Targeting of HBP1/TIMP3 axis as a novel strategy against breast cancer.

Malignant proliferation and metastasis are the main causes of breast cancer death. The transcription factor high mobility group (HMG) box-containing protein 1 (HBP1) is an important tumor suppressor whose deletion or mutation is closely related to the appearance of tumors. Here, we investigated the role of HBP1 in breast cancer suppression. HBP1 enhances the activity of the tissue inhibitors of metalloproteinases 3 (TIMP3) promoter, thereby increasing protein and mRNA levels of TIMP3. TIMP3 increases the phosphatase and tensin homolog (PTEN) protein level by inhibiting its degradation and acts as a metalloproteinase inhibitor to inhibit the protein levels of MMP2/9. In this study, we demonstrated that the HBP1/TIMP3 axis plays a crucial role in inhibiting the tumorigenesis of breast cancer. HBP1 deletion interferes with the regulation of the axis and induces the occurrence and malignant progression of breast cancer. In addition, the HBP1/TIMP3 axis promotes the sensitivity of breast cancer to radiation therapy and hormone therapy. Our study opens new perspectives on the treatment and prognosis of breast cancer.

Anti-inflammatory and immunomodulatory activity of Mangifera indica L. reveals the modulation of COX-2/mPGES-1 axis and Th17/Treg ratio.

In the context of inflammation and immunity, there are fragmented and observational studies relating to the pharmacological activity of Mangifera indica L. and its main active component, mangiferin. Therefore, we aimed to analyze the potential beneficial effects of this plant extract (MIE, 90 % in mangiferin) in a mouse model of gouty arthritis, to allow the evaluation of cellular immune phenotypes and the biochemical mechanism/s beyond MIE activity. Gouty arthritis was induced by the intra-articular administration of MSU crystals (200 µg 20 µl-1), whereas MIE (0.1-10 mg kg-1) or corresponding vehicle (DMSO/saline 1:3) were orally administrated concomitantly with MSU (time 0), 6 and 12 h after the stimulus. Thereafter, knee joint score and oedema were evaluated in addition to western blot analysis for COX-2/mPGES-1 axis. Moreover, the analysis of pro/anti-inflammatory cyto-chemokines coupled with the phenotyping of the cellular infiltrate was performed. Treatment with MIE revealed a dose-dependent reduction in joint inflammatory scores with maximal inhibition observed at 10 mg kg-1. MIE significantly reduced leukocyte infiltration and activation and the expression of different pro-inflammatory cyto-chemokines in inflamed tissues. Furthermore, biochemical analysis revealed that MIE modulated COX-2/mPGES-1 and mPGDS-1/PPARγ pathways. Flow cytometry analysis also highlighted a prominent modulation of inflammatory monocytes (CD11b+/CD115+/LY6Chi), and Treg cells (CD4+/CD25+/FOXP3+) after MIE treatment. Collectively, the results of this study demonstrate a novel function of MIE to positively affect the local and systemic inflammatory/immunological perturbance in the onset and progression of gouty arthritis.

Novel in vivo experimental viability assays with high sensitivity and throughput capacity using a bdelloid rotifer.

Rotifers have been used in biological research as well-characterized models of aging. Their multi-organ characters and their sensitivity for chemicals and environmental changes make them useful as in vivo toxicological and lifespan models. Our aim was to create a bdelloid rotifer model to use in high-throughput viability and non-invasive assays. In order to identify our species Philodina acuticornis odiosa (PA), 18S rDNA-based phylogenetic analysis was carried out and their species-specific morphological markers identified. To execute the rotifer-based experiments, we developed an oil-covered water-drop methodology adapted from human in vitro fertilization techniques. This enables toxicological observations of individual one-housed rotifers in a closed and controllable micro-environment for up to several weeks. Hydrogen peroxide (H2O2) and sodium azide (NaN3) exposures were used as well-understood toxins. The toxicity and survival lifespan (TSL), the bright light disturbance (BLD) the mastax contraction frequency (MCF) and the cellular reduction capacity (CRC), indices were recorded. These newly developed assays were used to test the effects of lethal and sublethal doses of the toxins. The results showed the expected dose-dependent decrease in indices. These four different assays can either be used independently or as an integrated system for studying rotifers. These new indices render the PA invertebrate rotifer model a quantitative system for measuring viability, toxicity and lifespan (with TSL), systemic reaction capacity (with BLD), organic functionality (with MCF) and reductive capability of rotifers (with CRC), in vivo. This novel multi-level system is a reliable, sensitive and replicable screening tool with potential application in pharmaceutical science.

Montelukast potentiates the anticonvulsant effect of phenobarbital in mice: an isobolographic analysis.

Although leukotrienes have been implicated in seizures, no study has systematically investigated whether the blockade of CysLT1 receptors synergistically increases the anticonvulsant action of classic antiepileptics. In this study, behavioral and electroencephalographic methods, as well as isobolographic analysis, are used to show that the CysLT1 inverse agonist montelukast synergistically increases the anticonvulsant action of phenobarbital against pentylenetetrazole-induced seizures. Moreover, it is shown that LTD4 reverses the effect of montelukast. The experimentally derived ED50mix value for a fixed-ratio combination (1:1 proportion) of montelukast plus phenobarbital was 0.06±0.02 µmol, whereas the additively calculated ED50add value was 0.49±0.03 µmol. The calculated interaction index was 0.12, indicating a synergistic interaction. The association of montelukast significantly decreased the antiseizure ED50 for phenobarbital (0.74 and 0.04 µmol in the absence and presence of montelukast, respectively) and, consequently, phenobarbital-induced sedation at equieffective doses. The demonstration of a strong synergism between montelukast and phenobarbital is particularly relevant because both drugs are already used in the clinics, foreseeing an immediate translational application for epileptic patients who have drug-resistant seizures.

Dietary salidroside supplementation improves meat quality and antioxidant capacity and regulates lipid metabolism in broilers.

We aimed to explore the effect of salidroside (SAL) on meat quality, antioxidant capacity, and lipid metabolism in broilers. The results demonstrated that SAL significantly reduced the yellowness (b*), shear force, cooking loss, drip loss, MDA, TBARS, and carbonyl content in breast (P < 0.05), while increasing the pH value (P < 0.05), suggesting an improvement in meat quality. SAL lowered the lipid contents in liver and serum (P < 0.05), while increasing the proportion of unsaturated fatty acids in breast (P < 0.05), indicating effective regulation of lipid metabolism by SAL. SAL increased the activity of antioxidant enzymes and the expression of antioxidant genes in both liver and muscle (P < 0.05). Additionally, SAL improved the meat quality and antioxidant capacity of breast subjected to repeated freeze-thaw treatment. SAL may enhance meat quality by improving antioxidative stability and regulating lipid metabolism, potentially serving as a dietary supplement for broilers.

Foam and fluid properties of purified saponins and non-purified water extracts from Camellia oleifera cake (by-product).

The physicochemical and foam properties of non-purified water extracts (WE) and purified tea saponins (TS) from Camellia oleifera cake (byproduct) were compared. WE showed different fluid properties at equal saponin concentrations (1.0 wt%) compared to TS. Particularly, it exhibited limited micelle size (average 434.1 nm), effective viscosity (0.15 Pa·s), and surface tension (43.9 mN/m) independently of pH. Moreover, the foam properties of WE were comparable to TS and better than sodium caseinate, especially foam stability. WE foam was more stable than TS foam under pH (3-7) and heating (40-80 °C). In the presence of NaCl, sucrose, and ethanol (5-20 wt%), WE and TS were effective and had similar foam behavior. Low concentrations of sucrose (<10 wt%)/ethanol (<20 wt%) significantly increased the foam capacity, while ethanol over 30 wt% was unfavorable. WE/TS foam contributes significantly to the desired physicochemical and sensory attributes (taste, texture, and appearance) of foods.

Synthesis and characterization of thermosensitive 2-hydroxypropyl-trimethylammonium chitin and its antibacterial sponge for noncompressible hemostasis and tissue regeneration.

Noncompressible hemorrhage is a leading cause of preventable death in battlefield/civilian trauma. The development of novel injectable and biodegradable hemostatic sponges, with rapid shape recovery and excellent antibacterial activity that can control hemorrhage in noncompressible bleeding sites and promote in situ tissue regeneration is still urgently needed. In this study, thermo/pH sensitive 2-hydroxypropyl-trimethylammonium chitins (QCHs) with low degree of quaternization substitution (DS: 0.07-0.23) and high degree of acetylation (DA: 0.91-0.94) were synthesized homogeneously for the first time. Their chemical compositions including DS and DA were characterized accurately by proton NMR for the first time. High strength QCH based sponges with good water/blood absorbency, rapid shape recovery and good antibacterial activity were prepared without using any crosslinkers but only due to their thermosensitive property, since they are soluble at low temperature but insoluble at high temperature. Compared with commercial products, the QCH sponges with cationic groups had the stronger pro-coagulant ability, better hemostatic effect in normal/heparinized liver perforation and femoral artery models in rats and porcine subclavian arteriovenous resection model. Moreover, the porous structure and biodegradability of the QCH sponges could promote in situ tissue regeneration. Overall, the QCH sponges show great clinical translational potential for noncompressible hemorrhage and tissue regeneration.

Construction and application of nano ZnO/eugenol@yam starch/microcrystalline cellulose active antibacterial film.

The goal of this study was to develop new biocomposite films that can better protect and prolong the shelf life of food. Here, a ZnO: eugenol@yam starch/microcrystalline cellulose (ZnO:Eu@SC) antibacterial active film was constructed. Because of the advantages of metal oxides and plant essential oils, codoping with these can effectively improve the physicochemical and functional properties of composite films. The addition of an appropriate amount of nano-ZnO improved the compactness and thermostability, reduced the moisture sensitivity, and enhanced the mechanical and barrier properties of the film. ZnO:Eu@SC exhibited good controlled release of nano-ZnO and Eu in food simulants. Nano-ZnO and Eu release was controlled by two mechanisms: diffusion (primary) and swelling (secondary). After loading Eu, the antimicrobial activity of ZnO:Eu@SC was significantly enhanced, resulting in a synergistic antibacterial effect. Z4:Eu@SC film extended the pork shelf life by 100 % (25 °C). In humus, the ZnO:Eu@SC film was effectively degraded into fragments. Therefore, the ZnO:Eu@SC film has excellent potential in food active packaging.

Effect of thawing under an alternating magnetic field on rainbow trout (Oncorhynchus mykiss) fillet characteristics.

Low thawing rates affects the quality of the product, which necessitates the use of new thawing technologies. In this study, the effect of alternating magnetic field (MF) (1-80 Hz) on the thawing rate, physicochemical properties, protein denaturation, and structure of rainbow trout fillet was studied and compared with refrigerator thawing (RT) (4 °C). Thawing time remarkably decreased in MF thawing as compared to RT. The results revealed that the water holding capacity of RT was significantly lower than that of MF, which was consistent with the results of structural investigation characterized by Scanning electron microscopy. Particle size distribution, Fourier transform infrared spectroscopy, and Differential scanning calorimetry indicated that MF could unfold and aggregate the protein structure at 40 and 80 Hz. The findings of this study indicated the potential of the MF in accelerating the thawing process. However, more studies are needed to clarify all aspects of the process.

Investigating the migration hypothesis: Effects of trypsin-like protease on the quality of muscle proteins of red shrimp (Solenocera crassicornis) during cold storage.

This study aimed to investigate the effect of trypsin-like protease (TLP) on the quality of muscle proteins in red shrimp (Solenocera crassicornis) during cold storage. The results indicated that the activity of TLP decreased significantly in the head of shrimp but increased significantly in the muscle tissues during the cold storage. The myofibril fragmentation index (MFI) value of intact shrimp was significantly higher than that of beheaded shrimp, while the Ca2+-ATPase activity of intact shrimp was significantly lower than that of beheaded shrimp. SDS-PAGE analysis showed that the molecular weight of purified TLP from the shrimp head was about 24 kDa, and the TLP showed high activity at 50 °C and pH 8, indicating that the TLP belongs to the trypsin family. Results from in vitro simulation experiments indicated that the process of TLP incubation significantly reduced the particle size and enlarged the distribution of myofibrillar proteins (MPs) in shrimp muscle tissues. The comparisons were made with respect to the control samples. It can be inferred that TLP migrated from the shrimp head to the muscle tissues during storage and thus promoted the degradation of MPs in red shrimp. The beheading treatment could be an effective mean to maintain better quality and extend the commercialization of shrimp products.

Preparation and structural properties of selenium modified heteropolysaccharide from the fruits of Akebia quinata and in vitro and in vivo antitumor activity.

Cancer is a complex disease, and blocking tumor angiogenesis has become one of the most promising approaches in cancer therapy. Here, an exopoly heteropolysaccharide (AQP70-2B) was firstly isolated from Akebia quinata. Monosaccharide composition indicated that the AQP70-2B was composed of rhamnose, glucose, galactose, and arabinose. The backbone of AQP70-2B consisted of →1)-l-Araf, →3)-l-Araf-(1→, →5)-l-Araf-(1→, →3,5)-l-Araf-(1→, →2,5)-l-Araf-(1→, →4)-d-Glcp-(1→, →6)-d-Galp-(1→, and →1)-d-Rhap residues. Based on the close relationship between selenium and anti-tumor activity, AQP70-2B was modified with selenium to obtain selenized polysaccharide Se-AQP70-2B. Then, a series of methods for analysis and characterization, especially scanning electron microscopy coupled with energy dispersive spectrometry (SEM-EDS), indicated that Se-AQP70-2B was successfully synthesized. Furthermore, zebrafish xenografts and anti-angiogenesis experiments indicated that selenization could improve the antitumor activity by inhibiting tumor cell proliferation and migration and blocking angiogenesis.

Improvements in the methodology for fatty acids analysis in meat products: One-stage transmethylation and fast-GC method.

The quantification of fatty acids (FA) in meat products is frequently carried out by two-stage methylation procedures followed by long gas chromatography (GC) runs. This work aimed to simplify this methodology by means of a one-stage transmethylation method and a fast GC run, evaluating the influence of sample preparation, reagents and type of heating on the amount of FA in different meat products and optimizing a fast GC-FID (flame ionization detector) run. This allowed to establish the optimum combination of parameters (methanol + chlorotrimethylsilane, lyophilized samples and oven heating) to achieve the quantification of the highest possible amount of FA and to reduce the time of GC run from 60 to 10 min. The quality evaluation of this method obtained satisfactory results. Thus, the quantification of FA in meat products was achieved in a straightforwardly and quickly way by using a one-stage transmethylation procedure followed by a fast GC-FID run.

Hydrophobic bonds-dominated key off-odors/silver carp myofibrillar protein interactions, and their binding characteristics at cold storage and oral temperatures.

This study revealed the interaction mechanism between silver carp myofibrillar protein (MP) and key off-odors by combining fluorescence spectroscopy with molecular dynamics (MD) simulation. Spectroscopic results exhibited a dynamic quenching mechanism between MP and off-odors. Thermodynamic analysis indicated that the MP/off-odors interaction was spontaneous (ΔG° < 0) and dominated by hydrophobic interactions (ΔH° > 0, ΔS° > 0). Meanwhile, the binding affinity was in the order of nonanal (n = 1.38) > hexanal (n = 0.89) > 1-octen-3-ol (n = 0.65), which was further verified by the MD results. Among off-odors, nonanal had the highest binding energy with myosin (8105.66 kJ/mol) and formed more hydrophobic binding sites to Trp residues in myosin head (e.g., Trp820 and Trp822), thereby changing myosin conformations via both physical and chemical interactions. Additionally, higher binding energies of myosin/off-odors were observed at oral temperature (37 °C) than at cold storage temperature (4 °C), implying that less off-odors were released at 37 °C.

Encapsulation of bioactives within electrosprayed κ-carrageenan nanoparticles.

In this study, an electrospray synthesis approach was utilized in which a solution mixture of a sensitive bioactive agent, d-limonene (DL, R-(+)-Limonene), and a nature-inspired polymer, κ-carrageenan (κC) was applied to design DL-κC nanoparticles (NPs) in a one step process. The engineered DL-κC NPs displayed spherical morphology and the maximum encapsulation efficiency of NPs was about 97 % by altering the mass ratio of DL to κC. The developed DL-κC NPs showed a pH-dependent release manner in vitro. Both photostability and thermostability of DL were promoted by increasing the κC concentration, and >85 % of the original DL could be preserved following 120 min of UV-light exposure in the NPs with 0.5 % κC. The results demonstrated that electrosprayed κC NPs are promising candidates for the design of high-loading pH-sensitive NPs for encapsulation of highly sensitive bioactive agents.

Carboxylated cellulose nanocrystal films with tunable chiroptical properties.

Carboxylated cellulose nanocrystals prepared by TEMPO-mediated oxidation exhibit a distinct ability to form nematic order, however, their ability to form chiral nematic films remains relatively unexplored. In this study, bleached cotton pulp hydrolyzed with hydrochloric acid and oxidized by TEMPO-mediated oxidation produce carboxylated cellulose nanocrystals with different aspect ratios 33.1, 32.8, 30.9, 29.0 and 28.9, and surface charge densities 0.16, 0.56, 1.00, 1.25, and 1.42 e·nm-2. By tuning the aspect ratio and surface charge density, the optimal carboxylated cellulose nanocrystals producing left-handed chiral nematic films by evaporation-induced self-assembly are obtained. The left-handed chiral nematic films enable selective reflection of left-handed circularly polarized light with the peak wavelength tunable from the visible to the near-infrared regime by modifying the characteristics of nanorods and suspensions. Such carboxylated cellulose nanocrystal films transform spontaneous luminescence to right-handed circularly polarized luminescence with the peak luminescence dissymmetry factor of -0.51.

Effect of lactic acid fermentation of watermelon juice on its sensory acceptability and volatile compounds.

Fermentation increases food shelf-life but is characterized by changes that affect product's perception. Watermelon juice was fermented with Lactobacillus plantarum (WJ-LP), L. rhamnosus (WJ-LR), L. casei (WJ-LC), L. brevis (WJ-LB) and Pediococcus pentosaceus (WJ-PP). Their sensory characteristics and volatile compounds were investigated by consumers and Headspace Solid Phase Microextraction integrated with Gas Chromatography-Mass Spectrometry, respectively. WJ-PP and WJ-LB were most liked and perceived with 'watermelon-flavor', 'natural taste', 'sweet' and 'watermelon-color' while WJ-LC, WJ-LP and WJ-LR were least liked and perceived as 'sour', 'bitter', 'off-flavor', 'aftertaste' and 'intense-flavor'. Fifty-four volatiles were identified. After fermentation, alcohols, ketones, monoterpenes, acids, and furans increased while aldehydes and alkanes decreased. Lactic acid fermentation introduced 4-decanone and 2,3-butanedione in WJ-LB, WJ-LC, WJ-LP and WJ-LR, however, heptanal, 2-heptenal, 2,6-nonadienal, 2-decenal, and 2,4-decadienal in WJ-LC, heptanal, 2-hexenal, 2-heptenal, 2,6-nonadienal, 2-decenal and octanal in WJ-LR and 2,6-dimethyl-2,6-octadiene in WJ-LP disappeared. Juice sensory profiles were associated with their volatile compounds.

The kinetics and release behaviour of curcumin loaded pH-responsive PLGA/chitosan fibers with antitumor activity against HT-29 cells.

The bioavailability and clinical effect of curcumin (Cur) are greatly restricted due to its physicochemical instability and high hydrophobicity. To overcome the disadvantages, the nanofibers of poly(lactide-glycolide)/chitosan loaded with Cur (PLGA/CS/Cur) was developed here by electrospinning technique for controlled Cur delivery. The incorporated Cur was well-dispersed and maintained crystalline form in PLGA/CS fiber matrix by hydrogen bonding. The incorporation of Cur had no obvious influence on the fiber size and morphology but exerted impacts on thermal stability. At pH 7.4, the release followed Fickian diffusion mechanism; while at pH 2.0, the release followed the coexistence of diffusion and erosion mechanisms. In addition, the amount of Cur released at pH 2.0 was much higher than that at pH 7.4. As a result, the nanofibers demonstrated higher anticancer activity at acidic environment. Therefore, the PLGA/CS/Cur nanofibers may be served as a potential pH responsive vehicle for the controlled drug delivery.

Vitamin D3 cress seed mucilage -ß-lactoglobulin nanocomplexes: Synthesis, characterization, encapsulation and simulated intestinal fluid in vitro release.

Vitamin D3 (VD3) as an essential lipid-soluble active ingredient with numerous applications in food and pharmaceutical sectors; however, poor water solubility reduces its bioavailability significantly. Application of protein-polysaccharide complexes as a promising way to protect and trigger programmed release of bioactive molecules has established an optimal window in nutraceutical delivery systems. In this study, complexes of ß-lactoglobulin (Blg) and cress seed mucilage (CSM) were used to retain VD3 at undesirable circumstances, such as acidic pH values. The interaction of CSM-Blg was studied by rheological tests and the best formulation was chosen for encapsulation of VD3 via crosslinking with calcium ions (2-10 mM). The results demonstrated that complexation protect VD3 at low pH values with the maximum encapsulation efficiency of 84.2 %. The in vitro study indicated that Blg-CSM-VD3 was more stable in simulated gastric fluid, and in turn VD3 was released in simulated intestinal fluid; the complexes treated with calcium ions had a slower release rate than normal complexes. The release trend of VD3 followed the diffusion-Fickian law and the principal interactions included hydrophobic, electrostatic and hydrogen bonding. The results indicated that Blg-CSM complexes can retain VD3 at acidic environment and induce sustained release, which brings about practical advantages for vitamin delivery in the food and pharmaceutical sectors.

Biotransformation of aflatoxin B1 by Lactobacillus helviticus FAM22155 in wheat bran by solid-state fermentation.

Lactobacillus helveticus FAM22155 was the most efficient among five lactic acid bacteria at removing aflatoxin B1 (AFB1) during solid-state fermentation on wheat bran substrate. The mechanism of removal was explored by comparing different fermentation modes. Liquid fermentation had little effect on the breakdown of AFB1. However, a protein extract from the fermented bran was equally effective at degrading aflatoxin B1 as living cell digestion. After treatment with heat and protease K, the degrading capacity of the protein extract was significantly reduced. Taken together, the observed biotransformation of AFB1 was mainly associated with proteins produced during bran fermentation. Four products of U-[13C17]-AFB1 were found by mass spectrometry, including Ⅱ-1 (C11H10O4), Ⅱ-2 (C11H10O4), III (C15H12O5), and IV (C14H10O4). These products all lack the lactone ring indicating lower toxicity than aflatoxin B1.

Effect of the apple cultivar on cloudy apple juice fermented by a mixture of Lactobacillus acidophilus, Lactobacillus plantarum, and Lactobacillus fermentum.

This study aimed to evaluate the fermentation performance of a mixture of Lactobacillus spp. in cloudy apple juices from nine cultivars. The results showed that cultivar influenced most the properties of the fermented cloudy apple juice. The fermented cloudy apple juices made from Changfu had the highest viable bacterial count and acetic acid contents (6.37 × 108 CFU/mL and 2.67 mg/mL, respectively). It also had higher sensory score, second only to Huaniu. The highest total sugar consumption, utilising fructose, glucose, and sucrose (33.07 mg/mL), was seen with Golden Delicious. Qinguan fermented cloudy apple juice had the highest contents of lactic acid (6.74 mg/mL) and total esters (921.36 µg/L); d-limonene also detected in this fermented cloudy apple juice. Of the nine cultivars examined in this study, Changfu, Qinguan, and Golden Delicious were the most suitable for producing fermented cloudy apple juice with better taste, higher viable count and more intense aroma.