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Hydrogen sulfide (H2S) is a gasotransmitter that exerts a multitude of functions in both physiologic and pathophysiologic processes. H2S-synthesizing enzymes are increased in a variety of human malignancies, including colon, prostate, breast, renal, urothelial, ovarian, oral squamous cell, and thyroid cancers. In cancer, H2S promotes tumor growth, cellular and mitochondrial bioenergetics, migration, invasion, angiogenesis, tumor blood flow, metastasis, epithelia–mesenchymal transition, DNA repair, protein sulfhydration, and chemotherapy resistance Additionally, in some malignancies, increased H2S-synthesizing enzyme expression correlates with a worse prognosis and a higher tumor stage. Here we review the role of H2S in cancer, with an emphasis on the molecular mechanisms by which H2S promotes cancer development, progression, dedifferentiation, and metastasis.

Recent research demonstrates a reciprocal relationship between gut microbiota-derived metabolites and the host in controlling the energy homeostasis in mammals. On the one hand, to thrive, gut bacteria exploit nutrients digested by the host. On the other hand, the host utilizes numerous products of gut bacteria metabolism as a substrate for ATP production in the colon. Finally, bacterial metabolites seep from the gut into the bloodstream and interfere with the host’s cellular bioenergetics machinery. Notably, there is an association between alterations in microbiota composition and the development of metabolic diseases and their cardiovascular complications. Some metabolites, like short-chain fatty acids and trimethylamine, are considered markers of cardiometabolic health. Others, like hydrogen sulfide and nitrite, demonstrate antihypertensive properties. Scientific databases were searched for pre-clinical and clinical studies to summarize current knowledge on the role of gut microbiota metabolites in the regulation of mammalian bioenergetics and discuss their potential involvement in the development of cardiometabolic disorders. Overall, the available data demonstrates that gut bacteria products affect physiological and pathological processes controlling energy and vascular homeostasis. Thus, the modulation of microbiota-derived metabolites may represent a new approach for treating obesity, hypertension and type 2 diabetes.

Background. The medical relevance of therapeutic gases can range from use in burns and stroke victims to hypoxia therapy in children. However, medical gases such as oxygen, hydrogen, helium and xenon have recently come under increased exploration for their potential therapeutic use on various brain disease states, including traumatic brain injuries, hypoxia-ischemia and, cerebral hemorrhages. Objective. This synthetic review aims to rigorously select related articles and identify within their content the main possible uses of therapeutic gases and physiological mechanisms. The objective of this article is to present the various therapeutic mechanisms that have been proposed in the current literature and the medical relevance of various therapeutic gases used in balneotherapy or medical rehabilitation. Methods. To elaborate our synthesis review, we have searched for relevant open access articles in 6 international databases: Cochrane, Elsevier, NCBI/PubMed, NCBI/PMC, PEDro, and ISI Web of Knowledge/Science, published from January 2011 until December 2020. The contextually quested keywords combinations/ syntaxes used specified on this page. The eligible articles were analyzed in detail regarding pathologies addressed by therapeutic gases. All articles with any design (reviews, randomized controlled trials, non-randomized controlled trials, case-control studies, cross-sectional studies), if eligible according to the above-mentioned selection methodology, containing in the title or abstract the above-mentioned combinations, were included in the analysis. Articles were excluded in the second phase if they did not reach the relevance criterion. Results. Our search identified, first, 225 articles. After eliminating the duplicates, remained 180 articles. In the second phase, we applied a relevance criterion. Although our team - including the authors of this paper – have quite long and consistent expertise in achieving systematic literature reviews, the marked heterogeneity of both the item composing the subject we have approached and inherently the wase of presentations in the respective quite vast and diverse domain of medical gases, prevented us to fulfil, at least regarding this initial work, a systematic literature review. Instead, we succeeded to make a hopefully interesting and valuable narrative synthetic-related literature review. At the end of the second phase, 63 articles passed the relevance criterion and were included in this synthetic review. Conclusions. Therapeutic gases are not fully understood and used adequately for sanogenic or medical purposes. More research is needed to fully understand the mechanisms and importance of therapeutic gases. The link between balneotherapy and medical rehabilitation regarding the usage of therapeutical gases emphasises the unity for this medical speciality. Keywords: "Therapeutic gas"/ "Oxygen therapy"/ "Carbon dioxide"/ "CO2 therapy"/ "Carbon monoxide"/ "Mofette"/ "Hydrogen Sulfide"/ "H2S"/ "Helium"/ "Xenon"/ "Ozone therapy"/ "Radon"/ "Hydrogen therapy"/ "Nitric oxide"/ "Heliox" AND "Rehabilitation".

While heart disease remains a common cause of mortality, cerebrovascular disease also increases with age, and has been implicated in Alzheimer's disease and related dementias (ADRD). We have described hydrogen sulfide (H2S), a signaling molecule important in vascular homeostasis, as a biomarker of cardiovascular disease. We hypothesize that plasma H2S and its metabolites also relate to vascular and cognitive dysfunction in ADRD. We used analytical biochemical methods to measure plasma H2S metabolites and MRI to evaluate indicators of microvascular disease in ADRD. Levels of total H2S and specific metabolites were increased in ADRD versus controls. Cognition and microvascular disease indices were correlated with H2S levels. Total plasma sulfide was the strongest indicator of ADRD, and partially drove the relationship between cognitive dysfunction and white matter lesion volume, an indicator of microvascular disease. Our findings show that H2S is dysregulated in dementia, providing a potential biomarker for diagnosis and intervention., Scheme for sulfide dysregulation in ADRD. In ADRD, increased accumulation of sulfides, measured in plasma, may reflect increased formation of H2S metabolites produced in the vascular compartment. Several sulfide species are known to impair blood brain barrier leading to persistent excitotoxic stress and subsequent destructive changes in brain microvascular structure and cognitive function seen in ADRD.

The study of exhaust H 2 S and NO 2 gases using activated carbon has been conducted. In this study, activated carbon was prepared from mendong plant (Frimbistylis umbellaris) , which was activated using zinc chloride (ZnCl 2 ) with concentrations of 2.5; 5; 7.5; and 10 % w/v to determine the efficiency of H 2 S adsorption. Mendong charcoal was obtained from the process of using a modified tool. Activation was done by maceration using ZnCl 2 activator (w/v) for 24 hours. The adsorption of H 2 S and NO 2 was analyzed using UV-Vis spectrophotometry. Determinations of H 2 S gas carried out using the blue methylene’s method for 1 hour showed the highest effectiveness of mendong activated carbon was of that at the concentration of 2.5 % ZnCl 2 w/v with 80% of H 2 S removal. Further, the mendong activated carbon with the concentration of 2.5% ZnCl 2 w/v was used for NO 2 adsorption. The adsorption of NO 2 gas was conducted for 1 hour using Griess Saltzman’s method. The result showed that the largest concentration of NO 2 gas was adsorbed when the HNO 3 concentration was 1.5 M (0.057 µg/mL). The percentage of NO 2 efficiency adsorbed was at 28%.

Aims The current study aimed to explore the expression of transient receptor potential A1 ion channels (TRPA1) in the rat ureter and to assess if TRPA1-active compounds modulate ureter function. Methods The expression of TRPA1 in rat ureter tissue was studied by immunofluorescence. The TRPA1 distribution was compared to calcitonin gene-related peptide (CGRP), alpha-actin (SMA1), anoctamin-1 (ANO1), and c-kit. For in vivo analyses, a catheter was implanted in the right ureter of 50 rats. Ureter peristalsis and pressures were continuously recorded by a data acquisition set-up during intraluminal infusion of saline (baseline), saline plus protamine sulfate (PS; to disrupt the urothelium), saline plus PS with hydrogen sulfide (NaHS) or cinnamaldehyde (CA). Comparisons were made between rats treated systemically with vehicle or a TRPA1-antagonist (HC030031). Results TRPA1-immunoreactive nerves co-expressed CGRP and were mainly located in the suburothelial region of the ureter. Immunoreactivity for TRPA1 was also encountered in c-kit-positive but ANO1-negative cells of the ureter suburothelium and wall. In vivo, HC030031-treated rats had elevated baseline peristaltic frequency (p < 0.05) and higher intraluminal pressures (p < 0.01). PS increased the frequency of ureter peristalsis versus baseline in vehicle-treated rats (p < 0.001) but not in HC030031-treated rats. CA (p < 0.001) and NaHS (p < 0.001) decreased ureter peristalsis. This was counteracted by HC030031 (p < 0.05 and p < 0.01). Conclusions In rats, TRPA1 is expressed on cellular structures considered of importance for peristaltic and mechanoafferent functions of the ureter. Functional data indicate that TRPA1-mediated signals regulate ureter peristalsis. This effect was pronounced after mucosal disruption and suggests a role for TRPA1 in ureter pathologies involving urothelial damage. Funding Agencies|Gester Foundation, Helsingborg, Sweden

Graphical abstract, Highlights • H2S derived from CSE/CBS inhibits inflammation and calcification of valvular interstitial cells. • H2S releasing molecules inhibits inflammation and calcification of valvular interstitial cells. • H2S inhibits inflammation and calcification in aortic valve of apolipoprotein E deficient mice. • H2S suppresses nuclear translocation of NF-κB and subsequent expression of IL-1β and TNF-α. • Activation of Runx2, its nuclear translocation is mediated by NF-κB in calcifying conditions. • Inflammation and calcification are connected via master transcription factors, NF-κB and Runx2., Introduction Hydrogen sulfide (H2S) was revealed to inhibit aortic valve calcification and inflammation was implicated in the pathogenesis of calcific aortic valve disease (CAVD). Objectives We investigate whether H2S inhibits mineralization via abolishing inflammation. Methods and results Expression of pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) were increased in patients with CAVD and in calcified aortic valve of ApoE-/- mice. Administration of H22S releasing donor (4-methoxyphenyl piperidinylphosphinodithioc acid (AP72)) exhibited inhibition on both calcification and inflammation in aortic valve of apolipoprotein E knockout mice (ApoE-/-) mice is reflected by lowering IL-1β and TNF-α levels. Accordingly, AP72 prevented the accumulation of extracellular calcium deposition and decreased nuclear translocation of nuclear factor-κB (NF-κB) in human valvular interstitial cells (VIC). This was also accompanied by reduced cytokine response. Double-silencing of endogenous H2S producing enzymes, Cystathionine gamma-lyase (CSE) and Cystathionine beta-synthase (CBS) in VIC exerted enhanced mineralization and higher levels of IL-1β and TNF-α. Importantly, silencing NF-κB gene or its pharmacological inhibition prevented nuclear translocation of runt-related transcription factor 2 (Runx2) and subsequently the calcification of human VIC. Increased levels of NF-κB and Runx2 and their nuclear accumulation occurred in ApoE-/- mice with a high-fat diet. Administration of AP72 decreased the expression of NF-κB and prevented its nuclear translocation in VIC of ApoE-/- mice on a high-fat diet, and that was accompanied by a lowered pro-inflammatory cytokine level. Similarly, activation of Runx2 did not occur in VIC of ApoE-/- mice treated with H2S donor. Employing Stimulated Emission Depletion (STED) nanoscopy, a strong colocalization of NF-κB and Runx2 was detected during the progression of valvular calcification. Conclusions Hydrogen sulfide inhibits inflammation and calcification of aortic valve. Our study suggests that the regulation of Runx2 by hydrogen sulfide (CSE/CBS) occurs via NF-κB establishing a link between inflammation and mineralization in vascular calcification.

Based on the III International Consensus on the definition of Sepsis and Septic Shock (Sepsis-3), the modern definition of septic shock was proposed: “Septic shock is a type of sepsis that is accompanied by severe hemodynamic, metabolic and cellular disorders, and these disorders are associated with a higher risk fatal outcome”. Despite the classic idea of septic shock development (proinflammatory, immunosuppressive phases and, finally, multiple organ failure with distinct shock organs), the theory of activation of the caspase, endocannabioid system and system of protein of programmed death-1 in evolving septic shock are promising approaches to development of new diagnostic and therapeutic methods. Lymphopenia is already observed at an early stage of septic shock, which further leads to deep immunosuppression. Previous experimental studies have revealed some treatment methods to reduce the pro-inflammatory stage, which, however, did not show desired results in clinics. Now it is necessary to look for ways to inhibit apoptosis, depletion of lymphocytes, macrophages and other immune cells in the course of septic shock. It is known that caspases mediate innate detection of pathogenic microorganisms, cause pyroptosis, activation of monocytes. It has been proven that inhibition of caspase-8, caspase-11 leads to decreased monocyte functioning and cytokine release, which plays an important role in immunopathogenesis of septic shock. Associations of PD-1 and PD-2 expression on CD4+ lymphocytes and monocytes are also shown to be connected with immune dysfunctions, decrease in lymphocyte proliferation, and increased interleukin-10 concentration. Stimulation of the cannabinoid receptors is able to reduce inflammation by inhibiting cytopathic and immunosuppressive effects of pathogens. It has been shown that classic septic shock biomarkers (pro-inflammatory, anti-inflammatory cytokines; procalcitonin, lactate, etc.) do not have predictive power in relation to the outcome of the disease. Circulating and citrullated histones, determined by mass spectrometry, may serve as potential diagnostic markers of septic shock, but they require further study. Use of oxidized phospholipid oxPAPC (Oxidized 1-palmitoyl-2-arachidonoyl-snglycero-3-phosphocholine), hydrogen sulfide and Fasciola hepatica fatty acid binding proteins (hepatic fluke) prevents oxidative stress, synthesis of pro-inflammatory cytokines and provides maturation of macrophages and dendritic cells. Further study of immunological reactions during septic shock is of great importance for substantiation of new approaches to the diagnostics and therapy of septic shock.

Significance Tuberculosis (TB) is responsible for millions of deaths each year and several billion people are latently infected with Mycobacterium tuberculosis (Mtb). Mtb modulates host factors, such as endogenous gaseous signalling molecules, to persist in humans for decades. H2S has diverse biological functions, including modulation of immunity and cellular respiration. However, the role of H2S in TB is unclear. We found that mice deficient in H2S production are more resistant to Mtb infection than WT mice. Upon infection, Mtb increases host H2S, which suppresses central carbon metabolism and increases inflammation. Distribution of H2S-producing enzymes in human TB lungs showed that H2S is produced at the site of infection. These findings identify glycolysis and H2S-producing enzymes as targets for TB host-directed therapies., The ubiquitous gasotransmitter hydrogen sulfide (H2S) has been recognized to play a crucial role in human health. Using cystathionine γ-lyase (CSE)-deficient mice, we demonstrate an unexpected role of H2S in Mycobacterium tuberculosis (Mtb) pathogenesis. We showed that Mtb-infected CSE−/− mice survive longer than WT mice, and support reduced pathology and lower bacterial burdens in the lung, spleen, and liver. Similarly, in vitro Mtb infection of macrophages resulted in reduced colony forming units in CSE−/− cells. Chemical complementation of infected WT and CSE−/− macrophages using the slow H2S releaser GYY3147 and the CSE inhibitor DL-propargylglycine demonstrated that H2S is the effector molecule regulating Mtb survival in macrophages. Furthermore, we demonstrate that CSE promotes an excessive innate immune response, suppresses the adaptive immune response, and reduces circulating IL-1β, IL-6, TNF-α, and IFN-γ levels in response to Mtb infection. Notably, Mtb infected CSE−/− macrophages show increased flux through glycolysis and the pentose phosphate pathway, thereby establishing a critical link between H2S and central metabolism. Our data suggest that excessive H2S produced by the infected WT mice reduce HIF-1α levels, thereby suppressing glycolysis and production of IL-1β, IL-6, and IL-12, and increasing bacterial burden. Clinical relevance was demonstrated by the spatial distribution of H2S-producing enzymes in human necrotic, nonnecrotic, and cavitary pulmonary tuberculosis (TB) lesions. In summary, CSE exacerbates TB pathogenesis by altering immunometabolism in mice and inhibiting CSE or modulating glycolysis are potential targets for host-directed TB control.

Antioxidant system is of great importance for organisms to regulate the level of excessive reactive oxygen species (ROS) under the environmental stresses including antibiotics stress. Effects of norfloxacin (NOR) on cystathionine-β-synthase (CBS), nitric oxide synthase (NOS) and antioxidant enzymes were investigated, and interaction between NO and H2S and their regulation on the antioxidant system of Vibrio alginolyticus under NOR were determined as well in the present study. After treated with 2 µg/mL NOR (1/2 MIC), CBS content, H2S and NO contents decreased while H2O2 accumulation and the antioxidant-related genes mRNA level increased. Additionally, the endogenous H2S content in V. alginolyticus was increased by the exogenous NO, while H2O2 accumulation and the relative expression level of SOD (Superoxide dismutase gene) decreased under exogenous NO or H2S. And the content of endogenous NO and NOS in V. alginolyticus increased under the exogenous H2S as well. Taken together, these results showed that anti-oxidative ability in V. alginolyticus was respectively enhanced by the gas molecules of H2S and NO under NOR-induced stress, and there may be a crosstalk regulative mechanism between H2S and NO. These results lay a foundation for the research of regulation network of H2S and NO, and provide a hint to synthesize anti-vibrio drugs in the future.

Hydrogen sulfide (H2S) has been shown in previous studies to cause hypothermia and hypometabolism in mice, and its thermoregulatory effects were subsequently investigated. However, the molecular target through which H2S triggers its effects on deep body temperature has remained unknown. We investigated the thermoregulatory response to fast-(Na2S) and slow-releasing (GYY4137) H2S donors in C57BL/6 mice, and then tested whether their effects depend on the transient receptor potential ankyrin-1 (TRPA1) channel in Trpa1 knockout (Trpa1−/−) and wild-type (Trpa1+/+) mice. Intracerebroventricular administration of Na2S (0.5–1 mg/kg) caused hypothermia in C57BL/6 mice, which was mediated by cutaneous vasodilation and decreased thermogenesis. In contrast, intraperitoneal administration of Na2S (5 mg/kg) did not cause any thermoregulatory effect. Central administration of GYY4137 (3 mg/kg) also caused hypothermia and hypometabolism. The hypothermic response to both H2S donors was significantly (p &lt, 0.001) attenuated in Trpa1−/− mice compared to their Trpa1+/+ littermates. Trpa1 mRNA transcripts could be detected with RNAscope in hypothalamic and other brain neurons within the autonomic thermoeffector pathways. In conclusion, slow- and fast-releasing H2S donors induce hypothermia through hypometabolism and cutaneous vasodilation in mice that is mediated by TRPA1 channels located in the brain, presumably in hypothalamic neurons within the autonomic thermoeffector pathways.

Human immunodeficiency virus (HIV) attacks the immune system and weakens the ability to fight infections/disease. Furthermore, HIV infection confers approximately two-fold higher risk of cardiac events compared with the general population. The pathological mechanisms responsible for the increased incidence of cardiovascular disease in HIV patients are largely unknown. We hypothesized that increased oxidative stress and attenuated circulating levels of the cardioprotective gaseous signaling molecules, nitric oxide (NO), and hydrogen sulfide (H2S) were involved in the cardiovascular pathobiology observed in HIV patients. Plasma samples from both HIV patients and age–matched normal subjects were used for all assays. Oxidative stress was determined by analyzing the levels of advanced oxidation protein products (AOPP) and H2O2. Antioxidant levels were determined by measuring the levels of trolox equivalent capacity. ADMA, hs-CRP, and IL-6 were determined by using ELISA. The levels of H2S (free H2S and sulfane sulfur) and NO2 (nitrite) were determined in the plasma samples by using gas chromatography and HPLC, respectively. In the present study we observed a marked induction in the levels of oxidative stress and decreased antioxidant status in the plasma of HIV patients as compared with the controls. Circulating levels of the cardiovascular disease biomarkers: ADMA, hs-CRP (high-sensitivity C-reactive protein), and IL-6 were significantly increased in the circulatory system of HIV patients. The levels of both nitrite and H2S/sulfane sulfur were significantly reduced in the plasma of HIV patients as compared with normal subjects. Our data demonstrate significant increases in circulating biomarkers of oxidative stress and cardiovascular (CV) in conjunction with decreased bioavailability of H2S and NO in HIV patients. Diminished levels of these two cardioprotective gaseous signaling molecules may be involved in the pathogenesis of CV disease in the setting of HIV.

Hydrogen sulfide (H2S) has long been recognized as a putrid, toxic gas. However, as a result of intensive biochemical research in the past two decades, H2S is now considered to be the third gasotransmitter alongside nitric oxide (NO) and carbon monoxide (CO) in mammalian systems. H2S-producing enzymes are expressed in all organs, playing an important role in their physiology. In the kidney, H2S is a critical regulator of vascular and cellular function, although the mechanisms that affect (sub)cellular levels of H2S are not precisely understood. H2S modulates systemic and renal blood flow, glomerular filtration rate and the renin-angiotensin axis through direct inhibition of nitric oxide synthesis. Further, H2S affects cellular function by modulating protein activity via post-translational protein modification: a process termed persulfidation. Persulfidation modulates protein activity, protein localization and protein-protein interactions. Additionally, acute kidney injury (AKI) due to mitochondrial dysfunction, which occurs during hypoxia or ischemia-reperfusion (IR), is attenuated by H2S. H2S enhances ATP production, prevents damage due to free radicals and regulates endoplasmic reticulum stress during IR. In this review, we discuss current insights in the (sub)cellular regulation of H2S anabolism, retention and catabolism, with relevance to spatiotemporal regulation of renal H2S levels. Together, H2S is a versatile gasotransmitter with pleiotropic effects on renal function and offers protection against AKI. Unraveling the mechanisms that modulate (sub)cellular signaling of H2S not only expands fundamental insight in the regulation of functional effects mediated by H2S, but can also provide novel therapeutic targets to prevent kidney injury due to hypoxic or ischemic injury.

Hepatic fibrosis is caused by chronic inflammation and characterized as the excessive accumulation of extra cellular matrix (ECM) by activated hepatic stellate cells (HSCs). Gasotransmitters like NO and CO are known to modulate inflammation and fibrosis, however, little is known about the role of the gasotransmitter hydrogen sulfide (H2S) in liver fibrogenesis and stellate cell activation. Endogenous H2S is produced by the enzymes cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CTH) and 3-mercaptopyruvate sulfur transferase (MPST) [1]. The aim of this study was to elucidate the role of endogenously produced and/or exogenously administered H2S on rat hepatic stellate cell activation and fibrogenesis. Primary rat HSCs were culture-activated for 7 days and treated with different H2S releasing donors (slow releasing donor GYY4137, fast releasing donor NaHS) or inhibitors of the H2S producing enzymes CTH and CBS (DL-PAG, AOAA). The main message of our study is that mRNA and protein expression level of H2S synthesizing enzymes are low in HSCs compared to hepatocytes and Kupffer cells. However, H2S promotes hepatic stellate cell activation. This conclusion is based on the fact that production of H2S and mRNA and protein expression of its producing enzyme CTH are increased during hepatic stellate cell activation. Furthermore, exogenous H2S increased HSC proliferation while inhibitors of endogenous H2S production reduce proliferation and fibrotic makers of HSCs. The effect of H2S on stellate cell activation correlated with increased cellular bioenergetics. Our results indicate that the H2S generation in hepatic stellate cells is a target for anti-fibrotic intervention and that systemic interventions with H2S should take into account cell-specific effects of H2S.

Background: Hydrogen Sulfide (H2S), a third member of gasotransmitter family along with nitric oxide (NO) and carbon monoxide (CO), exerts a wide range of cellular and molecular actions in our body. There is a large body of evidence suggesting that H2S plays an important role in cancer metastasis; however, the molecular mechanisms of H2S-mediated acceleration of cancer metastasis remain unknown. Methods: We examined the promote effects of H2S on phenotype of gastric cancer (GC) cells (including those of express wild type CD36 and mutant CD36) in vitro and in vivo. GC patients' samples were used for clinical translational significance evaluation. Findings: H2S triggered lipid metabolism reprogramming by significantly up-regulating the expression of the fatty-acid receptor CD36 (CD36) and directly activating CD36 in GC cells. Mechanistically, a disulfide bond located between cysteine (Cys)333 and Cys272 within the CD36 protein structure that was labile to H2S-mediated modification. The long chain-fatty acid (LC-FA) binding pocket was capped by a turn in the CD36 protein, located between helical and sheet structures that were stabilized by the Cys333-Cys272. This limited the secondary binding between LC-FAs and lysine (Lys)334. Breaking the Cys333-Cys272 disulfide bond restored the second LC-FA binding conformation of CD36. Targeting CD36 in vivo blocked H2S-promoted metastasis and improved animal survival. Interpretation: These findings identify that the Cys333-Cys272 disulfide bond disrupted the integrity of the second LC-FA binding conformation of CD36. Therefore, CD36 can directly activate LC-FA access to the cytoplasm by acting as a direct target molecule for H2S. Keywords: H2S, CD36, Disulfide bond, Long chain-fatty acid, Nrf2, Metastasis

The aim of this study was to investigate the protective roles of H2S on acute renal damage in urinary-derived sepsis. Totally 40 male rabbits were randomly divided into the Control, Sham, Sepsis, NaHS and the dl-propargylglycine (PAG) groups. White blood cell counts (WBC), C-reactive protein (CRP), creatinine (Cr) and blood urea nitrogen were determined in peripheral blood samples. Hematoxylin and eosin staining was performed to detect the morphological changes. The mRNA and protein expression levels were detected by semi-quantitative reverse transcriptase PCR (sqRT-PCR) and Western blot analysis. The results showed that, 72 h after surgery, the WBC and CRP levels in the Sepsis group were significantly elevated, and the expression levels of inducible nitric oxide synthase (iNOS) and HO-1 were significantly up-regulated, compared with the Control and Sham groups, indicating renal damage induced by urinary-derived sepsis. Compared with the Sepsis group, the expression levels of iNOS in the renal tissues of the PAG group were significantly up-regulated, whereas the expression levels of HO-1 in the renal tissue were significantly down-regulated, indicating aggravated renal damage. On the other hand, compared with the Sepsis group, the expression levels of iNOS in the renal tissue of the NaHS group were declined, whereas the expression levels of HO-1 were elevated, together with the declined WBC and CRP levels, indicating alleviated renal functions. We could conclude that iNOS and HO-1 expression levels are elevated in the renal tissue of urinary-derived sepsis. H2S could exert protective effects on the urinary-derived sepsis-associated renal damages by down-regulating iNOS expression and up-regulating HO-1 expression.

The aim of this study was to evaluate the mutual relationship among perivascular adipose tissue (PVAT) and endogenous and exogenous H2S in vasoactive responses of isolated arteries from adult normotensive (Wistar) rats and hypertriglyceridemic (HTG) rats, which are a nonobese model of metabolic syndrome. In HTG rats, mild hypertension was associated with glucose intolerance, dyslipidemia, increased amount of retroperitoneal fat, increased arterial contractility, and endothelial dysfunction associated with arterial wall injury, which was accompanied by decreased nitric oxide (NO)-synthase activity, increased expression of H2S producing enzyme, and an altered oxidative state. In HTG, endogenous H2S participated in the inhibition of endothelium-dependent vasorelaxation regardless of PVAT presence, on the other hand, aortas with preserved PVAT revealed a stronger anticontractile effect mediated at least partially by H2S. Although we observed a higher vasorelaxation induced by exogenous H2S donor in HTG rats than in Wistar rats, intact PVAT subtilized this effect. We demonstrate that, in HTG rats, endogenous H2S could manifest a dual effect depending on the type of triggered signaling pathway. H2S within the arterial wall contributes to endothelial dysfunction. On the other hand, PVAT of HTG is endowed with compensatory vasoactive mechanisms, which include stronger anti-contractile action of H2S. Nevertheless, the possible negative impact of PVAT during hypertriglyceridemia on the activity of exogenous H2S donors needs to be taken into consideration.

The involvement of nitric oxide (NO) and hydrogen sulfide (H2S) in countermanding heat-inhibited photosynthetic features were studied in wheat (Triticum aestivum L.). Heat stress (HS) was employed at 40 °C after establishment for 6 h daily, and then plants were allowed to recover at 25 °C and grown for 30 days. Glucose (Glc) content increased under HS and repressed plant photosynthetic ability, but the application of sodium nitroprusside (SNP, as NO donor) either alone or with sodium hydrosulfide (NaHS, as H2S donor) reduced Glc-mediated photosynthetic suppression by enhancing ascorbate-glutathione (AsA-GSH) metabolism and antioxidant system, which reduced oxidative stress with decreased H2O2 and TBARS content. Oxidative stress reduction or inhibiting Glc repression was maximum with combined SNP and NaHS treatment, which was substantiated by 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) and hypotaurine (HT), scavengers for NO and H2S, respectively. The scavenge of H2S reduced NO-mediated alleviation of HS suggesting of its downstream action in NO-mediated heat-tolerance. However, a simultaneous decrease of both (NO and H2S) led to higher Glc-mediated repression of photosynthesis and oxidative stress in terms of increased H2O2 content that was comparable to HS plants. Thus, NO and H2S cooperate to enhance photosynthesis under HS by reducing H2O2-induced oxidative stress and excess Glc-mediated photosynthetic suppression., N.I. is thankful to Science and Engineering Research Board (DST-SERB) for providing financial assistance in the form of National Post-Doctoral Fellowship (N-PDF, File No. PDF/2019/000770, Diary No. SERB/F/8191/2019-2020).

Over the last several decades, hydrogen sulfide (H2S) has gained attention as a new signaling molecule, with extensive physiological and pathophysiological roles in human disorders affecting vascular biology, immune functions, cellular survival, metabolism, longevity, development, and stress resistance. Apart from its known functions in oxidative stress and inflammation, new evidence has emerged revealing that H2S carries out physiological functions by targeting proteins, enzymes, and transcription factors through a post-translational modification known as persulfidation. This review article provides a critical overview of the current state of the literature addressing the role of H2S in obesity-associated metabolic disturbances, with particular emphasis on its mechanisms of action in obesity, diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases This work was partially supported by research grants PI19/01712 from the Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) from Spain and VII Spanish Diabetes Association grants to Basic Diabetes Research Projects led by young researchers. CIBEROBN Fisiopatología de la Obesidad y Nutrición is an initiative from the Instituto de Salud Carlos III.

Background: Hydrogen sulfide(H2S) is a bacterial metabolite produced as a result of bacterial growth in subgingival pockets, suggested to partake in the pathogenesis of periodontitis. H2S has previously been shown to induce the secretion of the pro-inflammatory cytokines IL-1β and IL-18 via the NLRP3 inflammasome in monocytes. Objective: To investigate the non-NLRP3 inflammasome-dependent immunological response of human peripheral blood mononuclear cells (PBMCs) of periodontitis patients and healthy controls exposed to H2S in vitro. Methods: PBMCs of periodontitis patients(N = 31) and healthy controls(N = 32) were exposed to 1 mM sodium hydrosulfide (NaHS) at 37°C for 24 h and the secretion of cytokines was compared to resting cells. TNF-α, IFN-γ, IL-6, IL-8, IL-12p40, IL-12p70, IL-17, MCP-1, and IL-1Ra secretions were measured with Bio-Plex Pro™ Human Cytokine Assay. Results: H2S triggered the secretion of the pro-inflammatory IFN-γ, IL-6, IL-17, TNF-α, IL-12p40, and IL-12p70, while the reverse was seen for IL-1Ra. In addition, a higher basal secretion of IFN-γ, IL-6, IL-12p70, IL-17 and MCP-1 was seen from PBMCs of periodontitis patients compared to healthy controls. Conclusion: The bacterial metabolite H2S triggers the secretion of pro-inflammatory cytokines from PBMCs and may thus have a prominent role in the host-bacteria interplay in periodontitis.

Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency are two rare genetic disorders that are caused by impairment of the mitochondrial enzyme sulfite oxidase. Sulfite oxidase is catalyzing the terminal reaction of cellular cysteine catabolism, the oxidation of sulfite to sulfate. Absence of sulfite oxidase leads to the accumulation of sulfite, which has been identified as a cellular toxin. However, the molecular pathways leading to the production of sulfite are still not completely understood. In order to identify novel treatment options for both disorders, the understanding of cellular cysteine catabolism - and its alterations upon loss of sulfite oxidase - is of utmost importance. Here we applied a new detection method of sulfite in cellular extracts to dissect the contribution of cytosolic and mitochondrial glutamate oxaloacetate transaminase (GOT) in the transformation of cysteine sulfinic acid to sulfite and pyruvate. We found that the cytosolic isoform GOT1 is primarily responsible for the production of sulfite. Moreover, loss of sulfite oxidase activity results in the accumulation of sulfite, H2S and persulfidated cysteine and glutathione, which is consistent with an increase of SQR protein levels. Surprisingly, none of the known H2S-producing pathways were found to be upregulated under conditions of sulfite toxicity suggesting an alternative route of sulfite-induced shift from oxidative to H2S dependent cysteine catabolism.

The role of endogenous hydrogen sulfide (H2S) as an antioxidant regulator has sparked interest in its function within inflammatory diseases. Cigarette and alcohol use are major causes of premature death, resulting from chronic oxidative stress and subsequent tissue damage. The activation of the Nrf2 antioxidant response by H2S suggests that this novel gasotransmitter may function to prevent or potentially reverse disease progression caused by cigarette smoking or alcohol use. The purpose of this study is to review the interrelationship between H2S signaling and cigarette smoking or alcohol drinking. Based on the databases of cellular, animal, and clinical studies from Pubmed using the keywords of H2S, smoking, and/or alcohol, this review article provides a comprehensive insight into disrupted H2S signaling by alcohol drinking and cigarette smoking-caused disorders. Major signaling and metabolic pathways involved in H2S-derived antioxidant and anti-inflammatory responses are further reviewed. H2S supplementation may prove to be an invaluable asset in treating or preventing diseases in those suffering from cigarette or alcohol addiction.

Fish are a convenient model for the study of reparative and post-traumatic processes of central nervous system (CNS) recovery, because the formation of new cells in their CNS continues throughout life. After a traumatic injury to the cerebellum of juvenile masu salmon, Oncorhynchus masou, the cell composition of the neurogenic zones containing neural stem cells (NSCs)/neural progenitor cells (NPCs) in the acute period (two days post-injury) changes. The presence of neuroepithelial (NE) and radial glial (RG) neuronal precursors located in the dorsal, lateral, and basal zones of the cerebellar body was shown by the immunohistochemical (IHC) labeling of glutamine synthetase (GS). Progenitors of both types are sources of neurons in the cerebellum of juvenile O. masou during constitutive growth, thus, playing an important role in CNS homeostasis and neuronal plasticity during ontogenesis. Precursors with the RG phenotype were found in the same regions of the molecular layer as part of heterogeneous constitutive neurogenic niches. The presence of neuroepithelial and radial glia GS+ cells indicates a certain proportion of embryonic and adult progenitors and, obviously, different contributions of these cells to constitutive and reparative neurogenesis in the acute post-traumatic period. Expression of nestin and vimentin was revealed in neuroepithelial cerebellar progenitors of juvenile O. masou. Patterns of granular expression of these markers were found in neurogenic niches and adjacent areas, which probably indicates the neurotrophic and proneurogenic effects of vimentin and nestin in constitutive and post-traumatic neurogenesis and a high level of constructive metabolism. No expression of vimentin and nestin was detected in the cerebellar RG of juvenile O. masou. Thus, the molecular markers of NSCs/NPCs in the cerebellum of juvenile O. masou are as follows: vimentin, nestin, and glutamine synthetase label NE cells in intact animals and in the post-traumatic period, while GS expression is present in the RG of intact animals and decreases in the acute post-traumatic period. A study of distribution of cystathionine &beta, synthase (CBS) in the cerebellum of intact young O. masou showed the expression of the marker mainly in type 1 cells, corresponding to NSCs/NCPs for other molecular markers. In the post-traumatic period, the number of CBS+ cells sharply increased, which indicates the involvement of H2S in the post-traumatic response. Induction of CBS in type 3 cells indicates the involvement of H2S in the metabolism of extracellular glutamate in the cerebellum, a decrease in the production of reactive oxygen species, and also arrest of the oxidative stress development, a weakening of the toxic effects of glutamate, and a reduction in excitotoxicity. The obtained results allow us to consider H2S as a biologically active substance, the numerous known effects of which can be supplemented by participation in the processes of constitutive neurogenesis and neuronal regeneration.

Background Cadmium (Cd) is a nonessential heavy metal with potentially deleterious effects on different organisms. The organisms have evolved sophisticated defense system to alleviate heavy metal toxicity. Hydrogen sulfide (H2S) effectively alleviates heavy metal toxicity in plants and reduces oxidative stress in mammals. However, the function of H2S for alleviating heavy metal toxicity in aquatic organisms remains less clear. Tetrahymena thermophila is an important model organism to evaluate toxic contaminants in an aquatic environment. In this study, the molecular roles of exogenously H2S application were explored by RNA sequencing under Cd stress in T. thermophila. Results The exposure of 30 μM Cd resulted in T. thermophila growth inhibition, cell nigrescence, and malondialdehyde (MDA) content considerably increase. However, exogenous NaHS (donor of H2S, 70 μM) significantly alleviated the Cd-induced toxicity by inhibiting Cd absorbtion, promoting CdS nanoparticles formation and improving antioxidant system. Comparative transcriptome analysis showed that the expression levels of 9152 genes changed under Cd stress (4658 upregulated and 4494 downregulated). However, only 1359 genes were differentially expressed with NaHS treatment under Cd stress (1087 upregulated and 272 downregulated). The functional categories of the differentially expressed genes (DEGs) by gene ontology (GO) revealed that the transcripts involved in the oxidation–reduction process, oxidoreductase activity, glutathione peroxidase activity, and cell redox homeostasis were the considerable enrichments between Cd stress and NaHS treatment under Cd stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that the carbon metabolism, glutathione metabolism, metabolism of xenobiotics by cytochrome P450, and ABC transporters were significantly differentially expressed components between Cd stress and NaHS treatment under Cd stress in T. thermophila. The relative expression levels of six DEGs were further confirmed through quantitative real-time polymerase chain reaction (qRT-PCR). Conclusion NaHS alleviated Cd stress mainly through inhibiting Cd absorbtion, promoting CdS nanoparticles formation, increasing oxidation resistance, and regulation of transport in free-living unicellular T. thermophila. These findings will expand our understanding for H2S functions in the freshwater protozoa.

For centuries, hydrogen sulfide (H2S) was considered primarily as a poisonous gas and environmental hazard. However, with the discovery of prokaryotic and eukaryotic enzymes for H2S production, breakdown, and utilization, H2S has emerged as an important signaling molecule in a wide range of physiological and pathological processes. Hence, H2S is considered a gasotransmitter along with nitric oxide (•NO) and carbon monoxide (CO). Surprisingly, despite having overlapping functions with •NO and CO, the role of host H2S in microbial pathogenesis is understudied and represents a gap in our knowledge. Given the numerous reports that followed the discovery of •NO and CO and their respective roles in microbial pathogenesis, we anticipate a rapid increase in studies that further define the importance of H2S in microbial pathogenesis, which may lead to new virulence paradigms. Therefore, this review provides an overview of sulfide chemistry, enzymatic production of H2S, and the importance of H2S in metabolism and immunity in response to microbial pathogens. We then describe our current understanding of the role of host-derived H2S in tuberculosis (TB) disease, including its influences on host immunity and bioenergetics, and onMycobacterium tuberculosis(Mtb)growth and survival. Finally, this review discusses the utility of H2S-donor compounds, inhibitors of H2S-producing enzymes, and their potential clinical significance.

Myocardial ischemic injury is among the top 10 leading causes of death from cardiovascular diseases worldwide. Myocardial ischemia is caused mainly by coronary artery occlusion or obstruction. It usually occurs when the heart is insufficiently perfused, oxygen supply to the myocardium is reduced, and energy metabolism in the myocardium is abnormal. Pathologically, myocardial ischemic injury generates a large number of inflammatory cells, thus inducing a state of oxidative stress. This sharp reduction in the number of normal cells as a result of apoptosis leads to organ and tissue damage, which can be life-threatening. Therefore, effective methods for the treatment of myocardial ischemic injury and clarification of the underlying mechanisms are urgently required. Gaseous signaling molecules, such as NO, H2S, H2, and combined gas donors, have gradually become a focus of research. Gaseous signaling molecules have shown anti-apoptotic, anti-oxidative and anti-inflammatory effects as potential therapeutic agents for myocardial ischemic injury in a large number of studies. In this review, we summarize and discuss the mechanism underlying the protective effect of gaseous signaling molecules on myocardial ischemic injury.

Objective: Hepatic encephalopathy (HE) characterized by neuropsychiatric abnormalities is a major complication of cirrhosis with high mortality. However, the pathogenesis of HE has not been fully elucidated. This study aimed to determine endogenous hydrogen sulfide (H2S) in the blood of HE patients and investigate the role of H2S in an astrocytic model of HE. Methods: Patients with and without HE were recruited to determine plasma H2S levels and blood microbial 16S rRNA gene. Rat astrocytes were employed as a model of HE by treatment of NH4Cl. Exogenous H2S was preadded. Cell viability was measured by Cell Counting Kit-8 (CCK-8) assay, and cell death was evaluated by lactate dehydrogenase (LDH) release. Apoptosis was determined by Hoechst 33342/Propidium Iodide (PI) Double Staining and Western blot analysis of apoptosis-related protein expression. Intracellular reactive oxygen species (ROS) levels were assessed by flow cytometer. Expressions of Nrf2 and its downstream regulated genes were examined by immunofluorescence staining and Western blot, respectively. Nrf2 gene knockdown was performed by antisense shRNA of Nrf2 gene. Results: There was a significant decrease in H2S levels in cirrhotic patients with HE compared with without HE. Blood microbiota analyses revealed that certain strains associated with H2S production were negatively correlated with HE. In vitro, H2S markedly attenuated NH4Cl-induced cytotoxicity, oxidative stress, and apoptosis. This effect was mediated by Nrf2/ARE signaling, and knockdown of Nrf2 expression abolished the antagonistic effect of H2S on NH4Cl-induced neurotoxicity in astrocytes. Conclusion: Levels of H2S and bacteria associated with H2S production are decreased in HE, and H2S functions as the neuroprotector against NH4Cl-induced HE by activating Nrf2/ARE signaling of astrocytes.

Three waste-derived adsorbent materials (wood-derived biochar, sludge-derived activated carbon and activated ash) were pre-activated at the laboratory scale to apply them for the removal of H2S from a biogas stream. The H2S removal capabilities of each material were measured by a mass spectrometer, to detect the H2S concentration after the adsorption in an ambient environment. The activated ash adsorbent has the highest removal capacity at 3.22 mgH2S g&minus, 1, while wood-derived biochar has slightly lower H2S removal capability (2.2 mgH2S g&minus, 1). The physicochemical properties of pristine and spent materials were characterized by the thermogravimetric analyzer, elemental analysis, X-ray fluorescence spectroscopy and N2 adsorption and desorption. Wood-derived biochar is a highly porous material that adsorbs H2S by physical adsorption of the mesoporous structure. Activated ash is a non-porous material which adsorbs H2S by the reaction between the alkaline compositions and H2S. This study shows the great potential to apply waste-derived adsorbent materials to purify a biogas stream by removing H2S.

Introduction Kawasaki disease (KD) is an idiopathic, acute systemic vasculitis typically affecting medium-sized blood vessels with an inclination towards the coronary arteries. There is no specific diagnostic test established for it yet. Hence, our study aims to evaluate serum N-terminal pro-brain natriuretic peptide (NT-proBNP), hydrogen sulfide (H2S), and interleukin-6 (IL-6) levels as potential diagnostic tools in children with KD and determine its relationship with the development of coronary artery lesions (CAL) in the pediatric population visiting a tertiary care hospital in Karachi. Methods A prospective observational study was performed on a sample of 500 children at a tertiary care hospital over a period of two years from June 2017 to June 2019. Blood samples were collected from two groups labeled CAL and non-coronary artery lesion (NCAL), and different biomarkers including NT-proBNP, IL-6, and H2S were compared between them to predict the diagnostic properties of each marker. Results Among the 500 children, 50% were between the age of one to five years. All presented with fever and varying degrees of associated symptoms. On lab investigations, levels of NT-proBNP and IL-6 during the acute phase of the disease were found to be higher in the CAL group than the NCAL and control groups (p

The present study was designed to investigate the role of amylin, H2S, and connexin 43 in vascular dysfunction and enhanced ischemia–reperfusion (I/R)-induced myocardial injury in diabetic rats. A single dose of streptozotocin (65 mg/kg) was employed to induce diabetes mellitus. After 8 weeks, there was a significant decrease in the plasma levels of amylin, an increase in I/R injury to isolated hearts (increase in CK-MB and cardiac troponin release) on the Langendorff apparatus. Moreover, there was a significant impairment in vascular endothelium function as assessed by quantifying acetylcholine-induced relaxation in norepinephrine-precontracted mesenteric arteries. There was also a marked decrease in the expression of H2S and connexin 43 in the hearts following I/R injury in diabetic rats. Treatment with amylin agonist, pramlintide (100 and 200 µg/kg), and H2S donor, NaHS (10 and 20 μmol/kg) for 2 weeks improved the vascular endothelium function, abolished enhanced myocardial injury and restored the levels of H2S along with connexin 43 in diabetic animals. However, pramlintide and NaHS failed to produce these effects the presence of gap junction blocker, carbenoxolone (20 and 40 mg/kg). Carbenoxolone also abolished the myocardial levels of connexin 43 without affecting the plasma levels of amylin and myocardial levels of H2S. The decrease in the amylin levels with a consequent reduction in H2S and connexin 43 may contribute to inducing vascular dysfunction and enhancing I/R-induced myocardial injury in diabetic rats.

The activation of capsaicin-sensitive lung vagal (CSLV) afferents can elicit airway reflexes. Hypersensitivity of these afferents is known to contribute to the airway hypersensitivity during airway inflammation. Hydrogen sulfide (H2S) has been suggested as a potential therapeutic agent for airway hypersensitivity diseases, such as asthma, because of its relaxing effect on airway smooth muscle and anti-inflammatory effect. However, it is still unknown whether H2S affects airway reflexes. Our previous study demonstrated that exogenous application of H2S sensitized CSLV afferents and enhanced Ca2+ transients in CSLV neurons. The present study aimed to determine whether the H2S-induced sensitization leads to functional changes in airway reflexes and elevates the electrical excitability of the CSLV neurons. Our results showed that, first and foremost, in anesthetized, spontaneously breathing rats, the inhalation of aerosolized sodium hydrosulfide (NaHS, a donor of H2S, 5 mg/mL, 3 min.) caused an enhancement in apneic response evoked by several stimulants of the CSLV afferents. This enhancement effect was found 5 min. after NaHS inhalation and returned to control 30 min. later. However, NaHS no longer enhanced the apneic response after perineural capsaicin treatment on both cervical vagi that blocked the conduction of CSLV fibers. Furthermore, the enhancing effect of NaHS on apneic response was totally abolished by pretreatment with intravenous HC-030031 (a TRPA1 antagonist, 8 mg/kg), whereas the potentiating effect was not affected by the pretreatment with the vehicle of HC-030031. We also found that intracerebroventricular infusion pretreated with HC-030031 failed to alter the potentiating effect of NaHS on the apneic response. Besides, the cough reflex elicited by capsaicin aerosol was enhanced by inhalation of NaHS in conscious guinea pigs. Nevertheless, this effect was entirely eliminated by pretreatment with HC‐030031, not by its vehicle. Last but not least, voltage-clamp electrophysiological analysis of isolated rat CSLV neurons showed a similar pattern of potentiating effects of NaHS on capsaicin-induced inward current, and the involvement of TRPA1 receptors was also distinctly shown. In conclusion, these results suggest that H2S non-specifically enhances the airway reflex responses, at least in part, through action on the TRPA1 receptors expressed on the CSLV afferents. Therefore, H2S should be used with caution when applying for therapeutic purposes in airway hypersensitivity diseases.

Ammonium tetrathiomolybdate (ATTM) has been used in breast cancer therapy for copper chelation, as elevated copper promotes tumor growth. ATTM is also an identified H2S donor and endogenous H2S facilitates VitB12-induced S-adenosylmethionine (SAM) generation, which have been confirmed in m6A methylation and lung cancer development. The m6A modification was recently shown to participate in lung adenocarcinoma (LUAD) progression. These conflicting analyses of ATTM's anticancer vs. H2S's carcinogenesis suggest that H2S should not be ignored during LUAD's treatment with ATTM. This study was aimed to explore ATTM's effects on LUAD cells and mechanisms associated with H2S and m6A. It was found that treatment with ATTM inhibited cell growth at high concentrations, while enhanced cell growth at low concentrations in three LUAD cell lines (A549, HCC827, and PC9). However, another copper chelator triethylenetetramine, without H2S releasing activity, was not found to induce cell growth. Low ATTM concentrations also elevated m6A content in A549 cells. Analysis of differentially expressed genes in TCGA cohort indicated that m6A writer METTL3 and reader YTHDF1 were upregulated while eraser FTO was downregulated in LUAD tissues, consistent with the findings of protein expression in patient tissues. ATTM treatment of A549 cells significantly increased METTL3/14 and YTHDF1 while decreased FTO expression. Furthermore, inhibition of m6A with shMETTL3 RNA significantly attenuated eukaryotic translation initiation factor (eIF) expressions in A549 cells. Correlation analysis indicated that small nuclear ribonucleic protein PRPF6 was positively expressed with YTHDF1 in LUAD tissues. Knockdown of YTHDF1 partially blocked both basal and ATTM-induced PRPF6 expression, as well as A549 cell growth. Lastly, ATTM treatment not only raised intracellular H2S content but also upregulated H2S-producing enzymes. Exogenous H2S application mimicked ATTM's aforementioned effects, but the effects could be weakened by zinc-induced H2S scavenging. Collectively, H2S impedes ATTM-induced anticancer effects through YTHDF1-dependent PRPF6 m6A methylation in lung adenocarcinoma cells.

Exposure to toxic metals and metalloids is an important cause of preventable diseases worldwide. Inorganic arsenic (iAs) affects several organs and tissues, causing neurobehavioral alterations in the central nervous system (CNS) that might lead to neurodegeneration. In this work, we wanted to explore the time- and dose-related changes on glutathione (GSH) levels in several regions of the CNS, such as the cortex, striatum, hippocampus, and cerebellum, to identify the initial cellular changes associated to GSH depletion due to iAs exposure. Mice received a single intraperitoneal injection containing 5 or 14 mg/kg sodium arsenite. Animals were killed at 2, 6, and 24 h. Significant depletion of GSH levels was observed in the cortex at 2 and 6 h, while on the striatum, hippocampus, or cerebellum regions, no significant changes were observed. GSH depletion in the cortex was associated with the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NFκB) pathways, which led to the upregulation of xCT, excitatory amino acid carrier 1 (EAAC1), glutamate/aspartate transporter (GLAST), and glial glutamate transporter 1 (GLT-1), and the activation of the transsulfuration pathways, which led to the overproduction of H2S in the cortex and increased levels of GSH in the cortex and cerebellum at 24 h. In the cortex, the N-methyl-D-aspartate (NMDA) receptor subunits NR2A and NR2B were also altered at 24 h. These early effects were not homogeneous among different brain regions and indicate early neurotoxic alterations in the cortex and cerebellum.

Background To investigate the effect and mechanisms of exogenous hydrogen sulfide in surgery-induced neuroinflammatory cognitive dysfunction. Methods C57BL/6 J male mice (n = 140) were used and randomly divided into seven groups: the sham group, surgery group, GYY4137 group, L-NAME group, surgery+GYY4137 group, surgery +L-NAME group, and surgery+GYY4137 + L-NAME group. After the interventions, open field tests (OFT) and the Morris water maze (MWM) test were conducted to evaluate learning and memory abilities in the mice. ELISAs, nitrate reductase assays, and Western blots (WB) were conducted to evaluate interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and antioxidant enzyme superoxide dismutase (SOD) levels. Furthermore, the expression level of microglial marker ionized calcium binding adaptor molecule 1 (IBA) in the hippocampal CA1 and CA3 areas was detected by an immunohistochemical (IHC) assay and apoptotic cells were observed using terminal deoxynucleotidyl transferase dUTP end-labeling (TUNEL) staining kits. Results We found that surgery induced neuroinflammatory cognitive dysfunction, oxidative stress, microglial activation, and cell apoptosis in the hippocampus. Moreover, following surgery, NO and iNOS levels were elevated in the hippocampus. Notably, all the effects caused by surgery were reversed by the H2S donor GYY4137 or the iNOS inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME). However, the combined application of GYY4137 and L-NAME was not superior to treatment with either agent alone and the effect of GYY4137 was similar to that of L-NAME. Conclusion The long-acting hydrogen sulfide donor GYY4137 had an ability to reversed the cognitive deficits and inflammation caused by carotid artery exposure surgery. This implies that NO signaling pathways might participate in this process. These results indicate that exogenous H2S may be a promising therapy for POCD.

Nitric Oxide (NO) is internationally regarded as a signal molecule involved in several functions in the respiratory tract under physiological and pathogenic conditions. Hydrogen Sulfide (H2S) has also recently been recognized as a new gasotransmitter with a diverse range of functions similar to those of NO. Depending on their respective concentrations, both these molecules act synergistically or antagonistically as signals or damage promoters. Nevertheless, available evidence shows that the complex biological connections between NO and H2S involve multiple pathways and depend on the site of action in the respiratory tract, as well as on experimental conditions. This review will provide an update on these two gasotransmitters in physiological and pathological processes.

Excessive exposure to hydrogen sulfide (H2S) and acetic acid (CH3COOH) gases is extremely dangerous in a confined space. An effective indoor air pollutant removal porous carbon filter was developed using NaOH impregnated on activated carbon (NaOH/AC) for the adsorption of H2S and CH3COOH. Activated carbon (NaOH/AC) filter was characterized using various methods, indicating good physical and chemical properties (especially ‐OH functional groups) for the adsorption of air pollutants. The prepared NaOH/AC filter was cured at different curing temperatures and residence times to understand the effect of the curing conditions on the adsorption performance. The best results were obtained with NaOH/AC filter cured at 100°C for 20 minutes as it eliminated the initial concentration of 400 ppm of CH3COOH in 15 minutes and H2S in 30 minutes at 20°C and 60% relative humidity. Isotherm and kinetic models were used to analyze the adsorption process. Langmuir isotherm and pseudo‐second order kinetic models provided the best fit to the adsorption of CH3COOH and H2S on NaOH/AC filter. The adsorption mechanism was controlled by the intraparticle diffusion combined with film diffusion. The maximum adsorption capacity of NaOH/AC filter was 473 mg/g for H2S adsorption, and 550 mg/g for CH3COOH adsorption. In addition, the spent NaOH/AC filter was regenerated for reuse. This study is expected to develop low‐cost and effective porous carbon filter using NaOH‐modified activated carbon for indoor air purification.

Chronic persistent stress is an important cause of gastritis, but the underlying mechanism remains to be further researched, especially the role of the gastric microbiota in this process. Here, we used the water avoidance stress (WAS) test in mouse models for chronic stress‐induced gastritis to investigate the underlying mechanisms of this disease. The effect of stress on the gastric microbiota was analyzed based on 16S rRNA sequencing; the changes in hydrogen sulfide (H2S) and inflammatory cytokine levels in gastric tissues were detected by Western blotting, ELISA, immunofluorescence, and qRT‐PCR. Hematoxylin and eosin staining was used as an indicator of the gastritis histological score. This finding is consistent with previous studies showing that gastric H2S is negatively associated with the inflammatory index and might protect the gastrointestinal tract from inflammation. WAS‐induced gastritis was associated with a reduction in H2S release, which appeared to affect the homeostasis of the gastric microbiota of mice. Inflammation and microbial dysbiosis were partially reversed by sodium hydrosulfide (NaHS) and vitamin B6 (VB6) supplementation, suggesting the therapeutic potential of VB6 supplementation for the treatment of stress‐induced gastritis. Gastritis has a serious impact on health and quality of life. An increasing number of people are suffering from chronic gastritis linked to a high‐stress lifestyle, and our research provides clues for the prevention and treatment of stress‐induced gastritis., Chronic persistent stress is an important cause of gastritis, but the underlying mechanism remains to be further researched. Here, we used the water avoidance stress test in mouse models for chronic stress‐induced gastritis to investigate the underlying mechanisms of this disease. Stress‐induced gastritis was associated with a reduction in hydrogen sulfide release, which appeared to affect the homeostasis of the gastric microbiota of mice.

Background/Aims: Deguelin is a natural rotenoid that shows anti-inflammatory and antimicrobial activities. Rotenoids prevent oxidative damage and potentiate natural antioxidant activity in diabetic conditions, suggesting utility in treating diabetes and its complications. Here, we evaluate the potential efficacy of deguelin against diabetic neuropathy (DN). Methods: DN was induced by streptozotocin followed by daily treatment with deguelin (4, 6 or 8 mg/kg) for 14 days. Blood glucose was measured, neurobehavioral tests for nociception and motor coordination were performed, and neuron conduction velocities were analysed electrophysiologically. We also assessed (Na+-K+) ATPase activity, performed a reactive oxygen species assay, measured the levels of various markers of oxidative stress, and of hydrogen sulphide (H2S) in dorsal root ganglion (DRG) neurons, conducted immunoblotting studies for proteins and ELISA for inflammatory cytokines. Results: Deguelin significantly suppressed mechanical and thermal hyperalgesia, as well as cold allodynia, and partially restored the conduction velocities of neurons in DN rats. Significantly decreased expression levels of capspase-3 in DRG neurons, and increased (Na+-K+) ATPase activity in sciatic nerves, were observed. In addition, deguelin decreased glucose levels, attenuated oxidative stress and neuroinflammation, and elevated levels of H2S, nuclear respiratory factor 2 (Nrf2) and heme oxygenase-1, suggesting a disease-attenuating effect of deguelin in DN rats. To shed light on the underlying mechanism of action of deguelin, insulin- and dimethyl fumarate (BG-12)-treated groups were also included. Insulin suppressed glucose levels and BG-12 produced effects on Nrf2 levels similar to 8 mg/kg deguelin, confirming involvement of the Nrf2 pathway in the beneficial effects of deguelin against DN. Conclusions: Deguelin attenuated DN by decreasing oxidative stress and plasma glucose levels via the Nrf2 signalling pathway.

Background: Cardiovascular disease is the leading cause of death. The etiology of this disease is multifactorial, with unhealthy nutrition being one of the main risk factors. Diets high in animal fats and saturated fatty acid have been associated with an increased risk for cardiovascular diseases. However, the results of investigations on the effects of lard (LO)- and palm oil (PO) on cardiovascular risk are still controversial due to the dosages used and the age of the animals investigated. Objective: We investigated whether LO or PO consumption led to different effects on blood pressure, vascular functions, and lipid profiles within middle-aged rats. Methods: The study was performed in middle-aged male rats, n = 6 for each group. LO, PO, or distilled water (control) 1 or 3 ml/kg were orally gavaged once a day for 6 weeks. Basal blood pressure and heart rate were measured in anesthetized rats. Fasting serum lipids were measured by enzymatic methods. The vascular functions of isolated thoracic aorta were studied using pharmacological techniques in the absence or presence of N-nitro-L-arginine, a nitric oxide synthase (eNOS) inhibitor and or DL-propargylglycine (PAG), a cystothionine-γ-lyase (CSE) inhibitor. Additionally, the aortic wall eNOS and CSE protein expression were measured by Western blotting. Results: In comparison to the control group (distilled water, DW), no differences were observed in any of the parameters studied after the rats took 1 ml/kg of LO or PO. However, PO caused an increase in neutrophil/lymphocyte ratio and body fat. At 3 ml/kg dosage, LO caused increased basal blood pressure (LO, 153.4 ± 3.2; DW, 131.4 ± 3.2 mm Hg for systolic blood pressure and LO, 130.9 ± 2.5; DW, 107.9 ± 5.8 mmHg for diastolic blood pressure) body and liver cell lipid accumulation, while PO led to increased body fat and fasting serum triglyceride (PO, 131.5 ± 13.2; DW, 91.8 ± 4.8 mg %). Neither LO nor PO treatment had any effect on vascular contraction to phenylephrine, except in the presence of PAG which led to an increased contractile response to phenylephrine. PO but not LO treatment caused increased vascular wall CSE protein expression. Conclusion : The results document how both LO and PO at a dose of 3 ml/kg (corresponding to three servings of Thai fast food) cause increased cardiovascular risk factors. However, the blood vessel H 2 S production increased while the lower dose had a minimal effect. Keywords : Lard oil; Palm oil; blood vessel; liver lipid; NO; H 2 S