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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 (H 2 S) and, therefore, H 2 S-donors could have a central role in the prevention and treatment of overweight/obesity. The main natural sources of H 2 S-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 H 2 S, derive from the hydrolysis of alliin from Alliaceae and glucosinolates from Brassicaceae/Moringaceae, respectively. In this review, we describe the emerging role of endogenous H 2 S in regulating adipose tissue function and the potential efficacy of natural H 2 S-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., (© 2024 John Wiley & Sons Ltd.)

Polysulfides have received increased interest in redox biology due to their role as the precursors of H 2 S and persulfides. However, the compounds that are suitable for biological investigations are limited to cysteine- and glutathione-derived polysulfides. In this work, we report the preparation and evaluation of a novel polysulfide derived from thioglucose, which represents the first carbohydrate-based polysulfide. This compound, thioglucose tetrasulfide (TGS4), showed excellent stability and water solubility. H 2 S and persulfide production from TGS4, as well as its associated antioxidative property were also demonstrated. Additionally, TGS4 was demonstrated to significantly induce cellular sulfane sulfur level increase, in particular for the formation of hydropersulfides/trisulfides. These results suggest that TGS4 is a useful tool for polysulfide research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Per/polysulfide species that are generated from endogenously produced hydrogen sulfide have critical regulatory roles in a wide range of cellular processes. However, the lack of delivery systems that enable controlled and sustained release of these unstable species in biological systems hinders the advancement of sulfide biology research, as well as the translation of knowledge to therapeutic applications. Here, a novel approach is developed to generate per/polysulfide species in cells by combining an H 2 S donor and manganese porphyrin-containing polymeric micelles (MnPMCs) that catalyze oxidization of H 2 S to per/polysulfide species. MnPMCs serve as a catalyst for H 2 S oxidation in aerobic phosphate buffer. HPLC-MS/MS analysis reveals that H 2 S oxidation by MnPMCs in the presence of glutathione results in the formation of glutathione-SnH (n = 2 and 3). Furthermore, co-treatment of human umbilical vein endothelial cells with the H 2 S donor anethole dithiolethione and MnPMCs increases intracellular per/polysulfide levels and induces a proangiogenic response. Co-delivery of MnPMCs and an H 2 S donor is a promising approach for controlled delivery of polysulfides for therapeutic applications., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Hydrogen sulfide (H 2 S) and polysulfides (H 2 S n , n ≥ 2) produced by enzymes play a role as signalling molecules regulating neurotransmission, vascular tone, cytoprotection, inflammation, oxygen sensing, and energy formation. H 2 S n , which have additional sulfur atoms to H 2 S, and other S-sulfurated molecules such as cysteine persulfide and S-sulfurated cysteine residues of proteins, are produced by enzymes including 3-mercaptopyruvate sulfurtransferase (3MST). H 2 S n are also generated by the chemical interaction of H 2 S with NO, or to a lesser extent with H 2 O 2 . S-sulfuration (S-sulfhydration) has been proposed as a mode of action of H 2 S and H 2 S n to regulate the activity of target molecules. Recently, we found that H 2 S/H 2 S 2 regulate the release of neurotransmitters, such as GABA, glutamate, and D-serine, a co-agonist of N-methyl-D-aspartate (NMDA) receptors. H 2 S facilitates the induction of hippocampal long-term potentiation, a synaptic model of memory formation, by enhancing the activity of NMDA receptors, while H 2 S 2 achieves this by activating transient receptor potential ankyrin 1 (TRPA1) channels in astrocytes, potentially leading to the activation of nearby neurons. The recent findings show the other aspects of TRPA1 channels-that is, the regulation of the levels of sulfur-containing molecules and their metabolizing enzymes. Disturbance of the signalling by H 2 S/H 2 S n has been demonstrated to be involved in various diseases, including cognitive and psychiatric diseases. The physiological and pathophysiological roles of these molecules will be discussed.

Hydrogen sulfide (H 2 S) has been extensively studied as a signal molecule in the body for the past 30 years. Researchers have conducted studies using both natural and synthetic sources of H 2 S, known as H 2 S donors, which have different characteristics in terms of how they release H 2 S. These donors can be inorganic salts or have various organic structures. In recent years, certain types of sulfur compounds found naturally in foods have been characterized as H 2 S donors and explored for their potential health benefits. These compounds are referred to as "sulfanutraceuticals," a term that combines "nutrition" and "pharmaceutical". It is used to describe products derived from food sources that offer additional health advantages. By introducing the terms "sulfaceuticals" and "sulfanutraceuticals," we categorize sulfur-containing substances based on their origin and their use in both preclinical and clinical research, as well as in dietary supplements., Competing Interests: Declaration of Competing Interest The authors Vincenzo Calderone and Giuseppe Cirino are owners of the following trademarks: G. Cirino, V. Calderone, Trademark "sulfaceutix". Italian Ministry of Economic Development. Registration number 302019000059121; 2019. G. Cirino, V. Calderone, Trademark "sulfanutraceutix". Italian Ministry of Economic Development. Registration number 302019000059139; 2019. These trademark registrations are cited in the text and in the bibliography (number 45 and 46, respectively, in the bibliography section). The authors declare that they have no further known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Some relevant food systems release tiny amounts of sulfidic gases, whose measurement is difficult because of their inherent instability. The present paper demonstrates that Cu(I) solutions trap quantitatively and stabilize sulfidic gases. Once trapped, the gases remain stable for weeks at 4 °C and at least 8 days at 75 °C. Trapped gases can be quantitatively released with tris(2-carboxyethyl) phosphine (TCEP) and brine dilution and then determined by GC. Trapping solutions, placed in 20-mL opened vials housed in 100 mL hermetically-sealed flasks containing wine in anoxia, have been used to monitor the release of sulfidic gases by wines, revealing that at 50 °C, up to 400 μg/L of H 2 S and 58 μg/L of MeSH can be released in 68 days, and 3-5 times more at 75 °C in 28 days. The possibility to differentiate between released and accumulated amounts provides key clues to understanding the fate of sulfidic gases in wine and other food systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Removal of hydrogen sulfide (H 2 S) can be achieved using the sustainable biological desulfurization process, where H 2 S is converted to elemental sulfur using sulfide-oxidizing bacteria (SOB). A dual-bioreactor process was recently developed where an anaerobic (sulfidic) bioreactor was used between the absorber column and micro-oxic bioreactor. In the absorber column and sulfidic bioreactor, polysulfides (S x 2- ) are formed due to the chemical equilibrium between H 2 S and sulfur (S 8 ). S x 2- is thought to be the intermediate for SOB to produce sulfur via H 2 S oxidation. In this study, we quantify S x 2- , determine their chain-length distribution under high H 2 S loading rates, and elucidate the relationship between biomass and the observed biological removal of sulfides under anaerobic conditions. A linear relationship was observed between S x 2- concentration and H 2 S loading rates at a constant biomass concentration. Increasing biomass concentrations resulted in a lower measured S x 2- concentration at similar H 2 S loading rates in the sulfidic bioreactor. S x 2- of chain length 6 (S 6 2- ) showed a substantial decrease at higher biomass concentrations. Identifying S x 2- concentrations and their chain lengths as a function of biomass concentration and the sulfide loading rate is key in understanding and controlling sulfide uptake by the SOB. This knowledge will contribute to a better understanding of how to reach and maintain a high selectivity for S 8 formation in the dual-reactor biological desulfurization process.

The study of polysulfides has been a recent topic of interest for wine research due to the possibility of these compounds to release hydrogen sulfide (H 2 S) during storage. However, studying these compounds has been challenging for several reasons. Polysulfides are low in concentration in natural samples, they are chemically unstable and pure standards of the single compounds (RS n R with n > 2) are not commercially available. In the present study, a method was developed in order to collect a single polysulfide and study its degradation and the consequent formation of H 2 S. For this approach, ultra-high pressure liquid chromatography was used with an integrated fraction collector and subsequently coupled to high resolution mass spectrometry. After fractionation, the degradation of the di-cysteinyl pentasulfide (CS 5 C) was induced by exposure to 30 °C and the H 2 S formation was measured in parallel using ion-exchange chromatography. This method showed the evolutions of different polysulfides and the H 2 S release originating from the target compound, an observation that to the best of our knowledge has never been made before. The method in the present study demonstrated promising applications for polysulfide studies and brought us a step closer to the understanding of the chemistry of polysulfides in wine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Hydrogen sulfide (H 2 S) emerged as an essential signaling molecule exerting beneficial effects in various cardiovascular, neurodegenerative, or musculoskeletal diseases with an inflammatory component, such as osteoarthritis. These protective effects were initially attributed to protein S-sulfhydration, a posttranslational modification of reactive cysteine residues. However, recent studies suggest that polysulfides and not H 2 S are responsible for S-sulfhydration. To distinguish between H 2 S and polysulfide-mediated effects in this study, we used the slow-releasing H 2 S and persulfide donor P*, which can be decomposed into polysulfides. The effects of P* on IL-1β-induced inducible nitric oxide synthase (iNOS), a pro-inflammatory mediator in osteoarthritis, were determined by nitrite measurement, qPCR, and Western blotting in the murine chondrocyte-like cell line ATDC5. Decomposed P* significantly reduced IL-1β-induced iNOS signaling via polysulfides, independently of H 2 S. In line with this, the fast-releasing H 2 S donor NaHS was ineffective. In RAW 264.7 macrophages, similar results were obtained. P*-derived polysulfides further diminished IL-1β-induced CCAAT/enhancer-binding protein (C/EBP) β and δ expression in ATDC5 cells, which might play a critical role in P*-mediated iNOS decline. In conclusion, our data support the view that polysulfides are essential signaling molecules as well as potential mediators of H 2 S signaling. Moreover, we propose that C/EBPβ/δ might be a novel target involved in H 2 S and polysulfide-mediated anti-inflammatory signaling., (Copyright © 2022. Published by Elsevier Inc.)

Reactive sulfur species (RSS) have been recognized in the last two decades as very important molecules in redox regulation. They are involved in metabolic processes and, in this way, they are responsible for maintenance of health. This review summarizes current information about the essential biological RSS, including H2S, low molecular weight persulfides, protein persulfides as well as organic and inorganic polysulfides, their synthesis, catabolism and chemical reactivity. Moreover, the role of RSS disturbances in various pathologies including vascular diseases, chronic kidney diseases, diabetes mellitus Type 2, neurological diseases, obesity, chronic obstructive pulmonary disease and in the most current problem of COVID-19 is presented. The significance of RSS in aging is also mentioned. Finally, the possibilities of using the precursors of various forms of RSS for therapeutic purposes are discussed., (© 2022 The Author(s).)

The progressive decline of bone mass and the deterioration of bone microarchitecture are hallmarks of the bone aging. The resulting increase in bone fragility is the leading cause of bone fractures, a major cause of disability. As the frontline pharmacological treatments for osteoporosis suffer from low patients' adherence and occasional side effects, the importance of diet regimens for the prevention of excessive bone fragility has been increasingly recognized. Indeed, certain diet components have been already associated to a reduced fracture risk. Organosulfur compounds are a broad class of molecules containing sulfur. Among them, several molecules of potential therapeutic interest are found in edible plants belonging to the Allium and Brassica botanical genera. Polysulfides derived from Alliaceae and isothiocyanates derived from Brassicaceae hold remarkable nutraceutical potential as anti-inflammatory, antioxidants, vasorelaxant and hypolipemic. Some of these effects are linked to the ability to release the gasotrasmitter hydrogen sulfide (H 2 S). Recent preclinical studies have investigated the effect of organosulfur compounds in bone wasting and metabolic bone diseases, revealing a strong potential to preserve skeletal health by exerting cytoprotection and stimulating the bone forming activity by osteoblasts and attenuating bone resorption by osteoclasts. This review is intended for revising evidence from preclinical and epidemiological studies on the skeletal effects of organosulfur molecules of dietary origin, with emphasis on the direct regulation of bone cells by plant-derived polysulfides, glucosinolates and isothiocyanates. Moreover, we highlight the potential molecular mechanisms underlying the biological role of these compounds and revise the importance of the so-called 'H 2 S-system' on the regulation of bone homeostasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gambari, Grigolo and Grassi.)

Aqueous root extract from Acanthopanax senticosus (ASRE) has a wide range of medicinal effects. The present work was aimed at studying the influence of sulfide, cysteine and glutathione on the antioxidant properties of ASRE and some of its selected phytochemical components. Reduction of the 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazol-1-yloxy-3-oxide ( ● cPTIO) stable radical and plasmid DNA (pDNA) cleavage in vitro assays were used to evaluate antioxidant and DNA-damaging properties of ASRE and its individual components. We found that the interaction of ASRE and its two components, caffeic acid and chlorogenic acid (but not protocatechuic acid and eleutheroside B or E), with H 2 S/HS - , cysteine or glutathione significantly increased the reduction of the ● cPTIO radical. In contrast, the potency of ASRE and its selected components was not affected by Na 2 S 4 , oxidized glutathione, cystine or methionine, indicating that the thiol group is a prerequisite for the promotion of the antioxidant effects. ASRE interacting with H 2 S/HS - or cysteine displayed a bell-shaped effect in the pDNA cleavage assay. However, ASRE and its components inhibited pDNA cleavage induced by polysulfides. In conclusion, we suggest that cysteine, glutathione and H 2 S/HS - increase antioxidant properties of ASRE and that changes of their concentrations and the thiol/disulfide ratio can influence the resulting biological effects of ASRE.

Hydrogen sulfide is a signalling molecule with a well-established impact on both plant and animal physiology. Intense investigation into the regulation of autophagy by sulfide in Arabidopsis thaliana has revealed that the post-translational modification of persulfidation/S-sulfhydration plays a key role. In this review focused on plants, we discuss the nature of the sulfide molecule involved in the regulation of autophagy, the final outcome of this modification and the persulfidated autophagy proteins identified so far. A detailed outline of the actual knowledge of the regulation mechanism of the autophagy-related proteins ATG4a and ATG18a from Arabidopsis by sulfide is also included. This information will be instrumental for furthering research on the regulation of autophagy by sulfide., (© 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Hydrogen sulfide (H 2 S) and inorganic polysulfides are important signaling molecules; however, little is known about their role in adipose tissue. We examined the effect of H 2 S and polysulfides on insulin sensitivity of the adipose tissue in rats. Plasma glucose, insulin, non-esterified fatty acids, and glycerol were measured after administration of H 2 S and the polysulfide donors, Na 2 S and Na 2 S 4 , respectively. In addition, the effect of Na 2 S and Na 2 S 4 on insulin-induced glucose uptake and inhibition of lipolysis was studied in adipose tissue explants ex vivo. Na 2 S and Na 2 S 4 administered in vivo at a single dose of 100 μmol/kg had no effect on plasma glucose and insulin concentrations. In addition, Na 2 S and Na 2 S 4 did not modify the effect of insulin on plasma glucose, fatty acids, and glycerol concentrations. Na 2 S and Na 2 S 4 had no effect on the antilipolytic effect of insulin in adipose tissue explants ex vivo. The effect of insulin on 2-deoxyglucose uptake by adipose tissue was impaired in obese rats which was accompanied by lower insulin-induced tyrosine phosphorylation of IRS-1 and Akt. Na 2 S 4 , but not Na 2 S, improved insulin signaling and increased insulin-stimulated 2-deoxyglucose uptake by adipose tissue of obese rats. The results suggest that polysulfides may normalize insulin sensitivity, at least in the adipose tissue, in obesity/metabolic syndrome.

After the discovery of hydrogen sulfide (H 2 S) in the central nervous system by Abe and Kimura in 1996, the physiopathological role of H 2 S has been widely investigated in several systems such as the cardiovascular. In particular, H 2 S plays a pivotal role in the control of vascular tone, exhibiting mechanisms of action able to induce vasodilation: for instance, activation of potassium channels (KATP and Kv7) and inhibition of 5-phosphodiesterase (5-PDE). These findings paved the way for the research of natural and synthetic exogenous H 2 S-donors (i.e., molecules able to release H 2 S) in order to have new tools for the management of hypertension. In this scenario, some natural molecules derived from Alliaceae (i.e., garlic) and Brassicaceae (i.e., rocket or broccoli) botanical families show the profile of slow H 2 S-donors able to mimic the endogenous production of this gasotransmitter and therefore can be viewed as interesting potential tools for management of hypertension or pre-hypertension. In this article, the preclinical and clinical impacts of these natural H 2 S-donors on hypertension and vascular integrity have been reviewed in order to give a complete panorama of their potential use for the management of hypertension and related vascular diseases.

Significance: Hydrogen sulfide (H 2 S) is reported to be an important mediator involved in numerous physiological processes. H 2 S and hydropersulfides (RSSH) species are intimately linked biochemically. Therefore, interest in the mechanisms of the biological activity of H 2 S has led to investigations of the chemical biology of RSSH since they are likely to coexist in a biological system. Currently it is hypothesized that RSSH may be responsible for a least part of the observed H 2 S-mediated biology/physiology. Recent Advances: It has been recently touted that thiols (RSH) and RSSH have some important differences in terms of their chemical biology and that the generation of RSSH from RSH is purposeful to exploit these chemical differences as a response to a physiological or biological stress. This transformation may represent an unappreciated/unrecognized biological mechanism for dealing with cellular stresses. Critical Issues: Although recent studies indicate a diverse and potentially important chemical biology associated with RSSH species, these ideas have their foundations in early studies (some over 60 years old). It is vital to recognize the nature of this early work to fully appreciate the current ideas regarding RSSH biology. Importantly, these early studies were performed before the realization of purposeful H 2 S biosynthesis (before 1996). Future Directions: Taking clues from the past studies of RSSH chemistry and biology, progress in delineating the chemical biology of RSSH will continue. Determination of the possible relevance of RSSH chemical biology to signaling and cellular physiology will be a primary focus of many future studies. Antioxid. Redox Signal. 36, 244-255.

Hydrogen sulfide (H 2 S) and inorganic polysulfides are important signaling molecules; however, little is known about their role in the adipose tissue. We examined the effect of H 2 S and polysulfides on adipose tissue lipolysis. H 2 S and polysulfide production by mesenteric adipose tissue explants in rats was measured. The effect of Na 2 S and Na 2 S 4 , the H 2 S and polysulfide donors, respectively, on lipolysis markers, plasma non-esterified fatty acids (NEFA) and glycerol, was examined. Na 2 S but not Na 2 S 4 increased plasma NEFA and glycerol in a time- and dose-dependent manner. Na 2 S increased cyclic AMP but not cyclic GMP concentration in the adipose tissue. The effect of Na 2 S on NEFA and glycerol was abolished by the specific inhibitor of protein kinase A, KT5720. The effect of Na 2 S on lipolysis was not abolished by propranolol, suggesting no involvement of β-adrenergic receptors. In addition, Na 2 S had no effect on phosphodiesterase activity in the adipose tissue. Obesity induced by feeding rats a highly palatable diet for 1 month was associated with increased plasma NEFA and glycerol concentrations, as well as greater H 2 S production in the adipose tissue. In conclusion, H 2 S stimulates lipolysis and may contribute to the enhanced lipolysis associated with obesity.

Since the first description of hydrogen sulfide (H 2 S) as a toxic gas in 1713 by Bernardino Ramazzini, most studies on H 2 S have concentrated on its toxicity. In 1989, Warenycia et al. demonstrated the existence of endogenous H 2 S in the brain, suggesting that H 2 S may have physiological roles. In 1996, we demonstrated that hydrogen sulfide (H 2 S) is a potential signaling molecule, which can be produced by cystathionine β-synthase (CBS) to modify neurotransmission in the brain. Subsequently, we showed that H 2 S relaxes vascular smooth muscle in synergy with nitric oxide (NO) and that cystathionine γ-lyase (CSE) is another producing enzyme. This study also opened up a new research area of a crosstalk between H 2 S and NO. The cytoprotective effect, anti-inflammatory activity, energy formation, and oxygen sensing by H 2 S have been subsequently demonstrated. Two additional pathways for the production of H 2 S with 3-mercaptopyruvate sulfurtransferase (3MST) from l- and d-cysteine have been identified. We also discovered that hydrogen polysulfides (H 2 S n , n ≥ 2) are potential signaling molecules produced by 3MST. H 2 S n regulate the activity of ion channels and enzymes, as well as even the growth of tumors. S -Sulfuration ( S -sulfhydration) proposed by Snyder is the main mechanism for H 2 S/H 2 S n underlying regulation of the activity of target proteins. This mini review focuses on the key findings on H 2 S/H 2 S n signaling during the first 25 years.

Type 2 diabetes mellitus (T2DM) represents the most common age-related metabolic disorder, and its management is becoming both a health and economic issue worldwide. Moreover, chronic hyperglycemia represents one of the main risk factors for cardiovascular complications. In the last years, the emerging evidence about the role of the endogenous gasotransmitter hydrogen sulfide (H 2 S) in the pathogenesis and progression of T2DM led to increasing interest in the pharmacological modulation of endogenous "H 2 S-system". Indeed, H 2 S directly contributes to the homeostatic maintenance of blood glucose levels; moreover, it improves impaired angiogenesis and endothelial dysfunction under hyperglycemic conditions. Moreover, H 2 S promotes significant antioxidant, anti-inflammatory, and antiapoptotic effects, thus preventing hyperglycemia-induced vascular damage, diabetic nephropathy, and cardiomyopathy. Therefore, H 2 S-releasing molecules represent a promising strategy in both clinical management of T2DM and prevention of macro- and micro-vascular complications associated to hyperglycemia. Recently, growing attention has been focused on dietary organosulfur compounds. Among them, garlic polysulfides and isothiocyanates deriving from Brassicaceae have been recognized as H 2 S-donors of great pharmacological and nutraceutical interest. Therefore, a better understanding of the therapeutic potential of naturally occurring H 2 S-donors may pave the way to a more rational use of these nutraceuticals in the modulation of H 2 S homeostasis in T2DM., (© 2020 John Wiley & Sons Ltd.)

Hydrogen sulfide (H2S) and hydrogen polysulfides are recognized as important signaling molecules that are generated physiologically in the body, including the central nervous system (CNS). Studies have shown that these two molecules are involved in cytoprotection against oxidative stress and inflammatory response. In the brain system, H2S and polysulfides exert multiple functions in both health and diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), memory decline, and glioma. Mechanistically, S-Persulfidation (also known as S-sulfuration or S-sulfhydration) of target proteins is believed to be a fundamental mechanism that underlies H2S-regulated signaling pathways. Cysteine S-Persulfidation is an important paradigm of post translational protein modification in the process of H2S signaling. This model is established as a critical redox mechanism to regulate numerous biological functions, especially in H2S-mediated neuroprotection and neurogenesis. Although the current research of S-Persulfidation is still in its infancy, accumulative evidence suggests that protein S-Persulfidation may share similar characteristics with protein S-nitrosylation. In this review, we will provide a comprehensive insight into the S-Persulfidation biology of H2S and polysulfides in neurological ailments and presume potential avenues for therapeutic development in these disorders based on S-Persulfidation of target proteins., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Significance: Sulfur has a critical role in protein structure/function and redox status/signaling in all living organisms. Although hydrogen sulfide (H 2 S) and sulfane sulfur (SS) are now recognized as central players in physiology and pathophysiology, the full scope and depth of sulfur metabolome's impact on human health and healthy longevity has been vastly underestimated and is only starting to be grasped. Since many pathological conditions have been related to abnormally low levels of H 2 S/SS in blood and/or tissues, and are amenable to treatment by H 2 S supplementation, development of safe and efficacious H 2 S donors deserves to be undertaken with a sense of urgency; these prodrugs also hold the promise of becoming widely used for disease prevention and as antiaging agents. Recent Advances: Supramolecular tuning of the properties of well-known molecules comprising chains of sulfur atoms (diallyl trisulfide [DATS], S 8 ) was shown to lead to improved donors such as DATS-loaded polymeric nanoparticles and SG1002. Encouraging results in animal models have been obtained with SG1002 in heart failure, atherosclerosis, ischemic damage, and Duchenne muscular dystrophy; with TC-2153 in Alzheimer's disease, schizophrenia, age-related memory decline, fragile X syndrome, and cocaine addiction; and with DATS in brain, colon, gastric, and breast cancer. Critical Issues: Mode-of-action studies on allyl polysulfides, benzyl polysulfides, ajoene, and 12 ring-substituted organic disulfides and thiosulfonates led several groups of researchers to conclude that the anticancer effect of these compounds is not mediated by H 2 S and is only modulated by reactive oxygen species, and that their central model of action is selective protein S-thiolation. Future Directions: SG1002 is likely to emerge as the H 2 S donor of choice for acquiring knowledge on this gasotransmitter's effects in animal models, on account of its unique ability to efficiently generate H 2 S without byproducts and in a slow and sustained mode that is dose independent and enzyme independent. Efficient tuning of H 2 S donation characteristics of DATS, dibenzyl trisulfide, and other hydrophobic H 2 S prodrugs for both oral and parenteral administration will be achieved not only by conventional structural modification of a lead molecule but also through the new "supramolecular tuning" paradigm.

Hydrogen sulfide (H 2 S) together with polysulfides (H 2 S n , n > 2) are signalling molecules like NO with various physiological roles including regulation of neuronal transmission, vascular tone, inflammation and oxygen sensing. H 2 S and H 2 S n diffuse to the target proteins for S-sulfurating their cysteine residues that induces the conformational changes to alter the activity. On the other hand, 3-mercaptopyruvate sulfurtransferase transfers sulfur from a substrate 3-mercaptopyruvate to the cysteine residues of acceptor proteins. A similar mechanism has also been identified in S-nitrosylation. S-sulfuration and S-nitrosylation by enzymes proceed only inside the cell, while reactions induced by H 2 S, H 2 S n and NO even extend to the surrounding cells. Disturbance of signalling by these molecules as well as S-sulfuration and S-nitrosylation causes many nervous system diseases. This review focuses on the signalling by H 2 S and H 2 S n with S-sulfuration comparing to that of NO with S-nitrosylation and discusses on their roles in physiology and pathophysiology., (© 2020 The British Pharmacological Society.)

Sulfur is an essential element in determining the productivity and quality of agricultural products. It is also an element associated with tolerance to biotic and abiotic stress in plants. In agricultural practice, sulfur has broad use in the form of sulfate fertilizers and, to a lesser extent, as sulfite biostimulants. When used in the form of bulk elemental sulfur, or micro- or nano-sulfur, applied both to the soil and to the canopy, the element undergoes a series of changes in its oxidation state, produced by various intermediaries that apparently act as biostimulants and promoters of stress tolerance. The final result is sulfate S +6 , which is the source of sulfur that all soil organisms assimilate and that plants absorb by their root cells. The changes in the oxidation states of sulfur S 0 to S +6 depend on the action of specific groups of edaphic bacteria. In plant cells, S +6 sulfate is reduced to S -2 and incorporated into biological molecules. S -2 is also absorbed by stomata from H 2 S, COS, and other atmospheric sources. S -2 is the precursor of inorganic polysulfides, organic polysulfanes, and H 2 S, the action of which has been described in cell signaling and biostimulation in plants. S -2 is also the basis of essential biological molecules in signaling, metabolism, and stress tolerance, such as reactive sulfur species (RSS), SAM, glutathione, and phytochelatins. The present review describes the dynamics of sulfur in soil and plants, considering elemental sulfur as the starting point, and, as a final point, the sulfur accumulated as S -2 in biological structures. The factors that modify the behavior of the different components of the sulfur cycle in the soil-plant-atmosphere system, and how these influences the productivity, quality, and stress tolerance of crops, are described. The internal and external factors that influence the cellular production of S -2 and polysulfides vs. other S species are also described. The impact of elemental sulfur is compared with that of sulfates, in the context of proper soil management. The conclusion is that the use of elemental sulfur is recommended over that of sulfates, since it is beneficial for the soil microbiome, for productivity and nutritional quality of crops, and also allows the increased tolerance of plants to environmental stresses.

In addition to nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H 2 S) has recently emerged as the novel gasotransmitter involved in the regulation of the nervous system, cardiovascular functions, inflammatory response, gastrointestinal system, and renal function. H 2 S is synthesized from L-cysteine and/or L-homocysteine by cystathionine β-synthase, cystathionine γ-lyase, and cysteine aminotransferase together with 3-mercaptopyruvate sulfurtransferase. In addition, H 2 S is enzymatically metabolized in mitochondria by sulfide:quinone oxidoreductase, persulfide dioxygenase, and sulfite oxidase to thiosulfate, sulfite, and sulfate which enables to regulate its level by factors such as oxygen pressure, mitochondria density, or efficacy of mitochondrial electron transport. H 2 S modifies protein structure and function through the so-called sulfuration or persulfidation, that is, conversion of cysteine thiol (-SH) to persulfide (-SSH) groups. This, as well as other signaling mechanisms, is partially mediated by more oxidized H 2 S-derived species, polysulfides (H 2 S n ). In addition, H 2 S is able to react with reactive oxygen and nitrogen species to form other signaling molecules such as thionitrous acid (HSNO), nitrosopersulfide (SSNO - ), and nitroxyl (HNO). All H 2 S-synthesizing enzymes are expressed in the vascular wall, and H 2 S has been demonstrated to regulate vascular tone, endothelial barrier permeability, angiogenesis, vascular smooth muscle cell proliferation and apoptosis, and inflammatory reaction. H 2 S-modifying therapies are promising approach for diseases such as arterial hypertension, diabetic angiopathy, and atherosclerosis.

Hydrogen sulfide (H 2 S) has been demonstrated to have physiological roles such as neuromodulation, vascular tone regulation, cytoprotection, oxygen sensing, inflammatory regulation, and cell growth. Recently, hydrogen polysulfides (H 2 S n ) have been found to be produced by 3-mercaptopyruvate sulfurtransferase and to regulate the activity of ion channels, tumor suppressers, and protein kinases. Furthermore, some of the effects previously reported to be mediated by H 2 S are now ascribed to H 2 S n . Cysteine persulfide and cysteine polysulfide may also be involved in cellular redox regulation. The chemical interaction between H 2 S and nitric oxide (NO) can also produce H 2 S n , nitroxyl, and nitrosopersulfide, suggesting their involvement in the reactions previously thought to be mediated by NO alone. This Forum focuses on and critically discusses the recent progress in the study of H 2 S n , H 2 S, and NO as well as other per- or polysulfide species. Antioxid. Redox Signal. 00, 000-000.

Significance: Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level., Critical Issues: To better characterize the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems, and effects on cellular, organ, and whole-organism bioenergetics using system-level/network analyses., Future Directions: Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other forms of stress will provide new prevention/intervention opportunities for personalized medicine. Antioxid. Redox Signal. 00, 000-000.

Significance: For >20 years, physiological signaling associated with the endogenous generation of hydrogen sulfide (H 2 S) has been of significant interest. Despite its presumed importance, the biochemical mechanisms associated with its actions have not been elucidated. Recent Advances: Recently it has been found that H 2 S-related or derived species are highly prevalent in mammalian systems and that these species may be responsible for some, if not the majority, of the biological actions attributed to H 2 S. One of the most prevalent and intriguing species are hydropersulfides (RSSH), which can be present at significant levels. Indeed, it appears that H 2 S and RSSH are intimately linked in biological systems and likely to be mutually inclusive., Critical Issues: The fact that H 2 S and polysulfides such as RSSH are present simultaneously means that the biological actions previously assigned to H 2 S can be instead because of the presence of RSSH (or other polysulfides). Thus, it remains possible that hydropersulfides are the biological effectors, and H 2 S serves, to a certain extent, as a marker for persulfides and polysulfides. Addressing this possibility will to a large extent be based on the chemistry of these species., Future Directions: Currently, it is known that persulfides possess unique and novel chemical properties that may explain their biological prevalence. However, significantly more work will be required to establish the possible physiological roles of these species. Moreover, an understanding of the regulation of their biosynthesis and degradation will become important topics in piecing together their biology. Antioxid. Redox Signal. 00, 000-000.

The rotten-egg odour of hydrogen sulfide (H2S) produced by the yeast Saccharomyces cerevisiae has attracted considerable research interest due to its huge impact on the sensory quality of fermented foods and beverages. To date, the yeast genetic mechanisms of H2S liberation during wine fermentation are well understood and yeast strains producing low levels of H2S have been developed. Studies have also revealed that H2S is not just a by-product in the biosynthesis of the sulfur-containing amino acids, but indeed a vital molecule involved in detoxification, population signalling and extending cellular life span. Moreover, polysulfides have recently emerged as key players in signalling and the sensory quality of wine because their degradation leads to the release of H2S. This review will focus on the recent findings on the production of H2S and polysulfides in S. cerevisiae and summarise their potential roles in yeast survival and winemaking. Recent advances in techniques for the detection of H2S and polysulfides offer an exciting opportunity to uncover the novel genes and pathways involved in their formation from different sulfur sources. This knowledge will not only provide further insights into yeast sulfur metabolism, but could potentially improve the sensory quality of wine., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

It was in the 1950s that the term polysulfide or persulfide was introduced in biological studies. The unfamiliar term "sulfane sulfur" sometimes appeared in papers published in the 1970s, and was defined in the review article by Westley in 1983. In the article, sulfane sulfur is described as sulfur atoms that are covalently bound only with sulfur atoms, and as this explanation was somewhat difficult to comprehend, it was not generally accepted. Thus, in the early 1990s, we redefined these sulfur species as "bound sulfur", which easily converts to hydrogen sulfide on reduction with a thiol reducing agent. In other words, bound sulfur refers to a sulfur atom that exists in a zero to divalent form (0 to -2). The first part of this review focuses on the fluorescent derivatization HPLC method-which we developed for measurement of bound sulfur-and explains the distribution of bound sulfur and the hydrogen sulfide-producing ability of various tissues, as clarified by this method. Next, we discuss diverse physiological functions and involvement of polysulfide, a typical type of bound sulfur, in the redox regulation system. Additionally, we also address its possible physiological role in the central nervous system, based on its action of scavenging reactive carbonyl compounds.

Over the past several years, hydrogen sulfide (H 2 S) has been shown to be an important player in a variety of physiological functions, including neuromodulation, vasodilation, oxidant regulation, inflammation, and angiogenesis. H 2 S is synthesized primarily through metabolic processes from the amino acid cysteine and homocysteine in various organ systems including neuronal, cardiovascular, gastrointestinal, and kidney. Derangement of cysteine and homocysteine metabolism and clearance, particularly in the renal vasculature, leads to H 2 S biosynthesis deregulation causing or contributing to existing high blood pressure. While a variety of environmental influences, such as diet can have an effect on H 2 S regulation and function, genetic factors, and more recently epigenetics, also have a vital role in H 2 S regulation and function, and therefore disease initiation and progression. In addition, new research into the role of gut microbiota in the development of hypertension has highlighted the need to further explore these microorganisms and how they influence the levels of H 2 S throughout the body and possibly exploiting microbiota for use of hypertension treatment. In this review, we summarize recent advances in the field of hypertension research emphasizing renal contribution and how H 2 S physiology can be exploited as a possible therapeutic strategy to ameliorate kidney dysfunction as well as to control blood pressure., Competing Interests: The authors declare there are no competing interests., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The health benefits of garlic and other organosulfur-containing foods are well recognized and have been attributed to both prooxidant and antioxidant activities. The effects of garlic are surprisingly similar to those of hydrogen sulfide (H2S), which is also known to be released from garlic under certain conditions. However, recent evidence suggests that polysulfides, not H2S, may be the actual mediator of physiological signaling. In this study, we monitored formation of H2S and polysulfides from garlic oil in buffer and in human embryonic kidney (HEK) 293 cells with fluorescent dyes, 7-azido-4-methylcoumarin and SSP4, respectively and redox activity with two redox indicators redox-sensitive green fluorescent protein (roGFP) and DCF. Our results show that H2S release from garlic oil in buffer requires other low-molecular-weight thiols, such as cysteine (Cys) or glutathione (GSH), whereas polysulfides are readily detected in garlic oil alone. Administration of garlic oil to cells rapidly increases intracellular polysulfide but has minimal effects on H2S unless Cys or GSH are also present in the extracellular medium. We also observed that garlic oil and diallyltrisulfide (DATS) potently oxidized roGFP in buffer but did not affect DCF. This appears to be a direct polysulfide-mediated oxidation that does not require a reactive oxygen species intermediate. Conversely, when applied to cells, garlic oil became a significant intracellular reductant independent of extracellular Cys or GSH. This suggests that intracellular metabolism and further processing of the sulfur moieties are necessary to confer antioxidant properties to garlic oil in vivo., (Copyright © 2016 the American Physiological Society.)

Hydrogen sulfide is ubiquitous in biological systems and exerts function over a wide range of important physiological processes. Complementing free H2S, the reductant-labile sulfur pool plays significant roles in the translocation and action of sulfide, however the chemistry of reductant-labile sulfide sources has not been studied systematically. Using a combination of NMR and UV-Vis spectroscopy, we investigated the spectroscopic properties and reactivity of three isolated organic persulfides and report a simple model for persulfide reactivity, including their roles as nucleophiles, electrophiles, and sulfide donors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Hydrogen sulfide (H2S) is known to induce persulfidation of protein thiols. However, the process of H2S-induced persulfidation is not fully understood as it requires an additional oxidant. There are several mechanistic possibilities and it is of interest to determine which pathway is kinetically most relevant. Here, we detail in vitro assays for the real-time monitoring of thiol redox states in two model proteins with oxidizable cysteines, PTEN, and roGFP2. These allow kinetic measurements of the response of defined protein thiols (or disulfides) to sulfide and sulfane sulfur species. The combination of these assays with cold cyanolysis reveals the role of intermediary sulfane sulfur species in H2S-induced protein thiol oxidation., (© 2015 Elsevier Inc. All rights reserved.)

Hydrogen sulfide (H2S) is an endogenously generated and putative signaling/effector molecule. Despite its numerous reported functions, the chemistry by which it elicits its functions is not understood. Moreover, recent studies allude to the existence of other sulfur species besides H2S that may play critical physiological roles. Herein, the basic chemical biology of H2S as well as other related or derived species is discussed and reviewed. This review particularly focuses on the per- and polysulfides which are likely in equilibrium with free H2S and which may be important biological effectors themselves., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Hydrogen sulfide (H2S) has been considered to be a physiological mediator since the identification of endogenous sulfides in the mammalian brain. H2S is produced from L-cysteine by enzymes such as cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (3MST), and cysteine aminotransferase (CAT). CSE and CAT are regulated by Ca(2+). At steady-state low intracellular concentrations of Ca(2+), CSE and the 3MST/CAT pathway produce H2S. However, after intracellular concentrations of Ca(2+) increase in stimulated cells, the production of H2S by these enzymes decreases. We recently identified a fourth pathway, by which H2S is produced from D-cysteine by the enzymes D-amino acid oxidase (DAO) and 3MST. This pathway is mainly localized in the cerebellum and the kidney. The production of H2S from D-cysteine is 80 times more efficient than that from L-cysteine in the kidney, and the administration of D-cysteine to mice ameliorates renal ischemia-reperfusion injury more effectively than L-cysteine. These results suggest that D-cysteine might be used to treat renal diseases or even increase the success of kidney transplantation. We found that H2S-derived polysulfides exist in the brain and activate transient receptor potential ankyrin-1 (TRPA1) channels 300 times more potently than H2S. Although TRPA1 channels mediate sensory transduction and respond to a variety of stimuli, including cold temperature, pungent compounds and environmental irritants, their endogenous ligand(s) has not been identified. The sulfane sulfur of polysulfides is a reactive electrophile that is readily transferred to a nucleophilic protein thiolate to generate the protein persulfide or bound sulfane sulfur by sulfhydration (as referred to as sulfuration). The bound sulfane sulfur-producing activity of polysulfides is much greater than that of H2S. This review focuses on the physiological roles of H2S and H2S-derived polysulfides as signaling molecules., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Hydrogen sulfide (H2S) is an important signaling molecule with physiological endpoints similar to those of nitric oxide (NO). Growing interest in its physiological roles and pharmacological potential has led to large sets of contradictory data. The principle cause of these discrepancies can be the common neglect of some of the basic H2S chemistry. This study investigates how the experimental outcome when working with H2S depends on its source and dose and the methodology employed. We show that commercially available NaHS should be avoided and that traces of metal ions should be removed because these can reduce intramolecular disulfides and change protein structure. Furthermore, high H2S concentrations may lead to a complete inhibition of cell respiration, mitochondrial membrane potential depolarization and superoxide generation, which should be considered when discussing the biological effects observed upon treatment with high concentrations of H2S. In addition, we provide chemical evidence that H2S can directly react with superoxide. H2S is also capable of reducing cytochrome c(3+) with the concomitant formation of superoxide. H2S does not directly react with nitrite but with NO electrodes that detect H2S. In addition, H2S interferes with the Griess reaction and should therefore be removed from the solution by Cd(2+) or Zn(2+) precipitation prior to nitrite quantification. 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) is reduced by H2S, and its use should be avoided in combination with H2S. All these constraints must be taken into account when working with H2S to ensure valid data., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Hydrogen sulfide (H2S) is a well-known toxic gas that has the smell of rotten eggs. This pungent gas was considered as a physiological mediator, after the identification of endogenous sulfides in the mammalian brain. H2S is produced from L-cysteine by enzymes such as cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase (CAT). We recently identified a fourth pathway, where H2S is produced from D-cysteine by the enzyme D-amino acid oxidase (DAO) along with 3MST. We demonstrated that H2S is a neuromodulator that facilitates hippocampal long-term potentiation (LTP) by enhancing the activity of N-methyl-D-aspartate (NMDA) receptors. It also induces Ca(2+) influx in the astrocytes by activating the transient receptor potential ankyrin-1 (TRPA1) channels. In addition to being a signaling molecule, it also functions as a neuroprotective agent by enhancing the production of glutathione, a major intracellular antioxidant that scavenges the reactive oxygen species (ROS) in the mitochondria. H2S regulates the activity of the enzymes by incorporating the bound sulfane sulfur to cysteine residues. This modification is known as sulfhydration or sulfuration. The neuroprotective ubiquitin E3 ligase, parkin, enhances its neuroprotective activity by this modification. This review is focused on the functional role of H2S as a signaling molecule and as a cytoprotectant in the nervous system. In addition, this review shows the recent findings that indicate that the H2S-derived polysulfides found in the brain activate TRPA1 channels more potently than parental H2S., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Hydrogen sulfide (H2S) is an endogenous transmitter with the potential to regulate aqueous humor dynamics and protect retinal neurons from degeneration. The aim of the present study was two-fold: (a) to evaluate the release of H2S from two polysulfides, diallyl disulfide (DADS), and diallyl trisulfide (DATS); and (b) to investigate their ocular hypotensive actions in normotensive male and female rabbits in the presence and absence of GSH. Materials and Methods: H2S was quantified hourly for up to 6 h using a H2S-Biosensor (World Precision Instruments, Sarasota, Fl). Intraocular pressure (IOP) was assessed in normotensive New Zealand Albino rabbits using a pneumotonometer (model 30 classic; Reichert Ophthalmic Instruments, Depew, NY, USA). Results: In the presence of GSH, there was an increase in the in vitro release of H2S produced by DADS and DATS. Both DADS and DATS also caused a dose-dependent reduction in IOP in male and female rabbits, in both treated and untreated eyes. For instance, in male animals, the presence of GSH (3% and 5%) significantly (p < 0.05, n = 5) enhanced the ocular hypotensive action of DADS (2%) and DATS (2%) from 14.02 ± 2.89% to 18.67 ± 5.6% and from 16.22 ± 3.48 to 23.62 ± 5.79%, respectively. Conclusions: GSH enhanced both H2S release and ocular hypotensive action of the polysulfides in a manner that was dependent on the number of sulfur atoms present in each polysulfide. Furthermore, female animals were less sensitive to the IOP-lowering action of the polysulfides, when compared to their male counterparts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Elemental sulfur and its derivatives, polysulfides, play a key role in hydrogen sulfide oxidation processes in anoxic basins. Having low solubility, elemental sulfur is mainly represented by suspended forms. However, in sulfide waters, it forms highly soluble polysulfides. This article studies elemental sulfur and polysulfides in the upper part of the Black Sea anoxic water column in 2017–2019 and 2022 at stations located on the continental slope off the coast of the Caucasus and Crimea. Sulfur was sampled, filtered, and determined under strictly anoxic conditions in an argon atmosphere. The concentration of elemental sulfur (zero-valent sulfur (ZVS)–elemental sulfur together with polysulfides) increases with depth and hydrogen sulfide content from 0.01 µmol/kg at the redox interface to 0.67 µmol/kg at a depth of 600 m. The elemental sulfur fraction in the composition of ZVS is 23 ± 5%. Based on thermodynamic data, calculation of the polysulfide concentration in equilibrium with suspended sulfur shows that deeper than 20–25 m of the upper boundary of the anoxic zone, their concentration was higher than ZVS and at a depth of 600 m they differed about threefold. The predominance of elemental sulfur over sulfide sulfur in the composition of polysulfides in the anoxic zone at depths of 450 and 600 m may be the reason for the fractionation of its isotopic composition by 2.2‰ with respect to dissolved sulfide sulfur (–41.0‰ VCDT). [ABSTRACT FROM AUTHOR]

Polysulfides have received increased interest in redox biology due to their role as the precursors of H2S and persulfides. However, the compounds that are suitable for biological investigations are limited to cysteine- and glutathione-derived polysulfides. In this work, we report the preparation and evaluation of a novel polysulfide derived from thioglucose, which represents the first carbohydrate-based polysulfide. This compound, thioglucose tetrasulfide (TGS4), showed excellent stability and water solubility. H2S and persulfide production from TGS4, as well as its associated antioxidative property were also demonstrated. Additionally, TGS4 was demonstrated to significantly induce cellular sulfane sulfur level increase, in particular for the formation of hydropersulfides/trisulfides. These results suggest that TGS4 is a useful tool for polysulfide research.

Volatile sulfur compounds (VSCs) are important aroma and flavour characters in food and beverage products. The identification and quantification of these extremely reactive and volatile compounds pose analytical challenges which demand selective and sensitive methods. In this study, a novel quantification method was developed to analyse sulfhydryls as well as the total pool of sulfhydryls which can be released after tris(2-carboxyethyl)phosphine (TCEP) addition from disulfides, polysulfides, metal-bound and other yet to be identified sources naturally present in wine. The majority of methods for VSC quantification analyse VSCs in wine headspace, whereas this method measures sulfhydryls and TCEP-releasable sulfhydryl species, which likely include free and metal-bound sulfhydryl forms, in the liquid phase of wine using UHPLC-MS/MS. Sulfhydryls were derivatised with N-(2-ferroceneethyl) maleimide (FEM), subsequently, followed by differential labelling of sulfhydryls released after TCEP addition with ferrocenecarboxylic acid-(2-maleimidoyl)ethylamide (FMEA). Analysis of commercial wines revealed the presence of hydrogen sulfide, methanethiol, ethanethiol, and 2-mercaptoethanol at aroma-active concentrations. Significant positive correlations were found between MeSH and CH3–S-R TCEP-releasable species, and significant positive correlations were found between EtSH and CH3–CH2–S-R TCEP-releasable species. This method provides important information on sulfhydryls, and may also provide insights into a wine's risk of developing ‘reductive’ faults post-bottling from latent sources.

Hydrogen sulfide (H2S) and polysulfides (H2Sn, n ≥ 2) are signaling molecules produced by 3-mercaptopyruvate sulfurtransferase (3MST) that play various physiological roles, including the induction of hippocampal long-term potentiation (LTP), a synaptic model of memory formation, by enhancing N-methyl-d-aspartate (NMDA) receptor activity. However, the presynaptic action of H2S/H2Sn on neurotransmitter release, regulation of LTP induction, and animal behavior are poorly understood. Here, we showed that H2S/H2S2 applied to the rat hippocampus by in vivo microdialysis induces the release of GABA, glutamate, and d-serine, a co-agonist of NMDA receptors. Animals with genetically knocked-out 3MST and the target of H2S2, transient receptor potential ankyrin 1 (TRPA1) channels, revealed that H2S/H2S2, 3MST, and TRPA1 activation play a critical role in LTP induction, and the lack of 3MST causes behavioral hypersensitivity to NMDA receptor antagonism, as in schizophrenia. H2S/H2Sn, 3MST, and TRPA1 channels have therapeutic potential for psychiatric diseases and cognitive deficits. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) has been extensively studied as a signal molecule in the body for the past 30 years. Researchers have conducted studies using both natural and synthetic sources of H2S, known as H2S donors, which have different characteristics in terms of how they release H2S. These donors can be inorganic salts or have various organic structures. In recent years, certain types of sulfur compounds found naturally in foods have been characterized as H2S donors and explored for their potential health benefits. These compounds are referred to as ''sulfanutraceuticals,'' a term that combines ''nutrition'' and ''pharmaceutical''. It is used to describe products derived from food sources that offer additional health advantages. By introducing the terms ''sulfaceuticals'' and ''sulfanutraceuticals,'' we categorize sulfur-containing substances based on their origin and their use in both preclinical and clinical research, as well as in dietary supplements.

Hydrogen sulfide (H2S) and its oxidation product zero-valent sulfur (S0) play important roles in animals, plants, and bacteria. Inside cells, S0 exists in various forms, including polysulfide and persulfide, which are collectively referred to as sulfane sulfur. Due to the known health benefits, the donors of H2S and sulfane sulfur have been developed and tested. Among them, thiosulfate is a known H2S and sulfane sulfur donor. We have previously reported that thiosulfate is an effective sulfane sulfur donor in Escherichia coli; however, it is unclear how it converts thiosulfate to cellular sulfane sulfur. In this study, we showed that one of the various rhodaneses, PspE, in E. coli was responsible for the conversion. After the thiosulfate addition, the ΔpspE mutant did not increase cellular sulfane sulfur, but the wild type and the complemented strain ΔpspE::pspE increased cellular sulfane sulfur from about 92 μM to 220 μM and 355 μM, respectively. LC-MS analysis revealed a significant increase in glutathione persulfide (GSSH) in the wild type and the ΔpspE::pspE strain. The kinetic analysis supported that PspE was the most effective rhodanese in E. coli in converting thiosulfate to glutathione persulfide. The increased cellular sulfane sulfur alleviated the toxicity of hydrogen peroxide during E. coli growth. Although cellular thiols might reduce the increased cellular sulfane sulfur to H2S, increased H2S was not detected in the wild type. The finding that rhodanese is required to convert thiosulfate to cellular sulfane sulfur in E. coli may guide the use of thiosulfate as the donor of H2S and sulfane sulfur in human and animal tests. [ABSTRACT FROM AUTHOR]

Over the past three decades, the perception of hydrogen sulfide (H2S) in living organisms has changed drastically. From being considered a toxic molecule, H2S is now considered a multifunctional signaling molecule that is involved directly or indirectly in a myriad of physiological processes in animal and plant cells but also in the mechanism of responses against adverse or pathological situations that usually have associated cellular oxidative stress. This Forum editorial introduces a set of articles (four reviewers and a research article) that emphasizes the relevance of H2S in the research area of plants and mammals as well as it also highlights the future directions of investigations. Antioxid. Redox Signal. 39, 980–982. [ABSTRACT FROM AUTHOR]

Reactive sulfur species, or persulfides and polysulfides, such as cysteine hydropersulfide and glutathione persulfide, are endogenously produced in abundance in both prokaryotes and eukaryotes, including mammals. Various forms of reactive persulfides occur in both low-molecular-weight and protein-bound thiols. The chemical properties and great supply of these molecular species suggest a pivotal role for reactive persulfides/polysulfides in different cellular regulatory processes (e.g., energy metabolism and redox signaling). We demonstrated earlier that cysteinyl-tRNA synthetase (CARS) is a new cysteine persulfide synthase (CPERS) and is responsible for the in vivo production of most reactive persulfides (polysulfides). Some researchers continue to suggest that 3-mercaptopyruvate sulfurtransferase (3-MST), cystathionine β-synthase (CBS), and cystathionine γ-lyase (CSE) may also produce hydrogen sulfide and persulfides that may be generated during the transfer of sulfur from 3-mercaptopyruvate to the cysteine residues of 3-MST or direct synthesis from cysteine by CBS/CSE, respectively. We thus used integrated sulfur metabolome analysis, which we recently developed, with 3-MST knockout (KO) mice and CBS/CSE/3-MST triple-KO mice, to elucidate the possible contribution of 3-MST, CBS, and CSE to the production of reactive persulfides in vivo. We therefore quantified various sulfide metabolites in organs derived from these mutant mice and their wild-type littermates via this sulfur metabolome, which clearly revealed no significant difference between mutant mice and wild-type mice in terms of reactive persulfide production. This result indicates that 3-MST, CBS, and CSE are not major sources of endogenous reactive persulfide production; rather, CARS/CPERS is the principal enzyme that is actually involved in and even primarily responsible for the biosynthesis of reactive persulfides and polysulfides in vivo in mammals. [ABSTRACT FROM AUTHOR]

An incomplete Sox system lacking sulfane dehydrogenase SoxCD may produce and accumulate sulfane sulfur when oxidizing thiosulfate. However, how bacteria alleviate the pressure of sulfane sulfur accumulation remains largely unclear. In this study, we focused on the bacterium Cupriavidus pinatubonensis JMP134, which contains a complete Sox system. When soxCD was deleted, this bacterium temporarily produced sulfane sulfur when oxidizing thiosulfate. Persulfide dioxygenase (PDO) in concert with glutathione oxidizes sulfane sulfur to sulfite. Sulfite can spontaneously react with extra persulfide glutathione (GSSH) to produce thiosulfate, which can feed into the incomplete Sox system again and be oxidized to sulfate. Furthermore, the deletion strain lacking PDO and SoxCD produced volatile H2S gas when oxidizing thiosulfate. By comparing the oxidized glutathione (GSSG) between the wild-type and deletion strains, we speculated that H2S is generated during the interaction between sulfane sulfur and the glutathione/oxidized glutathione (GSH/GSSG) redox couple, which may reduce the oxidative stress caused by the accumulation of sulfane sulfur in bacteria. Thus, PDO and H2S release play a critical role in alleviating sulfane sulfur toxicity after the loss of soxCD in C. pinatubonensis JMP134. [ABSTRACT FROM AUTHOR]