Effects of Sulfur Thermal Water inhalations in long-COVID syndrome: spa-centred, double-blinded, randomised case-control pilot study.

BACKGROUND: The long-COVID syndrome is characterised by a plethora of symptoms. Given its social and economic impact, many studies have stressed the urgency of proposing innovative strategies other than hospital settings. In this double-blind randomised case-control trial, we investigate the effects of sulfur thermal water inhalations, rich in H2S, compared to distilled water inhalations on symptoms, inflammatory markers, nasal microbiome in long-COVID patients. METHODS: 30 outpatients aged 18-75, with positive diagnosis for long-COVID were randomised in two groups undergoing 12 consecutive days of inhalations. The active Group (STW) received sulfur thermal water inhalations whereas the placebo group received inhalations of sterile distilled non-pyrogenic water (SDW). Each participant was tested prior treatment at day 1 (T0), after the inhalations at day 14 (T1) and at 3 months follow-up (T2). At each time point, blood tests, nasal swabs for microbiome sampling, pulmonary functionality tests (PFTs) and pro-inflammatory marker measure were performed. RESULTS: The scores obtained in the administered tests (6MWT, Borg score, and SGRQ) at T0, showed a significant variation in STW group, at T1 and T2. Serum cytokine levels and other inflammatory biomarkers reported a statistically significant decrease. Some specific parameters of PFT's showed ameliorations in STW group only. Changes in the STW nasopharyngeal microbiota composition were noticed, especially from T0 to T2. CONCLUSIONS: Inhalations of sulfur thermal water exerted objective and subjective improvements on subjects affected by long-COVID. Significant reduction of inflammatory markers, dyspnea scores and quantitative and qualitative changes in the nasopharyngeal microbiome were also assessed.

Green synthesis and two-step chromatographic separation of thiocanthal and thiocanthol: Two novel biologically active sulfur derivatives of oleocanthal and oleacein from extra virgin olive oil.

Oleocanthal and oleacein are the two major secoiridoids exclusively present in extra virgin olive oil (EVOO). Both compounds exert important pharmacological activities, including anti-inflammatory, anti-tumoral, neuro- and cardiovascular protective effects. Due to their enormous potential as possible drugs the extraction of these two bioactive natural products from EVOO has been extensively investigated in the last years and is generally supported by the use of organic chemistry. It is quite difficult to produce large quantities of these two compounds, either by organic solvent extraction and purification or by chemical synthesis, and furthermore organic processes such as cleaning, defatting, and extraction of EVOO pose a threat to the environment and are potentially harmful to workers. In this work we set up a novel aqueous extraction and isolation method from EVOO by transforming oleocanthal and oleacein into two water-soluble sulfonated products. The two derived compounds, here named thiocanthal and thiocanthol, were isolated by a two-step organic free chromatographic strategy, chemically characterized, and evaluated for their inhibitory activity on cyclooxygenase (COX). The results demonstrate that thiocanthal and thiocanthol possess anti-inflammatory effect, which is comparable to their precursors and higher than the well-known non-steroidal anti-inflammatory drug ibuprofen. Computational docking studies were performed to obtain and analyse putative models of the interaction of thiocanthal and thiocanthol with COX-1 and COX-2 binding sites. Predicted binding energy values suggested that both compounds might preferentially bind COX-2, which may have a significant pharmacological impact. Therefore, thiocanthal and thiocanthol, obtained by this novel green process, are extremely interesting both as new bioactive compounds per se and as lead compounds for the development of novel non-steroidal anti-inflammatory drugs (NSAIDs).

Synthesis and Biological Activity of Homohypotaurine Obtained by the Enzyme-Based Conversion of Homocysteine Sulfinic Acid Using Recombinant Escherichia Coli Glutamate Decarboxylase.

l-Homocysteine, formed from S-adenosyl methionine following demethylation and adenosine release, accumulates when the methionine recycling pathway and other pathways become impaired, thus leading to hyperhomocysteinemia, a biomarker in cardiovascular diseases, neurological/psychiatric disorders, and cancer. The partial oxidation of the l-homocysteine thiol group and its decarboxylation on C-alpha lead to the formation of l-homocysteinesulfinic acid (l-HCSA) and homohypotaurine (HHT), respectively. Both compounds are not readily available from commercial suppliers, which hinders the investigation of their biological activities. Herein, the chemical synthesis of l-HCSA, from l-homocystine, was the starting point for establishing the bio-based synthesis of HHT using recombinant Escherichia coli glutamate decarboxylase (EcGadB), an enzyme already successfully employed for the bio-based synthesis of GABA and its phosphinic analog. Prior to HHT synthesis, kcat (33.92 ± 1.07) and KM (38.24 ± 3.45 mM) kinetic constants were determined for l-HCSA on EcGadB. The results of our study show that the EcGadB-mediated synthesis of HHT can be achieved with good yields (i.e., 40% following enzymatic synthesis and column chromatography). Purified HHT was tested in vitro on primary human umbilical vein endothelial cells and rat cardiomyoblasts and compared to the fully oxidized analog, homotaurine (OT, also known as tramiprosate), in widespread pharmaceutical use. The results show that both cell lines display statistically significant recovery from the cytotoxic effects induced by H2O2 in the presence of HHT.

Balneotherapy using thermal mineral water baths and dermatological diseases: a systematic review.

Balneotherapy includes practices and methods using medically and legally recognized mineral-medicinal waters, muds and natural gases from natural springs for therapeutic purposes. One of the most widely used method in balneotherapy is bathing with thermal mineral water. In the course of the years, scientific community has produced an increasing number of evidences that this practice is an effective method for treating signs and symptoms of several pathologies such as rheumatic, cardiovascular and dermatological diseases. This systematic review is aimed at evaluating the effect of balneotherapy with thermal water baths as a treatment to manage signs and symptoms of patients affected by all types of dermatological diseases. The systematic review was conducted according to the PRISMA Statement, and its protocol was registered on PROSPERO platform (CRD42022295913). The research was performed on the databases Pubmed, Scopus, Web of Science and Cochrane. We included clinical trials evaluating the effects of balneotherapy using thermal mineral water baths for managing dermatological diseases in humans, published in English and Italian language. Eight studies were included, seven of them enrolled adults affected by psoriasis and one studied atopic dermatitis patients. The common result of all the articles included was a clear improvement of signs and symptoms of psoriasis and eczematous diseases after use of thermal mineral water baths. These effects seem to be strictly related to physical and chemical properties of thermal water used for balneotherapy. However, studies in this field are still limited to support robust evidence of the effectiveness of balneotherapy using thermal mineral water baths and often their quality is low. Thus, new clinical studies need to be carried out, using more correct methods for conducting the studies and for processing statistical data.

Balneotherapy for osteoarthritis: a systematic review.

This systematic review is aimed to evaluate the effects of balneotherapy with thermal mineral water for managing the symptoms and signs of osteoarthritis located at any anatomical site. The systematic review was conducted according to the PRISMA Statement. The following databases were consulted: PubMed, Scopus, Web of Science, Cochrane Library, DOAJ and PEDro. We included clinical trials evaluating the effects of balneotherapy as a treatment for patients with osteoarthritis, published in English and Italian language, led on human subjects. The protocol was registered in PROSPERO. Overall, 17 studies have been included in the review. All of these studies were performed on adults or elderly patients suffering from osteoarthritis localized to knees, hips, hands or lumbar spine. The treatment assessed was always the balneotherapy with thermal mineral water. The outcomes evaluated were pain, palpation/pressure sensibility, articular tenderness, functional ability, quality of life, mobility, deambulation, ability to climb stairs, medical objective and patients' subjective evaluation, superoxide dismutase enzyme activity, serum levels of interleukin-2 receptors. The results of all the included studies agree and demonstrated an improvement of all the symptoms and signs investigated. In particular, pain and quality of life were the main symptoms evaluated and both improved after the treatment with thermal water in all the studies included in the review. These effects can be attributed to physical and chemical-physical properties of thermal mineral water used. However, the quality of many studies resulted not so high due and, consequently, it is necessary to perform new clinical trial in this field using more correct methods for conducting the study and for processing statistical data.

Natural Mineral Water and Diuresis: A Systematic Review.

The present systematic review is aimed at evaluating the diuretic effects determined according to the natural mineral water consumption on healthy individuals. This systematic review has been performed following the guidelines of the PRISMA (preferred reporting items for systematic reviews and meta-analyses) Statement, investigating PubMed, Scopus, Web of Science and Cochrane Library from inception to November 2022. Studies performed both on animals and on humans were considered. After screening, a total of 12 studies have been identified. Of these, 11 studies were performed in Italy and 1 in Bulgaria. The time range of publication is very wide, ranging from 1962 to 2019 for human studies and from 1967 to 2001 for animal studies. All the included studies found an increase in diuresis determined according to the consumption of natural mineral water, in some cases after just one administration of the tested water. However, the quality of the studies is not so high, especially for the research conducted many years ago. Thus, it would be desirable to carry out new clinical studies using more appropriate methodological approaches and more refined methods of statistical data processing.

Effect of Natural Deep Eutectic Solvents on trans-Resveratrol Photo-Chemical Induced Isomerization and 2,4,6-Trihydroxyphenanthrene Electro-Cyclic Formation.

trans-Resveratrol is a natural bioactive compound with well-recognized health promoting effects. When exposed to UV light, this compound can undergo a photochemically induced trans/cis isomerization and a 6π electrochemical cyclization with the subsequent formation of 2,4,6-trihydroxyphenanthrene (THP). THP is a potentially harmful compound which can exert genotoxic effects. In this work we improved the chromatographic separation and determination of the two resveratrol isomers and of THP by using a non-commercial pentafluorophenyl stationary phase. We assessed the effect of natural deep eutectic solvents (NaDES) as possible photo-protective agents by evaluating cis-resveratrol isomer and THP formation under different UV-light exposure conditions with the aim of enhancing resveratrol photostability and inhibiting THP production. Our results demonstrate a marked photoprotective effect exerted by glycerol-containing NaDES, and in particular by proline/glycerol NaDES, which exerts a strong inhibitory effect on the photochemical isomerization of resveratrol and significantly limits the formation of the toxic derivative THP. Considering the presence of resveratrol in various commercial products, these results are of note in view of the potential genotoxic risk associated with its photochemical degradation products and in view of the need for the development of green, eco-sustainable and biocompatible resveratrol photo-stable formulations.

Pharmacokinetic properties of a novel formulation of S-adenosyl-L-methionine phytate.

S-adenosyl-L-methionine (SAM), the main endogenous methyl donor, is the adenosyl derivative of the amino acid methionine, which displays many important roles in cellular metabolism. It is widely used as a food supplement and in some countries is also marketed as a drug. Its interesting nutraceutical and pharmacological properties prompted us to evaluate the pharmacokinetics of a new form of SAM, the phytate salt. The product was administered orally to rats and pharmacokinetic parameters were evaluated by comparing the results with that obtained by administering the SAM tosylated form (SAM PTS). It was found that phytate anion protects SAM from degradation, probably because of steric hindrance exerted by the counterion, and that the SAM phytate displayed significant better pharmacokinetic parameters compared to SAM PTS. These results open to the perspective of the use of new salts of SAM endowed with better pharmacokinetic properties.

Legacy effect of green manure crops fertilized with calcium phosphite on maize production and soil properties.

Recycling phosphorus (P) is crucial to meet future P demand for crop production. We investigated the possibility to use calcium phosphite (Ca-Phi) waste, an industrial by-product, as P fertilizer following the oxidation of phosphite (Phi) to phosphate (Pi) during green manure (GM) cropping in order to target P nutrition of subsequent maize crop. In a greenhouse experiment, four GM crops were fertilized (38 kg P ha-1) with Ca-Phi, triple super phosphate (TSP) or without P (Control) in sandy and clay soils. The harvested GM biomass (containing Phi after Ca-Phi fertilization) was incorporated into the soil before maize sowing. Incorporation of GM residues containing Phi slowed down organic carbon mineralization in clay soil and mass loss of GM residues in sandy soil. Microbial enzymatic activities were affected by Ca-Phi and TSP fertilization at the end of maize crop whereas microbial biomass was similarly influenced by TSP and Ca-Phi in both soils. Compared to Control, Ca-Phi and TSP increased similarly the available P (up to 5 mg P kg-1) in sandy soil, whereas in clay soil available P increased only with Ca-Phi (up to 6 mg P kg-1), indicating that Phi oxidation occurred during GM crops. Accordingly, no Phi was found in maize biomass. However, P fertilization did not enhance aboveground maize productivity and P export, likely because soil available P was not limiting. Overall, our results indicate that Ca-Phi might be used as P source for a subsequent crop since Phi undergoes oxidation during the preliminary GM growth.

Valorization of calcium phosphite waste as phosphorus fertilizer: Effects on green manure productivity and soil properties.

The potential to use calcium phosphite (Ca-Phi) as phosphorus (P) fertilizer may represent an effective recycling of P-containing by-products. A greenhouse experiment was conducted to investigate the effect of Ca-Phi (38 kg P ha-1) on soil properties and the growth parameters of four green manure species in clay and sandy soils using Ca-Phi, TSP (triple superphosphate) and control (no fertilization) as treatments. Eight weeks after sowing, we measured aboveground biomass yield, phosphite (Phi) concentration in plant biomass, different soil P pools as well as microbial biomass nutrients. Compared to control, the addition of Ca-Phi did not negatively affect green manure yield, except for lupine (Lupinus albus L.) in clay soil. The Phi concentration in plant biomass varied across species and soil type with a maximum concentration of about 400 mg Phi kg-1 for mustard (Brassica juncea L.) in clay soil. Compared to control, TSP and Ca-Phi fertilization had a similar effect on different P pools and microbial biomass nutrients (C, N and P) although the response was soil-type dependent. In the sandy soil, after Ca-Phi addition the amount of available P (PNHCO3) increased to the same extent as in the TSP treatment (i.e. around 6 mg P kg-1) suggesting that Ca-Phi was, at least partly, oxidized. In the clay soil with high P fixing capacity, Ca-Phi promoted higher PNaHCO3 than TSP likely due to different solubility of chemical P forms. Additional studies are however required to better understand soil microbial responses and to quantify the P agronomical efficiency for the following crop under Ca-Phi fertilization.

Paraneoplastic Neuromyelitis Optica Spectrum Disorder Associated With Lung Adenocarcinoma: A Case Report.

Neuromyelitis Optica spectrum disorder is an inflammatory demyelinating disease affecting the central nervous system (CNS), characterized by triad optic neuritis, transverse myelitis, and area postrema syndrome. Antibodies directed against aquaporin-4 (AQP-4), a water channel expressed on the astrocytic membrane, are supposed to play a pathogenic role and are detected in ~80% of cases. Clinical signs of Neuromyelitis Optica spectrum disorder (NMOSD) in elderly patients should arouse the suspicion of paraneoplastic etiology. In this article, we discussed a case of a 76-year-old woman with a 2-month history of confusion, dysarthria, and progressive bilateral leg weakness. A whole-body CT scan showed a neoformation of 5 cm in diameter in the median lobe infiltrating the mediastinal pleura. The tumor had already spread to both the upper and lower right lobes, parietal pleura, and multiple lymph nodes. Pleural cytology revealed adenocarcinoma cells. The brain MRI documented hyperintense alteration in fluid-attenuated inversion recovery (FLAIR) images, involving the anterior portion of the corpus callosum and the periependymal white matter surrounding the lateral ventricles, with mild contrast enhancement on the same areas and meningeal tissue. T2-weighted spinal cord MRI sequences showed extended signal hyperintensity from bulbo-cervical junction to D7 metamer, mainly interesting the central component and the gray matter. Cerebrospinal fluid analysis revealed no neoplastic cells. Serum AQP-4 immunoglobulin (IgG) antibodies were found. Meanwhile, the patient rapidly developed progressive paraparesis and decreased level of consciousness. High-dose intravenous methylprednisolone therapy was started but her conditions rapidly deteriorated. No other treatment was possible.

Pheomelanin Effect on UVB Radiation-Induced Oxidation/Nitration of l-Tyrosine.

Pheomelanin is a natural yellow-reddish sulfur-containing pigment derived from tyrosinase-catalyzed oxidation of tyrosine in presence of cysteine. Generally, the formation of melanin pigments is a protective response against the damaging effects of UV radiation in skin. However, pheomelanin, like other photosensitizing substances, can trigger, following exposure to UV radiation, photochemical reactions capable of modifying and damaging cellular components. The photoproperties of this natural pigment have been studied by analyzing pheomelanin effect on oxidation/nitration of tyrosine induced by UVB radiation at different pH values and in presence of iron ions. Photoproperties of pheomelanin can be modulated by various experimental conditions, ranging from the photoprotection to the triggering of potentially damaging photochemical reactions. The study of the photomodification of l-Tyrosine in the presence of the natural pigment pheomelanin has a special relevance, since this tyrosine oxidation/nitration pathway can potentially occur in vivo in tissues exposed to sunlight and play a role in the mechanisms of tissue damage induced by UV radiation.

Reduced Biliverdin Reductase-A Expression in Visceral Adipose Tissue is Associated with Adipocyte Dysfunction and NAFLD in Human Obesity.

Biliverdin reductase A (BVR-A) is an enzyme involved in the regulation of insulin signalling. Knockout (KO) mice for hepatic BVR-A, on a high-fat diet, develop more severe glucose impairment and hepato-steatosis than the wild type, whereas loss of adipocyte BVR-A is associated with increased visceral adipose tissue (VAT) inflammation and adipocyte size. However, BVR-A expression in human VAT has not been investigated. We evaluated BVR-A mRNA expression levels by real-time PCR in the intra-operative omental biopsy of 38 obese subjects and investigated the association with metabolic impairment, VAT dysfunction, and biopsy-proven non-alcoholic fatty liver disease (NAFLD). Individuals with lower VAT BVR-A mRNA levels had significantly greater VAT IL-8 and Caspase 3 expression than those with higher BVR-A. Lower VAT BVR-A mRNA levels were associated with an increased adipocytes' size. An association between lower VAT BVR-A expression and higher plasma gamma-glutamyl transpeptidase was also observed. Reduced VAT BVR-A was associated with NAFLD with an odds ratio of 1.38 (95% confidence interval: 1.02-1.9; χ2 test) and with AUROC = 0.89 (p = 0.002, 95% CI = 0.76-1.0). In conclusion, reduced BVR-A expression in omental adipose tissue is associated with VAT dysfunction and NAFLD, suggesting a possible involvement of BVR-A in the regulation of VAT homeostasis in presence of obesity.

Chemistry and Biochemistry of Sulfur Natural Compounds: Key Intermediates of Metabolism and Redox Biology.

Sulfur contributes significantly to nature chemical diversity and thanks to its particular features allows fundamental biological reactions that no other element allows. Sulfur natural compounds are utilized by all living beings and depending on the function are distributed in the different kingdoms. It is no coincidence that marine organisms are one of the most important sources of sulfur natural products since most of the inorganic sulfur is metabolized in ocean environments where this element is abundant. Terrestrial organisms such as plants and microorganisms are also able to incorporate sulfur in organic molecules to produce primary metabolites (e.g., methionine, cysteine) and more complex unique chemical structures with diverse biological roles. Animals are not able to fix inorganic sulfur into biomolecules and are completely dependent on preformed organic sulfurous compounds to satisfy their sulfur needs. However, some higher species such as humans are able to build new sulfur-containing chemical entities starting especially from plants' organosulfur precursors. Sulfur metabolism in humans is very complicated and plays a central role in redox biochemistry. The chemical properties, the large number of oxidation states, and the versatile reactivity of the oxygen family chalcogens make sulfur ideal for redox biological reactions and electron transfer processes. This review will explore sulfur metabolism related to redox biochemistry and will describe the various classes of sulfur-containing compounds spread all over the natural kingdoms. We will describe the chemistry and the biochemistry of well-known metabolites and also of the unknown and poorly studied sulfur natural products which are still in search for a biological role.

Green Route for the Isolation and Purification of Hyrdoxytyrosol, Tyrosol, Oleacein and Oleocanthal from Extra Virgin Olive Oil.

Extra virgin olive oil (EVOO) phenols represent a significant part of the intake of antioxidants and bioactive compounds in the Mediterranean diet. In particular, hydroxytyrosol (HTyr), tyrosol (Tyr), and the secoiridoids oleacein and oleocanthal play central roles as anti-inflammatory, neuro-protective and anti-cancer agents. These compounds cannot be easily obtained via chemical synthesis, and their isolation and purification from EVOO is cumbersome. Indeed, both processes involve the use of large volumes of organic solvents, hazardous reagents and several chromatographic steps. In this work we propose a novel optimized procedure for the green extraction, isolation and purification of HTyr, Tyr, oleacein and oleocanthal directly from EVOO, by using a Natural Deep Eutectic Solvent (NaDES) as an extracting phase, coupled with preparative high-performance liquid chromatography. This purification method allows the total recovery of the four components as single pure compounds directly from EVOO, in a rapid, economic and ecologically sustainable way, which utilizes biocompatible reagents and strongly limits the use or generation of hazardous substances.

Platelet Rich Fibrin (PRF) and Its Related Products: Biomolecular Characterization of the Liquid Fibrinogen.

Liquid fibrinogen is an injectable platelet concentrate rich in platelets, leukocytes, and fibrinogen obtained by blood centrifugation. The aim of this study was to analyze the release of different growth factors in the liquid fibrinogen at different times and to assess possible correlations between growth factors and cell counts. The concentration of transforming growth factor beta 1 (TGF-ß1), platelet-derived growth factor-AB (PDGF-AB), platelet-derived growth factor-BB (PDGF-BB), bone morphogenetic protein 2 (BMP-2), fibroblast growth factor 2 (FGF-2) and vascular endothelial growth factor (VEGF) released by liquid fibrinogen were examined with ELISA at three time points (T0, time of collection; T7, 7 days; T14, 14 days). The cellular content of the liquid fibrinogen and whole blood was also calculated for each volunteer. A mean accumulation of platelets of almost 1.5-fold in liquid fibrinogen compared to whole blood samples was found. An increase of TGF-ß1, PDGF-AB, FGF-2, and VEGF levels was detected at T7. At T14, the level of TGF-ß1 returned to T0 level; PDGF-AB amount remained high; the levels of FGF-2 and VEGF decreased with respect to T7, but remained higher than the T0 levels; PDGF-BB was high at all time points; BMP-2 level was low and remained constant at all time points. TGF-ß1, PDGF-AB, and PDGF-BB showed a correlation with platelet amount, whereas BMP-2, FGF-2, and VEGF showed a mild correlation with platelet amount. Due to the high concentration of platelets, liquid fibrinogen does contain important growth factors for the regeneration of both soft and hard tissue. The centrifugation protocol tested in this study provides a valid solution to stimulate wound healing in oral and periodontal surgery.

One- and Two-Electron Oxidations of ß-Amyloid25-35 by Carbonate Radical Anion (CO3•-) and Peroxymonocarbonate (HCO4-): Role of Sulfur in Radical Reactions and Peptide Aggregation.

The ß-amyloid (Aß) peptide plays a key role in the pathogenesis of Alzheimer's disease. The methionine (Met) residue at position 35 in Aß C-terminal domain is critical for neurotoxicity, aggregation, and free radical formation initiated by the peptide. The role of Met in modulating toxicological properties of Aß most likely involves an oxidative event at the sulfur atom. We therefore investigated the one- or two-electron oxidation of the Met residue of Aß25-35 fragment and the effect of such oxidation on the behavior of the peptide. Bicarbonate promotes two-electron oxidations mediated by hydrogen peroxide after generation of peroxymonocarbonate (HCO4-, PMC). The bicarbonate/carbon dioxide pair stimulates one-electron oxidations mediated by carbonate radical anion (CO3•-). PMC efficiently oxidizes thioether sulfur of the Met residue to sulfoxide. Interestingly, such oxidation hampers the tendency of Aß to aggregate. Conversely, CO3•- causes the one-electron oxidation of methionine residue to sulfur radical cation (MetS•+). The formation of this transient reactive intermediate during Aß oxidation may play an important role in the process underlying amyloid neurotoxicity and free radical generation.

Thiotaurine: From Chemical and Biological Properties to Role in H2S Signaling.

In the last decade thiotaurine, 2-aminoethane thiosulfonate, has been investigated as an inflammatory modulating agent as a result of its ability to release hydrogen sulfide (H2S) known to play regulatory roles in inflammation. Thiotaurine can be included in the "taurine family" due to structural similarity to taurine and hypotaurine, and is characterized by the presence of a sulfane sulfur moiety. Thiotaurine can be produced by different pathways, such as the spontaneous transsulfuration between thiocysteine - a persulfide analogue of cysteine - and hypotaurine as well as in vivo from cystine. Moreover, the enzymatic oxidation of cysteamine to hypotaurine and thiotaurine in the presence of inorganic sulfur can occur in animal tissues and last but not least thiotaurine can be generated by the transfer of sulfur from mercaptopyruvate to hypotaurine catalyzed by a sulfurtransferase. Thiotaurine is an effective antioxidant agent as demonstrated by its ability to counteract the damage caused by pro-oxidants in the rat. Recently, we observed the influence of thiotaurine on human neutrophils functional responses. In particular, thiotaurine has been found to prevent human neutrophil spontaneous apoptosis suggesting an alternative or additional role to its antioxidant activity. It is likely that the sulfane sulfur of thiotaurine may modulate neutrophil activation via persulfidation of target proteins. In conclusion, thiotaurine can represent a biologically relevant sulfur donor acting as a biological intermediate in the transport, storage and release of sulfide.

Amino Acids and Hypertension in Adults.

Accumulating evidence suggests a potential role of dietary protein among nutritional factors interfering with the regulation of blood pressure. Dietary protein source (plant versus animal protein), and especially, protein composition in terms of amino acids has been postulated to interfere with mechanisms underlying the development of hypertension. Recently, mounting interest has been directed at amino acids in hypertension focusing on habitual dietary intake and their circulating levels regardless of single amino acid dietary supplementation. The aim of the present review was to summarize epidemiological evidence concerning the connection between amino acids and hypertension. Due to the large variability in methodologies used for assessing amino acid levels and heterogeneity in the results obtained, it was not possible to draw robust conclusions. Indeed, some classes of amino acids or individual amino acids showed non-causative association with blood pressure as well as the incidence of hypertension, but the evidence was far from being conclusive. Further research should be prompted for a thorough understanding of amino acid effects and synergistic actions of different amino acid classes on blood pressure regulation.

Reduced biliverdin reductase-A levels are associated with early alterations of insulin signaling in obesity.

Biliverdin reductase-A (BVR-A) is a serine/threonine/tyrosine kinase involved in the regulation of insulin signaling. In vitro studies have demonstrated that BVR-A is a substrate of the insulin receptor and regulates IRS1 by avoiding its aberrant activation, and in animal model of obesity the loss of hepatic BVR-A has been associated with glucose/insulin alterations and fatty liver disease. However, no studies exist in humans. Here, we evaluated BVR-A expression levels and activation in peripheral blood mononuclear cells (PBMC) from obese subjects and matched lean controls and we investigated the related molecular alterations of the insulin along with clinical correlates. We showed that BVR-A levels are significantly reduced in obese subjects and associated with a hyper-activation of the IR/IRS1/Akt/GSK-3ß/AS160/GLUT4 pathway. Low BVR-A levels also associate with the presence of obesity, metabolic syndrome, NASH and visceral adipose tissue inflammation. These data suggest that the reduction of BVR-A may be responsible for early alterations of the insulin signaling pathway in obesity and in this context may represent a novel molecular target to be investigated for the comprehension of the process of insulin resistance development in obesity.