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Odour complaints are frequent nowadays, particularly nearby industrial facilities emitting odorous compounds. Among all compounds susceptible of causing odour annoyance, reduced sulphur compounds (RSC) were studied, due to their unpleasant odour and low odour threshold. RSC ambient air mixing ratios, meteorological conditions and population complaints were analysed in an area of complex topography in order to identify their potential sources. Mixing ratios of three compounds, dimethyl sulphide (DMS), carbon disulphide (CDS) and dimethyl disulphide (DMDS), were continuously monitored using an online gas chromatograph coupled with a mass spectrometer detector (GC-MSD), which was placed in a mobile air quality monitoring unit. Measurement campaigns were performed during 2012 and 2013 for periods of 7–25 days in an urban area (four campaigns, N  = 1368) and an urban area surrounded by industrial activities (three campaigns, N  = 564). During such campaigns, RSC mixing ratios were frequently above their odour thresholds, which did not always involve citizen complaints. Average RSC ambient air mixing ratios tended to be lower in the urban area (DMS 0.06–0.33, CDS 0.05–0.10, DMDS 0.07–0.30 μg m −3 ) than in the industry surrounded one (DMS 0.30–2.39, 0.05–0.18, DMDS 0.09–0.62 μg m −3 ). The DMS/DMDS mixing ratio was frequently above 1, being a paper mill one of the main sources of RSC in the area. DMS/DMDS ratios below 1 were also recorded, suggesting a waste treatment plant as the RSC source or older air masses coming from the paper mill.

Many nanoscale biomaterials fail to reach the clinical trial stage due to a poor understanding of the fundamental principles of their in vivo behaviour. Here we describe the transport, transformation and bioavailability of MoS 2 nanomaterials through a combination of in vivo experiments and molecular dynamics simulations. We show that after intravenous injection molybdenum is significantly enriched in liver sinusoid and splenic red pulp. This biodistribution is mediated by protein coronas that spontaneously form in the blood, principally with apolipoprotein E. The biotransformation of MoS 2 leads to incorporation of molybdenum into molybdenum enzymes, which increases their specific activities in the liver, affecting its metabolism. Our findings reveal that nanomaterials undergo a protein corona-bridged transport–transformation–bioavailability chain in vivo, and suggest that nanomaterials consisting of essential trace elements may be converted into active biological molecules that organisms can exploit. Our results also indicate that the long-term biotransformation of nanomaterials may have an impact on liver metabolism. Understanding the in vivo biotransformation of nanomaterials used for biomedical applications might shed light on their long-term effects and safety. Here the authors show that molybdenum derived from nanomaterials is mainly transported in the liver, in a corona-mediated process, and is incorporated in molybdoenzymes, with an effect on liver metabolism.

Aging proteins in the lens become increasingly aggregated and insoluble, contributing to presbyopia. In this study, we investigated the ability of aggrelyte‐2 (N,S‐diacetyl‐L‐cysteine methyl ester) to reverse the water insolubility of aged human lens proteins and to decrease stiffness in cultured human and mouse lenses. Water‐insoluble proteins (WI) of aged human lenses (65–75 years) were incubated with aggrelyte‐2 (500 μM) for 24 or 48 h. A control compound that lacked the S‐acetyl group (aggrelyte‐2C) was also tested. We observed 19%–30% solubility of WI upon treatment with aggrelyte‐2. Aggrelyte‐2C also increased protein solubility, but its effect was approximately 1.4‐fold lower than that of aggrelyte‐2. The protein thiol contents were 1.9‐ to 4.9‐fold higher in the aggrelyte‐2‐ and aggrelyte‐2C‐treated samples than in the untreated samples. The LC–MS/MS results showed Nε‐acetyllysine (AcK) levels of 1.5 to 2.1 nmol/mg protein and 0.6 to 0.9 nmol/mg protein in the aggrelyte‐2‐ and aggrelyte‐2C‐treated samples. Mouse (C57BL/6J) lenses (incubated for 24 h) and human lenses (incubated for 72 h) with 1.0 mM aggrelyte‐2 showed significant decreases in stiffness with simultaneous increases in soluble proteins (human lenses) and protein‐AcK levels, and such changes were not observed in aggrelyte‐2C‐treated lenses. Mass spectrometry of the solubilized protein revealed AcK in all crystallins, but more was observed in α‐crystallins. These results suggest that aggrelyte‐2 increases protein solubility and decreases lens stiffness through acetylation and disulfide reduction. Aggrelyte‐2 might be useful in treating presbyopia in humans. Presbyopia is a major vision‐impeding problem for many people over 40. Lens hardening (stiffening), due to protein insolubilization and aggregation, significantly contributes to presbyopia. Aggrelyte‐2 solubilizes aggregated proteins and reduces lens stiffness through lysine acetylation and disulfide reduction.

Disulfide bonds are important structural moieties of proteins: they ensure proper folding, provide stability, and ensure proper function. With the increasing use of proteins for biotherapeutics, particularly monoclonal antibodies, which are highly disulfide bonded, it is now important to confirm the correct disulfide bond connectivity and to verify the presence, or absence, of disulfide bond variants in the protein therapeutics. These studies help to ensure safety and efficacy. Hence, disulfide bonds are among the critical quality attributes of proteins that have to be monitored closely during the development of biotherapeutics. However, disulfide bond analysis is challenging because of the complexity of the biomolecules. Mass spectrometry (MS) has been the go-to analytical tool for the characterization of such complex biomolecules, and several methods have been reported to meet the challenging task of mapping disulfide bonds in proteins. In this review, we describe the relevant, recent MS-based techniques and provide important considerations needed for efficient disulfide bond analysis in proteins. The review focuses on methods for proper sample preparation, fragmentation techniques for disulfide bond analysis, recent disulfide bond mapping methods based on the fragmentation techniques, and automated algorithms designed for rapid analysis of disulfide bonds from liquid chromatography–MS/MS data. Researchers involved in method development for protein characterization can use the information herein to facilitate development of new MS-based methods for protein disulfide bond analysis. In addition, individuals characterizing biotherapeutics, especially by disulfide bond mapping in antibodies, can use this review to choose the best strategies for disulfide bond assignment of their biologic products.

It is widely accepted that the redox status of protein thiols is of central importance to protein structure and folding and that glutathione is an important low-molecular-mass redox regulator. However, the total cellular pools of thiols and disulfides and their relative abundance have never been determined. In this study, we have assembled a global picture of the cellular thiol-disulfide status in cultured mammalian cells. We have quantified the absolute levels of protein thiols, protein disulfides, and glutathionylated protein (PSSG) in all cellular protein, including membrane proteins. These data were combined with quantification of reduced and oxidized glutathione in the same cells. Of the total protein cysteines, 6% and 9.6% are engaged in disulf ide bond formation in HEK and HeLa cells, respectively. Furthermore, the steady- state level of PSSG is < 0.1% of the total protein cysteines in both cell types. However, when cells are exposed to a sublethal dose of the thiol-specific oxidant diamide, PSSG levels increase to > 15% of all protein cysteine. Glutathione is typically characterized as the \"cellular redox buffer\"; nevertheless, our data show that protein thiols represent a larger active redox pool than glutathione. Accordingly, protein thiols are likely to be directly involved in the cellular defense against oxidative stress.

Diallyl disulfide (DADS) is one of the major volatile components of garlic oil. DADS has various biological properties, including anticancer, antiangiogenic, and antioxidant effects. However, the anticancer mechanisms of DADS in human breast cancer have not been elucidated, particularly in vivo. In this study, we demonstrated that the expression of miR-34a was up-regulated in DADS-treated MDA-MB-231 cells. miR-34a not only inhibited breast cancer growth but also enhanced the antitumor effect of DADS, both in vitro and in vivo. Furthermore, Src was identified as a target of miR-34a, with miR-34a inhibiting SRC expression and consequently triggering the suppression of the SRC/Ras/ERK pathway. These results suggest that DADS could be a promising anticancer agent for breast cancer. miR-34a may also demonstrate a potential gene therapy agent that could enhance the antitumor effects of DADS.

Mercaptocarboxylic acids and their esters, a class of difunctional compounds bearing both a mercapto and a carboxylic acid or ester functional group, are industrial chemicals of potential environmental concern. Biodegradation of such compounds was systematically investigated here, both by literature search and by experiments (Closed Bottle Test OECD 301D and Manometric Respirometry Test OECD 301F). These compounds were found either readily biodegradable or at least biodegradable to a significant extent. Some related compounds of divalent sulfur were tested for comparison (mercaptans, sulfides, disulfides). For the two relevant monofunctional compound classes, carboxylic acids/esters and mercaptans, literature data were compiled, and by comparison with structurally similar compounds without these functional groups, the influence of COOH/COOR’ and SH groups on biodegradability was evaluated. Thereby, an existing rule of thumb for biodegradation of carboxylic acids/esters was supported by experimental data, and a rule of thumb could be formulated for mercaptans. Concurrent to biodegradation, abiotic processes were observed in the experiments, rapid oxidative formation of disulfides (dimerisation of monomercaptans and cyclisation of dimercaptans) and hydrolysis of esters. Some problems that compromise the reproducibility of biodegradation test results were discussed.

This study evaluated the neuroprotective potential of Allium sativum against monosodium glutamate (MSG)-induced neurotoxicity with respect to its impact on short-term memory in rats. Forty male Wistar albino rats were assigned into four groups. The control group received distilled water. The second group was administered Allium sativum powder (200 mg/kg of body weight) orally for 7 successive days, then was left without treatment until the 30th day. The third group was injected intraperitoneally with MSG (4 g/kg of body weight) for 7 successive days, then left without treatment until the 30th day. The fourth group was injected with MSG in the same manner as the third group and was treated with Allium sativum powder in the same manner as the second group, simultaneously. Phytochemical analysis of Allium sativum powder identified the presence of diallyl disulphide, carvone, diallyl trisulfide, and allyl tetrasulfide. MSG-induced excitotoxicity and cognitive deficit were represented by decreased distance moved and taking a long time to start moving from the center in the open field, as well as lack of curiosity in investigating the novel object and novel arm. Moreover, MSG altered hippocampus structure and increased MDA concentration and protein expression of glial fibrillary acidic protein (GFAP), calretinin, and caspase-3, whereas it decreased superoxide dismutase (SOD) activity and protein expression of Ki-67 in brain tissue. However, Allium sativum powder prevented MSG-induced neurotoxicity and improved short-term memory through enhancing antioxidant activity and reducing lipid peroxidation. In addition, it decreased protein expression of GFAP, calretinin, and caspase-3 and increased protein expression of Ki-67 in brain tissues and retained brain tissue architecture. This study indicated that Allium sativum powder ameliorated MSG-induced neurotoxicity through preventing oxidative stress-induced gliosis and apoptosis of brain tissue in rats.

Background and Objectives: Sarcopenic obesity (SO), characterized by the coexistence of excess adiposity and reduced muscle mass/function, is associated with adverse outcomes in older adults. Oxidative stress has been implicated in the pathogenesis of both obesity and sarcopenia. This study aimed to evaluate the association between thiol/disulfide homeostasis (TDH), ischemia-modified albumin (IMA), and SO in obese older adults. Materials and Methods: In this cross-sectional study, 132 obese individuals aged ≥65 years were enrolled from a geriatrics outpatient clinic. SO was defined based on the ESPEN/EASO criteria, incorporating anthropometric, body composition, and muscle function measures. Serum native and total thiol levels, disulfide concentrations, and IMA were assessed. Logistic regression identified independent predictors of SO, and ROC analysis evaluated the discriminatory power of oxidative parameters. Results: SO was present in 15.2% (n = 20) of participants. Patients with SO exhibited significantly lower native (p = 0.003) and total thiol levels (p < 0.001), and higher disulfide/native thiol (p = 0.009) and disulfide/total thiol ratios (p = 0.009). IMA levels were slightly elevated in SO but not significantly different (p = 0.13). In multivariable regression, age and disulfide/native thiol ratio were independent predictors of SO (OR = 5.71, p = 0.041). ROC analysis showed that disulfide/native thiol ratio had moderate predictive accuracy (AUC = 0.684, p = 0.008), with a cut-off > 6.63 yielding 92.86% specificity. Conclusions: Older adults with SO exhibit disrupted redox balance, as evidenced by altered TDH parameters. The disulfide/native thiol ratio may serve as a useful oxidative biomarker for identifying SO. These findings highlight the potential role of oxidative stress in SO and warrant further research into targeted antioxidant strategies.

On-pump coronary artery bypass grafting (CABG) method affect almost allbiochemicalreactions by disrupting the patient's redox homeostasis. Detection of systemic redox hemostasis in the patient is critical for the CABG method's success and the prognosis of the disease. In this study, thiol/disulfide parameters, which are indicators of redox homeostasis, and ischemia-modified albumin levels in the plasma and pericardial fluid of patients who underwent CABG were investigated. Sixty patients who underwent an on-pump CABG operation with the cardiopulmonary bypass method were included in this study. Blood samples were taken from the patients before and after cardiopulmonary bypass. Pericardia fluid samples were taken before cardiopulmonary bypass. Then, thiol/disulfide homeostasis, albumin, and ischemia-modified albumin levels in the pericardial fluid and the patients' plasma levels were compared. Albumin and ischemia-modified albumin levels were significantly higher in the postoperative period compared to the preoperative one (P<0.001). Thiol/disulfide parameters were higher and statistically significant in preoperative than in postoperative examinations (P<0.001). A negative correlation was found between pericardial fluid ischemia-modified albumin and thiol-disulfide parameters (P<0.001). Changes in thiol/disulfide homeostasis, albumin, and ischemia-modified albumin levels at different times during the on-pump CABG may be caused by foreign non-endothelial surfaces, filters, the reperfusion process, and pharmacological effects in the extracorporeal circulation. Thiol/disulfide homeostasis, albumin, and ischemia-modified albumin levels should be monitored during the on-pump CABG and should be intervened with appropriate therapeutic strategies. In this way, secondary pathologies can be avoided by preventing cellular damage and excessive inflammatory responses.