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To realize the potential for the use of N -chlorotaurine (NCT) in healthcare, a better understanding of the long-term stability of the compound in water is needed. An array of analytical procedures is required that can measure changes in NCT concentration over time and allow for the detection and identification of contaminants and likely degradation end products. We used UV-Vis and NMR spectroscopy, HPLC, and LCMS to establish the stability of NCT in solutions subjected to prolonged ambient and elevated temperatures. Stability proved to be dependent on concentration with half-lives of ~120 days and ~236 days for 1% and 0.5% solutions of NCT at ~20 °C. Regardless of initial pH, all solutions shifted toward and maintained a pH of ~8.3 at 20 °C and 40 °C. NCT at 500 µg/mL and 250 µg /mL inhibited biofilm formation by Pseudomonas aeruginosa and Staphylococcus aureus but did not disperse established biofilms. NCT exposure to the biofilms had profound effects on the viability of both bacteria, reducing live organisms by >90%. Exposure of Interleukin-6 (IL-6) to 11 µM NCT reduced the binding of IL-6 to an immobilized specific antibody by ~48%, which is 5× the amount required for HOCl to bring about the same effect in this test system. Our data demonstrate the potency of the compound as an antimicrobial agent with potential benefits in the management of infected chronic wounds and suggest that NCT may contribute to anti-inflammatory processes in vivo by direct modification of cytokine mediators.

The kinetics of amyloid aggregation was studied indirectly by monitoring the changes in the polydispersity of mixed dispersion of amyloid β peptide (1-40) and composite liposomes. The liposomes were prepared from the 1,2-dioleoyl-sn-glicero-3-phoshocholine (DOPC) phospholipid and stabilised by the electrostatic adsorption of κ-carrageenan. The produced homotaurine-loaded and unloaded liposomes had a highly negative electrokinetic potential and remarkable stability in phosphate buffer (pH 4 and 7.4). For the first time, the appearance and evolution of the aggregation of Aβ were presented through the variation in the standard percentile readings (D10, D50, and D90) obtained from the particle size distribution analysis. The kinetic experiments indicated the appearance of the first aggregates almost 30 min after mixing the liposomes and peptide solution. It was observed that by adding unloaded liposomes, the size of 90% of the particles in the dispersion (D90) increased. In contrast, the addition of homotaurine-loaded liposomes had almost minimal impact on the size of the fractions of larger particles during the kinetic experiments. Despite the specific bioactivity of homotaurine in the presence of natural cell membranes, this study reported an additional inhibitory effect of the compound on the amyloid peptide aggregation due to the charge effects and 'molecular crowding'.

Wound dressing diligently facilitate healing by fostering hemostasis, immunoregulation, the angiogenesis, and collagen deposition. Our methodology entails fabricating chitosan-taurine nanoparticles (CS-Tau) through an ionic gelation method. The morphology of CS-Tau was observed utilizing Transmission electron microscopy (TEM), scanning electron microscopy (SEM) and Dynamic Light Scattering (DLS). The nanoparticles are subsequently incorporated into carboxymethyl chitosan hydrogels for crosslinking by EDC-NHS, yielding hydrogel dressings (CMCS-CS-Tau) designed to extend the duration of taurine release. In vitro investigations confirmed that these innovative compound dressings displayed superior biodegradation, biocompatibility, cytocompatibility, and non-toxicity, in addition to possessing anti-inflammatory properties, and stimulating the proliferation and mobility of human umbilical vein endothelial cells (HUVECs). Experiments conducted on mice models with full-thickness skin removal demonstrated that CMCS-CS-Tau efficaciously aided in wound healing by spurring angiogenesis, and encouraging collagen deposition. CMCS-CS-Tau can also minimize inflammation and promote collagen deposition in chronic diabetic wound. Hence, CMCS-CS-Tau promotes both acute and chronic diabetic wound healing. Furthermore, the sustained release mechanism of CMCS-CS-Tau on taurine reveals promising potential for extending its clinical utility in relation to various biological effects of taurine., 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.)

Ruxolitinib (RXL) is a Janus kinase inhibitor used for treating intermediate- or high-risk myelofibrosis. This study presents an electrode modified with electrochemically polymerized taurine on a carbon paste electrode via cyclic voltammetry (CV). The surface characterization of the poly(taurine)-CP electrode was evaluated by using electrochemical (electrochemical impedance spectroscopy─EIS, CV), morphological (scanning electron microscope─SEM), and spectroscopic (Fourier-transform infrared spectroscopy─FT-IR) techniques. Under optimized conditions, RXL exhibited good linearity within the 0.01-1.0 μM concentration range, with a limit of detection (LOD) of 0.005 μM. The proposed electrochemical sensor demonstrated excellent selectivity, accuracy, precision, and repeatability. Furthermore, it effectively detected RXL in human urine and pharmaceutical samples.

Background: The relationship between circulating bile acids (BAs) and kidney function among patients with type 2 diabetes is unclear. We aimed to investigate the associations of circulating concentrations of BAs, particularly individual BA subtypes, with chronic kidney disease (CKD) in patients of newly diagnosed type 2 diabetes., Methods: In this cross-sectional study, we included 1234 newly diagnosed type 2 diabetes who participated in an ongoing prospective study, the Dongfeng-Tongji cohort. Circulating primary and secondary unconjugated BAs and their taurine- or glycine-conjugates were measured using ultraperformance liquid chromatography-tandem mass spectrometry. CKD was defined as eGFR < 60 ml/min per 1.73 m 2 . Logistic regression model was used to compute odds ratio (OR) and 95% confidence interval (CI)., Results: After adjusting for multiple testing, higher levels of total primary BAs (OR per standard deviation [SD] increment: 0.78; 95% CI: 0.65-0.92), cholate (OR per SD: 0.78; 95% CI: 0.66-0.92), chenodeoxycholate (OR per SD: 0.81; 95% CI: 0.69-0.96), glycocholate (OR per SD: 0.81; 95% CI: 0.68-0.96), and glycochenodeoxycholate (OR per SD: 0.82; 95% CI: 0.69-0.97) were associated with a lower likelihood of having CKD in patients with newly diagnosed type 2 diabetes. No significant relationships between secondary BAs and odds of CKD were observed., Conclusions: Our findings showed that higher concentrations of circulating unconjugated primary BAs and their glycine-conjugates, but not taurine-conjugates or secondary BAs, were associated with lower odds of having CKD in patients with type 2 diabetes., (© 2024. The Author(s).)

Taurine/α-ketoglutarate dioxygenase is an important enzyme that takes part in the cysteine catabolism process in the human body and selectively hydroxylates taurine at the C 1 -position. Recent computational studies showed that in the gas-phase the C 2 -H bond of taurine is substantially weaker than the C 1 -H bond, yet no evidence exists of 2-hydroxytaurine products. To this end, a detailed computational study on the selectivity patterns in TauD was performed. The calculations show that the second-coordination sphere and the protonation states of residues play a major role in guiding the enzyme to the right selectivity. Specifically, a single proton on an active site histidine residue can change the regioselectivity of the reaction through its electrostatic perturbations in the active site and effectively changes the C 1 -H and C 2 -H bond strengths of taurine. This is further emphasized by many polar and hydrogen bonding interactions of the protein cage in TauD with the substrate and the oxidant that weaken the pro-R C 1 -H bond and triggers a chemoselective reaction process. The large cluster models reproduce the experimental free energy of activation excellently., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Owing to the poor outcomes and adverse side effects of existing ulcerative colitis drugs, the study aimed to develop an alternative nano-based treatment approach. The study was designed to characterize the in vitro and in vivo properties of taurine, taurine-loaded chitosan pectin nanoparticles (Tau-CS-PT-NPs) and chitosan pectin nanoparticles (CS-PT-NPs) in the therapy of acetic acid (AA)-induced colitis in rats. CS-PT-NPs and Tau-CS-PT-NPs were prepared by ionic gelation method then in vitro characterized, including transmission electron microscopy (TEM), polydispersity index (PDI), zeta potential, Fourier transform infrared (FTIR) spectroscopy, encapsulation efficiency (EE), and drug release profile. Following colitis induction, rats were orally administrated with free taurine, Tau-CS-PT-NPs, and CS-PT-NPs once per day for six days. The sizes of Tau-CS-PT-NPs and CS-PT-NPs were 74.17 ± 2.88 nm and 42.22 ± 2.41 nm, respectively. EE was about 69.09 ± 1.58%; furthermore, 60% of taurine was released in 4 h in simulated colon content. AA-induced colitis in untreated rats led to necrosis of colon tissues and a significant increase in interleukin-1beta (IL-1β), Tumor Necrosis Factor-alpha (TNF-α), myeloperoxidase (MPO), and malondialdehyde (MDA) levels associated with a remarkable reduction in glutathione (GSH) level in colon tissue in comparison to control group. Treatment with taurine, Tau-CS-PT-NPs, and CS-PT-NPs partly reversed these effects. The present study demonstrated that the administration of free taurine, CS-PT-NPs, and Tau-CS-PT-NPs exerted beneficial effects in acetic acid-induced colitis by their anti-inflammatory and antioxidant activities. The best therapeutic effect was observed in animals treated with taurine-loaded chitosan pectin nanoparticles., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Out of the five isoforms of human flavin-containing monooxygenase (hFMO), FMO1 and FMO3 are the most relevant to Phase I drug metabolism. They are involved in the oxygenation of xenobiotics including drugs and pesticides using NADPH and FAD as cofactors. Majority of the characterization of these enzymes has involved hFMO3, where intermediates of its catalytic cycle have been described. On the other hand, research efforts have so far failed in capturing the same key intermediate that is responsible for the monooxygenation activity of hFMO1. In this work we demonstrate spectrophotometrically the formation of a highly stable C4a-hydroperoxyflavin intermediate of hFMO1 upon reduction by NADPH and in the presence of O 2 . The measured half-life of this flavin intermediate revealed it to be stable and not fully re-oxidized even after 30 min at 15 °C in the absence of substrate, the highest stability ever observed for a human FMO. In addition, the uncoupling reactions of hFMO1 show that this enzyme is <1% uncoupled in the presence of substrate, forming small amounts of H 2 O 2 with no observable superoxide as confirmed by EPR spin trapping experiments. This behaviour is different from hFMO3, that is shown to form both H 2 O 2 and superoxide anion radical as a result of ∼50% uncoupling. These data are consistent with the higher stability of the hFMO1 intermediate in comparison to hFMO3. Taken together, these data demonstrate the different behaviours of these two closely related enzymes with consequences for drug metabolism as well as possible toxicity due to reactive oxygen species., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Taurine is a naturally occurring sulfur-containing amino acid that is found abundantly in excitatory tissues, such as the heart, brain, retina and skeletal muscles. Taurine was first isolated in the 1800s, but not much was known about this molecule until the 1990s. In 1985, taurine was first approved as the treatment among heart failure patients in Japan. Accumulating studies have shown that taurine supplementation also protects against pathologies associated with mitochondrial defects, such as aging, mitochondrial diseases, metabolic syndrome, cancer, cardiovascular diseases and neurological disorders. In this review, we will provide a general overview on the mitochondria biology and the consequence of mitochondrial defects in pathologies. Then, we will discuss the antioxidant action of taurine, particularly in relation to the maintenance of mitochondria function. We will also describe several reported studies on the current use of taurine supplementation in several mitochondria-associated pathologies in humans.

Hyperlipidemia, an independent risk factor for atherosclerosis, is regarded as a lipid metabolism disorder associated with elevated plasma triglyceride and/or cholesterol. Genetic factors and unhealthy lifestyles, such as excess caloric intake and physical inactivity, can result in hyperlipidemia. Taurine, a sulfur-containing non-essential amino acid, is abundant in marine foods and has been associated with wide-ranging beneficial physiological effects, with special reference to regulating aberrant lipid metabolism. Its anti-hyperlipidemic mechanism is complex, which is related to many enzymes in the process of fat anabolism and catabolism (e.g., HMGCR, CYP7A1, LDLR, FXR, FAS and ACC). Anti-inflammatory and antioxidant molecular targets, lipid autophagy, metabolic reprogramming and gut microbiota will also be reviewed., (Copyright © 2021. Published by Elsevier Inc.)

The inelastic interaction between the incident photons and acoustic phonons in the taurine single crystal was investigated by using Brillouin spectroscopy. Three acoustic phonons propagating along the crystallographic b -axis were investigated over a temperature range of -185 to 175 °C. The temperature dependences of the sound velocity, the acoustic absorption coefficient, and the elastic constants were determined for the first time. The elastic behaviors could be explained based on normal lattice anharmonicity. No evidence for the structural phase transition was observed, consistent with previous structural studies. The birefringence in the ac -plane indirectly estimated from the split longitudinal acoustic modes was consistent with one theoretical calculation by using the extrapolation of the measured dielectric functions in the infrared range.

Taurine (Tau) has some important ameliorating effects on human health and is present in bivalve. For the selective analysis of Tau with other amino acids, we designed a derivatization reagent, 2,5-dioxopyrrolidin-1-yl(4-(((2-nitrophenyl)sulfonyl)oxy)-6-(3-oxomorpholino)quinoline-2-carbonyl)pyrrolidine-3-carboxylate (Ns-MOK-β-Pro-OSu). After derivatization with Ns-MOK-β-Pro-OSu, amino acids with Tau in Japanese littleneck clams were determined through ultra-high-performance-liquid chromatography with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) using an octadecyl silica column. We could detect 18 amino acids within 10 min. Tau, valine, glutamine, glutamic acid, and arginine in the clams were determined in the negative ion mode using the characteristic fragment ion, C 6 H 4 N 1 O 5 S, which corresponded to the 2-nitrobenzenesulfonylate moiety. The fragment ion, C 6 H 4 N 1 O 5 S, was recognized as a common feature regardless of the amino acid to be derivatized, and it was convenient for detecting amino acid derivatives with high selectivity and sensitivity. Therefore, highly selective quantification using UHPLC-HRMS/MS was possible using Ns-MOK-β-Pro-OSu.

Although numerous in vitro studies have shown that osmolytes are capable of stabilizing proteins, their effect on protein folding in vivo has been less understood. In this work, we investigated the effect of osmolytes, including glycerol, sorbitol, betaine, and taurine, on the folding of a protein GB3 variant in E. coli cells using NMR spectroscopy. 400 mM osmolytes were added to E. coli cells; only glycerol stabilizes the folded protein, whereas betaine and taurine considerably destabilize the protein through modulating folding and unfolding rates. Further investigation indicates that betaine and taurine can enhance the quinary interaction between the protein and cellular environment and manifestly weaken the electrostatic attraction in protein salt bridges. The combination of the two factors causes destabilization of the protein in E. coli cells. These factors counteract the preferential exclusion mechanism that is adopted by osmolytes to stabilize proteins.

Taurine is a compatible osmolyte that confers stability to proteins. Recent studies have revealed that liquid-liquid phase separation (LLPS) of proteins underlie the formation of membraneless organelles in cells. In the present study, we evaluated the role of taurine on LLPS of hen egg lysozyme. We demonstrated that taurine decreases the turbidity of the polyethylene glycol-induced crowding solution of lysozyme. We also demonstrated that taurine attenuates LLPS-dependent cloudiness of lysozyme solution with 0.5 or 1 M NaCl at a critical temperature. Moreover, we observed that taurine inhibits LLPS formation of a heteroprotein mix solution of lysozyme and ovalbumin. These data indicate that taurine can modulate the formation of LLPS of proteins.

Pyridoxal 5́-phosphate (PLP) is an important cofactor for amino acid decarboxylases with many biological functions, including the synthesis of signalling molecules, such as serotonin, dopamine, histamine, γ-aminobutyric acid, and taurine. Taurine is an abundant amino acid with multiple physiological functions, including osmoregulation, pH regulation, antioxidative protection, and neuromodulation. In mammalian tissues, taurine is mainly produced by decarboxylation of cysteine sulphinic acid to hypotaurine, catalysed by the PLP-dependent cysteine sulphinic acid decarboxylase (CSAD), followed by oxidation of the product to taurine. We determined the crystal structure of mouse CSAD and compared it to other PLP-dependent decarboxylases in order to identify determinants of substrate specificity and catalytic activity. Recognition of the substrate involves distinct side chains forming the substrate-binding cavity. In addition, the backbone conformation of a buried active-site loop appears to be a critical determinant for substrate side chain binding in PLP-dependent decarboxylases. Phe94 was predicted to affect substrate specificity, and its mutation to serine altered both the catalytic properties of CSAD and its stability. Using small-angle X-ray scattering, we further showed that CSAD presents open/close motions in solution. The structure of apo-CSAD indicates that the active site gets more ordered upon internal aldimine formation. Taken together, the results highlight details of substrate recognition in PLP-dependent decarboxylases and provide starting points for structure-based inhibitor design with the aim of affecting the biosynthesis of taurine and other abundant amino acid metabolites., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

It is a widely known that heat stress induces a reduction in milk production in cows and impairs their overall health. Studies have shown that taurine protects tissues and organs under heat stress. However, there have yet to be studies showing the functions of taurine in mammary alveolar cells-large T antigen (MAC-T) (a bovine mammary epithelial cell line) cells under heat shock. Therefore, different concentrations of taurine (10 mM, 50 mM, and 100 mM) were tested to determine the effects on heat-induced MAC-T cells. The results showed that taurine protected the cells against heat-induced damage as shown by morphological observations in conjunction with suppressed the translocation and expression of heat shock factor 1 (HSF1). Moreover, taurine not only reversed the decline in antioxidase (superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX)) activities but also attenuated the accumulation of malondialdehyde (MDA). Meanwhile, mitochondrial damage (morphology and complex I activity) resulting from heat exposure was mitigated. Taurine also alleviated the rates of cell apoptosis and markedly depressed the mRNA expressions of BCL2 associated X, apoptosis regulator (BAX) and caspase3. Furthermore, compared with the heat stress (HS) group, the protein levels of caspase3 and cleaved caspase3 were decreased in all taurine groups. In summary, taurine improves the antioxidant and anti-apoptosis ability of MAC-T cells thereby alleviates damage of cells due to heat insults.

An efficient and environmentally sustainable synthetic protocol has been presented to synthesize structurally diverse spiroxindoles spiroannulated with indenopyrroloimidazoles, pyranopyrroloimidazoles, chromenopyrroloimidazoles, and imidazopyrrolopyrimidines involving three-component reaction of isatins, hydantoin, and β-diketones in the presence of green and sustainable bio-organic catalyst, β-amino acid, 2-aminoethanesulfonic acid (taurine), in aqueous media. The synthetic efficiency, operational simplicity, and reusability of catalyst make the present synthetic protocol cost effective, time efficient, and eco-friendly to synthesize molecules with structural diversity and molecular complexity and expected to contribute significantly not only to drug discovery research but also to pharmaceutical and medicinal chemistry.

Visual pigment consists of opsin covalently linked to the vitamin A-derived chromophore, 11- cis -retinaldehyde. Photon absorption causes the chromophore to isomerize from the 11- cis- to all- trans -retinal configuration. Continued light sensitivity necessitates the regeneration of 11- cis -retinal via a series of enzyme-catalyzed steps within the visual cycle. During this process, vitamin A aldehyde is shepherded within photoreceptors and retinal pigment epithelial cells to facilitate retinoid trafficking, to prevent nonspecific reactivity, and to conserve the 11- cis configuration. Here we show that redundancy in this system is provided by a protonated Schiff base adduct of retinaldehyde and taurine (A1-taurine, A1T) that forms reversibly by nonenzymatic reaction. A1T was present as 9- cis , 11- cis , 13- cis , and all- trans isomers, and the total levels were higher in neural retina than in retinal pigment epithelium (RPE). A1T was also more abundant under conditions in which 11- cis -retinaldehyde was higher; this included black versus albino mice, dark-adapted versus light-adapted mice, and mice carrying the Rpe65-Leu450 versus Rpe65-450Met variant. Taurine levels paralleled these differences in A1T. Moreover, A1T was substantially reduced in mice deficient in the Rpe65 isomerase and in mice deficient in cellular retinaldehyde-binding protein; in these models the production of 11- cis -retinal is compromised. A1T is an amphiphilic small molecule that may represent a mechanism for escorting retinaldehyde. The transient Schiff base conjugate that the primary amine of taurine forms with retinaldehyde would readily hydrolyze to release the retinoid and thus may embody a pool of 11- cis -retinal that can be marshalled in photoreceptor cells., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Antonio Francioso et al.)

In ionexchange chromatography, the pH gradient mode becomes more and more popular today for the analysis of therapeutic proteins as this mode can provide higher or alternative selectivity to the commonly used salt gradient mode. Ideally, a linear pH response is expected when performing linear gradients. However up to now, only a very few buffer systems have been developed and are commercially available which can perform nearly linear pH responses when flowing through a given column. It is also known that a selected buffer system (mobile phase) can work well on one column but can fail on other column. The goal of this study was to practically evaluate the effects that ionexchange columns (weak and strong exchangers) might have on effluent pH, when performing linear pH gradient separations of therapeutic monoclonal antibodies. To attain this objective, the pH was monitored on-line at the column outlet using a specific setup. To make comprehensive observations of the phenomenon, four different mobile phase conditions and five cation exchange columns (weak and strong exchangers) were employed. The obtained pH responses were systematically compared to responses measured in the absence of the columns. From this work, it has become clear that both the column and mobile phase can have significant effects on pH gradient chromatography and that their combination must be considered when developing a new method. Phase systems (column + mobile phase) providing linear pH responses are indeed the most suitable for separating mAbs with different isoelectric points and, with them, it is possible to elute mAbs across wide retention time ranges and with high selectivity., 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 © 2020. Published by Elsevier B.V.)

N-acyltaurines (NATs) are amides of fatty acids that can be structurally related to endocannabinoids. They show interesting physiological and pharmacological properties. We have synthesized a homologous series of NATs with saturated acyl chains (n = 9-18) and investigated their supramolecular structure and thermotropic phase transitions by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The d-spacings obtained from PXRD increase linearly with chain length with an increment of ∼0.847 Å per additional CH 2 moiety suggesting that NATs adopt a tilted bilayer structure with similar packing in crystal lattice. Results obtained from DSC studies indicate that the endothermic transition temperature (T t ) of NATs showed a gradually increasing trend with increasing acyl chain length. The enthalpy (ΔH t ) and entropy (ΔS t ) of transition show odd-even alternations with odd-chain compounds having higher values than the even-chain compounds. The critical micellar concentration (CMC) of NATs was determined in water at room temperature by fluorescence spectroscopy by monitoring the spectral changes of 8-anilinonaphthalene-1-sulfonic acid (ANS). The CMCs of NATs were found to decrease with increase in acyl chain length. The present results provide a thermodynamic and structural basis for investigating the interaction of NATs with other membrane lipids and proteins, which in turn can shed light in understanding how they function in vivo (in biological membranes)., 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 © 2020 Elsevier B.V. All rights reserved.)

Neurodegenerative diseases (NDs) are characterized by the accumulation of misfolded proteins. The hallmarks of protein aggregation in NDs proceed with impairment in the mitochondrial function, besides causing an enhancement in endoplasmic reticulum (ER) stress, neuroinflammation and synaptic loss. As accumulation of misfolded proteins hampers normal neuronal functions, it triggers ER stress, which leads to the activation of downstream effectors formulating events along the signaling cascade-referred to as unfolded protein response (UPRER) -thereby controlling cellular gene expression. The absence of disease-modifying therapeutic targets in different NDs, and the exponential increase in the number of cases, makes it critical to explore new approaches to treating these devastating diseases. In one such approach, osmolytes (low molecular weight substances), such as taurine have been found to promote protein folding under stress conditions, thereby averting aggregation of the misfolded proteins. Maintaining the structural integrity of the protein, taurine-mediated resumption of protein folding prompts a shift in folding homeostasis more towards functionality than towards aggregation and degradation. Together, taurine enacts protection in NDs by causing misfolded proteins to refold, so as to regain their stability and functionality. The present study provides recent and useful insights into understanding the progression of NDs, besides summarizing the genetics of NDs in correlation with mitochondrial dysfunction, ER stress, neuroinflammation and synaptic loss. It also highlights the structural and functional aspects of taurine in imparting protection against the aggregation/misfolding of proteins, thereby shifting the focus more towards the development of effective therapeutic modules that could avert the development of NDs.

PEGylation has been used as a strategy to enhance pharmacokinetic properties of therapeutic proteins by pharmaceutical industry. Imaged CIEF (iCIEF) is the current industry standard technology for pI determination and charge variant quantification of proteins and antibodies. However, the charge variants of PEGylated proteins merge into one broad peak during iCIEF, most likely due to masking of proteins by the surrounding PEG chain as well as the increased hydrodynamic volume due to PEGylation. Here, we report our novel matrix formula with a combination of glycine and taurine that significantly improved the separation of charge variants in PEGylated proteins. As a result, it is no longer necessary to conduct IEF of proteins prior to PEGylation, which does not reflect the changes caused by PEGylation and purification processes. The novel matrix (glycine and taurine) enables iCIEF analysis of PEGylated proteins in their real conjugated states., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

With the surge in the cases of Alzheimer's disease (AD) over the years, several targets have been explored to curb the disease. Cholinesterases, namely acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), remain to be the available targets that are amendable to currently approved treatments. In this study, a series of novel compounds based on tramiprosate, a highly specific amyloid beta (Aβ) inhibitor, was designed to inhibit AChE, BuChE, and Aβ aggregation. In particular, the addition of a pyridinium/isoquinolinium ring to the tramiprosate moiety (to give compounds 3a-j) led to an increase in the binding affinity for the catalytic active site of cholinesterase, which was hampered by the presence of sulfonic acid. Exclusion of the sulfonic acid moiety led to a novel but effective class of cholinesterase inhibitors (9a-w). in vitro Aβ aggregation inhibition assay indicated that compounds 3a-j, 9e-f, 9i-l, 9q, 9r, 9u-w, and 12 could inhibit over 10% Aβ aggregation at 1 mM concentration. Cholinesterase inhibition assay suggested that compounds 9g, 9h, 9o, and 9q-t exhibit over 70% inhibition on both AChE and BuChE at a concentration of 100 μM. Amongst the designed molecules, compound 9r (ca 18% at 1 mM) showed comparable inhibitory effect on the inhibition of Aβ aggregation with tramiprosate (ca 20% at 1 mM), along with impressive cholinesterase inhibitory potential (AChE IC 50 = 13 μM and BuChE IC 50 = 12 μM), acceptable toxicity and ability to pass through blood brain barrier, which could be used to ameliorate the phenotypes of AD in preclinical models., (© 2019 Wiley Periodicals, Inc.)

Intrinsically disordered proteins (IDPs) are involved in various important biological processes, such as cell signalling, transcription, translation, cell division regulation etc. Many IDPs need to maintain their disordered conformation for proper function. Osmolytes, natural organic compounds responsible for maintaining osmoregulation, have been believed to regulate the functional activity of macromolecules including globular proteins and IDPs due to their ability of modulating the macromolecular structure, conformational stability, and functional integrity. In the present study, we have investigated the effect of all classes of osmolytes on two model IDPs, α- and β-casein. It was observed that osmolytes can serve either as folding inducers or folding evaders. Folding evaders, in general, do not induce IDP folding and therefore had no significant effect on structural and functional integrity of IDPs. On the other hand, osmolytes taurine and TMAO serve as folding inducers by promoting structural collapse of IDPs that eventually leads to altered structural and functional integrity of IDPs. This study sheds light on the osmolyte-induced regulation of IDPs and their possible role in various disease pathologies.

Hexavalent chromium [(Cr(VI)] is widely used in several industries, but human exposure results in multiple organ toxicity. Enhanced generation of free radicals and reactive species is thought to play a key role in Cr(VI)-induced toxicity. We have examined the effect of taurine, a simple sulphur-containing amino acid and an antioxidant, on potassium dichromate [K 2 Cr 2 O 7 , a Cr(VI) compound]-induced cytotoxicity and genotoxicity in human blood cells. Erythrocytes were treated with K 2 Cr 2 O 7 , either alone or after incubation with different concentrations of taurine. Treatment of erythrocytes with K 2 Cr 2 O 7 alone led to marked increase in generation of reactive oxygen and nitrogen species, lipid and protein oxidation. This was accompanied by decrease in total sulfhydryl and glutathione content and lowered antioxidant power of the cells. This suggests that Cr(VI) induces oxidative stress in the cells. Incubation of erythrocytes with taurine prior to addition of K 2 Cr 2 O 7 , resulted in a concentration-dependent decrease in the generation of reactive oxygen and nitrogen species, mitigation of oxidative stress and amelioration of antioxidant power of these cells. It also restored the activities of several metabolic, antioxidant and membrane-bound enzymes. Cr(VI)-induced damage to erythrocyte membrane and lymphocyte DNA was also significantly attenuated by prior administration of taurine. These results suggest that taurine can function as a chemoprotectant against Cr(VI)-induced oxidative injury and can be potentially used to mitigate the toxic effects of this transition metal ion.

Well-dispersed and graft-crosslinked gold nanoparticles (AuNPs) were synthesized by the reduction of tetrachloroaurate with hydrazine at room temperature. The AuNPs possess a high density of surface defects which is due to grafting of n-octanoic acid to polyvinylpyrrolidone. The physical and chemical properties of the resulting AuNPs were characterized by UV-vis, XRD, TEM/HRTEM, SAED, and XPS, respectively. The modified AuNPs were placed on a glassy carbon electrode (GCE) in an electropolymerized taurine layer to obtain a sensitive, selective, stable and rapid electrochemical dopamine sensor. The peak current, typically measured at 0.17 V (vs. SCE), increases linearly in the 1.0 to 120 μM dopamine concentration range, and the limit of detection (at S/N = 3) is 0.16 μM with a sensitivity of 2.94 μA·μM -1 ·cm -2 . The sensor was successfully applied to the determination of dopamine in injections and spiked serum samples. The recoveries from spiked serum samples range from 97.5 to 102.4%, with RSDs ranging between 2.8 and 3.4%. Graphical abstract Schematic representation of a glassy carbon electrode modified with in-situ graft-crosslinked gold nanoparticles combined with an electropolymerized polytaurine membrane. The sensor exhibits excellent features towards dopamine determination.

Iron(II)- and 2-(oxo)-glutarate-dependent (Fe/2OG) oxygenases catalyze a diverse array of oxidation reactions via a common iron(IV)-oxo (ferryl) intermediate. Although the intermediate has been characterized spectroscopically, its short lifetime has precluded crystallograhic characterization. In solution, the ferryl was first observed directly in the archetypal Fe/2OG hydroxylase, taurine:2OG dioxygenase (TauD). Here, we substitute the iron cofactor of TauD with the stable vanadium(IV)-oxo (vanadyl) ion to obtain crystal structures mimicking the key ferryl complex. Intriguingly, whereas the structure of the TauD·(V IV -oxo)·succinate·taurine complex exhibits the expected orientation of the V≡O bond- trans to the His255 ligand and toward the C-H bond to be cleaved, in what has been termed the in-line configuration-the TauD·(V IV -oxo) binary complex is best modeled with its oxo ligand trans to Asp101. This off-line-like configuration is similar to one recently posited as a means to avoid hydroxylation in Fe/2OG enzymes that direct other outcomes, though neither has been visualized in an Fe/2OG structure to date. Whereas an off-line ( trans to the proximal His) or off-line-like ( trans to the carboxylate ligand) ferryl is unlikely to be important in the hydroxylation reaction of TauD, the observation that the ferryl may deviate from an in-line orientation in the absence of the primary substrate may explain the enzyme's mysterious self-hydroxylation behavior, should the oxo ligand lie trans to His99. This finding reinforces the potential for analogous functional off-line oxo configurations in halogenases, desaturases, and/or cyclases.

The purpose of this study is to produce injectable taurine (Tr)-loaded alginate (Agn) hydrogel for age-related macular degeneration (AMD) treatment by inducing the regeneration of RPE (retinal pigment epithelium) cells. Porosity and swelling ratio were measured to evaluate the mechanical properties of the hydrogels, and Fourier transform infrared spectroscopy (FTIR) was used to evaluate the physical and chemical properties. RPE cells extracted from the pigmented epithelium of rabbits were encapsulated in the Tr/Agn hydrogels. Cells proliferation and migration were improved in Tr/Agn hydrogels with an enhanced expression of RPE-specific genes including RPE65, CRALBP, NPR-A, MITF and collagen type I and II. In vivo tests demonstrated the excellent biocompatibility and biodegradability without inflammatory response by the host when implanted with the hydrogel. Moreover, when the Tr/Agn hydrogels were injected into the sub-retinal space, high adhesion of RPE cells and retinal regeneration were confirmed. These results demonstrated a potential role of injectable Tr/Agn hydrogels as potential therapeutic tools for the treatment of retinal diseases, including AMD., (Copyright © 2019. Published by Elsevier B.V.)

Six new polyhydroxylated steroids conjugated with taurine, microdiscusols A-F, were isolated from the alcoholic extract of the Arctic starfish Asterias microdiscus. Three of them have been found to have additional sulfate groups in tetracyclic cores. The structures of new compounds were established by 1D and 2D NMR and HRESIMS techniques. The found steroid taurine conjugates resemble, by their structures, salts of bile acids and alcohols of lower vertebrates., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Taurine is an indispensable amino acid for many fish species and taurine supplementation is needed when plant-based diets are used as the primary protein source for these species. However, there is limited information available to understand the physiological or metabolic effects of taurine on fish. In this study, 1 H nuclear magnetic resonance (NMR)-based metabolomic analysis was conducted to identify the metabolic profile change in the fish intestine with the aim to assess the effect of dietary taurine supplementation on the physiological and metabolomic variation of fish, and reveal the possible mechanism of taurine's metabolic effect. Grouper ( Epinephelus coioides ) were divided into four groups and fed diets containing 0.0%, 0.5%, 1.0%, and 1.5% taurine supplementation for 84 days. After extraction using aqueous and organic solvents, 25 significant taurine-induced metabolic changes were identified. These metabolic changes in grouper intestine were characterized by differences in carbohydrate, amino acid, lipid and nucleotide. The results reflected both the physiological state and growth of the fish, and indicated that taurine supplementation significantly affects the metabolome of fish, improves energy utilization and amino acid uptake, promotes protein, lipid and purine synthesis, and accelerates fish growth.

There is continual demand to maximize CHO cell culture productivity of a biotherapeutic while maintaining product quality. In this study, a comprehensive multi-omics analysis is performed to investigate the cellular response to the level of dosing of the amino acid cysteine (Cys) in the production of a monoclonal antibody (mAb). When Cys feed levels are insufficient, there is a significant decrease in protein titer. Multi-omics (metabolomics and proteomics, with support from RNAseq) is performed over the time course of the CHO bioprocess producing an IgG1 mAb in 5 L bioreactors. Pathway analysis reveals that insufficient levels of Cys in the feed lead to Cys depletion in the cell. This depletion negatively impacts antioxidant molecules, such as glutathione (GSH) and taurine, leading to oxidative stress with multiple deleterious cellular effects. In this paper, the resultant ER stress and subsequent apoptosis that affects cell viability and viable cell density has been considered. Key metabolic enzymes and metabolites are identified that can be potentially monitored as the process progresses and/or increased in the cell either by nutrient feeding or genetic engineering. This work reinforces the centrality of redox balance to cellular health and success of the bioprocess as well as the power of multi-omics to provide an in-depth understanding of the CHO cell biology during biopharmaceutical production., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Alzheimer's Disease affects approximately 33 million people worldwide and is characterized by progressive loss of memory at the cognitive level. The formation of toxic amyloid oligomers, extracellular amyloid plaques and amyloid angiopathy in brain by amyloid beta peptides are considered a part of the identified mechanism involved in disease pathogenesis. The optimal treatment approach leads toward finding a chemical compound able to form a noncovalent complex with the amyloid peptide thus blocking the process of amyloid aggregation. This direction gained an increasing interest lately, many studies demonstrating that mass spectrometry is a valuable method useful for the identification and characterization of such molecules able to interact with amyloid peptides. In the present review we aim to identify in the scientific literature low molecular weight chemical compounds for which there is mass spectrometric evidence of noncovalent complex formation with amyloid peptides and also there are toxicity reduction results which verify the effects of these compounds on amyloid beta toxicity towards cell cultures and transgenic mouse models developing Alzheimer's Disease., Competing Interests: AD, Alzheimer’s Disease; Aβ, Amyloid-beta; APP, Amyloid Precursor Protein; FAD, Familial Alzheimer’s Disease; ABCA1 modulation, ATP binding cassette transporter A1; AD model with Npc1-deficient mice, a novel mouse model of "Juvenile Alzheimer's Disease” carrying a D1005G-Npc1 mutation; GluA1 and GluA2 subunits of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors; GluN2A, the main subunit of N-methyl-d-aspartate receptors; PSD-95, a membrane-associated guanylate kinase, is the major scaffolding protein in the excitatory postsynaptic density (PSD) and a potent regulator of synaptic strength; ESI, Electrospray ionization; MALDI, Matrix Assisted Laser Desorption and Ionization; iPSCs, Induced pluripotent stem cells; PS1, Presenilin 1; PS2, Presenilin 2; SH-SY5Y, Human neuroblastoma cell line; GAP-43, Growth-Associated Protein; NeuN, Neuronal Nuclei; SYN, Synaptophysin; SV2, Synaptic Vesicle Protein II; NSE, Neuron Specific Enolase; MAP, Microtubule Associated protein; GFAP, Glial Fibrillary Acidic Protein; SK-N-SH, Original Human Neuroblastoma Cell Line from which SH-SY5Y was derived; TH, Tyrosine Hydroxylase; GSK3 beta, Glycogen synthase kinase 3 beta; HN, Humanin peptide; Acm, Acetamidomethyl; NHS-Activated Sepharose, N-hydroxysuccinimide - Activated Sepharose; MALDI-TOF, Matrix Assisted Laser Desorption and Ionization – Time Of Flight; nano-ESI-FTICR, Nano-Electrospray Ionization - Fourier Transform Ion Cyclotron Resonance; PC12, Rat phaeochromocytoma; Bcl-2, B-cell lumphoma 2, antiapoptotic protein; Bax, Bcl-2-like protein 4, proapoptotic protein, Bax gene; icv, intracerebroventricular; ip, intraperitoneal; APPswe/PS1dE9 mice, double transgenic mouse model carrying APP Swedish mutation and deletion of presenilin 1 in exon 9; APPswe, tauP310L, PS1M146V mice, triple transgenic mouse model carrying APP Swedish mutation, Tau mutation P310L and presenilin 1 mutation M146V; 3xTg-AD mice, triple transgenic mouse model of Alzheimer’s disease; Q-TOF, Quadrupole – Time Of Flight; LC/MS, Liquid Cromatography/Mass Spectrometry; Glu-C, Endoprotease V8 from Staphylococcus aureus; N2a, mouse neuroblastoma cell line; Tg2576 mice, transgenic mice overexpressing APP695 carrying Swedish mutation K670N and M671L; TgCRND8 mice, transgenic mouse model of Alzheimer’s Disease overexpressing APP695 and carrying Swedish mutation K670N and M671L and Indiana mutation V717F; HP-β-CD, 1-hydroxypropyl-β-cyclodextrin; Tg19959 mice, transgenic mouse model of Alzheimer’s disease, which overexpress human APP with the Swedish and Indiana familial AD mutations; Fmoc, 9-Fluorenyl- methyloxycarbonyl; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; fAβ-Cu, Amyloid- beta fibrils Cu complex; ROS, Reactive Oxygen Species.

A novel electrochemical sensor was developed towards recognition of malondialdehyde (MDA) with modifying the glassy carbon electrode (GCE) by self-assembled riboflavin-taurine (RFPT) as organic substrate and silver nanoparticle (Ag NPs) as inorganic nano-catalyst. Therefore, a novel biocompatible and anti-bacterial substrate were prepared for the construction of electrode. In proposed sensor, the RF-PT polymer film led to the emergence of electroactive and suitable substrate for the immobilization of Ag NPs. The use of the proposed nano-hybrid significantly amplified the electrochemical signals the redox behavior was investigated using various electrochemical methods including cyclic voltammetry (CV), differential pulse voltammetry (DPV), square wave voltammetry (SWV), and linear sweep voltammetry (LSV). It is the adaptation of the established RF-PT-Ag NPs organic-inorganic hybrid for a selective, robust, and generalizable sensing system that is the emphasis of this work. The results show that the proposed platform has a good sensitivity in the detecting of MDA with a low limit of quantification (LLOQ) of 0.59 ± 0.05 μM. In addition, the modified electrode reveals promising efficiency against MDA oxidation and its side-products destructive effects. For the first time, the engineered sensor was used to non-invasive determination MDA in exhaled breath condensate (EBC) samples without the need to extra sample preparation steps. The results show RF-PT-AgNPs as a novel biocompatible interface can provide appropriate, reliable, in-expensive, fast, and user-friendly diagnostic tools in the detection of MDA in human real samples., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: Taurine-conjugated bile acids possess positive formulation-stabilization effects, which are desirable in diabetes treatments. The taurine-conjugated bile acid, taurocholic acid (TCA), has shown promising formulation-stabilizing effects on the delivery of the antioxidant drug, probucol (PB), but success is limited due to its poor release profile. This study aimed to design new PB-TCA formulations using new polymers, and examine antioxidant and antidiabetic effects using β-cells for PB with or without TCA., Materials and Methods: Different formulations using alginate-insoluble esters of polymethylacrylate polymers encapsulating PB and TCA were developed, microencapsulated and examined for stability and biological activity., Results: TCA addition to new PB matrices improved osmotic and mechanical properties, and this effect was dependent on polymethylacrylate composition and concentration., Conclusion: TCA can optimize the oral delivery of anti-diabetic compounds.

Five new water-soluble amido- and aminoanthraquinone pigments, hypalocrinins A-E (1-5), the new amidoanthraquinone biaryls hypalocrinin F (6) and hypalocrinin G (7), and the known compounds 6-bromoemodic acid (8), crinemodin (9), and crinemodin sulfate (10) were isolated from the deep sea crinoid Hypalocrinus naresianus collected off Japan. The structures of the compounds were elucidated by NMR spectroscopy and mass spectrometry. Amido- and aminoquinones are quite unusual among natural products. The hypalocrinins are the first naturally occurring anthraquinones and anthraquinone biaryls conjugated with taurine.

Cholestasis can be induced by obstruction of bile ducts or intrahepatic toxicity of drugs and chemicals. However, the mode of cell death during cholestasis, i.e., apoptosis or necrosis, has been controversial. There are fundamental reasons for the controversies, both of which are discussed here, namely the design of experiments and the use of parameters with limited specificity for a certain mode of cell death. Based on the assumption that cholestatic liver injury is caused by accumulation of bile acids, rodent (mainly rat) hepatocytes have been exposed to hydrophobic, glycine-conjugated bile acids, which resulted in apoptotic cell death. The problems with this experimental design are that in rodents bile acids are predominantly taurine conjugated and rodent hepatocytes are never exposed to these levels of glycine-conjugated bile acids. In contrast, taurine-conjugated bile acids trigger inflammatory gene activation in rodent hepatocytes and a necro-inflammatory injury in vivo. On the other hand, human hepatocytes are more resistant to glycine-conjugated bile acids and die by necrosis when exposed to high biliary levels of these bile acids. In this chapter, we describe multiple assays including the caspase activity assay, which is specific for apoptosis, and the general cell death assays alanine aminotransferase or lactate dehydrogenase activities in cell culture medium or plasma. An increase in these enzyme activities without caspase activity indicates necrotic cell death. Thus, both the experimental design and the selection of cell death parameters are critical for the relevance of the experiments for the human pathophysiology.

Previous research found that ochratoxin A (OTA) could promote PCV2 replication by inducing autophagy. The aim of this study is to evaluate the effect of dietary amino acid derivative taurine on OTA-promoted PCV2 replication and explore the underlying mechanism. The results showed that taurine could inhibit OTA-promoted PCV2 replication in PK-15 cells. The effect of taurine could be mediated by its ability to attenuate ROS level and block OTA-promoted autophagy. Indeed, induction of autophagy by rapamycin could suppress the inhibitory effect of taurine on OTA-promoted PCV2 replication. Furthermore, taurine supplementation inhibited 5'AMP-activated protein kinase (AMPK) and activated mammalian target of rapamycin (mTOR). Activation of AMPK by acadesine (AICAR) could suppress the effect of taurine. In conclusion, taurine treatment suppresses autophagy by regulating the ROS/AMPK/mTOR signaling axis, thereby inhibiting OTA-promoted PCV2 replication. These findings provide the rationale for the use of taurine as an intervention against PCV2 infection., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Osmolytes are small organic compounds that can affect the stability of proteins in living cells. The mechanism of osmolytes' protective effects on protein structure and dynamics has not been fully explained, but in general, two possibilities have been suggested and examined: a direct interaction of osmolytes with proteins (water replacement hypothesis), and an indirect interaction (vitrification hypothesis). Here, to investigate these two possible mechanisms, we studied myoglobin-osmolyte systems using FTIR, UV-vis, CD, and femtosecond IR pump-probe spectroscopy. Interestingly, noticeable changes are observed in both the lifetime of the CO stretch of CO-bound myoglobin and the spectra of UV-vis, CD, and FTIR upon addition of the osmolytes. In addition, the temperature-dependent CD studies reveal that the protein's thermal stability depends on molecular structure, hydrogen-bonding ability, and size of osmolytes. We anticipate that the present experimental results provide important clues about the complicated and intricate mechanism of osmolyte effects on protein structure and dynamics in a crowded cellular environment., Competing Interests: References

The protective effect of taurine against inflammation, apoptosis and oxidative stress in traumatic brain injury was investigated in the present study. Taurine is a non‑proteogenic and essential amino acid in animals. It plays a critical nutritional role in brain cell growth, differentiation, and development. Taurine is involved in regeneration and neuroprotection in the injured nervous system, and is an effective antioxidant against lead‑, cadmium‑, and exercise‑induced oxidative stress. Astrocytes and neuron cells were co‑cultured and cells were treated with different concentrations of taurine (100, 200 and 300 mg/l) for 72 h, and the levels of reactive oxygen species, malondialdehyde, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, acetylcholinesterase, tumor necrosis factor‑α, interleukin‑6, caspase‑3, p53, B‑cell lymphoma 2 and Bcl‑2‑associated X protein were determined. These inflammatory, apoptotic, and oxidative stress markers were substantially increased in injured cells, and returned to normal levels following taurine supplementation. Thus, taurine supplementation may be effective against oxidative stress, apoptosis, and inflammation in injured brain cells.

Taurine or 2-aminoethanesulfonic has many fundamental biological roles such as conjugation of bile acids, antioxidation, osmoregulation, membrane stabilization, and modulation of calcium signaling. It is essential for cardiovascular function and development and function of the skeletal muscle, the retina, and the central nervous system. Functions of taurine include osmoregulation; membrane stabilization; modulation of calcium levels; and antioxidation, antiapoptotic, anti-inflammatory, and antilipid activities. Taurine was first discovered as a component of ox (Bos taurus, from which its name is derived) bile in 1827; it had taken over a century before insights into its physiological functions were made. The present review throws light on the multifactorial properties of taurine and its potential to be used in periodontal therapy., Competing Interests: None

Background: ALZ-801 is an oral, small-molecule inhibitor of beta amyloid (Aβ) oligomer formation in clinical development for Alzheimer's disease (AD). ALZ-801 is a prodrug of tramiprosate with improved pharmacokinetic properties and gastrointestinal tolerability. During clinical studies, we discovered that the primary metabolite of tramiprosate and its prodrug ALZ-801, 3-sulfopropanoic acid (3-SPA), is an endogenous molecule in the human brain and present in the cerebrospinal fluid (CSF) of patients with AD and other neurodegenerative brain diseases., Objective: The objectives of this research were to (1) identify and confirm the presence of 3-SPA in CSF samples from elderly, drug-naïve patients with memory deficits; (2) quantify the levels of 3-SPA in the CSF of patients with AD from tramiprosate phase III North American (NA) trial; (3) evaluate the in vitro anti-Aβ42 oligomer activity of 3-SPA; and (4) characterize the pharmacokinetics and brain-penetration properties of 3-SPA., Methods: Lumbar CSF samples from 64 drug-naïve patients with cognitive deficits (Mini-Mental State Examination [MMSE] score range 15-30) and six patients with AD treated with tramiprosate 150 mg twice daily in the phase III trial, at week 78, were analyzed. We used liquid chromatography-tandem mass spectrometry to confirm the structural molecular identity of endogenous 3-SPA with a 3-SPA reference standard and ion-mobility spectrometry-mass spectrometry with molecular dynamics to characterize interactions of 3-SPA with Aβ42 monomers, and the resultant conformational alterations. Rat studies using oral (30 mg/kg) and intravenous (10 mg/kg) doses were conducted to characterize the pharmacokinetic properties and brain penetration of 3-SPA., Results: We confirmed the presence of 3-SPA in the CSF of drug-naïve patients with cognitive deficits (mean concentration 11.7 ± 4.3 nM). The mean concentration of 3-SPA in patients with AD treated with tramiprosate was 135 ± 51 nM. In vitro studies revealed a multi-ligand interaction of 3-SPA with monomeric Aβ42 that inhibits the aggregation of Aβ42 into small oligomers. Comparisons of the molecular interactions of tramiprosate and 3-SPA with Aβ42 are also presented. Furthermore, in rat preclinical studies, 3-SPA displayed 100% oral bioavailability and 25% brain penetration, indicating that the metabolite is well absorbed and crosses the blood-brain barrier., Conclusions: We confirmed the endogenous presence of 3-SPA, the major metabolite of tramiprosate, in the CSF of drug-naïve elderly patients with memory deficits due to AD and a variety of other neurodegenerative disorders. The levels of 3-SPA were up to 12.6-fold greater in patients with AD receiving tramiprosate than in drug-naïve patients. In addition, we showed that 3-SPA has potent anti-Aβ oligomer activity, inhibiting aggregation of Aβ42 into small oligomers with efficacy comparable to that of tramiprosate. 3-SPA displays excellent oral availability and brain penetration in rats, suggesting that the higher CSF concentrations of 3-SPA in the human brain after oral administration of ALZ-801 or tramiprosate (and subsequent conversion to 3-SPA) result from the penetration of the metabolite into the central nervous system. These data suggest that 3-SPA is an endogenous agent with potential activity stabilizing the conformational flexibility of Aβ monomers that, in turn, inhibit Aβ misfolding and formation of soluble toxic Aβ oligomers in humans, thereby preventing the initial pathogenic step in the progression of AD. Clinical improvements observed in patients with AD carrying the ε4 allele of the apolipoprotein E gene in tramiprosate phase III studies may in part be explained by the therapeutic effects of excess levels of the metabolite in the brains of these patients. The potential protective role of 3-SPA in AD pathogenesis, as well as its therapeutic role in AD and other neurodegenerative disorders, warrants further investigation.

Here, a facile method for the preparation of polymeric particles from a sugar molecule, maltitol (ML) in single step was reported via microemulsion polymerization/crosslinking technique with a high yield, 89 ± 6%. Furthermore, poly(Maltitol) (p(ML)) particles were chemically modified to induce different physicochemical characteristic using different anionic and cationic modifying agents such as taurine (TA) and diethylenetriamine (DETA) to prepare m-p(ML)/TA and m-p(ML)/DETA. The blood compatibility of the p(ML) particles and their modified forms were tested with fresh blood, and found that p(ML) and m-(ML)/DETA particles are blood compatible with about 5% hemolysis, and above 80% blood clotting indices. Moreover, the cytotoxicity results against L929 fibroblast cell line revealed that p(ML) based particle are biocompatible up to 100 μg/mL with 85% cell viability regardless of their nature, and at 200 μg/mL dosage of p(ML), m-p(ML)/TA and m-p(ML)/DETA particles, the cell viabilities were determined as 83.33, 64.03 and 73.89% on for L929 fibroblast cells implying the slightly less biocompatibility nature of m-p(ML)/TA in accord with the blood compatibility results. Additionally, the apoptotic and necrotic indices were determination for p(ML) based particles on L929 fibroblast cells, and the results revealed that these particles do not induce any and stress on the cells. Also, it does not have genotoxic effect as determined against CHO cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are key transmembrane proteins leading to reactive oxygen species (ROS) overproduction. However, the detailed roles of NOXs in retinal pigment epithelial (RPE) cell metabolic stress induced by Earle's balanced salt solution (EBSS) through starvation remain unclear. In this study, we investigated what roles NOXs play in regard to calpain activity, endoplasmic stress (ER), autophagy, and apoptosis during metabolic stress in ARPE-19 cells. We first found that EBSS induced an increase in NOX2, NOX4, p22phox, and NOX5 compared to NOX1. Secondly, suppression of NOXs resulted in reduced ER stress and autophagy, decreased ROS generation, and alleviated cell apoptosis. Thirdly, silencing of NOX4, NOX5, and p22phox resulted in reduced levels of cell damage. However, silencing of NOX1 was unaffected. Finally, taurine critically mediated NOXs in response to EBSS stress. In conclusion, this study demonstrated for the first time that NOX oxidases are the upstream regulators of calpain-2, ER stress, autophagy, and apoptosis. Furthermore, the protective effect of taurine is mediated by the reduction of NOX-derived ROS, leading to sequential suppression of calpain induction, ER stress, autophagy, and apoptosis.

Sepsis, an overwhelming systemic inflammatory disease, is the leading cause of acute lung injury (ALI). Despite plenty of researches have been done, effective drugs treating septic ALI are still eagerly needed in the clinic. Dexmedetomidine (Dex), a potent alpha-2 adrenoreceptor agonist, has been reported to possess antioxidant, anti-apoptosis and anti-inflammatory abilities. Taurine, a kind of intracellular free amino acid, has been used to treat various diseases. This study aimed to explore the combination effect of Dex and Taurine on septic ALI and the underlying mechanism in vivo. The establishment of septic ALI was set up in SD rats by cecal ligation and puncture (CLP) operation. Results indicated that Dex or Taurine could reduce septic ALI-induced cell apoptosis via decreasing caspase-3 activity. However, the combination of Dex or Taurine produced greater effect. Besides that, Dex combined with Taurine could better promote cell proliferation with remarkably elevated Ki67 expression. The combination of Dex and Taurine significantly suppressed the activation of NF-κB pathway via inhibiting P65 phosphorylation and P65 nuclear translocation, leading to the down-regulation of interleukin (IL)-6 and IL-1β. Moreover, co-administration of Dex and Taurine alleviated the imbalance of Th1/Th2 induced by septic ALI to a great extent. All in all, our study suggested the synergistic therapeutic effect of Dex and Taurine on septic ALI., (Copyright © 2018. Published by Elsevier Masson SAS.)

A major problem limiting reproducible use of liquid extraction surface analysis (LESA) array sampling of dried surface-deposited liquid samples is the unwanted spread of extraction solvent beyond the dried sample limits, resulting in unreliable data. Here, we explore the use of the Droplet Microarray (DMA), which consists of an array of superhydrophilic spots bordered by a superhydrophobic material giving the potential to confine both the sample spot and the LESA extraction solvent in a defined area. We investigated the DMA method in comparison with a standard glass substrate using LESA analysis of a mixture of biologically relevant compounds with a wide mass range and different physicochemical properties. The optimized DMA method was subsequently applied to urine samples from a human intervention study. Relative standard deviations for the signal intensities were all reduced at least 3-fold when performing LESA-MS on the DMA surface compared with a standard glass surface. Principal component analysis revealed more tight clusters indicating improved spectral reproducibility for a human urine sample extracted from the DMA compared to glass. Lastly, in urine samples from an intervention study, more significant ions (145) were identified when using LESA-MS spectra of control and test urine extracted from the DMA. We demonstrate that DMA provides a surface-assisted LESA-MS method delivering significant improvement of the surface extraction repeatability leading to the acquisition of more robust and higher quality data. The DMA shows potential to be used for LESA-MS for controlled and reproducible surface extraction and for acquisition of high quality, qualitative data in a high-throughput manner.

Regular usage of cosmetic products and drugs in dermatological vehicles may cause irritant contact dermatitis. For example, aluminum chloride (AlCl 3 ), the most efficacious antiperspirant salt to treat hyperhidrosis, shows high irritancy potential. To mitigate the irritant contact dermatitis caused by topical application of products containing AlCl 3 , we investigated the anti-irritating effects of aloe extract and taurine in vitro and in vivo . In an in vitro experiment, reconstructed human epidermis model, EpiDerm, was tested with AlCl 3 in the presence or absence of taurine and aloe extract. In a human clinical study, 12 adult subjects were tested with two products, a commercial AlCl 3 antiperspirant product and a prototype 12% AlCl 3 formulation containing 0.1% taurine and 0.1% aloe extract. Skin irritation potential in vitro and in vivo was measured by the release of pro-inflammatory cytokine, IL-1α, and chemokine, IL-8. Taurine and aloe extract significantly ( p < 0.05) reduced IL-lα and IL-8 production in vitro and in vivo after topical application of formulations containing AlCl 3 . The blend of taurine and aloe extract demonstrated boosted anti-irritation benefits on AlCl 3 irritated skin both in vitro and in vivo . These results suggest that the combination of these anti-irritating actives may possibly be effective in mitigating irritant contact dermatitis caused by other dermatological vehicles containing irritating agents, but further research is warranted to assess their effects.

Gold deposition with diagonal angle towards boehmite-based nanostructure creates random arrays of horse-bean-shaped nanostructures named gold-nanofève (GNF). GNF generates many electromagnetic hotspots as surface-enhanced Raman spectroscopy (SERS) excitation sources, and enables large-area visualization of molecular vibration fingerprints of metabolites in human cancer xenografts in livers of immunodeficient mice with sufficient sensitivity and uniformity. Differential screening of GNF-SERS signals in tumours and those in parenchyma demarcated tumour boundaries in liver tissues. Furthermore, GNF-SERS combined with quantum chemical calculation identified cysteine-derived glutathione and hypotaurine (HT) as tumour-dominant and parenchyma-dominant metabolites, respectively. CD44 knockdown in cancer diminished glutathione, but not HT in tumours. Mechanisms whereby tumours sustained HT under CD44-knockdown conditions include upregulation of PHGDH, PSAT1 and PSPH that drove glycolysis-dependent activation of serine/glycine-cleavage systems to provide one-methyl group for HT synthesis. HT was rapidly converted into taurine in cancer cells, suggesting that HT is a robust anti-oxidant for their survival under glutathione-suppressed conditions.

Taurine, a β-amino acid that is abundantly available in the tissues of human and animals, is efficiently used as a green bio-organic catalyst in the preparation of some of the biologically active barbituric and thiobarbituric acid derivatives. In the presence of taurine, 5-Arylidene (thio) barbituric acid derivatives were prepared via Knovenagel reaction between aldehydes and (thio)barbituric acid. Using this reagent also pyrano[2,3-d]pyrimidinone(thione) derivatives were synthesized through a three-component reaction between aldehydes, (thio)barbituric and malononitrile. Both reactions are performed in water with good to excellent yields during acceptable reaction times. No organic solvent was used during reaction or separation steps and no extra-purification was exerted. Meanwhile, reusability of taurine was easy and noticeably high., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Pre-column derivatization with fluorescence labeling reagents involves many problems including crowded chromatograms, possibility of the introduction of analytical errors, and poor selectivity. Herein we report a novel purification tag/fluorophore dual labeling approach based on a multi-component reaction to solve this major problem. Glyoxylic acid was recently identified as an early biomarker for diabetes, thus it was selected as a model analyte for our new dual labeling approach. Using the multi-component Petasis reaction, we could introduce a fluorophore (1-pyreneboronic acid, 1-PyBA) and a purification tag (taurine) to our target analyte (glyoxylic acid) in one step reaction. Using taurine as the amine reactant in Petasis reaction leads to the formation of a reaction product with a terminal sulfonic acid group which can be selectively retained on an anion exchange sorbent allowing excess fluorescent 1-PyBA reagent and its fluorescent decomposition products to be washed away. Then, quantification of the formed analyte-fluorophore-purification tag adduct was carried out by a simple isocratic HPLC-fluorescence detection method. The newly developed technique allowed highly selective, very rapid and efficient determination of glyoxylic acid in human serum eliminating endogenous components and excess reagent interference. Glyoxylic acid was determined in serum at a final concentration down to 30nM (600 fmol/injection) with good recovery (87.0%), accuracy (- 2.2 to 9.2) and precision (%RSD ≤ 8.7)., (Copyright © 2017 Elsevier B.V. All rights reserved.)