The Optimization of Renal Graft Preservation Temperature to Mitigate Cold Ischemia-Reperfusion Injury in Kidney Transplantation

Renal transplantation is the preferred treatment for patients with end-stage renal disease. The current gold standard of kidney preservation for transplantation is static cold storage (SCS) at 4 °C. However, SCS contributes to renal ischemia-reperfusion injury (IRI), a pathological process that negatively impacts graft survival and function. Recent efforts to mitigate cold renal IRI involve preserving renal grafts at higher or subnormothermic temperatures. These temperatures may be beneficial in reducing the risk of cold renal IRI, while also maintaining active biological processes such as increasing the expression of mitochondrial protective metabolites. In this review, we discuss different preservation temperatures for renal transplantation and pharmacological supplementation of kidney preservation solutions with hydrogen sulfide to determine an optimal preservation temperature to mitigate cold renal IRI and enhance renal graft function and recipient survival.     

Design,Synthesis and Evaluation of Novel Molecular Hybrids between Antiglaucoma Drugs and H2S Donors

Glaucoma is a group of eye diseases consisting of optic nerve damage with corresponding loss of field vision and blindness. Hydrogen sulfide (H₂S) is a gaseous neurotransmitter implicated in various pathophysiological processes. It is involved in the pathological mechanism of glaucomatous neuropathy and exerts promising effects in the treatment of this disease. In this work, we designed and synthetized new molecular hybrids between antiglaucoma drugs and H₂S donors to combine the pharmacological effect of both moieties, providing a heightened therapy. Brinzolamide, betaxolol and brimonidine were linked to different H₂S donors. The H₂S-releasing properties of the new compounds were evaluated in a phosphate buffer solution by the amperometric approach, and evaluated in human primary corneal epithelial cells (HCEs) by spectrofluorometric measurements. Experimental data showed that compounds 1c, 1d and 3d were the hybrids with the best properties, characterized by a significant and long-lasting production of the gasotransmitter both in the aqueous solution (in the presence of L-cysteine) and in the intracellular environment. Because, to date, the donation of H₂S by antiglaucoma H₂S donor hybrids using non-immortalized corneal cells has never been reported, these results pave the way to further investigation of the potential efficacy of the newly synthesized compounds.     

Hydrogen Sulfide and Its Donors: Keys to Unlock the Chains of Nonalcoholic Fatty Liver Disease

Hydrogen sulfide (H₂S) has emerged as the third “gasotransmitters” and has a crucial function in the diversity of physiological functions in mammals. In particular, H₂S is considered indispensable in preventing the development of liver inflammation in the case of excessive caloric ingestion. Note that the concentration of endogenous H₂S was usually low, making it difficult to discern the precise biological functions. Therefore, exogenous delivery of H₂S is conducive to probe the physiological and pathological roles of this gas in cellular and animal studies. In this review, the production and metabolic pathways of H₂S in vivo, the types of donors currently used for H₂S release, and study evidence of H₂S improvement effects on nonalcoholic fatty liver disease are systematically introduced.     

Inhalative as well as Intravenous Administration of H2S Provides Neuroprotection after Ischemia and Reperfusion Injury in the Rats’ Retina

Background: Neuronal ischemia-reperfusion injury (IRI), such as it can occur in glaucoma or strokes, is associated with neuronal cell death and irreversible loss of function of the affected tissue. Hydrogen sulfide (H₂S) is considered a potentially neuroprotective substance, but the most effective route of application and the underlying mechanism remain to be determined. Methods: Ischemia-reperfusion injury was induced in rats by a temporary increase in intraocular pressure (1 h). H₂S was then applied by inhalation (80 ppm at 0, 1.5, and 3 h after reperfusion) or by intravenous administration of the slow-releasing H₂S donor GYY 4137. After 24 h, the retinas were harvested for Western blotting, qPCR, and immunohistochemical staining. Retinal ganglion cell survival was evaluated 7 days after ischemia. Results: Both inhalative and intravenously delivered H₂S reduced retinal ganglion cell death with a better result from inhalative application. H₂S inhalation for 1.5 h, as well as GYY 4137 treatment, increased p38 phosphorylation. Both forms of application enhanced the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and inhalation showed a significant increase at all three time points. H₂S treatment also reduced apoptotic and inflammatory markers, such as caspase-3, intracellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase (iNOS). The protective effect of H₂S was partly abolished by the ERK1/2 inhibitor PD98059. Inhalative H₂S also reduced the heat shock response including heme oxygenase (HO-1) and heat shock protein 70 (HSP-70) and the expression of radical scavengers such as superoxide dismutases (SOD1, SOD2) and catalase. Conclusion: Hydrogen sulfide acts, at least in part, via the mitogen-activated protein kinase (MAPK) ERK1/2 to reduce apoptosis and inflammation. Both inhalative H₂S and intravenous GYY 4137 administrations can improve neuronal cell survival.     

The intermolecular interaction studies in the complexes of isothiocyanic acid (HNCS) and its derivatives with H2S: a computational study

The computational investigations are carried out on the complexes of isothiocyanic acid (HNCS) and its derivatives with H₂S through MP2/aug-cc-PVTZ//MP2/aug-cc-PVDZ level. Five, four, three and four structures are located on the potential energy surface of the HNCS?H₂S, HSCN? H₂S, HCNS? H₂S and HSNC?H₂S heterodimers, respectively. The calculated results reveal that the most stable heterodimers among all heterodimers obtained for the HNCS?H₂S, HSCN?H₂S, HCNS?H₂S and HSNC?H₂S systems belong to HSCN?H₂S system. Therefore, HSCN?H₂S system has a key role in the atmosphere.     

The Effects of H2S on the Activities of CYP2B6, CYP2D6, CYP3A4, CYP2C19 and CYP2C9 in Vivo in Rat

Hydrogen sulfide (H₂S) is a colorless, flammable, extremely hazardous gas with a “rotten egg” smell. The human body produces small amounts of H₂S and uses it as a signaling molecule. The cocktail method was used to evaluate the influence of H₂S on the activities of CYP450 in rats, which were reflected by the changes of pharmacokinetic parameters of five specific probe drugs: bupropion, metroprolol, midazolam, omeprazole and tolbutamide, respectively. The rats were randomly divided into two groups, control group and H₂S group. The H₂S group rats were given 5 mg/kg NaHS by oral administration once a day for seven days. The mixture of five probes was given to rats through oral administration and the blood samples were obtained at a series of time-points through the caudal vein. The concentrations of probe drugs in rat plasma were measured by LC-MS. In comparing the H₂S group with the control group, there was a statistically pharmacokinetics difference for midazolam and tolbutamide; the area under the plasma concentration-time curve (AUC) was decreased for midazolam (p < 0.05) and increased for tolbutamide (p < 0.05); while there was no statistical pharmacokinetics difference for bupropion, metroprolol and omeprazole. H₂S could not influence the activities of CYP2B6, CYP2D6 and CYP2C19 in rats, while H₂S could induce the activity of CYP3A4 and inhibit the activity of CYP2C9 in rats.     

Combined In Silico,Ex Vivo,and In Vivo Assessment of L-17, a Thiadiazine Derivative with Putative Neuro- and Cardioprotective and Antidepressant Effects

Depression associated with poor general medical condition, such as post-stroke (PSD) or post-myocardial infarction (PMID) depression, is characterized by resistance to classical antidepressants. Special treatment strategies should thus be developed for these conditions. Our study aims to investigate the mechanism of action of 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17), a recently designed thiadiazine derivative with putative neuro- and cardioprotective and antidepressant-like effects, using combined in silico (for prediction of the molecular binding mechanisms), ex vivo (for assessment of the neural excitability using c-Fos immunocytochemistry), and in vivo (for direct examination of the neuronal excitability) methodological approaches. We found that the predicted binding affinities of L-17 to serotonin (5-HT) transporter (SERT) and 5-HT₃ and 5-HT_1A receptors are compatible with selective 5-HT serotonin reuptake inhibitors (SSRIs) and antagonists of 5-HT₃ and 5-HT_1A receptors, respectively. L-17 robustly increased c-Fos immunoreactivity in the amygdala and decreased it in the hippocampus. L-17 dose-dependently inhibited 5-HT neurons of the dorsal raphe nucleus; this inhibition was partially reversed by the 5-HT_1A antagonist WAY100135. We suggest that L-17 is a potent 5-HT reuptake inhibitor and partial antagonist of 5-HT₃ and 5-HT_1A receptors; the effects of L-17 on amygdaloid and hippocampal excitability might be mediated via 5-HT, and putatively mediate the antidepressant-like effects of this drug. Since L-17 also possesses neuro- and cardioprotective properties, it can be beneficial in PSD and PMID. Combined in silico predictions with ex vivo neurochemical and in vivo electrophysiological assessments might be a useful strategy for early assessment of the efficacy and neural mechanism of action of novel CNS drugs.     

Effects of H2S and process conditions in the synthesis of mixed alcohols from syngas over alkali promoted cobalt-molybdenum sulfide

The present work is an investigation of how the process conditions influence the synthesis of mixed alcohols from syngas over a K₂CO₃/Co/MoS₂/C catalyst. The emphasis in the investigations is upon the effects of H₂S in the syngas feed. However the effects of the temperature and of the partial pressures of H₂ and CO are also investigated. With or without H₂S in the feed the pre-sulfided catalyst requires an initiation period to reach a stabilized behavior, but the duration of this period depends upon the H₂S level. Operation with a feed containing more than 103 ppmv H₂S leads to a fairly rapid stabilization of the product distribution and ensures that higher alcohols are the dominant reaction products. With less than 57 ppmv H₂S in the feed the stabilization of the product distribution is much slower, and methanol is the dominant product. An investigation of the reaction kinetics indicates a high CO coverage and low hydrogen coverage. Hydrogen sulfide in the syngas feed generally promotes chain growth for both alcohols and hydrocarbons, but lowers the alcohol selectivity by enhancing the hydrocarbon formation. The highest alcohol productivity reached in these investigations was 0.276 g/g cat./h, and this was achieved at 350 °C, 100 bar, GHSV = 5244 h⁻¹, Feed: 49.9 vol% H₂, 50.1 vol% CO. Finally it is found that sulfur fed to the reactor as H₂S is incorporated into the condensed alcohol product, and the incorporation of sulfur species into the product continues for some time after H₂S has been removed from the feed. When the catalyst is operated with an S-free syngas feed, the amount of sulfur in the condensed liquid product decreases over time, but after 35 h of operation with an S-free syngas the alcohol product still contains 340 ppmw of sulfur. Thiols appear to be the dominant sulfur compounds in the product.     

The Benefits of Fibrinolysis Combined with Venous Systemic Oxygen Persufflation (VSOP) in a Rat Model of Donation after Circulatory Death and Orthotopic Liver Transplantation

Organ shortage has led to the increasing utilization of livers retrieved from donors after circulatory death (DCD). These pre-damaged organs are susceptible to further warm ischemia and exhibit minimal tolerance for cold storage. The aim was thus to examine the effects of fibrinolysis combined with Venous Systemic Oxygen Persufflation (VSOP) on the preservation of DCD livers in vivo. Livers of male Lewis rats were explanted after 45 min of warm ischemia, cold-stored for 18 h, and transplanted into a recipient animal. Livers were left untreated or underwent either VSOP or fibrinolysis via Streptokinase (SK) or received combined SK and VSOP. Combined treatment exhibited improved microvascular flow at 168 h (p = 0.0009) and elevated microperfusion velocity at 24 h post-transplantation (p = 0.0007). Combination treatment demonstrated increased portal venous flow (PVF) at 3 and 24 h post-transplantation (p = 0.0004, p < 0.0001), although SK and VSOP analogously achieved increases at 24 h (p = 0.0036, p = 0.0051). Enzyme release was decreased for combination treatment (p = 0.0002, p = 0.0223) and lactate dehydrogenase (LDH) measurements were lower at 24 h post-transplantation (p = 0.0287). Further supporting findings have been obtained in terms of serum cytokine levels and in the alterations of endothelial injury markers. The combination treatment of SK + VSOP might provide improved organ integrity and viability and may therefore warrant further investigation as a potential therapeutic approach in the clinical setting of DCD.     

The effects of a potassium overlayer on the reaction pathway of CH2 and C2H5 on Rh(111)

The effect of potassium on the reaction pathways of adsorbed CH₂ and C₂H₅ species on Rh(111) was investigated by means of reflection absorption infrared spectroscopy (RAIRS) and temperature programmed desorption (TDS). Hydrocarbon fragments were produced by thermal and photo-induced dissociation of the corresponding iodo compounds. Potassium adatoms markedly stabilized the adsorbed CH₂ and converted it into C₂H₄, the formation of which was not observed for K-free Rh(111). New routes of the surface reactions of C₂H₅ have been also opened in the presence of potassium, namely its transformation into butane and butene.     

Electrochemical behavior and its electrocatalytic properties of chemically modified electrode with Keggin-type [SiNi(H2O)W11O39]

A monolayer of Keggin-type heteropolyanion [SiNi(H₂O)W₁₁O₃₉]⁶⁻ was fabricated by electrodepositing [SiNi(H₂O)W₁₁O₃₉]⁶⁻ on cysteamine modified gold electrode. The monolayer of [SiNi(H₂O)W₁₁O₃₉]⁶⁻ modified gold electrode was characterized by atomic force microscopy (AFM) and electrochemical method. AFM results showed the [SiNi(H₂O)W₁₁O₃₉]⁶⁻ uniformly deposited on the electrode surface and formed a porous monolayer. Cyclic voltammetry exhibited one oxidation peak and two reduction peaks in 1.0 M H₂SO₄ in the potential range of −0.2 to 0.7 V. The constructed electrode could exist in a large pH (0-7.6) range and showed good catalytic activity towards the reduction of bromate anion (BrO₃⁻) and nitrite (NO₂⁻), and oxidation of ascorbic acid (AA) in acidic solution. The well catalytic active of the electrode was ascribed to the porous structure of the [SiNi(H₂O)W₁₁O₃₉]6⁻ monolayer.     

An In Vivo Study of a Rat Fluid-Percussion-Induced Traumatic Brain Injury Model with [11C]PBR28 and [18F]flumazenil PET Imaging

Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [¹¹C]PBR28 and [¹⁸F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [¹¹C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [¹⁸F]flumazenil is a radioligand for GABA_A-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [¹¹C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [¹⁸F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [¹¹C]PBR28 and [¹⁸F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.     

A computational study of adsorption H2S gas on the surface of the pristine,Al&P-doped armchair and zigzag BNNTs

Density function theory is used to study the H₂S adsorption on the surface of pristine, Al-, P- and Al&P- doped (4, 4) armchair and (8, 0) zigzag BNNTs. All considered different models for H₂S adsorption on the exterior and interior surface of nanotube are optimized by using B3LYP/6-31G (d, P) level of theory. The adsorption energy values (E_ads) of the B-I, B-II,C-I, D-I, D-II, F-I, F-II and H-II models are negative, while the E_ads values for the A-III, B-III, C-III, D-III, E-III, F-III, G-III and H-III models are positive. On the other hand, Al, P and Al&P doped in all models increase significantly the adsorption energy of H₂S on the surface of BNNTs, and so the selectivity of nanotube for adsorbing and making a sensor of H₂S increase significantly from original state. The positive values of the charge transfer parameters (ΔN) and more values of the electronic chemical potentials of H₂S gas for all studied models demonstrate that H₂S gas in this system has a donor electron effect on the nanotube. The MEP results display that a low charge transfer occurs from H₂S gas toward nanotube, resulting in a weak ionic bonding in the BNNTs’ surface.     

Influence of the Type of Reducing Agent (H2, CO, C3H6 and C3H8) on the Reduction of Stored NOX in a Pt/BaO/Al2O3 Model Catalyst

In this investigation, a comparative study for a NO _X storage catalytic system was performed focusing on the parameters that affect the reduction by using different reductants (H₂, CO, C₃H₆ and C₃H₈) and different temperatures (350, 250 and 150 °C), for a Pt/BaO/Al₂O₃ catalyst. Transient experiments show that H₂ and CO are highly efficient reductants compared to C₃H₆ which is somewhat less efficient. H₂ shows a significant reduction effect at relatively low temperature (150 °C) but with a low storage capacity. We find that C₃H₈does not show any NO _X reduction ability for NO _X stored in Pt/BaO/Al₂O₃ at any of the temperatures. The formation of ammonia and nitrous oxide is also discussed.     

The oxidation of Fe(II) with Cu(II) in acidic sulfate solutions with air at elevated pressures

The oxidation of ferrous ions in acidic sulfate solutions in the presence of cupric ions at elevated air pressures was investigated in a high-intensity gas–liquid contactor. The study was required for the design of the regeneration steps of the novel Vitrisol^® desulphurization process. The effects of the Fe²⁺ concentration, Cu²⁺ concentration, Fe³⁺ concentration, initial H₂SO₄ concentration, and partial oxygen pressure on the reaction rate were determined at three different temperatures, i.e., T?=?50?°C, 70?°C, and 90?°C. Most of the experiments were determined to be affected by the mass transfer of oxygen, and therefore true intrinsic kinetics could not be fully determined. An increase in Fe²⁺ and Cu²⁺ concentrations, as well as the partial pressure of oxygen and temperature, increased the Fe²⁺ oxidation rate. H₂SO₄ did not influence the Fe²⁺ oxidation rate. An increase in Fe³⁺ concentration decreased the Fe²⁺ oxidation rate. Although determined from experiments partially affected by mass transfer, a first order of reaction in Fe²⁺ was observed, fractional orders in both Cu²⁺ and O₂ were measured, a zero order in H₂SO₄ was determined, and a negative, fractional order in Fe³⁺ was obtained. The activation energy was estimated to be 31.3?kJ/mol.     

Kinetic effect of electrolytes on the oligomerization of hydrosulfide into polysulfides and colloidal sulfur with iron(III) trans-1,2-diaminocyclohexanetetraacetic acid in anoxic aqueous solutions

The kinetic electrolyte effect of dissolved NaCl, LiCl and Na₂SO₄ on the oligomerization of the hydrosulfide ion (HS^-) into polysulfides then in colloidal sulfur assisted by iron(III) trans-1,2,-diaminocyclohexanetetraacetate (iron(III)-cdta) complexes was studied in anoxic alkaline solutions at . The three electrolytes have been confirmed to boost the HS^- oligomerization reaction considerably. For example, the HS^- half-life decreased from 16.7 min in demineralized water (pH=10.5) to 12.4 min for the corresponding 0.01 mol/L NaCl solution. It further decreased to 5.1 min for a 0.1 mol/L NaCl solution. The kinetic enhancement factor is attributed to the cationic species (i.e. Na⁺, Li⁺) both affecting the reactive species’ activity coefficients within experimental and calculation accuracy. It improves the initial HS^- and iron(III)-cdta reaction rates, reduces the induction period for elemental sulfur formation which in turn enhance the overall HS^- consumption rate. The HS^- and iron(III)-cdta concentration profiles were also fitted with corresponding rate laws derived from a simplified HS^- oligomerization mechanism and application of kinetic electrolyte constants on the activity coefficient Hückel equation.     

The Preparation of Molybdenum Oxynitride by Hydrazine Reduction of MoO3 at Moderate Temperature and Its Application in the Selective Hydrogenation of Long-Chain Linear Alkadienes

Molybdenum oxynitride was prepared by hydrazine reduction of MoO₃ at moderate temperatures. The anhydrous condition was favorable to production of amorphous molybdenum oxynitride, and the presence of hydrogen favored the reduction of Mo⁶⁺ and Mo⁴⁺ species to Mo ⁺ (0 < < 4) species. These molybdenum oxynitrides exhibited activity for hydrogenation which depended on the amount of Mo ⁺ (0 < < 4) species produced under reaction conditions. The amorphous molybdenum oxynitride MoO_1.83N_0.36 catalyst showed a good catalytic activity, selectivity, and resistance to poisoning of H₂S for liquid-phase hydrogenation of longer-chain alkadienes.