40 research outputs found

    Lipidomics Provides Novel Insights into Understanding the Bee Pollen Lipids Transepithelial Transport and Metabolism in Human Intestinal Cells

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    Bee pollen (BP) shows profound gut-protecting potentials. BP lipids (BPLs) mainly composed by phospholipids and polyunsaturated fatty acids might be one of the important contributors, while how BPL exerts gut-protecting effects and is transported through intestinal cell monolayers need to be investigated. Here, we exploited a strategy that combines an UPLC-Q-exactive orbitrap/MS-based lipidomics approach with a human intestinal cell (Caco-2) monolayer transport model, to determine the transepithelial transportation of BPL from Camellia sinensis L. (BPL-Cs), in pathological conditions. The results showed that BPL-Cs protected Caco-2 cells against dextran sulfate sodium (DSS)-induced intestinal barrier dysfunction by improving cell viability, maintaining membrane integrity, increasing tight junctions (ZO-1 and Claudin-1), and eliciting the expressions of antioxidative-related genes (NQO1, Nrf2, Txnrd1, and GSTA1). Lipidomics analysis revealed that DSS suppressed the transport and uptake of most of BPL-Cs including glycero­phospholipids, sphingo­myelins, and glycosyl­sphingolipids. Pretreatment with BPL-Cs significantly regulated glycerophospholipid and sphingolipid metabolisms, potentially involved in building permeability barriers and alleviating intestinal oxidative stress. Finally, eight classes of lipids were identified as the potential biomarkers for evaluating DSS-induced Caco-2 cell dysfunctions and BPL-intervened modulation. These findings shed light on the development of BPL as gastrointestinal protective food supplements in the future

    A cinnamate liquid crystal for rapid optical recording

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    Photorecording materials have been applied for information recording. Herein, a cinnamate liquid crystal with an enantiotropic nematic phase was synthesised, which can be isomerised and polymerised under the irradiation of the 365-nm UV light. Cholesteric liquid crystal polymer network (CLCN) films were prepared using the mixtures of it, LC242, a chiral dopant and a photoinitiator. The CLCN films possess a slight gradient helical pitch which increases from the bottom to the top of the films. The formation of this structure should be driven by the photoisomerisation of the cinnamate. Under the irradiation of 365-nm UV light with a low intensity, the CLC mixtures show a photochromic behaviour which is proposed to be driven by the formation of oligomers. Based on this, the CLC mixtures can be applied for optical recording.</p

    Stress Response in the Honeybee (Apis mellifera L.) Gut Induced by Chlorinated Paraffins at Residue Levels Found in Bee Products

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    Chlorinated paraffins (CPs) have become global pollutants and are of considerable concern as a result of their persistence and long-distance transmission in the environment and toxicity to mammals. However, their risks to pollinating insects are unknown. Honeybees are classical pollinators and sensitive indicators of environmental pollution. Herein, the effects of CPs on the gut microenvironment and underlying mechanisms were evaluated and explored using Apis mellifera L. Both short- and medium-chain CPs had significant sublethal effects on honeybees at a residue dose of 10 mg/L detected in bee products but did not significantly alter the composition or diversity of the gut microbiota. However, this concentration did induce significant immune, detoxification, and antioxidation responses and metabolic imbalances in the midgut. The mechanisms of CP toxicity in bees are complicated by the complex composition of these chemicals, but this study indicated that CPs could substantially affect intestinal physiology and metabolic homeostasis. Therefore, CPs in the environment could have long-lasting impacts on bee health. Future studies are encouraged to identify novel bioindicators of CP exposure to detect early contamination and uncover the detailed mechanisms underlying the adverse effects of CPs on living organisms, especially pollinating insects

    Self-Assembled Gemcitabine Prodrug Nanoparticles Show Enhanced Efficacy against Patient-Derived Pancreatic Ductal Adenocarcinoma

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    Effective new therapies for pancreatic ductal adenocarcinoma (PDAC) are desperately needed as the prognosis of PDAC patients is dismal and treatment remains a major challenge. Gemcitabine (GEM) is commonly used to treat PDAC; however, the clinical use of GEM has been greatly compromised by its low delivery efficacy and drug resistance. Here, we describe a very simple yet cost-effective approach that synergistically combines drug reconstitution, supramolecular nanoassembly, and tumor-specific targeting to address the multiple challenges posed by the delivery of the chemotherapeutic drug GEM. Using our developed PUFAylation technology, the GEM prodrug was able to spontaneously self-assemble into colloidal stable nanoparticles with sub-100 nm size on covalent attachment of hydrophobic linoleic acid via amide linkage. The prodrug nanoassemblies could be further refined by PEGylation and PDAC-specific peptide ligand for preclinical studies. In vitro cell-based assays showed that not only were GEM nanoparticles superior to free GEM but also the decoration with PDAC-homing peptide facilitated the intracellular uptake of nanoparticles and thereby augmented the cytotoxic activity. In two separate xenograft models of human PDAC, one of which was a patient-derived xenograft model, the administration of targeted nanoparticles resulted in marked inhibition of tumor progression as well as alleviated systemic toxicity. Together, these data unequivocally confirm that the hydrophilic and rapidly metabolized drug GEM can be feasibly transformed into a pharmacologically efficient nanomedicine through exploiting the PUFAylation technology. This strategy could also potentially be applied to rescue many other therapeutics that show unfavorable outcomes in the preclinical studies because of pharmacologic obstacles

    Synergistic Utilization of a CeO<sub>2</sub>‑Anchored Bifunctionalized Metal–Organic Framework in a Polymer Nanocomposite toward Achieving High Power Density and Durability of PEMFC

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    The free radicals produced during the long-term operation of fuel cells can accelerate the chemical degradation of the proton exchange membrane (PEM). In the present work, the widely used free radical scavenger CeO2 was anchored on amino-functionalized metal–organic frameworks, and flexible alkyl sulfonic acid side chains were tethered onto the surface of inorganic nanoparticles. The prepared CeO2-anchored bifunctionalized metal–organic framework (CeO2-MNCS) was used as a promising synergistic filler to modify the Nafion matrix for addressing the detrimental effect of pristine CeO2 on the performance and durability of PEMs, including decreased proton conductivity and the migration problem of CeO2. The obtained hybrid membranes exhibited a high proton conductivity up to 0.239 S cm–1, enabling them to achieve a high power density of 591.47 mW cm–2 in a H2/air PEMFC single cell, almost 1.59 times higher than that of recast Nafion. After 115 h of acceleration testing, the OCV decay ratio of the hybrid membrane was decreased to 0.54 mV h–1, which was significantly lower than that of recast Nafion (2.18 mV h–1). The hybrid membrane still maintained high power density, low hydrogen crossover, and unabated catalytic activity of the catalyst layer after the durability test. This study provides an effective one-stone-two-birds strategy to develop highly durable PEMs by immobilizing CeO2 without sacrificing proton conductivity, allowing for the realization of improvement on the performance and sustained durability of PEMFC simultaneously

    Sialic Acid-Modified O‑GlcNAc Transferase Inhibitor Liposome Presents Antitumor Effect in Hepatocellular Carcinoma

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    O-linked-N-acetylglucosaminylation (O-GlcNAcylation) plays a key role in hepatocellular carcinoma (HCC) development, and the inhibition of O-GlcNAcylation has therapeutic potential. To decrease the systemic adverse events and increase targeting, we used sialic acid (SA)-decorated liposomes loaded with OSMI-1, an inhibitor of the O-GlcNAcylation, to further improve the anti-HCC effect. Fifty pairs of HCC tissue samples and the cancer genome atlas database were used to analyze the expression of O-GlcNAc transferase (OGT) and its effects on prognosis and immune cell infiltration. OSMI-1 cells were treated with SA and liposomes. Western blotting, immunofluorescence, cell proliferation assay, flow cytometry, enzyme-linked immunosorbent assay, immunohistochemistry, and tumorigenicity assays were used to investigate the antitumor effect of SA-modified OSMI-1 liposomes in vitro and in vivo. OGT was highly expressed in HCC tissues, negatively correlated with the degree of tumor infiltration of CD8+ and CD4+T cells and prognosis, and positively correlated with the degree of Treg cell infiltration. SA-modified OSMI-1 liposome (OSMI-1-SAL) was synthesized with stable hydrodynamic size distribution. Both in vitro and in vivo, OSMI-1-SAL exhibited satisfactory biosafety and rapid uptake by HCC cells. Compared to free OSMI-1, OSMI-1-SAL had a stronger capacity for suppressing the proliferation and promoting the apoptosis of HCC cells. Moreover, OSMI-1-SAL effectively inhibited tumor initiation and development in mice. OSMI-1-SAL also promoted the release of damage-associated molecular patterns, including anticalreticulin, high-mobility-group protein B1, and adenosine triphosphate, from HCC cells and further promoted the activation and proliferation of the CD8+ and CD4+T cells. In conclusion, the OSMI-1-SAL synthesized in this study can target HCC cells, inhibit tumor proliferation, induce tumor immunogenic cell death, enhance tumor immunogenicity, and promote antitumor immune responses, which has the potential for clinical application in the future

    Bee Pollen Extracts Modulate Serum Metabolism in Lipopolysaccharide-Induced Acute Lung Injury Mice with Anti-Inflammatory Effects

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    Bee pollen (BP) collected from different floras possesses various potential bioactivities, but the mechanism-related research on anti-inflammatory effects is limited. Here, three types of BP originating from Camellia sinensis L. (BP-Cs), Nelumbo nucifera Gaertn. (BP-Nn), and Brassica campestris L. (BP-Bc) were assessed using molecular and metabolomics methods to determine their anti-inflammatory effects. The differences in polyphenolic abundance of three types of BP extracts were determined by HPLC-DAD/Q-TOF-MS. In vitro anti-inflammatory effects of three BP extracts were evaluated in a lipopolysaccharide (LPS)-induced RAW 264.7 cells model. BP-Cs extract with the most abundant polyphenols was found to be the most effective in reducing inflammation by downregulating inflammatory-related genes expression and blocking the activation of MAPK and NF-κB signaling pathways. Polyphenol-rich BP-Cs was further evaluated for their in vivo anti-inflammatory effect in a LPS-induced acute lung injury mouse model. An UPLC-Q-TOF/MS-based metabolomics approach was applied to analyze metabolite changes in mouse serum. Weshowed that the pretreated BP-Cs extract alleviated inflammation and regulated glycerophospholipid metabolism significantly. Our findings provide a foundation for developing and justifying BP as a potential anti-inflammatory ingredient in functional foods or nutraceutical formulations
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