Garlic oil supplementation blocks inflammatory pyroptosis-related acute lung injury by suppressing the NF-κB/NLRP3 signaling pathway via H2S generation.

Acute lung injury (ALI) is a major cause of acute respiratory failure with a high morbidity and mortality rate, and effective therapeutic strategies for ALI remain limited. Inflammatory response is considered crucial for the pathogenesis of ALI. Garlic, a globally used cooking spice, reportedly exhibits excellent anti-inflammatory bioactivity. However, protective effects of garlic against ALI have never been reported. This study aimed to investigate the protective effects of garlic oil (GO) supplementation on lipopolysaccharide (LPS)-induced ALI models. Hematoxylin and eosin staining, pathology scores, lung myeloperoxidase (MPO) activity measurement, lung wet/dry (W/D) ratio detection, and bronchoalveolar lavage fluid (BALF) analysis were performed to investigate ALI histopathology. Real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were conducted to evaluate the expression levels of inflammatory factors, nuclear factor-κB (NF-κB), NLRP3, pyroptosis-related proteins, and H2S-producing enzymes. GO attenuated LPS-induced pulmonary pathological changes, lung W/D ratio, MPO activity, and inflammatory cytokines in the lungs and BALF. Additionally, GO suppressed LPS-induced NF-κB activation, NLRP3 inflammasome expression, and inflammatory-related pyroptosis. Mechanistically, GO promoted increased H2S production in lung tissues by enhancing the conversion of GO-rich polysulfide compounds or by increasing the expression of H2S-producing enzymes in vivo. Inhibition of endogenous or exogenous H2S production reversed the protective effects of GO on ALI and eliminated the inhibitory effects of GO on NF-κB, NLRP3, and pyroptotic signaling pathways. Overall, these findings indicate that GO has a critical anti-inflammatory effect and protects against LPS-induced ALI by suppressing the NF-κB/NLRP3 signaling pathway via H2S generation.

Synergistic interplay between melatonin and hydrogen sulfide enhances cadmium-induced oxidative stress resistance in stock (Matthiola incana L.).

Ornamental crops particularly cut flowers are considered sensitive to heavy metals (HMs) induced oxidative stress condition. Melatonin (MLT) is a versatile phytohormone with the ability to mitigate abiotic stresses induced oxidative stress in plants. Similarly, signaling molecules such as hydrogen sulfide (H2S) have emerged as potential options for resolving HMs related problems in plants. The mechanisms underlying the combined application of MLT and H2S are not yet explored. Therefore, we evaluated the ability of individual and combined applications of MLT (100 µM) and H2S in the form of sodium hydrosulfide (NaHS), a donor of H2S, (1.5 mM) to alleviate cadmium (Cd) stress (50 mg L-1) in stock (Matthiola incana L.) plants by measuring various morpho-physiological and biochemical characteristics. The results depicted that Cd-stress inhibited growth, photosynthesis and induced Cd-associated oxidative stress as depicted by excessive ROS accumulation. Combined application of MLT and H2S efficiently recovered all these attributes. Furthermore, Cd stress-induced oxidative stress markers including electrolyte leakage, malondialdehyde, and hydrogen peroxide are partially reversed in Cd-stressed plants by MLT and H2S application. This might be attributed to MLT or H2S induced antioxidant plant defense activities, which effectively reduce the severity of oxidative stress indicators. Overall, MLT and H2S supplementation, favorably regulated Cd tolerance in stock; yet, the combined use had a greater effect on Cd tolerance than the independent application.

Natural H2S-donors: A new pharmacological opportunity for the management of overweight and obesity.

The prevalence of overweight and obesity has progressively increased in the last few years, becoming a real threat to healthcare systems. To date, the clinical management of body weight gain is an unmet medical need, as there are few approved anti-obesity drugs and most require an extensive monitoring and vigilance due to risk of adverse effects and poor patient adherence/persistence. Growing evidence has shown that the gasotransmitter hydrogen sulfide (H2S) and, therefore, H2S-donors could have a central role in the prevention and treatment of overweight/obesity. The main natural sources of H2S-donors are plants from the Alliaceae (garlic and onion), Brassicaceae (e.g., broccoli, cabbage, and wasabi), and Moringaceae botanical families. In particular, polysulfides and isothiocyanates, which slowly release H2S, derive from the hydrolysis of alliin from Alliaceae and glucosinolates from Brassicaceae/Moringaceae, respectively. In this review, we describe the emerging role of endogenous H2S in regulating adipose tissue function and the potential efficacy of natural H2S-donors in animal models of overweight/obesity, with a final focus on the preliminary results from clinical trials. We conclude that organosulfur-containing plants and their extracts could be used before or in combination with conventional anti-obesity agents to improve treatment efficacy and reduce inflammation in obesogenic conditions. However, further high-quality studies are needed to firmly establish their clinical efficacy.

Hydrogen sulfide and ethylene regulate sulfur-mediated stomatal and photosynthetic responses and heat stress acclimation in rice.

The gaseous signaling molecules, ethylene (ET) and hydrogen sulfide (H2S) are well known for their ability to mitigate abiotic stress, but how they interact with mineral nutrients under heat stress is unclear. We have studied the involvement of ET and H2S in adaptation of heat stress on the availability of sulfur (S) levels in rice (Oryza sativa L.). Heat stress (40 °C) negatively impacted growth and photosynthetic-sulfur use efficiency (p-SUE), with accumulation of reactive oxygen species (ROS) in six rice cultivars, namely PS 2511, Birupa, Nidhi, PB 1509, PB 1728, and Panvel. Supplementation of S at 2.0 mM SO42- in the form of MgSO4, improved growth and photosynthetic attributes more than 1.0 mM SO42- under control (28 °C), and mitigated heat stress effects more prominently in PS 2511 (heat-tolerant) than in PB 1509 (heat-sensitive) cultivar. The higher heat stress mitigation potential of 2.0 mM SO42- in heat-tolerant cultivar was correlated with higher S-assimilation, activity of antioxidant enzymes, stomatal (stomatal conductance) and non-stomatal limitations, activity of carbonic anhydrase and Rubisco, and mesophyll conductance. The use of norbornadiene (NBD) and hypotaurine (HT), ET and H2S inhibitors, respectively, resulted in the lowest values for photosynthetic efficiency, stomatal and non-stomatal factors, implying the mediation of ET and H2S in heat stress acclimation. The connectivity of ET and H2S with S-assimilation through a common metabolite cysteine (Cys) improved heat stress adaptation in which H2S acted downstream to ET-mediated responses. Thus, the better adaptability of rice plants to heat stress may be obtained through modulation of ET and H2S via S.

Effect of water sulfate and dietary bismuth subsalicylate on feed and water intake, ruminal hydrogen sulfide concentration, and trace-mineral status of growing beef heifers.

In the Northern Great Plains, cattle may be exposed to water with an elevated sulfate concentration resulting in ruminal hydrogen sulfide (H2S) production and risk of copper deficiency. There are currently few strategies available to help mitigate effects arising from high-sulfate water (HS). The objective of this study was to evaluate the effects of feeding a moderate-forage diet with or without bismuth subsalicylate (BSS; 0.0% vs. 0.4% DM basis) when provided water with a low- (LS; 346 ±â€…13) or HS (4,778 ±â€…263 mg/L) concentration on feed and water intake, ruminal H2S concentration, and liver and serum trace-mineral concentrations. Twenty-four Limousin × Simmental cross beef heifers (221 ±â€…41 kg) were stratified based on initial liver Cu into a completely randomized block design with a 2 × 2 factorial treatment arrangement. Feed and water intake (measured weekly), ruminal H2S concentration (measured on days 42 and 91), liver (measured on days -13 and 91), and serum trace-mineral concentrations (measured on days 1, 28, 56, and 91) were evaluated. Initial liver trace-mineral concentrations were used as a covariate in the statistical model. Water intake tended to be reduced with the inclusion of BSS (P = 0.095) but was not affected by water sulfate (P = 0.40). Water sulfate and BSS did not affect dry matter intake (DMI; P ≥ 0.89). Heifers consuming HS had a ruminal H2S concentration that was 1.58 mg/L more (P < 0.001) than LS. The inclusion of BSS reduced (P = 0.035) ruminal H2S concentration by more than 44% (1.35 vs. 0.75 mg/L). Regardless of the water sulfate concentration, heifers fed BSS had lesser liver Cu concentration (average of 4.08 mg/kg) than heifers not provided BSS, and when not provided BSS, HS had lesser Cu than LS (42.2 vs. 58.3; sulfate × BSS, P = 0.019). The serum concentration of Cu did not differ over time for heifers not provided BSS; whereas, heifers provided BSS had lesser serum Cu concentration on day 91 than on days 28 and 55 (BSS × time, P < 0.001). The liver concentration of selenium was reduced (P < 0.001) with BSS inclusion but the selenium concentration in serum was not affected by sulfate, BSS, or time (P ≥ 0.16). BSS reduced ruminal H2S concentration, but depleted liver Cu and Se. Moreover, sulfate concentration in water did not appear to affect DMI, water intake, or growth, but increased ruminal H2S and reduced liver Cu concentration.

Water containing a high concentration of sulfate increases the risk of hydrogen sulfide production in the rumen and consequently of polioencephalomalacia. In addition, water with a high-sulfate concentration may induce copper deficiency indicated by depleted liver copper concentration. Bismuth subsalicylate (BSS) can bind to sulfides and may reduce the risk of hydrogen sulfide production and therefore may mitigate risks associated with high-sulfate water. In this study, the effects of water sulfate concentrations (346 ±â€…13 vs. 4,778 ±â€…263 mg/L) were tested along with 0.0% vs. 0.4% of dietary BSS. Water intake tended to be reduced with the inclusion of BSS but was not affected by water sulfate. Water sulfate concentration and BSS did not affect dry matter intake (DMI). Heifers consuming high-sulfate water (HS) had a ruminal H2S concentration that was 1.58 mg/L more than low-sulfate water (LS). The inclusion of BSS reduced ruminal H2S concentration by 44% (1.35 vs. 0.75 mg/L). Regardless of the water sulfate concentration, heifers fed BSS had lesser liver Cu concentration than heifers not provided BSS, and when not provided BSS, HS had lesser Cu than LS. BSS reduced ruminal hydrogen sulfide concentration but depleted liver Cu. Sulfate concentration in water did not affect DMI, water intake, or growth, but increased ruminal hydrogen sulfide concentration and reduced liver Cu concentration.

Mitigating salt toxicity and overcoming phosphate deficiency alone and in combination in pepper (Capsicum annuum L.) plants through supplementation of hydrogen sulfide.

While it is widely recognized that hydrogen sulfide (H2S) promotes plant stress tolerance, the precise processes through which H2S modulates this process remains unclear. The processes by which H2S promotes phosphorus deficiency (PD) and salinity stress (SS) tolerance, simulated individually or together, were examined in this study. The adverse impacts on plant biomass, total chlorophyll and chlorophyll fluorescence were more pronounced with joint occurrence of PD and SS than with individual application. Malondialdehyde (MDA), hydrogen peroxide (H2O2), and electrolyte leakage (EL) levels in plant leaves were higher in plants exposed to joint stresses than in plants grown under an individual stress. When plants were exposed to a single stress as opposed to both stressors, sodium hydrosulfide (NaHS) treatment more efficiently decreased EL, MDA, and H2O2 concentrations. Superoxide dismutase, peroxidase, glutathione reductase and ascorbate peroxidase activities were increased by SS alone or in conjunction with PD, whereas catalase activity decreased significantly. The favorable impact of NaHS on all the evaluated attributes was reversed by supplementation with 0.2 mM hypotaurine (HT), a H2S scavenger. Overall, the unfavorable effects caused to NaHS-supplied plants by a single stress were less severe compared with those caused by the combined administration of both stressors.

Selenium-Based Catalytic Scavengers for Concurrent Scavenging of H2 S and Reactive Oxygen Species.

Hydrogen sulfide (H2 S) is an endogenous gasotransmitter that plays important roles in redox signaling. H2 S overproduction has been linked to a variety of disease states and therefore, H2 S-depleting agents, such as scavengers, are needed to understand the significance of H2 S-based therapy. It is known that elevated H2 S can induce oxidative stress with elevated reactive oxygen species (ROS) formation, such as in H2 S acute intoxication. We explored the possibility of developing catalytic scavengers to simultaneously remove H2 S and ROS. Herein, we studied a series of selenium-based molecules as catalytic H2 S/H2 O2 scavengers. Inspired by the high reactivity of selenoxide compounds towards H2 S, 14 diselenide/monoselenide compounds were tested. Several promising candidates such as S6 were identified. Their activities in buffers, as well as in plasma- and cell lysate-containing solutions were evaluated. We also studied the reaction mechanism of this scavenging process. Finally, the combination of the diselenide catalyst and photosensitizers was used to achieve light-induced H2 S removal. These Se-based scavengers can be useful tools for understanding H2 S/ROS regulations.

Resistant effects determination of Lactobacillus supplementation on broilers to consecutive hydrogen sulfide exposure.

Hydrogen sulfide (H2S) is one of the most irritant gases present in rearing stalls that suppress broilers' healthy growth, which is seriously required an effective alleviation method. In this study, Lactobacillus was supplemented to investigate the alleviative effects on broilers reared under consecutive H2S exposure. A total of 180 healthy 1-day-old male AA broilers with similar body weight (40.8 ± 1.0 g) were randomly allotted into the control treatment (CON), the hydrogen sulfide treatment (H2S), and the Lactobacillus supplement under H2S exposure treatment (LAC) for a 42-d-long feeding process. Growth and carcass performances, immunity-related parameters, intestinal development and cecal microbial communities, and blood metabolites were measured. Results showed that Lactobacillus supplement significantly increased the body weight gain (BWG) while reduced the mortality rate, abdominal fat and bursa of fabricius weight during the whole rearing time compared with H2S treatment (P < 0.05). Serum LPS, IL-1ß, IL-2, and IL-6 contents were observed significantly increased after H2S treatment while remarkably decreased after Lactobacillus supplementation(P < 0.05). Intestinal morphology results showed a significant higher in the development of ileum villus height (P < 0.05). Cecal microbiota results showed the bacterial composition was significantly altered after Lactobacillus supplement (P < 0.05). Specifically, Lactobacillus supplement significantly decreased the relative abundance of Faecalibacterium, while significantly proliferated the relative abundance of Lactobacillus, Bifidobacterium, Clostridium, and Campylobacter (P<0.05). Metabolic results indicated that Lactobacillus supplement may alleviate the harmful effects caused by H2S through regulating the pyrimidine metabolism, starch and sucrose metabolism, fructose and mannose degradation, and beta-alanine metabolism. In summary, Lactobacillus supplement effectively increased BWG and decreased mortality rate of broilers under H2S exposure by enhancing the body's immune capacity, proliferating beneficial microbes (e.g., Lactobacillus and Bifidobacterium), and regulating the physiological pyrimidine metabolism, starch and sucrose metabolism, and beta-alanine metabolism.

Positive association of acetylcholinesterase (AChE) with the neutrophil-to-lymphocyte ratio and HbA1c, and a negative association with hydrogen sulfide (H2S) levels among healthy African Americans, and H2S-inhibition and high-glucose-upregulation of AChE in cultured THP-1 human monocytes.

The incidence of Alzheimer's disease (AD) is higher in people over the age of 65 and in African Americans (AA). Elevated acetylcholinesterase (AChE) activity has been considered a major player in the onset of AD symptoms. As a result, many FDA-approved AD drugs target AChE inhibition to treat AD patients. Hydrogen sulfide (H2S) is a signaling molecule known to downregulate oxidative stress and inflammation. The neutrophil-to-lymphocyte ratio (NLR) in the blood is widely used as a biomarker to monitor inflammation and immunity. This study examined the hypothesis that plasma AChE levels have a negative association with H2S levels and that a positive association exists between levels of NLR, HbA1c, and ROS with the AChE in the peripheral blood. The fasting blood sample was taken from 114 African Americans who had provided written informed consent approved by the IRB. The effect of H2S and high-glucose treatment on AChE activity levels was also investigated in THP-1 human monocytes. There was a significant negative relationship between AChE and the levels of H2S (r = -0.41, p = 0.001); a positive association between the levels of AChE with age (r = 0.26, p = 0.03), NLR (r = 0.23, p = 0.04), ROS (r = 0.23, p = 0.04) and HbA1c levels (r = 0.24, p = 0.04), in AA subjects. No correlation was seen between blood levels of AChE and acetylcholine (ACh). Blood creatinine had a negative correlation (r = -0.23, p = 0.04) with ACh levels. There was a significant effect of H2S on AChE inhibition and of high glucose in upregulating AChE activity in cultured monocytes. This study suggests hyperglycemia and lower H2S status can contribute to an increase in the AChE activity levels. Future clinical studies are needed to examine the potential benefits of supplementation with hydrogen sulfide pro-drugs/compounds in reducing the AChE and the cognitive dysfunctions associated with AD.

Hydrogen sulfide: From a toxic gas to a potential therapy for COVID-19 and inflammatory disorders.

COVID-19 has been shown to induce inflammatory disorders and CNS manifestations. Swift and efficient treatment strategies are urgently warranted for the management of COVID, inflammatory and neurological disorders. Hydrogen sulfide (H2S) has been associated with several clinical disorders due to its potential to influence a broad range of biological signalling pathways. According to recent clinical studies, COVID patients with lower physiological H2S had higher fatality rates. These findings clearly demonstrate an inverse correlation between H2S levels and the severity of COVID-19. H2S has been proposed as a protective molecule because of its antioxidant, anti-inflammatory, and antiviral properties. Various H2S-releasing prodrugs, hybrids and natural compounds have been tested for their therapeutic efficacy in viral infections and inflammatory disorders. In this review, I am highlighting the rationale for using H2S-based interventions for the management of COVID-19 and post-infection inflammatory disorders including neuroinflammation. I am also proposing therepurposing of existing H2S-releasing prodrugs, developing new NO-H2S-hybrids, targeting H2S metabolic pathways, and using H2S-producing dietary supplements as viable defensive strategies against SARS-CoV-2 infection and COVID-19 pathologies.

Deficiency of hydrogen sulfide production and pregnancy rate in an experimental model: Association with preterm delivery.

PROBLEM: Pro-inflammatory phenomena drive preterm delivery (PTD). Hydrogen sulfide is a gasotransmitter with anti-inflammatory properties produced through the activity of the enzyme cystathionine-γ-lyase (CSE), and its impact was studied in models of normal delivery and PTD in mice. METHOD OF STUDY: Female CSE+/+ and CSE-/- mice were mated with male CSE+/+ mice; mating was done with drinking water unsupplemented and supplemented with cysteine. The pregnancy rate was monitored. PTD was induced by the intraperitoneal injection of bacterial lipopolysaccharide (LPS) on day 14.5 of pregnancy. Mice were sacrificed for tissue collection and splenocyte isolation after 6 and 12 h. Isolated splenocytes were stimulated for the production of tumor necrosis factor-alpha (TNFα), interleukin (IL)-10 and interferon-gamma (IFNγ); TNFα and vascular endothelial growth factor (VEGF) were measured in the fetuses and the placenta. RESULTS: The successful pregnancy rate was lower in CSE-/- mice and it was restored with cysteine supplementation. CSE deficiency was associated with higher tissue concentrations of TNFα in the fetuses, attenuated IL-10 responses and higher IFNγ production from splenocytes. CSE deficiency was not associated with PTD. Following PTD induction, CSE-/- mice did not show attenuated IL-10 responses but the production of TNFα and IFNγ was lowered over-time; placental VEGF was also increased over-time. CONCLUSIONS: CSE deficiency has an unfavorable impact on pregnancy. H2 S deficiency through CSE does not drive PTD but mediates pro-inflammatory phenomena in fetuses.

Inhibition of the voltage-gated potassium channel Kv1.5 by hydrogen sulfide attenuates remodeling through S-nitrosylation-mediated signaling.

The voltage-gated K+ channel plays a key role in atrial excitability, conducting the ultra-rapid rectifier K+ current (IKur) and contributing to the repolarization of the atrial action potential. In this study, we examine its regulation by hydrogen sulfide (H2S) in HL-1 cardiomyocytes and in HEK293 cells expressing human Kv1.5. Pacing induced remodeling resulted in shorting action potential duration, enhanced both Kv1.5 channel and H2S producing enzymes protein expression in HL-1 cardiomyocytes. H2S supplementation reduced these remodeling changes and restored action potential duration through inhibition of Kv1.5 channel. H2S also inhibited recombinant hKv1.5, lead to nitric oxide (NO) mediated S-nitrosylation and activated endothelial nitric oxide synthase (eNOS) by increased phosphorylation of Ser1177, prevention of NO formation precluded these effects. Regulation of Ikur by H2S has important cardiovascular implications and represents a novel and potential therapeutic target.

Titanium dioxide nanoparticles require K+ and hydrogen sulfide to regulate nitrogen and carbohydrate metabolism during adaptive response to drought and nickel stress in cucumber.

Crop plants face severe yield losses worldwide owing to their exposure to multiple abiotic stresses. The study described here, was conducted to comprehend the response of cucumber seedlings to drought (induced by 15% w/v polyethylene glycol 8000; PEG) and nickel (Ni) stress in presence or absence of titanium dioxide nanoparticle (nTiO2). In addition, it was also investigated how nitrogen (N) and carbohydrate metabolism, as well as the defense system, are affected by endogenous potassium (K+) and hydrogen sulfide (H2S). Cucumber seedlings were subjected to Ni stress and drought, which led to oxidative stress and triggered the defense system. Under the stress, N and carbohydrate metabolism were differentially affected. Supplementation of the stressed seedlings with nTiO2 (15 mg L-1) enhanced the activity of antioxidant enzymes, ascorbate-glutathione (AsA-GSH) system and elevated N and carbohydrates metabolism. Application of nTiO2 also enhanced the accumulation of phytochelatins and activity of the enzymes of glyoxalase system that provided additional protection against the metal and toxic methylglyoxal. Osmotic stress brought on by PEG and Ni, was countered by the increase of proline and carbohydrates levels, which helped the seedlings keep their optimal level of hydration. Application nTiO2 improved the biosynthesis of H2S and K+ retention through regulating Cys biosynthesis and H+-ATPase activity, respectively. Observed outcomes lead to the conclusion that nTiO2 maintains redox homeostasis, and normal functioning of N and carbohydrates metabolism that resulted in the protection of cucumber seedlings against drought and Ni stress. Use of 20 mM tetraethylammonium chloride (K+- channel blocker), 500 µM sodium orthovanadate (PM H+-ATPase inhibitor), and 1 mM hypotaurine (H2S scavenger) demonstrate that endogenous K+ and H2S were crucial for the nTiO2-induced modulation of plants' adaptive responses to the imposed stress.

Hydrogen sulfide alleviates heart failure with preserved ejection fraction in mice by targeting mitochondrial abnormalities via PGC-1α.

AIM: Increasing evidence has proposed that mitochondrial abnormalities may be an important factor contributing to the development of heart failure with preserved ejection fraction (HFpEF). Hydrogen sulfide (H2S) has been suggested to play a pivotal role in regulating mitochondrial function. Therefore, the present study was designed to explore the protective effect of H2S on mitochondrial dysfunction in a multifactorial mouse model of HFpEF. METHODS: Wild type, 8-week-old, male C57BL/6J mice or cardiomyocyte specific-Cse (Cystathionine γ-lyase, a major H2S-producing enzyme) knockout mice (CSEcko) were given high-fat diet (HFD) and l-NAME (an inhibitor of constitutive nitric oxide synthases) or standardized chow. After 4 weeks, mice were randomly administered with NaHS (a conventional H2S donor), ZLN005 (a potent transcriptional activator of PGC-1α) or vehicle. After additional 4 weeks, echocardiogram and mitochondrial function were evaluated. Expression of PGC-1α, NRF1 and TFAM in cardiomyocytes was assayed by Western blot. RESULTS: Challenging with HFD and l-NAME in mice not only caused HFpEF but also inhibited the production of endogenous H2S in a time-dependent manner. Meanwhile the expression of PGC-1α and mitochondrial function in cardiomyocytes were impaired. Supplementation with NaHS not only upregulated the expression of PGC-1α, NRF1 and TFAM in cardiomyocytes but also restored mitochondrial function and ultrastructure, conferring an obvious improvement in cardiac diastolic function. In contrast, cardiac deletion of CSE gene aggravated the inhibition of PGC-1α-NRF1-TFAM pathway, mitochondrial abnormalities and diastolic dysfunction. The deleterious effect observed in CSEcko HFpEF mice was partially counteracted by pre-treatment with ZLN005 or supplementation with NaHS. CONCLUSION: Our findings have demonstrated that H2S ameliorates left ventricular diastolic dysfunction by restoring mitochondrial abnormalities via upregulating PGC-1α and its downstream targets NRF1 and TFAM, suggesting the therapeutic potential of H2S supplementation in multifactorial HFpEF.

Wastewater Treatment Plants as a Source of Malodorous Substances Hazardous to Health, Including a Case Study from Poland.

Using Poland as an example, it was shown that 41.6% of the requests for intervention in 2016-2021 by Environmental Protection Inspections were related to odour nuisance. Further analysis of the statistical data confirmed that approximately 5.4% of wastewater treatment plants in the group of municipal facilities were subject to complaints. Detailed identification of the subject of odour nuisance at wastewater treatment plants identified hydrogen sulphide (H2S), ammonia (NH3) and volatile organic compounds (VOCs) as the most common malodorous substances within these facilities. Moreover, the concentrations of hydrogen sulphide and ammonia exceed the reference values for some substances in the air (0.02 mg/m3 for H2S and 0.4 mg/m3 for NH3). A thorough assessment of the properties of these substances made it clear that even in small concentrations they have a negative impact on the human body and the environment, and their degree of nuisance is described as high. In the two WWTPs analysed in Poland (WWTP 1 and WWTP 2), hydrogen sulphide concentrations were in the range of 0-41.86 mg/m3 (Long-Term Exposure Limit for H2S is 7.0 mg/m3), ammonia 0-1.43 mg/m3 and VOCs 0.60-134.79 ppm. The values recognised for H2S cause lacrimation, coughing, olfactory impairment, psychomotor agitation, and swelling of the cornea with photophobia. Recognition of the methods used in practice at WWTPs to reduce and control malodorous emissions indicates the possibility of protecting the environment and human health, but these solutions are ignored in most facilities due to the lack of requirements specified in legislation.

Improving endothelial health with food-derived H2S donors: an in vitro study with S-allyl cysteine and with a black-garlic extract enriched in sulfur-containing compounds.

A healthy vascular endothelium plays an essential role in modulating vascular tone by producing and releasing vasoactive factors such as nitric oxide (NO). Endothelial dysfunction (ED), the loss of the endothelium physiological functions, results in the inability to properly regulate vascular tone, leading to hypertension and other cardiovascular risk factors. Alongside NO, the gasotransmitter hydrogen sulfide (H2S) has emerged as a key molecule with vasodilatory and antioxidant activities. Since a reduction in H2S bioavailability is related to ED pathogenesis, natural H2S donors are very attractive. In particular, we focused on the sulfur-containing amino acid S-allyl cysteine (SAC), a bioactive metabolite, of which black garlic is particularly rich, with antioxidant activity and, among others, anti-diabetic and anti-hypertensive properties. In this study, we analyzed the protective effect of SAC against ED by evaluating reactive oxygen species level, H2S release, eNOS phosphorylation, and NO production (by fluorescence imaging and western blot analysis) in Bovine Aortic Endothelial cells (BAE-1). Furthermore, we chemically characterized a Black Garlic Extract (BGE) for its content in SAC and other sulfur-containing amino acids. BGE was used to carry out an analysis on H2S release on BAE-1 cells. Our results show that both SAC and BGE significantly increase H2S release. Moreover, SAC reduces ROS production and enhances eNOS phosphorylation and the consequent NO release in our cellular model. In this scenario, a natural extract enriched in SAC could represent a novel therapeutic approach to prevent the onset of ED-related diseases.

Mechanism determination on the interactive effects between host immunity and gut microbiome to resist consecutive hydrogen sulfide inhalation of laying hens.

The study aims to investigate the underlying mechanism of the interactions between intestinal microbiota and host immunity-related parameters in response to H2S inhalation of layer hens. A total of 180 healthy 300-day-old Lohmann pink hens with similar body weight were randomly allotted into the control (CON) and the hydrogen sulfide (H2S) treatments for an 8-wk-long feeding procedure. Productive performances, antioxidant capacities, immunity-related parameters, blood metabolites, and cecal microbiota were measured to determine the physiological and gastrointestinal responses to H2S treatment. Results showed that feed intake, egg production, eggshell strength, Haugh unit, and relative yolk weight significantly declined under H2S treatment compared with CON (P < 0.05). Antioxidant and immunity-related parameters showed that glutathione peroxidase, IL-4, and TNF-α contents significantly decreased, whereas contents of IL-1ß, IL-2, and IL-6 significantly increased after H2S treatment (P < 0.05). Further metabolic results showed H2S treatment upregulated 2-mercaptobenzothiazole, D-glucopyranuronic acid, deoxyuridine, cholic acid, and mimosine, etc., which mainly enriched into the pyrimidine metabolism, beta-alanine metabolism, valine, leucine, and isoleucine biosynthesis, and pantothenate and CoA biosynthesis pathways. Meanwhile, aceturic acid, 9-oxodecenoic acid, palmitoleic acid, lauric acid, linoleic acid, oleic acid, and valeric acid mainly contributed to the downregulated metabolites, and enriched into the biosynthesis of unsaturated fatty acids, amino sugar and nucleotide sugar metabolism, tryptophan metabolism and linoleic metabolism. Moreover, H2S treatment significantly proliferated the relative abundances of Faecalibacterium, Ruminococcaceae, and Streptococcus, while decreased Prevotella, Lactobacillus, Bifidobacterium, Clostridium, and Campylobacter (P < 0.05). The altered bacteria were functionally enriched in the carbohydrate metabolism, amino acid metabolism, and metabolism of cofactors and vitamins pathways. H2S treatment also significantly downregulated the expression of ZO-1, Claudin 4, and Claudin 7 (P < 0.05). In summary, intestinal microbial communities altered significantly to make proper adaptations in interacting with the host immune systems through the immunity-related metabolites secretion, and epithelial tight-junction-related genes expressions, purposely to regulate the productive performance under hydrogen sulfide inhalation.

Facile synthesis of non-modified yellow emission silicon quantum dots and their visualization of hydrogen sulfide in living cells and onion tissues.

Yellow fluorescent silicon quantum dots (y-SiQDs) with 22.2% fluorescence quantum yield were synthesized by a simple hydrothermal method using 3-glycidoxypropyl triethoxysilane (GOTS) and m-aminophenol. The excitation wavelength is 550 nm with an emission wavelength of 574 nm, which effectively avoids the interference of biological autofluorescence. Notably, the synthesis approach does not require any post-modification and the y-SiQDs can be directly used for hydrogen sulfide (H2S) quantification due to static quenching. It exhibits high sensitivity and excellent selectivity for H2S with a 0.2-10 µM (R2 = 0.9953) linear range and detection limit of 54 nM. y-SiQDs have excellent stability and biocompatibility and can be used for H2S imaging in living cells and onion tissues.

Cysteine-responsive prodrug of the anti-cancer drug amonafide: fluorogenic adjuvant drug delivery with hydrogen sulfide (H2S).

L-Cysteine (Cys)-responsive turn-on fluorogenic prodrug AM-ITC was developed for the adjuvant delivery of the anti-cancer drug amonafide and the gasotransmitter hydrogen sulfide (H2S) in aqueous and cellular media. Considering the cytoprotective roles of H2S, the present adjuvant strategy would be helpful in minimizing the anti-cancer drug-induced side-effects.

Exogenous hydrogen sulfide and methylglyoxal alleviate cadmium-induced oxidative stress in Salix matsudana Koidz by regulating glutathione metabolism.

BACKGROUND: Cadmium (Cd) is a highly toxic element for plant growth. In plants, hydrogen sulfide (H2S) and methylglyoxal (MG) have emerged as vital signaling molecules that regulate plant growth processes under Cd stress. However, the effects of sodium hydrosulfide (NaHS, a donor of H2S) and MG on Cd uptake, physiological responses, and gene expression patterns of Salix to Cd toxicity have been poorly understood. Here, Salix matsudana Koidz. seedlings were planted in plastic pot with applications of MG (108 mg kg- 1) and NaHS (50 mg kg- 1) under Cd (150 mg kg- 1) stress. RESULTS: Cd treatment significantly increased the reactive oxygen species (ROS) levels and malondialdehyde (MDA) content, but decreased the growth parameters in S. matsudana. However, NaHS and MG supplementation significantly decreased Cd concentration, ROS levels, and MDA content, and finally enhanced the growth parameters. Cd stress accelerated the activities of antioxidative enzymes and the relative expression levels of stress-related genes, which were further improved by NaHS and MG supplementation. However, the activities of monodehydroascorbate reductase (MDHAR), and dehydroascorbate reductase (DHAR) were sharply decreased under Cd stress. Conversely, NaHS and MG applications restored the MDHAR and DHAR activities compared with Cd-treated seedlings. Furthermore, Cd stress decreased the ratios of GSH/GSSG and AsA/DHA but considerably increased the H2S and MG levels and glyoxalase I-II system in S. matsudana, while the applications of MG and NaHS restored the redox status of AsA and GSH and further improved glyoxalase II activity. In addition, compared with AsA, GSH showed a more sensitive response to exogenous applications of MG and NaHS and plays more important role in the detoxification of Cd. CONCLUSIONS: The present study illustrated the crucial roles of H2S and MG in reducing ROS-mediated oxidative damage to S. matsudana and revealed the vital role of GSH metabolism in regulating Cd-induced stress.