All-in-one nanosponge with pluronic shell for synergistic anticancer therapy through effectively overcoming multidrug resistance in cancer.

Overexpression of P-glycoprotein (P-gp) on cancer cells is a major hurdle to effectively treat tumors with multidrug resistance (MDR). The current study aimed to explore anticancer drug and P-gp inhibitor delivery as a promising strategy to efficiently treat colorectal cancer with MDR. To this end, a multidrug-loaded all-in-one nanosponge (ANS) was developed to simultaneously deliver doxorubicin (DOX), paclitaxel (PTX), and the P-gp inhibitor tetrandrine (TET), referred to as DOX/PTX/TET@ANS, without chemical conjugation. ANS with high loading content and efficiency facilitated a pH-dependent and controlled release with different profiles. Compared to free drugs and DOX/PTX@ANS, DOX/PTX/TET@ANS exhibited more effective anticancer effects on P-gp-overexpressing colorectal cancer cells and solid tumor mouse xenografts, without major toxicity. Notably, ANS composed of pluronic shell induced in vitro P-gp inhibition compared to TET, implying a synergistic anticancer effect. These findings suggest that ANS can encapsulate multiple drugs to efficiently deliver chemotherapy, particularly in MDR tumors.

Effects of vitamin D2-fortified shiitake mushroom on bioavailability and bone structure.

Bioavailability and bone loss inhibitory effects of vitamin D2 derived from UV-irradiated shiitake mushroom were determined in vivo. The effect of the absence of ovaries on the bioavailability of vitamin D2 and bone structure was also investigated. Sham operated (sham) and ovariectomized (OVX) rats were divided in 3 groups according to their diets, i.e. control: only vitamin D-deficient diets; UV(X): vitamin D-deficient diets with non-irradiated mushroom powder; UV(O): vitamin D-deficient diets with irradiated mushroom powder. The obtained results showed that vitamin D2 from shiitake mushroom was able to increase bone mineral density and trabecular bone structure of femur bone as well as its bioavailability. The absence of estrogen induced adverse effects not only on bioavailability of vitamin D2 but also on trabecular bone. In conclusion, vitamin D2-fortified shiitake mushroom might help postmenopausal women increase vitamin D2 bioavailability and retard trabecular bone loss. Abbreviations: OVX: ovariectomized; 25(OH)D: 25-hydroxyvitamin D; 1,25(OH)2D: 1,25-dihydroxyvitamin D; BMD: bone mineral density; micro-CT: micro computed tomography; RSM: response surface methodology; RP-HPLC: Reverse phase-high performance liquid chromatography; MS/MS: tandem mass spectrometry; E2: estradiol; NTx: N-terminal telopeptide of type I collagen; BV/TV: bone volume/total volume; BS/BV: bone surface/bone volume; Tb.Th: trabecular thickness; Tb.Sp: trabecular separation.

Selective Production of p-Xylene from Dimethylfuran and Ethylene Over Tungstated Zirconia Catalysts.

p-Xylene (PX) is an important large-volume commodity chemical in the petrochemical industry. Therefore, research on producing PX from bio-mass-derived resources is a considerable interest in relation to future alternative technologies. Recently, a new potential route for the direct and selective production of bio-based PX was reported, referred to as the Diels-Alder cycloaddition of biomassderived 2,5-dimethylfuran (DMF) and ethylene followed by the dehydration of an intermediate. Here, we prepared tungstated zirconia (WOx-ZrO2) materials at different calcination temperatures and times as solid acid catalysts for PX production. From structural analyses and measurements of the surface acidity, the WOx-ZrO2 was found to be composed of mesopores with high surface acidity within the optimum calcination temperature and time range. This WOx-ZrO2 catalyst exhibited high catalytic activity upon the cycloaddition of DMF with ethylene as compared to commercial beta zeolite and previously reported silica-alumina catalysts.

Effect of Silica Content on Production of p-Xylene from Dimethylfuran/Ethylene Over Mesoporous SiO2­Al2O3 Catalysts.

Mesoporous SiO2­Al2O3 (SA) catalysts with different SiO2 contents were prepared, for the selective production of p-xylene from dimethylfuran/ethylene through the combination of cycloaddition and dehydrative aromatization reactions, by a co-precipitation method. For comparison, commercial SiO2­Al2O3 and ZSM-5 zeolites (Si/Al2 = 30, Si/Al2 = 80) were also employed as catalysts in the same reaction. The pore size of the catalysts played an important role in determining the catalytic performance in the production of p-xylene. Among the catalysts tested, the order of the yield and production rate of p-xylene was as follows: mesoporous SA > commercial SiO2­Al2O3 > commercial ZSM-5. In the mesoporous SA catalysts in particular, p-xylene yields showed a volcano-shaped trend with respect to the catalyst's SiO2 content. The SA-60 catalyst, with SiO2 = 52.3, showed the highest yield (75%) and production rate (57.7 mmol/g-cat · h) because of a catalyst structure with moderate pore size, which prevented side reactions.

Saccharomonopyrones A-C, New α-Pyrones from a Marine Sediment-Derived Bacterium Saccharomonospora sp. CNQ-490.

Intensive study of the organic extract of the marine-derived bacterium Saccharomonospora sp. CNQ-490 has yielded three new α-pyrones, saccharomonopyrones A-C (1-3). The chemical structures of these compounds were assigned from the interpretation of 1D, 2D NMR and mass spectrometry data. Saccharomonopyrone A (1) is the first α-pyrone microbial natural product bearing the ethyl-butyl ether chain in the molecule, while saccharomonopyrones B and C possess unusual 3-methyl and a 6-alkyl side-chain within a 3,4,5,6-tetrasubstituted α-pyrone moiety. Saccharomonopyrone A exhibited weak antioxidant activity using a cation radical scavenging activity assay with an IC50 value of 140 µM.

Reaction kinetics of substrate transglycosylation catalyzed by TreX of Sulfolobus solfataricus and effects on glycogen breakdown.

We studied the activity of a debranching enzyme (TreX) from Sulfolobus solfataricus on glycogen-mimic substrates, branched maltotetraosyl-ß-cyclodextrin (Glc4-ß-CD), and natural glycogen to better understand substrate transglycosylation and the effect thereof on glycogen debranching in microorganisms. The validation test of Glc4-ß-CD as a glycogen mimic substrate showed that it followed the breakdown process of the well-known yeast and rat liver extract. TreX catalyzed both hydrolysis of α-1,6-glycosidic linkages and transglycosylation at relatively high (>0.5 mM) substrate concentrations. TreX transferred maltotetraosyl moieties from the donor substrate to acceptor molecules, resulting in the formation of two positional isomers of dimaltotetraosyl-α-1,6-ß-cyclodextrin [(Glc4)2-ß-CD]; these were 6(1),6(3)- and 6(1),6(4)-dimaltotetraosyl-α-1,6-ß-CD. Use of a modified Michaelis-Menten equation to study substrate transglycosylation revealed that the kcat and Km values for transglycosylation were 1.78 × 10(3) s(-1) and 3.30 mM, respectively, whereas the values for hydrolysis were 2.57 × 10(3) s(-1) and 0.206 mM, respectively. Also, enzyme catalytic efficiency (the kcat/Km ratio) increased as the degree of polymerization of branch chains rose. In the model reaction system of Escherichia coli, glucose-1-phosphate production from glycogen by the glycogen phosphorylase was elevated ∼1.45-fold in the presence of TreX compared to that produced in the absence of TreX. The results suggest that outward shifting of glycogen branch chains via transglycosylation increases the number of exposed chains susceptible to phosphorylase action. We developed a model of the glycogen breakdown process featuring both hydrolysis and transglycosylation catalyzed by the debranching enzyme.

Introducing transglycosylation activity in Bacillus licheniformis α-amylase by replacement of His235 with Glu.

To understand the role of His and Glu in the catalytic activity of Bacillus licheniformis α-amylase (BLA), His235 was replaced with Glu. The mutant enzyme, H235E, was characterized in terms of its mode of action using labeled and unlabeled maltooctaose (Glc8). H235E predominantly produced maltotridecaose (Glc13) from Glc8, exhibiting high substrate transglycosylation activity, with Km=0.38mM and kcat/Km=20.58mM(-1)s(-1) for hydrolysis, and Km2=18.38mM and kcat2/Km2=2.57mM(-1)s(-1) for transglycosylation, while the wild-type BLA exhibited high hydrolysis activity exclusively. Glu235-located on a wide open groove near subsite +1-is likely involved in transglycosylation via formation of an α-1,4-glycosidic linkage and may recognize and stabilize the non-reducing end glucose of the acceptor molecule.

Fucoidan prevents high-fat diet-induced obesity in animals by suppression of fat accumulation.

This study examines the antiobesity effects of fucoidan in an animal model of diet-induced obesity. Mice were fed a standard diet or high-fat diet (HFD) for 5 weeks. After that, the mice were divided into four experimental groups, with 10 mice per group, including a standard diet group, HFD group, HFD containing 1% fucoidan (HFD + FUCO 1%) group and HFD containing 2% fucoidan (HFD + FUCO 2%) group. The fucoidan supplementation group had significantly decreased body-weight gain, food efficiency ratio and relative liver and epididymal fat mass compared with the HFD group. The mice supplemented with fucoidan showed significantly reduced triglyceride, total cholesterol and low-density lipoprotein levels in the plasma. Liver steatosis induced by the HFD improved in the fucoidan-supplemented group. Furthermore, fucoidan affected the down-regulation expression patterns of epididymal adipose tissue genes such as peroxisome proliferator-activated receptor γ, adipose-specific fatty acid binding protein and acetyl CoA carboxylase. Therefore, fucoidan may be considered for use in improving obesity.

Exosome Isolation Using Chitosan Oligosaccharide Lactate-1-Pyrenecarboxylic Acid-Based Self-Assembled Magnetic Nanoclusters.

Exosomes are small extracellular vesicles that play a crucial role in intercellular communication and offer significant potential for a wide range of biomedical applications. However, conventional methods for exosome isolation have limitations in terms of purity, scalability, and preservation of exosome structural integrity. To address these challenges, an exosome isolation platform using chitosan oligosaccharide lactate conjugated 1-pyrenecarboxylic acid (COL-Py) based self-assembled magnetic nanoclusters (CMNCs), is presented. CMNCs are characterized to optimize their size, stability, and interaction dynamics with exosomes. The efficiency of CMNCs in isolating exosomes is systematically evaluated using various analytical methods to demonstrate their ability to capture exosomes based on amphiphilic lipid bilayers. CMNC-based exosome isolation consistently yields exosomes with structural integrity and purity similar to those obtained using traditional methods. The reusability of CMNCs over multiple exosome isolation cycles underscores their scalability and offers an efficient solution for biomedical applications. These results are supported by western blot analysis, which demonstrated the superiority of CMNC-based isolation in terms of purity compared to conventional methods. By providing a scalable and efficient exosome isolation process that preserves both structural integrity and purity, CMNCs can constitute a new platform that can contribute to the field of exosome studies.

Phytochemical-Based Nanoantioxidants Stabilized with Polyvinylpyrrolidone for Enhanced Antibacterial, Antioxidant, and Anti-Inflammatory Activities.

Despite the inhibitory effect of phytoncide (Pht) on food-borne pathogenic bacterial growth, the hydrophobic nature and susceptibility to biodegradation under physiological conditions limits its applications. Here, we developed Pht-loaded polyvinylpyrrolidone (PVP) micelles (Pht@PVP MC) via micelle packing. Pht was solubilized using different types of PVP as micellar vehicles. The as-prepared Pht@PVP MCs were characterized using dynamic light scattering and transmission electron microscopy. The sizes of the Pht@PVP MCs were controlled from 301 ± 51 to 80 ± 3 nm by adjusting the PVP content. The polydispersity index of Pht@PVP MC was between 0.21 ± 0.03 and 0.16 ± 0.04, indicating homogeneous size. A colony-counting method was employed to evaluate the improvement in antibacterial activity after Pht encapsulation in PVP micelles. The reactive oxygen species (ROS)-scavenging activity and anti-inflammatory efficacy of Pht@PVP MC were analyzed in a concentration range of 10-100 µg/mL by evaluating in vitro ROS and nitric oxide levels using DCFDA and Griess reagents. PVP with both hydrophobic and hydrophilic moieties improved the aqueous solubility of Pht and stabilized it via steric hindrance. Higher-molecular-weight PVP at higher concentrations resulted in a smaller hydrodynamic diameter of Pht@PVP MC with uniform size distribution. The spherical Pht@PVP MC maintained its size and polydispersity index in a biological buffer for 2 weeks. Pht@PVP MC exhibited enhanced antibacterial activity compared to bare Pht. The growth of Staphylococcus aureus was effectively inhibited by Pht@PVP MC treatment. Furthermore, biocompatible Pht@PVP MC exhibited dose-dependent antioxidant and anti-inflammatory activities in vitro. Overall, Pht@PVP MC is an effective alternative to synthetic antibacterial, antioxidant, and anti-inflammatory chemicals.