Search Results (474)

Background: Resistance exercise (RE) is recognized for promoting the development of muscle strength and mass, as well as contributing positively to cardiovascular health. The combination of this type of exercise with the intake of foods rich in bioactive compounds, such as camu-camu (Myrciaria dubia), and creatine supplementation may be an interesting strategy to enhance the cardiovascular system. Objective: This study aimed to evaluate the effects of RE and supplementation with camu-camu and creatine on oxidative balance, mineral content, ATPase enzyme activity, and histological changes in the heart of Wistar rats. Methods: Forty-eight adult rats were divided into eight groups, with or without RE. The groups received a control diet (AIN-93M), camu-camu (200 mg/kg/day), creatine (300 mg/kg for 7 days and 50 mg/kg/day thereafter), or a combination of both. The RE protocol was performed on a vertical ladder three times a week for eight weeks. At the end, the animals were anesthetized and euthanized for tissue collection. Results: The trained control group that received a standard diet (AIN-T) showed greater activity of superoxide dismutase and catalase. The trained group receiving creatine and camu-camu supplementation (CC + Cr-T) showed higher total antioxidant capacity (FRAP), increased Mg²⁺-ATPase activity, higher nitric oxide levels, and a greater diameter of cardiac muscle fibers. No pathological changes were observed in heart histology in any group, indicating preservation of tissue integrity. Conclusions: RE associated with camu-camu and creatine supplementation may be an effective strategy for modulating antioxidant and functional aspects of the heart. Full article

Cardio-kidney-metabolic (CKM) syndrome represents an integrated clinical and molecular continuum encompassing metabolic dysfunction, cardiovascular disease and chronic kidney disease. This multidimensional disorder arises from interdependent biological pathways that extend beyond conventional risk factors. Emerging evidence highlights a group of adipokines and vascular modulators—including retinol-binding protein 4 (RBP4), lipocalin 2 (LCN2), apolipoprotein M (ApoM), Klotho and matrix Gla protein (MGP)—emerging molecular modulators with potential involvement in CKM pathophysiology. Pro-inflammatory adipokines such as RBP4 and LCN2 contribute to insulin resistance, oxidative stress and endothelial dysfunction. In contrast, protective molecules including ApoM and Klotho preserve nitric oxide bioavailability, lipid metabolism and antioxidant defense. MGP modulates vascular calcification and adipose remodeling, with its inactive form (dp-ucMGP) linked to vascular stiffness and renal decline. The combined dysregulation of these molecules sustains cycles of inflammation, oxidative stress and tissue remodeling that drive CKM progression. Collectively, current data support their dual role as biomarkers and therapeutic targets. Nonetheless, clinical translation remains limited, emphasizing the need for standardized assays, longitudinal validation, and integrative multimarker approaches within precision medicine frameworks for CKM syndrome. Full article

The small GTPase RhoA and its downstream effector Rho-kinase (ROCK) have emerged as pivotal regulators of vascular smooth muscle cell (VSMC) contraction, endothelial function, and vascular remodeling. Activation of the RhoA/ROCK pathway enhances calcium (Ca²⁺) sensitivity by inhibiting myosin light chain phosphatase (MLCP), thereby promoting sustained vascular tone independent of intracellular Ca²⁺ levels. In endothelial cells (ECs), RhoA/ROCK signaling contributes to nitric oxide (NO) dysregulation, oxidative stress, cytoskeletal reorganization, and inflammatory activation. Cumulative evidence implicates this pathway in the development and progression of hypertension and other cardiovascular diseases, where maladaptive vascular remodeling, VSMC proliferation, and endothelial dysfunction drive increased vascular resistance. Translational studies have identified ROCK inhibitors and indirect modulators such as statins as promising therapeutic strategies. This review integrates recent mechanistic insights into RhoA/ROCK regulation of vascular function with clinical and translational perspectives on targeting this pathway in hypertension. Full article

Combined oral contraceptives (COCs) remain one of the most popular reversible contraceptive methods worldwide. Still, regardless of the drug composition and duration of therapy, almost all COCs are associated with the risk of venous thrombosis. This review highlights the main pathogenetic mechanisms of thrombosis development during oral contraceptive use. Increase the production of certain clotting factors; a decrease in antithrombin and protein S levels; acquired resistance to activated protein C; a reduction in tissue factor pathway inhibitor (TFPI); indirect endothelial activation; inhibition of endogenous fibrinolysis; regulation of tissue factor by estradiol-sensitive microRNA; homocysteine imbalance caused by decreased intestinal reabsorption of folates and vitamin B-12; reduced bioavailability of nitric oxide (NO) due to high homocysteine levels; higher blood pressure, water retention, insulin resistance, increased levels of pro-inflammatory C-reactive protein (CRP) and uric acid, and antifibrinolytic (plasminogen activator inhibitor 1 type, PAI-1) biomarkers as consequences of NO deficiency; increased platelet adhesiveness and ADP-induced aggregation, which promote fibrinogen binding; and increased expression of pro-inflammatory cytokines are the main thrombotic effects of COCs use. Clinicians should carefully evaluate each patient’s individual risk factors when prescribing COCs and conduct regular monitoring to reduce the risk of complications. Full article

This study investigated how exogenous 2,4-epibrassinolide (EBR) and nitric oxide (NO) enhance the tolerance of cucumber (Cucumis sativus L.) seedlings to NaHCO₃-induced alkaline stress under hydroponic conditions. NaHCO₃ exposure caused severe sodium toxicity, reactive oxygen species (ROS) accumulation, and photosynthetic inhibition, which, together, suppressed plant growth. Treatments with either EBR or NO significantly improved plant performance by alleviating these adverse effects. Both regulators enhanced the ROS scavenging system, maintained ionic homeostasis, and alleviated sodium toxicity. They also stimulated the activities of vacuolar H⁺-ATPase, H⁺-PPase, and plasma membrane H⁺-ATPase, and increased the accumulation of citric and malic acids, thereby sustaining higher photosynthetic efficiency under stress conditions. qRT-PCR analysis further revealed that EBR and NO upregulated SOS1 and NHX2 (sodium transporters) as well as PIP1;2 and PIP2;4 (aquaporins), confirming their involvement in ionic and osmotic regulation. Pharmacological experiments showed that application of NO synthesis inhibitors, including tungstate and L-NAME, as well as the NO scavenger cPTIO, markedly weakened the protective effects of EBR. In contrast, application of the brassinosteroid biosynthesis inhibitor brassinazole (BRz) only had a limited effect on NO-mediated stress tolerance. Collectively, these findings demonstrate that NO functions as a downstream signaling mediator of EBR, coordinating multiple defense pathways including photosynthetic regulation, antioxidant protection, ion balance, aquaporin activity, and organic acid metabolism to enhance cucumber resistance to alkaline stress. Full article

As an important bioactive signaling molecule, nitric oxide (NO) participates in the responses of plants to various environmental stresses. The aim of this study was to investigate the influence of exogenous NO on the growth and cadmium (Cd) accumulation of alfalfa (Medicago sativa) during early growth. The results showed that Cd significantly inhibited alfalfa seedling growth and induced membrane lipid peroxidation. Addition of sodium nitroprusside (SNP, as an NO donor) significantly promoted seedling growth and induced the mobilization of seed photosynthate reserves, leading to an increase in total soluble sugar (SS) and reducing sugar (RS) contents. Application of SNP mitigated membrane peroxidation damage caused by Cd stress by enhancing catalase (CAT), ascorbate peroxidase (APX), superoxide dismutase (SOD) and peroxidase (POD) activities in order to eliminate reactive oxygen species (ROS), thereby improving Cd resistance and increasing Cd accumulation in alfalfa. This promoting effect of SNP depended on its concentration; the most optimal SNP concentration to promote the growth and Cd absorption of alfalfa under Cd stress was found to be 200 µM. The fresh weight (FW), dry weight (DW) and Cd accumulation of seedlings treated with 200 µM SNP increased significantly by 23.10%, 30.32% and 82.50%, respectively, on the fifth day, compared with the Cd-only treatment. Full article

Cyclic lipopeptides (CLPs), produced by beneficial rhizobacteria such as Bacillus and Pseudomonas species, are specialized metabolites retaining key functions for the plant protective activity of the producers, which shows their potential as biocontrol agents in agriculture. Beyond their strong antimicrobial properties, CLPs can act as potent elicitors of plant immunity and systemic resistance. However, the molecular mechanisms underlying these immune-modulatory effects and the role of CLPs’ structural diversity remain poorly understood. Here, we demonstrate that specific structural features of surfactin-type CLPs critically influence their ability to trigger early immune responses in plants, including reactive oxygen species bursts, nitric oxide (NO) production, calcium fluxes, and systemic resistance. In Arabidopsis thaliana roots, we show that surfactin-induced NO generation requires calcium signaling. Moreover, we reveal that contrasting immune effects of CLPs may stem from the ecological lifestyles of their microbial producers, shedding light on the evolutionary basis of plant–microbe interactions. Altogether, our findings underscore the importance of CLP structural variation in shaping plant defense responses and highlight the potential for structure-informed design of next-generation biosourced small molecules with broad-spectrum efficacy as plant protectants. Full article

Obesity is characterized by chronic low-grade inflammation, largely driven by macrophage infiltration into adipose tissue, which contributes to the development of insulin resistance. All-trans retinoic acid (ATRA), a biologically active metabolite of vitamin A, has demonstrated anti-inflammatory properties. This study examined the effects of ATRA on inflammation and insulin resistance using a coculture model comprising hypertrophied 3T3-L1 adipocytes and RAW264.7 macrophages. Coculture markedly elevated the production of pro-inflammatory mediators—including nitric oxide, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and interleukin-6—and increased free fatty acid release while suppressing the secretion of anti-inflammatory adiponectin. Treatment with ATRA (0.1, 1, and 10 μM) significantly reversed these coculture-induced alterations (p < 0.001). ATRA also inhibited the nuclear translocation of NF-κB and downregulated the expression of retinol-binding protein 4 (RBP4). Moreover, ATRA improved insulin-stimulated glucose uptake in adipocytes rendered insulin-resistant by coculture (p < 0.01), an effect associated with the restoration of glucose transporter 4 (GLUT4) and insulin receptor substrate-2 (IRS-2) expression. These findings suggest that ATRA effectively mitigates inflammation and insulin resistance arising from adipocyte–macrophage interactions, highlighting its potential as a therapeutic agent for obesity-related metabolic disorders. Full article

Background: L-arginine is a conditionally essential amino acid that serves as a substrate for nitric oxide synthase and regulates energy metabolism. While its ergogenic effects have been proposed, the mechanisms underlying its anti-fatigue properties are not fully understood. Methods: Male ICR mice were orally administered L-arginine (300, 600, or 1200 mg/kg bw/day) for 28 days. Fatigue was chronically induced using twice-weekly forced swimming or treadmill running, and fatigue resistance was then assessed under these paradigms. Blood, skeletal muscle, and liver were analyzed for biomarkers including glucose, lactate, LDH, CPK, NEFA, ammonia, glycogen, nitric oxide, cortisol, and antioxidant enzymes. In parallel, C2C12 myoblasts were treated with L-arginine under proliferative and differentiated conditions to assess hexokinase (HK) activity, myogenin expression, and ROS generation. Results: In vivo, L-arginine decreased serum LDH, CPK, NEFA, ammonia, nitric oxide, and cortisol, while enhancing blood glucose and glycogen storage in both muscle and liver. Forced swimming reduced serum lactate, whereas treadmill exercise elevated intramuscular lactate, suggesting context-dependent lactate regulation. Importantly, L-arginine did not significantly improve forced-swimming immobility time, whereas treadmill time-to-exhaustion increased at the highest dose. Antioxidant responses were improved, as reflected by normalized hepatic catalase activity. In vitro, L-arginine increased HK activity, promoted myogenin expression, and reduced ROS levels, supporting improved glucose utilization, muscle differentiation, and oxidative stress resistance. Conclusions: These findings demonstrate that L-arginine supplementation under chronic fatigue-inducing paradigms improves endurance and alleviates fatigue by enhancing energy metabolism, preserving glycogen, reducing muscle injury, and attenuating oxidative stress. L-arginine shows potential as a functional ingredient for promoting exercise performance and recovery. Full article

Aging, one of the main factors associated with cardiovascular diseases, induces vascular modifications through nitric oxide (NO) release and oxidative stress. Based on the antioxidant properties of the non-enzymatic spirulina extract (non-Enz-Spir-E) and that degrading enzymes enhances the extract bioactivity, the aim of this study was to analyze the in vitro effect of an Alcalase-assisted Enz-Spir-E on the vasodilator function of conduit and resistance arteries (which differently contribute to blood pressure regulation) in aging. Therefore, thoracic aorta (TA) and mesenteric arteries (MA) from male Sprague–Dawley rats (20–22 months-old) were divided into two groups: non-incubated vessels and vessels exposed to Enz-Spir-E (0.1% w/v) for 3 h. The vasodilation to acetylcholine (ACh), sodium nitroprusside (SNP, a NO donor), carbon-monoxide-releasing molecule (CORM), and cromakalim (a potassium channel opener), as well as NO and superoxide anion production, were studied. Enz-Spir-E increased the ACh-, SNP-, and CORM-induced responses in both types of arteries, while the cromalakim-induced relaxation was increased only in MA. Enz-Spir-E increased NO release (TA: 5.69-fold; MA: 1.79-fold), while it reduced superoxide anion formation (TA: 0.52-fold; MA: 0.66-fold). These results indicate that Enz-Spir-E improves aging-associated vasodilation through increasing NO release/bioavailability in both types of arteries and hyperpolarizing mechanisms only in MA. Full article

The nitric oxide (NO) pathway is a fundamental regulator of vascular tone, myocardial function, and inflammation. In heart failure (HF), especially in advanced stages, dysregulation of NO–soluble guanylate cyclase (sGC)–cyclic guanosine monophosphate (cGMP) signaling contributes to endothelial dysfunction, increased vascular resistance, myocardial fibrosis, and impaired cardiac performance. Chronic inflammation further reduces NO bioavailability, exacerbating HF progression This review synthesizes current knowledge on the role of the NO pathway in HF pathophysiology, with a focus on stable and advanced HF. Special attention is given to patient subgroups with comorbidities such as chronic kidney disease, where modulation of NO signaling may be particularly beneficial. We also evaluate therapeutic strategies targeting NO bioavailability and sGC stimulation. Evidence shows that impaired NO signaling promotes systemic and pulmonary vasoconstriction, elevates ventricular afterload, and worsens cardiac remodeling. Pharmacological agents that restore NO levels or activate downstream effectors such as sGC improve vasodilation, reduce fibrosis, and enhance myocardial relaxation. These effects are especially relevant in advanced HF patients and those with renal impairment, who often exhibit limited responses to conventional therapies. The NO pathway represents a promising therapeutic target in both stable and advanced HF. Modulating this pathway could improve outcomes, particularly in complex populations with multiple comorbidities, highlighting the need for further clinical research and tailored treatments. Full article

In response to the actual needs of pure copper bonding wires, it is crucial to develop a chromium-free passivator that is environmentally friendly and has excellent corrosion resistance. In this study, three different composite organic formulations of chromium-free passivation solutions are selected: 2-Amino-5-mercapto-1,3,4 thiadiazole (AMT) + 1-phenyl-5-mercapto tetrazolium (PMTA), 2-mercaptobenzimidazole (MBI) + PMTA, and Hexadecanethiol (CHS) + sodium dodecyl sulfate (SDS). The performance analysis and corrosion mechanism were compared with traditional hexavalent chromium passivation through characterization techniques such as XRD, SEM, and XPS. The results show that the best corrosion resistance formula is the combination of the PMTA and MBI passivation agent, and all its performances are superior to those of hexavalent chromium. The samples treated with this passivation agent corrode within 18 s in the nitric acid drop test, which is better than the 16 s for Cr⁶⁺ passivation. The samples do not change color after being immersed in salt water for 48 h. Electrochemical tests and high-temperature oxidation test also indicate better corrosion resistance than Cr⁶⁺ passivation. Through the analysis of functional groups and bonding, the excellent passivation effect is demonstrated to be achieved by the synergistic action of the chemical adsorption film formation of PMTA and the anchoring effect of MBI. Eventually, a dense Cu-PMTA-BMI film is formed on the surface, which effectively blocks the erosion of the corrosive medium and significantly improves the corrosion resistance. Full article

Pulmonary arterial hypertension (PAH) is a rare condition characterized by high pulmonary artery pressure leading to right ventricular dysfunction and potential life-threatening consequences. It primarily affects the pre-capillary pulmonary vascular system. The exact pathophysiological mechanisms underlying PAH are not entirely known. Environmental factors; genetic predisposition; mitochondrial and microRNA dysfunction; and inflammatory, metabolic, and hormonal mechanisms may be involved. A central role is played by the dysfunction of the pulmonary vascular endothelium. This alteration is characterized by a reduction in vasodilatory and antiproliferative factors such as prostacyclin and nitric oxide and an increase in vasoconstrictive and mitogenic substances such as endothelin and thromboxane A2. Such imbalance leads to a progressive increase in pulmonary vascular resistance. The aim of the present review is to focus on the vascular endothelium and its role as a potential therapeutic target in PAH. Full article

Ammonia-oxidizing bacteria (AOB) are key to the nitrogen cycle, but their resistance to nitrite (NO₂⁻-N) accumulation is unclear. This study examined N.eA1, an AOB from the completely autotrophic nitrogen removal over nitrite (CANON) process, assessing its adaptive responses to NO₂⁻-N. The ammonia oxidation and N₂O emission were evaluated at varying NO₂⁻-N levels, and 3D fluorescence, extracellular polymeric substances (EPS), and soluble microbial products (SMP) analysis were used to probe stress responses. Cellular respiration and key enzyme activities were measured, and proteomics was applied to study protein expression changes. Results showed that higher NO₂⁻-N levels boosted N₂O production, inhibited nitrification, and stimulated denitrification in N.eA1. At 100 mg·L⁻¹ NO₂⁻-N, EPS rose and SMP fell, with ammonia monooxygenase (AMO) suppressed and nitrite reductase (NIR) as well as nitric oxide reductase (NOR) enhanced. Gene expression analysis revealed decreased AMO, hydroxylamine oxidoreductase (HAO), and energy transport-related enzymes, but increased NIR and NOR genes. The downregulation of electron transport complex genes offered insights into molecular adaptation to nitrite stress of N.eA1, highlighting the interplay between metabolic and genetic responses, which is essential for developing sustainable and efficient nitrogen management strategies. Full article

Aluminum (Al) toxicity is a major limiting factor for plant growth and development in acidic soils. Melatonin, a plant growth regulator and signaling molecule, enhances resistance to multiple stresses. Recent studies show that melatonin alleviates Al toxicity through several complementary mechanisms. Here, we first outline the physiological and molecular impacts of Al stress and the external and internal strategies plants use to cope with it. We then summarize melatonin biosynthesis and its broader roles in stress adaptation. We focus on recent advances in melatonin-mediated mitigation of Al toxicity, highlighting four principal mechanisms: (i) the activation of antioxidant defense systems, (ii) the stimulation of organic acid anion exudation that chelates Al in the rhizosphere, (iii) the modification of cell wall composition to reduce Al binding sites, and (iv) the promotion of intracellular Al sequestration. We also discuss the crosstalk between melatonin and nitric oxide, as well as interactions with phytohormone signaling. Collectively, this review comprehensively synthesizes the current understanding regarding the role of melatonin in alleviating Al toxicity in plants, offering a promising strategy for crop production in acidic environments. Full article