Search Results (132)

Peripheral artery disease (PAD) is a chronic progressive accumulation of atherosclerotic lesions with varying degrees of arterial obstruction determining ischemic symptoms of the involved extremities. PAD is associated with decreased bioavailable nitric oxide due to endothelial cell dysfunction and the development and progression of vascular arterial stiffening (VAS). Atherosclerosis also plays an essential role in the development and progression of vascular arterial stiffening (VAS), which is associated with endothelial cell activation and dysfunction that results in a proinflammatory endothelium with a decreased ability to produce bioavailable nitric oxide (NO). NO is one of three gasotransmitters, along with carbon monoxide and hydrogen sulfide, that promotes vasodilation. NO plays a crucial role in the regulation of PAD, and a deficiency in its bioavailability is strongly linked to the development of atherosclerosis, VAS, and PAD. A decreased arterial patency may also occur due to a reduction in the elasticity or diameter of the vessel wall due to the progressive nature of VAS and atherosclerosis in PAD. Progressive atherosclerosis and VAS promote narrowing over time, which leads to impairment of vasorelaxation and extremity blood flow. This narrative review examines how atherosclerosis, aging and hypertension, metabolic syndrome and type 2 diabetes, tobacco smoking, and endothelial cell activation and dysfunction with decreased NO and VAS with its increased damaging pulsatile pulse pressure result in microvessel remodeling. Further, the role of ischemia and ischemia–reperfusion injury is discussed and how it contributes to ischemic skeletal muscle remodeling, ischemic neuropathy, and pain perception in PAD. Full article

(1) Background: The relationship between air pollution and the risk of developing aphasia is still unclear. We aimed to evaluate air pollution exposure as a risk factor for developing aphasia in Taiwan. (2) Methods: This retrospective population-based cohort study used the Longitudinal Generation Tracking Database (LGTD) and the Taiwan Air Quality Monitoring Database (TAQMD). The incidence rate ratio (IRR) and adjusted hazard ratio (aHR) were calculated to examine the association between aphasia and exposure to six air pollutants: sulfur oxide (SO₂), carbon monoxide (CO), nitric oxide (NO), nitrogen oxide (NOx), and particulate matter (PM_2.5, PM₁₀) from 2003 to 2017. (3) Results: The incidence rate ratio (IRR) of aphasia showed that individuals with high levels of SO₂, CO, and NO were at a higher risk of developing aphasia. Increased exposure to airborne particulate matter (PM_2.5 and PM₁₀) also increased the risk of developing aphasia. The adjusted HRs of the aphasia risk were statistically significant for all the air pollutants at higher concentrations. (4) Conclusions: Individuals exposed to ambient air pollutants have a significantly higher risk of developing aphasia. The greater the exposure to airborne particulate matter and gaseous pollutants, the more likely individuals are to develop aphasia. Full article

In recent years, frequent open biomass burning (OBB) activities such as agricultural residue burning and forest fires have led to severe air pollution and carbon emissions across South and Southeast Asia (SSEA). We selected this area as our study area and divided it into two sub-regions based on climate characteristics and geographical location: the South Asian Subcontinent (SEAS), which includes India, Laos, Thailand, Cambodia, etc., and Equatorial Asia (EQAS), which includes Indonesia, Malaysia, etc. However, existing methods—primarily emission inventories relying on burned area, fuel load, and emission factors—often lack accuracy and temporal resolution for capturing fire dynamics. Therefore, in this study, we employed high-resolution fire point data from China’s Feng Yun-4A (FY-4A) geostationary satellite and the Fire Radiative Power (FRP) method to construct a daily OBB emission inventory at a 5 km resolution in this region for 2020–2022. The results show that the average annual emissions of carbon (C), carbon dioxide (CO₂), carbon monoxide (CO), methane (CH₄), non-methane organic gases (NMOGs), hydrogen (H₂), nitrogen oxide (NO_X), sulfur dioxide (SO₂), fine particulate matter (PM_2.5), total particulate matter (TPM), total particulate carbon (TPC), organic carbon (OC), black carbon (BC), ammonia (NH₃), nitric oxide (NO), nitrogen dioxide (NO₂), non-methane hydrocarbons (NMHCs), and particulate matter ≤ 10 μm (PM₁₀) are 178.39, 598.10, 33.11, 1.44, 4.77, 0.81, 1.02, 0.28, 3.47, 5.58, 2.29, 2.34, 0.24, 0.58, 0.43, 0.99, 1.87, and 3.84 Tg/a, respectively. Taking C emission as an example, 90% of SSEA’s emissions come from SEAS, especially concentrated in Laos and western Thailand. Due to the La Niña climate anomaly in 2021, emissions surged, while EQAS showed continuous annual growth at 16.7%. Forest and woodland fires were the dominant sources, accounting for over 85% of total emissions. Compared with datasets such as the Global Fire Emissions Database (GFED) and the Global Fire Assimilation System (GFAS), FY-4A showed stronger sensitivity and regional adaptability, especially in SEAS. This work provides a robust dataset for carbon source identification, air quality modeling, and regional pollution control strategies. Full article

Age-related oxidative stress is a critical factor in vascular dysfunction, contributing to hypertension and atherosclerosis. Smooth muscle cells and endothelial cells are particularly susceptible to oxidative damage, which exacerbates vascular aging through cellular senescence, chronic inflammation, and arterial stiffness. Gasotransmitters—hydrogen sulfide (H₂S), nitric oxide (NO), and carbon monoxide (CO)—are emerging as promising therapeutic agents for counteracting these processes. This review synthesizes findings from recent studies focusing on the mechanisms by which H₂S, NO, and CO influence vascular smooth muscle and endothelial cell function. Therapeutic strategies involving exogenous gasotransmitter delivery systems and combination therapies were analyzed. H₂S enhances mitochondrial bioenergetics, scavenges ROS, and activates antioxidant pathways. NO improves endothelial function, promotes vasodilation, and inhibits platelet aggregation. CO exhibits cytoprotective and anti-inflammatory effects by modulating heme oxygenase activity and ROS production. In preclinical studies, gasotransmitter-releasing molecules (e.g., NaHS, SNAP, CORMs) and targeted delivery systems show significant promise. Synergistic effects with lifestyle modifications and antioxidant therapies further enhance their therapeutic potential. In conclusion, gasotransmitters hold significant promise as therapeutic agents to combat age-related oxidative stress in vascular cells. Their multifaceted mechanisms and innovative delivery approaches make them potential candidates for treating vascular dysfunction and promoting healthy vascular aging. Further research is needed to translate these findings into clinical applications. Full article

The search for alternative fuels is driven by increasing environmental and health concerns across the globe. Water-in-diesel emulsions (WiDEs) have been explored over the years as a potential fuel for diesel engines to mitigate emissions of greenhouse gases, especially nitrogen oxides and smoke. Researchers have been developing and testing different formulations of emulsified fuels with the common goal of stabilizing the mixture and minimizing pollutant emissions without significantly compromising engine performance. In this work, a novel approach is taken by developing a hydrophilic emulsion formulation optimized for engine operating temperatures, overcoming the storage-related stability issues that most studies focus on. Two different mixtures of WiDE were heated and supplied to a Hatz 1B40 single-cylinder diesel engine. The engine was coupled to an eddy current dynamometer to measure speed, torque, and power values. Emissions of carbon monoxide (CO), carbon dioxide (CO₂), hydrocarbons (HCs), nitric oxide (NO), and oxygen (O₂) were measured by an AVL DiGas 1000 exhaust gas analyzer. Smoke emissions were measured by an AVL DiSmoke 480. This study represents a contribution to the field of alternative fuels for diesel engines by providing experimental evidence that formulating WiDE for operating temperatures can be advantageous and significantly improve thermal efficiency and reduce emissions of NO and smoke at specific engine operating conditions, with a maximum reduction of 46.86% for NO emissions and a maximum reduction of 83.67% for smoke emissions obtained when compared to diesel. Full article

Preeclampsia (PE) is a major cause of maternal mortality and morbidity, affecting 3–6% of pregnancies worldwide and ranking among the top six causes of maternal deaths in the U.S. PE typically develops after 20 weeks of gestation and is characterized by new-onset hypertension and/or end-organ dysfunction, with or without proteinuria. Current management strategies for PE emphasize early diagnosis, blood pressure control, and timely delivery. For prevention, low-dose aspirin (81 mg/day) is recommended for high-risk women between 12 and 28 weeks of gestation. Magnesium sulfate is also advised to prevent seizures in preeclamptic women at risk of eclampsia. Emerging management approaches include antiangiogenic therapies, hypoxia-inducible factor suppression, statins, and supplementation with CoQ10, nitric oxide, and hydrogen sulfide donors. Black women are at particularly high risk for PE, potentially due to higher rates of hypertension and cholesterol, compounded by healthcare disparities and possible genetic factors, such as the APOL1 gene. This review explores current and emerging strategies for managing PE and addresses the underlying causes of health disparities, offering potential solutions to improve outcomes. Full article

Plants face a range of environmental stresses, such as heat and drought, that significantly reduce their growth, development, and yield. Plants have developed complex signaling networks to regulate physiological processes and improve their ability to withstand stress. The key regulators of plant stress responses include polyamines (PAs) and gaseous signaling molecules (GSM), such as hydrogen sulfide (H₂S), nitric oxide (NO), methane (CH₄), carbon monoxide (CO), carbon dioxide (CO₂), and ethylene (ET). The functions of PAs and GSM in stress perception, signal transduction, and stress-responsive pathways have been explored. However, there is a lack of detailed, updated information on the interaction of PAs and GSM in the adaptation of drought and heat stress. This review explores the interaction between PAs and GSM for the adaptation to drought and heat stress. It explores their synergistic effects in mitigating the negative impacts of drought and heat stress on plant growth, development, and productivity. Moreover, a comprehensive analysis of physiological, biochemical, and molecular approaches demonstrates that their interaction activates key stress-responsive pathways, enhances antioxidant systems, and modulates gene expression. These combined effects contribute to improved drought and heat tolerance in plants. The information presented in the review provides valuable insights into plant stress resilience strategies and suggests potential measures for developing climate-resilient crops to address the increasing environmental challenges. Full article

Hemoglobin is an oxygen-transport protein in red blood cells that interacts with multiple ligands, e.g., oxygen, carbon dioxide, carbon monoxide, and nitric oxide. Genetic variations in hemoglobin chains, such as those underlying sickle cell disease and thalassemias, present substantial clinical challenges. Here, we review the progress in research, including the use of allosteric modulators, pharmacological chaperones, and antioxidant treatments, which has begun to improve hemoglobin stability and oxygen affinity. According to UniProt (as of 7 August 2024), 819 variants of the α-hemoglobin subunit and 771 variants of the β-hemoglobin subunit have been documented, with over 116 classified as unstable. These data demonstrate the urgent need to develop variant-specific stabilizing options. Beyond small-molecule drugs/binders, novel protein-based strategies—such as engineered hemoglobin-binding proteins (including falcilysin, llama-derived nanobodies, and α-hemoglobin-stabilizing proteins)—offer promising new options. As our understanding of hemoglobin’s structural and functional diversity grows, so does the potential for genotype-driven approaches. Continued research into hemoglobin stabilization and ligand-binding modification may yield more precise, effective treatments and pave the way toward effective strategies for hemoglobinopathies. Full article

Carbon monoxide (CO) is recognized as a signaling molecule in plants, inducing various physiological responses. This article briefly examines the physiological functions of CO in seed biology and seedlings’ responses to environmental stresses. The activity of heme oxygenase (HO), the main enzyme responsible for CO synthesis, is a key factor controlling CO levels in plant cells. CO can influence seed germination by regulating seed dormancy through interactions with genes and hormones. Additionally, CO positively affects seedling growth by enhancing the antioxidant system, thereby increasing resistance to oxidative damage caused by stress. CO has beneficial effects on root development, root length, stomatal closure, and regulation of the photosynthetic system. Its interaction with reactive oxygen species (ROS) mediates hormone- and light-dependent growth processes during the early stages of plant development under stress. Furthermore, CO interacts with other signaling molecules, such as nitric oxide (NO), molecular hydrogen (H₂), and hydrogen sulfide (H₂S). By gaining a better understanding of the molecular mechanisms underlying these processes, CO can be more effectively utilized to improve seed germination and seedling growth in agricultural practices. Full article

Polygonum aviculare L. (PAL), commonly known as knotgrass, has been utilized as a traditional folk medicine across Asian, African, Latin American and Middle Eastern countries to treat various inflammatory diseases, including arthritis and airway inflammation. Numerous medicinal herbs exert anti-inflammatory and antioxidative effects that are mediated through the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the inhibition of nuclear factor kappa B (NF-κB). However, the underlying molecular mechanisms linking the antioxidative and anti-inflammatory effects remain poorly understood. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that catalyzes heme degradation, ultimately leading to the production of carbon monoxide (CO). Elevated levels of CO have been correlated with the decreased level of inducible nitric oxide synthase (iNOS). In this study, we examined whether HO-1 plays a key role in the relationship between the antioxidative and anti-inflammatory properties of PAL. The anti-inflammatory and antioxidative activities of PAL in an in vitro system were evaluated by determining NF-κB activity, antioxidant response element (ARE) activity, pro-inflammatory cytokine and protein levels, as well as antioxidant protein levels. To examine whether HO-1 inhibition interfered with the anti-inflammatory effect of PAL, we measured nitrite, reactive oxygen species, iNOS, and HO-1 levels in RAW 264.7 murine macrophages pre-treated with Tin protoporphyrin (SnPP, an HO-1 inhibitor). Our results demonstrated that PAL increased ARE activity and the Nrf2-regulated HO-1 level, exerting antioxidative activities in RAW 264.7 macrophages. Additionally, PAL reduced cyclooxygenase-2 (COX-2) and iNOS protein levels by inactivating NF-κB in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Further investigation using the HO-1 inhibitor revealed that HO-1 inhibition promoted iNOS expression, subsequently elevating nitric oxide (NO) generation in LPS-activated RAW 264.7 macrophages treated with PAL compared to those in the macrophages without the HO-1 inhibitor. Overall, our findings suggest that HO-1 induction by PAL may exert anti-inflammatory effects through the reduction of the iNOS protein level. Hence, this study paves the way for further investigation to understand molecular mechanisms underlying the antioxidative and anti-inflammatory activities of medicinal herbs. Full article

Background: There is increasing evidence that nitric oxide (nitrogen monoxide, NO) significantly influences immune cellular responses, including those from polymorphonuclear leukocytes (PMNs). Objective: The aim of this study was to examine a possible effect of NO on PMNs’ function (chemotaxis, production of reactive oxygen species (ROS), and NETosis) using live cell imaging. Moreover, we investigated PMN surface epitope and neutrophil oxidative burst under the influence of NO by flow cytometric analysis. Methods: Whole blood samples were obtained from healthy volunteers, and PMNs were isolated by density centrifugation. Live cell imaging using type I collagen matrix in µSlide IBIDI chemotaxis chambers was conducted in order to observe N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP)-stimulated PMN chemotaxis, ROS production, and NETosis. In the test group, NO was continuously redirected into the climate chamber of the microscope, so the chemotaxis chambers were surrounded by NO. The same experimental setup without NO served as a control. In addition, isolated PMNs were incubated with nitrogen monoxide (NO) or without (the control). Subsequently, flow cytometry was used to analyze neutrophil antigen expression and oxidative burst. Results: Our live cell imaging results demonstrated a migration-promoting effect of NO on PMNs. We observed that in the case of prior stimulation by fMLP, NO has no effect on the time course of neutrophil ROS production and NET release. However, flow cytometric analyses demonstrated an increase in ROS production after pretreatment with NO. No NO-dependent differences for the expression of CD11b, CD62L, or CD66b could be observed. Conclusions: We were able to demonstrate a distinct effect of NO on PMNs’ function. The complex interaction between NO and PMNs remains a major research focus, as the exact mechanisms and additional influencing factors remain elusive. Future studies should explore how varying NO concentrations and the timing of NO exposure relative to PMN activation affect its influence. Full article

Myocardial ischaemia reperfusion injury (IRI) occurring from acute coronary artery disease or cardiac surgical interventions such as bypass surgery can result in myocardial dysfunction, presenting as, myocardial “stunning”, arrhythmias, infarction, and adverse cardiac remodelling, and may lead to both a systemic and a localised inflammatory response. This localised cardiac inflammatory response is regulated through the nucleotide-binding oligomerisation domain (NACHT), leucine-rich repeat (LRR)-containing protein family pyrin domain (PYD)-3 (NLRP3) inflammasome, a multimeric structure whose components are present within both cardiomyocytes and in cardiac fibroblasts. The NLRP3 inflammasome is activated via numerous danger signals produced by IRI and is central to the resultant innate immune response. Inhibition of this inherent inflammatory response has been shown to protect the myocardium and stop the occurrence of the systemic inflammatory response syndrome following the re-establishment of cardiac circulation. Therapies to prevent NLRP3 inflammasome formation in the clinic are currently lacking, and therefore, new pharmacotherapies are required. This review will highlight the role of the NLRP3 inflammasome within the myocardium during IRI and will examine the therapeutic value of inflammasome inhibition with particular attention to carbon monoxide, nitric oxide, and hydrogen sulphide as potential pharmacological inhibitors of NLRP3 inflammasome activation. Full article

Hydrogen selenide (H₂Se) is an emerging biomolecule of interest with similar properties to that of other gaseous signaling molecules (i.e., gasotransmitters that include nitric oxide, carbon monoxide, and hydrogen sulfide). H₂Se is enzymatically generated in humans where it serves as a key metabolic intermediate in the production of selenoproteins and other selenium-containing biomolecules. However, beyond its participation in biosynthetic pathways, its involvement in cellular signaling or other biological mechanisms remains unclear. To uncover its true biological significance, H₂Se-specific chemical tools capable of functioning under physiological conditions are required but lacking in comparison to those that exist for other gasotransmitters. Recently, researchers have begun to fill this unmet need by developing new H₂Se-releasing compounds, along with pioneering methods for selenide detection and quantification. In combination, the chemical tools highlighted in this review have the potential to spark groundbreaking explorations into the chemical biology of H₂Se, which may lead to its branding as the fourth official gasotransmitter. Full article

Impaired lung gas exchange is commonly seen in patients with pulmonary involvement related to SARS-CoV-2 acute infection or post-acute COVID-19 syndrome (PACS). The primary aim of our study was to assess lung gas transfer, measuring the pulmonary diffusion capacity for nitric oxide (D_LNO) and carbon monoxide (D_LCO) in all COVID-19 patients. Our secondary aim was to decipher the respective roles of perturbed lung membrane conductance (D_M) and reduced pulmonary capillary volume (V_C) in patients with impaired lung gas exchange. From May to October 2020, we measured D_LNO-D_LCO in 118 patients during their post-COVID-19 period (4.6 months after infection) to decipher alveolo-capillary gas transfer disturbances. D_LNO-D_LCO measurement was also performed in 28 healthy non-smokers as controls. Patients were classified into three groups according to the severity (mild, moderate, and severe) of acute COVID-19 infection. Patients with mild COVID-19 had normal lung volumes and airways expiratory flows but impaired pulmonary gas exchange, as shown by the significant decreases in D_LNO, D_LCO, D_M, and V_C as compared with controls. V_C was significantly impaired and the D_LNO/D_LCO ratio was increased in patients with moderate (n = 4, 11%) and severe COVID-19 (n = 23, 49%). Abnormal membrane conductance was also seen in all three groups of post-COVID-19 patients. These findings suggest a persistent alveolo-capillary gas transfer defect, implying not only reduced membrane conductance but also abnormal pulmonary vascular capacitance in all PACS patients, even those with a milder form of COVID-19 infection. Full article

The sole known heme enzyme of the parasitic protist Giardia intestinalis is a flavohemoglobin (gFlHb) that acts as a nitric oxide dioxygenase (NOD) and protects the organism from the free radical nitric oxide. To learn more about the properties of this enzyme, we measured its nitric oxide dioxygenase, NADH oxidase, and cytochrome c reductase activities and compared these to the activities of the E. coli flavohemoglobin (Hmp). The turnover number for the NOD activity of gFlHb (23 s⁻¹) is about two-thirds of that of Hmp (34 s⁻¹) at pH 6.5 and 37 °C. The two enzymes differ in their sensitivity towards molecules that act as heme ligands. For both gFlHb and Hmp, inhibition with miconazole, a large imidazole ligand, is adequately described by simple competitive inhibition, with K_I = 10 μM and 0.27 μM for gFlHb and Hmp, respectively. Inhibition plots with the small ligand imidazole were biphasic, which is consistent with previous experiments with carbon monoxide as a probe that show that the active site of flavohemoglobins exists in two conformations. Interestingly, the largest difference is observed with nitrite, which, like imidazole, also shows a biphasic inhibition plot; however, nitrite inhibits gFlHb at sub-millimolar concentrations while Hmp is not significantly affected. NADH oxidase activity measured under aerobic conditions in the absence of nitric oxide for Hmp was more than twice the activity of gFlHb. The addition of 1 mM hydrogen peroxide in these assays stimulated the NADH oxidase activity of gFlHb but not Hmp. Both enzymes had nearly identical cytochrome c reductase activities but the extent of the contribution of indirect reduction by flavohemoglobin-generated superoxide was much lower with gFlHb (4% SOD-inhibited) than with Hmp (17% SOD-inhibited). Although the active sites of the two enzymes share the same highly conserved residues that are important for catalysis, differences in the distal ligand binding site may account for these differences in activity and sensitivity towards NOD inhibitors. The differences observed in the NADH oxidase and cytochrome c reductase assays suggest that gFlHb may have evolved to protect the protist, which lacks both superoxide dismutase and catalase, from the damaging effects of superoxide by minimizing its production and from peroxide by actively reducing it. Full article