Cyanidin-3-O-glucoside impacts fecal discharge of polystyrene microplastics in mice: Potential role of microbiota-derived metabolites.

Microplastic particles degraded from plastic litters are recognized as a global environmental pollutant, which can be transferred and enriched via the food chain to impact ecosystems and human health. A balanced gut microbiota contributes to human health through host-gut interactions, environmentally-driven factors such as microplastic exposure would disturb the gut bacteria and affect its functionality. Dietary compounds can remodel the compositions of gut microbes, and interact with bacteria exerting profound effects on host physiology. This study explored the effects of bayberry-derived anthocyanin cyanidin-3-O-glucoside (C3G) and microplastic polystyrene (PS) on the gut microbiome in C57BL/6 mice, especially the alterations in gut bacteria and its metabolites. Using 16S rRNA high-throughput sequencing, variations in gut bacterial composition and enrichment of functional pathways were found upon PS and C3G administration. Meanwhile, the differential metabolites and metabolic pathways were identified by metabolomic analysis. Importantly, colonic and fecal PS levels were found to be strongly correlated with key microbiota-derived metabolites, which are associated with xenobiotic metabolism via regulation of xenobiotics-metabolizing enzymes and transporters. These results may offer new insights regarding the protective effects of C3G against xenobiotic PS exposure and the roles of gut bacterial metabolites.

Structure-Function Relationships of a Tertiary Amine-Based Polycarboxybetaine.

Zwitterionic polycarboxybetaine (PCB) materials have attracted noticeable interest for biomedical applications, such as wound healing/tissue engineering, medical implants, and biosensors, due to their excellent antifouling properties and design flexibility. Antifouling materials with buffering capability are particularly useful for many biomedical applications. In this work, an integrated zwitterionic polymeric material, poly(2-((2-hydroxyethyl)(2-methacrylamidoethyl)ammonio)acetate) (PCBMAA-1T), was synthesized to carry desired properties (antifouling, switchability and buffering capability). A tertiary amine was used to replace quaternary ammonium as the cation to endow the materials with buffering capability under neutral pH. Through this study, a better understanding on the structure-property relationship of zwitterionic materials was obtained. The tertiary amine cation does not compromise antifouling properties of zwitterionic materials. The amount of adsorbed proteins on PCBMAA-1T polymer brushes is less than 0.8 ng/cm(2) for fibrinogen and 0.3 ng/cm(2) (detection limit of the surface plasmon resonance sensor) for both undiluted blood plasma and serum. It is found that the tertiary amine is favorable to obtain good lactone ring stability in switchable PCB materials. Titration study showed that PCBMAA-1T could resist pH changes under both acidic (pH 1-3) and neutral/basic (pH 7-9) conditions. To the best of our knowledge, such an all-in-one material has not been reported. We believe this material might be potentially used for a variety of applications, including tissue engineering, chronic wound healing and medical device coating.

Dextran-peptide hybrid for efficient gene delivery.

Gene therapy has drawn significant interest in the past two decades since it provides a promising strategy to treat both genetic disorders and acquired diseases. However, the transfer of gene therapy to clinical applications is troubled with many difficulties, since many current systems are of toxicity, low transfection efficiency and low biodegradability. To address these challenges, we developed a dextran-peptide hybrid system as a safe and efficient vector for gene therapy and investigated the structure-function-cytotoxicity relationship of this dextran-peptide hybrid system. Dextrans (Dex10, Dex20, and Dex70) with different molecular weights (10, 20 and 70 kDa) were conjugated with a cationic peptide, R5H5, at various degrees of substitution. Gene expression and cytotoxicity mediated by this delivery system were evaluated against SKOV-3 human ovarian carcinoma cells and compared to 25 kDa branched poly(ethylenimine) (PEI). The results showed that Dex10-R5H5 and Dex20-R5H5 hybrids derived from low molecular weight dextrans induced higher gene expression and lower cytotoxicity than Dex70-R5H5 hybrid from higher molecular weight dextran. The best performance on gene expression was achieved by Dex10-R5H5 at 40% substitution of R5H5, which induced greater gene expression than PEI at a low N/P ratio of 5. Dex10-R5H5/DNA complexes at 40% substitution of R5H5 also showed much higher cell viability (93%) than PEI/DNA (66%) at the same N/P ratio. These results indicate that the Dex-R5H5 hybrid with the low molecular weight of dextran and the high degree of substitution of R5H5 is a very promising material for safe and efficient gene therapy.

Selective gene delivery to cancer cells using an integrated cationic amphiphilic peptide.

Gene therapy provides a number of potential treatments that could be applied in clinic to prevent deaths from cancer. However, the transfer of gene therapy to the clinical application has proven difficult because many problems remain to be solved concerning the transfection efficiency, target specificity, and safety issues. To overcome these barriers, a peptide-based vector, K(12)H(6)V(8)SSQHWSYKLRP (KHV-LHRH) that comprises four functional blocks, is studied in this work for the targeted delivery of a model gene drug to cancer cells. KHV-LHRH peptide, which contains a luteinizing hormone-releasing hormone (LHRH) sequence, can specifically target cancer cells expressing LHRH receptors. The gene expression, cytotoxicity, and cellular uptake mediated by this vector were evaluated against MCF-7 human breast cancer cells (LHRH-receptor-positive) and SKOV-3 human ovarian carcinoma cells (LHRH-receptor-negative) and compared to a peptide vector (K(12)H(6)V(8)) (KHV) without the LHRH ligand and poly(ethylenimine) (PEI). The results showed that KHV-LHRH enhanced the DNA internalization and induced significantly higher gene expression than KHV in LHRH-receptor-positive MCF-7 cells. Also, the peptide-based vectors had low cytotoxicity compared to that of PEI. The high specificity and transfection efficiency of the integrated peptide-based vector make it a very promising material for targeted gene delivery in cancer therapy.

Traditional uses, phytochemical constituents and pharmacological properties of Osmanthus fragrans: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Osmanthus fragrans Lour., is a medicinal plant distributed widely in some Asian countries including Japan and Korea and southwestern China. It has been used traditionally for the treatment of weakened vision, halitosis, panting, asthma, cough, toothache, stomachache, diarrhea, rheumatism, physique pain and hepatitis. AIM OF THE REVIEW: Recent advances in traditional uses, botanical characteristics, distribution, taxonomy, phytochemical constituents, biological effects as well as the toxicities of O. fragrans are comprehensively presented and critically evaluated, and the underlying mechanism associated with the bioactivities of extracts, essential oil and components from this plant is also well summarized. In order to provide comprehensive scientific basis for the medical application and help interested researchers discover food and medicinal natural products from O. fragrans. MATERIALS AND METHODS: All information was systematically gathered from globally accepted scientific databases by Internet databases, including Elsevier, ScienceDirect, PubMed, Web of Science, Wiley, Springer, SciFinder, ACS Publications, CNKI, WanFang, Google Scholar, Baidu Scholar, The Plant List Database, and other literature sources (Ph.D. and MSc dissertations). All published contributions on O. fragrans different languages were included and cited. The chemical structures of all isolated compounds were drawn by using ChemBioDraw Ultra 14.0 software. RESULTS: To date, more than 183 compounds were isolated and structurally identified from different plant parts of O. fragrans. Among them, ionone, ionol, flavonoids, polyphenols and iridoids, as the major bioactive substances, have been extensively studied and displayed the best bioactivity. Pharmacological studies demonstrated that O. fragrans and its active components had a wide range of biological activities, such as antioxidant, antitumor, anti-inflammatory, anti-hyperglycemic, anti-thrombotic, anti-melanogenesis, neuroprotective, and hepatoprotective activities, etc. CONCLUSION: O. fragrans, as a food and medicinal resource, has a good health care function and important edible and medicinal value, and thus has good prospects for utilization. However, many studies on biological activities were mainly based on extracts and the bioactive ingredients of this plant, and the mechanism responsible for these extracts and ingredients have not been well identified and there is a gap in research regarding clinical effect and safety. Therefore, the detail in vitro and in vivo studies on the mechanisms of action of the pure bioactive compounds and more clinical studies are encouraged to be conducted to ensure safety and effectiveness of the plant for human use.

Is Adolescents' Free Sugar Intake Associated with the Free Sugar Intake of Their Parents?

High free sugar intake can lead to increased dental caries, obesity, and other health risks among adolescents. Studies have shown that family factors, especially parents, are one of the primary factors influencing adolescents' sugar intake. This study aims to investigate the influence of adolescent parents' free sugar intake, knowledge, attitude, and practice (KAP) on adolescents' free sugar intake. A total of 1090 pairs of adolescents and their parents from 10 secondary schools in Changsha were enrolled in a cross-sectional study. Free sugar intakes of parents and adolescents were measured using the food frequency questionnaire (FFQ). The current status of parents' knowledge, attitude, and practice in consuming free sugar was investigated using online and offline questionnaires. Parental free sugar intake was 11.55 (5.08, 21.95) g/d, and that of adolescents was 41.13 (19.06, 80.58) g/d. Parental free sugar intake, free sugar knowledge level, intake behavior, and guidance behavior were associated with adolescent free sugar intake. A superior level of parental free sugar knowledge (adjusted OR = 0.726, 95% CI: 0.557~0.946) was a protective factor for adolescent free sugar intake. Moderate and high levels of parental free sugar intake (adjusted OR = 1.706, 95% CI: 1.212~2.401; adjusted OR = 2.372, 95% CI: 1.492~3.773, respectively) were risk factors for free sugar intake in adolescents. Given the importance of parental influence on the adolescent free sugar intake, further limiting parental intake and increasing awareness of free sugars could play an active role in future interventions for adolescents' free sugar intake.

Food-derived cyanidin-3-O-glucoside reverses microplastic toxicity via promoting discharge and modulating the gut microbiota in mice.

Microplastics (MPs) ingested and accumulated by organisms would ultimately pose a threat to humans via the food chain. A balanced gut microbiota contributes to many health benefits, which is readily influenced by environmental chemicals such as MPs. Cyanidin-3-O-glucoside (C3G), a bioactive compound of the anthocyanin family, possesses a variety of functional effects including anti-oxidant and anti-inflammatory, as well as gut microbiota modulation. C3G has been demonstrated to prevent polystyrene (PS) induced toxicities in Caco-2 cells and Caenorhabditis elegans (C. elegans) via activating autophagy and promoting discharge. In the present study, we aimed to explore the alleviation effect of C3G on PS induced toxicities in C57BL/6 mice. Our results showed that the supplementation of C3G effectively reduced the tissue accumulation and promoted the fecal PS discharge, leading to alleviation of the PS-caused oxidative stress and inflammatory response. Meanwhile, C3G modulated PS-associated gut microbiome perturbations and regulated functional bacteria in inflammation such as Desulfovibrio, Helicobacter, Oscillospiraceae and Lachnoclostridium. Also, C3G administration initiated alterations in functional pathways in response to xenobiotic PS, and reduced bacterial functional genes related to inflammation and human diseases. These findings may offer evidence for the protective role of C3G in the intervention of PS-induced toxicity and gut dysbiosis.

Bilateral, buccinator myomucosal advancement flaps to reconstruct central upper labial myomucosal defects after ablation of early-stage cancer in minor salivary glands.

BACKGROUND: Reconstruction of upper labial myomucosal defects is surgically challenging. AIMS: We evaluated whether central defects could be repaired using bilateral, buccinator myomucosal advancement flaps (b-BMAFs). METHODS: We evaluated five patients with early-stage, minor salivary gland mucoepidermoid carcinomas (low-grade [n = 2], intermediate-grade [n = 2], and high-grade [n = 1]) who underwent central, upper labial myomucosal reconstruction using b-BMAFs after cancer ablation. We treated two men and three women aged 25-59 years. Tumors ranged in size from 1.8 × 1.8 to 2.5 × 2.2 cm. Clinical stages were I and II in two and three patients, respectively. Defect dimensions ranged from 2.8 × 2.8 to 3.5 × 3.2 cm. RESULTS: All patients underwent successful reconstruction of central, upper labial myomucosal defects using b-BMAFs and were satisfied with the esthetic results. Adequate orbicularis oris and speech function were maintained. No reduction in mouth opening was observed. Patients were followed up for 24-36 months; one pulmonary metastasis was observed at 36 months postoperatively. CONCLUSION: Placement of b-BMAFs is safe and feasible when reconstructing central, upper labial myomucosal defects after ablation of early-stage, minor salivary gland cancer.

Canidin-3-glucoside prevents nano-plastics induced toxicity via activating autophagy and promoting discharge.

Increasing attention has been brought to microplastics pollution recently, while emerging evidences indicate that nano-plastics degraded from microplastics are more of research significance owing to stronger toxicity. However, there is little study focused on the prevention of nano-plastics induced toxicity until now. Canidin-3-glucoside (C3G), a natural anthocyanin proved to possess multiple functions like antioxidant and intestinal tissue protection. Thus, we proposed whether C3G could act as a molecular weapon against nano-plastics induced toxicity. In Caco2 cell and Caenorhabditis elegans (C. elegans) models, we found that polystyrene (PS) nano-plastics exposure resulted in physiological toxicity and oxidative damage, which could be restored by C3G. More significantly in Caco2 cells, we observed that autophagy was activated via Sirt1-Foxo1 signaling pathway to attenuate PS induced toxicity after C3G intervention and further verified by adding autophagy inhibitor 3-Methyladenine (3-MA). Meanwhile, PS co-localization with lysosomes was observed, indicating the encapsulation and degradation of PS. In C. elegans, by detecting LGG-1/LC3 expression in GFP-targeted LGG-1 report gene (LGG-1:GFP) labeled transgenic DA2123 strain, the co-localization of LGG-1:GFP with PS was found as well, means that autophagy is involved in C3G's beneficial effects. Furthermore, we were surprised to find that C3G could promote the discharge of PS from N2 nematodes, which reduces PS toxicity more directly.

Recent advances of zwitterionic carboxybetaine materials and their derivatives.

Zwitterionic polycarboxybetaine (pCB)-based materials have drawn special attention due to their outstanding properties of resisting proteins adsorption, biofilm formation and cell attachment on a variety of substrates and surfaces, reducing the uptake of pCB-coated nanosized materials, as well as providing the capability of further functionalization. Zwitterionic pCBs have been proven to be excellent choices for many applications, not only limited to the field of antifouling. This review will summarize the recent progress on the development of pCB materials and the understanding of the structure-function-property relationships of carboxybetaine materials.

Cholesterol-peptide hybrids to form liposome-like vesicles for gene delivery.

In this paper, four amphiphilic cholesterol-peptide conjugates (Ch-R5H5, Ch-R3H3, Ch-R5 and Ch-R5) were designed and synthesized, and their properties in gene delivery were evaluated in vitro with an aim of developing more efficient gene delivery carriers. These amphiphilic cholesterol-peptide conjugates are composed of hydrophobic cholesterol and positively charged peptides. They were able to self-assemble into micelles at low concentrations and their critical micelle concentrations in phosphate buffered saline (pH 7.4) are ≤85 µg/mL. Amphiphilic cholesterol-peptide conjugates condensed DNA more efficiently than a hydrophilic cationic oligoarginine (R10) peptide with no hydrophobic segment. Their transfection efficiencies were at least two orders of magnitude greater than that of R10 peptide in HEK-293 cells. Moreover, the introduction of histidine residues in cholesterol-peptide conjugates led to higher gene expression efficiency compared with cholesterol-peptides without histidine (Ch-R5 and Ch-R3), and the luciferase expression level was comparable or even higher than that induced by PEI at its optimal N/P ratio. In particular, Ch-R5H5 condensed DNA into smaller nanoparticles than Ch-R3H3 at higher N/P ratios, and the minimum size of Ch-R5H5/DNA complexes was 180 nm with zeta potential of 23 mV, achieved at the N/P ratio of 30. This liposome-like vesicle may be a promising gene delivery carrier for intravenous therapy.

The impact of structure on elasticity, switchability, stability and functionality of an all-in-one carboxybetaine elastomer.

In this work, we designed and synthesized an all-in-one zwitterionic material (poly2-((2-hydroxyethyl)(2-methacrylamidoethyl)(methyl)ammonio)acetate (pCBMAA-1)) bearing elasticity, switchable antimicrobial/antifouling properties, and stability. Zwitterionic materials have drawn special attention due to their outstanding antifouling properties; however, conventional zwitterionic materials lack tunable elasticity, stability and antimicrobial properties. We addressed these challenges by integrating all desired properties into a single zwitterionic molecule through rational design. pCBMAA-1 hydrogel showed typical elastomeric stress-strain curves with low Young's modulus and high yield strain, in both tensile and compression tests. About 65% tensile strain and 85% compressive strain were achieved. pCBMAA-1 hydrogel can switch between cationic antimicrobial form and zwitterionic antifouling form. In its cationic ring form, pCBMAA-1 hydrogel killed 99.5% of attached bacterial cells and then released 95% of killed cells. pCBMAA-1 surfaces highly resisted the protein adsorption from 100% blood plasma and serum. The amount of adsorbed protein was below the detection limit (0.3 ng cm(-2)) of the SPR sensor. Compared to existing zwitterionic materials, this material showed the dramatically improved stability in both basic and acidic conditions. We believe that this all-in-one material will broaden the application spectrum of zwitterionic materials to a great extent.

Switchable antimicrobial and antifouling hydrogels with enhanced mechanical properties.

New switchable hydrogels are developed. Under acidic conditions, hydrogels undergo self-cyclization and can catch and kill bacteria. Under neutral/basic conditions, hydrogels undergo ring-opening and can release killed bacterial cells and resist protein adsorption and bacterial attachment. Smart hydrogels also show a dramatically improved mechanical property, which is highly desired for biomedical applications.