Effects of melatonin on inhibiting quality deterioration of postharvest water bamboo shoots.

Water bamboo shoots (Zizania latifolia) is prone to quality deterioration during cold storage after harvest, which causes the decline of commodity value. Chlorophyll synthesis and lignin deposition are the major reasons for quality degradation. This paper studied the influence of exogenous melatonin (MT) on the cold storage quality of water bamboo shoots. MT treatment could delay the increase in skin browning, hardness and weight loss rate, inhibit chlorophyll synthesis and color change of water bamboo shoots, while maintain the content of total phenols and flavonoids, and inhibit lignin deposition by inhibiting the activity and gene expression of phenylpropanoid metabolism related enzymes as PAL, C4H, 4CL, CAD, and POD. The results indicate that exogenous MT treatment can effectively inhibit the quality degradation of cold stored water bamboo shoots.

Novel approach for enhancing skin allograft survival by bioadhesive nanoparticles loaded with rapamycin.

Skin graft rejection is a significant challenge in skin allografts for skin defects, particularly in extensive burn injury patients when autografts are insufficient. Enhancing the survival duration of allogeneic skin grafts can improve the success rate of subsequent autologous skin grafting, thereby promoting the therapeutic efficacy for wound healing. Rapamycin (Rapa), a potent immunosuppressant with favorable efficacy in organ transplantation, is limited by its systemic administration-associated toxicity and side effects. Therefore, addressing the short survival time of allogeneic skin grafts and minimizing the toxicity related to systemic application of immunosuppressive agents is an urgent requirement. Here, we present a topical formulation based on bioadhesive poly (lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs) with surface-modified encapsulation of Rapamycin (Rapa/BNPs), applied for local immunosuppression in a murine model of allogeneic skin grafts. Our Rapa/BNPs significantly prolong nanoparticle retention, reduce infiltration of T lymphocytes and macrophages, decrease the level of pro-inflammatory cytokines and ultimately extend skin allograft survival with little systemic toxicity compared to free Rapa or Rapamycin-loaded non-bioadhesive nanoparticles (Rapa/NNPs) administration. In conclusion, Rapa/BNPs effectively deliver local immunosuppression and demonstrate potential for enhancing skin allograft survival while minimizing localized inflammation, thus potentially increasing patient survival rates for various types of skin defects.

Occurrences of eight common-used pesticide adjuvants in ten vegetable species and implications for dietary intake in North China.

Pesticide adjuvants (PAs) are important components of pesticide products. However, limited information is available regarding their occurrences in foodstuffs. Herein, eight common-used PAs were investigated in vegetables in North China in 2014-2016. The residue levels of total PAs in vegetables from markets and farms were 500 and 661 µg/kg, respectively. The highest residues of total PAs were found in cauliflowers (average: 1.53 × 103 µg/kg, market vegetables) and spinaches (average: 3.72 × 103 µg/kg, farm vegetables), respectively. In addition, Tristyrylphenol ethoxylates (TPE) dominated the total 8 PAs concentrations in most vegetable species. Moreover, the risk assessment showed that the human health risks associated with TPE and nonylphenol (NP) exposure via vegetables for adults were acceptable, and the estimated daily intakes (EDIs) of other six PAs were in the range of <0.010-0.89 µg/kg bw/day, which were less likely to pose a threat to human health.

Ratiometric fluorescent sensing carbendazim in fruits and vegetables via its innate fluorescence coupling with UiO-67.

A ratiometric fluorescent sensor was facilely fabricated using innate fluorescence of carbendazim (MBC) and fluorescent UiO-67 to sensitively and selectively detect MBC in food matrixes. The innate fluorescence of MBC provided a signal at 311 nm (F311), and the fluorescent UiO-67 at 408 nm (F408) could recognize MBC through π-π stacking inducing fluorescent quenching relied on photoelectron transfer (PET). The ratio (F311/F408) of the fluorescence enhancement of MBC and the quenching of UiO-67 linearly responded to the MBC concentrations of 0-47.6 µmol/L with a low limit of detection (LOD) of 3.0 × 10-3 µmol/L. The reverse response signals of the sensor enhanced the sensitivity toward MBC and presented remarkable anti-interference capability in complex matrices. The as-prepared sensor was applied to detect MBC residues in apple, cucumber and cabbage, obtaining satisfactory accuracy and precision with the recovery of 90.82-103.45% and RSDs of lower than 3.03%.

Novel combination of non-invasive morphological and solid-state characterisation of drug-loaded core-shell electrospun fibres.

In recent years, core-shell nanofibrous drug delivery systems have received increasing attention due to their ability to incorporate two or more active pharmaceutical ingredients (APIs) individually into the desired layer (either core or sheath) and thereby finely tune the release profiles of even incompatible drugs in one system. This study aims to perform formulation and solid-state characterisation of levofloxacin-loaded polylactic acid (PLA) - naproxen-sodium-loaded polyvinyl pyrrolidone (PVP) bicomponent core-shell fibrous sheets and examine the electro spinnability of the precursor combinations. The selected drugs have potential therapeutic relevance in similar systems intended for wound healing; however, in this study, they are used as model drugs to understand the physicochemical properties of a drug loaded system. In order to determine the best core- and shell-solution combination, a full factorial experimental design is used. A combination of various morphological (scanning electron microscopy and transmission electron microscopy) and microstructural characterisation techniques (X-ray photoelectron spectroscopy and Raman spectroscopy) was applied to non-invasively obtain information about the structure of the fibres and the embedded drugs. The results indicate that core-shell fibres of different compositions could be successfully prepared with various structural homogeneities. The best core-shell structure was obtained using a combination of 15% (w/w) shell concentration and 8% (w/w) PLA solution concentration. In addition to the conventional core-shell structural verification methods, the Raman spectroscopy method was implemented to reveal not only the core-shell structure of the PLA/PVP nanofibers but also the form of the embedded drugs. The Raman mapping of the fibres confirm the above results, and it is shown that an amorphous solid dispersion is formed as a result of the coaxial electrospinning process.

Cu-metal-organic framework supported on chitosan for efficient condensation of aromatic aldehydes and malononitrile.

In this study, a novel copper-based metal-organic framework (Cu-MOF)-immobilized modified chitosan (CS-CA), CS-CA/Cu-MOF, has been constructed easily and applied as an extremely efficient and economic mesoporous catalyst for the Knoevenagel condensation between aromatic aldehydes with malononitrile under mild reaction conditions. The resultant catalyst is characterized via various techniques including FTIR, XRD, FE-SEM, EDX, TEM, BET and STA analyses. The CS-CA/Cu-MOF was reused eight times without a noteworthy decrease in the catalytic activity. The use of CS-CA/Cu-MOF results in outstanding catalytic activity, high recyclability, very short reaction time at 25 °C, and an easy work-up process for the Knoevenagel condensation.

The key role of straight fluid jet in predicting the drug dissolution from electrospun nanofibers.

In nanopharmaceutics, a robust manipulation of the preparation process and an accurate prediction of the final product size are very important for developing novel nano drug delivery systems. In the present study, for the first time, a process parameter, i.e. the length of the straight fluid jet, L, is correlated with an experimental parameter, i.e. fluid flow rate, F; a nanofiber property, i.e. diameter, D; and the corresponding drug-sustained release profile. Using a mixed solution consisting of 15% (w/v) polyacrylonitrile and 3% (w/v) ketoprofen in acetone and N,N-dimethylformamide (2:8, v:v) as a spinnable working fluid, a series of medicated nanofibers were prepared under variable F and were characterized. The analysis results disclosed the quantitative relationships among different types of parameters. The process parameter L exhibited a better linear relationship with the nanofibers' diameter (D) than the processing parameter F. These results give a hint that process parameters can be exploited as useful tools for accurately predicting and tailoring the resultant nanofibers' D, and in turn their functional performances. The strategy proposed here presents a new approach to investigate the electrohydrodynamic process and manipulate the functions of nanoproducts through process-property-performance relationships.

Oleuropein aglycone and hydroxytyrosol interfere differently with toxic Aß1-42 aggregation.

Oleuropein aglycone (OleA), the most abundant polyphenol in extra virgin olive oil (EVOO), and Hydroxythyrosol (HT), the OleA main metabolite, have attracted our interest due to their multitarget effects, including the interference with amyloid aggregation path. However, the mechanistic details of their anti-amyloid effect are not known yet. We report here a broad biophysical approach and cell biology techniques that enabled us to characterize the different molecular mechanisms by which OleA and HT modulate the Aß1-42 fibrillation, a main histopathological feature of Alzheimer's disease (AD). In particular, OleA prevents the growth of toxic Aß1-42 oligomers and blocks their successive growth into mature fibrils following its interaction with the peptide N-terminus, while HT speeds up harmless fibril formation. Our data demonstrate that, by stabilizing oligomers and fibrils, both polyphenols reduce their seeding activity and aggregate/membrane interaction on human neuroblastoma SH-SY5Y cells. These findings highlight the great potential of EVOO polyphenols and offer the possibility to validate and to optimize their use for possible AD prevention and therapy.

Patulin removal from apple juice using a novel cysteine-functionalized metal-organic framework adsorbent.

Patulin (PAT) is one of the most common toxic contaminants of apple juice, which causes severe food safety issues throughout the apple industry. In order to remove PAT efficiently, a metal-organic framework-based adsorbent (UiO-66(NH2)@Au-Cys) was successfully synthesized and used for PAT removal from juice-pH simulation solution and real apple juice. Batch adsorption experiments were systematically performed to study the adsorption behavior for PAT. The results showed that adsorption process could be well described by the Pseudo-second order model and Freundlich isotherm model. The maximum adsorption capacity (4.38 µg/mg) was 10 times higher than the microbe-based biosorbents. Thermodynamic investigation demonstrated that adsorption process was spontaneous and endothermic. Furthermore, no marked cytotoxicity on NIH 3T3 cell lines was observed when the concentration of the adsorbent was lower than 10 µg/mL. Therefore, UiO-66(NH2)@Au-Cys is a potential adsorbent for PAT removal from apple juice with little quality changes.

One-pot preparation of an acryloyled ß-cyclodextrin-silica hybrid monolithic column and its application for determination of carbendazim and carbaryl.

This work describes, for the first time, an acryloyled ß-cyclodextrin hybrid monolith column was synthesized, under aqueous-phase conditions, and used for solid-phase microextraction of carbendazim and carbaryl. The monolithic column was characterized using scanning electron microscopy, nitrogen adsorption-desorption, thermogravimetric analysis and Fourier transform infrared spectroscopy, and used as the adsorbent for solid phase microextraction (SPME) of carbendazim and carbaryl. After optimization of the SPME conditions, a simple and sensitive SPME-HPLC method was developed for the determination of carbendazim and carbaryl in leafy vegetables. The method exhibited a good liner response in the range 5-400 µg/kg (R2 = 0.9994) for carbendazim and 10-400 µg/kg (R2 = 0.9996) for carbaryl, respectively. The limits of detection were 1.0 and 1.5 µg/kg for carbendazim and carbaryl, respectively, in leafy vegetables. Recoveries ranged from 92.6% to 110.1%, and the relative standard deviations were less than 6.1%.

Chitosan oligosaccharide-N-chlorokojic acid mannich base polymer as a potential antibacterial material.

Here, a nontoxic antibacterial material based on Chitosan Oligosaccharide-N-Chlorokojic acid Mannich base (COS-N-MB) that was synthesized by using the selective partial alkylation reaction displaying excellent activity against bacterial infection. The proposed mechanism of the action of COS-N-MB is that this antibacterial material with positive charge and synergistic antibacterial effects can promote it's adsorption to bacterial cell wall through electrostatic interaction and chelating metal cations. It changed the permeability of the membrane, caused cellular leakage, and destroyed the membrane integrity, leading to complete membrane disruption and eventually death of the bacteria. Besides, COS-N-MB can interact with membrane proteins, causing deformation in the structure and functionality. The good biocompatibility, noncytotoxic, and low hemolysis made this novel material a promising and effective compound for antibacterial applications.

Fast dissolving drug delivery membrane based on the ultra-thin shell of electrospun core-shell nanofibers.

Structural nanocomposites that provide fast dissolving drug release profiles are highly in demand in pharmaceutics. In this study, a poorly water-soluble drug such as quercetin or tamoxifen citrate (TC) was selected as a model active pharmaceutical ingredient. Core-shell nanofibers with ultra-thin shells were designed and prepared using modified coaxial electrospinning. Polyvinylpyrrolidone (PVP) K90 or Polycaprolactone (PCL) was selected as core. The drugs and PVP K10 were selected as shell. All types of solutions can be used as the shell fluids in modified coaxial process regardless of their electrospinnability, which means the increasing functional ingredients and unspinnable matrix can be processed. Evaluations via SEM and TEM demonstrated that the core-shell nanofibers had linear morphology with a shell thickness smaller than 100 nm. XRD and FTIR results showed that the model drug was distributed in the polymeric matrix amorphously and that PVP K10 had good compatibility with quercetin or TC. In vitro dissolution tests suggested that the core-shell nanofibers with ultra-thin shells released the loaded cargoes in the dissolution media within 1 min. The present investigation paved a new way for implementing the modified coaxial processes, which can be utilized to fabricate structural nanocomposites with ultra-thin shells for enhancing the fast dissolution of poorly water-soluble drugs.

The effect of poly (lactic-co-glycolic) acid composition on the mechanical properties of electrospun fibrous mats.

The aim of this study was to investigate the influence of polymer molecular structure on the electrospinnability and mechanical properties of electrospun fibrous mats (EFMs). Polymers with similar molecular weight but different composition ratios (lactic acid (LA) and glycolic acid (GA)) were dissolved in binary mixtures of N,N-dimethylformamide (DMF) and tetrahydrofuran (THF). The intrinsic viscosity and rheological properties of polymer solutions were investigated prior to electrospinning. The morphology and mechanical properties of the resulting EFMs were characterized by scanning electron microscope (SEM) and dynamic mechanical analysis (DMA). Sufficiently high inter-molecular interactions were found to be a prerequisite to ensure the formation of fibers in the electrospinning process, regardless the polymer composition. The higher the amount of GA in the polymer composition, the more ordered and entangled molecules were formed after electrospinning from the solution in THF-DMF, which resulted in higher Young's modulus and tensile strength of the EFMs. In conclusion, this study shows that the mechanical properties of EFMs, which depend on the polymer molecule-solvent affinity, can be predicted by the inter-molecular interactions in the starting polymer solutions and over the drying process of electrospinning.

Preparation of functionalized cotton fabrics by means of melatonin loaded ß-cyclodextrin nanosponges.

Biofunctional textiles are a new category of advanced materials which combine conventional textiles with advanced drug delivery systems to obtain fabrics able to release active principles through skin. The work presents the synthesis of hyper cross-linked ß-cyclodextrins nanosponges with the carbonyl group acting as bridge between cyclodextrin molecules. The result of the synthesis is a 3-D porous structure, where melatonin molecules have been complexed. The complex has been characterized by elemental analysis, DSC, SEM, XRD and FT-IR spectroscopy and the results confirm that melatonin interacts with the synthesized nanosponge at molecular level. Melatonin loaded nanosponges have been dispersed on cotton fibres, which have proved to be a suitable substrate for durable nanosponge adsorption. The in vitro release tests from the funtionalized fabrics have shown a zero order kinetics, which is typical of a reservoir diffusion controlled system.

HDAC 3-selective inhibitor RGFP966 demonstrates anti-inflammatory properties in RAW 264.7 macrophages and mouse precision-cut lung slices by attenuating NF-κB p65 transcriptional activity.

The increasing number of patients suffering from chronic obstructive pulmonary disease (COPD) represents a major and increasing health problem. Therefore, novel therapeutic approaches are needed. Class I HDACs 1, 2 and 3 play key roles in the regulation of inflammatory gene expression with a particular pro-inflammatory role for HDAC 3. HDAC 3 has been reported to be an important player in inflammation by deacetylating NF-κB p65, which has been implicated in the pathology of COPD. Here, we applied the pharmacological HDAC 3-selective inhibitor RGFP966, which attenuated pro-inflammatory gene expression in models for inflammatory lung diseases. Consistent with this, a robust decrease of the transcriptional activity of NF-κB p65 was observed. HDAC 3 inhibition affected neither the acetylation status of NF-κB p65 nor histone H3 or histone H4. This indicates that HDAC 3 inhibition does not inhibit NF-κB p65 transcriptional activity by affecting its deacetylation but rather by inhibiting enzymatic activity of HDAC 3. Taken together, our findings indicate that pharmacological HDAC 3-selective inhibition by inhibitors such as RGFP966 may provide a novel and effective approach toward development of therapeutics for inflammatory lung diseases.

Poly(L-lactide)/branched ß-cyclodextrin blends: Thermal, morphological and mechanical properties.

In this work we develop poly(L-lactide)/branched ß-cyclodextrin (bßCD) blends in an attempt to obtain new biocompatible and biodegradable materials to be used in the emerging fields of pharmaceutical, biomedicine and food industry. Ionic branched ß-cyclodextrin (bßCD) was obtained by polycondensation of the ß-CD monomer and it was blended with a commercially available PLLA. Fourier transform infrared spectroscopy (FTIR) has been applied to study the occurring interactions between both partners. Thermal properties of blends have been analyzed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), while the phase structure of the blends was analyzed by scanning electron microscopy (SEM). Finally, dynamic mechanical analysis (DMA) has been used to provide further insights into the features controlling miscibility between PLLA and bßCD. Results show the presence of a single phase irrespectively of the blend composition. Overall, this work opens new perspectives for the development of naturally available materials with tunable functional properties for applications in which cyclodextrins emerge as a new class of promising candidates.

Development of a pharmaceutical cocrystal with solution crystallization technology: Preparation, characterization, and evaluation of myricetin-proline cocrystals.

Myricetin shows low oral bioavailability (<10%) in rats due to poor aqueous solubility, although it has demonstrated various pharmacological activities such as those related to anticancer, anti-diabetes, and hepatic protection. To overcome this issue, in this study, pharmaceutical cocrystals were designed to efficiently deliver myricetin by oral administration. A 1:2 stoichiometric cocrystal of myricetin with proline was prepared successfully by solution crystallization based on the ternary phase diagram (TPD) principle, and it is presented as a new sphericity-like crystalline phase characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The formation of myricetin-proline cocrystals was a spontaneous and exothermic process, probably due to the supramolecular interactions between themselves, which were determined by Fourier transform-infrared spectroscopy (FT-IR). Consequently, the dissolution efficiency of myricetin from cocrystals was increased 7.69-fold compared with that of coarse myricetin, and the oral bioavailability of myricetin cocrystals in rats was enhanced by approximately 3.03 times compared with that of pure myricetin. The present study provides useful information for the potential application of cocrystal technology for water-insoluble drugs, especially flavonoid compounds.

Effect of PEGylated chitosan as multifunctional stabilizer for deacetyl mycoepoxydience nanosuspension design and stability evaluation.

Here a series of multifunctional stabilizers was designed and used in a nanosuspension stability enhancement study. Methoxypolyethylene glycol (M PEG)-grafted chitosan, accompanied by space steric hindrance, an electrostatic repulsion function, and a solvation effect, is a multifunctional stabilizer. Deacetyl mycoepoxydience (DM) nanosuspension was prepared using the anti-solvent precipitation approach. The effects of the DM and the multifunctional stabilizer concentration, solvent to anti-solvent ratio, crystallization and storage temperature, and ultrasonic time on drug particle formation during the anti-solvent processing were investigated and the nanosuspension stability was studied. The nanosuspension showed dendritic-like nanostructures and a crystalline state in a morphology and crystalline state study. The optimized drug and multifunctional stabilizer concentration range were selected through the response surface optimization method. The most appropriate and stable nanosuspension could be obtained through the optimal parameters. This study demonstrated that M PEG-grafted chitosan (M PEGC) could be used as a multifunctional stabilizer to control particle size and improve nanosuspension stability.

A micelle-like structure of poloxamer-methotrexate conjugates as nanocarrier for methotrexate delivery.

The purpose of this study was to develop a novel featured and flexible methotrexate (MTX) formulation, in which MTX was physically entrapped and chemically conjugated in the same drug delivery system. A series of poloxamer-MTX (p-MTX) conjugates was synthesized, wherein MTX was grafted to poloxamer through an ester bond. p-MTX conjugates could self-assemble into micelle-like structures in aqueous environment and the MTX end was in the inner-core of micelles. Moreover, free MTX could be physically entrapped into p-MTX micelles hydrophobic core region to increase the total drug loading. Importantly, the resulting MTX-loaded p-MTX micelles showed a biphasic release of MTX, with a relative fast release of the entrapped MTX (about 6-7h) followed by a sustained release of the conjugated MTX. The pharmacokinetics study showed that the mean residence time (MRT) was extended in the case of MTX-loaded p-MTX micelles, indicating a delayed MTX elimination from the bloodstream and prolonged in vivo residence time. Besides, the area under curve (AUC) of MTX-loaded p-MTX micelles was greater than free MTX, indicating a drug bioavailability improvement. Overall, MTX-loaded p-MTX micelles might be a promising nanosized drug delivery system for the cancer therapy.

Protein encapsulated core-shell structured particles prepared by coaxial electrospraying: investigation on material and processing variables.

Biodegradable polymeric particles have been extensively investigated for controlled drug delivery of various therapeutic agents. 'Coaxial' electrospraying was successfully employed in this study, to fabricate core-shell PLGA particles containing bovine serum albumin (BSA) as the model protein, and the results were also compared to particles prepared by 'emulsion' electrospraying. Two different molecular weights of PLGA were employed to encapsulate the protein. Solution properties and processing parameters were found to influence the morphology of the core-shell particles. Depending on the type of solvent used to dissolve the polymer as well as the polymer concentration and molecular weight, the mean diameter of the particles varied between 3.0 to 5.5 µm. Fluorescence microscopic analysis of the electrosprayed particles using FITC-conjugated BSA demonstrated the core-shell structure of the developed particles. The encapsulation efficiency and release behavior of BSA was influenced by shell:core feeding ratio, protein concentration, and the electrospraying method. The encapsulation efficiency of BSA within the core-shell particles of high and low molecular weight PLGA was found 15.7% and 25.1% higher than the emulsion electrosprayed particles, respectively. Moreover, the total amount of BSA released from low molecular weight PLGA particles was significantly higher than high molecular weight PLGA particles within 43 days of release studies, with negligible effect on encapsulation efficiency. The technique of coaxial electrospraying has high potential for encapsulation of susceptible protein-based therapeutic agents such as growth factors for multiple drug delivery applications.