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Dysbiosis of the microbiome correlates with many neurological disorders, yet very little is known about the chemistry that controls the production of neuromodulatory molecules by gut microbes. Here, we found that an enzyme glutamate decarboxylase ( Bf GAD) of a gut microbe Bacteroides fragilis forms multiple neuromodulatory molecules such as γ-aminobutyric acid (GABA), hypotaurine, taurine, homotaurine, and β-alanine. We evolved Bf GAD and doubled its taurine productivity. Additionally, we increased its specificity towards the substrate L-glutamate. Here, we provide a chemical strategy via which the Bf GAD activity could be fine-tuned. In future, this strategy could be used to modulate the production of neuromodulatory molecules by gut microbes., Competing Interests: Declaration of interests. Aspects of this research are part of a pending patent application.

We aimed to characterize the metabolomic profiles in preterm small-for-gestational age (SGA) infants using cord blood. We conducted a gestational age (GA)-matched case-control study that included 30 preterm infants who were categorized into two groups: SGA infants, with a birth weight (BW) < 10th percentile for GA (n = 15) and non-SGA infants, with BW ≥ 10th percentile for GA (n = 15). SGA infants with chromosomal or genetic abnormalities were excluded. At birth, the umbilicus was double-clamped, and the cord blood was sampled from the umbilical vein. Metabolomic analyses were performed using capillary electrophoresis time-of-flight mass spectrometry. The median GA at birth was not significantly different between the two groups [SGA, 32 (26-36) weeks; non-SGA, 32 (25-35) weeks; p = 0.661)]. Of the 255 metabolites analyzed, 19 (7.5%) showed significant differences between SGA and non-SGA infants. There were significant reductions in the carnosine, hypotaurine, and S-methylcysteine levels in SGA infants as compared to non-SGA infants (p < 0.05). Carnosine was correlated with gestational age, BMI before pregnancy, body weight gain during pregnancy (p = 0.002, p = 0.023, and p = 0.020, respectively). In conclusion, preterm SGA infants have low levels of cord blood antioxidative- and antiglycation-related metabolites, making them vulnerable to oxidative stress., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

The evidence supports a strong link between immune cells and intracerebral hemorrhage (ICH). Nonetheless, the specific cause-and-effect associations between immune cells and ICH remain indeterminate. Here, our primary investigation compared immune cell infiltration in the ICH and sham groups using the GSE24265 dataset. Afterward, we extensively examined the relationship between immune cells and ICH by applying a two-sample Mendelian randomization (MR) analysis to identify the particular immune cells that may be associated with the initiation and advancement of ICH. Nevertheless, the specific processes that regulate the cause-and-effect connection between immune cells and ICH remain unknown. In this study, our objective was to investigate the connections between immune cell characteristics and plasma metabolites, as well as the links between plasma components and ICH. Our investigation uncovered that the levels of hypotaurine play a key role in the advancement of ICH, influencing the ratio of switched memory B cells among lymphocytes. Thus, our findings provide novel insights into the potential biological mechanisms underlying immune cell-mediated ICH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Hypotaurine, a precursor to taurine, is known for its antioxidant properties and is prominently present in fetal plasma and the placenta. Our previous research revealed that ezrin-knockout mice experience fetal growth retardation, coinciding with reduced hypotaurine levels in fetal plasma. This study aims to elucidate the expression and role of hypotaurine transporters within the placenta., Methods: We employed quantitative RT-PCR to measure mRNA expression of GAT transporter family members in the placenta during mid-to-late gestation. LC/MS/MS was used to analyze the distribution of hypotaurine in different placental subregions. Immunohistochemistry was utilized to examine the localization of GAT2 in mice. Placental hypotaurine uptake from fetal circulation was studied via umbilical perfusion in rats., Results: Among hypotaurine transporters, GAT2 exhibited increased mRNA and protein expression in murine placenta during mid-to-late gestation. Notably, GAT2/Slc6a13 mRNA and hypotaurine were most concentrated in the labyrinth of murine placenta. In contrast, enzymes responsible for hypotaurine synthesis, such as cysteine dioxygenase, cysteine sulfinic acid decarboxylase, and 2-aminoethanethiol dioxygenase, showed minimal expression in the labyrinth. These findings suggest that GAT2 is a key determinant of hypotaurine levels in the placental labyrinth. Immunohistochemical examination unveiled that GAT2 was predominantly localized on the fetal-facing plasma membrane within syncytiotrophoblasts, which co-localized with ezrin. In rat umbilical perfusion experiments, the GAT2/3 and TauT inhibitor, SNAP-5114, significantly reduced hypotaurine extraction from fetal circulation to the placenta., Discussion: The results suggest that GAT2 plays a pivotal role in the concentrative uptake of hypotaurine from fetal plasma within syncytiotrophoblasts of the placenta., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The in vitro production (IVP) of bovine embryos has gained popularity worldwide and in recent years and its use for producing embryos from genetically elite heifers and cows has surpassed the use of conventional superovulation-based embryo production schemes. There are, however, several issues with the IVP of embryos that remain unresolved. One limitation of special concern is the low efficiency of the IVP of embryos. Exposure to reactive oxygen species (ROS) is one reason why the production of embryos with IVP is diminished. These highly reactive molecules are generated in small amounts through normal cellular metabolism, but their abundances increase in embryo culture because of oocyte and embryo exposure to temperature fluctuations, light exposure, pH changes, atmospheric oxygen tension, suboptimal culture media formulations, and cryopreservation. When uncontrolled, ROS produce detrimental effects on the structure and function of genomic and mitochondrial DNA, alter DNA methylation, increase lipid membrane damage, and modify protein activity. Several intrinsic enzymatic pathways control ROS abundance and damage, and antioxidants react with and reduce the reactive potential of ROS. This review will focus on exploring the efficiency of supplementing several of these antioxidant molecules on oocyte maturation, sperm viability, fertilization, and embryo culture.

Background: Alzheimer's disease (AD) is the most common type of dementia in the elderly. Incomplete knowledge about the pathogenesis of this disease determines the absence of medications for the treatment of AD today. Animal models can provide the necessary knowledge to understand the mechanisms of biochemical processes occurring in the body in health and disease., Objective: To identify the most promising metabolomic predictors and biomarkers reflecting metabolic disorders in the development of AD signs., Methods: High resolution 1H NMR spectroscopy was used for quantitative metabolomic profiling of the hippocampus of OXYS rats, an animal model of sporadic AD, which demonstrates key characteristics of this disease. Animals were examined during several key periods: 20 days group corresponds to the "preclinical" period preceding the development of AD signs, during their manifestation (3 months), and active progression (18 months). Wistar rats of the same age were used as control., Results: Ranges of variation and mean concentrations were established for 59 brain metabolites. The main metabolic patterns during aging, which are involved in energy metabolism pathways and metabolic shifts of neurotransmitters, have been established. Of particular note is the significant increase of scyllo-inositol and decrease of hypotaurine in the hippocampus of OXYS rats as compared to Wistars for all studied age groups., Conclusions: We suggest that the accumulation of scyllo-inositol and the reduction of hypotaurine in the brain, even at an early age, can be considered as predictors and potential biomarkers of the development of AD signs in OXYS rats and, probably, in humans.

The study aimed to investigate the role of hydrogen sulfide (H 2 S) in regulating chromium stress (Cr-S) tolerance of tomato plants treated with citric acid (CA). Prior to the Cr treatment, tomato plants were foliar-fed with CA (100 μM) daily for 3 days. Subsequently, the plants were grown for another ten days in a hydroponic system in a 50 μM Cr (VI) solution. Chromium treatment reduced photosynthetic pigments and plant biomass, but boosted the levels of hydrogen peroxide (H 2 O 2 ) malondialdehyde (MDA), H 2 S, phytochelatins (PCs), and glutathione (GSH), electrolyte leakage (EL), and antioxidant enzyme activity in tomato plants. However, the foliar spray of CA mitigated the levels of H 2 O 2 , MDA, and EL, promoted plant growth and chlorophyll content, enhanced antioxidant enzymes' activities, and increased H 2 S production in Cr-S-tomato plants. CA also increased the levels of GSH and PCs, potentially reducing the toxicity of Cr through regulated sequestration. Additionally, the application of sodium hydrogen sulfide (NaHS), a donor of H 2 S, improved CA-induced Cr stress tolerance. The addition of CA promoted Cr accumulation in root cell wall and leaf vacuoles to suppress its toxicity. To assess the involvement of H 2 S in CA-mediated Cr-S tolerance, 0.1 mM hypotaurine (HT), an H 2 S scavenger, was provided to the control and Cr-S-plants along with CA and CA + NaHS. HT reduced the beneficial effects of CA by decreasing H 2 S production in tomato plants. However, the NaHS addition with CA + HT inverted the adverse impacts of HT, indicating that H 2 S is required for CA-induced Cr-S tolerance in tomato plants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Prostate cancer is among the leading cancers according to both incidence and mortality. Due to the high molecular, morphological and clinical heterogeneity, the course of prostate cancer ranges from slow growth that usually does not require immediate therapeutic intervention to aggressive and fatal disease that spreads quickly. However, currently available biomarkers cannot precisely predict the course of a disease, and novel strategies are needed to guide prostate cancer management. Amino acids serve numerous roles in cancers, among which are energy production, building block reservoirs, maintenance of redox homeostasis, epigenetic regulation, immune system modulation and resistance to therapy. In this article, by using The Cancer Genome Atlas (TCGA) data, we found that the expression of amino acid metabolism-related genes is highly aberrant in prostate cancer, which holds potential to be exploited in biomarker design or in treatment strategies. This change in expression is especially evident for catabolism genes and transporters from the solute carrier family. Furthermore, by using recursive partitioning, we confirmed that the Gleason score is strongly prognostic for progression-free survival. However, the expression of the genes SERINC3 (phosphatidylserine and sphingolipids generation) and CSAD (hypotaurine generation) can refine prognosis for high and low Gleason scores, respectively. Therefore, our results hold potential for novel prostate cancer progression biomarkers.

The effects of blue light on human body have attracted attention. The human skin in contact with the outside environment is often exposed to blue light, and the effects of this exposure remain to be fully determined. Therefore, in this study, we investigated the effect of blue light, at the intensity typically found in sunlight, on lipids in the skin from an oxidation perspective. Peroxide value (POV) and ultraweak photon emission (UPE) measurements were conducted to evaluate lipid oxidation. Our results confirmed that blue light irradiation induced lipid oxidation, similar to ultraviolet A (UVA) irradiation. Also, the effects of various reagents on the blue light-induced UPE were evaluated; however, the results differed from those of the DPPH radical-scavenging ability. We speculated that this is due to the difference in the evaluation principle; nevertheless, among reagents, hypotaurine not only showed a high antioxidant effect but was also more effective against blue light-induced oxidation than UVA. Based on the difference in the antioxidant effect of the lipid sample in this study, the oxidation reaction induced by blue light may be different from the UVA-induced reaction. Our study provides new insights into the effects of blue light on lipids in the human skin, thereby promoting research regarding photooxidation., (© 2022. The Author(s).)

Pathological examination of formalin-fixed paraffin-embedded (FFPE) needle-biopsied samples by certified pathologists represents the gold standard for differential diagnosis between ductal carcinoma in situ (DCIS) and invasive breast cancers (IBC), while information of marker metabolites in the samples is lost in the samples. Infrared laser-scanning large-area surface-enhanced Raman spectroscopy (SERS) equipped with gold-nanoparticle-based SERS substrate enables us to visualize metabolites in fresh-frozen needle-biopsied samples with spatial matching between SERS and HE staining images with pathological annotations. DCIS ( n = 14) and IBC ( n = 32) samples generated many different SERS peaks in finger-print regions of SERS spectra among pathologically annotated lesions including cancer cell nests and the surrounding stroma. The results showed that SERS peaks in IBC stroma exhibit significantly increased polysulfide that coincides with decreased hypotaurine as compared with DCIS, suggesting that alterations of these redox metabolites account for fingerprints of desmoplastic reactions to distinguish IBC from DCIS. Furthermore, the application of supervised machine learning to the stroma-specific multiple SERS signals enables us to support automated differential diagnosis with high accuracy. The results suggest that SERS-derived biochemical fingerprints derived from redox metabolites account for a hallmark of desmoplastic reaction of IBC that is absent in DCIS, and thus, they serve as a useful method for precision diagnosis in breast cancer., Competing Interests: The authors declare no conflict of interest. M.S. (Megumi Shiota) and FUJIFILM Corporation have no conflict of interest to be disclosed.

The disulfide-containing molecule cystamine and the thiosulfonate thiotaurine are of interest as therapeutics. Both are precursors of taurine, but the chemistry of their metabolism is not clear. The rates at which these molecules are metabolized is also unknown. The chemistry and rate constants have been determined for a process in which cystamine is converted in four reactions to thiotaurine. Cystamine is oxidized by diamine oxidase with a specificity constant comparable to other diamine substrates. The rapid hydrogen peroxide-mediated oxidation of cystaldimine yields reactive glyoxal and thiocysteamine, which quickly performs transsulfuration with hypotaurine. Thiotaurine reacts spontaneously with hydrogen peroxide to form taurine and sulfite, but it is 15-fold less reactive than hypotaurine as an antioxidant. An estimation of biological rates of reaction indicates that cystamine is likely to be oxidized by diamine oxidase in vivo, but its metabolic products will be diverted to molecules other than thiotaurine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Taurine is considered the most abundant free amino acid in the brain. Even though there are endogenous mechanisms for taurine production in neural cells, an exogenous supply of taurine is required to meet physiological needs. Taurine is required for optimal postnatal brain development; however, its brain concentration decreases with age. Synthesis of taurine in the central nervous system (CNS) occurs predominantly in astrocytes. A metabolic coupling between astrocytes and neurons has been reported, in which astrocytes provide neurons with hypotaurine as a substrate for taurine production. Taurine has antioxidative, osmoregulatory, and anti-inflammatory functions, among other cytoprotective properties. Astrocytes release taurine as a gliotransmitter, promoting both extracellular and intracellular effects in neurons. The extracellular effects include binding to neuronal GABA A and glycine receptors, with subsequent cellular hyperpolarization, and attenuation of N -methyl-D-aspartic acid (NMDA)-mediated glutamate excitotoxicity. Taurine intracellular effects are directed toward calcium homeostatic pathway, reducing calcium overload and thus preventing excitotoxicity, mitochondrial stress, and apoptosis. However, several physiological aspects of taurine remain unclear, such as the existence or not of a specific taurine receptor. Therefore, further research is needed not only in astrocytes and neurons, but also in other glial cells in order to fully comprehend taurine metabolism and function in the brain. Nonetheless, astrocyte's role in taurine-induced neuroprotective functions should be considered as a promising therapeutic target of several neuroinflammatory, neurodegenerative and psychiatric diseases in the near future. This review provides an overview of the significant relationship between taurine and astrocytes, as well as its homeostatic and neuroprotective role in the nervous system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ramírez-Guerrero, Guardo-Maya, Medina-Rincón, Orrego-González, Cabezas-Pérez and González-Reyes.)

The rate at which taurine is synthesized in cells is unclear. This study reports the rate constants for taurine, hypotaurine, and other precursor molecules with hydrogen peroxide and superoxide. Raman spectroscopy permitted direct observation of reactions between hydrogen peroxide and the sulfinate and dithiol precursors of taurine. No observable reaction occurred between hydrogen peroxide and the sulfonates taurine or cysteate. Superoxide reacts with hypotaurine, taurine, and cysteate, although hypotaurine engages in rapid side reactions with a tetrazolium dye. Superoxide-produced radical intermediates for hypotaurine and taurine reacted with the nitroxyl radical-containing molecule TEMPONE. Hypotaurine oxidation by superoxide is calculated to occur at a rate sufficient to produce intracellular concentrations of taurine in humans. Hypotaurine's and taurine's reactions as antioxidants are predicted to occur at a fraction of the rate of enzyme-based antioxidant systems, but they may reach similar rates when hypotaurine is present at millimolar concentration in an intracellular compartment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Amino acids and sulfonic acid derivatives (Taurine-Tau; Hypotaurine-HypTau; Homotaurine-HTau) of 26 different species of commercial macroalgae, microalgae and 10 algae-enriched food products from the market were quantified in a single chromatographic run. Tau and analogues were predominantly distributed in red species followed by green and brown species. Palmaria palmata, Gracilaria longissima and Porphyra sp. were the species with the highest content of Tau and total sulfonic acid derivatives (TAD). Notwithstanding, relatively high concentrations of HTau were found in green algae Ulva lactuca and G. vermicullophyla as well as in the brown algae Undaria pinnatifida. HTau and HypTau were found at lower concentrations than Tau in all species, except in Ulva lactuca. The samples with the highest protein content were the green species Chlorella vulgaris, Nannochloropsis, and Afanizomenon-flos aquae, followed by the red algae Gracilaria longissima and Gracilaria vermicullophyla. Samples of pasta formulated with algae ingredients contained the highest levels of sulfonic acid derivatives, evidencing that these products can provide levels of TAD comparable to those found in foods of animal origin. This study provides, for the first time, quantitative information regarding the distribution of sulfonic acid derivatives and total amino acids in multiple algae species as well as the nutritional impact of the inclusion of algae ingredients in commercial food matrices., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The liver has been thought to protect against oxidative stress through mechanisms involving reduced glutathione (GSH) that consumes high-energy phosphor-nucleotides on its synthesis. However, hepatoprotective mechanisms in acute liver failure (ALF) where the phosphor-nucleotides are decreased in remain to be solved. Liver tissues were collected from patients with ALF and liver cirrhosis (LC) and living donors (HD) who had undergone liver transplantation. Tissues were used for metabolomic analyses to determine metabolites belonging to the central carbon metabolism, and to determine sulfur-containing metabolites. ALF and LC exhibited a significant decline in metabolites of glycolysis and pentose phosphate pathways and high-energy phosphor-nucleotides such as adenosine triphosphate as compared with HD. Conversely, methionine, S -adenosyl-l-methionine, and the ratio of serine to 3-phosphoglycerate were elevated significantly in ALF as compared with LC and HD, suggesting a metabolic boost from glycolysis towards trans-sulfuration. Notably in ALF, the increases in hypotaurine (HTU) + taurine (TU) coincided with decreases in the total amounts of reduced and oxidized glutathione (GSH + 2GSSG). Plasma NH 3 levels correlated with the ratio of HTU + TU to GSH + 2GSSG. Increased tissue levels of HTU + TU vs total glutathione appear to serve as a biomarker correlating with hyperammonemia, suggesting putative roles of the HTU-TU pathway in anti-oxidative protective mechanisms., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2022 JCBN.)

Fruit development is modified by different types of epigenetics. Histone methylation is an important way of epigenetic modification. Eight genes related to H3K4 methyltransferase, named VvH3K4s, were identified and isolated from the grape genome based on conserved domain analysis, which could be divided into 3 categories by the phylogenetic relationship. Transcriptome data showed that VvH3K4-5 was obviously up-regulated during fruit ripe, and its expression level was significantly different between 'Kyoho' and 'Fengzao'. The VvH3K4s promoters contains cis-acting elements of in response to stress, indicating that they may be involved in the metabolic pathways regulated by ROS signaling. The subcellular localization experiment and promoter activity analysis experiment on VvH3K4-5 showed that VvH3K4s may be regulated by H 2 O 2 . With H 2 O 2 and Hypotaurine treatment, it was found that the expression pattern of most genes was opposite, and the expression level showed different expression trend with the extension of treatment time., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Photosynthesis is a pivotal process that determines the synthesis of carbohydrates required for sustaining growth under normal or stress situation. Stress exposure reduces the photosynthetic potential owing to the excess synthesis of reactive oxygen species that disturb the proper functioning of photosynthetic apparatus. This decreased photosynthesis is associated with disturbances in carbohydrate metabolism resulting in reduced growth under stress. We evaluated the importance of melatonin in reducing heat stress-induced severity in wheat ( Triticum aestivum L.) plants. The plants were subjected to 25 °C (optimum temperature) or 40 °C (heat stress) for 15 days at 6 h time duration and then developed the plants for 30 days. Heat stress led to oxidative stress with increased production of thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H 2 O 2 ) content and reduced accrual of total soluble sugars, starch and carbohydrate metabolism enzymes which were reflected in reduced photosynthesis. Application of melatonin not only reduced oxidative stress through lowering TBARS and H 2 O 2 content, augmenting the activity of antioxidative enzymes but also increased the photosynthesis in plant and carbohydrate metabolism that was needed to provide energy and carbon skeleton to the developing plant under stress. However, the increase in these parameters with melatonin was mediated via hydrogen sulfide (H 2 S), as the inhibition of H 2 S by hypotaurine (HT; H 2 S scavenger) reversed the ameliorative effect of melatonin. This suggests a crosstalk of melatonin and H 2 S in protecting heat stress-induced photosynthetic inhibition via regulation of carbohydrate metabolism.

In the present study, the role of hydrogen sulfide (H 2 S) in alleviating NaCl (20 mM) induced toxicity on growth, photosynthetic pigments and photochemistry of PS II, and impact on oxidative stress and antioxidant systems of eggplant and tomato was studied. To confirm the role of H 2 S (donor sodium hydrogen sulphide (NaHS; 40 μM)) under stress, H 2 S scavenger; hypotaurine (HT; 200 μM) and inhibitor, propargylglycine (PAG; 100 μM) in combination with NaHS was added to the growth medium of NaCl stressed seedlings. The NaCl reduced the overall growth of the seedlings as the Na + uptake was increased which led to removal of K + , thereby Na + /K + homeostasis was disturbed. This condition caused severe impact on photosynthetic pigments and PS II photochemistry, thus significant decline in the values of fluorescence kinetics parameters such as F v /F m , F V /F 0 , φE 0 , ѱ 0, PI ABS except F 0 /F V and enhancement in energy flux parameters such as ABS/RC, TR 0 /RC, ET 0 /RC and DI 0 /RC was obtained. Exogenous H 2 S not only abolished the toxic symptoms in test seedlings but also completely alleviated the decline in growth in case of tomato seedlings. Reactive oxygen species accumulation was significantly declined in both the seedlings as evident by in vitro and in vivo analysis with the supplementation of NaHS, indicating appreciable recovery in membrane damage caused by NaCl toxicity. Antioxidative enzymes: SOD, POD, CAT and GST activities were further stimulated in response to H 2 S (NaHS) supplementation to the stressed seedlings, thus maintaining the redox homeostasis of cell and bringing the seedlings back to the healthy state. Moreover, the role of endogenous and exogenous H 2 S was also justified using the scavenger of H 2 S (HT; 200 μM) and inhibitor of enzymes of H 2 S (PAG; 100 μM). Thus, present study emphasizes the role of NaHS as H 2 S donor in alleviating NaCl stress in crops particularly vegetables tomato and eggplant, and may be considered as a part of important strategies to cope up with NaCl toxicity which is prevailing in natural field condition., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Colorectal cancer (CRC) is one of the most common malignant tumors, and previous metabolomics work has demonstrated great promise in identifying specific small molecules of tumor phenotype. In the present study, we analyzed the metabolites of resected tissues through gas chromatography-mass spectrometry (GC-MS), and found that the concentration of taurine in CRC tissues diminished whereas the concentration of hypotaurine increased. The results in vitro demonstrated that taurine significantly suppressed cellular proliferation, metastasis, and colony formation whereas it induced apoptosis in CRC cells. Furthermore, taurine regulated the expression levels of epithelial mesenchymal transition (EMT)-associated genes in a dose-dependent manner. Taurine also alleviated hypotaurine-induced CRC progression, which was linked to the inhibition of the ERK/RSK-signaling pathway and diminution in intracellular hypotaurine. Taurine additionally attenuated hypotaurine-induced tumor growth and metastasis in vivo. Patients with CRC exhibited lower levels of serum taurine, suggesting that taurine might be a promising biomarker reflecting a poor prognosis in CRC. Collectively, our results demonstrated that taurine-attenuated, hypotaurine-induced CRC progression provides a potential target for CRC therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hou, Hu, Zhao, Wei, Zhao, Li and Li.)

The myelinating activity of living Schwann cells in coculture with neuronal cells was examined in situ in a Raman microprobe spectroscope. The Raman label-free approach revealed vibrational fingerprints directly related to the activity of Schwann cells' metabolites and identified molecular species peculiar to myelinating cells. The identified chemical species included antioxidants, such as hypotaurine and glutathione, and compartmentalized water, in addition to sphingolipids, phospholipids, and nucleoside triphosphates also present in neuronal and nonmyelinating Schwann cells. Raman maps at specific frequencies could be collected, which clearly visualized the myelinating action of Schwann cells and located the demyelinated ones. An important finding was the spectroscopic visualization of confined water in the myelin structure, which exhibited a quite pronounced Raman signal at ∼3470 cm -1 . This peculiar signal, whose spatial location precisely corresponded to a low-frequency fingerprint of hypotaurine, was absent in unmyelinating cells and in bulk water. Raman enhancement was attributed to frustration in the hydrogen-bond network as induced by interactions with lipids in the myelin sheaths. According to a generally accepted morphological model of myelin, an explanation was offered of the peculiar Raman scattering of water confined in intraperiod lines, according to an ordered hydrogen bonding structure. The possibility of concurrently mapping antioxidant molecules and compartmentalized water structure with high spectral accuracy and microscopic spatial resolution enables probing myelinating activity and might play a key-role in future studies of neuronal pathologies. Compatible with life, Raman microprobe spectroscopy with the newly discovered probes could be suitable for developing advanced strategies in the reconstruction of injured nerves and nerve terminals at neuromuscular junctions.

Hypotaurine (HT) is a routine component of porcine embryo culture medium, functioning as an antioxidant, but its requirement may be diminished as most embryo culture systems now use 5% O 2 instead of atmospheric (20%) O 2 . Our objective was to determine the effects of removing HT from the culture medium on porcine preimplantation embryo development. Embryos cultured in 20% O 2 without HT had decreased blastocyst development compared to culture with HT or in 5% O 2 with or without HT. Notably, differences in blastocyst development or total cell number were not detected between embryos cultured in 5% O 2 with or without HT. After culture in 5% O 2 without HT and embryo transfer, healthy fetuses were retrieved from two pregnancies on Day 42, confirming in vivo developmental competence. Transcript abundance of proapoptotic markers was decreased in embryos cultured without HT regardless of oxygen tension; however, assays for apoptosis did not demonstrate differences between groups. Additionally, no differences were observed in the development or apoptosis of somatic cell nuclear transfer-derived embryos cultured in 5% O 2 with or without HT. With decreased utility in 5% O 2 , removing HT from porcine embryo culture medium would also have economic advantages because it is undoubtedly the most expensive component., (© 2020 The Authors. Molecular Reproduction and Development Published by Wiley Periodicals LLC.)

Bi-allelic mutations in the dedicator of cytokinesis 8 ( DOCK8 ) are responsible for a rare autosomal recessive primary combined immunodeficiency syndrome, characterized by atopic dermatitis, elevated serum Immunoglobulin E (IgE) levels, recurrent severe cutaneous viral infections, autoimmunity, and predisposition to malignancy. The molecular link between DOCK8 deficiency and atopic skin inflammation remains unknown. Severe atopic dermatitis (AD) and DOCK8 deficiency share some clinical symptoms, including eczema, eosinophilia, and increased serum IgE levels. Increased serum IgE levels are characteristic of, but not specific to allergic diseases. Herein, we aimed to study the metabolomic profiles of DOCK8-deficient and AD patients for potential disease-specific biomarkers using chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS). Serum samples were collected from DOCK8-deficient ( n = 10) and AD ( n = 9) patients. Metabolomics profiling using CIL LC-MS was performed on patient samples and compared to unrelated healthy controls ( n = 33). Seven metabolites were positively identified, distinguishing DOCK8-deficient from AD patients. Aspartic acid and 3-hydroxyanthranillic acid (3HAA, a tryptophan degradation pathway intermediate) were up-regulated in DOCK8 deficiency, whereas hypotaurine, leucyl-phenylalanine, glycyl-phenylalanine, and guanosine were down-regulated. Hypotaurine, 3-hydroxyanthranillic acid, and glycyl-phenyalanine were identified as potential biomarkers specific to DOCK8 deficiency. Aspartate availability has been recently implicated as a limiting metabolite for tumour growth and 3HAA; furthermore, other tryptophan metabolism pathway-related molecules have been considered as potential novel targets for cancer therapy. Taken together, perturbations in tryptophan degradation and increased availability of aspartate suggest a link of DOCK8 deficiency to oncogenesis. Additionally, perturbations in taurine and dipeptides metabolism suggest altered antixidation and cell signaling states in DOCK8 deficiency. Further studies examining the mechanisms underlying these observations are necessary.

Despite advances in vitrification techniques for sperm cryopreservation, cryo-damages of sperm caused by generation of reactive oxygen species (ROS) continue to impede implementation of this technique. This study analyses the effects of taurine and hypotaurine as anti-oxidants during vitrification of human sperms. The study was performed in two steps. In the first step, 20 normospermic semen samples were vitrified in the presence of varying concentrations of taurine and hypotaurine, and their effects as anti-oxidant agents on classical sperm parameters, hyaluronan-binding assay (HBA), lipid peroxidation (LPO) and acrosome reaction (AR) were studied. Statistical analyses showed that the sperm parameters in all vitrified groups decreased significantly (P < 0.05) compared to the fresh group. However, HBA and acrosome integrity in vitrified groups containing taurine and 50 mM of hypotaurine were better than in the control group (P < 0.05). The morphology of the vitrified group was good only in the group that contained 50 mM of hypotaurine (P < 0.05). Based on the results from the first step, 50 mM of hypotaurine was considered the ideal anti-oxidant formulation and further tests were carried out on 10 normospermic semen samples with this protecting agent. In addition to the mentioned parameters, the expression of heat shock proteinA2 (HSPA2) was studied in the vitrified group with 50 mM hypotaurine, warmed under two different warming temperatures 37 and 42 °C. 50 mM Hypotaurine was found to equally improve motility, morphology, HBA, and AR after warming at 37 °C and 42 °C (P < 0.05). However, at both warming temperatures, the expression of HSPA2 was reduced in all vitrified groups comparing to the fresh group (P < 0.05). In conclusion, taurine and hypotaurine antioxidants, especially 50 mM hypotaurine, are able to reduce deleterious cryo-injuries on morphology, acrosome and HBA and improve sperm recovery at both warming temperatures (37 and 42 °C). However, they do not have any protective action on expression of HSPA2., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A fast and reliable method for the simultaneous quantification of Taurine, Homotaurine, Hypotaurine and 19 amino acids in algae samples by Ultra-performance liquid chromatography coupled with diode array and tandem mass spectrometry (UHPLC-DAD-MS/MS) was optimized and validated. Target compounds were chromatographically resolved in less than 15 min. (ESI)-MS/MS electrospray ionization and pure analytical standards were used to confirm the identity of all analytes, while quantitation was carried out with diode array detection. Validation parameters of the method were satisfactory: Resolution of peak pairs was always higher than 1.55; all analytical curves showed R 2  > 0.99, with working ranges between 0.04 mg/g to 33.1 mg/g and 9.13 mg/g to 107 mg/g and the Lack-of-fit test was not significant. The intra and inter-day precision of the method (expressed as relative standard deviation) were lower than 6% and recovery values ranged between 95% and 105%. The method was demonstrated to be robust to small deliberate variations of seven variables such sample weight, volume of hydrolysis reagent, hydrolysis time and temperature, derivatization time, column temperature and flow rate. The mean expanded uncertainty for all the target compounds were 0.7 mg/g with a coverage factor of 2. Method Limits of detection and quantification varied from 0.005 * 10 -3 mg/g to 0.11 * 10 -3 mg/g and 0.01* 10 -3 mg/g to 0.22 * 10 -3 mg/g respectively, allowing the routine determination of these bioactive compounds in algae extracts. Therefore, the method was successfully applied for the quantitative determination of the 22 target compounds in five seaweed commercial samples. Relevant compounds were quantified for the first time in the five algae species, namely: i) Taurine in Gracilaria longissima and Chlorella spp., ii) Gamma-aminobutyric acid in G. longissima and L. japonica, iii) Hydroxyproline in G. longissima, Ulva lactuca, Porphyra spp., and L. japonica and iv) Homotaurine and Hypotaurine in the five species studied., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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 (H 2 S) 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.

Mammalian γ-aminobutyric acid (GABA) transporter subtype 1 (GAT-1) is a specific transporter for GABA, an inhibitory neurotransmitter in GABA-ergic neurons. GAT-1 belongs to the GAT group, in which five related transporters, GAT-2, GAT-3, GAT-4, CT1, and TAUT are known in mammals. By contrast, the deep-sea mussel, Bathymodiolus septemdierum has only two GAT group members, BsGAT-1 and BsTAUT, and their function in environmental adaptation is of interest to better understand the physiology of deep-sea organisms. Compared with BsTAUT, the function of BsGAT-1 is unknown. Here, we report the functional characterization of BsGAT-1. Analyses of BsGAT-1 expressed in Xenopus oocytes showed that it could transport GABA in a Na + - and Cl - -dependent manner, with Km and Vmax values of 0.58 μM and 1.97 pmol/oocyte/h, respectively. BsGAT-1 activity was blocked by the GAT-1 selective inhibitors SKF89976A and ACHC. Competition assays indicated that BsGAT-1 has no affinity for taurine and thiotaurine. These characteristics were common with those of mammalian GAT-1, suggesting its conserved function in the nervous system. However, BsGAT-1 showed a certain affinity for hypotaurine, which is involved in sulfide detoxification in hydrothermal vent-specific animals. This result suggests an additional role for BsGAT-1 in sulfide detoxification, which may be specific to the deep-sea mussel. In a tissue distribution analysis, BsGAT-1 mRNA expression was observed in various tissues. The expression in the adductor and byssus retractor muscles, labial palp, and foot, which possibly contain ganglia, suggested a function in the neural system, while BsGAT-1 expression in other tissues might be related to sulfide detoxification., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This manuscript summarizes the effect of certain cell culture medium additives on antibody drug substance coloration and acidic charge variants. It has been shown previously that B-vitamins and iron in the cell culture medium could significantly impact color intensity. In this manuscript, we detail the effect of several other cell culture components that have been shown to impact coloration. It is shown that if cystine is used instead of cysteine in the cell culture medium, coloration was reduced. Hydrocortisone has been shown to reduce coloration and boost specific productivity. The effect of a peptone/hydrolysate on coloration was investigated in cell culture experiments, which showed its use can lead to reduced coloration. Mechanisms by which these compounds influence coloration will be briefly discussed. Since it has been previously shown that antibody oxidation could potentially lead to coloration, the current effort was focused on screening for specific antioxidant additives to the culture medium to reduce coloration. An in-vitro incubation model was used to screen antioxidant compounds, several of which were found to significantly reduce antibody color, while some led to significantly increased color. Hypotaurine and carboxymethylcysteine, which had the most significant color reducing effect in the incubation study, were further tested in small-scale bioreactor cell culture experiments. These studies demonstrated that these compounds lead to reduced coloration in cell culture without affecting cell growth and titer. Hypotaurine, hydrocortisone, peptone, and cystine were also shown to reduce the acidic charge variant levels, which was previously shown to correlate with color. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018 © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1298-1307, 2018., (© 2018 American Institute of Chemical Engineers.)

Background: The amino acid taurine (2-Aminoethanesulfonic acid) modulates inhibitory neurotransmitter receptors. This study aimed to determine if the dual action of taurine on GABA C -ρ1R relates to its structure. To address this, we tested the ability of the structurally related compounds homotaurine, hypotaurine, and isethionic acid to modulate GABA C -ρ1R., Results: In Xenopus laevis oocytes, hypotaurine and homotaurine partially activate heterologously expressed GABA C -ρ1R, showing an increment in its deactivation time with no changes in channel permeability, whereas isethionic acid showed no effect. Competitive assays suggest that hypotaurine and homotaurine compete for the GABA-binding site. In addition, their effects were blocked by the ion-channel blockers picrotixin and Methyl(1,2,5,6-tetrahydropyridine-4-yl) phosphinic acid. In contrast to taurine, co-application of GABA with hypotaurine or homotaurine revealed that the dual effect is present separately for each compound: hypotaurine modulates positively the GABA current, while homotaurine shows a negative modulation, both in a dose-dependent manner. Interestingly, homotaurine diminished hypotaurine-induced currents. Thus, these results strongly suggest a competitive interaction between GABA and homotaurine or hypotaurine for the same binding site. "In silico" modeling confirms these observations, but it also shows a second binding site for homotaurine, which could explain the negative effect of this compound on the current generated by GABA or hypotaurine, during co-application protocols., Conclusions: The sulfur-containing compounds structurally related to taurine are partial agonists of GABA C -ρ1R that occupy the agonist binding site. The dual effect is unique to taurine, whereas in the case of hypotaurine and homotaurine it presents separately; hypotaurine increases and homotaurine decreases the GABA current.

Hypotaurine is a precursor of taurine and a physiological antioxidant that circulates in adult and fetal plasma. The purpose of the present study was to clarify whether hypotaurine is a substrate of Slc6a/gamma-aminobutyric acid (GABA) transporter family members. Radiolabeled hypotaurine was synthesized from radiolabeled cysteamine and 2-aminoethanethiol dioxygenase. The uptakes of [ 3 H]GABA, [ 3 H]taurine, and [ 14 C]hypotaurine by HEK293 cells expressing mouse GAT1/Slc6a1, TAUT/Slc6a6, GAT3/Slc6a11, BGT1/Slc6a12, and GAT2/Slc6a13 were measured. TAUT and GAT2 showed strong [ 14 C]hypotaurine uptake activity, while BGT1 showed moderate activity, and GAT1 and GAT3 showed slight but significant activity. Mouse TAUT and GAT2 both showed Michaelis constants of 11 µM for hypotaurine uptake. GAT2-expressing cells pretreated with hypotaurine showed resistance to H 2 O 2 -induced oxidative stress. These results suggest that under physiological conditions, TAUT and GAT2 would be major contributors to hypotaurine transfer across the plasma membrane, and that uptake of hypotaurine via GAT2 contributes to the cellular resistance to oxidative stress.

Hypotaurine and taurine are amino acid derivatives and abundant molecules in many eukaryotes. The biological reaction in which hypotaurine is converted to taurine remains poorly understood. Here, hypotaurine and taurine were observed to react with superoxide anion in vitro to form the novel molecule peroxytaurine. In contrast, hypotaurine reacts with hydrogen peroxide to form taurine, but taurine does not react with hydrogen peroxide in vitro. Mass and NMR spectrometry as well as FTIR and Raman spectroscopy support the molecular characterization of peroxytaurine. Gravitometric and spectroscopy experiments suggest a stoichiometry of two superoxide anions reacting with one hypotaurine or two taurines. The newly identified molecule is a semi-stable, organic peroxysulfonic acid that may be an intermediate metabolite in taurine synthesis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Copper-zinc superoxide dismutase (SOD) is considered one of the most important mammalian antioxidant defenses and plays a relevant role due to its main function in catalyzing the dismutation of superoxide anion to oxygen and hydrogen peroxide. However, interaction between SOD and H 2 O 2 produced a strong copper-bound oxidant (Cu(II) • OH) that seems able to contrast the self-inactivation of the enzyme or oxidize other molecules through its peroxidase activity. The bicarbonate presence enhances the peroxidase activity and produces the carbonate anion radical (CO 3 •- ). CO 3 •- , which spreads out of the binding site and oxidizes hypotaurine and cysteine sulfinic acid to the respective sulfonates through an efficient reaction. These findings suggest a defense role for sulfinates against the damage caused by CO • . The effect of hypotaurine and cysteine sulfinic acid on the CO 3 •- , which spreads out of the binding site and oxidizes hypotaurine and cysteine sulfinic acid to the respective sulfonates through an efficient reaction. These findings suggest a defense role for sulfinates against the damage caused by CO 3 . The effect of hypotaurine and cysteine sulfinic acid against SOD inactivation by H •- . The effect of hypotaurine and cysteine sulfinic acid on the CO 3 (~42% protection of enzyme activity) has also been investigated. Interestingly, hypotaurine and cysteine sulfinic acid partially avoid the H •- -mediated oxidation of the peroxidase probe ABTS to ABTS cation radical (ABTS •+ -mediated SOD inactivation, suggesting that the two sulfinates may have access to the SOD reactive site and preserve it by reacting with the copper-bound oxidant. In this way hypotaurine and cysteine sulfinic acid not only intercept CO 3 •- . The effect of hypotaurine and cysteine sulfinic acid against SOD inactivation by H 2 O 2 (~42% protection of enzyme activity) has also been investigated. Interestingly, hypotaurine and cysteine sulfinic acid partially avoid the H 2 O 2 -mediated SOD inactivation, suggesting that the two sulfinates may have access to the SOD reactive site and preserve it by reacting with the copper-bound oxidant. In this way hypotaurine and cysteine sulfinic acid not only intercept CO 3 •- which could move out from the reactive site and cause oxidative damage, but also prevents the inactivation of SOD.

Considerable strides have been made in understanding the oxidative mechanisms involved in the final steps of the cysteine pathway leading to taurine. The oxidation of sulfinates, hypotaurine and cysteine sulfinic acid, to the respective sulfonates, taurine and cysteic acid, has never been associated with any specific enzyme. Conversely, there is strong evidence that in vivo formation of taurine and cysteic acid is the result of sulfinate interaction with a variety of biologically relevant oxidants. In the last decade, many experiments have been performed to understand whether peroxynitrite, nitrogen dioxide and carbonate radical anion could be included in the biologically relevant reactive species capable of oxidizing sulfinates. Thanks to this work, it has been possible to highlight two possible reaction mechanisms (direct and indirect reaction) of sulfinates with reactive oxygen and nitrogen species.The sulfinates oxidation, mediated by peroxynitrite, is an example of both reaction mechanisms: through a two-electron-direct-reaction with peroxynitrite or through a one-electron-indirect-transfer reaction. In the indirect mechanism, the peroxynitrite homolysis releases hydroxyl and nitrogen dioxide radical and in addition the degradation of short-lived adduct formed by peroxynitrite and CO 2 can generate carbonate radical anion. The reaction of hypotaurine and cysteine sulfinic acid with peroxynitrite-derived radicals is accompanied by extensive oxygen uptake with the generation of transient intermediates, which can begin a reaction by an oxygen-dependent mechanism with the sulfonates, taurine, and cysteic acid as final products. Due to pulse radiolysis studies, it has been shown that transient sulfonyl radicals (RSO 2 ) have been produced during the oxidation of both sulfinates by one-electron transfer reaction.The purpose is to analyze all the aspects of the reactive mechanism in the sulfinic group oxidation of hypotaurine and cysteine sulfinic acid through the results obtained from our laboratory in recent years.• ) have been produced during the oxidation of both sulfinates by one-electron transfer reaction.The purpose is to analyze all the aspects of the reactive mechanism in the sulfinic group oxidation of hypotaurine and cysteine sulfinic acid through the results obtained from our laboratory in recent years.

Metabolomics has shown significant potential in identifying small molecules specific to tumor phenotypes. In this study we analyzed resected tissue metabolites using capillary electrophoresis-mass spectrometry and found that tissue hypotaurine levels strongly and positively correlated with glioma grade. In vitro studies were conducted to show that hypotaurine activates hypoxia signaling through the competitive inhibition of prolyl hydroxylase domain-2. This leads to the activation of hypoxia signaling as well as to the enhancement of glioma cell proliferation and invasion. In contrast, taurine, the oxidation metabolite of hypotaurine, decreased intracellular hypotaurine and resulted in glioma cell growth arrest. Lastly, a glioblastoma xenograft mice model was supplemented with taurine feed and exhibited impaired tumor growth. Taken together, these findings suggest that hypotaurine is an aberrantly produced oncometabolite, mediating tumor molecular pathophysiology and progression. The hypotaurine metabolic pathway may provide a potentially new target for glioblastoma diagnosis and therapy.

Hydrothermal vent environmental conditions are characterized by high sulfide concentrations, fluctuating osmolality, and irregular temperature elevations caused by vent effluents. These parameters represent potential stressors for organisms that inhabit the area around hydrothermal vents. Here, we aimed to obtain a better understanding of the adaptation mechanisms of marine species to hydrothermal vent environments. Specifically, we examined the effect of sulfide, osmolality, and thermal stress on the expression of taurine transporter (TAUT) mRNA in the gill of the deep-sea mussel Bathymodiolus septemdierum, which is a dominant species around hydrothermal vent sites. We analyzed TAUT mRNA levels by quantitative real-time polymerase chain reaction (PCR) in the gill of mussels exposed to sulfide (0.1 or 1mg/L Na2S·9H2O), hyper- (115% seawater) and hypo- (97.5%, 95.5%, and 85% seawater) osmotic conditions, and thermal stresses (12°C and 20°C) for 24 and 48h. The results showed that mussels exposed to relatively low levels of sulfide (0.1mg/L) and moderate heat stress (12°C) exhibited higher TAUT mRNA levels than the control. Although hyper- and hypo-osmotic stress did not significantly change TAUT mRNA levels, slight induction was observed in mussels exposed to low osmolality. Our results indicate that TAUT is involved in the coping mechanism of mussels to various hydrothermal vent stresses., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Hypotaurine is a precursor of taurine and an antioxidant, and is concentrated in fetal plasma compared to maternal plasma. Hypotaurine is significantly decreased in fetal plasma of ezrin (Vil2) knock-out mice, and fetuses show intrauterine growth retardation. The aim of this study was to characterize the mechanism through which cellular hypotaurine level is maintained in placental trophoblasts, and the effect of hypotaurine on oxidative stress induced by hydrogen peroxide (H2O2)., Methods: Hypotaurine transfer from extracellular fluid and antioxidant effect of hypotaurine were analyzed in rat placental trophoblast TR-TBT 18d-1 cells., Results: We found that hypotaurine is concentrated into rat placental trophoblast TR-TBT 18d-1 cells, and the level of hypotaurine was markedly reduced by culture in medium supplemented with dialyzed fetal bovine serum (FBS) instead of normal FBS. The hypotaurine level recovered almost completely when hypotaurine was added to the culture medium, indicating that intracellular hypotaurine is predominantly supplied by transport across the plasma membrane from extracellular fluid rather than by biosynthesis. Hypotaurine showed a cytoprotective effect against H2O2-induced oxidative damage in TR-TBT 18d-1 cells. Hypotaurine treatment of TR-TBT 18d-1 cells increased antioxidant capacity against hydroxyl radical and peroxyl radical. The concentration of intracellular hydroxyl radical induced by H2O2 in TR-TBT 18d-1 cells was significantly reduced by hypotaurine treatment., Discussion: These results indicate that intracellular hypotaurine is mainly supplied to placental trophoblasts by transfer from extracellular fluid across the plasma membrane, and may play a role in cell protection by scavenging reactive oxygen species., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Non-alcoholic fatty liver disease (NAFLD) is the commonest form of chronic liver disease in developed countries. Non-alcoholic steatohepatitis (NASH), which represents advanced stage NAFLD, is increasingly being recognized as a major cause of liver-related morbidity and mortality. However, no effective drugs against NASH have yet been developed. Therefore, we searched for candidate therapeutic agents based on the changes in levels of hepatic metabolites via gas chromatography mass spectrometry (GC/MS)-based metabolome analysis of livers from methionine-choline deficient (MCD) diet-fed mice, a mouse model of NASH., Methods: The metabolites were extracted from the livers of the MCD diet-fed mice and then analyzed using GC/MS. Subsequently, the MCD diet-fed mice were supplemented with hypotaurine, and the therapeutic effects of hypotaurine against steatohepatitis were evaluated., Results: Ninety-nine metabolites were detected in the livers of the MCD diet-induced steatohepatitis model mice. Among these metabolites, hypotaurine exhibited the greatest decrease in its concentration in the mice. Supplementation with 2 mmol/kgBW hypotaurine attenuated liver injuries and fat accumulation caused by the MCD diet-induced steatohepatitis. Furthermore, 10 mmol/kgBW hypotaurine supplementation ameliorated fibrosis and oxidative stress induced by the MCD diet., Conclusion: The present metabolome analysis-based study demonstrated that hypotaurine is a novel candidate therapeutic agent for NASH., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Hydrogen sulfide (H2S) is considered as a cellular signaling intermediate in higher plants, but corresponding molecular mechanisms and signal transduction pathways in plant biology are still limited. In the present study, a combination of pharmacological and biochemical approaches was used to study the effect of H2S on the alleviation of GA-induced programmed cell death (PCD) in wheat aleurone cells. The results showed that in contrast with the responses of ABA, GA brought about a gradual decrease of l-cysteine desulfhydrase (LCD) activity and H2S production, and thereafter PCD occurred. Exogenous H2S donor sodium hydrosulfide (NaHS) not only effectively blocked the decrease of endogenous H2S release, but also alleviated GA-triggered PCD in wheat aleurone cells. These responses were sensitive to hypotaurine (HT), a H2S scavenger, suggesting that this effect of NaHS was in an H2S-dependent fashion. Further experiment confirmed that H2S, rather than other sodium- or sulphur-containing compounds derived from the decomposing of NaHS, was attributed to the rescuing response. Importantly, the reversing effect was associated with glutathione (GSH) because the NaHS triggered increases of endogenous GSH content and the ratio of GSH/oxidized GSH (GSSG) in GA-treated layers, and the NaHS-mediated alleviation of PCD was markedly eliminated by l-buthionine-sulfoximine (BSO, a selective inhibitor of GSH biosynthesis). The inducible effect of NaHS was also ascribed to the modulation of heme oxygenase-1 (HO-1), because the specific inhibitor of HO-1 zinc protoporphyrin IX (ZnPP) significantly suppressed the NaHS-related responses. By contrast, the above inhibitory effects were reversed partially when carbon monoxide (CO) aqueous solution or bilirubin (BR), two of the by-products of HO-1, was added, respectively. NaHS-triggered HO-1 gene expression in GA-treated layers was also confirmed. Together, the above results clearly suggested that the H2S-delayed PCD in GA-treated wheat aleurone cells was associated with the modulation of GSH homeostasis and HO-1 gene expression., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Nitric oxide (NO) and hydrogen sulfide (H2S) are important gaseous molecules, serving as important secondary messengers in plant response to various biotic and abiotic stresses. However, the interaction between NO and H2S in plant stress response was largely unclear. In this study, endogenous NO and H2S were evidently induced by cadmium stress treatment in bermudagrass, and exogenous applications of NO donor (sodium nitroprusside, SNP) or H2S donor (sodium hydrosulfide, NaHS) conferred improved cadmium stress tolerance. Additionally, SNP and NaHS treatments alleviated cadmium stress-triggered plant growth inhibition, cell damage and reactive oxygen species (ROS) burst, partly via modulating enzymatic and non-enzymatic antioxidants. Moreover, SNP and NaHS treatments also induced the productions of both NO and H2S in the presence of Cd. Interestingly, combined treatments with inhibitors and scavengers of NO and H2S under cadmium stress condition showed that NO signal could be blocked by both NO and H2S inhibitors and scavengers, while H2S signal was specifically blocked by H2S inhibitors and scavengers, indicating that NO-activated H2S was essential for cadmium stress response. Taken together, we assigned the protective roles of endogenous and exogenous NO and H2S in bermudagrass response to cadmium stress, and speculated that NO-activated H2S might be essential for cadmium stress response in bermudagrass., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Study Question: Can selection of spermatozoa by density gradient centrifugation prior to cryopreservation and/or hypotaurine supplementation improve the post-thaw quality of sperm from infertile men with oligoasthenoteratozoospermia?, Summary Answer: Sperm selection by density gradient centrifugation before freezing and supplementation of the media by hypotaurine is beneficial for the cryopreservation of semen samples of patients with oligoasthenoteratozoospermia., What Is Known Already: Sperm from men with oligoasthenoteratozoospermia are more susceptible than normal to cryoinjury. Density gradient centrifugation before sperm freezing may allow the selection of a subpopulation of spermatozoa more resistant to cryopreservation. Hypotaurine is an antioxidant with a protective effect on sperm functions., Study Design, Size, Duration: The experiment was carried out according to a factorial design involving two binary factors resulting in four treatment combinations which were randomly allocated in oligoasthenoteratozoospermia sperm samples from 64 patients recruited between January 2009 and June 2010., Participants/materials, Setting, Methods: Semen was provided by 64 men undergoing evaluation for infertility at the Centre for Reproductive Medicine of the University Hospital in Clermont-Ferrand, France, between January 2009 and June 2010. Four treatment combinations were tested: sperm freezing before selection without (F-S/H-; n = 16) and with hypotaurine supplementation (F-S/H+; n = 16); sperm selection before freezing without (S-F/H-; n = 16) and with hypotaurine supplementation (S-F/H+; n = 16). Measurements of sperm recovery rates and markers of apoptosis (externalization of phosphatidylserine (PS), mitochondrial membrane potential and DNA fragmentation) were compared in recovered spermatozoa after each procedure., Main Results and the Role of Chance: Higher recovery rates of progressive and total motile spermatozoa were observed when sperm selection was performed before freezing (P < 0.05). The protective effect of hypotaurine was only observed on the percentage of live spermatozoa with PS externalization among total live spermatozoa (AN+ PI-/((AN+ PI-) + (AN- PI-)) when the sperm selection by density gradient centrifugation was performed before freezing (S-F/H+ versus S-F/H-: 6.8 ± 1.09 versus 11.8 ± 2.03%, P = 0.04). The percentage of mitochondrial membrane potential (DiOC6(3) (high)) spermatozoa was higher (P = 0.001) when sperm selection was done before freezing compared with procedures in which sperm selection was done after sperm freezing with (S-F/H+ versus F-S/H+: 58.1 ± 3.50 versus 46.7 ± 5.48%) or without (S-F/H- versus F-S/H-: 57.0 ± 5.18 versus 35.4 ± 4.99%) hypotaurine supplementation. The percentages of TUNEL+ spermatozoa were significantly lower (P = 0.001) when sperm selection was done before sperm freezing compared with procedures in which sperm selection was done after sperm freezing with (S-F/H+ versus F-S/H+: 38.6 ± 9.59 versus 55.7 ± 5.88%) or without hypotaurine supplementation (S-F/H- versus F-S/H-: 37.2 ± 7.91 versus 71.0 ± 5.66%)., Limitations, Reasons for Caution: The ICSI outcomes were not assessed and the fertility of the spermatozoa remains unknown., Wider Implications of the Findings: Sperm selection by density gradient centrifugation before freezing and hypotaurine supplementation could improve the cryopreservation of sperm from oligoasthenoteratozoospermic men and make a larger number of functional spermatozoa available for ICSI., Study Funding/competing Interets(s): This work was supported by a hospital grant (Projet Hospitalier Recherche Clinique, CHU Clermont Ferrand, France). None of the authors has any conflict of interest to declare.

Metabolome analyses assisted by capillary electrophoresis-mass spectrometry (CE-MS) have allowed us to systematically grasp changes in small molecular metabolites under disease conditions. We applied CE-MS to mine out biomarkers in hepatic ischemia-reperfusion. Rat livers were exposed to ischemia by clamping of the portal inlet followed by reperfusion. Metabolomic profiling revealed that l contents of taurine in liver and plasma were significantly increased. Of interest is an elevation of hypotaurine, collectively suggesting significance of hypotaurine/taurine in post-ischemic responses. Considering the anti-oxidative capacity of hypotaurine, we examined if supplementation of the compound or its precursor amino acids could affect hepatocellular viability and contents of taurine in liver and plasma. Administration of hypotaurine, N-acetylcysteine or methionine upon reperfusion comparablly attenuated the post-ischemic hepatocellular injury but with different metabolomic profiling among groups: rats treated with methionine or N-acetylcysteine but not those treated with hypotaurine, exhibited significant elevation of hepatic lactate generation without notable recovery of the energy charge. Furthermore, the group treated with hypotaurine exhibited elevation of the plasma taurine, suggesting that the exogenously administered compound was utilized as an antioxidant. These results suggest that taurine serves as a surrogate marker for ischemia-reperfusion indicating effectiveness of hypotaurine as an energy-saving hepatoprotective amino acid.