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BACKGROUND: Flaxseed orbitides have health‐promoting properties, particularly potent anti‐cancer activity. However, flaxseed orbitides containing a methionine structure, such as [1‐9‐NαC]‐linusorb B2 (CLB), are easily oxidized to sulfoxide ([1‐9‐NαC],[1‐Rs,Ss‐MetO]‐linusorb‐B2 (CLC)) and sulfone ([1–9‐NαC], [1‐MetO]‐linusorb B2 (CLK)), with CLC having less anti‐cancer ability than CLB. It is unclear why oxidized flaxseed orbitides are less effective against cancer than non‐oxidized flaxseed orbitide. RESULTS: Non‐oxidized ([1‐9‐NαC]‐linusorb‐B3 (CLA) and CLB) and oxidized (CLC and CLK) flaxseed orbitides were found to significantly upregulate the levels of pro‐apoptotic proteins, including Bax/Bcl‐2, CytoC, caspase‐3, and caspase‐8, in a dose‐dependent manner, with non‐oxidized flaxseed orbitides being more effective than oxidized flaxseed orbitides. Mechanically, the cellular absorption of non‐oxidized flaxseed orbitides was higher than that of oxidized flaxseed orbitides. Moreover, the significant fluorescence quenching of DR4 protein by flaxseed orbitides (especially non‐oxidized orbitides) indicated the formation of a DR4–orbitide complex. Molecular docking demonstrated that non‐oxidized orbitides could easily dock into the active cavity of DR4 protein. Further blocking DR4 significantly reduced the ability of non‐oxidized flaxseed orbitides to stimulate caspase‐3 expression, whereas oxidized flaxseed orbitides retained this ability. CONCLUSION: Non‐oxidized flaxseed orbitides are more effective against cancer than oxidized flaxseed orbitides due to higher cellular uptake and activation of the DR4‐mediated death receptor signaling pathway. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

This article explores the metabolic features of chronic rhinosinusitis with polyps (CRSwNP). The study focuses on the metabolic dysregulation in nasal polyps and its potential relationship with metabolic syndrome (MS). The researchers conducted a transcriptomic analysis of nasal polyp tissues and healthy control nasal mucosa to identify characteristic genes associated with metabolic aspects in nasal polyps. They found that disrupted energy metabolism may be a distinctive feature of CRSwNP and that metabolic reprogramming of fibroblasts may play a role in promoting the occurrence and development of nasal polyps. Further research and validation are needed to fully understand the relationship between CRSwNP and metabolic dysregulation. [Extracted from the article]

Human nasal mucosa is susceptible to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and serves as a reservoir for viral replication before spreading to other organs (e.g. the lung and brain) and transmission to other individuals. Chronic rhinosinusitis (CRS) is a common respiratory tract disease and there is evidence suggesting that susceptibility to SARS‐CoV‐2 infection differs between the two known subtypes, eosinophilic CRS and non‐ECRS (NECRS). However, the mechanism of SARS‐CoV‐2 infection in the human nasal mucosa and its association with CRS has not been experimentally validated. In this study, we investigated whether the human nasal mucosa is susceptible to SARS‐CoV‐2 infection and how different endotypes of CRS impact on viral infection and progression. Primary human nasal mucosa tissue culture revealed highly efficient SARS‐CoV‐2 viral infection and production, with particularly high susceptibility in the NECRS group. The gene expression differences suggested that human nasal mucosa is highly susceptible to SARS‐CoV‐2 infection, presumably due to an increase in ACE2‐expressing cells and a deficiency in antiviral immune response, especially for NECRS. Importantly, patients with NECRS may be at a particularly high risk of viral infection and transmission, and therefore, close monitoring should be considered. [ABSTRACT FROM AUTHOR]

Objective: The discovery of carbon monoxide (CO) and hydrogen sulfide (H2S) as pathogenic signaling molecules in airway-related diseases has led to significant insights into the pathophysiologic mechanisms underlying the development of allergic rhinitis (AR). The potential crosstalk between CO and H2S signaling pathways in AR has not been adequately investigated. This study was performed to elucidate the mechanistic relationship between CO and H2S in AR.Study Design: Experimental prospective animal study.Setting: Animal laboratory of Tongji Hospital, Tongji University, Shanghai, China.Subjects and Methods: A well-established model of AR was used whereby guinea pigs (N=24) were randomly divided into 4 treatment groups (n=6 for each group): The first group received ovalbumin only; the second group was administered exogenous hemin, a CO-binding metalloporphyrin; the third group received zinc protoporphyrin, an inhibitor of heme oxygenase-1. A control group was challenged using only saline. Symptoms of AR were recorded, and quantitation of plasma CO and H2S levels was performed. Expression of heme oxygenase-1 and H2S-generating enzyme cystathionine-γ-lyase (CSE) were measured from nasal mucosa.Results: Plasma CO and heme oxygenase-1 expression levels of nasal mucosa were significantly increased in the AR group compared to controls, whereas H2S concentrations were significantly decreased. Exogenous administration of CO exacerbated allergic symptoms, resulting in higher levels of both CO and heme oxygenase-1 expression, and a further reduction in H2S levels and CSE expression. Zinc protoporphyrin decreased CO concentrations and increased levels of both H2S and CSE expression.Conclusions: Results indicated an inverse relationship between H2S levels and CO in the pathogenesis of AR. [ABSTRACT FROM AUTHOR]

A facile synthesis of a series of saccharide-binding arylboronic acid derivatives of indoloquinoline was described. The key synthetic steps were polyphosphoric acid-mediated cyclization, chlorinative aromatization, and amidation. Mass spectrometry experiments revealed these synthetic arylboronic acid derivatives of indoquinolines could bind to biologically important carbohydrates (sialic acid, fucose, glucose, and galactose) by forming boronate di-esters in alkaline aqueous solution. Most of the arylboronic acid derivatives of indoquinolines inhibited human breast cancer cell (MDA-231) proliferation at a concentration of 5 μ m, whereas the compound 17 exhibited highest percentages (76.74%) of the cancer cell proliferation inhibition. [ABSTRACT FROM AUTHOR]

This research letter discusses the emerging role of SAMSN1+ mast cells in chronic sinusitis and obesity. The authors conducted Mendelian randomization and transcriptomic analyses to explore the genetic and molecular mechanisms linking these two conditions. The results suggest that obesity may increase the risk of chronic sinusitis, but there is no evidence of chronic sinusitis contributing to obesity. Additionally, the study found that SAMSN1+ mast cells are associated with the activation of the TGF-β pathway in chronic sinusitis, highlighting a potential therapeutic target. [Extracted from the article]