Beneficial Effects of Spirulina Supplementation in the Management of Cardiovascular Diseases.

In recent decades, as a result of rising mortality rates due to cardiovascular diseases (CVDs), there has been a growing urgency to find alternative approaches to conventional pharmaceutical treatment to prevent the onset of chronic diseases. Arthrospira platensis, commonly known as Spirulina, is a blue-green cyanobacterium, classified as a "superfood", used worldwide as a nutraceutical food supplement due to its remarkable nutritional value, lack of toxicity, and therapeutic effects. Several scientific studies have evaluated the cardioprotective role of Spirulina. This article presents a comprehensive review of the therapeutic benefits of Spirulina in improving cardio- and cerebrovascular health. It focuses on the latest experimental and clinical findings to evaluate its antihypertensive, antidiabetic, and antihyperlipidemic properties. The objective is to highlight its potential in preventing and managing risk factors associated with cardiovascular disease (CVD).

α acid fraction from Hop extract exerts an endothelium-derived hyperpolarization vasorelaxant effect through TRPV4 employing the feedforward mechanism of PKCα.

Until now, the beneficial vascular properties of Hop reported in the literature have been mainly attributed to specific compound classes, such as tannins and phenolic acids. However, the potential vascular action of a Hop subfraction containing a high amount of α or ß acids remains completely understood. Therefore, this study aims to investigate the vascular effects of the entire Hop extract and to fraction the Hop extract to identify the main bioactive vascular compounds. A pressure myograph was used to perform vascular reactivity studies on mouse resistance arteries. Phytocomplex fractionation was performed on a semi-prep HPLC system and characterized by UHPLC-PDA-MS/MS coupled to mass spectrometry. Western blot analysis was performed to characterize the phosphorylation site enrolled. The entire Hop extract exerts a direct dose-dependent endothelial vascular action. The B1 subfraction, containing a high concentration of α acids, recapitulates the vascular effect of the crude extract. Its vasorelaxant action is mediated by the opening of Transient Receptor Potential Vanilloid type 4 (TRPV4), potentiated by PKCα, and subsequent involvement of endothelial small-conductance calcium-activated potassium channels (SKCa) and intermediate-conductance calcium-activated potassium channels (IKCa) that drives endothelium-dependent hyperpolarization (EDH) through heterocellular myoendothelial gap junctions (MEGJs). This is the first comprehensive investigation of the vascular function of Hop-derived α acids in resistance arteries. Overall, our data suggest that the B1 subfraction from Hop extracts, containing only α acids, has great potential to be translated into the useful armamentarium of natural bioactive compounds with cardiovascular benefits.

C2CD4B Evokes Oxidative Stress and Vascular Dysfunction via a PI3K/Akt/PKCα-Signaling Pathway.

High glucose-induced endothelial dysfunction is an important pathological feature of diabetic vasculopathy. While genome-wide studies have identified an association between type 2 diabetes mellitus (T2DM) and increased expression of a C2 calcium-dependent domain containing 4B (C2CD4B), no study has yet explored the possible direct effect of C2CD4B on vascular function. Vascular reactivity studies were conducted using a pressure myograph, and nitric oxide and oxidative stress were assessed through difluorofluorescein diacetate and dihydroethidium, respectively. We demonstrate that high glucose upregulated both mRNA and protein expression of C2CD4B in mice mesenteric arteries in a time-dependent manner. Notably, the inhibition of C2CD4B expression by genetic knockdown efficiently prevented hyperglycemia-induced oxidative stress, endothelial dysfunction, and loss of nitric oxide (NO) bioavailability. Recombinant C2CD4B evoked endothelial dysfunction of mice mesenteric arteries, an effect associated with increased reactive oxygen species (ROS) and decreased NO production. In isolated human umbilical vein endothelial cells (HUVECs), C2CD4B increased phosphorylation of endothelial nitric oxide synthase (eNOS) at the inhibitory site Thr495 and reduced eNOS dimerization. Pharmacological inhibitors of phosphoinositide 3-kinase (PI3K), Akt, and PKCα effectively attenuated oxidative stress, NO reduction, impairment of endothelial function, and eNOS uncoupling induced by C2CD4B. These data demonstrate, for the first time, that C2CD4B exerts a direct effect on vascular endothelium via a phosphoinositide 3-kinase (PI3K)/Akt/PKCα-signaling pathway, providing a new perspective on C2CD4B as a promising therapeutic target for the prevention of oxidative stress in diabetes-induced endothelial dysfunction.

Detection of syntonies between multiple spike trains using a coarse-grain binarization of spike count distributions.

At very short timescales neuronal spike trains may be compared to binary streams where each neuron gives at most one spike per bin and therefore its state can be described by a binary variable. Time-averaged activity like the mean firing rate can be generally used on longer timescales to describe the dynamics; nevertheless, enlarging the space of the possible states up to the continuum may seriously bias the true statistics if the sampling is not accurate. We propose a simple transformation on binary variables which allows us to fix the dimensionality of the space to sample and to vary the temporal resolution of the analysis. For each time length interactions among simultaneously recorded neurons are evaluated using log-linear models. We illustrate how to use this method by analysing two different sets of data, recorded respectively in the temporal cortex of freely moving rats and in the inferotemporal cortex of behaving monkeys engaged in a visual fixation task. A detailed study of the interactions is provided for both samples. In both datasets we find that some assemblies share robust interactions, invariant at different time lengths, while others cooperate only at delimited time resolutions, yet the size of the samples is too small to allow an unbiased estimate of all possible interactions. We conclude that an extensive application of our method to larger samples of data, together with the development of techniques to correct the bias in the estimate of the coefficients, would provide significant information about the structure of the interactions in populations of neurons.

Replica-free evaluation of the neuronal population information with mixed continuous and discrete stimuli: from the linear to the asymptotic regime.

Recent studies have explored theoretically the ability of populations of neurons to carry information about a set of stimuli, both in the case of purely discrete or purely continuous stimuli, and in the case of multidimensional continuous angular and discrete correlates, in the presence of additional quenched disorder in the distribution. An analytical expression for the mutual information has been obtained in the limit of large noise by means of the replica trick. Here, we show that the same results can actually be obtained in most cases without the use of replicas, by means of a much simpler expansion of the logarithm. Fitting the theoretical model to real neuronal data, we show that the introduction of correlations in the quenched disorder improves the fit, suggesting a possible role of signal correlations-actually detected in real data-in a redundant code. We show that even in the more difficult analysis of the asymptotic regime, an explicit expression for the mutual information can be obtained without resorting to the replica trick despite the presence of quenched disorder, both with a Gaussian and with a more realistic thresholded-Gaussian model. When the stimuli are mixed continuous and discrete, we find that with both models the information seem to grow logarithmically to infinity with the number of neurons and with the inverse of the noise, even though the exact general dependence cannot be derived explicitly for the thresholded-Gaussian model. In the large noise limit, lower values of information were obtained with the thresholded-Gaussian model, for a fixed value of the noise and of the population size. On the contrary, in the asymptotic regime, with very low values of the noise, a lower information value is obtained with the Gaussian model.

Replica symmetric evaluation of the information transfer in a two-layer network in the presence of continuous and discrete stimuli.

In a previous paper we have evaluated analytically the mutual information between the firing rates of N independent units and a set of multidimensional continuous and discrete stimuli, for a finite population size and in the limit of large noise. Here, we extend the analysis to the case of two interconnected populations, where input units activate output ones via Gaussian weights and a threshold linear transfer function. We evaluate the information carried by a population of M output units, again about continuous and discrete correlates. The mutual information is evaluated solving saddle-point equations under the assumption of replica symmetry, a method that, by taking into account only the term linear in N of the input information, is equivalent to assuming the noise to be large. Within this limitation, we analyze the dependence of the information on the ratio M/N, on the selectivity of the input units and on the level of the output noise. We show analytically, and confirm numerically, that in the limit of a linear transfer function and of a small ratio between output and input noise, the output information approaches asymptotically the information carried in input. Finally, we show that the information loss in output does not depend much on the structure of the stimulus, whether purely continuous, purely discrete or mixed, but only on the position of the threshold nonlinearity, and on the ratio between input and output noise.