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Archives of Toxicology Aug 2020Arsenic is a well-known environmental carcinogen and chronic exposure to arsenic through drinking water has been reported to cause skin, bladder and lung cancers, with... (Review)
Review
Arsenic is a well-known environmental carcinogen and chronic exposure to arsenic through drinking water has been reported to cause skin, bladder and lung cancers, with arsenic metabolites being implicated in the pathogenesis. In contrast, arsenic trioxide (AsO) is an effective therapeutic agent for the treatment of acute promyelocytic leukemia, in which the binding of arsenite (iAs) to promyelocytic leukemia (PML) protein is the proposed initial step. These findings on the two-edged sword characteristics of arsenic suggest that after entry into cells, arsenic reaches the nucleus and triggers various nuclear events. Arsenic is reduced, conjugated with glutathione, and methylated in the cytosol. These biotransformations, including the production of reactive metabolic intermediates, appear to determine the intracellular dynamics, target organs, and biological functions of arsenic.
Topics: Animals; Antineoplastic Agents; Arsenic Poisoning; Arsenic Trioxide; Arsenicals; Biotransformation; Humans; Leukemia, Promyelocytic, Acute; Risk Assessment; Toxicity Tests
PubMed: 32435915
DOI: 10.1007/s00204-020-02772-9 -
Biomedical Materials (Bristol, England) Mar 2021Click chemistry is not a single specific reaction, but describes ways of generating products which emulate examples in nature. Click reactions occur in one pot, are not...
Click chemistry is not a single specific reaction, but describes ways of generating products which emulate examples in nature. Click reactions occur in one pot, are not disturbed by water, generate minimal and inoffensive byproducts, and are characterized by a high thermodynamic driving force, driving the reaction quickly and irreversibly towards a high yield of a single reaction product. As a result, over the past 15 years it has become a very useful bio-orthogonal method for the preparation of chemical cross-linked biopolymer-based hydrogel, in the presence of e.g. growth factors and live cells, or in-vivo. Biopolymers are renewable and non-toxic, providing a myriad of potential backbone toolboxes for hydrogel design. The goal of this review is to summarize recent advances in the development of click chemistry-based biopolymeric hydrogels, and their applications in regenerative medicine. In particular, various click chemistry approaches, including copper-catalyzed azide-alkyne cycloaddition reactions, copper-free click reactions (e.g. the Diels-Alder reactions, the strain-promoted azide-alkyne cycloaddition reactions, the radical mediated thiol-ene reactions, and the oxime-forming reactions), and pseudo-click reactions (e.g. the thiol-Michael addition reactions and the Schiff base reactions) are highlighted in the first section. In addition, numerous biopolymers, including proteins (e.g. collagen, gelatin, silk, and mucin), polysaccharides (e.g. hyaluronic acid, alginate, dextran, and chitosan) and polynucleotides (e.g. deoxyribonucleic acid), are discussed. Finally, we discuss biopolymeric hydrogels, cross-linked by click chemistry, intended for the regeneration of skin, bone, spinal cord, cartilage, and cornea. This article provides new insights for readers in terms of the design of regenerative medicine, and the use of biopolymeric hydrogels based on click chemistry reactions.
Topics: Alginates; Animals; Biocompatible Materials; Biopolymers; Cartilage; Click Chemistry; Collagen; Copper; Cross-Linking Reagents; Cycloaddition Reaction; Drug Delivery Systems; Gelatin; Humans; Hyaluronic Acid; Hydrogels; Mice; Polymers; Proteins; Rats; Regenerative Medicine; Stress, Mechanical; Sulfhydryl Compounds; Tissue Engineering; Wound Healing
PubMed: 33049725
DOI: 10.1088/1748-605X/abc0b3 -
Acta Neuropathologica Communications Jan 2023We recently discovered that the expression of PRKN, a young-onset Parkinson disease-linked gene, confers redox homeostasis. To further examine the protective effects of...
We recently discovered that the expression of PRKN, a young-onset Parkinson disease-linked gene, confers redox homeostasis. To further examine the protective effects of parkin in an oxidative stress model, we first combined the loss of prkn with Sod2 haploinsufficiency in mice. Although adult prkn//Sod2 animals did not develop dopamine cell loss in the S. nigra, they had more reactive oxidative species and a higher concentration of carbonylated proteins in the brain; bi-genic mice also showed a trend for more nitrotyrosinated proteins. Because these redox changes were seen in the cytosol rather than mitochondria, we next explored the thiol network in the context of PRKN expression. We detected a parkin deficiency-associated increase in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) in murine brain, PRKN-linked human cortex and several cell models. This shift resulted from enhanced recycling of GSSG back to GSH via upregulated glutathione reductase activity; it also correlated with altered activities of redox-sensitive enzymes in mitochondria isolated from mouse brain (e.g., aconitase-2; creatine kinase). Intriguingly, human parkin itself showed glutathione-recycling activity in vitro and in cells: For each GSSG dipeptide encountered, parkin regenerated one GSH molecule and was S-glutathionylated by the other (GSSG + P-SH [Formula: see text] GSH + P-S-SG), including at cysteines 59, 95 and 377. Moreover, parkin's S-glutathionylation was reversible by glutaredoxin activity. In summary, we found that PRKN gene expression contributes to the network of available thiols in the cell, including by parkin's participation in glutathione recycling, which involves a reversible, posttranslational modification at select cysteines. Further, parkin's impact on redox homeostasis in the cytosol can affect enzyme activities elsewhere, such as in mitochondria. We posit that antioxidant functions of parkin may explain many of its previously described, protective effects in vertebrates and invertebrates that are unrelated to E3 ligase activity.
Topics: Adult; Mice; Humans; Animals; Glutathione Disulfide; Glutathione; Proteins; Oxidation-Reduction; Oxidative Stress; Ubiquitin-Protein Ligases; Antioxidants; Cysteine; Brain; Sulfhydryl Compounds; Mammals
PubMed: 36691076
DOI: 10.1186/s40478-022-01488-4 -
Food Chemistry Jun 2020Gluten network formation by the oxidation of glutenin sulfhydryl group majorly impacts the subsequent dough and bread properties, and an evolutionary list of chemical... (Comparative Study)
Comparative Study
Gluten network formation by the oxidation of glutenin sulfhydryl group majorly impacts the subsequent dough and bread properties, and an evolutionary list of chemical oxidants has been used as improvers in bread making. A systematic comparison between azodicarbonamide (ADA), Vc, wheat protein disulfide isomerase (wPDI) and disulfide bond formation protein C (DsbC) of their effects on the alveographic characters of dough and texture properties of subsequent bread was performed. Results show that wPDI improves dough alveographic characters and bread texture properties better in most aspects than other reagents. Free sulfhydryl analysis finds that addition of wPDI increased the free sulfhydryl content in both dough and bread. Compare with inorganic reagents and its bacterial homologue, improving the dough and bread properties with less oxidation of sulfhydryl lead to the proposal that wPDI acts by catalyzing the formation of rheologically active disulfide and reduction of inactive ones in a substrate specific manner.
Topics: Azo Compounds; Bread; Dietary Proteins; Disulfides; Flour; Glutens; Protein Disulfide-Isomerases; Rheology; Sulfhydryl Compounds; Triticum
PubMed: 31991256
DOI: 10.1016/j.foodchem.2020.126242 -
ChemSusChem Oct 2022The dissolution of elemental noble metals (NMs) such as gold, platinum, palladium, and copper is necessary for their recycling but carries a high environmental burden...
The dissolution of elemental noble metals (NMs) such as gold, platinum, palladium, and copper is necessary for their recycling but carries a high environmental burden due to the use of strong acids and toxic reagents. Herein, a new approach was developed for the rapid dissolution of elemental NMs in organic solvents using mixtures of triphenylphosphine dichloride or oxalyl chloride and hydrogen peroxide, forming metal chloride salts directly. Almost quantitative dissolution of metallic Au, Pd, and Cu was observed within minutes at room temperature. For Pt, dissolution was achieved, albeit more slowly, using the chlorinating oxidant alone but was inhibited on addition of hydrogen peroxide. After leaching, transfer of Pt and Pd chloride salts from the organic phase into a 6 m HCl aqueous phase facilitated their separation by precipitation of Pt using a simple diamide ligand. In contrast, the retention of Au chloridometalate in the organic phase allowed its selective separation from Ni and Cu from a leachate solution obtained from electronic CPUs. This new approach has potential application in the hydrometallurgical leaching and purification of NMs from ores, spent catalysts, and electronic and nano-wastes.
Topics: Electronic Waste; Palladium; Copper; Chlorides; Platinum; Hydrogen Peroxide; Solubility; Ligands; Diamide; Salts; Recycling; Gold; Solvents; Oxidants
PubMed: 35929761
DOI: 10.1002/cssc.202201285 -
Cellular & Molecular Immunology Mar 2023
Topics: Humans; Arsenic Trioxide; Necrosis; Apoptosis; Antineoplastic Agents; Arsenicals
PubMed: 36693921
DOI: 10.1038/s41423-023-00976-4 -
Molecules (Basel, Switzerland) Sep 2020In this study, we demonstrate that small charged molecules (NH, GluA, dHA) can form physical cross-links between hyaluronan chains, facilitating polymerization reactions...
In this study, we demonstrate that small charged molecules (NH, GluA, dHA) can form physical cross-links between hyaluronan chains, facilitating polymerization reactions between synthetically introduced thiol groups (HA-DTPH). These hybrid hydrogels can be obtained under physiological conditions ideally suited for 3D cell culture systems. The type and concentration of a physical crosslinker can be adjusted to precisely tune mechanical properties as well as degradability of the desired hydrogel system. We analyze the influence of hydrogen bond formation, concentration and additional ionic interactions on the polymerization reaction of HA-DTPH hydrogels and characterize the resulting hydrogels in regard to mechanical and biocompatibility aspects.
Topics: Biocompatible Materials; Cell Culture Techniques; Cell Survival; Cross-Linking Reagents; Disulfides; Elastic Modulus; Fibroblasts; Humans; Hyaluronic Acid; Hydrogel, Polyethylene Glycol Dimethacrylate; Hydrogen Bonding; Ions; Oligopeptides; Polymerization; Polymers; Skin; Stress, Mechanical; Sulfhydryl Compounds; Tissue Engineering
PubMed: 32933012
DOI: 10.3390/molecules25184166 -
Food Chemistry Mar 2022Interactions between pea protein and whey protein isolates in co-precipitates and blends consist of a combination of disulphide bonds, hydrophobic and electrostatic...
Interactions between pea protein and whey protein isolates in co-precipitates and blends consist of a combination of disulphide bonds, hydrophobic and electrostatic interactions. The present study aims to clarify if the two proteins with free thiols, β-lactoglobulin (β-lg) and legumin, played a significant role for these interactions. This study used different reagents to modify the conditions of interactions: N-ethylmaleimide (NEM) was used to block reactive thiols, while NaCl and SDS were used to prevent electrostatic or hydrophobic interactions, respectively. The effects of treatments were studied on protein solubility, structure and stability. SDS had no effect, while NEM and NaCl both had great effect, especially in combination. The results showed that interactions of β-lg and legumin in both co-precipitates and blends are a synergism of electrostatic interactions and disulphide bonds. Thus, β-lg and legumin are the main proteins responsible for previously observed interactions in protein isolates of whey and pea.
Topics: Ethylmaleimide; Fabaceae; Hydrophobic and Hydrophilic Interactions; Lactoglobulins; Whey Proteins
PubMed: 34774378
DOI: 10.1016/j.foodchem.2021.131509 -
Comparative Biochemistry and... Sep 2023In nature, arsenic is mostly found in the form of inorganic compounds. Inorganic arsenic compounds have a variety of uses and are currently used in the manufacture of... (Review)
Review
In nature, arsenic is mostly found in the form of inorganic compounds. Inorganic arsenic compounds have a variety of uses and are currently used in the manufacture of pesticides, preservatives, pharmaceuticals, etc. While inorganic arsenic is widely used, arsenic pollution is increasing worldwide. Public hazards caused by arsenic contamination of drinking water and soil are becoming increasingly evident. Epidemiological and experimental studies have linked inorganic arsenic exposure to the development of many diseases, including cognitive impairment, cardiovascular failure, cancer, etc. Several mechanisms have been proposed to explain the effects caused by arsenic, such as oxidative damage, DNA methylation, and protein misfolding. Understanding the toxicology and potential molecular mechanisms of arsenic can help mitigate its harmful effects. Therefore, this paper reviews the multiple organ toxicity of inorganic arsenic in animals, focusing on the various toxicity mechanisms of arsenic-induced diseases in animals. In addition, we have summarized several drugs that can have therapeutic effects on arsenic poisoning in pursuit of reducing the harm of arsenic contamination from different pathways.
Topics: Animals; Arsenic; Arsenicals; Arsenic Poisoning; Environmental Pollution; Drinking Water
PubMed: 37230210
DOI: 10.1016/j.cbpc.2023.109654 -
Experimental Eye Research Nov 2023Lewisite (LEW) is an arsenical vesicant that can be a potentially dangerous chemical warfare agent (CWA). Eyes are particularly susceptible to vesicant induced injuries...
Lewisite (LEW) is an arsenical vesicant that can be a potentially dangerous chemical warfare agent (CWA). Eyes are particularly susceptible to vesicant induced injuries and ocular LEW exposure can act swiftly, causing burning of eyes, edema, inflammation, cell death and even blindness. In our previous studies, we developed a LEW exposure-induced corneal injury model in rabbit and showed increased inflammation, neovascularization, cell death, and structural damage to rabbit corneas upon LEW exposure. In the present study, we further assessed the metabolomic changes to delineate the possible mechanisms underlying the LEW-induced corneal injuries. This information is vital and could help in the development of effective targeted therapies against ocular LEW injuries. Thus, the metabolomic changes associated with LEW exposures in rabbit corneas were assessed as a function of time, to delineate pathways from molecular perturbations at the genomic and proteomic levels. New Zealand white rabbit corneas (n = 3-6) were exposed to LEW vapor (0.2 mg/L; flow rate: 300 ml/min) for 2.5 min (short exposure; low dose) or 7.5 min (long-exposure; high dose) and then collected at 1, 3, 7, or 14 days post LEW exposure. Samples were prepared using the automated MicroLab STAR® system, and proteins precipitated to recover the chemically diverse metabolites. Metabolomic analysis was carried out by reverse phase UPLC-MS/MS and gas chromatography (GC)-MS. The data obtained were analyzed using Metabolon's software. The results showed that LEW exposures at high doses were more toxic, particularly at the day 7 post exposure time point. LEW exposure was shown to dysregulate metabolites associated with all the integral functions of the cornea and cause increased inflammation and immune response, as well as generate oxidative stress. Additionally, all important metabolic functions of the cells were also affected: lipid and nucleotide metabolism, and energetics. The high dose LEW exposures were more toxic, particularly at day 7 post LEW exposure (>10-fold increased levels of histamine, quinolinate, N-acetyl-β-alanine, GMP, and UPM). LEW exposure dysregulated integral functions of the cornea, caused inflammation and heightened immune response, and generated oxidative stress. Lipid and nucleotide metabolism, and energetics were also affected. The novel information about altered metabolic profile of rabbit cornea following LEW exposure could assist in delineating complex molecular events; thus, aid in identifying therapeutic targets to effectively ameliorate ocular trauma.
Topics: Animals; Rabbits; Irritants; Chromatography, Liquid; Proteomics; Tandem Mass Spectrometry; Cornea; Corneal Injuries; Arsenicals; Inflammation; Nucleotides; Lipids
PubMed: 37797797
DOI: 10.1016/j.exer.2023.109672