Targeting the Renin–Angiotensin–Aldosterone System to Prevent Hypertension and Kidney Disease of Developmental Origins

The renin-angiotensin-aldosterone system (RAAS) is implicated in hypertension and kidney disease. The developing kidney can be programmed by various early-life insults by so-called renal programming, resulting in hypertension and kidney disease in adulthood. This theory is known as developmental origins of health and disease (DOHaD). Conversely, early RAAS-based interventions could reverse program processes to prevent a disease from occurring by so-called reprogramming. In the current review, we mainly summarize (1) the current knowledge on the RAAS implicated in renal programming; (2) current evidence supporting the connections between the aberrant RAAS and other mechanisms behind renal programming, such as oxidative stress, nitric oxide deficiency, epigenetic regulation, and gut microbiota dysbiosis; and (3) an overview of how RAAS-based reprogramming interventions may prevent hypertension and kidney disease of developmental origins. To accelerate the transition of RAAS-based interventions for prevention of hypertension and kidney disease, an extended comprehension of the RAAS implicated in renal programming is needed, as well as a greater focus on further clinical translation.     

Therapeutic Potential of Carbon Monoxide (CO) and Hydrogen Sulfide (H2S) in Hemolytic and Hemorrhagic Vascular Disorders—Interaction between the Heme Oxygenase and H2S-Producing Systems

Over the past decades, substantial work has established that hemoglobin oxidation and heme release play a pivotal role in hemolytic/hemorrhagic disorders. Recent reports have shown that oxidized hemoglobins, globin-derived peptides, and heme trigger diverse biological responses, such as toll-like receptor 4 activation with inflammatory response, reprogramming of cellular metabolism, differentiation, stress, and even death. Here, we discuss these cellular responses with particular focus on their mechanisms that are linked to the pathological consequences of hemorrhage and hemolysis. In recent years, endogenous gasotransmitters, such as carbon monoxide (CO) and hydrogen sulfide (H₂S), have gained a lot of interest in connection with various human pathologies. Thus, many CO and H₂S-releasing molecules have been developed and applied in various human disorders, including hemolytic and hemorrhagic diseases. Here, we discuss our current understanding of oxidized hemoglobin and heme-induced cell and tissue damage with particular focus on inflammation, cellular metabolism and differentiation, and endoplasmic reticulum stress in hemolytic/hemorrhagic human diseases, and the potential beneficial role of CO and H₂S in these pathologies. More detailed mechanistic insights into the complex pathology of hemolytic/hemorrhagic diseases through heme oxygenase-1/CO as well as H₂S pathways would reveal new therapeutic approaches that can be exploited for clinical benefit.     

Crosstalk between Melatonin and Reactive Oxygen Species in Plant Abiotic Stress Responses: An Update

Melatonin acts as a multifunctional molecule that takes part in various physiological processes, especially in the protection against abiotic stresses, such as salinity, drought, heat, cold, heavy metals, etc. These stresses typically elicit reactive oxygen species (ROS) accumulation. Excessive ROS induce oxidative stress and decrease crop growth and productivity. Significant advances in melatonin initiate a complex antioxidant system that modulates ROS homeostasis in plants. Numerous evidences further reveal that melatonin often cooperates with other signaling molecules, such as ROS, nitric oxide (NO), and hydrogen sulfide (H₂S). The interaction among melatonin, NO, H₂S, and ROS orchestrates the responses to abiotic stresses via signaling networks, thus conferring the plant tolerance. In this review, we summarize the roles of melatonin in establishing redox homeostasis through the antioxidant system and the current progress of complex interactions among melatonin, NO, H₂S, and ROS in higher plant responses to abiotic stresses. We further highlight the vital role of respiratory burst oxidase homologs (RBOHs) during these processes. The complicated integration that occurs between ROS and melatonin in plants is also discussed.     

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Sepsis, a potentially lethal condition resulting from failure to control the initial infection, is associated with a dysregulated host defense response to pathogens and their toxins. Sepsis remains a leading cause of morbidity, mortality and disability worldwide. The pathophysiology of sepsis is very complicated and is not yet fully understood. Worse still, the development of effective therapeutic agents is still an unmet need and a great challenge. Gases, including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H₂S), are small-molecule biological mediators that are endogenously produced, mainly by enzyme-catalyzed reactions. Accumulating evidence suggests that these gaseous mediators are widely involved in the pathophysiology of sepsis. Many sepsis-associated alterations, such as the elimination of invasive pathogens, the resolution of disorganized inflammation and the preservation of the function of multiple organs and systems, are shaped by them. Increasing attention has been paid to developing therapeutic approaches targeting these molecules for sepsis/septic shock, taking advantage of the multiple actions played by NO, CO and H₂S. Several preliminary studies have identified promising therapeutic strategies for gaseous-mediator-based treatments for sepsis. In this review article, we summarize the state-of-the-art knowledge on the pathophysiology of sepsis; the metabolism and physiological function of NO, CO and H₂S; the crosstalk among these gaseous mediators; and their crucial effects on the development and progression of sepsis. In addition, we also briefly discuss the prospect of developing therapeutic interventions targeting these gaseous mediators for sepsis.     

Hydrogen Sulfide Plays an Important Role by Regulating Endoplasmic Reticulum Stress in Diabetes-Related Diseases

Endoplasmic reticulum (ER) plays important roles in protein synthesis, protein folding and modification, lipid biosynthesis, calcium storage, and detoxification. ER homeostasis is destroyed by physiological and pharmacological stressors, resulting in the accumulation of misfolded proteins, which causes ER stress. More and more studies have shown that ER stress contributes to the pathogenesis of many diseases, such as diabetes, inflammation, neurodegenerative diseases, cancer, and autoimmune diseases. As a toxic gas, H₂S has, in recent years, been considered the third most important gas signal molecule after NO and CO. H₂S has been found to have many important physiological functions and to play an important role in many pathological and physiological processes. Recent evidence shows that H₂S improves the body’s defenses to many diseases, including diabetes, by regulating ER stress, but its mechanism has not yet been fully understood. We therefore reviewed recent studies of the role of H₂S in improving diabetes-related diseases by regulating ER stress and carefully analyzed its mechanism in order to provide a theoretical reference for future research.     

Surface reactions of nitrogen oxide and ethylene on rhodium (111)

Temperature programming of NO and C₂H₂ coadsorbed on Rh(111) gives rise to the desorption of a number of gases. Where H₂, H₂O, CO₂ and N₂ are the main products at low C₂H₂ coverages, significant amounts of HCN, CO and NO evolve at higher C₂H₄ coverages. Static SIMS indicates the formation of a large supply of adsorbed CN species, part of which desorbs as HCN, while the remainder decomposes and is responsible for delayed formation of N₂. For the highest C₂H₄ coverages the majority of the initially adsorbed NO desorbs as HCN.     

The Hidden Role of Hydrogen Sulfide Metabolism in Cancer

Hydrogen Sulfide (H₂S), an endogenously produced gasotransmitter, is involved in various important physiological and disease conditions, including vasodilation, stimulation of cellular bioenergetics, anti-inflammation, and pro-angiogenesis. In cancer, aberrant up-regulation of H₂S-producing enzymes is frequently observed in different cancer types. The recognition that tumor-derived H₂S plays various roles during cancer development reveals opportunities to target H₂S-mediated signaling pathways in cancer therapy. In this review, we will focus on the mechanism of H₂S-mediated protein persulfidation and the detailed information about the dysregulation of H₂S-producing enzymes and metabolism in different cancer types. We will also provide an update on mechanisms of H₂S-mediated cancer progression and summarize current options to modulate H₂S production for cancer therapy.     

Catalytic performance of NO oxidation over LaMeO3 (Me = Mn,Fe, Co) perovskite prepared by the sol–gel method

The catalytic performance of LaMeO₃ (Me = Mn, Fe, Co) perovskite prepared by a sol–gel method was studied. These catalysts were characterized by X-ray diffraction (XRD), N₂ adsorption (BET), H₂ temperature programmed reduction (TPR), NO temperature programmed desorption (TPD) and CO–O₂ pulse. LaCoO₃ exhibited the best activity than that of LaFeO₃ and LaMnO₃ even after hydrothermal ageing. The activity sequence is in accordance with the reducibility of the samples. The activated oxygen species and adsorbed NO play key roles in the NO oxidation reaction.     

Adiabatic fixed bed gasification of dairy biomass with air and steam

Including dairy biomass (DB) as feedstock in gasification processes for locally based power generation could mitigate the environmental impact from DB produced in large US farms (56 million dry tons per year) and fossil-fuels emissions, since biomass is a CO₂ neutral fuel. The current paper presents experimental results obtained from adiabatic, fixed bed gasification of DB using air and steam as oxidizers. The effect of equivalence ratio (ER) and steam to fuel ratio (S:F) ratio on temperature profile, gas composition (CO, CO₂, H₂, N₂, CH₄, and C₂H₆), gross heating value (HHV) and energy conversion efficiency (ECE) are discussed. The results show that the peak temperature (T_peak), ECE, and CO decrease and H₂ and CO₂ increase with increase in ER; the increase in S:F at same ER increases H₂, CO₂, CH₄, HHV, and ECE, and decreases CO.     

Effect of co-combustion of chicken litter and coal on emissions in a laboratory-scale fluidized bed combustor

Co-combustion of chicken litter (CL) with coal was performed in a laboratory-scale fluidized bed combustor to investigate the effect of CL combustion on pollutant emissions. The emissions of major gaseous pollutants including CO, SO₂, H₂S and NO and temperature distribution along the combustor were measured during the tests. Effects of CL fraction and secondary air on combustion characteristics were studied. The experimental results show that CL introduction increases CO emissions and reduces the levels of SO₂. The ratio of H₂S/SO₂ increases with increasing fraction of CL. NO emissions either increase or decrease depending on the percentage of CL in the mixed fuels. The temperature in the freeboard region increases with increasing the fraction of CL while the reverse is true for the bed temperature.     

Hydrogen Sulfide and Its Donors: Keys to Unlock the Chains of Nonalcoholic Fatty Liver Disease

Hydrogen sulfide (H₂S) has emerged as the third “gasotransmitters” and has a crucial function in the diversity of physiological functions in mammals. In particular, H₂S is considered indispensable in preventing the development of liver inflammation in the case of excessive caloric ingestion. Note that the concentration of endogenous H₂S was usually low, making it difficult to discern the precise biological functions. Therefore, exogenous delivery of H₂S is conducive to probe the physiological and pathological roles of this gas in cellular and animal studies. In this review, the production and metabolic pathways of H₂S in vivo, the types of donors currently used for H₂S release, and study evidence of H₂S improvement effects on nonalcoholic fatty liver disease are systematically introduced.     

Effects of catalyst aging on the activity and selectivity of commercial three-way catalysts

A Pd catalyst is particularly effective for the oxidation of CO and C₃H₆ at low temperatures, while the Pt/Rh/Ce catalyst is active for NO reduction. The TWC activity of both catalysts generally decreased as the catalyst mileage increased. However, the NO reduction activity was less affected by catalyst aging compared to the oxidation reactions. The selectivity of the catalysts in favor of the CO–O₂ reaction (vs. C₃H₆–O₂ reaction) in the O₂ partitioning experiments became less pronounced as the catalyst aged. The NO partitioning experiments reveal the superior capability of H₂ in NO reduction to the other reductants (CO and C₃H₆) examined in the present study. The reactivities of NO with both H₂ and CO were found to decrease upon catalyst aging, resulting in decreased overall NO removal activity.     

Removal of Gas Pollutants of a Thermal Oxidizer with a Dynamic Scrubber

The absorption of gas pollutants including CO₂, CO, NO, NO₂, SO₂, and H₂S from the exhaust of a paint recuperative oxidizer into NaOH solution has been studied using an industrial scale dynamic scrubber. Experimental results show the influence of the absorbent concentration on the pollutant removal efficiency. The best removal efficiencies of CO₂, CO, NO, NO₂, SO₂, and H₂S were 79, 80, 80, 100, 75 and 88 %, respectively, with 2 % NaOH as the absorbent. A comparison of these results with previous studies shows that the liquid‐to‐gas flow rate ratio (F_L/F_G) in this dynamic scrubber is much smaller than for traditional NaOH scrubbers and spray dryers.     

Sphingosine 1-Phosphate Receptor 5 (S1P5) Knockout Ameliorates Adenine-Induced Nephropathy

S1P and its receptors have been reported to play important roles in the development of renal fibrosis. Although S1P₅ has barely been investigated so far, there are indications that it can influence inflammatory and fibrotic processes. Here, we report the role of S1P₅ in renal inflammation and fibrosis. Male S1P₅ knockout mice and wild-type mice on a C57BL/6J background were fed with an adenine-rich diet for 7 days or 14 days to induce tubulointerstitial fibrosis. The kidneys of untreated mice served as respective controls. Kidney damage, fibrosis, and inflammation in kidney tissues were analyzed by real-time PCR, Western blot, and histological staining. Renal function was assessed by plasma creatinine ELISA. The S1P₅ knockout mice had better renal function and showed less kidney damage, less proinflammatory cytokine release, and less fibrosis after 7 days and 14 days of an adenine-rich diet compared to wild-type mice. S1P₅ knockout ameliorates tubular damage and tubulointerstitial fibrosis in a model of adenine-induced nephropathy in mice. Thus, targeting S1P₅ might be a promising goal for the pharmacological treatment of kidney diseases.     

Electrochemical promotion of catalytic reactions with Pt/C (or Pt/Ru/C)//PBI catalysts

The paper is an overview of the results of the investigation on electrochemical promotion of three catalytic reactions: methane oxidation with oxygen, NO reduction with hydrogen at 135 °C and Fischer–Tropsch synthesis (FTS) at 170 °C in the [CH₄/O₂(or NO/H₂ or CO/H₂)/Ar//Pt (or Pt/Ru)//PBI(H₃PO₄)/H₂, Ar] fuel cell. It has been shown that the partial methane oxidation to C₂H₂ and the C₂ selectivity were electrochemically promoted by the negative catalyst polarization. This was also the case in NO reduction with hydrogen for low NO and H₂ partial pressures. In both cases the catalytic reactions have been promoted by the electrochemically produced hydrogen. It has been found that the NO reduction with hydrogen on the Pt/PBI strongly depends on NO and hydrogen partial pressures in the working gas mixture. At higher NO and H₂ partial pressures the catalysis is promoted by the electrochemical pumping of H⁺ from the catalyst, i.e. at positive polarization. FTS demonstrated the highest methane production rate (11% of CO conversion) at zero fuel cell voltage.     

Developmental Programming and Reprogramming of Hypertension and Kidney Disease: Impact of Tryptophan Metabolism

The concept that hypertension and chronic kidney disease (CKD) originate in early life has emerged recently. During pregnancy, tryptophan is crucial for maternal protein synthesis and fetal development. On one hand, impaired tryptophan metabolic pathway in pregnancy impacts fetal programming, resulting in the developmental programming of hypertension and kidney disease in adult offspring. On the other hand, tryptophan-related interventions might serve as reprogramming strategies to prevent a disease from occurring. In the present review, we aim to summarize (1) the three major tryptophan metabolic pathways, (2) the impact of tryptophan metabolism in pregnancy, (3) the interplay occurring between tryptophan metabolites and gut microbiota on the production of uremic toxins, (4) the role of tryptophan-derived metabolites-induced hypertension and CKD of developmental origin, (5) the therapeutic options in pregnancy that could aid in reprogramming adverse effects to protect offspring against hypertension and CKD, and (6) possible mechanisms linking tryptophan metabolism to developmental programming of hypertension and kidney disease.     

Kinetic modeling of storage and reduction with different reducing agents (CO, H2, and C2 H4) on a Pt–Ba/-Al2O3 catalyst in the presence of CO2 and H2O

In this paper a global reaction kinetic model is used to understand and describe the NO_x storage/reduction process in the presence of CO₂ and H₂O. Experiments have been performed in a packed bed reactor with a Pt–Ba/γ-Al₂O₃ powder catalyst (1 wt% Pt and 30 wt% Ba) with different lean/rich cycle timings at different temperatures (200, 250, and ) and using different reductants (H₂, CO, and C₂H₄). Model simulations and experimental results are compared. H₂O inhibits the NO oxidation capability of the catalyst and no NO₂ formation is observed. The rate of NO storage increases with temperature. The reduction of stored NO with H₂ is complete for all investigated temperatures. At temperatures above , the water gas shift (WGS) reaction takes place and H₂ acts as reductant instead of CO. At , CO and C₂H₄ are not able to completely regenerate the catalyst. At the higher temperatures, C₂H₄ is capable of reducing all the stored NO, although C₂H₄ poisons the Pt sites by carbon decomposition at . The model adequately describes the NO breakthrough profile during 100 min lean exposure as well as the subsequent release and reduction of the stored NO. Further, the model is capable of simulating transient reactor experiments with 240 s lean and 60 s rich cycle timings.     

The positive effect of hydrogen on the reaction of nitric oxide with carbon monoxide over platinum and rhodium catalysts

The effect of adding 330–4930 ppm hydrogen to a reaction mixture of NO and CO (2000 ppm each) over platinum and rhodium catalysts has been investigated at temperatures around 200–250°C. Hydrogen causes large increases in the conversion of NO and, surprisingly, also of CO. Oxygen atoms from the additional NO converted are eventually combined with CO to give CO₂ rather than react with hydrogen to form water. This reaction is described by CO + NO +3/2H₂ CO₂ + NH₃ and accounts for 50–100% of the CO₂ formed with Pt/Al₂O₃ and 20–50% with Rh/Al₂O₃. With the latter catalyst a substantial amount of NO converted produces nitrous oxide. Comparison with a known study of unsupported noble metals suggests that isocyanic acid (HNCO) might be an important intermediate in a reaction system with NO, CO and H₂ present.     

Competitive no,co and hydrocarbon oxidation reactions over a diesel oxidation catalyst

The oxidation of NO, CO and hydrocarbons (HC) individually, in mixtures, and with NO₂ were investigated over a monolith‐supported Pt/Al₂O₃ catalyst under oxidising conditions. Although competitive adsorption and inhibition by other species on oxidation reactions is a relatively well‐known phenomenon, this study represents a more comprehensive examination of such effects between key components in vehicle exhaust gases. NO₂ was completely reduced by CO and C₃H₆, under NO₂ limited conditions, at temperatures as low as 110°C and at temperatures above 140°C with dodecane and m‐xylene. NO₂ was then again observed once the extent of oxidation of the other species by oxygen was significant. Under the conditions tested, NO, CO and HC oxidation was inhibited by NO₂ in the feed gas mixture. HC were also found to inhibit the oxidation of NO and other HC species due to site adsorption competition. For CO, HC did not change the onset of oxidation, but did inhibit the extent after their light off began. At low temperatures, CO was initially found to inhibit NO oxidation, but at higher temperatures, once CO oxidation was significant, CO promoted NO conversion to NO₂. The observed inhibition effects of the different gases on HC oxidation were not additive, indicating one species would cause inhibition, but once its inhibition ended, another species could still then cause inhibition. The combined effect of C₃H₆, NO and NO₂ on CO conversion was found to be additive. This is because CO oxidation started prior C₃H₆. © 2011 Canadian Society for Chemical Engineering