Pills of Multi-Target H2S Donating Molecules for Complex Diseases.

Among the various drug discovery methods, a very promising modern approach consists in designing multi-target-directed ligands (MTDLs) able to modulate multiple targets of interest, including the pathways where hydrogen sulfide (H2S) is involved. By incorporating an H2S donor moiety into a native drug, researchers have been able to simultaneously target multiple therapeutic pathways, resulting in improved treatment outcomes. This review gives the reader some pills of successful multi-target H2S-donating molecules as worthwhile tools to combat the multifactorial nature of complex disorders, such as inflammatory-based diseases and cancer, as well as cardiovascular, metabolic, and neurodegenerative disorders.

Synergy of Target-Induced Magnetic Network and Single-Drop Chromogenic System for Ultrasensitive "All-in-Tube" Detection of miRNA in Whole Blood.

The development of liquid biopsy methods for the accurate and reliable detection of miRNAs in whole blood is critical for the early diagnosis and monitoring of diseases. However, accurate quantification of miRNA expression levels remains challenging due to the complex matrix and low abundance of miRNAs in blood samples. Herein, we report a contactless signal output strategy with low background interference that ensures "zero-contact" between the reaction system and the colorimetry system. The designed target-induced magnetic ZnS/ZIF-90/ZnS network can serve as a unique signal amplifier and transducer. It releases hydrogen sulfide (H2S) gas in an acidic solution which can be concentrated in a droplet of only a few microliters in volume, etching the silver layer of Au@Ag nanostars (NSTs) in the droplet. This will lead to changes in the localized surface plasmon resonance signals of the NSTs. Finally, quantitative detection of let-7a is realized by measuring the offset value of the UV-vis absorption peak. Therefore, by virtue of the synergistic action of quadruple signal amplification methods, including catalytic hairpin assembly, ZnS/ZIF-90/ZnS, magnetic separation, and microextraction, the "All-in-Tube" ultrasensitive detection of low-abundance let-7a in whole blood is achieved with a detection limit as low as the aM level. In addition, the "zero-contact" signal output mode effectively solves the problem of complex matrix interference, demonstrating the great potential of this method for miRNA quantification in complex samples, such as whole blood.

Responsive ß-Diketonate-europium(III) Complex-Based Probe for Time-Gated Luminescence Detection and Imaging of Hydrogen Sulfide In Vitro and In Vivo.

As a crucial biological gasotransmitter, hydrogen sulfide (H2S) plays important roles in many pathological and physiological processes. Highly selective and sensitive detection of H2S is significant for the precise diagnosis and evaluation of diverse diseases. Nevertheless, challenges remain in view of the interference of autofluorescence in organisms and the stronger reactivity of H2S itself. Herein, we report the design and synthesis of a novel H2S-responsive ß-diketonate-europium(III) complex-based probe, [Eu(DNB-Npketo)3(terpy)], for background-free time-gated luminescence (TGL) detection and imaging of H2S in autofluorescence-rich biological samples. The probe, consisting of a 2,4-dinitrobenzenesulfonyl (DNB) group coupled to a ß-diketonate-europium(III) complex, shows almost no luminescence owing to the existence of intramolecular photoinduced electron transfer. The cleavage of the DNB group by a H2S-triggered reaction results in the recovery of the long-lived luminescence of the Eu3+ complex, allowing the detection of H2S in complicated biological samples to be performed in TGL mode. The probe showed a fast response, high specificity, and high sensitivity toward H2S, which enabled it to be successfully used for the quantitative TGL detection of H2S in tissue homogenates of mouse organs. Additionally, the low cytotoxicity of the probe allowed it to be further used for the TGL imaging of H2S in living cells and mice under different stimuli. All of the results suggested the potential of the probe for the investigation and diagnosis of H2S-related diseases.

Metabolomics and transcriptomics combined with physiology reveal key metabolic pathway responses in tobacco roots exposed to NaHS.

Hydrogen sulfide (H2S) has emerged as a novel endogenous gas signaling molecule, joining the ranks of nitric oxide (NO) and carbon monoxide (CO). Recent research has highlighted its involvement in various physiological processes, such as promoting root organogenesis, regulating stomatal movement and photosynthesis, and enhancing plant growth, development, and stress resistance. Tobacco, a significant cash crop crucial for farmers' economic income, relies heavily on root development to affect leaf growth, disease resistance, chemical composition, and yield. Despite its importance, there remains a scarcity of studies investigating the role of H2S in promoting tobacco growth. This study exposed tobacco seedlings to different concentrations of NaHS (an exogenous H2S donor) - 0, 200, 400, 600, and 800 mg/L. Results indicated a positive correlation between NaHS concentration and root length, wet weight, root activity, and antioxidant enzymatic activities (CAT, SOD, and POD) in tobacco roots. Transcriptomic and metabolomic analyses revealed that treatment with 600 mg/L NaHS significantly effected 162 key genes, 44 key enzymes, and two metabolic pathways (brassinosteroid synthesis and aspartate biosynthesis) in tobacco seedlings. The addition of exogenous NaHS not only promoted tobacco root development but also potentially reduced pesticide usage, contributing to a more sustainable ecological environment. Overall, this study sheds light on the primary metabolic pathways involved in tobacco root response to NaHS, offering new genetic insights for future investigations into plant root development.

[Sargassum seaweed assaults the French West Indies]. / Algues sargasses à l'assaut des Antilles.

SARGASSUM SEAWEED AS SAULTS THE FRENCH WEST INDIES. Since 2011, Martinique and the islands of Guadeloupe have been affected by repeated groundings, culminating in an exceptional wave in 2018. While the sargassum ( Sargassum natans and S. fluitans ) involved in these phenomena are neither toxic nor urticating, indirect toxicity linked to the presence of microorganisms and heavy metals (arsenic, mercury, etc.) in sargassum clusters has been described. Similarly, after a 24 to 48 hours stay on the shore, sargassum algae enter a putrefaction cycle responsible to produce hydrogen sulfide (H2S) and ammonia (NH3). The acute toxicity of these gases is well known. However, very few data are available on the clinical effects of prolonged exposure to low doses of H2S and NH3. Our team has recently described the syndromic features of chronic exposure, supposing for deleterious effects on the cardiovascular, respiratory and neurological systems.

ALGUES SARGASSES À L'ASSAUT DES ANTILLES. Depuis 2011, la Martinique et les îles de la Guadeloupe sont touchées par des échouements à répétition d'algues sargasses qui ont culminé avec une vague exceptionnelle en 2018. Si les sargasses (Sargassum natans et S. fluitans) impliquées dans ces phénomènes ne sont ni toxiques ni urticantes, une toxicité indirecte liée à la présence de micro-organismes et de métaux lourds (arsenic, mercure…) dans les amas de sargasses est décrite. De même, après un séjour de vingt-quatre à quarante-huit heures sur le littoral, les algues sargasses entrent dans un cycle de putréfaction responsable de la production d'hydrogène sulfuré (H2S) et d'ammoniac (NH3). La toxicité aiguë de ces gaz est bien connue. Il existe en revanche très peu de données disponibles sur les effets cliniques d'une exposition prolongée à de faibles doses d'H2S ou NH3. Notre équipe a récemment décrit le tableau syndromique de l'exposition chronique et suppose des effets délétères sur le système cardiovasculaire, respiratoire et neurologique.

Transdermal Hydrogen Sulfide Delivery Enabled by Open-Metal-Site Metal-Organic Frameworks.

Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter involved in many physiological processes that are integral to proper cellular functioning. Due to its profound anti-inflammatory and antioxidant properties, H2S plays important roles in preventing inflammatory skin disorders and improving wound healing. Transdermal H2S delivery is a therapeutically viable option for the management of such disorders. However, current small-molecule H2S donors are not optimally suited for transdermal delivery and typically generate electrophilic byproducts that may lead to undesired toxicity. Here, we demonstrate that H2S release from metal-organic frameworks (MOFs) bearing coordinatively unsaturated metal centers is a promising alternative for controlled transdermal delivery of H2S. Gas sorption measurements and powder X-ray diffraction (PXRD) studies of 11 MOFs support that the Mg-based framework Mg2(dobdc) (dobdc4- = 2,5-dioxidobenzene-1,4-dicarboxylate) is uniquely well-suited for transdermal H2S delivery due to its strong yet reversible binding of H2S, high capacity (14.7 mmol/g at 1 bar and 25 °C), and lack of toxicity. In addition, Rietveld refinement of synchrotron PXRD data from H2S-dosed Mg2(dobdc) supports that the high H2S capacity of this framework arises due to the presence of three distinct binding sites. Last, we demonstrate that transdermal delivery of H2S from Mg2(dobdc) is sustained over a 24 h period through porcine skin. Not only is this significantly longer than sodium sulfide but this represents the first example of controlled transdermal delivery of pure H2S gas. Overall, H2S-loaded Mg2(dobdc) is an easily accessible, solid-state source of H2S, enabling safe storage and transdermal delivery of this therapeutically relevant gas.

Nascent transcription reveals regulatory changes in extremophile fishes inhabiting hydrogen sulfide-rich environments.

Regulating transcription allows organisms to respond to their environment, both within a single generation (plasticity) and across generations (adaptation). We examined transcriptional differences in gill tissues of fishes in the Poecilia mexicana species complex (family Poeciliidae), which have colonized toxic springs rich in hydrogen sulfide (H2S) in southern Mexico. There are gene expression differences between sulfidic and non-sulfidic populations, yet regulatory mechanisms mediating this gene expression variation remain poorly studied. We combined capped-small RNA sequencing (csRNA-seq), which captures actively transcribed (i.e. nascent) transcripts, and messenger RNA sequencing (mRNA-seq) to examine how variation in transcription, enhancer activity, and associated transcription factor binding sites may facilitate adaptation to extreme environments. csRNA-seq revealed thousands of differentially initiated transcripts between sulfidic and non-sulfidic populations, many of which are involved in H2S detoxification and response. Analyses of transcription factor binding sites in promoter and putative enhancer csRNA-seq peaks identified a suite of transcription factors likely involved in regulating H2S-specific shifts in gene expression, including several key transcription factors known to respond to hypoxia. Our findings uncover a complex interplay of regulatory processes that reflect the divergence of extremophile populations of P. mexicana from their non-sulfidic ancestors and suggest shared responses among evolutionarily independent lineages.

A firm-push-to-open and light-push-to-lock strategy for a general chemical platform to develop activatable dual-modality NIR-II probes.

Activatable near-infrared (NIR) imaging in the NIR-II range is crucial for deep tissue bioanalyte tracking. However, designing such probes remains challenging due to the limited availability of general chemical strategies. Here, we introduced a foundational platform for activatable probes, using analyte-triggered smart modulation of the π-conjugation system of a NIR-II-emitting rhodamine hybrid. By tuning the nucleophilicity of the ortho-carboxy moiety, we achieved an electronic effect termed "firm-push-to-open and light-push-to-lock," which enables complete spirocyclization of the probe before sensing and allows for efficient zwitterion formation when the light-pushing aniline carbamate trigger is transformed into a firm-pushing aniline. This platform produces dual-modality NIR-II imaging probes with ~50-fold fluorogenic and activatable photoacoustic signals in live mice, surpassing reported probes with generally below 10-fold activatable signals. Demonstrating generality, we successfully designed probes for hydrogen peroxide (H2O2) and hydrogen sulfide (H2S). We envision a widespread adoption of the chemical platform for designing activatable NIR-II probes across diverse applications.

Hydrogen sulfide maintains mitochondrial homeostasis and regulates ganoderic acids biosynthesis by SQR under heat stress in Ganoderma lucidum.

Hydrogen sulfide (H2S) has recently been recognized as an important gaseous transmitter with multiple physiological effects in various species. Previous studies have shown that H2S alleviated heat-induced ganoderic acids (GAs) biosynthesis, an important quality index of Ganoderma lucidum. However, a comprehensive understanding of the physiological effects and molecular mechanisms of H2S in G. lucidum remains unexplored. In this study, we found that heat treatment reduced the mitochondrial membrane potential (MMP) and mitochondrial DNA copy number (mtDNAcn) in G. lucidum. Increasing the intracellular H2S concentration through pharmacological and genetic means increased the MMP level, mtDNAcn, oxygen consumption rate level and ATP content under heat treatment, suggesting a role for H2S in mitigating heat-caused mitochondrial damage in G. lucidum. Further results indicated that H2S activates sulfide-quinone oxidoreductase (SQR) and complex III (Com III), thereby maintaining mitochondrial homeostasis under heat stress in G. lucidum. Moreover, SQR also mediated the negative regulation of H2S to GAs biosynthesis under heat stress. Furthermore, SQR might be persulfidated under heat stress in G. lucidum. Thus, our study reveals a novel physiological function and molecular mechanism of H2S signalling under heat stress in G. lucidum with broad implications for research on the environmental response of microorganisms.

The role of redox-active small molecules and oxidative protein post-translational modifications in seed aging.

Seed vigor is a crucial indicator of seed quality. Variations in seed vigor are closely associated with seed properties and storage conditions. The vigor of mature seeds progressively declines during storage, which is called seed deterioration or aging. Seed aging induces a cascade of cellular damage, including impaired subcellular structures and macromolecules, such as lipids, proteins, and DNA. Reactive oxygen species (ROS) act as signaling molecules during seed aging causing oxidative damage and triggering programmed cell death (PCD). Mitochondria are the main site of ROS production and change morphology and function before other organelles during aging. The roles of other small redox-active molecules in regulating cell and seed vigor, such as nitric oxide (NO) and hydrogen sulfide (H2S), were identified later. ROS, NO, and H2S typically regulate protein function through post-translational modifications (PTMs), including carbonylation, S-glutathionylation, S-nitrosylation, and S-sulfhydration. These signaling molecules as well as the PTMs they induce interact to regulate cell fate and seed vigor. This review was conducted to describe the physiological changes and underlying molecular mechanisms that in seed aging and provides a comprehensive view of how ROS, NO, and H2S affect cell death and seed vigor.

Rapidly responsive and highly selective NIR fluorescent probe for detecting hydrogen sulfide in food samples and living cells.

Hydrogen sulfide (H2S) is a pungent gas that is one of the key mediators of signal transduction in biological systems, and its presence is related to the freshness of some protein foods. Using phenothiazine derivatives as fluorophores and 2, 4-dinitrobenzene sulfonate (DNBS) fragments as reaction groups, a near-infrared (NIR) probe WX-HS for H2S identification was designed. With the addition of H2S, WX-HS appeared a strong fluorescence signal at 660 nm with short reaction time (90 s) and high sensitivity, and fluorescence state change from non-fluorescent to orange-red. In addition, WX-HS could effectively detect H2S produced during food oxidation. Based on its low cytotoxicity, the WX-HS probe further enabled the detection and imaging of H2S in A549 cells.

Practical NIR Assay Derived from Cyanine to Evaluate Intracellular H2S in Living Cell Imaging.

To monitor the biological function of H2S in real time, this investigation demonstrated the design and synthesis of a novel fluorescent probe integrated with cyanine and 2,4-dinitrophenol for the qualitative and quantitative detection of H2S. An NIR sensitive sensor (FS-HS-1) was provided with a straightforward process. Spectroscopy experiments elucidated that FS-HS-1 could selectively detect H2S in a PBS solution (containing 40% acetonitrile) with a 111-fold fluorescence enhancement at 715 nm (ex. 605 nm). The response towards NaHS occurred in less than 2 min, and the detection limit was confirmed to be as low as 4.47 ± 0.11 nmol/L. Furthermore, the probe is capable of monitoring changes in exogenous H2S concentrations within living cells with confocal and 2P imaging.

ADT-OH exhibits anti-metastatic activity on triple-negative breast cancer by combinatorial targeting of autophagy and mitochondrial fission.

High basal autophagy and enhanced mitochondrial fission in triple-negative breast cancer (TNBC) cells support cell migration and promote plasticity of cancer cell metabolism. Here, we suggest a novel combination therapy approach for the treatment of TNBC that targets Drp1-mediated mitochondrial fission and autophagy pathways. Hydrogen sulfide (H2S) mediates a myriad of biological processes, including autophagy and mitochondrial function. In this study, we demonstrated that 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), one of the most widely utilized sustained-release H2S donors, effectively suppresses metastasis of TNBC cells in the absence of proliferation inhibition in vitro and in vivo. ADT-OH treatment ameliorated autophagy flux by suppressing autophagosome formation and induced mitochondrial elongation through decreasing expression of dynamin-related protein 1 (Drp1) and increasing expression of mitochondrial fusion protein (Mfn2). At the same time, ADT-OH downregulated mitophagy flux and inhibited mitochondrial function, eventually leading to the inhibition of migration and invasion in TNBC cells. In vivo, intraperitoneal administration of ADT-OH revealed a potent anti-metastatic activity in three different animal models, the MDA-MB-231 orthotopic xenograft model, the 4T1-Luci orthotopic model and the 4T1-Luci tail vein metastasis model. However, ADT-OH has an extremely low water solubility, which is a significant barrier to its effectiveness. Thus, we demonstrated that the solubility of ADT-OH in water can be improved significantly by absorption with hydroxypropyl-ß-cyclodextrin (CD). Remarkably, the obtained CD-ADT-OH demonstrated superior anti-cancer effect to ADT-OH in vivo. Altogether, this study describes a novel regulator of mammalian mitochondrial fission and autophagy, with potential utility as an experimental therapeutic agent for metastatic TNBC.

Smartphone Imaging Device for Multimodal Detection of Hydrogen Sulfide Using Cu-Doped MOF Sensors.

Multimodal sensing platforms may offer reliable, fast results, but it is still challenging to incorporate biosensors with high discriminating ability in complex biological samples. Herein, we established a highly sensitive dual colorimetric/electrochemical monitoring approach for the detection of hydrogen sulfide (H2S) utilizing Cu-doped In-based metal-organic frameworks (Cu/In-MOFs) combined with a versatile color selector software-based smartphone imaging device. H2S can result in the enhancement of the electrochemical signal because of the electroactive substance copper sulfide (CuxS), the decrease of the colorimetric signal of the characteristic absorption response caused by the strong coordination effect on Cu/In-MOFs, and the obvious changes of red-green-blue (RGB) values of images acquired via an intelligent smartphone. Attractively, the Cu/In-MOFs-based multimodal detection guarantees precise and sensitive detection of H2S with triple-signal detection limits of 0.096 µM (electrochemical signals), 0.098 µM (colorimetric signals), and 0.099 µM (smartphone signals) and an outstanding linear response. This analytical toolkit provides an idea for fabricating a robust, sensitive, tolerant matrix and reliable sensing platform for rapidly monitoring H2S in clinical disease diagnosis and visual supervision.

Influence of oxidation-reduction potential and pH on polysulfide concentrations and chain lengths in the biological desulfurization process under haloalkaline conditions.

Biological desulfurization under haloalkaline conditions has been applied worldwide to remove hydrogen sulfide (H2S) from sour gas steams. The process relies on sulfide-oxidizing bacteria (SOB) to oxidize H2S to elemental sulfur (S8), which can then be recovered and reused. Recently, a dual-reactor biological desulfurization system was implemented where an anaerobic (sulfidic) bioreactor was incorporated as an addition to a micro-oxic bioreactor, allowing for higher S8 selectivity by limiting by-product formation. The highly sulfidic bioreactor environment enabled the SOB to remove (poly)sulfides (Sx2-) in the absence of oxygen, with Sx2- speculated as a main substrate in the removal pathway, thus making it vital to understand its role in the process. The SOB are influenced by the oxidation-reduction potential (ORP) set-point of the micro-oxic bioreactor as it is used to control the product of oxidation (S8 vs. SO42-), while the uptake of Sx2- by SOB has been qualitatively linked to pH. Therefore, to quantify these effects, this work determined the concentration and speciation of Sx2- in the biological desulfurization process under various pH values and ORP set-points. The total Sx2- concentrations in the sulfidic zone increased at elevated pH (8.9) compared to low pH (< 8.0), with on average 3.3 ± 1.0 mM-S more Sx2-. Chain lengths varied, with S72- only doubling in concentration while S52- increased 9 fold, which is in contrast with observations from abiotic systems. Changes to the ORP set-point of the micro-oxic reactor did not produce substantial changes in Sx2- concentration in the sulfidic zone. This illustrates that the reduction degree of the SOB in the micro-oxic bioreactor does not enhance their ability to interact with Sx2- in the sulfidic bioreactor. This increased understanding of how both pH and ORP affect changes in Sx2- concentration and chain length can lead to improved efficiency and design of the dual-reactor biological desulfurization process.

Hydrogen sulfide mitigates ox­LDL­induced NLRP3/caspase­1/GSDMD dependent macrophage pyroptosis by S­sulfhydrating caspase­1.

Macrophage pyroptosis mediates vascular inflammation and atherosclerosis (AS). Hydrogen sulfide (H2S) exerts a protective role in preventing inflammation and AS. However, its molecular mechanisms of regulating the pyroptosis signaling pathway and inhibiting macrophage pyroptosis remain unexplored. The present study aimed to determine whether H2S mitigates macrophage pyroptosis by downregulating the pyroptosis signaling pathway and S­sulfhydrating caspase­1 under the stimulation of oxidized low­density lipoprotein (ox­LDL), a pro­atherosclerotic factor. Macrophages derived from THP­1 monocytes were pre­treated using exogenous H2S donors sodium hydrosulfide (NaHS) and D,L­propargylglycine (PAG), a pharmacological inhibitor of endogenous H2S­producing enzymes, alone or in combination. Subsequently, cells were stimulated with ox­LDL or the desulfhydration reagent dithiothreitol (DTT) in the presence or absence of NaHS and/or PAG. Following treatment, the levels of H2S in THP­1 derived macrophages were measured by a methylene blue colorimetric assay. The pyroptotic phenotype of THP­1 cells was observed and evaluated by light microscopy, Hoechst 33342/propidium iodide fluorescent staining and lactate dehydrogenase (LDH) release assay. Caspase­1 activity in THP­1 cells was assayed by caspase­1 activity assay kit. Immunofluorescence staining was used to assess the accumulation of active caspase­1. Western blotting and ELISA were performed to determine the expression of pyroptosis­specific markers (NLRP3, pro­caspase­1, caspase­1, GSDMD and GSDMD­N) in cells and the secretion of pyroptosis­related cytokines [interleukin (IL)­1ß and IL­18] in the cell­free media, respectively. The S­sulfhydration of pro­caspase­1 in cells was assessed using a biotin switch assay. ox­LDL significantly induced macrophage pyroptosis by activating the pyroptosis signaling pathway. Inhibition of endogenous H2S synthesis by PAG augmented the pro­pyroptotic effects of ox­LDL. Conversely, exogenous H2S (NaHS) ameliorated ox­LDL­and ox­LDL + PAG­induced macrophage pyroptosis by suppressing the activation of the pyroptosis signaling pathway. Mechanistically, ox­LDL and the DTT increased caspase­1 activity and downstream events (IL­1ß and IL­18 secretion) of the caspase­1­dependent pyroptosis pathway by reducing S­sulfhydration of pro­caspase­1. Conversely, NaHS increased S­sulfhydration of pro­caspase­1, reducing caspase­1 activity and caspase­1­dependent macrophage pyroptosis. The present study demonstrated the molecular mechanism by which H2S ameliorates macrophage pyroptosis by suppressing the pyroptosis signaling pathway and S­sulfhydration of pro­caspase­1, thereby suppressing the generation of active caspase-1 and activity of caspase-1.

Role of hydrogen sulfide in the male reproductive system.

As an important gas signaling molecule, hydrogen sulfide (H2S) affects multiple organ systems, including the nervous, cardiovascular, digestive, and genitourinary, reproductive systems. In particular, H2S not only regulates female reproductive function but also holds great promise in the treatment of male reproductive diseases and disorders, such as erectile dysfunction, prostate cancer, varicocele, and infertility. In this review, we summarize the relationship between H2S and male reproductive organs, including the penis, testis, prostate, vas deferens, and epididymis. As lower urinary tract symptoms have a significant impact on penile erection disorders, we also address the potential ameliorative effects of H2S in erectile dysfunction resulting from bladder disease. Additionally, we discuss the regulatory role of H2S in cavernous smooth muscle relaxation, which involves the NO/cGMP pathway, the RhoA/Rho-kinase pathway, and K+ channel activation. Recently, various compounds that can alleviate erectile dysfunction have been reported to be at least partly dependent on H2S. Therefore, understanding the role of H2S in the male reproductive system may help develop novel strategies for the clinical treatment of male reproductive system diseases.

Hydrogen Sulfide can Scavenge Free Radicals to Improve Spinal Cord Injury by Inhibiting the p38MAPK/mTOR/NF-κB Signaling Pathway.

Spinal cord injury (SCI) causes irreversible cell loss and neurological dysfunctions. Presently, there is no an effective clinical treatment for SCI. It can be the only intervention measure by relieving the symptoms of patients such as pain and fever. Free radical-induced damage is one of the validated mechanisms in the complex secondary injury following primary SCI. Hydrogen sulfide (H2S) as an antioxidant can effectively scavenge free radicals, protect neurons, and improve SCI by inhibiting the p38MAPK/mTOR/NF-κB signaling pathway. In this report, we analyze the pathological mechanism of SCI, the role of free radical-mediated the p38MAPK/mTOR/NF-κB signaling pathway in SCI, and the role of H2S in scavenging free radicals and improving SCI.

Bimetal-organic framework-integrated electrochemical sensor for on-chip detection of H2S and H2O2 in cancer tissues.

Studies on the interaction between hydrogen sulfide (H2S) and hydrogen peroxide (H2O2) in redox signaling motivate the development of a sensitive sensing platform for their discriminatory and dynamic detection. Herein, we present a fully integrated microfluidic on-chip electrochemical sensor for the online and simultaneous monitoring of H2S and H2O2 secreted by different biological samples. The sensor utilizes a cicada-wing-like RuCu bimetal-organic framework with uniform nanorods architecture that grows on a flexible carbon fiber microelectrode. Owing to the optimized electronic structural merits and satisfactory electrocatalytic properties, the resultant microelectrode shows remarkable electrochemical sensing performance for sensitive and selective detection of H2S and H2O2 at the same time. The result exhibits low detection limits of 0.5 µM for H2S and 0.1 µM for H2O2, with high sensitivities of 61.93 µA cm-2 mM-1 for H2S, and 75.96 µA cm-2 mM-1 for H2O2. The integration of this biocompatible microelectrode into a custom wireless microfluidic chip enables the construction of a miniature intelligent system for in situ monitoring of H2S and H2O2 released from different living cells to differentiate between cancerous and normal cells. When applied for real-time tracking of H2S and H2O2 secreted by colorectal cancer tissues, it allows the evaluation of their chemotherapeutic efficacy. These findings hold paramount implications for disease diagnosis and therapy.

Supersulfide catabolism participates in maladaptive remodeling of cardiac cells.

The atrophic myocardium resulting from mechanical unloading and nutritional deprivation is considered crucial as maladaptive remodeling directly associated with heart failure, as well as interstitial fibrosis. Conversely, myocardial hypertrophy resulting from hemodynamic loading is perceived as compensatory stress adaptation. We previously reported the abundant presence of highly redox-active polysulfide molecules, termed supersulfide, with two or more sulfur atoms catenated in normal hearts, and the supersulfide catabolism in pathologic hearts after myocardial infarction correlated with worsened prognosis of heart failure. However, the impact of supersulfide on myocardial remodeling remains unclear. Here, we investigated the involvement of supersulfide metabolism in cardiomyocyte remodeling, using a model of adenosine 5'-triphosphate (ATP) receptor-stimulated atrophy and endothelin-1 receptor-stimulated hypertrophy in neonatal rat cardiomyocytes. Results revealed contrasting changes in intracellular supersulfide and its catabolite, hydrogen sulfide (H2S), between cardiomyocyte atrophy and hypertrophy. Stimulation of cardiomyocytes with ATP decreased supersulfide activity, while H2S accumulation itself did not affect cardiomyocyte atrophy. This supersulfide catabolism was also involved in myofibroblast formation of neonatal rat cardiac fibroblasts. Thus, unraveling supersulfide metabolism during myocardial remodeling may lead to the development of novel therapeutic strategies to improve heart failure.