Preparation and characterization of morphine gelatine microspheres.

Morphine is a widely used opioid analgesic. However, standard morphine dosages and administration methods exhibit a short half-life and pose a risk of respiratory depression. Sustained-release microspheres can deliver prolonged efficacy and reduce side effects. We present a new controlled-release morphine gelatine microsphere (MGM) prepared using an emulsification-crosslinking strategy. The gelatine microsphere design improves the bioavailability of morphine. And it not only increases the clinical analgesic efficacy but also the safety of clinical medication through a gradual, sustained release. Besides, we describe MGMs' preparation, release, pharmacodynamics, and pharmacokinetics. And the drug metabolism pathway. We calculate the release rate of morphine by measuring plasma morphine concentration over time and pharmacokinetic parameters. It optimized the manufacturing process of MGMs, which makes the analgesic effect have a longer duration. MGMs analgesic effect shows dose dependence. After they were administrated, MGMs were released more slowly. Peak concentration was reduced, and the relative bioavailability improved. It even reached 88.84%. Its pharmacokinetic process was consistent with the two-component first-order absorption model. MGMs deliver sustained-release and long-action pharmacokinetics. It shows design goals of improving drug bioavailability, prolonging drug residence time in vivo, and maintaining stable blood drug concentration.

Improvement of field emission performances by DMSO and PEDOT:PSS treated freestanding CNT clusters.

In this paper, we present two methods to improve the field emission (FE) performance of vertically aligned carbon nanotube emitters that are treated with dimethyl sulfoxide (DMSO) solution and poly(3,4-ethylene dioxythiophene):polystyrene sulfonate (PEDOT:PSS) solution, respectively, and compared their performances. Both treatments force CNTs to be bundled into clusters, but the formed structures are very different. After treatment, both methods reduced the threshold electric field due to the reduction in screening effects, whereas the PEDOT:PSS treatment significantly reduced the threshold field to far lower than that of DMSO treatment. In addition, the FE efficiency and lifetime of treated CNT emitters are significantly improved. For both treated emitters, there is only slight degradation of the emission current after 80 hours of continuous FE at around 50 µA. In addition, the uniformity of both treated CNT emitters is improved which enables more CNTs to contribute to the overall current emission. This, in turn, lowers the current emitted by individual CNTs, and thereby increases the lifetime of the emitters. Therefore, this study demonstrates that these simple treatment methods of bundling CNTs into unique cluster-structures significantly improve the lifetime of FE and make them excellent candidates for large currents and long-term FE.

Fabrication and characterization of a cannabidiol-loaded emulsion stabilized by a whey protein-maltodextrin conjugate and rosmarinic acid complex.

A cannabidiol (CBD)-loaded oil-in-water emulsion stabilized by a whey protein (WP)-maltodextrin (MD) conjugate and rosmarinic acid (RA) complex was fabricated, and its stability characteristics were investigated under various environmental conditions. The WP-MD conjugates were formed via dry-heating. The interaction between WP and MD was assessed by browning intensity, reduced amount of free amino groups, the formation of high molecular weight components in sodium dodecyl sulfate-PAGE, and changes in secondary structure of whey proteins. The WP-MD-RA noncovalent complex was prepared and confirmed by fluorescence quenching and Fourier-transform infrared spectroscopy spectra. Emulsions stabilized by WP, WP-MD, and WP-RA were used as references to evaluate the effect of WP-MD-RA as a novel emulsifier. Results showed that WP-MD-RA was an effective emulsifier to produce fine droplets for a CBD-loaded emulsion and remarkably improved the pH and salt stabilities of emulsions in comparison with WP. An emulsion prepared with WP-MD-RA showed the highest protection of CBD against UV and heat-induced degradation among all emulsions. The ternary complex kept emulsions in small particle size during storage at 4°C. Data from the current study may offer useful information for designing emulsion-based delivery systems which can protect active substance against environmental stresses.

Enhanced Stability and Oral Bioavailability of Cannabidiol in Zein and Whey Protein Composite Nanoparticles by a Modified Anti-Solvent Approach.

Wide applications of cannabidiol (CBD) in the food and pharmaceutical industries are limited due to its low bioavailability, sensitivity to environmental pressures and low water solubility. Zein nanoparticles were stabilized by whey protein (WP) for the delivery of cannabidiol (CBD) using a modified anti-solvent approach. Particle size, surface charge, encapsulation efficiency, and re-dispersibility of nanoparticles were influenced by the zein to WP ratio. Under optimized conditions at 1:4, zein-WP nanoparticles were fabricated with CBD (200 µg/mL) and further characterized. WP absorbed on zein surface via hydrogen bond, hydrophobic forces, and electrostatic attraction. The zein-WP nanoparticles showed excellent storage stability (4 °C, dark) and effectively protected CBD degradation against heat and UV light. In vivo pharmacokinetic study demonstrated that CBD in zein-WP nanoparticles displayed 2-times and 1.75-fold enhancement in maximum concentration (C max) and the area under curve (AUC) as compared to free-form CBD. The data indicated the feasibility of developing zein-WP based nanoparticles for the encapsulation, protection, and delivery of CBD.

Programmable Pump for Intrathecal Morphine Delivery to Cisterna Magna: Clinical Implications in Novel Management of Refractory Pain Above Middle Thoracic Vertebrae Level Utilizing a Prospective Trial Protocol and Review.

BACKGROUND: The cisterna Intrathecal Drug Delivery system (IDDS) with morphine has proven to be effective in treating refractory cancer pain above the middle thoracic vertebrae level in some countries. However, it has not been fully investigated in others. We designed the current project to investigate the efficacy and safety of cisterna IDDS for pain relief in refractory pain above the middle thoracic vertebrae level in advanced cancer patients. METHODS: This study protocol allows for eligible cancer patients to receive the cisterna IDDS operation. Pain intensity (Visual Analogue scale, VAS), quality of life (36-Item Short-Form Health Survey, SF-36), and depression (Self-Rating Depression scale, SDS) are assessed along with side effects in the postoperative follow-up visits. Recent literature suggests a potential role for cisterna IDDS morphine delivery for refractory pain states above the middle thoracic level. CONCLUSION: The results of this study may provide further evidence that cisterna IDDS of morphine can serve as an effective and safe pain relief strategy for refractory pain above the middle thoracic vertebrae level in advanced cancer patients.

pH-Dependent complexation between ß-lactoglobulin and lycopene: Multi-spectroscopy, molecular docking and dynamic simulation study.

This study aims to investigate the effect of pH levels (pH 7.0 and pH 8.1) on binding ability of ß-lactoglobulin (ß-LG) with lycopene (LYC) and elucidate interaction mechanisms using multi-spectroscopy and molecular docking study. ß-LG at pH 8.1 showed a stronger binding affinity to lycopene than that at pH 7.0 according to binding constant, binding number, energy transfer efficiency, and surface hydrophobicity. Lycopene bound to protein mainly by van der Waals force in the form of static quenching mode and preferred to interact with ß-LG at the top of barrel for both pH levels. Molecular dynamic simulation revealed that ß-LG/LYC complex at pH 8.1 was more stable than at pH 7.0. ß-LG/LYC complexes formed at pH 8.1 showed significantly higher ABTS radical scavenging activity than samples at pH 7.0 (p < 0.05). Data obtained may contribute valuable information for preparing a whey protein-based delivery system for lycopene.

Identification of dicyclohexyl phthalate as a glucocorticoid receptor antagonist by molecular docking and multiple in vitro methods.

The potential activities of phthalate esters (PAEs) that interfere with the endocrine system have been focused recently. However, information on modulating the glucocorticoid receptor (GR) of PAEs is scarce. Our aim was to evaluate the agonistic / antagonistic properties of PAEs on human GR. Luciferase reporter gene assay revealed that the tested chemicals displayed no agonistic effects but dicyclohexyl phthalate (DCHP) exerted antagonistic activity in a dose-responsive manner for GR in HeLa cells. The effects of DCHP on dexamethasone (DEX)-induced GR nuclear translocation and gene expression of glucocorticoid-responsive gene expression (G6Pase, PEPCK, FAS, GILZ and MKP-1), as well as protein expression of G6Pase and PEPCK were further examined by RT-qPCR and western blot analysis. DCHP antagonized DEX-induced GR nuclear translocation and suppressed gene expression in both mRNA and protein levels. Furthermore, the results of molecular docking and molecular dynamics simulation showed that DCHP could bind to GR and exhibited potential regulation on this target protein. Collectively, we demonstrate that DCHP may act as a GR antagonist in vitro and is considered to exert endocrine effects via human GR.

Characterization of ß-Sitosterol for Potential Selective GR Modulation.

BACKGROUND: Although glucocorticoids (GCs) are characterized as powerful agents to treat inflammatory afflictions, they are accompanied by metabolic side effects which limit their usage. ß-Sitosterol, as a minor component found in extraction of vegetable oil, was reported to have anti-inflammatory effects in RAW 264.7 cells. OBJECTIVE: To test whether ß-sitosterol has an effect to dissociate transrepression from transactivation as a selective novel GR binder, this work evaluated the dissociated characteristics of ß-sitosterol. METHODS: The probable binding interaction between ß-sitosterol and GR was explored by molecular docking. The GR transcriptional activity of ß-sitosterol was assessed in the reporter gene assay. The ability of ß-sitosterol to modulate the transactivation and transrepression of GR was evaluated by real-time quantitative PCR analysis. RESULTS AND DISCUSSION: In the present study, ß-sitosterol treatment cannot induce GR-mediated transactivation. ß-Sitosterol exerted a potential to inhibited the expression of GR target transrepressed gene without activating the expression of GR transactivation dependent gene. Molecular docking demonstrated that ß-Sitosterol was able to bind the ligand binding domain of GR but unable to induce GR activation. CONCLUSION: This work offers evidence that ß-sitosterol may serve as a selective GR modulator.

Phthalate esters and dexamethasone synergistically activate glucocorticoid receptor.

This study was conducted to determine the endocrine-disrupting effects of phthalate esters (PAEs) on the glucocorticoid receptor (GR) signaling. Potential (anti)glucocorticoid activities of six typical PAEs including di (2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), diethyl phthalate (DEP) and dimethyl phthalate (DMP) were evaluated on human GR using cell viability assessment, reporter gene expression analysis, mRNA analysis, and molecular docking and simulation. For all tested chemicals, co-treatment of DEHP and DINP with dexamethasone (DEX) exhibited a synergistic effect on GR transactivity in the reporter assays. Such co-treatment also synergistically enhanced DEX-induced upregulation of GR mediated gene (PEPCK, FAS and MKP-1) mRNA expression in HepG2 cells and A549 cells. Molecular docking and dynamics simulations showed that hydrophobic interactions may stabilize the binding between molecules and GR. In summary, DEHP and DINP may be involved in synergistic effects via human GR, which highlight the potential endocrine-disrupting activities of PAEs as contaminants.

Modeling the NaCl diffusion in beef during brining process.

An in-depth understanding of mass transfer during brining process is important for improving the quality and characteristics of meat products. In this study, a fitted equation of time and NaCl concentrations in the aqueous phase of beef was established to calculate the NaCl diffusion coefficient for simulation. A three-dimensional simulating model of mass transfer was developed to evaluate the NaCl diffusion in beef during brining process. And the validity of this simulating model was verified by comparing the NaCl concentrations evaluated by the numerical simulation simulated with the experimental measurements. The results indicated that the power function time variant equation can predict NaCl concentrations (R2 = 0.995) and accurately calculate the NaCl diffusion coefficient (8.46 × 10-10 m2 /s). The simulating model visually showed the NaCl diffusion in beef during brining process. Therefore, this research provided a new method for predicting the NaCl diffusion in realistic meat processing. PRACTICAL APPLICATION: This research gives a new method for predicting the NaCl diffusion in meat product. The method accurately evaluated NaCl concentrations in beef at different brining time and clearly showed NaCl diffusion in beef during brining process, which could be helpful in reducing the cost and the complexity of detecting NaCl concentrations in meat during brining process.

Intrathecal Morphine Delivery at Cisterna Magna to Control Refractory Cancer-Related Pain: A Prospective Cohort Study.

Background: For patients suffering from primary or metastatic cancer above the middle thoracic vertebrae, refractory pain management still remains a great challenge. Theoretically, inserting a catheter tip into the cisterna magna may be a promising solution. However, at present, there have been no reliable data regarding this novel technique. We therefore investigated the efficacy and safety of an advanced approach for pain relief in a specific population. Methods: Thirty participants from two hospitals received the intrathecal deliveries of opioid to either one of two sites: cisterna magna (n = 15) or lower thoracic region (n = 15). Pain relief (visual analogue scale, VAS), quality of life (short form (36) health survey, SF-36) as well as depression (self-rating depression scale, SDS) were assessed in the follow-up visits and compared between the two groups. Results: Patients receiving intrathecal morphine delivery to cisterna magna achieved greater pain improvement indicated as significant decrease of VAS scores at day 1 and 7, and achieved better improvement in physical function (day 7 and 30), role physical (day 7 and 30), body pain (day 7, 30 and 90), general health (day 7, 30 and 90), vitality (day 7, 30 and 90), social function (day 90), role emotional (day 7 and 90), mental health (day 7, 30 and 90) and SDS (day 1 and 7). Conclusions: Intrathecal morphine delivery to cisterna magna might be an effective and safe technique for patients suffering from cancer at the middle thoracic vertebrae or above to control refractory pain. Trial registration: No. ChiCTR-ONN-17010681.

Electrical impedance estimation for pork tissues during chilled storage.

The impedance and physicochemistry of pork loins at five chilled storage periods (0, 1, 3, 7, 15 days) were characterized in order to explore the effects of chilling on the cell physiological status of pork tissues. The impedance spectra were analyzed by an equivalent circuit model with needle and bar electrodes. Meat traits including cooking loss, color, pH, texture properties and electrical conductivity were measured. The conductivity and pH of pork increased, and the color and texture parameters all significantly differed. The measured impedance of pork tissues can be described well by a modified Hayden model. The impedance characteristics of samples revealed that the structures and integrity of cell membranes in pork tissues were damaged with the prolonged storage time. The findings prove the potential of electrical impedance spectroscopy in evaluating the physiological status of pork tissues during chilled storage.

Multi-Residue Method for the Analysis of Stilbene Estrogens in Milk.

The rapid analysis of stilbene estrogens is crucially important in the environment, food and health sectors, but quantitation of lower detection limit for stilbene estrogens persists as a severe challenge. We herein described a homologous and sensitive fluorescence polarization (FP) assay based on estrogen receptor α ligand binding domain (ER-LBD) to monitor stilbene estrogens in milk. Under optimal conditions, the half maximal inhibitory concentrations (IC50) of the FP assay were 9.27 nM, 12.94 nM, and 22.38 nM for hexestrol, dienestrol and diethylstilbestrol, respectively. And the corresponding limits of detection (LOD) values were 2.94 nM, 2.89 nM, and 3.12 nM. Finally, the assay was applied to determine the stilbenes in milk samples where the mean recoveries ranged from 95.76% to 112.78% and the coefficients of variation (CV) below 12.00%. Furtherly, we have focused our study on high cross-reactivity phenomena by using two in silico approaches, including molecular docking analysis and topology analysis. Overall, docking results show that several residues in the hydrophobic pocket produce hydrophobic interactions with the tested drug molecules, which contribute to the stability of their binding. In this paper, we conclude that the FP method is suitable for the rapid detection of stilbenes in milk samples, requiring no expensive analytical equipment or time-consuming sample preparation. This work offers a practical approach that applies bioscience technology in food safety testing and improves analytical speed and laboratory efficiency.

Browning control of fresh-cut Chinese yam by edible coatings enriched with an inclusion complex containing star anise essential oil.

Star anise essential oil (SAEO) has a variety of antioxygenic and antimicrobial properties, and is widely used in food preservation. However, its application is still challenging due to poor water solubility and physicochemical stability. We now report that encapsulation of SAEO in hydroxypropyl-ß-cyclodextrin (HPCD) enhances its water solubility, as well as its thermal, storage, and photostability. The solubility of SAEO encapsulated by HPCD was increased by 47.5 times at 45 °C, and the onset temperature of thermal volatilization was delayed by at least 200 °C. The encapsulated material is also more uniformly and more stably dispersed in xanthan gum, and is thus released in a controlled manner. Importantly, fresh-cut Chinese yam coated with xanthan gum containing encapsulated SAEO is more effectively preserved, as assessed using weight loss, L* value, browning index, and polyphenol oxidase activity. The data suggest that the encapsulated SAEO reduced the weight loss of the samples by more than 30%, and the encapsulation of HPCD increased the inhibitory effect of SAEO on browning and polyphenol oxidase activity of the samples by nearly 8 times and more than 7 times, respectively. Collectively, SAEO encapsulated in HPCD is promising as a preservative coat for fresh-cut fruits and vegetables.

Estrogen receptor-based multi-residue screening of bisphenol compounds in urine.

Human exposure to bisphenol compounds (BPs) has been implicated in the development of several chronic diseases. Instead of exploiting the traditional methods for determination of BPs, this work confirms that the human estrogen receptor α ligand binding domain (hERα-LBD) is a powerful recognition element that can be used to monitor multi-residue of BPs in urine samples by fluorescence polarization (FP) assay. Test parameters were optimized for the best performance. Under the optimal conditions, the IC50 values of BPs are in the range of 0.04-1.61 µg mL-1 . Recovery experiments were then performed to assess the accuracy and precision of the established method. The results detected by FP assay show good agreements with that of liquid chromatography-tandem mass spectrometry method with a fit of R2  = 0.9372 and 0.9640 for BPE and BPAP, respectively. A computational methodology, ligand-based pharmacophore model, was also employed to further explore the broad-specific of tested compounds. It was found that the two hydrogen bond acceptor features and one hydrophobic aliphatic feature were essential for the corresponding cross-reactivity results from the FP assay. All these results suggest that the established method can be successfully applied to monitor the occurrence of BPs in urine.

A Polysaccharide Purified from Morchella conica Pers. Prevents Oxidative Stress Induced by H2O2 in Human Embryonic Kidney (HEK) 293T Cells.

Morchella conica Pers. (M. conica) has been used both as a medical and edible mushroom and possesses antimicrobial properties and antioxidant activities. However, the antioxidant properties of polysaccharides purified from M. conica have not been studied. The aim of this study was to investigate the in vitro antioxidant properties of a polysaccharide NMCP-2 (neutral M. conica polysaccharides-2) purified from M. conica, as determined by radical scavenging assay and H2O2-induced oxidative stress in HEK 293T cells. Results showed that NMCP-2 with an average molecular weight of 48.3 kDa possessed a much stronger chelating ability on ferrous ions and a higher ability to scavenge radical scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) than the other purified fraction of NMCP-1 from M. conica. Moreover, 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetra-zolium bromide (MTT) assay showed that NMCP-2 dose-dependently preserved cell viability of H2O2-induced cells. The NMCP-2 pretreated group reduced the generation of reactive oxygen species (ROS) content and increased the mitochondria membrane potential (MMP) levels. In addition, Hoechst 33342 staining revealed cells treated with NMCP-2 declined nuclear condensation. Ultrastructural observation revealed that NMCP-2 pretreatment alleviated the ruptured mitochondria when exposed to H2O2. Furthermore, western blot analysis showed that NMCP-2 prevented significant downregulation of the protein expression of Bax, cleaved caspases 3, and upregulated Bcl-2 levels. These results suggest the protective effects of NMCP-2 against H2O2-induced injury in HEK 293T cells. NMCP-2 could be used as a natural antioxidant of functional foods and natural drugs.

Effect of Selective Encapsulation of Hydroxypropyl-ß-cyclodextrin on Components and Antibacterial Properties of Star Anise Essential Oil.

Star anise essential oil (SAEO) is a plant essential oil with good antibacterial activity, but its applications are limited due to its high volatility, strong smell, and unstable physical and chemical properties. The effect of selective encapsulation of SAEO by hydroxypropyl-ß-cyclodextrin (HPCD) on its compositions, volatility stability and antibacterial activity was investigated. The GC-MS results indicated that the compositions reduced and content of the compositions of SAEO changed after encapsulation. Most of the components in SAEO were successfully encapsulated by HPCD, which can be supported by data from FTIR and ¹H NMR. According to the molecular modeling results, the three guest molecules (trans-anethole, estragole and trans-foeniculin) were all docked in the cavity of HPCD on the isoallyl (or allyl) side. The volatile stability of SAEO before and after encapsulation was evaluated by electronic nose, and the results confirmed that encapsulation significantly reduced the irritating smell of SAEO and makes the clathrate have a sustained release effect. Furthermore, in the antibacterial test, the selective encapsulation of HPCD improved the inhibition effect of SAEO on Rhizopus stolonoifer, Saccharomyces cerevisiae, and E. coli and its antibacterial stability in 24 h.

Prediction of Firmness and pH for "Golden Delicious" Apple Based on Elasticity Index from Modal Analysis.

An experimental modal test system was established to extract the natural frequencies of "Golden Delicious" apple, after which the elasticity index was calculated to predict the apple quality parameters based on the orthogonal polynomials method. The elasticity index in every vibration mode changed dramatically (P = 0.01) along time revolution. The multivariate regression methods were used to model the predictive relationship between the elasticity index and the apple quality parameters. The models of the apple juice pH based on support vector regression presented adequate determination coefficients of calibration set (Q2  = 0.68) and prediction set (R2  = 0.55), respectively. The models based on partial least squares regression could be used for predicting the apple firmness parameter offset gradient (Q2  = 0.76 and R2  = 0.72). It helped understanding the fruit dynamic properties of the fruit and spontaneously obtaining the fruit chemical parameters. A nondestructive and portable device was viable for fruit quality estimation by the modal test system during storage, transport, and even growth on the tree. PRACTICAL APPLICATION: A nondestructive and portable device was provided for fruit quality detection during storage, transport and even growth based on experimental modal analysis. A systematic statistical analysis method about outlier detection, data set partitioning, parameter optimization, and multiple regression models were provided.

A comparison of food crispness based on the cloud model.

The cloud model is a typical model which transforms the qualitative concept into the quantitative description. The cloud model has been used less extensively in texture studies before. The purpose of this study was to apply the cloud model in food crispness comparison. The acoustic signals of carrots, white radishes, potatoes, Fuji apples, and crystal pears were recorded during compression. And three time-domain signal characteristics were extracted, including sound intensity, maximum short-time frame energy, and waveform index. The three signal characteristics and the cloud model were used to compare the crispness of the samples mentioned above. The crispness based on the Ex value of the cloud model, in a descending order, was carrot > potato > white radish > Fuji apple > crystal pear. To verify the results of the acoustic signals, mechanical measurement and sensory evaluation were conducted. The results of the two verification experiments confirmed the feasibility of the cloud model. The microstructures of the five samples were also analyzed. The microstructure parameters were negatively related with crispness (p < .01). PRACTICAL APPLICATIONS: The cloud model method can be used for crispness comparison of different kinds of foods. The method is more accurate than the traditional methods such as mechanical measurement and sensory evaluation. The cloud model method can also be applied to other texture studies extensively.

Numerical and experimental study of radiation induced conductivity change of carbon nanotube filled polymers.

Measuring the conductivity changes of sensing materials to detect a wide range of radiation energy and dosage is one of the major sensing mechanisms of radiation sensors. Carbon nanotube (CNT) filled composites are suitable for sensing radiation because of the extraordinary electrical properties of CNTs and the CNT-network formed inside the polymer matrix. Although the use of CNT-based nanocomposites as potential radiation sensing materials has been widely studied, there is still a lack of theoretical models to analyze the relationship between electrical conductivity and radiation dosages. In this article, we propose a 3D model to describe the electrical conductivity of CNT-based nanocomposites when being irradiated by ionizing radiation. The Monte Carlo method has been employed to calculate radiation intensity, CNT concentration and alignment's influence on the electrical conductivity. Our simulation shows a better agreement when CNT loading is between the percolation threshold and 3% volume fraction. Radiation experiments have been performed to verify the reliability of our model to illustrate a power function relationship between the electrical conductivity of a CNT-filled polymer and radiation intensity. In addition, the predicted alignment to obtain the best sensitivity for radiation sensing has been discussed to help with CNT-network building in the fabrication process.