DcMYB62, a transcription factor from carrot, enhanced cadmium tolerance of Arabidopsis by inducing the accumulation of carotenoids and hydrogen sulfide.

Cadmium (Cd) is a significant heavy metal contaminant within the environment, carrying a notable level of toxicity that presents a substantial hazard to both plant and human. Carrot (Daucus carota), a significant root vegetable crop globally, have evolved multiple transcriptional regulatory mechanisms to cope with Cd stress, with a crucial involvement of the myeloblastosis (MYB) transcription factor. In this study, the DcMYB62 gene encoding 288 amino acids, localized in the nucleus and demonstrated transcription activation property, was isolated from carrot (cv. 'Kuroda'). There was a positive relationship observed between the levels of DcMYB62 expression and the accumulation patterns of carotenoids in two distinct carrot cultivars. Further investigation revealed that the expression of DcMYB62 improved Cd tolerance of Arabidopsis by increasing seed germination rate, root length, and overall survival rate. The levels of carotenoids in DcMYB62 transgenic Arabidopsis surpassed those in wild type, accompanied by elevated expression levels of 15-cis-phytoene desaturase, zeta-carotene desaturase, and carotenoid isomerase. Meanwhile, the heterologous expression of DcMYB62 promoted the biosynthesis of abscisic acid (ABA) and hydrogen sulfide (H2S), which in turn suppressed the formation of hydrogen peroxide and superoxide anion, while also stimulating stomatal closure. Furthermore, the heterologous expression of DcMYB62 increased the transcription of genes associated with heavy metal resistance in Arabidopsis, notably nicotianamine synthase. Overall, this study contributes to understanding how DcMYB62 promote Cd stress resistance of plants by regulating the biosynthesis pathways of carotenoids, ABA, and H2S, which offers valuable insights into the regulatory mechanism connecting DcMYBs with Cd stress response of carrot.

Roles of Hydrogen Sulfide (H2S) as a Potential Therapeutic Agent in Cardiovascular Diseases: A Narrative Review.

Cardiovascular disease (CVD) stands as one of the leading causes of morbidity and mortality worldwide, and the continued search for novel therapeutics is vital for addressing this global health challenge. Over the past decade, hydrogen sulfide (H2S) has garnered significant attention in the field of medical research, as it has been proven to be a cardioprotective gaseous signaling molecule. It joins nitric oxide and carbon monoxide as endogenously produced gasotransmitters. As for its mechanism, H2S functions through the posttranslational addition of a sulfur group to cysteine residues on target proteins in a process called sulfhydration. As a result, the observed physiological effects of H2S can include vasodilation, anti-apoptosis, anti-inflammation, antioxidant effects, and regulation of ion channels. Various studies have observed the cardioprotective benefits of H2S in diseases such as myocardial infarction, ischemia-reperfusion injury, cardiac remodeling, heart failure, arrhythmia, and atherosclerosis. In this review, we discuss the mechanisms and therapeutic potential of H2S in various CVDs.

Cr(VI) induced hepatocyte apoptosis through the CTH/H2S/Drp1 signaling pathway.

Hexavalent chromium [Cr(VI)] is a highly hazardous heavy metal with multiple toxic effects. Occupational studies indicate that its accumulation in humans can lead to liver damage. However, the exact mechanism underlying Cr(VI)-induced hepatotoxicity remains unknown. In this study, we explored the role of CTH/H2S/Drp1 pathway in Cr(VI)-induced oxidative stress, mitochondrial dysfunction, apoptosis, and liver injury. Our data showed that Cr(VI) triggered apoptosis, accompanied by H2S reduction, reactive oxygen species (ROS) accumulation, and mitochondrial dysfunction in both AML12 cells and mouse livers. Moreover, Cr(VI) reduced cystathionine γ-lyase (CTH) and dynamin related protein 1 (Drp1) S-sulfhydration levels, and elevated Drp1 phosphorylation levels at Serine 616, which promoted Drp1 mitochondrial translocation and Drp1-voltage-dependent anion channel 1 (VDAC1) interactions, ultimately leading to mitochondria-dependent apoptosis. Elevated hydrogen sulfide (H2S) levels eliminated Drp1 phosphorylation at Serine 616 by increasing Drp1 S-sulfhydration, thereby preventing Cr(VI)-induced Drp1-VDAC1 interaction and hepatotoxicity. These findings indicated that Cr(VI) induced mitochondrial apoptosis and hepatotoxicity by inhibiting CTH/H2S/Drp1 pathway and that targeting either CTH/H2S pathway or Drp1 S-sulfhydration could serve as a potential therapy for Cr(VI)-induced liver injury.

Thioamides in medicinal chemistry and as small molecule therapeutic agents.

Thioamides, which are fascinating isosteres of amides, have garnered significant attention in drug discovery and medicinal chemistry programs, spanning peptides and small molecule compounds. This review provides an overview of the various applications of thioamides in small molecule therapeutic agents targeting a range of human diseases, including cancer, microbial infections (e.g., tuberculosis, bacteria, and fungi), viral infections, neurodegenerative conditions, analgesia, and others. Particular focus is given to design strategies of biologically active thioamide-containing compounds and their biological targets, such as kinases and histone methyltransferase ASH1L. Additionally, the review discusses the impact of the thioamide moiety on key properties, including potency, target interactions, physicochemical characteristics, and pharmacokinetics profiles. We hope that this work will offer valuable insights to inspire the future development of novel bioactive thioamide-containing compounds, facilitating their effective use in combating a wide array of human diseases.

Cystathionine gamma-lyase deficiency exaggerates diethylnitrosamine-induced liver damage in mice.

Cystathionine gamma-lyase (CSE) is a key enzyme in reverse transsulfuration pathway and contributes to the majority of H2S generation in liver tissues via cysteine metabolism. Dysfunction of the CSE/H2S system is linked to both chronic and acute liver damage. This study investigated the regulatory role of CSE deficiency on diethylnitrosamine (DEN)-induced liver damage in mice. A single injection of DEN was administered into 4-week-old male CSE knockout (CSE-KO) mice and wild-type (WT) littermates, and the mice were sacrificed at 28 weeks of age. Compared to age-matched WT mice, CSE-KO mice spontaneously developed steatosis with increased oxidative stress and higher expressions of inflammation and fibrosis-related genes at 28-weeks of age. Following DEN injection, CSE-KO mice experienced more severe liver damage in comparison with the WT group as reflected by elevated levels of lipid accumulation, increased activities of alanine aminotransferase and aspartate aminotransferase, higher oxidative stress and fibrosis development, and increased expressions of inflammation and fibrosis-related genes. No visible tumors were observed in both types of mice with DEN treatment. In addition, the expression levels of the three H2S-generating proteins (CSE, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase) and the H2S production rate in liver tissues were unaffected by DEN. Taken together, our study demonstrates that CSE provides a significant hepatoprotective effect and deficiency of CSE exaggerates DEN-induced liver damage in mice. Based on these findings, it can be suggested that targeting the CSE/H2S signaling pathway could be a potential therapeutic target for the treatment of liver diseases.

Rhizobia cystathionine γ-lyase-derived H2S delays nodule senescence in soybean.

Hydrogen sulphide (H2S) is required for optimal establishment of soybean (Glycine max)-Sinorhizobium fredii symbiotic interaction, yet its role in regulating the nitrogen fixation-senescence transition remains poorly understood. A S. fredii cystathionine γ-lyase (CSE) mutant deficient in H2S synthesis showed early nodule senescence characterized by reduced nitrogenase activity, structural changes in nodule cells, and accelerated bacteroid death. In parallel, the CSE mutant facilitated the generation of reactive oxygen species (ROS) and elicited antioxidant responses. We observed that H2S-mediated persulfidation of cysteine C31/C80 in ascorbate peroxidase (APX) and C32 in APX2 modulated enzyme activity, thereby participating in hydrogen peroxide (H2O2) detoxification and delaying nodule senescence. Comparative transcriptomic analysis revealed a significant up-regulation of GmMYB128, an MYB transcription factor (TF), in the CSE mutant nodules. Functional analysis through overexpression and RNAi lines of GmMYB128 demonstrated its role as a positive regulator in nodule senescence. MYB128-OE inoculated with the CSE mutant strain exhibited a reduction in nitrogenase activity and a significant increase in DD15 expression, both of which were mitigated by NaHS addition. Changes at the protein level encompassed the activation of plant defenses alongside turnover in carbohydrates and amino acids. Our results suggest that H2S plays an important role in maintaining efficient symbiosis and preventing premature senescence of soybean nodules.

Response Enhancement in High-Temperature H2S-Treated Metal Oxide Gas Sensors.

Metal oxide gas sensors (MOGS), crucial components in monitoring air quality and detecting hazardous gases, are well known for their poisoning effects when exposed to certain gas molecules, such as hydrogen sulfide. Surprisingly, our research reveals that high-temperature H2S treatment leads to an enhancement effect rather than response decay. This study investigates the time-decaying response enhancement, being attributed to the formation of metal sulfide and metal sulfate on the metal oxide's surface, enhancing the electronic sensitization. Such an enhancement effect is demonstrated for various gases, including CO, CH3CH2OH, CH4, HCHO, and NH3. Additionally, the impacts of H2S treatment on the response and recovery time are also observed. Surface compositional analysis are conducted with X-ray photoelectron spectroscopy. A proposed mechanism for the enhancement effect is elaborated, highlighting the role of electronic sensitization and the sulfide-sulfate component. This research offers valuable insights into the potential applications of metal oxide sensors in sulfide-presented harsh environments in gas sensing, encouraging future exploration of optimized sensor materials, operation temperature, and the development of hydrogen sulfide poisoning-resistant and higher sensitivity MOGS.

Melatonin-Induced Chromium Tolerance Requires Hydrogen Sulfide Signaling in Maize.

Both melatonin and hydrogen sulfide (H2S) mitigate chromium (Cr) toxicity in plants, but the specific interaction between melatonin and H2S in Cr detoxification remains unclear. In this study, the interaction between melatonin and H2S in Cr detoxification was elucidated by measuring cell wall polysaccharide metabolism and antioxidant enzyme activity in maize. The findings revealed that exposure to Cr stress (100 µM K2Cr2O7) resulted in the upregulation of L-/D-cysteine desulfhydrase (LCD/DCD) gene expression, leading to a 77.8% and 27.3% increase in endogenous H2S levels in maize leaves and roots, respectively. Similarly, the endogenous melatonin system is activated in response to Cr stress. We found that melatonin had a significant impact on the relative expression of LCD/DCD, leading to a 103.3% and 116.7% increase in endogenous H2S levels in maize leaves and roots, respectively. In contrast, NaHS had minimal effects on the relative mRNA expression of serotonin-Nacetyltransferase (SNAT) and endogenous melatonin levels. The production of H2S induced by melatonin is accompanied by an increase in Cr tolerance, as evidenced by elevated gene expression, elevated cell wall polysaccharide content, increased pectin methylesterase activity, and improved antioxidant enzyme activity. The scavenging of H2S decreases the melatonin-induced Cr tolerance, while the inhibitor of melatonin synthesis, p-chlorophenylalanine (p-CPA), has minimal impact on H2S-induced Cr tolerance. In conclusion, our findings suggest that H2S serves as a downstream signaling molecule involved in melatonin-induced Cr tolerance in maize.

The Impact of Vitamin D and L-Cysteine Co-Supplementation on Upregulating Glutathione and Vitamin D-Metabolizing Genes and in the Treatment of Circulating 25-Hydroxy Vitamin D Deficiency.

Vitamin D receptors are expressed in many organs and tissues, which suggests that vitamin D (VD) affects physiological functions beyond its role in maintaining bone health. Deficiency or inadequacy of 25(OH)VD is widespread globally. Population studies demonstrate that a positive association exists between a high incidence of VD deficiency and a high incidence of chronic diseases, including dementia, diabetes, and heart disease. However, many subjects have difficulty achieving the required circulating levels of 25(OH)VD even after high-dose VD supplementation, and randomized controlled clinical trials have reported limited therapeutic success post-VD supplementation. Thus, there is a discordance between the benefits of VD supplementation and the prevention of chronic diseases in those with VD deficiency. Why this dissociation exists is currently under debate and is of significant public interest. This review discusses the downregulation of VD-metabolizing genes needed to convert consumed VD into 25(OH)VD to enable its metabolic action exhibited by subjects with metabolic syndrome, obesity, and other chronic diseases. Research findings indicate a positive correlation between the levels of 25(OH)VD and glutathione (GSH) in both healthy and diabetic individuals. Cell culture and animal experiments reveal a novel mechanism through which the status of GSH can positively impact the expression of VD metabolism genes. This review highlights that for better success, VD deficiency needs to be corrected at multiple levels: (i) VD supplements and/or VD-rich foods need to be consumed to provide adequate VD, and (ii) the body needs to be able to upregulate VD-metabolizing genes to convert VD into 25(OH)VD and then to 1,25(OH)2VD to enhance its metabolic action. This review outlines the association between 25(OH)VD deficiency/inadequacy and decreased GSH levels, highlighting the positive impact of combined VD+LC supplementation on upregulating GSH, VD-metabolizing genes, and VDR. These effects have the potential to enhance 25(OH)VD levels and its therapeutic efficacy.

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.

Rational design of Near-Infrared fluorescent probe for monitoring HNO in plants.

Nitroxyl (HNO), a reactive nitrogen species (RNS), is essential for plant growth. However, the action of HNO in plants has been difficult to understand due to the lack of highly sensitive and real-time in-situ monitoring tools. Herein, we presented a near-infrared fluorescent probe, DCI-HNO, based on dicyanoisophorone fluorophore, for real-time mapping HNO in plants. The introduction of a phosphine moiety as a specific HNO recognition unit can inhibit the intramolecular charge transfer (ICT) of probe DCI-HNO. However, in the presence of HNO, the ICT process occurred, leading to the emission at 665 nm. Probe DCI-HNO exhibited high sensitivity (97 nM), rapid response time (8 min), large Stokes shift (135 nm) for detection of HNO in plants. The novel developed probe has successfully imaged endogenous HNO produced during NO/H2S cross-talk in plant tissues. Additionally, the up-regulated in HNO levels during tobacco aging and in response to stress has been confirmed. Therefore, probe DCI-HNO has provided a reliable method for monitoring the NO/H2S cross-talk and revealing the role of HNO in plants.

Tuning Tumor Targeting and Ratiometric Photoacoustic Imaging by Fine-Tuning Torsion Angle for Colorectal Liver Metastasis Diagnosis.

Photoacoustic (PA) tomography is an emerging biomedical imaging technology for precision cancer medicine. Conventional small-molecule PA probes usually exhibit a single PA signal and poor tumor targeting that lack the imaging reliability. Here, we introduce a series of cyanine/hemicyanine interconversion dyes (denoted Cy-HCy) for PA/fluorescent dual-mode probe development that features optimized ratiometric PA imaging and tunable tumor-targeting ability for precise diagnosis and resection of colorectal cancer (CRC). Importantly, Cy-HCy can be presented in cyanine (inherent tumor targeting and long NIR PA wavelength) and hemicyanine (poor tumor targeting and short NIR PA wavelength) by fine-tuning torsion angle and the ingenious transformation between cyanine and hemicyanine through regulation optically tunable group endows the NIR ratiometric PA and tunable tumor-targeting properties. To demonstrate the applicability of Cy-HCy dyes, we designed the first small-molecule tumor-targeting and NIR ratiometric PA probe Cy-HCy-H2S for precise CRC liver metastasis diagnosis, activated by H2S (a CRC biomarker). Using this probe, we not only visualized the subcutaneous tumor and liver metastatic cancers in CRC mouse models but also realized PA and fluorescence image-guided tumor excision. We expect that Cy-HCy will be generalized for creating a wide variety of inherently tumor-targeting NIR ratiometric PA probes in oncological research and practice.

Biofilm microenvironment-activated multimodal therapy nanoplatform for effective anti-bacterial treatment and wound healing.

Antimicrobial drug development faces challenges from bacterial resistance, biofilms, and excessive inflammation. Here, we design an intelligent nanoplatform utilizing mesoporous silica nanoparticles doped with copper ions for loading copper sulfide (DM/Cu2+-CuS). The mesoporous silica doped with tetrasulfide bonds responds to the biofilm microenvironment (BME), releasing Cu2+ions, CuS along with hydrogen sulfide (H2S) gas. The release of hydrogen sulfide within 72 h reached 793.5 µM, significantly higher than that observed with conventional small molecule donors. H2S induces macrophages polarization towards the M2 phenotype, reducing inflammation and synergistically accelerating endothelial cell proliferation and migration with Cu2+ions. In addition, H2S disrupts extracellular DNA within biofilms, synergistically photothermal enhanced peroxidase-like activity of CuS to effectively eradicate biofilms. Remarkably, DM-mediated consumption of endogenous glutathione enhances the anti-biofilm activity of H2S and improves oxygen species (ROS) destruction efficiency. The combination of photothermal therapy (PTT), chemodynamic therapy (CDT), and gas treatment achieves sterilization rates of 99.3 % and 99.6 % against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively, in vitro under 808 nm laser irradiation. Additionally, in vivo experiments demonstrate a significant biosafety and antibacterial potential. In summary, the H2S donor developed in this study exhibits enhanced biocompatibility and controlled release properties. By integrating BME-responsive gas therapy with antibacterial ions, PTT and CDT, a synergistic multimodal strategy is proposed to offer new therapeutic approaches for wound healing. STATEMENT OF SIGNIFICANCE: The advanced DMOS/Cu2+-CuS (DMCC) multimodal therapeutic nanoplatform has been developed for the treatment of drug-resistant bacterial wound infections and has exhibited enhanced therapeutic efficacy through the synergistic effects of photothermal therapy, chemodynamic therapy, Cu2+ions, and H2S. The DMCC exhibited exceptional biocompatibility and could release CuS, Cu2+, and H2S in response to elevated concentrations of glutathione within the biofilm microenvironment. H2S effectively disrupted the biofilm structure. Meanwhile, peroxidase activity of CuS combined with GSH-mediated reduction of Cu2+ to Cu+ generated abundant hydroxyl radicals under acidic conditions, leading to efficient eradication of pathogenic bacteria. Furthermore, both H2S and Cu2+ could modulate M2 macrophages polarization and regulate immune microenvironment dynamics. These strategies collectively provided a novel approach for developing antibacterial nanomedical platforms.

How the Western Diet Thwarts the Epigenetic Efforts of Gut Microbes in Ulcerative Colitis and Its Association with Colorectal Cancer.

Ulcerative colitis (UC) is an autoimmune disease in which the immune system attacks the colon, leading to ulcer development, loss of colon function, and bloody diarrhea. The human gut ecosystem consists of almost 2000 different species of bacteria, forming a bioreactor fueled by dietary micronutrients to produce bioreactive compounds, which are absorbed by our body and signal to distant organs. Studies have shown that the Western diet, with fewer short-chain fatty acids (SCFAs), can alter the gut microbiome composition and cause the host's epigenetic reprogramming. Additionally, overproduction of H2S from the gut microbiome due to changes in diet patterns can further activate pro-inflammatory signaling pathways in UC. This review discusses how the Western diet affects the microbiome's function and alters the host's physiological homeostasis and susceptibility to UC. This article also covers the epidemiology, prognosis, pathophysiology, and current treatment strategies for UC, and how they are linked to colorectal cancer.

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.

Tea tree oil inhibits hydrogen sulfide-induced oxidative damage in chicken lungs through CYP450s/ROS pathway.

A large amount of hydrogen sulfide (H2S) is produced in the process of chicken breeding, which can cause serious inflammation and oxidative damage to the respiratory system of chickens. Tea tree oil (TTO) has antioxidant and anti-inflammatory properties. No studies have been reported on the use of TTO in H2S-induced lung injury in chickens. Therefore, in this study, 240 one-day-old Roman pink laying hens were randomly and equally divided into 3 groups: control group (CON), H2S exposure group (AVG, containing H2S), and TTO treatment group (TTG, containing H2S and 0.02 mL/L TTO) to establish an experimental model of TTO treatment with H2S exposure for a period of 42 d. Hematoxylin and eosin (H&E) staining was used to detect lung histopathology. Gene expression profiles were analyzed using transcriptomics. The underlying mechanism of the amelioration of lung injury by TTO was further revealed by antioxidant enzyme assays and qRT-PCR. The results showed that H2S exposure induced significant gene expression of CYP450s (CYP1B1 and CYP1C1) (P < 0.05), and caused intense oxidative stress, apoptosis and inflammation compared with CON. TTO could reduce ROS production and enhance antioxidant capacity (SOD, CAT, T-AOC, and GSH-PX) by regulating the CYP450s/ROS pathway (P < 0.05). Compared with the control group, the treatment group showed significantly decreased expression of apoptotic (Caspase-8, Caspase-3, Bid and Fas) (P < 0.05) and inflammatory (IL-4, IL-16, NF-κB, TNF-α and IFN-γ) (P < 0.05) factors in the lung. This study revealed that TTO regulated CYP450s/ROS pathway to alleviate H2S-induced lung injury in chickens. These results enrich the theory of the action mechanism of TTO on H2S-exposed chicken lungs and are of great value for the treatment of H2S-exposed animals.

Hydrogen Sulfide-Induced Activatable Photodynamic Therapy Adjunct to Disruption of Subcellular Glycolysis in Cancer Cells by a Fluorescence-SERS Bimodal Iridium Metal-Organic Hybrid.

The practical application of photodynamic therapy (PDT) demands targeted and activatable photosensitizers to mitigate off-target phototoxicity common in "always on" photosensitizers during light exposure. Herein, a cyclometalated iridium complex-based activatable photodynamic molecular hybrid, Cy-Ir-7-nitrobenzofurazan (NBD), is demonstrated as a biomedicine for molecular precision. This design integrates a hydrogen sulfide (H2S)-responsive NBD unit with a hydroxy-appended iridium complex, Cy-Ir-OH. In normal physiological conditions, the electron-rich Ir metal center exerts electron transfer to the NBD unit, quenches the excited state dynamics, and establishes a PDT-off state. Upon exposure to H2S, Cy-Ir-NBD activates into the potent photosensitizer Cy-Ir-OH through nucleophilic substitution. This mechanism ensures exceptional specificity, enabling targeted phototherapy in H2S-rich cancer cells. Additionally, we observed that Cy-Ir-NBD-induced H2S depletion disrupts S-sulfhydration of the glyceraldehyde-3-phosphate dehydrogenase enzyme, impairing glycolysis and ATP production in the cellular milieu. This sequential therapeutic process of Cy-Ir-NBD is governed by the positively charged central iridium ion that ensures mitochondria-mediated apoptosis in cancer cells. Dual-modality SERS and fluorescence imaging validate apoptotic events, highlighting Cy-Ir-NBD as an advanced theranostic molecular entity for activatable PDT. Finally, as a proof of concept, clinical assessment is evaluated with the blood samples of breast cancer patients and healthy volunteers, based on their H2S overexpression capability through SERS and fluorescence, revealing Cy-Ir-NBD to be a promising predictor for PDT activation in advanced cancer phototherapy.

Therapeutic Potential of Hydrogen Sulfide in Reproductive System Disorders.

Hydrogen sulfide (H2S), previously regarded as a toxic exhaust and atmospheric pollutant, has emerged as the third gaseous signaling molecule following nitric oxide (NO) and carbon monoxide (CO). Recent research has revealed significant biological effects of H2S in a variety of systems, such as the nervous, cardiovascular, and digestive systems. Additionally, H2S has been found to impact reproductive system function and may have therapeutic implications for reproductive disorders. This paper explores the relationship between H2S and male reproductive disorders, specifically erectile dysfunction, prostate cancer, male infertility, and testicular damage. Additionally, it examines the impact of H2S regulation on the pathophysiology of the female reproductive system, including improvements in preterm birth, endometriosis, pre-eclampsia, fetal growth restriction, unexplained recurrent spontaneous abortion, placental oxidative damage, embryo implantation, recovery of myometrium post-delivery, and ovulation. The study delves into the regulatory functions of H2S within the reproductive systems of both genders, including its impact on the NO/cGMP pathway, the activation of K+ channels, and the relaxation mechanism of the spongy smooth muscle through the ROCK pathway, aiming to broaden the scope of potential therapeutic strategies for treating reproductive system disorders in clinical settings.

H2S-Powered Nanomotors for Active Therapy of Tumors by Inducing Ferroptosis and Lactate-Pyruvate Axis Disorders.

Disruption of the symbiosis of extra/intratumoral metabolism is a good strategy for treating tumors that shuttle resources from the tumor microenvironment. Here, we report a precision treatment strategy for enhancing pyruvic acid and intratumoral acidosis to destroy tumoral metabolic symbiosis to eliminate tumors; this approach is based on PEGylated gold and lactate oxidase-modified aminated dendritic mesoporous silica with lonidamine and ferrous sulfide loading (PEG-Au@DMSNs/FeS/LND@LOX). In the tumor microenvironment, LOX oxidizes lactic acid to produce pyruvate, which represses tumor cell proliferation by inhibiting histone gene expression and induces ferroptosis by partial histone monoubiquitination. In acidic tumor conditions, the nanoparticles release H2S gas and Fe2+ ions, which can inhibit catalase activity to promote the Fenton reaction of Fe2+, resulting in massive ·OH production and ferroptosis via Fe3+. More interestingly, the combination of H2S and LND (a monocarboxylic acid transporter inhibitor) can cause intracellular acidosis by lactate, and protons overaccumulate in cells. Multiple intracellular acidosis is caused by lactate-pyruvate axis disorders. Moreover, H2S provides motive power to intensify the shuttling of nanoparticles in the tumor region. The findings confirm that this nanomedicine system can enable precise antitumor effects by disrupting extra/intratumoral metabolic symbiosis and inducing ferroptosis and represents a promising active drug delivery system candidate for tumor treatment.

Hydrogel-based radio frequency H2S sensor for in situ periodontitis monitoring and antibacterial treatment.

Periodontitis, a chronic disease, can result in irreversible tooth loss and diminished quality of life, highlighting the significance of timely periodontitis monitoring and treatment. Meanwhile, hydrogen sulfide (H2S) in saliva, produced by pathogenic bacteria of periodontitis, is an important marker for periodontitis monitoring. However, the easy volatility and chemical instability of the molecule pose challenges to oral H2S sensing. Here, we report a wearable hydrogel-based radio frequency (RF) sensor capable of in situ H2S detection and antibacterial treatment. The RF sensor comprises an agarose hydrogel containing conjugated silver nanoparticles-chlorhexidine (AG-AgNPs-CHL hydrogel) integrated with split-ring resonators. Adhered to a tooth, the hydrogel-based RF sensor enables wireless transmission of sensing signals to a mobile terminal and a concurrent release of the broad-spectrum antibacterial agent chlorhexidine without complex circuits. With the selective binding of the AgNPs to the sulfidion, the RF sensor demonstrates good sensitivity, a wide detection range (2-30 µM), and a low limit of detection (1.2 µM). Compared with standard H2S measurement, the wireless H2S sensor can distinguish periodontitis patients from healthy individuals in saliva sample tests. The hydrogel-based wearable sensor will benefit patients with periodontitis by detecting disease-related biomarkers for practical oral health management.