Curcumin reduces myocardial ischemia-reperfusion injury, by increasing endogenous H2S levels and further modulating m6A.

BACKGROUND: Our previous research shows that Curcumin (CUR) attenuates myocardial ischemia-reperfusion injury (MIRI) by reducing intracellular total RNA m6A levels. However, the mechanism remains unknown. METHODS: For ischemia-reperfusion (IR), H9c2 cells were cultured for 6 h in serum-free low-glycemic (1 g/L) medium and a gas environment without oxygen, and then cultured for 6 h in high-glycemic (4.5 g/L) medium supplemented with 10% FBS and a 21% oxygen environment. The effects of different concentrations of CUR (5, 10, and 20 µM) treatments on signaling molecules in conventionally cultured and IR-treated H9c2 cells were examined. RESULTS: CUR treatment significantly up-regulated the H2S levels, and the mRNA and protein expression of cystathionine γ-lyase (CSE), and down-regulated the mRNAs and proteins levels of thiosulfate sulfurtransferase (TST) and ethylmalonic encephalopathy 1 (ETHE1) in H9c2 cells conventionally cultured and subjected to IR. Exogenous H2S supply (NaHS and GYY4137) significantly reduced intracellular total RNA m6A levels, and the expression of RNA m6A "writers" METTL3 and METTL14, and increased the expression of RNA m6A "eraser" FTO in H9c2 cells conventionally cultured and subjected to IR. CSE knockdown counteracted the inhibitory effect of CUR treatment on ROS production, promotion on cell viability, and inhibition on apoptosis of H9c2 cells subjected to IR. CONCLUSION: CUR attenuates MIRI by regulating the expression of H2S level-regulating enzymes and increasing the endogenous H2S levels. Increased H2S levels could regulate the m6A-related proteins expression and intracellular total RNA m6A levels.

AP39, a novel mitochondria-targeted hydrogen sulfide donor ameliorates doxorubicin-induced cardiotoxicity by regulating the AMPK/UCP2 pathway.

Doxorubicin (DOX) is a broad-spectrum, highly effective antitumor agent; however, its cardiotoxicity has greatly limited its use. Hydrogen sulfide (H2S) is an endogenous gaseous transmitter that exerts cardioprotective effects via the regulation of oxidative stress and apoptosis and maintenance of mitochondrial function, among other mechanisms. AP39 is a novel mitochondria-targeted H2S donor that, at appropriate concentrations, attenuates intracellular oxidative stress damage, maintains mitochondrial function, and ameliorates cardiomyocyte injury. In this study, DOX-induced cardiotoxicity models were established using H9c2 cells and Sprague-Dawley rats to evaluate the protective effect of AP39 and its mechanisms of action. Both in vivo and in vitro experiments showed that DOX induces oxidative stress injury, apoptosis, and mitochondrial damage in cardiomyocytes and decreases the expression of p-AMPK/AMPK and UCP2. All DOX-induced changes were attenuated by AP39 treatment. Furthermore, the protective effect of AP39 was significantly attenuated by the inhibition of AMPK and UCP2. The results suggest that AP39 ameliorates DOX-induced cardiotoxicity by regulating the expression of AMPK/UCP2.

Priming avocado with sodium hydrosulfide prior to frost conditions induces the expression of genes involved in protection and stress responses.

Priming plants with chemical agents has been extensively investigated as a means for improving their tolerance to many biotic and abiotic stresses. Earlier, we showed that priming young avocado (Persea americana Mill cv. 'Hass') trees with sodium hydrosulfide (NaHS), a donor of hydrogen sulfide, improves the response of photosynthesis to simulated frost (cold followed by high light) conditions. In the current study, we performed a transcriptome analysis to gain insight into the molecular response of avocado 'Hass' leaves to frost, with or without NaHS priming. The analysis revealed 2144 (down-regulated) and 2064 (up-regulated) differentially expressed genes (DEGs) common to both non-primed and primed trees. Non-primed trees had 697 (down) and 559 (up) unique DEGs, while primed trees exhibited 1395 (down) and 1385 (up) unique DEGs. We focus on changes in the expression patterns of genes encoding proteins involved in photosynthesis, carbon cycle, protective functions, biosynthesis of isoprenoids and abscisic acid (ABA), as well as ABA-regulated genes. Notably, the differential expression results depict the enhanced response of primed trees to the frost and highlight gene expression changes unique to primed trees. Amongst these are up-regulated genes encoding pathogenesis-related proteins, heat shock proteins, enzymes for ABA metabolism, and ABA-induced transcription factors. Extending the priming experiments to field conditions, which showed a benefit to the physiology of trees following chilling, suggests that it can be a possible means to improve trees' response to cold stress under natural winter conditions.

The CBS/H2S signalling pathway regulated by the carbon repressor CreA promotes cellulose utilization in Ganoderma lucidum.

Cellulose is an important abundant renewable resource on Earth, and the microbial cellulose utilization mechanism has attracted extensive attention. Recently, some signalling molecules have been found to regulate cellulose utilization and the discovery of underlying signals has recently attracted extensive attention. In this paper, we found that the hydrogen sulfide (H2S) concentration under cellulose culture condition increased to approximately 2.3-fold compared with that under glucose culture condition in Ganoderma lucidum. Further evidence shown that cellulase activities of G. lucidum were improved by 18.2-27.6% through increasing H2S concentration. Then, we observed that the carbon repressor CreA inhibited H2S biosynthesis in G. lucidum by binding to the promoter of cbs, a key gene for H2S biosynthesis, at "CTGGGG". In our study, we reported for the first time that H2S increased the cellulose utilization in G. lucidum, and analyzed the mechanism of H2S biosynthesis induced by cellulose. This study not only enriches the understanding of the microbial cellulose utilization mechanism but also provides a reference for the analysis of the physiological function of H2S signals.

H2S-driven chemotherapy and mild photothermal therapy induced mitochondrial reprogramming to promote cuproptosis.

The elevated level of hydrogen sulfide (H2S) in colon cancer hinders complete cure with a single therapy. However, excessive H2S also offers a treatment target. A multifunctional cascade bioreactor based on the H2S-responsive mesoporous Cu2Cl(OH)3-loaded hypoxic prodrug tirapazamine (TPZ), in which the outer layer was coated with hyaluronic acid (HA) to form TPZ@Cu2Cl(OH)3-HA (TCuH) nanoparticles (NPs), demonstrated a synergistic antitumor effect through combining the H2S-driven cuproptosis and mild photothermal therapy. The HA coating endowed the NPs with targeting delivery to enhance drug accumulation in the tumor tissue. The presence of both the high level of H2S and the near-infrared II (NIR II) irradiation achieved the in situ generation of photothermic agent copper sulfide (Cu9S8) from the TCuH, followed with the release of TPZ. The depletion of H2S stimulated consumption of oxygen, resulting in hypoxic state and mitochondrial reprogramming. The hypoxic state activated prodrug TPZ to activated TPZ (TPZ-ed) for chemotherapy in turn. Furthermore, the exacerbated hypoxia inhibited the synthesis of adenosine triphosphate, decreasing expression of heat shock proteins and subsequently improving the photothermal therapy. The enriched Cu2+ induced not only cuproptosis by promoting lipoacylated dihydrolipoamide S-acetyltransferase (DLAT) heteromerization but also performed chemodynamic therapy though catalyzing H2O2 to produce highly toxic hydroxyl radicals ·OH. Therefore, the nanoparticles TCuH offer a versatile platform to exert copper-related synergistic antitumor therapy.

Catalytic specificity and crystal structure of cystathionine γ-lyase from Pseudomonas aeruginosa.

The escalating drug resistance among microorganisms underscores the urgent need for innovative therapeutic strategies and a comprehensive understanding of bacteria's defense mechanisms against oxidative stress and antibiotics. Among the recently discovered barriers, the endogenous production of hydrogen sulfide (H2S) via the reverse transsulfuration pathway, emerges as a noteworthy factor. In this study, we have explored the catalytic capabilities and crystal structure of cystathionine γ-lyase from Pseudomonas aeruginosa (PaCGL), a multidrug-opportunistic pathogen chiefly responsible for nosocomial infections. In addition to a canonical L-cystathionine hydrolysis, PaCGL efficiently catalyzes the production of H2S using L-cysteine and/or L-homocysteine as alternative substrates. Comparative analysis with the human enzyme and counterparts from other pathogens revealed distinct structural features within the primary enzyme cavities. Specifically, a distinctly folded entrance loop could potentially modulate the access of substrates and/or inhibitors to the catalytic site. Our findings offer significant insights into the structural evolution of CGL enzymes across different pathogens and provide novel opportunities for developing specific inhibitors targeting PaCGL.

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.

H2S preconditioning induces long-lived perturbations in O2 metabolism.

Hydrogen sulfide exposure in moderate doses can induce profound but reversible hypometabolism in mammals. At a cellular level, H2S inhibits the electron transport chain (ETC), augments aerobic glycolysis, and glutamine-dependent carbon utilization via reductive carboxylation; however, the durability of these changes is unknown. We report that despite its volatility, H2S preconditioning increases P50(O2), the O2 pressure for half-maximal cellular respiration, and has pleiotropic effects on oxidative metabolism that persist up to 24 to 48 h later. Notably, cyanide, another complex IV inhibitor, does not induce this type of metabolic memory. Sulfide-mediated prolonged fractional inhibition of complex IV by H2S is modulated by sulfide quinone oxidoreductase, which commits sulfide to oxidative catabolism. Since induced hypometabolism can be beneficial in disease settings that involve insufficient or interrupted blood flow, our study has important implications for attenuating reperfusion-induced ischemic injury and/or prolonging the shelf life of biologics like platelets.

NO and H2S Contribute to Crop Resilience against Atmospheric Stressors.

Atmospheric stressors include a variety of pollutant gases such as CO2, nitrous oxide (NOx), and sulfurous compounds which could have a natural origin or be generated by uncontrolled human activity. Nevertheless, other atmospheric elements including high and low temperatures, ozone (O3), UV-B radiation, or acid rain among others can affect, at different levels, a large number of plant species, particularly those of agronomic interest. Paradoxically, both nitric oxide (NO) and hydrogen sulfide (H2S), until recently were considered toxic since they are part of the polluting gases; however, at present, these molecules are part of the mechanism of response to multiple stresses since they exert signaling functions which usually have an associated stimulation of the enzymatic and non-enzymatic antioxidant systems. At present, these gasotransmitters are considered essential components of the defense against a wide range of environmental stresses including atmospheric ones. This review aims to provide an updated vision of the endogenous metabolism of NO and H2S in plant cells and to deepen how the exogenous application of these compounds can contribute to crop resilience, particularly, against atmospheric stressors stimulating antioxidant systems.

A fluorescent probe for detecting H2O2 and delivering H2S in lysosomes and its application in maintaining the redox environments.

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that can be used as a marker for the occurrence of oxidative stress in the organism. Lysosomes serve as intracellular digestive sites, and when the concentration of H2O2 in them is abnormal, lysosomal function is often impaired, leading to the development of diseases. Hydrogen sulfide (H2S) acts as a gaseous signaling molecule that scavenges H2O2 from cells and tissues, thereby maintaining the redox environment of the body. However, most of the reported hydrogen peroxide fluorescent probes so far can only detect H2O2, but cannot maintain the intracellular redox environment. In this paper, an H2O2 fluorescent probe LN-HOD with lysosomal targeting properties was designed and synthesized by combining the H2O2 recognition site with a naphthylamine fluorophore via a thiocarbamate moiety. The probe has the advantages of large Stokes shift (110 nm), high sensitivity and good H2S release capability. The probe LN-HOD can be used to detect H2O2 in cells, zebrafish and plant roots. In addition, LN-HOD detects changes in the concentration of H2O2 in plant roots when Arabidopsis is stressed by cadmium ion (Cd2+). And through its ability to release H2S, it can help to remove excess H2O2 and maintain the redox environment in cells, zebrafish and plant roots. The present work provides new ideas for the detection and assisted removal of H2O2, which contributes to the in-depth study of the cellular microenvironment in organisms.

Hydrogen sulfide improves endothelial barrier function by modulating the ubiquitination degradation of KLF4 through TRAF7 S-sulfhydration in diabetic aorta.

Anomalous vascular endothelium significantly contributes to various cardiovascular diseases. VE-cadherin plays a vital role in governing the endothelial barrier. Krüppel-like factor 4(KLF4), as a transcription factor, which binds the VE-cadherin promoter and enhances its transcription. Tumor necrosis factor receptor-associated factor 7 (TRAF7) is an E3 ubiquitin ligase that has been shown to modulate the degradation of KLF4. H2S can covalently modify cysteine residues on proteins through S-sulfhydration, thereby influencing the structure and functionality of the target protein. However, the role of S-sulfhydration on endothelial barrier integrity remains to be comprehensively elucidated. This study aims to investigate whether protein S-sulfhydration in the endothelium regulates endothelial integrity and its underlying mechanism. In this study, we observed that protein S-sulfhydration was reduced in the endothelium during diabetes and TRAF7 was the main target. Overexpression of TRAF7-Cys327 mutant could mitigate the endothelial barrier damage by weakening TRAF7 interaction with KLF4 and reducing ubiquitination degradation of KLF4. In conclusion, our research demonstrates that H2S plays a pivotal role in regulating S-sulfhydration of TRAF7 at Cys327. This regulation effectively inhibits the ubiquitin-mediated degradation of KLF4, resulting in an upregulation of VE-cadherin levels. This molecular mechanism contributes to the prevention of endothelial barrier damage.

CmoPIP1-4 confers drought tolerance in pumpkin by altering hydrogen sulfide signaling.

Drought is a major limiting factor for the growth and development of pumpkins. Plasma membrane intrinsic proteins (PIPs) are major water channels that play a crucial role in the regulation of cellular water status and solute trafficking during drought conditions. CmoPIP1-4 is a plasma membrane-localized protein that is significantly upregulated in roots and leaves under drought-stress conditions. In this study, the overexpression of CmoPIP1-4 enhances drought resistance in yeast. In contrast, CRISPR-mediated CmoPIP1-4 knockout in pumpkin roots increased drought sensitivity. This increased drought sensitivity of CmoPIP1-4 knockout plants is associated with a decline in the levels of hydrogen sulfide (H2S) and abscisic acid (ABA), accompanied by an increase in water loss caused by greater levels of transpiration and stomatal conductance. In addition, the sensitivity of CmoPIP1-4 CRISPR plants is further aggravated by reduced antioxidative enzyme activity, decreased proline and sugar contents, and extensive root damage. Furthermore, expression profiles of genes such as CmoHSP70s, CmoNCED3, CmoNCED4, and others involved in metabolic activities were markedly reduced in CmoPIP1-4 CRISPR plants. Moreover, we also discovered an interaction between the drought-responsive gene CmoDCD and CmoPIP1-4, indicating their potential role in activating H2S-mediated signaling in pumpkin, which could confer drought tolerance. The findings of our study collectively demonstrate CmoPIP1-4 plays a crucial role in the regulation of H2S-mediated signaling, influencing stomatal density and aperture in pumpkin plants, and thereby enhancing their drought tolerance.

2H-Thiopyran-2-thione sulfine, a compound for converting H2S to HSOH/H2S2 and increasing intracellular sulfane sulfur levels.

Reactive sulfane sulfur species such as persulfides (RSSH) and H2S2 are important redox regulators and closely linked to H2S signaling. However, the study of these species is still challenging due to their instability, high reactivity, and the lack of suitable donors to produce them. Herein we report a unique compound, 2H-thiopyran-2-thione sulfine (TTS), which can specifically convert H2S to HSOH, and then to H2S2 in the presence of excess H2S. Meanwhile, the reaction product 2H-thiopyran-2-thione (TT) can be oxidized to reform TTS by biological oxidants. The reaction mechanism of TTS is studied experimentally and computationally. TTS can be conjugated to proteins to achieve specific delivery, and the combination of TTS and H2S leads to highly efficient protein persulfidation. When TTS is applied in conjunction with established H2S donors, the corresponding donors of H2S2 (or its equivalents) are obtained. Cell-based studies reveal that TTS can effectively increase intracellular sulfane sulfur levels and compensate for certain aspects of sulfide:quinone oxidoreductase (SQR) deficiency. These properties make TTS a conceptually new strategy for the design of donors of reactive sulfane sulfur species.

Cu/Biochar Bifunctional Catalytic Removal of COS and H2S:H2O Dissociation and CuO Anchoring Enhanced by Pyridine N.

Economic and environmentally friendly strategies are needed to promote the bifunctional catalytic removal of carbonyl sulfide (COS) by hydrolysis and hydrogen sulfide (H2S) by oxidation. N doping is considered to be an effective strategy, but the essential and intrinsic role of N dopants in catalysts is still not well understood. Herein, the conjugation of urea and biochar during Cu/biochar annealing produced pyridine N, which increased the combined COS/H2S capacity of the catalyst from 260.7 to 374.8 mg·g-1 and enhanced the turnover frequency of H2S from 2.50 × 10-4 to 5.35 × 10-4 s-1. The nucleophilic nature of pyridine N enhances the moderate basic sites of the catalyst, enabling the attack of protons and strong H2O dissociation. Moreover, pyridine N also forms cavity sites that anchor CuO, improving Cu dispersion and generating more reactive oxygen species. By providing original insight into the pyridine N-induced bifunctional catalytic removal of COS/H2S in a slightly oxygenated and humid atmosphere, this study offers valuable guidance for further C═S and C-S bond-breaking in the degradation of sulfur-containing pollutants.

Role of hydrogen sulfide in the regulation of lipid metabolism: Implications on cardiovascular health.

The World Health Organization (WHO) defines obesity as an urgency for health and a social emergency. Today around 39 % of people is overweight, of these over 13 % is obese. It is well-consolidated that the adipose cells are deputy to lipid storage under caloric excess; however, despite the classical idea that adipose tissue has exclusively a passive function, now it is known to be deeply involved in the regulation of systemic metabolism in physiological as well as under obesogenic conditions, with consequences on cardiovascular health. Beside two traditional types of adipose cells (white and brown), recently the beige one has been highlighted as the consequence of the healthy remodeling of white adipocytes, confirming their metabolic adaptability. In this direction, pharmacological, nutraceutical and nutrient-based approaches are addressed to positively influence inflammation and metabolism, thus contributing to reduce the obese-associated cardiovascular risk. In this scenario, hydrogen sulfide emerges as a new mediator that may regulate crucial targets involved in the regulation of metabolism. The current evidence demonstrates that hydrogen sulfide may induce peroxisome proliferator activated receptor γ (PPARγ), a crucial mediator of adipogenesis, inhibit the phosphorylation of perlipin-1 (plin-1), a protein implicated in the lipolysis, and finally promote browning process, through the release of irisin from skeletal muscle. The results summarized in this review suggest an important role of hydrogen sulfide in the regulation of metabolism and in the prevention/treatment of obese-associated cardiovascular diseases and propose new insight on the putative mechanisms underlying the release of hydrogen sulfide or its biosynthesis, delineating a further exciting field of application.

Effect of hydrogen sulfide on cabbage photosynthesis under black rot stress.

Hydrogen sulfide (H2S), as a potential gaseous signaling molecule, is involved in mediating biotic and abiotic stress in plants. Currently, there are no studies investigating the mechanism by which H2S improves photosynthesis under black rot (BR) stress caused by Xanthomonas campestris pv. Campestris (Xcc). In this study, we investigated the effect of exogenous H2S on Xcc induced photosynthetic impairment in cabbage seedlings. BR has an inhibitory effect on the photosynthetic ability of cabbage seedlings. Xcc infection can significantly reduce the chlorophyll content, photosynthetic characteristics, chlorophyll fluorescence, Calvin cycle related enzyme activity and gene expression in cabbage leaves. The use of H2S can alleviate this inhibitory effect, reduce chlorophyll decomposition, improve gas exchange, enhance the activity of Calvin cycle related enzymes, and increase the expression of related genes. Transcriptome analysis showed that all differential genes related to photosynthesis were up regulated under H2S treatment compared to normal inoculation. Therefore, spraying exogenous H2S can improve the photosynthetic capacity of cabbage seedlings, reduce Xcc induced photoinhibition, and improve plant resistance.

Allicin Promotes Glucose Uptake by Activating AMPK through CSE/H2S-Induced S-Sulfhydration in a Muscle-Fiber Dependent Way in Broiler Chickens.

SCOPE: Allicin, a product of enzymatic reaction when garlic is injured, plays an important role in maintaining glucose homeostasis in mammals. However, the effect of allicin on glucose homeostasis in the state of insulin resistance remains to be elucidated. This study investigates the effect of allicin on glucose metabolism using different muscle fibers in a chicken model. METHODS AND RESULTS: Day-old male Arbor Acres broilers are randomly divided into three groups and fed a basal diet supplemented with 0, 150, or 300 mg kg-1 allicin for 42 days. Results show that allicin improves the zootechnical performance of broilers at the finishing stage. The glucose loading test (2 g kg-1 body mass) indicates the regulatory role of allicin on glucose homeostasis. In vitro results demonstrate allicin increases glutathione (GSH) level and the expression of cystathionine γ lyase (CSE), leading to endogenous hydrogen sulfide (H2S) production in M. pectoralis major (PM) muscle-derived myotubes. Allicin stimulates adenosine monophosphate-activated protein kinase (AMPK) S-sulfhydration and AMPK phosphorylation to promote glucose uptake, which is suppressed in the presence of d,l-propargylglycine (PAG, a CSE inhibitor). CONCLUSION: This study demonstrates that allicin induces AMPK S-sulfhydration and AMPK phosphorylation to promote glucose uptake via the CSE/H2S system in a muscle fiber-dependent manner.

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.

The role of hydrogen sulfide regulation of pyroptosis in different pathological processes.

Pyroptosis is one kind of programmed cell death in which the cell membrane ruptures and subsequently releases cell contents and pro-inflammatory cytokines including IL-1ß and IL-18. Pyroptosis is caused by many types of pathological stimuli, such as hyperglycemia (HG), oxidative stress, and inflammation, and is mediated by gasdermin (GSDM) protein family. Increasing evidence indicates that pyroptosis plays an important role in multiple diseases, such as cancer, kidney diseases, inflammatory diseases, and cardiovascular diseases. Therefore, the regulation of pyroptosis is crucial for the occurrence, development, and treatment of many diseases. Hydrogen sulfide (H2S) is a biologically active gasotransmitter following carbon monoxide (CO) and nitrogen oxide (NO) in mammalian tissues. So far, three enzymes, including 3-mercaptopyruvate sulphurtransferase (3-MST), cystathionine γ- Lyase (CSE), and Cystine ß-synthesis enzyme (CBS), have been found to catalyze the production of endogenous H2S in mammals. H2S has been reported to have multiple biological functions including anti-inflammation, anti-oxidative stress, anti-apoptosis and so on. Hence, H2S is involved in various physiological and pathological processes. In recent years, many studies have demonstrated that H2S plays a critical role by regulating pyroptosis in various pathological processes, such as ischemia-reperfusion injury, alcoholic liver disease, and diabetes cardiomyopathy. However, the relevant mechanism has not been completely understood. Therefore, elucidating the mechanism by which H2S regulates pyroptosis in diseases will help understand the pathogenesis of multiple diseases and provide important new avenues for the treatment of many diseases. Here, we reviewed the progress of H2S regulation of pyroptosis in different pathological processes, and analyzed the molecular mechanism in detail to provide a theoretical reference for future related research.

The role and mechanism of hydrogen sulfide in liver fibrosis.

Hydrogen sulfide (H2S) is the third new gas signaling molecule in the human body after the discovery of NO and CO. Similar to NO, it has the functions of vasodilation, anti-inflammatory, antioxidant, and regulation of cell formation. Enzymes that can produce endogenous H2S, such as CSE, CSB, and 3-MST, are common in liver tissues and are important regulatory molecules in the liver. In the development of liver fibrosis, H2S concentration and expression of related enzymes change significantly, which makes it possible to use exogenous gases to treat liver diseases. This review summarizes the role of H2S in liver fibrosis and its complications induced by NAFLD and CCl4, and elaborates on the anti-liver fibrosis effect of H2S through the mechanism of reducing oxidative stress, inhibiting inflammation, regulating autophagy, regulating glucose and lipid metabolism, providing theoretical reference for further research on the treatment of liver fibrosis with H2S.