hydrogen sulfide

Overview

Hydrogen sulfide (H₂S) is a small, endogenously produced sulfur-containing gas that functions as a biologically active signaling molecule and, at higher concentrations, a toxic gas. In biomedical research it is often discussed as a gasotransmitter alongside nitric oxide and carbon monoxide, with roles in redox regulation, mitochondrial function, inflammation, vascular biology, and cellular stress responses. Its effects are highly context-dependent: physiologic or controlled donor-mediated H₂S exposure can be cytoprotective, whereas excessive environmental exposure is hazardous.

In recent translational studies, hydrogen sulfide has been investigated both as a therapeutic agent and as a mechanistic target. The provided publication contexts show its use in controlled-release donor systems, tumor-responsive nanoplatforms, myocardial repair materials, wound-healing hydrogels, and neuroprotective or mitochondrial-protective interventions. It is also a practical target in industrial biodesulfurization, where microbial systems are used to remove H₂S from natural gas.

Focus of Latest Publications

Recent studies have examined hydrogen sulfide in two broad settings: as a harmful gas to be removed from industrial streams, and as a bioactive mediator to be delivered or generated in disease models.

In the industrial context, pilot-scale Shell-Paques reactors were established to remove hydrogen sulfide from natural gas using an inoculum of indigenous sulfur-oxidizing bacteria (SOB). This work focused on microbial ecology and community dynamics in an in situ enriched system, emphasizing the biological conversion of H₂S during biodesulfurization rather than its pharmacology.

In biomedical research, several studies used hydrogen sulfide as a therapeutic signal. One injectable “gas-electro” bionic hydrogel was designed for myocardial infarction, enabling sustained H₂S release through a MeAC-PEG donor. The reported effects included anti-inflammatory, antioxidative, and pro-angiogenic activity, together with spatiotemporal monitoring and electrophysiological repair. Related cardiac work also included AP39-based or H₂S-centered mitochondrial protection strategies, with H₂S reported to mitigate hyperoxia-induced mitochondrial damage in developing airway smooth muscle and to support mitochondrial homeostasis.

Hydrogen sulfide was also incorporated into wound-healing and redox-modulating biomaterials. An injectable silk fibroin hydrogel encapsulating pH-responsive ZnS nanoparticles was reported to provide controlled release of therapeutic H₂S and Zn²⁺ under different pH conditions, supporting synergistic redox modulation and diabetic wound healing. In a related diabetic context, hydrogel and nanoplatform approaches were used to couple H₂S delivery with other bioactive components, reflecting interest in H₂S as part of multi-functional regenerative materials.

In oncology, hydrogen sulfide was used as a tumor-responsive effector molecule. A cascade-responsive H₂S-releasing nanoplatform for synergistic tumor photothermal-immunotherapy was reported to release H₂S and Cu⁺ within the tumor microenvironment, causing intracellular acidification, inhibiting Cu⁺ efflux via ATP7A downregulation, increasing mitochondrial Cu⁺ accumulation, and generating reactive oxygen species. Another engineered microbial nanohybrid was designed to locally produce H₂S in the hypoxic tumor microenvironment, where it damaged mitochondria and inhibited catalase, thereby enhancing ferroptosis immunotherapy through mitophagy inhibition. A separate cascade-responsive AND-logic-activatable nanoprobe for intraoperative fluorescence imaging of colorectal cancer used endogenous hydrogen sulfide together with lysosomal pH as activation cues, improving tumoral uptake and supporting NIR FL-guided CRC surgery.

Hydrogen sulfide was also studied in neurodegeneration. A paper on Parkinson’s disease reported that the H₂S donor sulforaphane inhibited NLRP3 inflammasome activation by inducing mitochondrial autophagy and mitigating CBS-H₂S axis damage in in-vitro and in-vivo models. This aligns with the broader view of H₂S as a neuroprotective mediator that can influence mitochondrial quality control, inflammatory signaling, and oxidative stress. Related entities in these studies included CASP1, NLRP3 inflammasome, serotonin, and hydrogen peroxide, all of which are consistent with H₂S-linked redox and inflammatory pathways.

Additional work used H₂S as a chemically responsive analyte or reaction partner in sensing systems. In one photoelectrochemical immunoassay, H₂S released after carcinoembryonic antigen recognition reacted with Sn(IV)-ZIS@ZnS to form a dual S-scheme heterojunction, linking H₂S chemistry to signal amplification. Another study used domain insertion to create sulfite reductases with chemical-dependent activity, enabling conditional sulfide production that could be monitored electrochemically from cells using a bioelectrochemical reactor.

Overall, these studies portray hydrogen sulfide as a versatile biomedical target: a toxic gas in environmental and industrial settings, a signaling molecule in cardiovascular, pulmonary, neurologic, and wound-healing contexts, and a chemically useful trigger or product in diagnostic and therapeutic nanotechnology.

Key Publications

NEWJun Pilot-scale biodesulfurization of natural gas: microbial ecology and community dynamics of an in situ enriched system. (Journal of applied microbiology, 2026, PMID 42261086): "Pilot-scale Shell-Paques reactors were established to remove hydrogen sulfide from natural gas, using an inoculum of indigenous SOB."
NEWJun An Injectable "Gas-Electro" Bionic Hydrogel for Spatiotemporal Monitoring and Repair of Myocardial Infarction via Sustained H2S Release and Electrophysiological Repair. (ACS applied materials & interfaces, 2026, PMID 42265838): "sustained H2S release via a MeAC-PEG donor for anti-inflammatory, antioxidative, and pro-angiogenic effects"
Jun An Engineered Microbial Nanohybrid for Enhanced Ferroptosis Immunotherapy via Hypoxia-Responsive Hydrogen Sulfide Generation and Mitophagy Inhibition. (ACS nano, 2026, PMID 42246518): "The engineered microbial nanohybrid could locally produce H2S in the hypoxic tumor microenvironment, damaging mitochondria and inhibiting catalase."
Jun Using Domain Insertion to Create Sulfite Reductases That Present Chemical-Dependent Activities. (ACS synthetic biology, 2026, PMID 42160704): "With one domain insertion variant, the conditional production of sulfide could be monitored electrochemically from cells using a bioelectrochemical reactor."
May Target-Induced Tandem Built-In Electric Fields in the Hollow SnS2/ZIS@ZnS Heterojunction for the Photoelectrochemical Immunoassay. (Analytical chemistry, 2026, PMID 42018287): "Following the release of H2S, after carcinoembryonic antigen (CEA) was specifically recognized via a sandwich-type immune reaction, the released H2S reacted with Sn(IV)-ZIS@ZnS to form dual S-scheme heterojunction SnS2/ZIS@ZnS."
May Injectable silk fibroin hydrogel encapsulating pH-Responsive ZnS nanoparticles for synergistic redox modulation and diabetic wound healing. (Biomaterials advances, 2026, PMID 41455286): "offering stable colloidal properties and controlled release of therapeutic H2S and Zn2+ under different pH conditions."
May Cascade-responsive hydrogen sulfide-releasing nanoplatform for synergistic tumor photothermal-immunotherapy. (Journal of colloid and interface science, 2026, PMID 41605106): "Within the tumor microenvironment (TME), DCTH synchronously released H2S and Cu+, inducing intracellular acidification, inhibiting Cu+ efflux (via ATP7A downregulation), enhancing mitochondrial Cu+ accumulation, and generating reactive oxygen species (ROS)."
Apr A Cascade-Responsive AND-Logic-Activatable Nanoprobe for Intraoperative Fluorescence Imaging of Colorectal Cancer. (Journal of the American Chemical Society, 2026, PMID 41985171): "...mediated by endogenous hydrogen sulfide (H2S) and lysosomal pH, resulting in significant tumoral uptake..."
Apr Hydrogen sulfide alleviates hyperoxia effects on mitochondria in human developing airway smooth muscle. (JCI insight, 2026, PMID 41805459): "Thus, mitochondrial homeostasis is highly relevant to ASM dysfunction and airway disease. We propose that hyperoxia in prematurity promotes mitochondrial dysfunction, and that the gasotransmitter hydrogen sulfide (H2S) mitigates O2-induced mitochondrial damage in developing ASM."
Apr The H2S donor sulforaphane inhibits NLRP3 inflammasome activation by inducing mitochondrial autophagy and mitigating CBS-H2S axis damage in in-vitro and in-vivo models of Parkinson's disease. (Bioorganic chemistry, 2026, PMID 41797134): "Hydrogen sulfide (H₂S) plays a crucial neuroprotective role in Parkinson's disease (PD)."