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Gases are essential for various applications relevant to human health, including in medicine, biomedical imaging, and pharmaceutical synthesis. However, gases are significantly more challenging to safely handle than liquids and solids. Herein, we review the use of porous materials, such as metal‐organic frameworks (MOFs), zeolites, and silicas, to adsorb medicinally relevant gases and facilitate their handling as solids. Specific topics include the use of MOFs and zeolites to deliver H2S for therapeutic applications, 129Xe for magnetic resonance imaging, O2 for the treatment of cancer and hypoxia, and various gases for use in organic synthesis. This Perspective aims to bring together the organic, inorganic, medicinal, and materials chemistry communities to inspire the design of next‐generation porous materials for the storage and delivery of medicinally relevant gases. [ABSTRACT FROM AUTHOR]

In studying CO for its pathophysiological roles, four metal/borane-carbonyl complexes have been widely used as CO-releasing molecules (CORMs) because of their commercial availability. The CO-release properties of CORM-2, CORM-3, and CORM-A1 have been rigorously characterized. In this study, we characterize CORM-401 for its CO-donating ability under various conditions relevant to studying CO biology. First, with regard to the "intrinsic" CO-release ability of CORM-401 and factors that could influence such ability, we found significant effects of added reagents such as thiol, peroxide, and dithionite on CO-release yields and rate. The variable nature of CO release from CORM-401 indicates the need for predetermining CO production yield and rate under the same conditions before biology experiments. Second, because of the commercial availability of CORM-401 in DMSO stock solution, we characterized its stability in such a preparation and found significantly diminished CO-release capacity of CORM-401 after exposing to DMSO or aqueous solution. Third, because carboxyhemoglobin (COHb) is an important indicator of the ability for a CO donor to supply CO in animal model work, we characterized the property for CORM-401 to elevate COHb. Fourth, quality assurance of such a metal complex is important to ensure consistency in results. Our findings indicate that the unstable nature of CORM-401 presents a quality assurance issue for end users. All these combined with the previously reported chemical reactivity of CORM-401could lead to intractable scenarios in obtaining meaningful results using CORM-401 that can be reasonably attributed to CO in biology experiments. [ABSTRACT FROM AUTHOR]

This review consolidates the evidence supporting endogenous HNO generation through enzymatic and non‐enzymatic pathways, emphasizing advancements in real‐time HNO sensing within living systems. Azanone (nitroxyl, HNO) is the one‐electron‐reduced congener of nitric oxide (NO•) and shares various biological actions. HNO exhibits unique properties, including positive inotropic and lusitropic effects, along with resistance to scavenging by reactive oxygen species (ROS), particularly superoxide. Research on HNO has intensified over the last two decades, focusing on its reactivity and the prospect of endogenous formation due to its potential significance. The high reactivity of HNO arises from reactions with biologically relevant species such as oxygen, NO•, and thiols, as well as self‐dimerization. Detecting and quantifying HNO has posed challenges, initially relying on nitrous oxide (N2O) detection, a byproduct of dimerization. Recent advancements, including fluorescent probes and a specific electrochemical nanomolar‐level sensor, have facilitated direct detection, enhancing understanding of HNO reactivity and formation. [ABSTRACT FROM AUTHOR]

Many living beings use exogenous and/or endogenous gases to attain evolutionary benefits. We make a comprehensive assessment of one of the major gaseous reservoirs in the human body, i.e., the bowel, providing extensive data that may serve as reference for future studies. We assess the intestinal gases in healthy humans, including their volume, composition, source and local distribution in proximal as well as distal gut. We analyse each one of the most abundant intestinal gases including nitrogen, oxygen, nitric oxide, carbon dioxide, methane, hydrogen, hydrogen sulfide, sulfur dioxide and cyanide. For every gas, we describe diffusive patterns, active trans -barrier transport dynamics, chemical properties, intra-/extra-intestinal metabolic effects mediated by intracellular, extracellular, paracrine and distant actions. Further, we highlight the local and systemic roles of gasotransmitters, i.e., signalling gaseous molecules that can freely diffuse through the intestinal cellular membranes. Yet, we provide testable hypotheses concerning the still unknown effects of some intestinal gases on the myenteric and submucosal neurons. • Many living beings make use the mechanical and/or chemical properties of gases. • We focus on an eminent gaseous reservoir in the human body, i.e., the healthy intestine. • We analyse volume, composition, local distribution and source of each intestinal gas. • We describe the intra-/extra-intestinal physiological roles of intestinal exogenous and endogenous gases. • We highlight the local and systemic roles of gasotransmitters. [ABSTRACT FROM AUTHOR]

Irisin is a myokine secreted under the influence of physical activity and exposure to low temperatures and through different exogenous stimuli by the cleavage of its precursor, fibronectin type III domain-containing protein 5 (FNDC5). It is mainly known for maintaining of metabolic homeostasis, promoting the browning of white adipose tissue, the thermogenesis process, and glucose homeostasis. Growing experimental evidence suggests the possible central role of irisin in the regulation of cardiometabolic pathophysiological processes. On the other side, hydrogen sulfide (H2S) is well recognized as a pleiotropic gasotransmitter that regulates several homeostatic balances and physiological functions and takes part in the pathogenesis of cardiometabolic diseases. Through the S-persulfidation of cysteine protein residues, H2S is capable of interacting with crucial signaling pathways, exerting beneficial effects in regulating glucose and lipid homeostasis as well. H2S and irisin seem to be intertwined; indeed, recently, H2S was found to regulate irisin secretion by activating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/FNDC5/irisin signaling pathway, and they share several mechanisms of action. Their involvement in metabolic diseases is confirmed by the detection of their lower circulating levels in obese and diabetic subjects. Along with the importance of metabolic disorders, these modulators exert favorable effects against cardiovascular diseases, preventing incidents of hypertension, atherosclerosis, heart failure, myocardial infarction, and ischemia–reperfusion injury. This review, for the first time, aims to explore the role of H2S and irisin and their possible crosstalk in cardiovascular diseases, pointing out the main effects exerted through the common molecular pathways involved. [ABSTRACT FROM AUTHOR]

Asprosin, a novel adipokine secreted mainly by white adipose tissue, regulates organismal responses to short-term fasting, initiates glucose synthesis and/or release from the liver and thus stimulates appetite, increases total energy reserves in adipose tissue. Determining the bioenergetic status of the organism, this hormone influences tissue oxygen content and, accordingly, oxygen-transporting function of blood in the case of overweight and insulin resistance. Individuals with an increased asprosin content associated with overweight and class 1 obesity, as well as insulin resistance, demonstrate a shift of the oxygen–hemoglobin dissociation curve, accompanied by an increase in the blood concentration of nitrogen monoxide gasotransmitter and a decrease in hydrogen sulfide levels. Asprosin is involved in the regulation of the gasotransmitter system and shaping the mechanisms for blood oxygen transport. Asprosin contribution to the formation oxygen supply and adaptive reserves in individuals with metabolic disorders reflects a new aspect of the mechanism of its action. [ABSTRACT FROM AUTHOR]

The role of carbon monoxide (CO) has evolved albeit controversial disputes on its toxicity. This biological gasotransmitter participates in the endogenous regulation of neurotransmitters and neuropeptides released in the nervous system. Exogenous CO gas inhalation at a lower concentration has been the subject of investigations, which have revealed its biological homeostatic mechanisms and protective effects against many pathological conditions. This therapeutic procedure of CO is, however, limited due to its immediate release, which favours haemoglobin at a high affinity with the subsequent generation of toxic carboxyhaemoglobin in tissues. In order to address this problem, carbon monoxide releasing molecule-2 (CORM-2) or also known as tricarbonyldichlororuthenium II dimer is developed to liberate a controlled amount of CO in the biological systems. In this review, we examine several potential mechanisms exerted by this therapeutic compound to produce the anti-nociceptive effect that has been demonstrated in previous studies. This review could shed light on the role of CORM-2 to reduce pain, especially in cases of chronic and neuropathic pain. [ABSTRACT FROM AUTHOR]

Certain deep-diving marine mammals [i.e., northern elephant seal (Mirounga angustirostris), Weddell seal (Leptonychotes weddellii)] have blood carbon monoxide (CO) levels that are comparable with those of chronic cigarette smokers. Most CO produced in humans is a byproduct of heme degradation, which is released when red blood cells (RBCs) are destroyed. Elevated CO can occur in humans when RBC lifespan decreases. The contribution of RBC turnover to CO concentrations in marine mammals is unknown. Here, we report the first RBC lifespans in two healthy marine mammal species with different diving capacities and heme stores, the shallow-diving bottlenose dolphin (Tursiops truncatus) and deep-diving beluga whale (Delphinapterus leucas), and we relate the lifespans to the levels of CO in blood and breath. The belugas, with high blood heme stores, had the longest mean RBC lifespan compared with humans and bottlenose dolphins. Both cetacean species were found to have three times higher blood CO content compared with humans. The estimated CO production rate from heme degradation indicates some marine mammals may have additional mechanisms for CO production, or delay CO removal from the body, potentially from long-duration breath-holds. [ABSTRACT FROM AUTHOR]

Significance: Gasotransmitters are small gas molecules that are endogenously generated and have well-defined physiological functions. The most well-defined gasotransmitters currently are nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), while other potent gasotransmitters include ammonia, methane, cyanide, hydrogen gas, and sulfur dioxide. Gasotransmitters play a role in various respiratory diseases such as asthma, chronic obstructive pulmonary disease, obstructive sleep apnea, lung infection, bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, and COVID-19. Recent Advances: Gasotransmitters can act as biomarkers that facilitate disease diagnosis, indicate disease severity, predict disease exacerbation, and evaluate disease outcomes. They also have cell-protective properties, and many studies have been conducted to explore their pharmacological applications. Innovative drug donors and drug delivery methods have been invented to amplify their therapeutic effects. Critical Issues: In this article, we briefly reviewed the physiological and pathophysiological functions of some gasotransmitters in the respiratory system, the progress in detecting exhaled gasotransmitters, as well as innovative drugs derived from these molecules. Future Directions: The current challenge for gasotransmitter research includes further exploring their physiological and pathological functions, clarifying their complicated interactions, exploring suitable drug donors and delivery devices, and characterizing new members of gasotransmitters. Antioxid. Redox Signal. 40, 168–185. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) was recognized as a gaseous signaling molecule, similar to nitric oxide (-NO) and carbon monoxide (CO). The aim of this review is to provide an overview of the formation of hydrogen sulfide (H2S) in the human body. H2S is synthesized by enzymatic processes involving cysteine and several enzymes, including cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), cysteine aminotransferase (CAT), 3-mercaptopyruvate sulfurtransferase (3MST) and D-amino acid oxidase (DAO). The physiological and pathological effects of hydrogen sulfide (H2S) on various systems in the human body have led to extensive research efforts to develop appropriate methods to deliver H2S under conditions that mimic physiological settings and respond to various stimuli. These functions span a wide spectrum, ranging from effects on the endocrine system and cellular lifespan to protection of liver and kidney function. The exact physiological and hazardous thresholds of hydrogen sulfide (H2S) in the human body are currently not well understood and need to be researched in depth. This article provides an overview of the physiological significance of H2S in the human body. It highlights the various sources of H2S production in different situations and examines existing techniques for detecting this gas. [ABSTRACT FROM AUTHOR]

There is a paucity of information on the role of iron nutrition in regulating H2S-mediated salinity tolerance in plants. The present work implies exogenous Fe and Na2S (H2S-donor) for investigating the interactive effects of Fe and H2S in regulating seedling growth, osmolyte accumulation, chlorophyll accumulation and antioxidative defense under salinity stress. To achieve this, an experiment was set up with seeds of tomato (Solanum lycopersicum L. var. romeo) grown in presence of NaCl concentration (80 mM). Control seedlings were grown using half strength hoagland nutrient solution without NaCl. Exogenous Fe (100 µM) and H2S was supplied in the form of Na2S (100 µM) individually and in combination both in presence and absence of NaCl. Growth parameters like shoot length and root lengths were taken along with chlorophyll, osmolyte contents, enzymatic and non-enzymatic antioxidants as well as content of H2S and L-DES activity were also measured. Results demonstrated that exogenous Fe and H2S to an extent provide protection to tomato seedlings subjected to salt stress through prevention membrane damage, increased antioxidative defense and there was significant increase in L-DES activity that led to increased H2S content. Exogenous Fe and Na2S application in tomato seedlings under salt stress exhibited decrease in malondialdehyde content by 19% and 50% respectively and H2O2 by 13.7% and 16.8% respectively. Combined application of Fe and Na2S increased the levels of antioxidative enzyme activities including CAT (53.8%), POX (14%), SOD (58%) and APX (11.7%) was observed under salt stress. However, tomato seedlings supplemented with combined application of Fe and H2S showed decreased H2S content as well as lower L-DES activity. Simultaneously, combined application of Fe and H2S to salt stressed tomato seedlings however showed increased activity of some of the antioxidative enzymes deciphering positive role of this interaction of Fe and Na2S under the influence of salt stress. [ABSTRACT FROM AUTHOR]

Due to protection of extracellular polymeric substances, the therapeutic efficiency of conventional antimicrobial agents is often impeded by their poor infiltration and accumulation in biofilm. Herein, one type of surface charge adaptable nitric oxide (NO) nanogenerator was developed for biofilm permeation, retention and eradication. This nanogenerator (PDG@Au–NO/PBAM) is composed of a core-shell structure: thermo-sensitive NO donor conjugated AuNPs on cationic poly(dopamine-co-glucosamine) nanoparticle (PDG@Au–NO) served as core, and anionic phenylboronic acid-acryloylmorpholine (PBAM) copolymer was employed as a shell. The NO nanogenerator featured long circulation and good biocompatibility. Once the nanogenerator reached acidic biofilm, its surface charge would be switched to positive after shell dissociation and cationic core exposure, which was conducive for the nanogenerator to infiltrate and accumulate in the depth of biofilm. In addition, the nanogenerator could sustainably generate NO to disturb the integrity of biofilm at physiological temperature, then generate hyperthermia and explosive NO release upon NIR irradiation to efficiently eradicate drug-resistant bacteria biofilm. Such rational design offers a promising approach for developing nanosystems against biofilm-associated infections.

Background: Hydrogen sulfide (H2S), an endogenous gasotransmitter, has potential applications in several conditions. However, its quantification in simulated physiological solutions is a major challenge due to its gaseous nature and other physicochemical properties. Aim: This study was designed to compare four commonly used H2S detection and quantification methods in aqueous solutions. Methods: The four techniques compared were one colorimetric, one chromatographic and two electrochemical methods. Results: Colorimetric and chromatographic methods quantified H2S in millimolar and micromole ranges, respectively. The electrochemical methods quantified H2S in the nanomole and picomole ranges and were less time-consuming. Conclusion: The H2S quantification method should be selected based on the specific requirements of a research project in terms of sensitivity, response time and cost-effectiveness.

Cyanobacteria, the prominent nitrogen fixers, are facing many stressful situations throughout their life span, hence in recent years the yield and productivity of paddy crops are highly compromised. To address this problem, this study is structured to investigate how signaling molecules can positively influence the ability of tested cyanobacteria to counteract the adverse effects of metal stress. Thus, the main objective of this study is to elucidate the importance and crosstalk of intracellular signaling molecules, nitric oxide (NO), and hydrogen peroxide (H2O2) during Cd stress tolerance in cyanobacteria. The effect of exogenous gasotransmitter, NO and redox molecule, H2O2, in mitigation of cadmium (Cd, 6 µM) toxicity on different physiological and biochemical activities were well recorded in economically important cyanobacteria Nostoc muscorum ATCC 27893 and Anabaena sp. PCC 7120. Under Cd stress increased Cd accumulation and oxidative stress in test cyanobacteria, impaired the functioning of the ascorbate-glutathione (AsA-GSH) cycle. Exogenous application of NO (10 µM) and H2O2 (1 µM) ameliorated the negative effects of Cd through boosting-up the activities of enzymatic (ascorbate peroxidase, glutathione reductase and dehydroascorbate reductase) and the contents of non-enzymatic (cysteine, proline, ascorbate, glutathione and non-protein-thiols) antioxidants. The application of NO scavenger (PTIO) or NO synthase enzyme inhibitor (LNAME) to the Cd-stressed cells abolished the recovery of the above parameters, even in the presence of exogenous H2O2. Notwithstanding to this, under similar stress exogenous addition of scavenger of H2O2 (NAC) or inhibitor of NADPH oxidase enzyme (DPI) to the growth medium could not restrict the recovery of the above parameters in the presence of NO, hence pointing towards the major role of NO in tolerance of the test organisms to Cd stress. In conclusion, the finding revealed that NO plays a vital role in H2O2 signaling to attain Cd stress tolerance in cyanobacteria. Moreover, the study has created a scope to search for deeper insight into signaling interactions between other gasotransmitters and redox molecules in cyanobacteria. Further, the current finding recommends using a lower dose of SNP (NO donor, a cost-effective chemical) in paddy fields may ensure better growth of cyanobacteria (biofertilizer) even under prevailing stress conditions for sustainable agriculture to maintain productivity of rice crops.

Plant root growth and developmental capacities reside in a few stem cells of the root apical meristem (RAM). Maintenance of these stem cells requires regenerative divisions of the initial stem cell niche (SCN) cells, self-maintenance, and proliferative divisions of the daughter cells. This ensures sufficient cell diversity to guarantee the development of complex root tissues in the plant. Damage in the root during growth involves the formation of a new post-embryonic root, a process known as regeneration. Post-embryonic root development and organogenesis processes include primary root development and SCN maintenance, plant regeneration, and the development of adventitious and lateral roots. These developmental processes require a fine-tuned balance between cell proliferation and maintenance. An important regulator during root development and regeneration is the gasotransmitter nitric oxide (NO). In this review we have sought to compile how NO regulates cell rate proliferation, cell differentiation, and quiescence of SCNs, usually through interaction with phytohormones, or other molecular mechanisms involved in cellular redox homeostasis. NO exerts a role on molecular components of the auxin and cytokinin signaling pathways in primary roots that affects cell proliferation and maintenance of the RAM. During root regeneration, a peak of auxin and cytokinin triggers specific molecular programs. Moreover, NO participates in adventitious root formation through its interaction with players of the brassinosteroid and cytokinin signaling cascade. Lately, NO has been implicated in root regeneration under hypoxia conditions by regulating stem cell specification through phytoglobins. [ABSTRACT FROM AUTHOR]

Carbon monoxide (CO) has been recognized as a crucial gasotransmitter mainly produced by heme oxygenase (HO)-catalyzed heme degradation in plant. Recent studies have shown that CO plays an important role in regulating growth and development of plant, as well as and responding to a variety of abiotic stresses. Meanwhile, many studies have reported on CO working in combination with other signal molecules to mitigate abiotic stress. Here, we presented a comprehensive overview of recent developments in which CO reduces plant damage caused by abiotic stresses. The regulation of antioxidant system, photosynthetic system, ion balance and transport are the main mechanisms of CO-alleviated abiotic stress. We also proposed and discussed the relationship between CO and other signal molecules, including nitric oxide (NO), hydrogen sulfide (H 2 S), hydrogen gas (H 2), abscisic acid (ABA), indole 3-acetic acid (IAA), gibberellin (GA), cytokine (CTK), salicylic acid (SA), jasmonic acid (JA), hydrogen peroxide (H 2 O 2) and calcium ion (Ca2+). Furthermore, the important role of HO genes in alleviating abiotic stress was also discussed. We proposed promising and new research directions for the study of plant CO, which can provide further insights on the role of CO in plant growth and development under abiotic stress. • CO/HO system alleviates abiotic stress by regulating antioxidant and photosynthetic system and ion balance. • CO/HO system interacts with gas molecules, phytohormones and plant growth regulators to enhance stress tolerance. • HO genes have no tissue specificity and can be induced by various abiotic stresses. [ABSTRACT FROM AUTHOR]

Irisin is a myokine secreted under the influence of physical activity and exposure to low temperatures and through different exogenous stimuli by the cleavage of its precursor, fibronectin type III domain-containing protein 5 (FNDC5). It is mainly known for maintaining of metabolic homeostasis, promoting the browning of white adipose tissue, the thermogenesis process, and glucose homeostasis. Growing experimental evidence suggests the possible central role of irisin in the regulation of cardiometabolic pathophysiological processes. On the other side, hydrogen sulfide (H2S) is well recognized as a pleiotropic gasotransmitter that regulates several homeostatic balances and physiological functions and takes part in the pathogenesis of cardiometabolic diseases. Through the S-persulfidation of cysteine protein residues, H2S is capable of interacting with crucial signaling pathways, exerting beneficial effects in regulating glucose and lipid homeostasis as well. H2S and irisin seem to be intertwined; indeed, recently, H2S was found to regulate irisin secretion by activating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/FNDC5/irisin signaling pathway, and they share several mechanisms of action. Their involvement in metabolic diseases is confirmed by the detection of their lower circulating levels in obese and diabetic subjects. Along with the importance of metabolic disorders, these modulators exert favorable effects against cardiovascular diseases, preventing incidents of hypertension, atherosclerosis, heart failure, myocardial infarction, and ischemia–reperfusion injury. This review, for the first time, aims to explore the role of H2S and irisin and their possible crosstalk in cardiovascular diseases, pointing out the main effects exerted through the common molecular pathways involved.

Reactive oxygen and nitrogen species may be produced during inflammation leading to the formation of NO, H2S or HNO. Enzymes such as iNOS, CSE and CBS might also be responsible for polysulfide production. Since these signalling molecules might have an impact on colonic motility, the aim of this study was to compare their effect on rat colonic slow phasic contractions (SPC). Organ bath measurements with strips obtained from rat proximal colon were performed using the polysulfide Na2S3, sodium nitroprusside (NaNP), sodium hydrogen sulfide (NaHS), Angeli's salt as NO, H2S, and HNO donors, respectively. TTX (1 µM) was used to block neuronal activity. All four molecules, concentration-dependently, inhibited the amplitude and frequency of SPC both in the circular and longitudinal muscle layer. The relative potency was NaNP>Angeli's salt>NaHS>Na2S3. The inhibitory response induced by NaNP (1 µM) and Angeli's salt (50 µM) was reversed by ODQ (10 µM) whereas the inhibitory effect of NaHS (1 mM) was reversed by apamin (1 µM) and glibenclamide (10 µM). Na2S3 (1 mM) response was partially reversed by apamin (1 µM) and glibenclamide (10 µM). High concentrations of Na2S3 caused an increase in tone. Low concentrations of NaHS or Na2S3 did not potentiate NaNP responses. All signalling molecules inhibit SPC in both muscle layers. The effect is independent of neural activity and involves guanylyl cyclase (NO and HNO) and SKCa and KATP channels (NaHS or Na2S3). Other pathways might also be involved in Na2S3 responses. Accordingly, complementary mechanisms of inhibition might be attributable to these signalling molecules. [ABSTRACT FROM AUTHOR]

The gaseous neurotransmitter hydrogen sulfide (H2S) exerts neuroprotective efficacy in the brain via post‐translational modification of cysteine residues by sulfhydration, also known as persulfidation. This process is comparable in biological impact to phosphorylation and mediates a variety of signalling events. Unlike conventional neurotransmitters, H2S cannot be stored in vesicles due to its gaseous nature. Instead, it is either locally synthesized or released from endogenous stores. Sulfhydration affords both specific and general neuroprotective effects and is critically diminished in several neurodegenerative disorders. Conversely, some forms of neurodegenerative disease are linked to excessive cellular H2S. Here, we review the signalling roles of H2S across the spectrum of neurodegenerative diseases, including Huntington's disease, Parkinson's disease, Alzheimer's disease, Down syndrome, traumatic brain injury, the ataxias, and amyotrophic lateral sclerosis, as well as neurodegeneration generally associated with ageing. [ABSTRACT FROM AUTHOR]

Numerous studies have revealed the gasotransmitter functions of hydrogen sulfide (H2S) in various biological processes. However, the involvement of H2S in sulfur metabolism and/or Cys synthesis makes its role as a signaling molecule ambiguous. The generation of endogenous H2S in plants is closely related to the metabolism of Cys, which play roles in a variety of signaling pathway occurring in various cellular processes. Here, we found that exogenous H2S fumigation and Cys treatment modulated the production rate and content of endogenous H2S and Cys to various degrees. Furthermore, we provided comprehensive transcriptomic analysis to support the gasotransmitter role of H2S besides as a substrate for Cys synthesis. Comparison of the differentially expressed genes (DEGs) between H2S and Cys treated seedlings indicated that H2S fumigation and Cys treatment caused different influences on gene profiles during seedlings development. A total of 261 genes were identified to respond to H2S fumigation, among which 72 genes were co-regulated by Cys treatment. GO and KEGG enrichment analysis of the 189 genes, H2S but not Cys regulated DEGs, indicated that these genes mainly involved in plant hormone signal transduction, plantpathogen interaction, phenylpropanoid biosynthesis, and MAPK signaling pathway. Most of these genes encoded proteins having DNA binding and transcription factor activities that play roles in a variety of plant developmental and environmental responses. Many stress-responsive genes and some Ca2+ signal associated genes were also included. Consequently, H2S regulated gene expression through its role as a gasotransmitter, rather than just as a substrate for Cys biogenesis, and these 189 genes were far more likely to function in H2S signal transduction independently of Cys. Our data will provide insights for revealing and enriching H2S signaling networks. [ABSTRACT FROM AUTHOR]

Inducing high levels of reactive oxygen species (ROS) inside tumor cells is a cancer therapy method termed chemodynamic therapy (CDT). Relying on delivery of Fenton reaction promoters such as Fe2+, CDT takes advantage of overproduced ROS in the tumor microenvironment. We developed a peptide‐H2S donor conjugate, complexed with Fe2+, termed AAN‐PTC–Fe2+. The AAN tripeptide was specifically cleaved by legumain, an enzyme overexpressed in glioma cells, to release carbonyl sulfide (COS). Hydrolysis of COS by carbonic anhydrase formed H2S, an inhibitor of catalase, an enzyme that detoxifies H2O2. Fe2+ and H2S together increased intracellular ROS levels and decreased viability in C6 glioma cells compared with controls lacking either Fe2+, the AAN sequence, or the ability to generate H2S. AAN‐PTC–Fe2+ performed better than temezolimide while exhibiting no cytotoxicity toward H9C2 cardiomyocytes. This study provides an H2S‐amplified, enzyme‐responsive platform for synergistic cancer treatment. [ABSTRACT FROM AUTHOR]

Inducing high levels of reactive oxygen species (ROS) inside tumor cells is a cancer therapy method termed chemodynamic therapy (CDT). Relying on delivery of Fenton reaction promoters such as Fe2+, CDT takes advantage of overproduced ROS in the tumor microenvironment. We developed a peptide‐H2S donor conjugate, complexed with Fe2+, termed AAN‐PTC–Fe2+. The AAN tripeptide was specifically cleaved by legumain, an enzyme overexpressed in glioma cells, to release carbonyl sulfide (COS). Hydrolysis of COS by carbonic anhydrase formed H2S, an inhibitor of catalase, an enzyme that detoxifies H2O2. Fe2+ and H2S together increased intracellular ROS levels and decreased viability in C6 glioma cells compared with controls lacking either Fe2+, the AAN sequence, or the ability to generate H2S. AAN‐PTC–Fe2+ performed better than temezolimide while exhibiting no cytotoxicity toward H9C2 cardiomyocytes. This study provides an H2S‐amplified, enzyme‐responsive platform for synergistic cancer treatment. [ABSTRACT FROM AUTHOR]

Inducing high levels of reactive oxygen species (ROS) inside tumor cells is a cancer therapy method termed chemodynamic therapy (CDT). Relying on delivery of Fenton reaction promoters such as Fe2+, CDT takes advantage of overproduced ROS in the tumor microenvironment. We developed a peptide‐H2S donor conjugate, complexed with Fe2+, termed AAN‐PTC–Fe2+. The AAN tripeptide was specifically cleaved by legumain, an enzyme overexpressed in glioma cells, to release carbonyl sulfide (COS). Hydrolysis of COS by carbonic anhydrase formed H2S, an inhibitor of catalase, an enzyme that detoxifies H2O2. Fe2+ and H2S together increased intracellular ROS levels and decreased viability in C6 glioma cells compared with controls lacking either Fe2+, the AAN sequence, or the ability to generate H2S. AAN‐PTC–Fe2+ performed better than temezolimide while exhibiting no cytotoxicity toward H9C2 cardiomyocytes. This study provides an H2S‐amplified, enzyme‐responsive platform for synergistic cancer treatment. [ABSTRACT FROM AUTHOR]

Inducing high levels of reactive oxygen species (ROS) inside tumor cells is a cancer therapy method termed chemodynamic therapy (CDT). Relying on delivery of Fenton reaction promoters such as Fe2+, CDT takes advantage of overproduced ROS in the tumor microenvironment. We developed a peptide‐H2S donor conjugate, complexed with Fe2+, termed AAN‐PTC–Fe2+. The AAN tripeptide was specifically cleaved by legumain, an enzyme overexpressed in glioma cells, to release carbonyl sulfide (COS). Hydrolysis of COS by carbonic anhydrase formed H2S, an inhibitor of catalase, an enzyme that detoxifies H2O2. Fe2+ and H2S together increased intracellular ROS levels and decreased viability in C6 glioma cells compared with controls lacking either Fe2+, the AAN sequence, or the ability to generate H2S. AAN‐PTC–Fe2+ performed better than temezolimide while exhibiting no cytotoxicity toward H9C2 cardiomyocytes. This study provides an H2S‐amplified, enzyme‐responsive platform for synergistic cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Aortic aneurysm and aortic dissection (AAD) are life-threatening vascular diseases, with endothelium being the primary target for AAD treatment. Protein S-sulfhydration is a newly discovered posttranslational modification whose role in AAD has not yet been defined. This study aims to investigate whether protein S-sulfhydration in the endothelium regulates AAD and its underlying mechanism. Methods: Protein S-sulfhydration in endothelial cells (ECs) during AAD was detected and hub genes regulating homeostasis of the endothelium were identified. Clinical data of patients with AAD and healthy controls were collected, and the level of the cystathionine γ lyase (CSE)/hydrogen sulfide (H2S) system in plasma and aortic tissue were determined. Mice with EC-specific CSE deletion or overexpression were generated, and the progression of AAD was determined. Unbiased proteomics and coimmunoprecipitation combined with mass spectrometry analysis were conducted to determine the upstream regulators of the CSE/H2S system and the findings were confirmed in transgenic mice. Results: Higher plasma H2S levels were associated with a lower risk of AAD, after adjustment for common risk factors. CSE was reduced in the endothelium of AAD mouse and aorta of patients with AAD. Protein S-sulfhydration was reduced in the endothelium during AAD and protein disulfide isomerase (PDI) was the main target. S-sulfhydration of PDI at Cys343 and Cys400 enhanced PDI activity and mitigated endoplasmic reticulum stress. EC-specific CSE deletion was exacerbated, and EC-specific overexpression of CSE alleviated the progression of AAD through regulating the S-sulfhydration of PDI. ZEB2 (zinc finger E-box binding homeobox 2) recruited the HDAC1-NuRD complex (histone deacetylase 1–nucleosome remodeling and deacetylase) to repress the transcription of CTH , the gene encoding CSE, and inhibited PDI S-sulfhydration. EC-specific HDAC1 deletion increased PDI S-sulfhydration and alleviated AAD. Increasing PDI S-sulfhydration with the H2S donor GYY4137 or pharmacologically inhibiting HDAC1 activity with entinostat alleviated the progression of AAD. Conclusions: Decreased plasma H2S levels are associated with an increased risk of aortic dissection. The endothelial ZEB2-HDAC1-NuRD complex transcriptionally represses CTH , impairs PDI S-sulfhydration, and drives AAD. The regulation of this pathway effectively prevents AAD progression. [ABSTRACT FROM AUTHOR]

Biofilm-associated infections (BAI) have posed serious threats to public health. Novel therapy based on carbon monoxide (CO) is being increasingly appreciated. However, CO therapy like inhaled gas treatment was impeded owing to its low bioavailability. Besides, the direct use of CO releasing molecules (CORM) showed low therapeutic efficacy in BAI. Therefore, it is vital to improve the efficiency of CO therapy. Herein, we proposed polymeric CO releasing micelles (pCORM) from self-assembly of amphiphilic copolymers containing CORM bearing block as hydrophobic part and acryloylmorpholine block as hydrophilic part. The catechol modified CORM were conjugated through pH cleavable boronate ester bonds and releasing CO passively under biofilm microenvironment. When combined with subminimal inhibitory concentration antibiotic amikacin, pCORM could significantly enhance its bactericidal efficiency against biofilm-encapsulated multidrug-resistant bacteria, representing a promising approach to combat BAI. [Display omitted] • pCORM showed acidic pH/thiol dual-responsive CO release property. • pCORM exhibited BME responsive significantly antibacterial ability. • The combination between pCORM and amikacin displayed noticeably enhanced bactericidal efficacy. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is endogenously produced in adipocytes and fat tissues and stimulates adipogenesis. The integrated pathogenic effects of H2S on the development of obesity and the underlying mechanisms, however, have been unclear. Here, we find that a decreased endogenous H2S level lowered lipid accumulation in mouse adipocytes. Exogenous H2S treatment significantly increased the adipogenesis of primary mouse preadipocytes after six days of adipogenic induction. In the early phase of adipogenesis, H2S increased cell proliferation and prepared cells to go through hyperplasia. After H2S treatment for ten days, preadipocytes exhibited significantly greater cell surface area and diameter, indicating cell hypertrophy. Although it stimulated lipid accumulation and adipogenesis, H2S had no effect on lipolysis. With nutrition overload and high glucose/insulin incubation, H2S further stimulated glucose consumption and deteriorated adipocyte hypertrophy. H2S upregulated hyperplasia genes (CCAAT/enhancer-binding protein (C/EBPβ), cell division cycle 25 (Cdc25), minichromosome maintenance 3 (Mcm3), and cell division cycle 45 (Cdc45)) and cyclin-dependent kinase 2 protein (Cdk2), which regulates cell proliferation. H2S also upregulated the insulin receptor β (Irβ)-activated mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) pathways, leading to adipogenesis. In conclusion, H2S increases adipocyte differentiation, hypertrophy, and hyperplasia, implying that it plays a pathogenic role in obesity disorder.

Environmental conditions greatly impact plant growth and development. In the current context of both global climate change and land degradation, abiotic stresses usually lead to growth restriction limiting crop production. Plants have evolved to sense and respond to maximize adaptation and survival; therefore, understanding the mechanisms involved in the different converging signaling networks becomes critical for improving plant tolerance. In the last few years, several studies have shown the plant responses against drought and salinity, high and low temperatures, mechanical wounding, heavy metals, hypoxia, UV radiation, or ozone stresses. These threats lead the plant to coordinate a crosstalk among different pathways, highlighting the role of phytohormones and reactive oxygen and nitrogen species (RONS). In particular, plants sense these reactive species through post-translational modification (PTM) of macromolecules such as nucleic acids, proteins, and fatty acids, hence triggering antioxidant responses with molecular implications in the plant welfare. Here, this review compiles the state of the art about how plant systems sense and transduce this crosstalk through PTMs of biological molecules, highlighting the S-nitrosylation of protein targets. These molecular mechanisms finally impact at a physiological level facing the abiotic stressful traits that could lead to establishing molecular patterns underlying stress responses and adaptation strategies. [ABSTRACT FROM AUTHOR]

As the third gasotransmitter, hydrogen sulfide (H2S) is involved in a variety of physiological and pathological processes wherein abnormal levels of H2S indicate various diseases. Therefore, an efficient and reliable monitoring of H2S concentration in organisms and living cells is of great significance. Of diverse detection technologies, electrochemical sensors possess the unique advantages of miniaturization, fast detection, and high sensitivity, while the fluorescent and colorimetric ones exhibit exclusive visualization. All these chemical sensors are expected to be leveraged for H2S detection in organisms and living cells, thus offering promising options for wearable devices. In this paper, the chemical sensors used to detect H2S in the last 10 years are reviewed based on the different properties (metal affinity, reducibility, and nucleophilicity) of H2S, simultaneously summarizing the detection materials, methods, linear range, detection limits, selectivity, etc. Meanwhile, the existing problems of such sensors and possible solutions are put forward. This review indicates that these types of chemical sensors competently serve as specific, accurate, highly selective, and sensitive sensor platforms for H2S detection in organisms and living cells. [ABSTRACT FROM AUTHOR]

Numerous studies have revealed the gasotransmitter functions of hydrogen sulfide (H2S) in various biological processes. However, the involvement of H2S in sulfur metabolism and/or Cys synthesis makes its role as a signaling molecule ambiguous. The generation of endogenous H2S in plants is closely related to the metabolism of Cys, which play roles in a variety of signaling pathway occurring in various cellular processes. Here, we found that exogenous H2S fumigation and Cys treatment modulated the production rate and content of endogenous H2S and Cys to various degrees. Furthermore, we provided comprehensive transcriptomic analysis to support the gasotransmitter role of H2S besides as a substrate for Cys synthesis. Comparison of the differentially expressed genes (DEGs) between H2S and Cys treated seedlings indicated that H2S fumigation and Cys treatment caused different influences on gene profiles during seedlings development. A total of 261 genes were identified to respond to H2S fumigation, among which 72 genes were co-regulated by Cys treatment. GO and KEGG enrichment analysis of the 189 genes, H2S but not Cys regulated DEGs, indicated that these genes mainly involved in plant hormone signal transduction, plant-pathogen interaction, phenylpropanoid biosynthesis, and MAPK signaling pathway. Most of these genes encoded proteins having DNA binding and transcription factor activities that play roles in a variety of plant developmental and environmental responses. Many stress-responsive genes and some Ca2+ signal associated genes were also included. Consequently, H2S regulated gene expression through its role as a gasotransmitter, rather than just as a substrate for Cys biogenesis, and these 189 genes were far more likely to function in H2S signal transduction independently of Cys. Our data will provide insights for revealing and enriching H2S signaling networks.

Hydrogen sulfide (H2S) was recognized as a gaseous signaling molecule, similar to nitric oxide (-NO) and carbon monoxide (CO). The aim of this review is to provide an overview of the formation of hydrogen sulfide (H2S) in the human body. H2S is synthesized by enzymatic processes involving cysteine and several enzymes, including cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), cysteine aminotransferase (CAT), 3-mercaptopyruvate sulfurtransferase (3MST) and D-amino acid oxidase (DAO). The physiological and pathological effects of hydrogen sulfide (H2S) on various systems in the human body have led to extensive research efforts to develop appropriate methods to deliver H2S under conditions that mimic physiological settings and respond to various stimuli. These functions span a wide spectrum, ranging from effects on the endocrine system and cellular lifespan to protection of liver and kidney function. The exact physiological and hazardous thresholds of hydrogen sulfide (H2S) in the human body are currently not well understood and need to be researched in depth. This article provides an overview of the physiological significance of H2S in the human body. It highlights the various sources of H2S production in different situations and examines existing techniques for detecting this gas.

Environmental conditions greatly impact plant growth and development. In the current context of both global climate change and land degradation, abiotic stresses usually lead to growth restriction limiting crop production. Plants have evolved to sense and respond to maximize adaptation and survival; therefore, understanding the mechanisms involved in the different converging signaling networks becomes critical for improving plant tolerance. In the last few years, several studies have shown the plant responses against drought and salinity, high and low temperatures, mechanical wounding, heavy metals, hypoxia, UV radiation, or ozone stresses. These threats lead the plant to coordinate a crosstalk among different pathways, highlighting the role of phytohormones and reactive oxygen and nitrogen species (RONS). In particular, plants sense these reactive species through post-translational modification (PTM) of macromolecules such as nucleic acids, proteins, and fatty acids, hence triggering antioxidant responses with molecular implications in the plant welfare. Here, this review compiles the state of the art about how plant systems sense and transduce this crosstalk through PTMs of biological molecules, highlighting the S-nitrosylation of protein targets. These molecular mechanisms finally impact at a physiological level facing the abiotic stressful traits that could lead to establishing molecular patterns underlying stress responses and adaptation strategies.

Nitric oxide (NO) is a diatomic gaseous molecule, which plays different roles in different strata of organisms. Discovered as a neurotransmitter in animals, NO has now gained a significant place in plant signaling cascade. NO regulates plant growth and several developmental processes including germination, root formation, stomatal movement, maturation and defense in plants. Due to its gaseous state, it is unchallenging for NO to reach different parts of cell and counterpoise antioxidant pool. Various abiotic and biotic stresses act on plants and affect their growth and development. NO plays a pivotal role in alleviating toxic effects caused by various stressors by modulating oxidative stress, antioxidant defense mechanism, metal transport and ion homeostasis. It also modulates the activity of some transcriptional factors during stress conditions in plants. Besides its role during stress conditions, interaction of NO with other signaling molecules such as other gasotransmitters (hydrogen sulfide), phytohormones (abscisic acid, salicylic acid, jasmonic acid, gibberellin, ethylene, brassinosteroids, cytokinins and auxin), ions, polyamines, etc. has been demonstrated. These interactions play vital role in alleviating plant stress by modulating defense mechanisms in plants. Taking all these aspects into consideration, the current review focuses on the role of NO and its interaction with other signaling molecules in regulating plant growth and development, particularly under stressed conditions. [Display omitted] • Various abiotic and biotic stressors adversely affect the growth, development and productivity of plants. • It becomes decisive to protect the plants from these stressors to meet the food demand of increasing population. • Nitric oxide (NO), a gaseous signaling molecule could enhance the crop production by increasing stress tolerance. • NO also interacts with other signaling molecules and may induce resistance in plants against different types of stresses. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H 2 S), known as the third gasotransmitter, exerts various physiological functions including cardiac protection, angiogenesis, anti-inflammatory, and anti-cancer capability. Given its promising therapeutic potential as well as severe perniciousness if improper use, the sustained and tunable H 2 S delivery systems are highly required for H 2 S-based gas therapy with enhanced bioactivity and reduced side effects. To this end, a series of stimuli-responsive compounds capable of releasing H 2 S (termed H 2 S donors) have been designed over the past two decades to mimic the endogenous generation of H 2 S and elucidate the biological functions. Further to improve the stability of H 2 S donors and achieve the targeted delivery, various delivery systems have been constructed. In this review, we focus on the recent advances of an emerging subset, biomolecular-based H 2 S delivery systems, which combine H 2 S donors with biomolecular vectors including polysaccharide, peptide, and protein. We demonstrated their basic structures, building strategies, and therapeutic applications respectively to unfold their inherent merits endued by biomolecules including biocompatibility, biodegradability as well as expansibility. The varied development potentials of biomolecular-based H 2 S delivery systems based on their specific properties are also discussed. At the end, brief future outlooks and upcoming challenges are presented as well. [Display omitted] • Biomolecule-based hydrogen sulfide delivery systems are reviewed. • Aided by biomolecules, hydrogen sulfide is effectively delivered to lesion sites. • Hydrogen sulfide-based gas therapy has been adopted for biomedical applications. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is an important gasotransmitter that is produced by mammalian cells and performs profound physiological and pathophysiological functions. Biomedical research on H2S metabolism and function in China began 20 years ago, which pioneered the examination of the correlation of abnormal H2S metabolism and cardiovascular diseases. Over the last two decades, research teams in China have made numerous breakthrough discoveries on the effects of H2S metabolism on hypertension, atherosclerosis, pulmonary hypertension, shock, angiogenesis, chronic obstructive pulmonary disease, pain, iron homeostasis, and testicle function, to name a few. These research developments, carried by numerous research teams all over China, build nationwide research network and advance both laboratory study and clinical applications. An integrated and collaborative research strategy would further promote and sustain H2S biomedical research in China and in the world. [ABSTRACT FROM AUTHOR]

• Tomato endogenous H 2 S-generation-associated enzymes were identified and analyzed. • H 2 S generation changed dynamically in developmental and environmental signals. • Dynamic changes of transcripts and activities of H 2 S-generation-associated enzymes. • Several sources of endogenous H 2 S had diverse response patterns in various signals. • Regulatory of H 2 S generation involved crosstalk with phytohormones signals. Increasing studies have confirmed the functions of hydrogen sulfide (H 2 S) as a gas signal molecule (gasotransmitter) in a variety of physiological activities in plants. However, the dynamic changes of endogenous H 2 S generation, especially the response speed and degree of H 2 S-generation-associated members, to both developmental and environmental cues in Solanum lycopersicum L. are still poorly understood. Here, we identified and charactered the H 2 S-generation-associated enzymes in tomato, including O-acetylserine (mercaptan) lyases (OAS-TL), L/D-Cysteine desulfhydrases (L/D-CDes) and nitrogen fixation S (NIFS)-like enzymes, possessing LCD-like activity. Analysis of cis -regulatory elements (CREs) showed that the promoter regions of these H 2 S-generation-associated genes contained lots of light-, hormone- and stresses-responsive CREs, and transcriptional factors (TFs) binding sites, suggesting that the regulatory mechanism of endogenous H 2 S generation might involve TFs mediated transcriptional regulation or/and interacting with phytohormones signals. Levels of endogenous H 2 S exhibited diversity in different organs and developmental stages in tomato, and the top and second highest level of H 2 S in flowers and ripened fruits hinted the significance of H 2 S signal in tomato reproduction and fruit development. Furthermore, the expression of SlOAS4, SlLCD, SlDCD2, SlNFS1 , and SlNFS2 enhanced continuously during fruit ripening, and the SlOAS4 expression exhibited the most significant up-regulation. The SlDCD enzymatic activity responded more quickly to fruit development cues, while the SlLCD remained at a higher level almost throughout the whole fruit ripening. During environmental stimulus, it was found that the transcriptions of SlDCD2 and SlOAS2 responded faster and stronger to heat stress, while SlOAS4 and SlLCD were activated more quickly and significantly by drought stress. Both SlLCD and SlDCD enzymatic activities could be enhanced by drought and heat stress to varying degrees, and it seemed that the SlLCD was activated to a greater extent and remained at the higher activity for a longer period. With the extension of exogenous phytohormones (ABA, SA, GA, JA, ACC, NAA) treatment, the SlLCD activity and the endogenous H 2 S content increased in a specific time-dependent manner, and ABA, SA and NAA had more rapid effects on SlLCD activity. By widely explored the dynamic responses of endogenous H 2 S generation, our study would provide some references for understanding the regulatory mechanism upstream of H 2 S signaling in tomato growth developments and environmental adaptations. [ABSTRACT FROM AUTHOR]

Purpose: Hydrogen sulfide (H2S) plays important roles in brain pathophysiology. However, nuclear imaging probes for the in vivo detection of brain H2S in living animals have not been developed. Here, we report the first nuclear imaging probe that enables in vivo imaging of endogenous H2S in the brain of live mice. Methods: Utilizing a bis(thiosemicarbazone) backbone, a fluorescent ATSM-FITC conjugate was synthesized. Its copper complex, Cu(ATSM-FITC) was thoroughly tested as a biosensor for H2S. The same ATSM-FITC ligand was quantitatively labeled with [64Cu]CuCl2 to obtain a radioactive [64Cu][Cu(ATSM-FITC)] imaging probe. Biodistribution and positron emission tomography (PET) imaging studies were performed in healthy mice and neuroinflammation models. Results: The Cu(ATSM-FITC) complex reacts instantly with H2S to release CuS and becomes fluorescent. It showed excellent reactivity, sensitivity, and selectivity to H2S. Endogenous H2S levels in living cells were successfully detected by fluorescence microscopy. Exceptionally high brain uptake of [64Cu][Cu(ATSM-FITC)] (> 9% ID/g) was observed in biodistribution and PET imaging studies. Subtle changes in brain H2S concentrations in live mice were accurately detected by quantitative PET imaging. Due to its dual modality feature, increased H2S levels in neuroinflammation models were characterized at the subcellular level by fluorescence imaging and at the whole-body scale by PET imaging. Conclusion: Our biosensor can be readily utilized to study brain H2S function in live animal models and shows great potential as a novel imaging agent for diagnosing brain diseases. [ABSTRACT FROM AUTHOR]

Melatonin, a molecule that was first identified in animal tissues, has been confirmed to be involved as a potential phytohormone in a variety of plant physiological responses. It is considered primarily as an antioxidant with important actions in controlling reactive oxygen and reactive nitrogen species. In addition to its role in regulating plant growth and development, phytomelatonin is involved in protection against abiotic and biotic stresses. The 'gasotransmitter'—that is, a gaseous signaling molecule—is a new concept that has been advanced in the past two decades, with functions in animal and plant physiological regulation. Gasotransmitters including nitric oxide, carbon monoxide, hydrogen sulfide, methane, and, more recently identified, hydrogen gas are critical and indispensable in a wide range of biological processes. This review investigates the interrelationship between phytomelatonin and the above-mentioned gasotransmitters from the perspective of biosynthetic origin and functions. Moreover, the potential future research directions for phytomelatonin and gasotransmitters interactions are discussed. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide has been recently identified as the third biological gasotransmitter, along with the more well studied nitric oxide (NO) and carbon monoxide (CO). Intensive studies on its potential as a therapeutic agent for cardiovascular, inflammatory, infectious and neuropathological diseases have been undertaken. Here we review the possible direct targets of H2S in mammals. H2S directly interacts with reactive oxygen/nitrogen species and is involved in redox signaling. H2S also reacts with hemeproteins and modulates metal-containing complexes. Once being oxidized, H2S can persulfidate proteins by adding -SSH to the amino acid cysteine. These direct modifications by H2S have significant impact on cell structure and many cellular functions, such as tight junctions, autophagy, apoptosis, vesicle trafficking, cell signaling, epigenetics and inflammasomes. Therefore, we conclude that H2S is involved in many important cellular and physiological processes. Compounds that donate H2S to biological systems can be developed as therapeutics for different diseases. [ABSTRACT FROM AUTHOR]

Following the discovery of nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2S) has been identified as the third gasotransmitter in humans. Increasing evidence have shown that H2S is of preventive or therapeutic effects on diverse pathological complications. As a consequence, it is of great significance to develop suitable approaches of H2S‐based therapeutics for biomedical applications. H2S‐releasing agents (H2S donors) play important roles in exploring and understanding the physiological functions of H2S. More importantly, accumulating studies have validated the theranostic potential of H2S donors in extensive repertoires of in vitro and in vivo disease models. Thus, it is imperative to summarize and update the literatures in this field. In this review, first, the background of H2S on its chemical and biological aspects is concisely introduced. Second, the studies regarding the H2S‐releasing compounds are categorized and described, and accordingly, their H2S‐donating mechanisms, biological applications, and therapeutic values are also comprehensively delineated and discussed. Necessary comparisons between related H2S donors are presented, and the drawbacks of many typical H2S donors are analyzed and revealed. Finally, several critical challenges encountered in the development of multifunctional H2S donors are discussed, and the direction of their future development as well as their biomedical applications is proposed. We expect that this review will reach extensive audiences across multiple disciplines and promote the innovation of H2S biomedicine. [ABSTRACT FROM AUTHOR]

Glaucoma is a neurodegenerative disease of visual system characterized by gradual loss of retinal ganglion cells (RGC). Since mitochondrial dysfunction of RGC is significantly involved in the pathological mechanisms of glaucoma, and hydrogen sulfide (H2S) takes part in the pathogeny of glaucoma and shows promising potential in restoring mitochondrial function in other neurons, the authors aimed to investigate the impact of H2S on mitochondrial function of RGC with a rat glaucoma model. An established chronic ocular hypertension (COH) rat model induced by injection of cross-linking hydrogel into anterior chamber was adopted, and a H2S donor, sodium hydrosulfide (NaHS), was selected to treat rats through intraperitoneal injection. After a period of 4 weeks, RGCs were isolated from the subjected rats with an immunopanning method and went through evaluations of mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (MPTP) opening, intracellular Ca2 + level, reactive oxygen species (ROS) level, and cytosolic Cytochrome C distribution. The results showed that the mitochondrial function of RGC in experimental glaucoma was markedly improved by H2S supplement, being presented as stabilization of MMP, alleviation of MPTP opening, improvement of intracellular Ca2+ hemostasis, reduction of ROS accumulation, and inhibition of Cytochrome C release. Our study implicated that preservation of mitochondrial function by H2S probably plays a key role in protecting RGC in the context of glaucomatous neuropathy, and it is worth further deepgoing research to benefit the development of glaucoma treatment. [ABSTRACT FROM AUTHOR]

After understanding the biological signaling roles of hydrogen sulfide and its involvement in various physiological processes, there has been enormous interest in exploring its therapeutic utility in areas such as cancer, inflammation, cardiovascular diseases, etc. There is also growing interest in using suitable H2S donors in combination with other drugs to improve the treatment outcome through the modulation of multiple pathways. The premature release of H2S from small molecule donors and the difficulty in controlling its spatio-temporal distribution are the major challenges during these efforts. Hence the development of appropriate carriers that can release this gasotransmitter along with the therapeutic entity of interest in a controlled manner has high significance. In this regard, this report presents a novel drug delivery system from oxanorbornane-based synthetic lipids that carries a H2S-releasing 1,2-dithiole-3-thione moiety as part of the head group. Nanoaggregates of the resulting conjugate are not only capable of efficiently entrapping a non-steroidal anti-inflammatory drug such as ibuprofen, but also release this drug and H2S in a controlled and sequential manner., (© 2024 Wiley‐VCH GmbH.)

Gasotransmitters are endogenous gaseous signaling molecules that can freely pass through cell membranes and transmit signals between cells, playing multiple roles in cell signal transduction. Due to extensive and ongoing research in this field, we have successfully identified many gasotransmitters so far, among which nitric oxide, carbon monoxide, and hydrogen sulfide are best studied. Gasotransmitters are implicated in various diseases related to necroptosis, such as cardiovascular diseases, inflammation, ischemia-reperfusion, infectious diseases, and neurological diseases. However, the mechanisms of their effects on necroptosis are not fully understood. This review focuses on endogenous gasotransmitter synthesis and metabolism and discusses their roles in necroptosis, aiming to offer new insights for the therapeutic approaches to necroptosis-associated diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Apart from nitric oxide (NO) and carbon monoxide (CO), hydrogen sulphide (H2S) has emerged as a potential gasotransmitter that has regulatory roles in root differentiation, proliferation and stress signalling. H2S metabolism in plants exhibits spatio‐temporal differences that are intimately associated with sulphide signalling in the cytosol and other subcellular components, e.g. chloroplast and mitochondria. H2S biosynthesis in plant organs uses both enzymatic and non‐enzymatic pathways. H2S generation in roots and aerial organs is modulated by developmental phase and changes in environmental stimuli. H2S has an influential role in root development and in the nodulation process. Studies have revealed that H2S is a part of the auxin and NO signalling pathways in roots, which induce lateral root formation. At the molecular level, exogenous application of H2S regulates expression of several transcription factors, viz. LBD (Lateral organ Boundaries Domain), MYB (myeloblastosis) and AP2/ERF (Apetala 2/ Ethylene Response Factor), which stimulate upregulation of PpLBD16 (Lateral organ boundaries domain 16), thereby significantly increasing the number of lateral roots. Concomitantly, H2S acts as a crucial signalling molecule in roots during various abiotic stresses, e.g. drought, salinity heavy metals (HMs), etc., and augments stress tolerance in plants. Interestingly, extensive crosstalk exists between H2S, NO, ABA, calcium and ethylene during stress, which escalate plant defence and regulate plant growth and productivity. Hence, the present review will elaborate the role of H2S in root development, stress alleviation, legume–Rhizobium symbiosis and rhizosphere signalling. The review also examines the mechanism of H2S‐mediated abiotic stress mitigation and cross‐talk with other signaling molecules. [ABSTRACT FROM AUTHOR]