scholarly journals Microbial Cysteine Degradation Drives Cryptic Sulfide Redox Chemistry in the Gut

2021 ◽  
Author(s):  
Sarah Wolfson ◽  
Reese Hitchings ◽  
Karina Peregrina ◽  
Ziv Cohen ◽  
Saad Khan ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Microbial Community ◽  
Dynamic Environment ◽  
Xenobiotic Metabolism ◽  
Sulfide Concentration ◽  
Bacterial Cultures ◽  
Redox Partner ◽  
First Time ◽  
Missing Feature

Abstract Although microbial biochemistry shapes a dynamic environment in the gut, how bacterial metabolites such as hydrogen sulfide (H2S) mechanistically alter the gut chemical landscape is poorly understood. Here we show for the first time that H2S generated during cysteine metabolism drives the reduction of azo (R-N=N-R’) xenobiotics in bacterial cultures, human fecal microbial communities, and in vivo mouse models. Thus, chemical-chemical interactions, derived from microbial community metabolism, are a key missing feature shaping xenobiotic metabolism in the gut. Changing dietary levels of the H2S xenobiotic redox partner Red 40 transiently decreases mouse fecal sulfide, confirming that a xenobiotic can attenuate sulfide concentration in vivo. Cryptic H2S redox thus modulates sulfur homeostasis in the gut and the fate of xenobiotics to which humans are regularly exposed.

Hydrogen sulfide and its possible roles in myocardial ischemia in experimental rats

2007 ◽  
Vol 102 (1) ◽  
pp. 261-268 ◽  
Author(s):  
Yi Zhun Zhu ◽  
Zhong Jing Wang ◽  
Peiying Ho ◽  
Yoke Yun Loke ◽  
Yi Chun Zhu ◽  
...  
Keyword(s):  
Cell Death ◽  
Hydrogen Sulfide ◽  
Rat Model ◽  
Protein Localization ◽  
Sodium Hydrosulfide ◽  
Infarct Area ◽  
Novel Approach ◽  
First Time

The role of hydrogen sulfide (H2S) in myocardial infarction (MI) has not been previously studied. We therefore investigated the effect of H2S in a rat model of MI in vivo. Animals were randomly divided into three groups ( n = 80) and received either vehicle, 14 μmol/kg of sodium hydrosulfide (NaHS), or 50 mg/kg propargylglycine (PAG) everyday for 1 wk before surgery, and the treatment was continued for a further 2 days after MI when the animals were killed. The mortality was 35% in vehicle-treated, 40% in PAG-treated, and 27.5% in NaHS-treated ( P < 0.05 vs. vehicle) groups. Infarct size was 52.9 ± 3.5% in vehicle-treated, 62.9 ± 7.6% in PAG-treated, and 43.4 ± 2.8% in NaHS-treated ( P < 0.05 vs. vehicle) groups. Plasma H2S concentration was significantly increased after MI (59.2 ± 7.16 μM) compared with the baseline concentration (i.e., 38.2 ± 2.07 μM before MI; P < 0.05). Elevated plasma H2S after MI was abolished by treatment of animals with PAG (39.2 ± 5.02 μM). We further showed for the first time cystathionine-gamma-lyase protein localization in the myocardium of the infarct area by using immunohistochemical staining. In the hypoxic vascular smooth muscle cells, we found that cell death was increased under the stimuli of hypoxia but that the increased cell death was attenuated by the pretreatment of NaHS (71 ± 1.2% cell viability in hypoxic vehicle vs. 95 ± 2.3% in nonhypoxic control; P < 0.05). In conclusion, endogenous H2S was cardioprotective in the rat model of MI. PAG reduced endogenous H2S production after MI by inhibiting cystathionine-gamma-lyase. The results suggest that H2S might provide a novel approach to the treatment of MI.

Endogenous hydrogen sulfide sulfhydrates IKKβ at cysteine 179 to control pulmonary artery endothelial cell inflammation

2019 ◽  
Vol 133 (20) ◽  
pp. 2045-2059 ◽  
Author(s):  
Da Zhang ◽  
Xiuli Wang ◽  
Siyao Chen ◽  
Selena Chen ◽  
Wen Yu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Endothelial Cell ◽  
Pulmonary Artery ◽  
Cell Model ◽  
Site Directed Mutagenesis ◽  
Critical Event ◽  
Hypertensive Rats ◽  
Pulmonary Artery Endothelial Cell

Abstract Background: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear. Methods: Purified recombinant human inhibitor of κB kinase subunit β (IKKβ) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein. Results: We showed that hydrogen sulfide (H2S) inhibited IKKβ activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine γ-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKKβ activity directly via sulfhydrating IKKβ at cysteinyl residue 179 (C179) in purified recombinant IKKβ protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKKβ inactivation. Furthermore, to demonstrate the significance of IKKβ sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKKβ. In purified IKKβ protein, C179S mutation of IKKβ abolished H2S-induced IKKβ sulfhydration and the subsequent IKKβ inactivation. In human PAECs, C179S mutation of IKKβ blocked H2S-inhibited IKKβ activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKKβ abolished the inhibitory effect of H2S on IKKβ activation and pulmonary vascular inflammation and remodeling. Conclusion: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKKβ via sulfhydrating IKKβ at Cys179 to inhibit nuclear factor-κB (NF-κB) pathway activation and thereby control PAEC inflammation in PAH.

ADT-OH, a Hydrogen Sulfide-Releasing Donor, Induces Apoptosis of Melanoma Cells and Inhibits Melanoma Development In Vivo

2019 ◽  
Author(s):  
Fangfang Cai ◽  
Nini Cao ◽  
Xiangyu Zhang ◽  
Jia Liu ◽  
Huangru Xu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Melanoma Cells

scholarly journals Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 819
Author(s):  
Nicolai Rügen ◽  
Timothy P. Jenkins ◽  
Natalie Wielsch ◽  
Heiko Vogel ◽  
Benjamin-Florian Hempel ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Galleria Mellonella ◽  
Systemic Reactions ◽  
Venom Composition ◽  
Assassin Bug ◽  
Molecular Components ◽  
First Time ◽  
Tissue Digestion

Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications.

Carbon dots derived from Fusobacterium nucleatum for intracellular determination of Fe3+ and bioimaging both in vitro and in vivo

2021 ◽  
Author(s):  
Lijuan Liu ◽  
Shengting Zhang ◽  
Xiaodan Zheng ◽  
Hongmei Li ◽  
Qi Chen ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Fusobacterium Nucleatum ◽  
Living Cells ◽  
First Time ◽  
Fluorescent Carbon Dots ◽  
Fluorescent Carbon

Fusobacterium nucleatum has been employed for the first time to synthesize fluorescent carbon dots which could be applied for the determination of Fe3+ ions in living cells and bioimaging in vitro and in vivo with excellent biocompatibility.

scholarly journals Anti-Tumor and Anti-Inflammatory Activity In Vivo of Apodanthera congestiflora Cogn. (Cucurbitaceae)

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 743
Author(s):  
Geovana F. G. Silvestre ◽  
Renally P. Lucena ◽  
Genil D. Oliveira ◽  
Helimarcos N. Pereira ◽  
Jhonatta A. B. Dias ◽  
...  
Keyword(s):  
Inflammatory Activity ◽  
Phytochemical Investigation ◽  
Significant Toxicity ◽  
Biological Tests ◽  
Ehrlich's Carcinoma ◽  
Anti Inflammatory ◽  
Pharmacological Potential ◽  
First Time ◽  
Anti Tumor Activity

This work aimed to carry out a study of Apodanthera congestiflora by investigating its chemical composition and pharmacological potential. From the dichloromethane phase (Dic-Ac) of the A. congestiflora stems, three compounds were identified: cayaponoside C5b (Ac-1), cabenoside C (Ac-2) and fevicordin C2 glucoside (Ac-3), being last identified for the first time as a natural product. These compounds were obtained by chromatographic methods and their structures were elucidated by means of spectroscopic analysis of IR, MS and NMR. In the quantification of Dic-Ac, it was possible to observe the presence of 7% of cayaponoside C5b. Dic-Ac showed significant toxicity for in vivo tests, with macroscopic and biochemical changes. The anti-inflammatory activity of Dic-Ac was investigated using the paw edema model. A decrease in inflammatory signs was observed in the first 5 h and the most effective dose in reducing edema with was 7.5 mg kg−1 (66.6%). Anti-tumor activity of Dic-Ac was evaluated by Ehrlich’s carcinoma model, which showed inhibition rate of 78.46% at 15 mg kg−1 dosage. The phytochemical investigation, together with the biological tests carried out in this study, demonstrated that A. congestiflora is a promising species in the search for therapeutics, since it contains substances with high pharmacological potential in its composition.

scholarly journals PSIX-9 Impacts of bunk management on feedlot performance, carcass characteristics, hydrogen sulfide concentration and blood oxygen saturation in steers fed 25 or 50% modified distillers grains plus solubles

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 422-422
Author(s):  
Rebecca L Moore ◽  
Cierrah J Kassetas ◽  
Leslie A LeKatz ◽  
Bryan W Neville
Keyword(s):  
Hydrogen Sulfide ◽  
Oxygen Saturation ◽  
Management Strategy ◽  
Distillers Grains ◽  
Feed Ratio ◽  
Sulfide Concentration ◽  
Blood Oxygen ◽  
Blood Oxygen Saturation ◽  
Feedlot Performance ◽  
Arterial Blood

Abstract One hundred and twenty-six yearling angus steers (initial body weight 445.87 ± 7.13 kg) were utilized in a 2 x 2 factorial design to evaluate the impacts of bunk management and modified distillers grains plus solubles (mDGS) inclusion on feedlot performance, hydrogen sulfide concentrations and blood oxygen saturation. Treatments included bunk management strategy either control bunk management (CON; clean bunks at the time of next day’s feeding) or long bunk management (LONG; feed remaining at time of next day’s feeding), and two inclusion rates of mDGS either 25% or 50% (DM Basis). On d 0, 7, 14, 21, 28 and 35 rumen gas samples were collected via rumenocentesis, and arterial blood samples were collected on two steers from each pen. No differences (P ≥ 0.09) were observed for dry matter intake, average daily gain and gain-to-feed ratio for bunk management or mDGS inclusion. Hot carcass weight, ribeye area, marbling score and quality grade were not affected (P ≥ 0.48) by either bunk management or mDGS inclusion. Back fat was greater (P = 0.04) for CON steers compared to LONG (1.30 vs 1.12 ± 0.05cm, respectively), but was not affected (P = 0.59) by mDGS inclusion. Steers on CON had greater (P = 0.03) yield grades compared to LONG (3.21 vs 2.96 ± 0.11, respectively). Bunk management strategy did not impact hydrogen sulfide concentrations or blood oxygen saturation (P = 0.82). Hydrogen sulfide concentrations increased (P &lt; 0.001) with increasing mDGS inclusion. Blood oxygen saturation was influenced by day of sampling (P = 0.01). Blood oxygen saturation was not affected (P = 0.07) by mDGS inclusion. The fact that ruminal hydrogen sulfide concentrations increased while blood oxygen saturation remained similar raises questions about the quantity of hydrogen sulfide and metabolic fate of excess hydrogen sulfide in the blood of ruminant animals.

scholarly journals The antimicrobial potential of cannabidiol

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mark A. T. Blaskovich ◽  
Angela M. Kavanagh ◽  
Alysha G. Elliott ◽  
Bing Zhang ◽  
Soumya Ramu ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Modern Medicine ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
New Class ◽  
Clostridioides Difficile ◽  
Excellent Activity ◽  
Induce Resistance ◽  
First Time

AbstractAntimicrobial resistance threatens the viability of modern medicine, which is largely dependent on the successful prevention and treatment of bacterial infections. Unfortunately, there are few new therapeutics in the clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation of the antimicrobial activity of cannabidiol, the main non-psychoactive component of cannabis. We confirm previous reports of Gram-positive activity and expand the breadth of pathogens tested, including highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile. Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism. More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the ‘urgent threat’ pathogen Neisseria gonorrhoeae. Structure-activity relationship studies demonstrate the potential to advance cannabidiol analogs as a much-needed new class of antibiotics.

scholarly journals Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 481
Author(s):  
Gemma G. Martínez-García ◽  
Raúl F. Pérez ◽  
Álvaro F. Fernández ◽  
Sylvere Durand ◽  
Guido Kroemer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Mammalian Cells ◽  
Tissue Homeostasis ◽  
In Vivo Studies ◽  
Protective Mechanism ◽  
Cardiac Damage ◽  
Wide Range ◽  
First Time

Autophagy is an essential protective mechanism that allows mammalian cells to cope with a variety of stressors and contributes to maintaining cellular and tissue homeostasis. Due to these crucial roles and also to the fact that autophagy malfunction has been described in a wide range of pathologies, an increasing number of in vivo studies involving animal models targeting autophagy genes have been developed. In mammals, total autophagy inactivation is lethal, and constitutive knockout models lacking effectors of this route are not viable, which has hindered so far the analysis of the consequences of a systemic autophagy decline. Here, we take advantage of atg4b−/− mice, an autophagy-deficient model with only partial disruption of the process, to assess the effects of systemic reduction of autophagy on the metabolome. We describe for the first time the metabolic footprint of systemic autophagy decline, showing that impaired autophagy results in highly tissue-dependent alterations that are more accentuated in the skeletal muscle and plasma. These changes, which include changes in the levels of amino-acids, lipids, or nucleosides, sometimes resemble those that are frequently described in conditions like aging, obesity, or cardiac damage. We also discuss different hypotheses on how impaired autophagy may affect the metabolism of several tissues in mammals.

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