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Walther Gross posted an update 3 months, 3 weeks ago
Fadi Meroueh talks to Andréia Azevedo Soares about ensuring health equity and harm reduction services in prisons, and the challenges presented by the COVID-19 pandemic.Pandemic-related school closures are impacting the sexual and reproductive health and rights of adolescent girls. Lynn Eaton reports.Capsaicin is the main component in chilli pepper, which contributes to the spiciness of the food. BAY-3605349 However, the role of capsaicin on aroma perception has been controversial in the literature. This is the first study exploring the impact of capsaicin on aroma release and perception simultaneously. Flavoured solutions with 3-methylbutanal (nutty note) were made with or without 5 mg/L capsaicin. Real-time APCI-MS analysis was applied to investigate in-nose aroma release during and after consumption of the solutions, and sensory tests were simultaneously conducted to reveal any temporal perception changes over 60 s. The results from 15 participants with triplicates indicated that capsaicin had no significant impact on aroma concentration from aqueous solutions, but the aroma perception rating was significantly higher (p less then 0.0001), increasing by 45%. Capsaicin also enhanced average saliva flow by 92% (p less then 0.0001), and lower saliva flow participants were found to have lower spiciness and aroma ratings.Inhalation exposure to environmental and occupational aerosol contaminants is associated with many respiratory health problems. To realistically mimic long-term inhalation exposure for toxicity testing, lung epithelial cells need to maintained and exposed under air-liquid interface (ALI) conditions for a prolonged period of time. In addition, to study cellular responses to aerosol particles, lung epithelial cells have to be co-cultured with macrophages. To that aim, we evaluated human bronchial epithelial Calu-3, 16HBE14o- (16HBE), H292, and BEAS-2B cell lines with respect to epithelial morphology, barrier function and cell viability under prolonged ALI culture conditions. Only the Calu-3 cells can retain the monolayer structure and maintain a strong tight junction under long-term ALI culture at least up to 2 weeks. As such, Calu-3 cells were applied as the structural barrier to create co-culture models with human monocyte-derived macrophages (MDMs) and THP-1 derived macrophages (TDMs). Adhesion of macrophages onto the epithelial monolayer was allowed for 4 h with a density of 5 × 104 macrophages/cm2. In comparison to the Calu-3 mono-culture model, Calu-3 + TDM and Calu-3 + MDM co-culture models showed an increased sensitivity in inflammatory responses to lipopolysaccharide (LPS) aerosol at Day 1 of co-culture, with the Calu-3 + MDM model giving a stronger response than Calu-3 + TDM. Therefore, the epithelial monolayer integrity and increased sensitivity make the Calu-3 + MDM co-culture model a preferred option for ALI exposure to inhaled aerosols for toxicity testing.
Silicosis is a chronic occupational lung disease. As was previously found by the authors, some proteins increased in the lung tissue of activated rats, and protein tyrosine phosphatase non-receptor type 2 (PTPN2), factor B, and vaccinia-related kinase 1 (VRK1) showed highly differential expressions.
In this study, serum and bronchoalveolar lavage fluid samples were collected from patients with silicosis and healthy people to verify the expression of PTPN2, factor B, and VRK1. The diagnostic value of differentially expressed proteins for silicosis was judged.
The expression levels of serum PTPN2, VRK1, and factor B in patients with silicosis were significantly higher than those in the control group (p < 0.01). Higher serum PTPN2 and factor B concentrations significantly and negatively correlated with the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV
/FVC), maximum vital capacity (VC
), FEV
, and FVC, suggesting that the high expression of PTPN2 and factor B is associated with decreased pulmonary ventilation function and restrictive ventilatory impairment in patients with silicosis. All area under curve (AUC) measurements generated from single detection events were >0.744, with PTPN2 reaching the highest value (0.858). The AUC, sensitivity, and specificity for the combined diagnosis using factor B and PTPN2 were 0.907, 86.91% and 85.07%, respectively, for factor B and PTPN2. The 3 differentially expressed proteins are potential classes of predictive biomarkers for silicosis.
Regarding the economy and test practicality, the best diagnostic combination is factor B and PTPN2 for the analysis of AUC, sensitivity and specificity. Int J Occup Med Environ Health. 2021;34(4)527-40.
Regarding the economy and test practicality, the best diagnostic combination is factor B and PTPN2 for the analysis of AUC, sensitivity and specificity. Int J Occup Med Environ Health. 2021;34(4)527-40.Transfer RNA (tRNA) is an adapter molecule that links a specific codon in mRNA with its corresponding amino acid during protein synthesis. tRNAs are enzymatically modified post-transcriptionally. A wide variety of tRNA modifications are found in the tRNA anticodon, which are crucial for precise codon recognition and reading frame maintenance, thereby ensuring accurate and efficient protein synthesis. In addition, tRNA-body regions are also frequently modified and thus stabilized in the cell. Over the past two decades, 16 novel tRNA modifications were discovered in various organisms, and the chemical space of tRNA modification continues to expand. Recent studies have revealed that tRNA modifications can be dynamically altered in response to levels of cellular metabolites and environmental stresses. Importantly, we now understand that deficiencies in tRNA modification can have pathological consequences, which are termed ‘RNA modopathies’. Dysregulation of tRNA modification is involved in mitochondrial diseases, neurological disorders and cancer.The human glycine transporter 1 (GlyT1) regulates glycine-mediated neuronal excitation and inhibition through the sodium- and chloride-dependent reuptake of glycine1-3. Inhibition of GlyT1 prolongs neurotransmitter signalling, and has long been a key strategy in the development of therapies for a broad range of disorders of the central nervous system, including schizophrenia and cognitive impairments4. Here, using a synthetic single-domain antibody (sybody) and serial synchrotron crystallography, we have determined the structure of GlyT1 in complex with a benzoylpiperazine chemotype inhibitor at 3.4 Å resolution. We find that the inhibitor locks GlyT1 in an inward-open conformation and binds at the intracellular gate of the release pathway, overlapping with the glycine-release site. The inhibitor is likely to reach GlyT1 from the cytoplasmic leaflet of the plasma membrane. Our results define the mechanism of inhibition and enable the rational design of new, clinically efficacious GlyT1 inhibitors.