Reconfigurable Skyrmion-Based Logic Gates: Versatile Design and Full-Scale Implementation.

Herein, we investigate the behavior of skyrmions within a racetrack design incorporating voltage-controlled magnetic anisotropy (VCMA) gates. Our analysis encompassed multiple forces, including spin currents and anisotropy gradients induced by bias voltages. As a result, the efficient control of skyrmion dynamics was achieved across various VCMA gate configurations. Building upon these findings, we propose an efficient approach to reconfigurable skyrmion logic (RSL) in a thin antiferromagnetic (AFM) film through a versatile design. Our RSL harnesses the selective integration of VCMA, spin-polarized currents, and skyrmion-skyrmion (sky-sky) interactions to implement multiple logic gates, including AND, OR, XOR, NOT, NAND, XNOR, and NOR. The design brings a significant advantage with its simplified fabrication process, making the implementation of the RSL practical and accessible for various applications. Furthermore, the RSL enables seamless dynamic switching between logic gates, thereby enhancing its multifunctionality. Additionally, the strategic incorporation of sky-sky interactions and skyrmion-edge repulsion prominently facilitates the realization of complex gates, such as NAND, XNOR, and NOR gates, that typically require intricate design efforts. Hence, this streamlined integration of RSL, coupled with its adaptability to changing computational needs, underscores its potential as a practical solution for implementing high-functionality skyrmion-based logic gates.

Cardioprotective strategies preserve the stability of respiratory chain supercomplexes and reduce oxidative stress in reperfused ischemic hearts.

Electron leakage from dysfunctional respiratory chain and consequent superoxide formation leads to mitochondrial and cell injury during ischemia and reperfusion (IR). In this work we evaluate if the supramolecular assembly of the respiratory complexes into supercomplexes (SCs) is associated with preserved energy efficiency and diminished oxidative stress in post-ischemic hearts treated with the antioxidant N-acetylcysteine (NAC) and the cardioprotective maneuver of Postconditioning (PostC). Hemodynamic variables, infarct size, oxidative stress markers, oxygen consumption and the activity/stability of SCs were compared between groups. We found that mitochondrial oxygen consumption and the activity of respiratory complexes are preserved in mitochondria from reperfused hearts treated with both NAC and PostC. Both treatments contribute to recover the activity of individual complexes. NAC reduced oxidative stress and maintained SCs assemblies containing Complex I, Complex III, Complex IV and the adapter protein SCAFI more effectively than PostC. On the other hand, the activities of CI, CIII and CIV associated to SCs assemblies were preserved by this maneuver, suggesting that the activation of other cardioprotective mechanisms besides oxidative stress contention might participate in maintaining the activity of the mitochondrial respiratory complexes in such superstructures. We conclude that both the monomeric and the SCs assembly of the respiratory chain contribute to the in vivo functionality of the mitochondria. However, although the ROS-induced damage and the consequent increased production of ROS affect the assembly of SCs, other levels of regulation as those induced by PostC, might participate in maintaining the activity of the respiratory complexes in such superstructures.

Uncoupling Protein Overexpression in Metabolic Disease and the Risk of Uncontrolled Cell Proliferation and Tumorigenesis.

In metabolic diseases such as obesity, metabolic syndrome and type II diabetes, the over-expression of uncoupling proteins (UCPs) in a response to increased reactive oxygen species (ROS) generation by mitochondrial respiratory complexes, and to the excess of free fatty acid (FFA) supply from adipose tissue, may protect cells from oxidative stress, lipotoxicity and in turn from death. UCPs by reducing superoxide anion and H2O2 generation trigger several signals to cell for their adaptation to the lipotoxic microenvironment. In mitochondria, a decrease of cytochrome c (cyt c) and proapoptotic protein release promotes cell survival and proliferation. The altered lipid metabolism also affects cardiolipin susceptibility to the peroxidation, a process involved in the dissociation of cyt c from mitochondrial inner membrane and its release, a key step of apoptosis. Therefore, UCPs by attenuating ROS generation and lipotoxicity may downregulate programmed cell death, a well-known physiological process controlling cell proliferation contributing to uncontrolled cell proliferation and tumorigenesis. In addition, tumor cells over-expressed UCPs, by inhibiting ROS generation acquire resistance to death during pharmacological treatment with oxidative stress drug inducers. Therefore, the aim of this review is to discuss recent findings regarding the role that UCPs play in cell survival by protecting against ROS generation and maintaining bioenergetic metabolism homeostasis to promote cell proliferation.

Medicinal agents and metabolic syndrome.

The definition of the Metabolic Syndrome (MS) has encountered difficulty in reaching a universal consensus although there exists an agreement of its main pathologies which are hypertension, obesity, dyslipidemia, insulin resistance, inflammation and renal damage. The prevalent opinion is that three of those alterations may define the syndrome. The incidence of the MS has increased globally, particularly in the last few years, to the point of being regarded as an epidemic. The treatment of the MS can be approached from different angles, since it may be a multifaceted health problem. A healthy lifestyle, which means the practice of regular exercise is suggested to MS patients. Increasing physical activity has anti-inflammatory effects since there is an inverse association of physical activity and inflammatory biomarker concentrations. An adequate diet is recommended, such as the Mediterranean, which contains fish, tomatoes, garlic, red peppers, olive oil and includes red wine, that is, antioxidants and non-saturated oils. There are also the traditional herbal preparations, used in the alternative medicine. Several therapeutic tools can be used; the most common are the pharmaceutical products to deal with obesity, hypertension, dyslipidemias, diabetes and inflammation. In addition several pharmacological therapies such as non steroidal anti-inflammatory drugs are recommended. Recently new mechanisms of action of statins, fibrates, metformin and thiazolidinediones have demonstrated their anti-inflammatory effect and potential use to treat MS.

Sex hormones, metabolic syndrome and kidney.

In the metabolic syndrome (MS), a condition that associates three or more pathologies such as hypertension, central obesity, type II diabetes, insulin resistance and dyslipidemias, the kidneys are severely affected. The pathological alterations in the kidneys, associated with MS, may be modified by sex hormone levels. In general, estrogens are a protection against the development of cardiovascular and renal diseases in humans and experimental models, but androgens may have an opposite effect. Among the metabolic systems that can be modulated by sex hormones in the kidney, the more important are: renin-angiotensin-aldosterone system, arachidonic acid metabolism, nitric oxide system and renal extra-cellular matrix proteins. These are metabolic pathways normally associated, in order to maintain the most efficient functioning of renal hemodynamics. There is a close interrelationship between sex hormones and some pathways involved in the metabolic syndrome; also pathways can modulate each other. The circulating concentrations of hormones may determine the degree of overall pathological alterations in the syndrome.

Medicinal agents in the metabolic syndrome.

The metabolic syndrome (MS) has become a worldwide health problem. It is difficult for patients to follow a diet/exercise regime that would improve their symptoms, therefore the investigation of agents that may deal with its more serious aspects is an important medical field for research. The cardiovascular consequences associated with the syndrome and some of the therapeutic approaches are discussed. The different agents can be divided into several groups: Inorganic/ organic: Zinc complexes with garlic components as insulino-mimetics; Selenium as antioxidant; Copper, Zinc and Manganese as microcomponents of antioxidant enzymes. Organic: Natural or Synthetic: Glycine is effective in lowering blood pressure, TBARS, intra-abdominal fat tissue and triglycerides in sucrose-fed rats. Pharmaceutical products: Fibrates, Lipid-lowering drugs. Antidiabetics. Anti-gout agents. On the other hand there are natural products such as those of animal origin: Sex hormones (also synthetic) used in the problems of menopause and hypoandrogenism frequently found in the MS, antioxidant Omega-3-oils (fish oils) or Vegetal: for example Digitalis pupurea, century-old cardiovascular medication as well as Magnolia officinalis; Spirulina maxima with beneficial effects as antioxidant and lipid-lowering agent, among others. Prickly Pear Cacti. (Opuntia Ficus- Indica Cochlospermum vitifolium (Willd.) Spreng) whose many properties against diabetes and hypercholesterolemia have been empirically known for many years. Perezone (from Perezia plants, a.k.a. Peonia) described as an antiplatelet aggregating agent. The mixed elements in the Mediterranean diet: Fish, salads (peppers, tomatoes), olive oil, garlic, red wine which combines fish oils, garlic and avocado as well as antioxidants from the rest of its components.

Detection of membrane fluidity in submitochondrial particles of platelets and erythrocyte membranes from Mexican patients with Alzheimer disease by intramolecular excimer formation of 1,3 dipyrenylpropane.

It has been suggested that mitochondrial dysfunction and defects in membrane structure could be implied in AD pathogenesis. The aim of the present work was the study of membrane fluidity in submitochondrial platelet particles and erythrocyte membranes from Mexican patients. Blood samples were obtained from 30 patients with Alzheimer disease and 30 aged-matched control subjects. Membrane fluidity determinations were done using a very low concentration of the fluorescent dipyrenylpropane probe incorporated in both types of membranes. This probe is able to give excimer and monomer fluorescence, therefore it can be used to monitor fluidity changes in biological membranes. The data obtained showed that in submitochondrial particles from AD patients, the excimer to monomer fluorescent intensity ratio was lower (0.231 +/- 0.008) than aged-matched control subjects (0.363 +/- 0.014). Therefore, membrane fluidity was lower in AD samples. On the other hand, we found similar membrane fluidity in erythrocytes from AD patients and aged-matched controls: the fluorescent intensity ratios were 0.312 +/- 0.03 and 0.305 +/- 0.033, respectively. In addition, lipid peroxidation in submitochondrial particles and erythrocyte membranes was higher in AD samples than in aged-matched controls. These data suggest that submitochondrial platelet particles are more sensitive to oxidative stress than erythrocyte membranes.

Effect of an avocado oil-rich diet over an angiotensin II-induced blood pressure response.

We studied the effect of an avocado oil-rich diet on (1) the blood pressure response to angiotensin II (AngII) and (2) the fatty acid composition of cardiac and renal membranes on male Wistar rats. The avocado oil-rich diet induced a slightly higher AngII-induced blood pressure response in the rats as compared to the control rats. In cardiac microsomes, avocado oil induced an increase in oleic acid content (13.18+/-0.33% versus 15.46+/-0.59%), while in renal microsomes, the oil decreased alpha-linolenic acid content (0.34+/-0.02% versus 0.16+/-0.12%), but increased the arachidonic acid proportion (24.02+/-0.54% versus 26.25+/-0.54%), compared to control. In conclusion, avocado oil-rich diet modifies the fatty acid content in cardiac and renal membranes in a tissue-specific manner. The rise in renal arachidonic acid suggests that diet content can be a key factor in vascular responses.

Effect of sucrose addition to drinking water, that induces hypertension in the rats, on liver microsomal Delta9 and Delta5-desaturase activities.

This study was undertaken with the aim of investigating the effect of sucrose addition to the drinking water of rats who were fed with the same diet as a control group, on Delta9- and Delta5-desaturase activities and on the fatty acid composition of serum and liver microsomes. Weanling male Wistar rats had 30% sucrose in their drinking water for 20 weeks. An increase in total calories consumed, visceral fat accumulation, insulin, triglycerides and blood pressure and a decrease in the food intake were observed in the sucrose-fed group as compared with the control group. A decrease in linoleic and alpha-linolenic acid (essential fatty acids) in all serum lipid fractions of sucrose-fed rats was found. This observation correlated with a low food intake by sucrose-fed rats. The conversion of [1 (14)C]-palmitic to [1 (14)C]-palmitoleic acid by Delta9-desaturase activity was increased in sucrose-fed compared with control rats, while the conversion of [1 (14)C]-dihomo-gamma-linolenic acids by Delta5-desaturase activity was depressed. In sucrose-fed as compared to control rats, the proportion of palmitoleic and oleic fatty acids was increased. Arachidonic acid was decreased in sucrose-fed rats. The 1,6-diphenylhexatriene fluorescence polarization of the microsomal membranes was significantly lower in the sucrose-fed group compared to the control group. These results indicate that the sucrose addition to the drinking water of the rats increased microsomal Delta9-desaturase activity and membrane disorder and decreased the activity of the Delta5-desaturase, a key enzyme in the biosynthesis of arachidonic acid, implicated in hypertension.

Possible relationship between altered fatty acid composition of serum, platelets, and aorta and hypertension induced by sugar feeding in rats.

To establish a relationship between alterations in fatty acid metabolism, induced by sugar ingestion, and hypertension, we analyzed fatty acid composition of serum, platelets and aorta in rats which had 30% of sugar in their drinking water for 18-20 weeks, and became hypertensive, hypertriglyceridemic and hyperinsulinemic. The fatty acid composition in sugar-fed as compared with that from control rats was as follows: in serum phospholipids, triglycerides and cholesterol ester fractions, palmitic, palmitoleic, oleic and cis-11-eicosadecaenoic acids were present in a higher proportion. In serum phospholipid fraction linoleic and arachidonic acids were decreased and a significant increase was observed in the proportion of dihomo-gamma-linolenic acid. In the membrane phospholipids of platelets and aorta, higher proportions of palmitoleic and of oleic acids were observed. Differences in fatty acid composition of phospholipids between sugar-fed and control rats are consistent with altered membrane fluidity. Altered membrane function is a potential mechanism involved hypertension in rats in sugar-induced.

Myocardial damage due to ischemia and reperfusion in hypertriglyceridemic and hypertensive rats: participation of free radicals and calcium overload.

OBJECTIVE: In a model of hypertriglyceridemia and hypertension in rats (HTG), induced by adding refined sugar to the animals' drinking water, we investigated the response to an acute stress, such as ischemia and reperfusion. In addition, we examined the contribution of calcium overload and free radical release to the injury caused by the post-ischemic reperfusion in a pathological state compared with the normal state. METHODS: Ischemia was induced in the whole anaesthetized animal, by occlusion of the left coronary artery for 4 min, followed by reperfusion for 6 min. To prevent either calcium overload or lipid oxidative processes during reperfusion, either Ketorolac (KET), a calcium ionophore-like drug, or alpha-Phenyl-N-ter-butyl nitrone (PBN), a spin-trapping agent, was administered beforehand. RESULTS: Ketorolac failed to protect the HTG animals from heart damage, as seen by the incidence of reperfusion dysrhythmias, release of lactate dehydrogenase and creatine kinase to the plasma, and non-recovery of the sinus rhythm. On the other hand, PBN was able to prevent these harmful events in the HTG heart by diminishing lipoperoxidation. CONCLUSIONS: The results suggest that, in HTG animals, the oxidative processes make a major contribution to the reperfusion injury and that the sole protection from calcium overload provided by KET is not sufficient to avoid damage compared with control rats.

In vivo plasma lipid oxidation in sugar-induced rat hypertriglyceridemia and hypertension.

Fe(II) and Fe(III) are required for the catalysis of lipid peroxidation through generation of reactive oxygen species that damage cell membranes. This study investigated the effect of free radicals and lipid peroxidation, induced by intraperitoneal injection of iron-dextran in vivo, in the plasma of the sugar-induced hypertriglyceridemic and hypertensive male and female rats. Lipid peroxidation was measured by the malondialdehyde (MDA) equivalent, using a fluorescence method of 2-thiobarbituric acid reactive substances (TBARS). Iron increased TBARS generation by fourfold (P<.0001) in male control rats and by twofold (P<.01) in female control rats, and the difference between TBARS concentration in female as compared with male animals was statistically significant (P<.05). In the case of the sugar-fed group, iron-dextran produced an increase of TBARS concentration by twofold in both male (P<.001) and female rats (P<.01), and no significant difference in TBARS concentration was observed between sugar-fed female and male rats. The analysis of fatty acid composition by gas chromatography showed a significant diminution of 50% in the proportion of arachidonic acid (C20:4n-6) in the male control group in comparison with the female group (P<.0001). In female control rats, a small diminution in the proportion of C20:4n-6 and in the other polyunsaturated fatty acids was observed (P<.05). A significant difference in the C20:4n-6 proportion was found between the male and female group of control rats. In the sugar-fed group, iron induced a significant diminution of arachidonic acid (P<.001) in both female and male rats in comparison with the sugar-fed group without iron.