- |||||||||| Hydrogen sulfide signaling in promoting the anti-tumor T cell response (Exhibit Hall; P930) - Apr 8, 2022 - Abstract #IMMUNOLOGY2022IMMUNOLOGY_1890;
Even greater tumor control was observed when ACT-treated mice were injected systemically with an H2S donor compound. These data provide evidence that anti-tumor T cells exposed to H2S possess an enhanced metabolic and stem-like phenotype that allows them to persist in the immunosuppressive tumor microenvironment and exert greater tumor control upon adoptive transfer into tumor-bearing hosts.
- |||||||||| Sulfhydration of β1 Subunit Mediates H2S-Stimulated Activation of Human Uterine Artery Smooth Muscle BKCa Channels. () - Apr 6, 2022 - Abstract #SRI2022SRI_285;
Therefore, fetal growth restriction in hypoxic pregnancy is not a prerequisite for programmed heart disease.Supported by The British Heart Foundation. The pregnancy-dependent human UA protein sulfhydration ex vivo and H2S-induced global hUASMC protein sulfhydration in vitro demonstrate that sulfhydration is an important mechanism for H2S to elicit its uterine vasodilatory effects; sulfhydration of BKβ1 results in SM BKCa activation which may serve as a novel mechanism to mediate the relaxation effect of H2S in UA (Supported by NIH grants HD105699, HL70562, and HD097498).
- |||||||||| Journal: The effect of hydrogen sulfide on the contractility of cerebral arterioles. A pilot study. (Pubmed Central) - Mar 3, 2022
Our findings revealed that in these pathologically important vessels (1) endogenously produced H2S is not a vasodilator, but a moderate vasoconstrictor; (2) H2S has a biphasic effect: low concentrations are moderate vasoconstrictors, while at higher concentrations the initial contraction is followed by dilatation; (3) that vasodilation is prevented by DIDS (4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid disodium, an inhibitor of the Cl-/HCO3 - exchanger). These studies confirm that H2S should be taken into consideration as a modulator of cerebral arteriolar tone in mammals.
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Journal: Hydrogen sulfide attenuates ferroptosis and stimulates autophagy by blocking mTOR signaling in sepsis-induced acute lung injury. (Pubmed Central) - Feb 22, 2022
(7) CLP + Chloroquine (80 mg/Kg) group...One unexpected finding was the extent to which the levels of ferritin and ferritin light chain increased after CLP, which may be a compensatory mechanism for storing abnormally increased iron. We also found that the expression of p-mTOR, P62, and Beclin1 was significantly increased and that LC3II/LC3I declined after LPS stimulation, but the effect was inhibited by treatment with GYY4137, indicating that GYY4137 could inhibit the activation of autophagy in sepsis-induced ALI by blocking mTOR signaling.
- |||||||||| GYY4137 / National University of Singapore
HYDROGEN SULFIDE BLOCKS HIV REBOUND BY MAINTAINING CELLULAR REDOX HOMEOSTASIS ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_805;
Mechanistically, GYY4137 treatment subverted HIV reactivation by inducing the Keap1-Nrf2 dependent antioxidant pathway, inhibiting NF-?B activity, and recruiting the epigenetic silencer, YY1, to the HIV promoter. In summary, this work provides mechanistic insight into H2S-mediated suppression of HIV reactivation and suggests the inclusion of an H2S donor in the current ART regimen to achieve a functional HIV cure.
- |||||||||| Review, Journal: HS Donors and Their Use in Medicinal Chemistry. (Pubmed Central) - Jan 6, 2022
Consequently, synthetic HS-releasing agents represent not only important research tools, but also potent therapeutic agents. This review has been designed in order to summarize the currently available HS donors; furthermore, herein we discuss their preparation, the HS-releasing mechanisms, and their -biological applications.
- |||||||||| Review, Journal: Role of hydrogen sulfide donors in cancer development and progression. (Pubmed Central) - Jan 4, 2022
Nonetheless, numerous signaling pathways have been reported to be altered following the treatments with HS donors which suggest their potential in cancer treatment. This review will analyze the potential of HS donors in cancer therapy by summarizing key cellular processes and mechanisms involved.
- |||||||||| Journal: Hydrogen Sulfide Inhibits Inflammatory Pain and Enhances the Analgesic Properties of Delta Opioid Receptors. (Pubmed Central) - Dec 27, 2021
The data further demonstrate the possible participation of potassium channels and the Nrf2 transcription factor signaling pathway in the pain-relieving activities of DADS and P-ITC. This study suggests that the systemic administration of DADS and P-ITC and local application of DOR agonists in combination with slow-releasing HS donors are two new strategies for the treatment of inflammatory pain.
- |||||||||| Journal: Role of Hydrogen Sulfide in Myocardial Ischemia-Reperfusion Injury. (Pubmed Central) - Dec 16, 2021
With advances in understanding of the molecular pathogenesis of MIRI and pharmacology studies, the design, the development and the pharmacological characterization of H2S-donor drugs have been made great important progress. This review summarizes the latest research progress on the role of H2S in MIRI, systematically explains the molecular mechanism of H2S affecting MIRI, and provides a new idea for the formulation of a myocardial protection strategy in the future.
- |||||||||| Preclinical, Journal: Myofiber / pro-inflammatory macrophage interplay controls muscle damage in mdx mice. (Pubmed Central) - Oct 28, 2021
These results identify an interplay between myofibers and macrophages where dystrophic myofibers contribute to the maintenance of a highly inflammatory environment sustaining a pro-inflammatory macrophage status, in turn favoring myofiber damage, myofiber branching and fibrosis establishment. They also identify H2S donors as a potential therapeutic strategy to improve dystrophic muscle phenotype by dampening chronic inflammation.
- |||||||||| GYY4137 / National University of Singapore
Journal: The Recovery of Cognitive and Affective Deficiencies Linked with Chronic Osteoarthritis Pain and Implicated Pathways by Slow-Releasing Hydrogen Sulfide Treatment. (Pubmed Central) - Oct 25, 2021
Using female mice with chronic osteoarthritic pain, the effects of natural, diallyl disulfide (DADS) or synthetic, morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex (GYY4137) slow-releasing HS donors, on associated cognitive and grip strength deficits and anxiodepressive-like behaviors, were assessed...These results might explain the recovery of memory and grip strength and the inhibition of allodynia and associated anxiodepressive-like behaviors by these treatments. In conclusion, this study revealed new properties of slow-releasing HS donors in cognitive impairment and affective disorders linked with chronic osteoarthritis pain and their effects on the central nervous system.
- |||||||||| [VIRTUAL] Effect of Hydrogen Sulfide on Alpha-Synuclein Aggregation () - Oct 21, 2021 - Abstract #ANA2021ANA_336;
The mechanism may be through alteration of aggregate conformation as supported by structural data. Further studies are needed, however the current findings suggest that H2S may offer a promising avenue of investigation in PD.
- |||||||||| GYY4137 / National University of Singapore
[VIRTUAL] Exogenous Hydrogen Sulfide Protects Kidneys of Diabetic Mice from Oxidative Injuries () - Oct 17, 2021 - Abstract #KIDNEYWEEK2021KIDNEY_WEEK_2038;
GYY4137 (20 mg/kg/day in 6 ml of drinking water，GYY+DM group, n=5) or vehicle (6 ml of drinking water, DM group, n=4) plus 60% fat diet were fed the mice 2 weeks after the initial STZ injection when blood glucose remained high relative to background mice...The levels of mRNA were not in agreement with the changes in proteins with all enzymes but HO2. Conclusion Our findings suggest that exogenous H2S may decrease ROS production and increase ROS cleavage in kidney via the affected enzymes, thus improve the renal oxidative damage in diabetic nephropathy.
- |||||||||| [VIRTUAL] Metal-organic frameworks for the therapeutic delivery of hydrogen sulfide (Room: Zoom Room 14) - Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_6277;
Last, we demonstrate that these MOFs are capable of alleviating reperfusion injury in H9c2 rat cardiomyoblast cells with an ischemia-reperfusion injury model. From our findings, we conclude that H2S-loaded MOFs are easily accessible, solid-state sources of H2S, enabling safe storage and delivery of the gas for use as a therapeutic agent.
- |||||||||| Journal: Hydrogen sulfide increases copper-dependent neurotoxicity via intracellular copper accumulation. (Pubmed Central) - Aug 11, 2021
Moreover, Cu/NaHS markedly suppressed the level of the Cu exporter ATP7A, but not ATP7B, protein, whereas the combination did not affect that of the Cu importer CTR1 protein. Taken together, we conclude that the marked decrease in the ATP7A protein level by Cu/NaHS promotes intracellular Cu accumulation and leads to increased Cu cytotoxicity.
- |||||||||| Review, Journal: H2S Donor and Bone Metabolism. (Pubmed Central) - Aug 10, 2021
Therefore, it is necessary to study H2S donors in detail. In this review, we summarize the current information about H2S donors related to bone metabolism diseases and discuss some mechanisms and biological applications.
- |||||||||| [VIRTUAL] Treatment with Slow-Releasing Hydrogen Sulfide Donors Inhibits Inflammatory Pain in MIce () - Jun 29, 2021 - Abstract #IASP2021IASP_477;
These data demonstrate the importance of not only HS, but also per-/polysulfides as bioactive signaling molecules with potent anti-inflammatory and, in particular, antioxidant properties. These findings suggest that the induction of H2S is a promising novel approach to treat inflammatory pain through the activation of endogenous antioxidant system in the peripheral nervous system.
- |||||||||| GYY4137 / National University of Singapore
[VIRTUAL] The Effects of Hydrogen Sulfide in the Oxidative Stress, Nociceptive, Inflammatory and Apoptotic Responses Induced by Chronic Osteoarthritis Pain () - Jun 29, 2021 - Abstract #IASP2021IASP_331;
These findings suggest that the induction of H2S is a promising novel approach to treat inflammatory pain through the activation of endogenous antioxidant system in the peripheral nervous system. These data suggest that treatment with two slow-releasing H2S donors might be an interesting strategy for the treatment of nociception, physical dysfunctions and the depressive-liked behaviors associated with chronic osteoarthritis pain and further demonstrate the antioxidant, antiinflammatory and anti-apoptotic effects of DADS and GYY4137 in the amygdala of animals with chronic osteoarthritis pain.
- |||||||||| GYY4137 / National University of Singapore
Journal: Hydrogen Sulfide: A Potential Therapeutic Target in the Development of Diabetic Retinopathy. (Pubmed Central) - May 13, 2021
Streptozotocin-induced diabetic mice were administered a slow releasing H2S donor GYY4137 for 6 months...Thus, supplementation of H2S donor prevents the development of diabetic retinopathy by ameliorating increase in oxidative stress and preserving the mitochondrial integrity. H2S donors may provide a novel therapeutic strategy to inhibit the development of diabetic retinopathy.
- |||||||||| Review, Journal: Trends in HS-Donors Chemistry and Their Effects in Cardiovascular Diseases. (Pubmed Central) - Apr 7, 2021
Considering the plethora of physiological effects of this gasotransmitter, the protective role of HS donors in different disease models has been extensively studied. Based on the growing interest in HS-releasing compounds and their importance as tools for biological and pharmacological studies, this review is an exploration of currently available HS donors, classifying them by the HS-releasing-triggered mechanism and highlighting those potentially useful as promising drugs in the treatment of cardiovascular diseases.
- |||||||||| Review, Journal: Endothelium as a Source and Target of HS to Improve Its Trophism and Function. (Pubmed Central) - Apr 7, 2021
Upregulation of HS producing enzymes and administration of HS donors can be considered as innovative therapeutic approaches to improve EC biology and function, to revert endothelial dysfunction or to prevent cardiovascular disease progression. This review will focus on the beneficial autocrine/paracrine properties of HS on ECs and the state of the art on HS potentiating drugs and tools.
- |||||||||| Review, Journal: Hydrogen Sulfide in Pharmacotherapy, Beyond the Hydrogen Sulfide-Donors. (Pubmed Central) - Mar 27, 2021
Hence, the therapeutic effect of these drugs may be partly the result of the release of HS occurring during drug metabolism and/or the effect of these drugs on the production of endogenous hydrogen sulfide. In this work, we review data regarding sulfur drugs commonly used in clinical practice that can support the hypothesis about HS-dependent pharmacotherapeutic effects of these drugs.
- |||||||||| [VIRTUAL] REPROGRAMMING HYPERTENSION PROGRAMMED BY HIGH-FAT DIET: THE ROLE OF GARLIC OIL (Mini-Orals Hall) - Mar 19, 2021 - Abstract #ERAEDTA2021ERA_EDTA_1269;
The beneficial effects of garlic oil were associated with increased renal mRNA expression and activity of H2S-generating enzymes, increased NO bioavailability, increased plasma SCFA levels, and alterations of gut microbiota composition. Our data revealed associations between H 2S-generating pathway in the gut and kidneys, NO system, gut microbiota, and microbiota-derived metabolites in hypertension programmed by HF intake and provided insight to garlic oil as a hypertension reprogramming strategy for further translational research.
- |||||||||| Journal: Hydrogen Sulfide Promotes Cell Proliferation and Melanin Synthesis in Primary Human Epidermal Melanocytes. (Pubmed Central) - Mar 19, 2021
Our data revealed associations between H 2S-generating pathway in the gut and kidneys, NO system, gut microbiota, and microbiota-derived metabolites in hypertension programmed by HF intake and provided insight to garlic oil as a hypertension reprogramming strategy for further translational research. This study demonstrates that H2S promotes cell proliferation and melanin synthesis in HEMs, which indicates pharmacologic regulation of H2S may be potential treatment for skin disorders caused by loss of melanocytes or dysfunction of melanogenesis.
- |||||||||| GYY4137 / National University of Singapore
[VIRTUAL] Hydrogen Sulfide and Airway Hyperreactivity in a Mouse Model of Neonatal Hyperoxia Exposure () - Mar 14, 2021 - Abstract #ATS2021ATS_3265;
Our data suggest that exogenous H2S is safe and effective in blunting neonatal hyperoxia-induced AHR in a mouse model. As an in vivo demonstration of H2S efficacy in hyperoxia effects, this study provides encouraging data towards the possible therapeutic use of H2S to prevent chronic lung disease of prematurity.
- |||||||||| GYY4137 / National University of Singapore
[VIRTUAL] Hydrogen Sulfide (H2S), Mitochondria and Oxygen in Developing Airway Smooth Muscle () - Mar 14, 2021 - Abstract #ATS2021ATS_596;
Cells were treated with the long-lasting H2S donor GYY4137 at increasing concentration (50, 100, 250, 400 uM) for 24 hours, then grown in normoxia (21% O2) vs. moderate hyperoxia (40% O2) for 48 hours...Our data suggest a potential protective role for the gasotransmitter H2S on mitochondrial function of developing ASM exposed to supplemental oxygen. Moreover, our dose response curve paves the way for future studies assessing H2S in vivo towards eventual application in prematurity as a novel bronchodilator.
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