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  • Barnes Schack posted an update 2 days, 11 hours ago

    Ultrasound (US)-induced sonodynamic therapy (SDT) is an efficient and precise method against tumor, and the integration of multiple cancer therapies has been proved as a promising strategy for better therapeutic effects. Herein, for the first time, a multifunctional nanoreactor has been fabricated by integrating Fe-MIL-88B-NH2, PFC-1, and glucose oxidase (GO x ) to form urchin-like Fe-MIL-88B-NH2@PFC-1-GO x (MPG) nanoparticles as Fenton’s reagent, a sonosensitizer, and a tumor microenvironment (TME) modulator. In detail, MPG can generate •OH for chemodynamic therapy (CDT) and deplete glutathione (GSH) to alleviate the antioxidant ability of cancer cells. Moreover, catalase (CAT)-like MPG can react with H2O2 to generate O2 for relieving hypoxia in TME, enhancing GO x -catalyzed glucose oxidation to produce H2O2 and gluconic acid. Then, the regenerated H2O2 can promote the Fenton reaction to achieve GO x catalysis-enhanced CDT. Owing to its large π-electron conjugated system, MPG also serves as an ideal sonosensitizer, realizing a burst generation of 1O2 under US irradiation for efficient SDT. Therefore, the tumor treatment will be notably enhanced by MPG-based synergetic CDT/SDT/starvation therapy via a series of cascade reactions. Overall, this work develops a versatile nanoreactor with improved tumor treatment effectiveness and broadens the application prospects of porous materials in the field of biomedical research.The present three-year field investigation on sediment in the eutrophic Pearl River in South China showed that concentrations of sulfonamides (SAs), fluoroquinolones (FQs), and macrolides (MLs) in the river areas where blooms occurred were 4.6, 2.4, and 3.4 times higher than those without blooms, respectively, but the respective concentrations of tetracycline (TC) and oxytetracycline (OTC) in the areas with blooms were 2.6 and 3.8 times lower than those without. Significant positive correlations were found between concentrations of chlorophyll a in water and most antibiotics in sediment. Further investigation in each season suggested that lower diffusion but higher sinking were possible reasons driving the burial of sulfapyridine (SPD), sulfamethoxazole (SMX), and trimethoprim (TMP) in sediment from areas where blooms occurred, with burial rates up to 14.86, 48.58, and 52.19 g month-1, respectively. Concentrations of TCs in both water and sediment were inversely correlated with phytoplankton biomass, which might be related to the enhanced biodegradation capacity of bacteria caused by phytoplankton blooms. Phytoplankton also affected concentrations of antibiotics in the snail, Bellamya purificata, with higher values in March but lower values in September. The concentration of antibiotics in snails positively correlated with that in sediment when snails were dormant but with antibiotics in water after dormancy.Plasticizers, due to the widespread use of plastics, occur ubiquitously in the environment. The reuse of waste resources (e.g., treated wastewater, biosolids, animal waste) and other practices (e.g., plastic mulching) introduce phthalates into agroecosystems. As a detoxification mechanism, plants are known to convert phthalates to polar monophthalates after uptake, which are followed by further transformations, including conjugation with endogenous biomolecules. The objective of this study was 2-fold to obtain a complete metabolic picture of the widely used di-n-butyl phthalate (DnBP) by using a suite of complementary techniques, including stable isotope labeling, 14C tracing, and high-resolution mass spectrometry, and to determine if conjugates are deconjugated in human microsomes to release bioactive metabolites. In Arabidopsis thaliana cells, the primary initial metabolite of DnBP was mono-n-butyl phthalate (MnBP), and MnBP was rapidly metabolized via hydroxylation, carboxylation, glycosylation, and malonylation to seven transformation products. One of the conjugates, MnBP-acyl-β-d-glucoside (MnBP-Glu), was incubated in human liver (HLM) and intestinal (HIM) microsomes and was found to undergo rapid transformations. Approximately 15% and 10% of MnBP-Glu were deconjugated to the free form MnBP in HIM and HLM, respectively. These findings highlight that phthalates, as diesters, are susceptible to hydrolysis to form monoesters that can be readily conjugated via a phase II metabolism in plants. Conjugates may be deconjugated to release bioactive compounds after human ingestion. Therefore, an accurate assessment of the dietary exposure of phthalates and other contaminants must consider plant metabolites, especially including conjugates, to better predict their potential environmental and human health risks.

    Historically, asthma was considered a disease predominantly of the large airways, but gradually small airways have been recognized as the major site of airflow obstruction. Small airway dysfunction (SAD) significantly contributes to the pathophysiology of asthma and it is present across all asthma severities. Promising pre-clinical findings documented enhanced beneficial effects of combination therapies on small airways compared to monocomponents, thus it was questioned whether this could translate into further clinical implications from bench-to-bedside. The aim of this review was to systematically assess the state of the art of small airway involvement in asthma, especially in response to different pharmacological treatments acting on the respiratory system.

    A comprehensive literature search was performed in MEDLINE for randomized controlled trials (RCTs) characterizing the impact on small airways of different pharmacological treatments acting on the respiratory system. The results were extracted and redifferent non-invasive techniques for an early detection of peripheral abnormalities and optimization of asthma therapy.

    Inhaled corticosteroids are the cornerstone for the treatment of stable asthma, however, when disease severity increases, escalating therapy to combinations of drugs acting on distinct signalling pathways is required. It is advantageous to providing evidence of a synergistic interaction across drug combinations, as it allows optimizing bronchodilation while lowering the dose of single agents. YUM70 In the respiratory pharmacology field, two statistical models are accepted as gold standard to characterize drug interactions, namely the Bliss Independence criterion and the Unified Theory. In this review, pharmacological interactions across drugs approved for the treatment of asthma have been systematically assessed.

    A comprehensive literature search was performed in MEDLINE for studies that used a validated pharmacological method for assessing drug interaction. The results were extracted and reported via qualitative synthesis.

    Overall, 45 studies were identified from literature search and 5 met the inclusion criteria.

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