Correction: Pickering emulsions stabilized with a spirulina protein-chitosan complex for astaxanthin delivery.

Correction for 'Pickering emulsions stabilized with a spirulina protein-chitosan complex for astaxanthin delivery' by Ronggang Liu et al., Food Funct., 2023, 14, 4254-4266, https://doi.org/10.1039/D3FO00092C.

Orally administered dual-targeted astaxanthin nanoparticles as novel dietary supplements for alleviating hepatocyte oxidative stress.

The enhancement of bioavailability of food bioactive compounds as dietary supplements can be achieved through the development of targeted delivery systems. This study aimed to develop a novel dual-targeted delivery system for hepatocytes and mitochondria using phacoemulsification self-assembly. The delivery systems were engineered by modifying whey protein isolate (WPI) with galactose oligosaccharide (GOS) and triphenylphosphonium (TPP) to improve AXT transport to the liver and promote hepatic well-being. The dual-targeted nanoparticles (AXT@TPP-WPI-GOS) significantly reduced reactive oxygen species in in vitro experiments, thereby slowing down apoptosis. The AXT@TPP-WPI-GOS exhibited a prominent mitochondrial targeting capacity with a Pearson correlation coefficient of 0.76 at 4 h. In vivo pharmacokinetic experiments revealed that AXT@TPP-WPI-GOS could enhance AXT utilization by 28.18 ± 11.69%. Fluorescence imaging in mice demonstrated significantly higher levels of AXT@TPP-WPI-GOS accumulation in the liver compared to that of free AXT. Therefore, these nanoparticles hold promising applications in nutrient fortification, improving the bioavailability of AXT and supporting hepatic well-being.

Preparation of Lutein Nanoparticles by Glycosylation of Saccharides and Casein for Protecting Retinal Pigment Epithelial Cells.

Age-related macular degeneration (AMD), a leading cause of visual impairment in the aging population, lacks effective treatment options due to a limited understanding of its pathogenesis. Lutein, with its strong antioxidant properties and ability to mitigate AMD by absorbing ultraviolet (UV) rays, faces challenges related to its stability and bioavailability in functional foods. In this study, we aimed to develop delivery systems using protein-saccharide conjugates to enhance lutein delivery and protect adult retinal pigment epithelial (ARPE-19) cells against sodium iodate (NaIO3)-induced damage. Various saccharides, including mannose, galactose, lactose, maltose, dextran, and maltodextrin, were conjugated to casein via the Maillard reaction for lutein delivery. The resulting lutein-loaded nanoparticles exhibited small size and spherical characteristics and demonstrated improved thermal stability and antioxidant capacity compared to free lutein. Notably, these nanoparticles were found to be nontoxic, as evidenced by reduced levels of cellular reactive oxygen species production (167.50 ± 3.81, 119.57 ± 3.45, 195.15 ± 1.41, 183.96 ± 3.11, 254.21 ± 3.97, 283.56 ± 7.27%) and inhibition of the mitochondrial membrane potential decrease (58.60 ± 0.29, 65.05 ± 2.91, 38.88 ± 1.81, 42.95 ± 1.39, 23.52 ± 1.04, 25.24 ± 0.08%) caused by NaIO3, providing protection against cellular damage and death. Collectively, our findings suggest that lutein-loaded nanoparticles synthesized via the Maillard reaction hold promise for enhanced solubility, oral bioavailability, and biological efficacy in the treatment of AMD.

A bifunctional hepatocyte-mitochondrion targeting nanosystem for effective astaxanthin delivery to the liver.

A bifunctional hepatocyte-mitochondrion targeting nanosystem was prepared for astaxanthin by conjugating lactobionic acid (LA) and triphenylphosphonium-modified 2-hydroxypropyl-ß-cyclodextrin onto sodium alginate. Hepatocyte-targeting evaluation indicated that the fluorescence intensity of HepaRG cells treated with the bifunctional nanosystem increased 90.3%, which was greater than that (38.7%) of the LA-only targeted nanosystem. The Rcoloc was 0.81 for the bifunctional nanosystem in mitochondrion-targeting analysis, which was greater than that (0.62) of the LA-only targeted nanosystem. The reactive oxygen species (ROS) level of the astaxanthin bifunctional nanosystem treated group significantly reduced to 62.20%, lower than that of free astaxanthin (84.01%) and LA-only targeted group (73.83%). Mitochondrial membrane potential recovered 97.35% in the astaxanthin bifunctional nanosystem treated group while the LA-only targeted group recovered 77.45%. The accumulation of bifunctional nanosystem in liver increased by 31.01% compared to the control. These findings indicated that the bifunctional nanosystem was beneficial for astaxanthin delivery in the liver precision nutrition intervention.

Pickering emulsions stabilized with a spirulina protein-chitosan complex for astaxanthin delivery.

Astaxanthin (AXT) is a lipid-soluble carotenoid with good anti-oxidation, hepatic steatosis reduction, anti-inflammation, and intestinal microbiota regulation ability, whose poor stability and pH vulnerability limit its bioavailability. Spirulina protein (SP) derived from spirulina has good emulsifying ability with potential application in nutraceuticals, medicines, and cosmetics. In this study, Pickering emulsions were prepared using a SP-chitosan (CS) complex as an emulsifier. The particle size, zeta potential, and three-phase contact angle of the SP-CS complex with different SP to CS ratios were investigated. A mass ratio of 1 : 2.5 SP-CS complex showed a good emulsifying ability in preparing Pickering emulsion. A higher storage modulus and viscoelasticity were observed with higher SP-CS complex concentrations and oil fractions. The SP-CS Pickering emulsion significantly improved the stability of AXT in different environments. The lipid release rate and AXT bioavailability after digestion of 3 wt% SP-CS complex-stabilized Pickering emulsion reached 70.54 ± 1.59% and 36.60 ± 3.44%, respectively. The results indicated that the SP-CS complex could act as a Pickering emulsion stabilizer and had the potential to deliver protective hydrophobic AXT.

Protein coronas formed by three blood proteins and food-borne carbon dots from roast mackerel: Effects on cytotoxicity and cellular metabolites.

Food-borne carbon dots (FCDs) produced naturally during food thermal processing are one of important factors affecting human health. The FCDs will inevitably encounter blood proteins after oral administration and spontaneously form protein coronas. In this study, the interaction of three major blood proteins, including albumin, gamma globulin, and fibrinogen, with FCDs from roasted mackerel was investigated for the first time. The purpose of the research is to explore the effect of the protein corona on the biological effects of cytotoxicity and the metabolic response. The results showed that FCDs spontaneously bound to the three blood proteins, and the process involved the participation of multiple interaction forces. Three protein coronas attenuated FCD-mediated cell viability damage, oxidative stress, and mitochondrial membrane potential. Further metabolomics analysis showed that FCDs disrupted cellular carbohydrate, amino acid, and nucleotide metabolism and significantly affected the expression of six metabolic pathways in normal rat kidney cells. The protein corona alleviated the disorder of energy and substance metabolism pathways. However, the protein corona inevitably expands the range of affected metabolic responses. The results of this study are of great value in exploring the toxicity characteristics of FCDs and their protein coronas.

Preparation and Evaluation of Undaria pinnatifida Nanocellulose in Fabricating Pickering Emulsions for Protection of Astaxanthin.

Pickering emulsions stabilized from natural sources are often used to load unstable bio-active ingredients, such as astaxanthin (AXT), to improve their functionality. In this study, AXT-loaded Pickering emulsions were successfully prepared by 2,2,6,6-tetramethy-1-piperidine oxide (TEMPO)-oxidized cellulose nanofibers (TOCNFs) from Undaria pinnatifida. The morphology analysis showed that TOCNFs had a high aspect ratio and dispersibility, which could effectively prevent the aggregation of oil droplets. The stable emulsion was obtained after exploring the influence of different factors (ultrasonic intensity, TOCNFs concentration, pH, and ionic strength). As expected, AXT-loaded Pickering emulsions showed good stability at 50 °C and 14 days of storage. The results of simulated in vitro digestion showed that the emulsions exhibited higher release of free fatty acids (FFAs) and bioaccessibility of AXT than those in sunflower oil. Hence, our work brought new insights into the preparation of Pickering emulsions and their applications in protection and sustained, controlled release of AXT.

Change of Cell Toxicity of Food-Borne Nanoparticles after Forming Protein Coronas with Human Serum Albumin.

Nanoparticles (NPs) can form protein coronas with plasma proteins after entering the biological environment due to their surface adsorption ability. In this study, the effects of protein coronas of roast squid food-borne nanoparticles (FNPs) with human serum albumin (HSA) on the HepG-2 and normal rat kidney (NRK) cells were investigated. The hydrodynamic diameters of the HSA and HSA-FNPs were 8 and 13 nm, respectively. The cytotoxicity and cell membrane damage of FNPs to HepG-2 cells increased with the increase of roasting temperature. The presence of 4.78 × 10-3 mol/L FNPs increased the numbers of cellular necrosis and prolonged the G2 phase of the cell cycle. The formation of protein coronas of squid FNPs mitigated the autophagy phenomenon by FNPs on HepG-2 cells. Moreover, protein coronas reduced the mitochondrial membrane potential in the HepG-2 and NRK cells and the production of reactive oxygen species caused by FNPs. The abnormal contents of oxidative stress indicators such as glutathione, superoxide dismutase, malondialdehyde, and catalase in HepG-2 and NRK cells induced by FNPs were alleviated due to the presence of HSA. These results suggested that the protein coronas formed by HSA on FNPs mitigated the cytotoxicity compared with the bare FNPs, thus providing insights into the interaction of squid FNPs with HSA.

Nanocorona Formation between Foodborne Nanoparticles Extracted from Roast Squid and Human Serum Albumin.

Foodborne nanoparticles (FNPs) produced by roasting have attracted the attention of people, owing to their safety risk to body health. Herein, we reported the formation, physicochemical properties, elemental composition, biodistribution, and binding with human serum albumin (HSA) of FNPs extracted from roast squid. The results showed that the FNP size gradually decreased from 4.1 to 2.3 nm as the roasting temperature changed from 190 to 250 °C. The main component elements of FNPs are carbon, oxygen, and nitrogen, and the carbon and nitrogen contents of FNPs increased with the roasting temperature rising. The surface of FNPs contained hydroxyl, amino, and carboxyl functional groups. The FNPs can emit fluorescence in ultraviolet light and show excitation-dependent emission behavior. Furthermore, it was found that the FNPs derived from roast squid could be accumulated in the stomach, intestine, and brain of BALB/c mice after oral feeding. Static fluorescence quenching of HSA was found by the Stern-Volmer equation and ultraviolet-visible spectrum analysis after interaction with the FNPs. After the addition of FNPs, the α-helix content of HSA decreased and the morphological height of HSA increased, which indicated that the FNPs could cause structural changes in HSA. The atomic force microscopy characterization showed the formation of nanocorona between FNPs and HSA.

Structure-activity relationship (SAR) optimization of 6-(indol-2-yl)pyridine-3-sulfonamides: identification of potent, selective, and orally bioavailable small molecules targeting hepatitis C (HCV) NS4B.

A novel, potent, and orally bioavailable inhibitor of hepatitis C RNA replication targeting NS4B, compound 4t (PTC725), has been identified through chemical optimization of the 6-(indol-2-yl)pyridine-3-sulfonamide 2 to improve DMPK and safety properties. The focus of the SAR investigations has been to identify the optimal combination of substituents at the indole N-1, C-5, and C-6 positions and the sulfonamide group to limit the potential for in vivo oxidative metabolism and to achieve an acceptable pharmacokinetic profile. Compound 4t has excellent potency against the HCV 1b replicon, with an EC50 = 2 nM and a selectivity index of >5000 with respect to cellular GAPDH. Compound 4t has an overall favorable pharmacokinetic profile with oral bioavailability values of 62%, 78%, and 18% in rats, dogs, and monkeys, respectively, as well as favorable tissue distribution properties with a liver to plasma exposure ratio of 25 in rats.

Discovery of GSK837149A, an inhibitor of human fatty acid synthase targeting the beta-ketoacyl reductase reaction.

GSK837149A has been identified as a selective inhibitor of human fatty acid synthase (FAS). The compound was first isolated as a minor impurity in a sample found to be active against the enzyme in a high-throughput screening campaign. The structure of this compound was confirmed by NMR and MS studies, and evaluation of the newly synthesized molecule confirmed its activity against FAS. The compound and other analogs synthesized, all being symmetrical structures containing a bisulfonamide urea, act by inhibiting the beta-ketoacyl reductase activity of the enzyme. GSK837149A inhibits FAS in a reversible mode, with a K(i) value of approximately 30 nm, and it possibly binds to the enzyme-ketoacyl-ACP complex. Although initial results suggest that cell penetration for these compounds is impaired, they still can be regarded as useful tools with which to probe and explore the beta-ketoacyl reductase active site in FAS, helping in the design of new inhibitors.

Identification of novel isoform-selective inhibitors within class I histone deacetylases.

Histone deacetylases (HDACs) represent an expanding family of protein modifying-enzymes that play important roles in cell proliferation, chromosome remodeling, and gene transcription. We have previously shown that recombinant human HDAC8 can be expressed in bacteria and retain its catalytic activity. To further explore the catalytic activity of HDACs, we expressed two additional human class I HDACs, HDAC1 and HDAC3, in baculovirus. Recombinant HDAC1 and HDAC3 fusion proteins remained soluble and catalytically active and were purified to near homogeneity. Interestingly, trichostatin (TSA) was found to be a potent inhibitor for all three HDACs (IC50 value of approximately 0.1-0.3 microM), whereas another HDAC inhibitor MS-27-275 (N-(2-aminophenyl)-4-[N-(pyridin-3-methyloxycarbonyl)-aminomethyl]benzamide) preferentially inhibited HDAC1 (IC50 value of approximately 0.3 microM) versus HDAC3 (IC50 value of approximately 8 microM) and had no inhibitory activity toward HDAC8 (IC50 value >100 microM). MS-27-275 as well as TSA increased histone H4 acetylation, induced apoptosis in the human colon cancer cell line SW620, and activated the simian virus 40 early promoter. HDAC1 protein was more abundantly expressed in SW620 cells compared with that of HDAC3 and HDAC8. Using purified recombinant HDAC proteins, we identified several novel HDAC inhibitors that preferentially inhibit HDAC1 or HDAC8. These inhibitors displayed distinct properties in inducing histone acetylation and reporter gene expression. These results suggest selective HDAC inhibitors could be identified using recombinantly expressed HDACs and that HDAC1 may be a promising therapeutic target for designing HDAC inhibitors for proliferative diseases such as cancer.

Induction and superinduction of growth arrest and DNA damage gene 45 (GADD45) alpha and beta messenger RNAs by histone deacetylase inhibitors trichostatin A (TSA) and butyrate in SW620 human colon carcinoma cells.

Histone deacetylase (HDAC) inhibitors such as trichostatin (TSA) and butyrate have been shown to inhibit cancer cell proliferation, induce apoptosis and regulate the expression of genes involved in cell cycle. Although the precise mechanism underlying HDAC inhibitor-induced cell growth arrest is not fully understood, induction of cell cycle related genes such as p21(cip/waf), is thought to be important. Here we showed that in the SW620 human colon cancer cell line, TSA and butyrate induced the growth arrest and DNA damage gene 45alpha (GADD45alpha) and GADD45beta. Furthermore, GADD45beta and p21(cip/waf) messenger RNA were induced in the absence of protein synthesis, indicating that both genes were immediate target genes for TSA. Cyclohexamide and TSA super-induced the expression of GADD45alpha and beta, but not p21(cip/waf). Interestingly while mitogen-activated kinase (MEK) inhibitor PD98059 and p38 kinase inhibitor SB242235 were unable to affect GADD45 induction, two serine/threonine protein kinase inhibitors (H7 and H8) as well as curcumin completely blocked the super-induction. Concomitant to the inhibition of GADD45 induction, H7 and H8 also blocked TSA-induced apoptosis. Taken together, these results suggest that GADD45 induction may play important role in TSA-induced cellular effects.

Osmium-Promoted Electrophilic Substitution of Anisoles: A Versatile New Method for the Incorporation of Carbon Substituents.

A structurally and electronically diverse set of anisoles are dihapto-coordinated to the pi-base pentaammineosmium(II) and treated with a variety of carbon electrophiles (e.g. Michael acceptors, acetals). After deprotonation of a 4H-anisolium intermediate with a tertiary amine base, C(4)-substituted anisole complexes are isolated. The functionalized arenes are removed from the metal center either by mild heating or treatment with an oxidant (e.g. AgOTf, DDQ, CAN). The resulting substituted anisoles are isolated with yields ranging from 55-95%.