p < 0.05) and the endothelial and myogenic components (non-significant). These data suggested a regulatory crosstalk between the peripheral (baroreceptors) and the microcirculatory units, which ultimately resulted in hypotension, inotropic reduction, and tachycardia. In conclusion, WA offered insight that simply could not be seen with only the perfusion curve and, thus, was an effective tool to investigate this cardiovascular mechanism of regulation.

The quantitative assessment of cardiovascular functions is particularly complicated, especially during any physiological challenge (e.g., exercise), with physiological signals showing intricate oscillatory properties. Signal complexity is one of such properties, and reflects the adaptability of the physiological systems that generated them. However, it is still underexplored in vascular physiology. In the present study, we calculate the complexity of photoplethysmography (PPG) signals and their frequency components obtained with the wavelet transform (WT), with two analytical tools—(i) texture analysis (TA) of WT scalograms, and (ii) multiscale entropy (MSE) analysis. PPG signals were collected from twelve healthy young subjects (26.0 ± 5.0 y.o.) during a unilateral leg lowering maneuver to evoke the venoarteriolar reflex (VAR) while lying supine, with the contralateral leg remaining stationary. Results showed that TA was able to detect a decrease in complexity, viewed as an increase in texture entropy (TE), of the PPG scalograms during VAR, similarly to MSE, suggesting that a decrease in the competence of vascular regulation mechanisms might be present during VAR. Nonetheless, TA showed lower sensitivity than MSE for low frequency spectral regions. TA seems to be a promising and straightforward analytical tool for the assessment of the complexity of PPG perfusion signals.

The peel represents a significant portion of the araticum fruit (about 40%), which becomes waste after its consumption or processing. Previous studies have shown that the araticum peel is rich in phenolic compounds; however, little is known about the ideal conditions for recovering these compounds. Therefore, response surface methodology, using a central composite rotatable design, was employed to optimize the extraction process to maximize the total phenolic compounds (TPCs) and enhance the Trolox equivalent antioxidant capacity (TEAC) from araticum peel. The variables optimized were ethanol concentration (EC; 20–80%, v/v), extraction time (ET; 5–45 min), and solid–solvent ratio (SSR; 10–100 mg/mL). Additionally, condensed tannins, antioxidant capacity against synthetic free radicals (TEAC and FRAP) and reactive oxygen species (ROS), and the phenolic compounds profile, were evaluated. Optimum extraction conditions were 50% (v/v) ethanol concentration, 5 min of extraction time, and 10 mg/mL solid–solvent ratio. Under these conditions, experimental TPCs and TEAC values were 70.16 mg GAE/g dw and 667.22 µmol TE/g dw, respectively, comparable with predicted models (68.47 mg GAE/g dw for TPCs and 677.04 µmol TE/g dw for TEAC). A high condensed tannins content (76.49 mg CE/g dw) was also observed and 12 phenolic compounds were identified, predominantly flavonoids (97.77%), including procyanidin B2, epicatechin, and catechin as the major compounds. Moreover, a potent antioxidant activity was observed against synthetic free radicals and ROS, especially in scavenging peroxyl and hydroxyl radicals. From this study, we obtained the ideal conditions for recovering phenolic compounds from araticum peel using a simple, fast, sustainable, and effective method, offering a promising opportunity for the management of this plant byproduct.

Cutaneous melanoma is an aggressive type of skin cancer that is recognized for its high metastatic potential and the challenges it presents in its treatment. There has been increasing interest in plant extracts and their potential applications in melanoma. The present study aimed to investigate the content of individual phenolic compounds in araçá-boi extract, evaluate their antioxidant activity, and explore their effects on cell viability, migration properties, oxidative stress levels, and protein expression in the human metastatic melanoma cell line SK-MEL-28. HPLC-DAD analysis identified 11 phenolic compounds in the araçá-boi extract. Trans-cinnamic acid was the main phenolic compound identified; therefore, it was used alone to verify its contribution to antitumor activities. SK-MEL-28 melanoma cells were treated for 24 h with different concentrations of araçá-boi extract and trans-cinnamic acid (200, 400, 600, 800, and 1600 µg/mL). Both the araçá-boi extract and trans-cinnamic acid reduced cell viability, cell migration, and oxidative stress in melanoma cells. Additionally, they modulate proteins involved in apoptosis and inflammation. These findings suggest the therapeutic potential of araçá-boi extract and its phenolic compounds in the context of melanoma, especially in strategies focused on preventing metastasis. Additional studies, such as the analysis of specific signaling pathways, would be valuable in confirming and expanding these observations.