Shellac Micelles Loaded with Curcumin Using a pH Cycle to Improve Dispersibility, Bioaccessibility, and Potential for Colon Delivery.

Delivery systems smaller than 50 nm are advantageous for cancer prevention. In this study, curcumin was dissolved in shellac micelles following co-dissolving at pH 13.0 and neutralization using glucono-delta-lactone. With 5% w/v shellac and 0.5-5 mg/mL curcumin, the loading capacity and encapsulation efficiency were up to 8.0 and 92.6%, respectively, and the nanocapsules had an average diameter of 20 nm. Differential scanning calorimetry, FTIR spectroscopy, and fluorescence spectroscopy results confirmed the encapsulation of curcumin in an amorphous state in shellac micelles. The neutral nanocapsule dispersions maintained the particle dimension and had less than 10% curcumin degradation during 4 week storage at 4 °C. Nanoencapsulating curcumin enhanced in vitro bioavailability and antiproliferation activity against colon cancer cells. After simulated digestions, ∼60% of the nanoencapsulated curcumin was not available for intestinal absorption, nanocapsules retained their structure, and nanoencapsulated curcumin remained active against colon cancer cells, indicating the potential delivery for colorectal cancer prevention.

BoPEP4, a C-Terminally Encoded Plant Elicitor Peptide from Broccoli, Plays a Role in Salinity Stress Tolerance.

Plant peptide hormones play various roles in plant development, pathogen defense and abiotic stress tolerance. Plant elicitor peptides (Peps) are a type of damage-associated molecular pattern (DAMP) derived from precursor protein PROPEPs. In this study, we identified nine PROPEP genes in the broccoli genome. qRT-PCR analysis indicated that the expression levels of BoPROPEPs were induced by NaCl, ABA, heat, SA and P. syringae DC3000 treatments. In order to study the functions of Peps in salinity stress response, we synthesized BoPep4 peptide, the precursor gene of which, BoPROPEP4, was significantly responsive to NaCl treatment, and carried out a salinity stress assay by exogenous application of BoPep4 in broccoli sprouts. The results showed that the application of 100 nM BoPep4 enhanced tolerance to 200 mM NaCl in broccoli by reducing the Na+/K+ ratio and promoting accumulation of wax and cutin in leaves. Further RNA-seq analysis identified 663 differentially expressed genes (DGEs) under combined treatment with BoPep4 and NaCl compared with NaCl treatment, as well as 1776 genes differentially expressed specifically upon BoPep4 and NaCl treatment. GO and KEGG analyses of these DEGs indicated that most genes were enriched in auxin and ABA signal transduction, as well as wax and cutin biosynthesis. Collectively, this study shows that there was crosstalk between peptide hormone BoPep4 signaling and some well-established signaling pathways under salinity stress in broccoli sprouts, which implies an essential function of BoPep4 in salinity stress defense.

Antrodia cinnamomea and its compound dehydroeburicoic acid attenuate nonalcoholic fatty liver disease by upregulating ALDH2 activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver disease, but currently has no specific medication in clinic. Antrodia cinnamomea (AC) is a medicinal fungus and it has been shown that AC can inhibit high fat diet (HFD)-induced lipid deposition in mouse livers, but the effective monomer in AC and mechanism against NAFLD remain unclear. It has been reported that aldehyde dehydrogenase 2 (ALDH2) activation shows protective effects on NAFLD. Our previous study demonstrates that AC and its monomer dehydroeburicoic acid (DEA) can upregulate the ALDH2 activity on alcoholic fatty liver disease mouse model, but it is not clear whether the anti-NAFLD effects of AC and DEA are mediated by ALDH2. AIM TO STUDY: To elucidate the active compound in AC against NAFLD, study whether ALDH2 mediates the anti-NAFLD effects of AC and its effective monomer. MATERIALS AND METHODS: WT mice, ALDH2-/- mice and ALDH2-/- mice re-expressed ALDH2 by lentivirus were fed with a methionine-choline deficient (MCD) diet or high fat diet (HFD) to induce NAFLD, and AC at the different doses (200 and/or 500 mg/kg body weight per day) was administrated by gavage at the same time. Primary hepatocytes derived from WT and ALDH2-/-mice were stimulated by oleic acid (OA) to induce lipid deposition, and the cells were treated with AC or DEA in the meantime. Lentivirus-mediated ALDH2-KD or ALDH2-OE were used to knock down or overexpress ALDH2 expression in HepG2 cells, respectively. Finally, the effects of DEA against NAFLD as well as its effects on upregulating liver ALDH2 and removing the harmful aldehyde 4-hydroxynonenal (4-HNE) were studied in the MCD diet-induced NAFLD mouse model. RESULTS: In WT mice fed with a MCD diet or HFD, AC administration reduced hepatic lipid accumulation, upregulated ALDH2 activity in mouse livers, decreased 4-HNE contents both in mouse livers and serum, inhibited lipogenesis, inflammation and oxidative stress and promoted fatty acid ß-oxidation. These effects were abolished in ALDH2 KO mice but could be restored by re-expression of ALDH2 by lentivirus. In primary hepatocytes of WT mice, AC and DEA inhibited OA-induced lipid accumulation and triglyceride (TG) synthesis, promoting the ß-oxidation of fatty acid in the meantime. However, these effects were lost in primary hepatocytes of ALDH2 KO mice. Moreover, the expression level of ALDH2 significantly affected the inhibitory effects of AC and DEA on OA-induced lipid deposition in HepG2 cells. The effects of AC and DEA on suppressing lipid deposition, inhibiting mitochondrial ROS levels, reducing TG synthesis, and promoting ß-oxidation of fatty acid were all enhanced with the overexpression of ALDH2 and reduced with the knockdown of ALDH2 expression. DEA showed dose-dependent effects on inhibiting liver lipid deposition, elevating ALDH2 activity and reducing 4-HNE levels in the livers of MCD diet-induced NAFLD mice. CONCLUSION: DEA is the effective compound in AC against NAFLD. The related anti-NAFLD mechanisms of AC and DEA were through upregulating ALDH2 expression and activity, thus enhancing the elimination of 4-HNE in the livers, and sequentially alleviating oxidative stress and inflammation, promoting fatty acid ß-oxidation and decreasing lipogenesis.

Inactivation of Escherichia coli K12 on raw almonds using supercritical carbon dioxide and thyme oil.

Raw almonds could be contaminated by pathogens, but the current pasteurization practice using propylene oxide in the U.S. has flammability and carcinogenicity concerns. Supercritical carbon dioxide (scCO2) is a water-free technology and is a solvent of essential oils that are effective antimicrobial preservatives. The objective of this study was to investigate the possibility of combining scCO2 and thyme oil (TO) to reduce Escherichia coli K12 inoculated on raw almonds. Raw almonds inoculated with ∼6 log CFU/g E. coli K12 were batch-treated with scCO2 alone or the combination of presoaking in pure TO followed by scCO2 treatments at different combinations of temperature, pressure, and duration. Compared to scCO2 alone treatments, the combination of TO and scCO2 treatments significantly improved the disinfection effectiveness. Temperature had the most significant effect on the log reduction. At 70 °C, the log reduction by the combination treatment was over 4-log CFU/g and the maximum reduction was 5.16 log CFU/g. The findings suggest that the combination of TO and scCO2 may be a potential water-free technology to meet the requirement of over 4-log reduction of target microorganism for almond and other tree nut products.

HPMC improves protective effects of naringenin and isonicotinamide co-crystals against abdominal aortic aneurysm.

PURPOSE: Abdominal aortic aneurysm (AAA) rupture is one of the most common causes of mortality in cardiovascular diseases, but currently there is no approved drug for AAA treatment or prevention in the clinic. Naringenin (NGN) has been reported to have anti-AAA effects. However, water solubility and in vivo absorption of NGN are not satisfactory, which leads to its low bioavailability, thus affecting its pharmacological effects. In this project, the improving effects of isonicotinamide (INT) co-crystal and hydroxy propyl methyl cellulose (HPMC) or polyvinyl pyrrolidone (PVP) on the solubility, in vivo absorption, and anti-AAA effects of NGN were evaluated. METHODS: In the current study, co-crystals of naringenin-isonicotinamide (NGN-INT) were prepared, and effects of PVP or HPMC on precipitation rate, supersaturation, and bioavailability of NGN were explored. In addition, with or without HPMC supply, the effects of NGN-INT co-crystal on anti-AAA efficacy of NGN were investigated on an elastase-induced AAA mouse model, and the results were compared with the efficacy of the NGN crude drug. RESULTS: Our results demonstrate that NGN-INT formulation, compared to the NGN crude drug, enhanced the dissolution rate of NGN and significantly increased Cmax and AUC(0-∞) of NGN by 18 times and 1.97 times, respectively. Addition of PVP or HPMC in NGN-INT co-crystal further increased bioavailability of NGN in NGN-INT. The in vivo pharmacodynamic study showed that NGN-INT with HPMC significantly improved the inhibitory effects of NGN against AAA. CONCLUSION: NGN-INT significantly improved the absorption and aortic protective effects of NGN. The supersaturation-prolonging effect of HPMC further enhanced bioavailability and anti-AAA effects of NGN-INT.

A Review of Research Progress on Agathis dammara and its Application Prospects for Cardiovascular Diseases and Fatty Liver Disease.

Cardiovascular diseases and fatty liver disease have become the leading causes of death in modern society. However, the currently existing drugs do not solve all issues related to these diseases; thus, it is expected that more potential drugs for clinical use will be developed. Undeniably, natural products have attracted increasing attention. It is of great significance to identify effective active monomer components for drug discovery and disease prevention. As a pure natural product, Agathis dammara (AD) has antioxidant, hypolipidemic, hypoglycemic, antitumor, and anti-inflammatory activities. However, at present, there are few reports regarding the effects of AD on chronic inflammatory cardiovascular diseases, such as aneurysm, atherosclerosis, myocardial ischemia-reperfusion injury, and cardiac hypertrophy and liver diseases such as fatty liver disease. AD and products derived from it have a very broad application prospect for cardiovascular diseases and fatty liver disease.

Caffeic Acid Phenethyl Ester Loaded in Skim Milk Microcapsules: Physicochemical Properties and Enhanced In Vitro Bioaccessibility and Bioactivity against Colon Cancer Cells.

Caffeic acid phenethyl ester (CAPE) has various biological activities but low water solubility and poor bioavailability. In this study, CAPE was encapsulated in skim milk powder (SMP) by spray drying warm aqueous ethanol solutions with different mass ratios of SMP and CAPE. The loading capacity and encapsulation efficiency were up to 10.1 and 41.7%, respectively. Differential scanning calorimetry and X-ray diffraction results confirmed the loss of crystallinity of CAPE after encapsulation. Fourier-transform infrared and fluorescence spectroscopy results indicated the hydrophobic binding between CAPE and caseins. Scanning electron microscopy and static light scattering results showed spherical capsules with an average diameter of around 26 µm. The CAPE loaded in SMP microcapsules showed significantly improved in vitro bioaccessibility and antiproliferation activity against human colon cancer cells compared to free CAPE. The simple, scalable, and low-cost approach in the present study may be significant for industrial encapsulation of CAPE and other lipophilic bioactive compounds.

Hydrochlorothiazide ameliorates polyuria caused by tolvaptan treatment of polycystic kidney disease in PCK rats.

BACKGROUND: Tolvaptan is an effective treatment for polycystic kidney disease (PKD), but also causes unfortunate polyuria. Hydrochlorothiazide (HCTZ) has been shown to reduce urine volume in nephrogenic diabetes insipidus, raising the possibility that HCTZ could also be effective in reducing tolvaptan-induced polyuria. In this study, we examined the combined administration of HCTZ and tolvaptan. METHODS: Male PCK rats were divided into four groups of normal chow (Cont), normal chow plus tolvaptan, gavage HCTZ treatment, and tolvaptan + HCTZ. Biochemical examinations of the plasma and urine were performed as well as histological and molecular (mRNA and protein expression) analyses. RESULTS: Groups treated with tolvaptan had significantly higher 24 h urine excretion, which was significantly reduced in the tolvaptan + HCTZ group after 2 weeks. Cyst size, pERK protein expression, and Cyclin D1 mRNA expression were all significantly reduced in both the tolvaptan and tolvaptan + HCTZ groups, indicating that HCTZ did not affect the beneficial functions of tolvaptan. Notably, aquaporin 2 redistribution from the apical to intracellular domains was observed in tolvaptan-treated rats and was partially reversed in the tolvaptan + HCTZ group. The renal glomerular filtration rate was reduced in the tolvaptan + HCTZ group. Significantly lowered mRNA expression of neuronal nitric oxide synthase, prostaglandin E synthase 2 and renin were also found in the medulla, but not in the cortex. CONCLUSION: HCTZ reduces tolvaptan-induced polyuria without altering its beneficial effects on PKD. This novel therapeutic combination could potentially lead to better PKD treatments and improved quality of life for the affected patients.

Research on Flow Field Perception Based on Artificial Lateral Line Sensor System.

In nature, the lateral line of fish is a peculiar and important organ for sensing the surrounding hydrodynamic environment, preying, escaping from predators and schooling. In this paper, by imitating the mechanism of fish lateral canal neuromasts, we developed an artificial lateral line system composed of micro-pressure sensors. Through hydrodynamic simulations, an optimized sensor structure was obtained and the pressure distribution models of the lateral surface were established in uniform flow and turbulent flow. Carrying out the corresponding underwater experiment, the validity of the numerical simulation method is verified by the comparison between the experimental data and the simulation results. In addition, a variety of effective research methods are proposed and validated for the flow velocity estimation and attitude perception in turbulent flow, respectively and the shape recognition of obstacles is realized by the neural network algorithm.

Red blood cell distribution width is associated with mortality in elderly patients with sepsis.

INTRODUCTION: RDW is a prognostic biomarker and associated with mortality in cardiovascular disease, stroke and metabolic syndrome. For elderly patients, malnutrition and multiple comorbidities exist, which could affect the discrimination ability of RDW in sepsis. The main purpose of our study was to evaluate the prognostic value of RDW in sepsis among elderly patients. METHODS: This was a retrospective cohort study conducted in emergency department intensive care units (ED-ICU) between April 2015 and November 2015. Elderly patients (≥65years old) who were admitted to the ED-ICU with a diagnosis of severe sepsis and/or septic shock were included. The demographic data, biochemistry data, qSOFA, and APACHE II score were compared between survivors and nonsurvivors. RESULTS: A total of 117 patients was included with mean age 81.5±8.3years old. The mean APACHE II score was 21.9±7.1. In the multivariate Cox proportional hazards model, RDW level was an independent variable for mortality (hazard ratio: 1.18 [1.03-1.35] for each 1% increase in RDW, p=0.019), after adjusting for CCI, any diagnosed malignancy, and eGFR. The AUC of RDW in predicting mortality was 0.63 (95% confidence interval [CI]: 0.52-0.74, p=0.025). In subgroup analysis, for qSOFA <2, nonsurvivors had higher RDW levels than survivors (17.0±3.3 vs. 15.3±1.4%, p=0.044). CONCLUSIONS: In our study, RDW was an independent predictor of in-hospital mortality in elderly patients with sepsis. For qSOFA scores <2, higher RDW levels were associated with poor prognosis. RDW could be a potential parameter used alongside the clinical prediction rules.

Association between early arterial blood gas tensions and neurological outcome in adult patients following in-hospital cardiac arrest.

OBJECTIVE: The early partial pressures of arterial O2 (PaO2) and CO2 (PaCO2) have been found in animal studies to be correlated with neurological outcome after brain injury. However, the relationship of early PaO2 and PaCO2 to the neurological outcomes of resuscitated patients after cardiac arrest was still not clear. METHODS: This was a retrospective observational cohort study in a single medical center. Adult patients who had in-hospital cardiac arrest between 2006 and 2012 and achieved sustained return of spontaneous circulation (ROSC) (ROSC>20min without resumption of chest compression) were included. Multivariable logistic regression analysis was used to identify factors associated with favorable neurological outcome at hospital discharge. The first PaO2 and PaCO2 values measured after first sustained ROSC were used for analysis. RESULTS: Of the 550 included patients, 154 (28%) survived to hospital discharge and 74 (13.5%) achieved favorable neurological outcome. The mean time from sustained ROSC to the measurement of PaO2 and PaCO2 was 136.8min. The mean PaO2 and PaCO2 were 167.4mmHg and 40.3mmHg, respectively. PaO2 between 70 and 240mmHg (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.08-3.64) and PaCO2 levels (OR 0.98, 95% CI 0.95-0.99) were positively and inversely associated with favorable neurological outcome, respectively. CONCLUSIONS: The early PaO2 and PaCO2 levels obtained after ROSC might be correlated with neurological outcome of patients with in-hospital cardiac arrest. However, because of the inherent limitations of the retrospective design, these results should be further validated in future studies.