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Endothelial cells play an obligatory role in regulating local vascular tone and maintaining homeostasis in vascular biology. Cell metabolism, converting food to energy in organisms, is the primary self-sustaining mechanism for cell proliferation and reproduction, structure maintenance, and fight-or-flight responses to stimuli. Four major metabolic processes take place in the energy-producing process, including glycolysis, oxidative phosphorylation, glutamine metabolism, and fatty acid oxidation. Among them, glycolysis is the primary energy-producing mechanism in endothelial cells. The present review focused on glycolysis in endothelial cells under both physiological and pathological conditions. Since the switches among metabolic processes precede the functional changes and disease developments, some prophylactic and/or therapeutic strategies concerning the role of glycolysis in cardiovascular disease are discussed.

The pharmacological effects of Amauroderma rugosum (AR), an edible mushroom found mainly in Southeast Asia, are not well studied, particularly its neuroprotective properties. This study investigated the neuroprotective effects of AR aqueous extract (ARW) in a d‐galactose‐induced accelerated aging mouse model and senescent SH‐SY5Y neuronal cells. Behavioral tests (open field, Morris water maze, Y‐maze, and rotarod) demonstrated that d‐galactose‐induced aging mice exhibited impaired cognitive function, memory loss, anxiety, and reduced locomotor ability, all of which were alleviated by ARW treatment. Histological analysis showed that ARW reduced neuropathological lesions in the hippocampus. In SH‐SY5Y neuronal cells, ARW and AR polysaccharide extract (ARP) enhanced cell viability and decreased intracellular reactive oxygen species (ROS) levels in a concentration‐dependent manner. ARW and ARP also reduced cellular senescence and apoptosis in d‐galactose‐treated cells. Western blot analysis indicated that ARW and ARP upregulated the phosphorylation of mTOR and increased the expression of antioxidant enzymes, including superoxide dismutase 1 and heme‐oxygenase‐1. Additionally, ARW altered the gut microbiota, increasing the relative abundance of beneficial bacteria such as Lactobacillus reuteri and decreasing harmful bacteria like Clostridium scindens. These findings suggest that AR exerts neuroprotective effects primarily through its polysaccharides by modulating oxidative stress, activating the mTOR‐dependent pathway, and influencing the gut microbiota. Consequently, AR could serve as a potential dietary supplement for the prevention and treatment of neurodegenerative diseases.

Cardiovascular disease remains a leading global cause of death, highlighting the need for new strategies to improve cardiovascular health. Time-restricted feeding (TRF), which limits daily food intake to a specific window, has shown promise in improving metabolic health and supporting weight control. This study investigated the effects of TRF in an obese rat model induced by a high-fat diet (HFD), focusing on early vascular, liver, and kidney structural changes, as well as oxidative stress and inflammation. Thirty male Sprague Dawley rats were assigned to five groups: a normal diet group (NOR), a normal chow with TRF (NOR + TRFNC), a continued HFD group (OB), an HFD with TRF group (OB + TRFHFD), and a group switched to TRF with normal chow (OB + TRFNC). Obesity was induced in three groups over six weeks, followed by a six-week intervention phase. TRF involved fasting for 16 h daily (5:00 p.m. to 9:00 a.m.). TRF led to improved lipid profiles and atherogenic indices in obese rats, regardless of diet. Elevated liver enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in obese rats were normalized by TRF. Additionally, TRF increased vascular superoxide dismutase (SOD) and decreased malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Histological analysis showed that fat infiltration and steatosis in the liver were reduced by TRF. Renal and vascular structures also showed improvement. In conclusion, TRF exhibits anti-atherosclerotic effects, likely due to reduced vascular oxidative stress, inflammation, improved liver and kidney function, and better atherogenic profiles. These benefits were supported by histopathological findings in hepatic and renal tissues.

Nuclear factor kappa B (NF-κB) activation contributes to many vascular inflammatory diseases. The present study tested the hypothesis that microRNA-17-3p (miR-17-3p) suppresses the pro-inflammatory responses via NF-κB signaling in vascular endothelium. Human umbilical vein endothelial cells (HUVECs), transfected with or without miR-17-3p agomir/antagomir, were exposed to lipopolysaccharide (LPS), and the inflammatory responses were determined. The cellular target of miR-17-3p was examined with dual-luciferase reporter assay. Mice were treated with miR-17-3p agomir and the degree of LPS-induced inflammation was determined. In HUVECs, LPS caused upregulation of miR-17-3p. Overexpression of miR-17-3p in HUVECs inhibited NIK and IKKβ binding protein (NIBP) protein expression and suppressed LPS-induced phosphorylation of inhibitor of kappa Bα (IκBα) and NF-κB-p65. The reduced NF-κB activity was paralleled by decreased protein levels of NF-κB-target gene products including pro-inflammatory cytokine [interleukin 6], chemokines [interleukin 8 and monocyte chemoattractant protein-1] and adhesion molecules [vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and E-selectin]. Immunostaining revealed that overexpression of miR-17-3p reduced monocyte adhesion to LPS-stimulated endothelial cells. Inhibition of miR-17-3p with antagomir has the opposite effect on LPS-induced inflammatory responses in HUVECs. The anti-inflammatory effect of miR-17-3p was mimicked by NIBP knockdown. In mice treated with LPS, miR-17-3p expression was significantly increased. Systemic administration of miR-17-3p for 3 days suppressed LPS-induced NF-κB activation and monocyte adhesion to endothelium in lung tissues of the mice. In conclusion, miR-17-3p inhibits LPS-induced NF-κB activation in HUVECs by targeting NIBP. The findings therefore suggest that miR-17-3p is a potential therapeutic target/agent in the management of vascular inflammatory diseases.

Synthetic ion channels may have potential therapeutic applications, provided they possess appropriate biological activities. The present study was designed to examine the ability of small molecule-based synthetic Cl(-) channels to modulate airway smooth muscle responsiveness. Changes in isometric tension were measured in rat tracheal rings. Relaxations to the synthetic chloride channel SCC-1 were obtained during sustained contractions to KCl. The anion dependency of the effect of SCC-1 was evaluated by ion substitution experiments. The sensitivity to conventional Cl(-) transport inhibitors was also tested. SCC-1 caused concentration-dependent relaxations during sustained contractions to potassium chloride. This relaxing effect was dependent on the presence of extracellular Cl(-) and HCO(3) (-). It was insensitive to conventional Cl(-) channels/transport inhibitors that blocked the cystic fibrosis transmembrane conductance regulator and calcium-activated Cl(-) channels. SCC-1 did not inhibit contractions induced by carbachol, endothelin-1, 5-hydroxytryptamine or the calcium ionophore A23187. SCC-1 relaxes airway smooth muscle during contractions evoked by depolarizing solutions. The Cl(-) conductance conferred by this synthetic compound is distinct from the endogenous transport systems for chloride anions.

Clinical outcomes for doxorubicin (Dox) are limited by its cardiotoxicity but a combination of Dox and agents with cardioprotective activities is an effective strategy to improve its therapeutic outcome. Natural products provide abundant resources to search for novel cardioprotective agents. Ganoderma lucidum (GL) is the most well-known edible mushroom within the Ganodermataceae family. It is commonly used in traditional Chinese medicine or as a healthcare product. Amauroderma rugosum (AR) is another genus of mushroom from the Ganodermataceae family, but its pharmacological activity and medicinal value have rarely been reported. In the present study, the cardioprotective effects of the AR water extract against Dox-induced cardiotoxicity were studied in vitro and in vivo. Results showed that both the AR and GL extracts could potentiate the anticancer effect of Dox. The AR extract significantly decreased the oxidative stress, mitochondrial dysfunction, and apoptosis seen in Dox-treated H9c2 rat cardiomyocytes. However, knockdown of Nrf2 by siRNA abolished the protective effects of AR in these cells. In addition, Dox upregulated the expression of proapoptotic proteins and downregulated the Akt/mTOR and Nrf2/HO-1 signaling pathways, and these effects could be reversed by the AR extract. Consistently, the AR extract significantly prolonged survival time, reversed weight loss, and reduced cardiac dysfunction in Dox-treated mice. In addition, oxidative stress and apoptosis were suppressed, while Nrf2 and HO-1 expressions were elevated in the heart tissues of Dox-treated mice after treatment with the AR extract. However, the GL extract had less cardioprotective effect against Dox in both the cell and animal models. In conclusion, the AR water extract demonstrated a remarkable cardioprotective effect against Dox-induced cardiotoxicity. One of the possible mechanisms for this effect was the upregulation of the mTOR/Akt and Nrf2/HO-1-dependent pathways, which may reduce oxidative stress, mitochondrial dysfunction, and cardiomyocyte apoptosis. These findings suggested that AR may be beneficial for the heart, especially in patients receiving Dox-based chemotherapy.

Diabetes mellitus contributes to macro- and microvascular complications, leading to adverse cardiovascular events. This study examined the effects of vitamin D deficiency on the vascular function and tissue oxidative status in the microcirculation of diabetic rats and to determine whether these effects can be reversed with calcitriol (active vitamin D metabolite) supplementation. Streptozotocin-induced diabetic rats were fed for 10 weeks with control diet (DC) or vitamin D-deficient diet without (DD) or with oral calcitriol supplementation (0.15 μg/kg) in the last four weeks (DDS) (10 rats each group). A nondiabetic rat group that received control diet was also included (NR). After 10 weeks, rats were sacrificed; mesenteric arterial rings with and without endothelium were studied using wire myograph. Western blotting of the mesenteric arterial tissue was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) enzyme. Antioxidant enzyme superoxide dismutase (SOD) activity and oxidative stress marker malondialdehyde (MDA) levels in the mesenteric arterial tissue were also measured. The DC group had significantly lower acetylcholine-induced relaxation and augmented endothelium-dependent contraction, with reduced eNOS expression, compared to NR rats. In mesenteric arteries of DD, acetylcholine-induced endothelium-dependent and sodium nitroprusside-induced endothelium-independent relaxations were lower than those in DC. Calcitriol supplementation in DDS restored endothelium-dependent relaxation. Mesenteric artery endothelium-dependent contraction of DD was greater than DC; it was not affected by calcitriol supplementation. The eNOS protein expression and SOD activity were significantly lower while MDA levels were greater in DD compared to DC; these effects were not observed in DDS that received calcitriol supplementation. In conclusion, vitamin D deficiency causes eNOS downregulation and oxidative stress, thereby impairing the vascular function and posing an additional risk for microvascular complications in diabetes. Calcitriol supplementation to diabetics with vitamin D deficiency could potentially be useful in the management of or as an adjunct to diabetes-related cardiovascular complications.

Background Mild hypothermia (34–35 °C) increases perioperative blood loss. Our previous studies showed that desmopressin could have in vitro beneficial effects on hypothermia-induced primary haemostasis impairment. In this study, we investigate the in vitro effects of desmopressin on hypothermia-induced primary haemostasis impairment under the influence of aspirin in healthy volunteers. Methods Sixty healthy volunteers were randomly allocated to taking aspirin 100 mg or placebo for three days. On the sixth day blood samples were taken before and after the injection of desmopressin (1.5 microgram or 5 microgram) or normal saline subcutaneously. Measurements including Platelet Function Analyzer (PFA-100®) closure times, plasma von Willebrand Factor antigen, haemoglobin and platelet levels were made at 32 °C and 37 °C respectively. Results Collagen/epinephrine closure time (EPICT) was significantly prolonged by 21.13 % (95 %CI 2.34–39.74 %, p  = 0.021) in aspirin group at 37 °C. While hypothermia alone prolonged both collagen/adenosine diphosphate (ADPCT) and EPICT by 17.63 % (95 %CI 13.5–20.85 %, p  < 0.001) and 8.0 % (95 %CI 6.38–10.04 %, p  = 0.024) respectively, addition of aspirin only further prolonged EPICT by 19.9 % (95 %CI 3.32–36.49 %, p  = 0.013). In aspirin group, desmopressin 1.5 microgram and 5 microgram significantly reduced ADPCT to below baseline levels at 37 °C ( p  = 0.025 and <0.001 respectively), whereas reduction in EPICT was seen with desmopressin 5 microgram ( p =0.008). The effect was less pronounced at 32 °C, with a significant reduction in EPICT obtained with a dosage of 5 microgram only ( p  = 0.011). Conclusion It was shown that aspirin could further potentiate the hypothermia-induced closure time prolongations. Low dose desmopressin (1.5 microgram) reduced PFA-100® closure times towards baseline. A higher dosage (5 microgram) further reduced the closure times below baseline. Therefore low dose desmopressin (1.5 microgram) might have the potential to correct hypothermia-induced primary haemostasis impairment under the influence of aspirin during the perioperative period. Trial registration ClinicalTrials.gov: NCT01382134

Aim: Endothelium-dependent relaxations to certain neurohumoral substances are mediated by pertussis toxin-sensitive Gi/o protein. Our experiments were designed to determine the role, if any, of pertussis toxin-sensitive G-proteins in relaxations attributed to endothelium-derived hyperpolarizing factor (EDHF). Methods: Pig coronary arterial rings with endothelia were suspended in organ chambers filled with Krebs-Ringer bicarbonate solution maintained at 37 °C and continuously aerated with 95%O 2 and 5% CO 2 . Isometric tension was measured during contractions to prostaglandin F 2α in the presence of indomethacin and N ω -nitro- L -arginine methyl ester ( L -NAME). Results: Thrombin, the thrombin receptor-activating peptide SFLLRN, bradykinin, substance P, and calcimycin produced dose-dependent relaxations. These relaxations were not inhibited by prior incubation with pertussis toxin, but were abolished upon the addition of charybdotoxin plus apamin. Relaxations to the α2-adrenergic agonist UK14304 and those to serotonin were abolished in the presence of indomethacin and L -NAME. Conclusion: Unlike nitric oxide-mediated relaxations, EDHF-mediated relaxations of pig coronary arteries do not involve pertussis toxin-sensitive pathways and are Gi/o protein independent.

Aim: Endothelium‐dependent relaxations to certain neurohumoral substances are mediated by pertussis toxin‐sensitive Gi/o protein. Our experiments were designed to determine the role, if any, of pertussis toxin‐sensitive G‐proteins in relaxations attributed to endothelium‐derived hyperpolarizing factor (EDHF). Methods: Pig coronary arterial rings with endothelia were suspended in organ chambers filled with Krebs‐Ringer bicarbonate solution maintained at 37 °C and continuously aerated with 95%O2 and 5% CO2. Isometric tension was measured during contractions to prostaglandin F2α in the presence of indomethacin and Nω‐nitro‐L‐arginine methyl ester (L‐NAME). Results: Thrombin, the thrombin receptor‐activating peptide SFLLRN, bradykinin, substance P, and calcimycin produced dose‐dependent relaxations. These relaxations were not inhibited by prior incubation with pertussis toxin, but were abolished upon the addition of charybdotoxin plus apamin. Relaxations to the α2‐adrenergic agonist UK14304 and those to serotonin were abolished in the presence of indomethacin and L‐NAME. Conclusion: Unlike nitric oxide‐mediated relaxations, EDHF‐mediated relaxations of pig coronary arteries do not involve pertussis toxin‐sensitive pathways and are Gi/o protein independent.