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2.
Opt Express ; 32(2): 2786-2803, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38297799

ABSTRACT

Here, a scheme for a controllable nonreciprocal phonon laser is proposed in a hybrid photonic molecule system consisting of a whispering-gallery mode (WGM) optomechanical resonator and a χ(2)-nonlinear WGM resonator, by directionally quantum squeezing one of two coupled resonator modes. The directional quantum squeezing results in a chiral photon interaction between the resonators and a frequency shift of the squeezed resonator mode with respect to the unsqueezed bare mode. We show that the directional quantum squeezing can modify the effective optomechanical coupling in the optomechanical resonator, and analyze the impacts of driving direction and squeezing extent on the phonon laser action in detail. Our analytical and numerical results indicate that the controllable nonreciprocal phonon laser action can be effectively realized in this system. The proposed scheme uses an all-optical and chip-compatible approach without spinning resonators, which may be more beneficial for integrating and packaging of the system on a chip. Our proposal may provide a new route to realize integratable phonon devices for on-chip nonreciprocal phonon manipulations, which may be used in chiral quantum acoustics, topological phononics, and acoustical information processing.

3.
Int J Biol Macromol ; 253(Pt 3): 126902, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37714233

ABSTRACT

Roselle is rich in an extensive diversity of beneficial substances, including phenolic acids, amino acids, anthocyanins, vitamins, and flavonoids. Herein, the chemical constituents in Roselle extract (RE) were identified by UPLC-DAD-QTOF-MS. Besides, its inhibitory effects on three digestive enzymes, i.e. α-amylase, α-glucosidase, and pancreatic lipase, were investigated in both in vitro and in vivo. Thirty-three constituents including hibiscus acid, 18 phenolic acids, 2 anthocyanins and 12 flavonoids were identified. The anthocyanins content in RE was 21.44 ± 0.68 %, while the contents of chlorogenic acids, rutin and quercetin were 17.76 ± 2.28 %, 0.31 ± 0.01 % and 0.32 ± 0.01 %, respectively. RE inhibited pancreatic lipase in a non-competitive way with an IC50 value of 0.84 mg/mL. Besides, it demonstrated a mixed-type inhibition on both α-glucosidase and α-amylase with IC50 values of 0.59 mg/mL and 1.93 mg/mL, respectively. Fluorescence quenching assays confirmed the binding of RE to the enzyme proteins. Furthermore, rats pre-treated with RE at doses of 50 and 100 mg/kg body weight (bwt) exhibited significant reductions in fat absorption and improvements in fat excretion through feces. Additionally, the in vivo study revealed that RE was effective in suppressing the increase of blood glucose after starch consumption, while its effects on maltose and sucrose consumption were relatively weak.


Subject(s)
Anthocyanins , Hibiscus , Rats , Animals , Hibiscus/chemistry , alpha-Glucosidases/metabolism , Enzyme Inhibitors/chemistry , Flavonoids/pharmacology , alpha-Amylases/chemistry , Lipase , Plant Extracts/chemistry , Gastrointestinal Agents , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry
4.
BMC Med Educ ; 23(1): 664, 2023 Sep 14.
Article in English | MEDLINE | ID: mdl-37710261

ABSTRACT

BACKGROUND: Simulation is an increasingly used novel method for the education of medical professionals. This study aimed to systematically review the efficacy of high-fidelity (HF) simulation compared with low-fidelity (LF) simulation or no simulation in advanced life support (ALS) training. METHODS: A comprehensive search of the PubMed, Chinese Biomedicine Database, Embase, CENTRAL, ISI, and China Knowledge Resource Integrated Database was performed to identify randomized controlled trials (RCTs) that evaluated the use of HF simulation in ALS training. Quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions version 5.0.1. The primary outcome was the improvement of knowledge and skill performance. The secondary outcomes included the participants' confidence and satisfaction at the course conclusion, skill performance at one year, skill performance in actual resuscitation, and patient outcomes. Data were synthesized using the RevMan 5.4 software. RESULTS: Altogether, 25 RCTs with a total of 1,987 trainees were included in the meta-analysis. In the intervention group, 998 participants used HF manikins, whereas 989 participants received LF simulation-based or traditional training (classical training without simulation). Pooled data from the RCTs demonstrated a benefit in improvement of knowledge [standardized mean difference (SMD) = 0.38; 95% confidence interval (CI): 0.18-0.59, P = 0.0003, I2 = 70%] and skill performance (SMD = 0.63; 95% CI: 0.21-1.04, P = 0.003, I2 = 92%) for HF simulation when compared with LF simulation and traditional training. The subgroup analysis revealed a greater benefit in knowledge with HF simulation compared with traditional training at the course conclusion (SMD = 0.51; 95% CI: 0.20-0.83, P = 0.003, I2 = 61%). Studies measuring knowledge at three months, skill performance at one year, teamwork behaviors, participants' satisfaction and confidence demonstrated no significant benefit for HF simulation. CONCLUSIONS: Learners using HF simulation more significantly benefited from the ALS training in terms of knowledge and skill performance at the course conclusion. However, further research is necessary to enhance long-term retention of knowledge and skill in actual resuscitation and patient's outcomes.


Subject(s)
High Fidelity Simulation Training , Humans , Computer Simulation , Educational Status , Randomized Controlled Trials as Topic
5.
Plant Foods Hum Nutr ; 78(2): 439-444, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37351712

ABSTRACT

Mung bean is a kind of legume commonly eaten by human. In the present study, a HPLC method for analyzing of two C-glycoside flavonoids, isovitexin and vitexin, in Mung bean was developed. Results showed that the flavonoids are mainly existed in Mung bean coat (MBC), while kernel contains very trace. The extraction of C-glycoside flavonoids from MBC was optimized. MBC extracts with isovitexin and vitexin contents of 29.0 ± 0.28% and 35.8 ± 0.19% were obtained with yield of 1.6 ± 0.21%. MBC extracts exhibited inhibitory activities on pancreatic lipase and α-glucosidase with IC50 values of 0.147 mg/ml and 0.226 mg/ml, respectively. The inhibitory kinetics revealed that MBC extracts showed mixed-type inhibition on these enzymes. Fluorescence quenching titration confirmed the binding of MBC extracts with the enzyme proteins. In vivo study revealed that pre-administration with MBC extracts significantly reduced the triglyceride absorption. Furthermore, it also improved postprandial hyperglycemia in rats through the inhibition of α-glucosidase.


Subject(s)
Fabaceae , Vigna , Rats , Humans , Animals , Flavonoids/pharmacology , Flavonoids/chemistry , Lipase , alpha-Glucosidases/metabolism , Vigna/metabolism , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Fabaceae/chemistry
6.
J Pharm Sci ; 112(12): 3056-3066, 2023 12.
Article in English | MEDLINE | ID: mdl-37356712

ABSTRACT

Luteolin loaded zein nanoparticles (Lut-ZNP) were prepared by using sodium caseinate as an electrostatic stabilizer. The formulation of the nanoparticles was optimized. Lut-ZNP were spray-dried, and the physicochemical properties were characterized by SEM, XRD, FT-IR and DSC. Then, the bioavailability of luteolin in rats was determined. Under the formulation of luteolin, zein and sodium caseinate with mass ratio of 1:5:15, the particle size, ζ-potential, encapsulation efficiency and loading efficiency of Lut-ZNP were 171.8 nm, -49.05 mV, 85.85% and 3.15%, respectively. Luteolin existed in the nanoparticles with amorphous form. Lut-ZNP exhibited good redispersibility in water after drying. Compared with free luteolin, the solubility, stability and release of luteolin in Lut-ZNP were greatly improved. Besides, the fecal excretion of luteolin in rats was significantly reduced after oral administration of Lut-ZNP. In addition to native luteolin, its metabolites including sulfate, glucuronidate and methylated glucuronidate were found in rat plasma. Lut-ZNP significantly increased the plasma concentrations of luteolin and its metabolites, and the bioavailability of luteolin was enhanced by 2.92 times.


Subject(s)
Nanoparticles , Zein , Rats , Animals , Zein/chemistry , Luteolin , Caseins/chemistry , Biological Availability , Spectroscopy, Fourier Transform Infrared , Nanoparticles/chemistry , Particle Size
7.
Microbiol Spectr ; 11(3): e0073323, 2023 06 15.
Article in English | MEDLINE | ID: mdl-37154775

ABSTRACT

As the α-subunit of the high-affinity receptor for the Fc portion of immunoglobulin E (FcεRIα), FcεRIα plays a central role in IgE-mediated allergic disorders and in the immunity and immunopathology of some parasitic infections. FcεRIα is specifically expressed on basophils and mast cells, but the mechanism that controls FcεRIα expression in these cells is poorly understood. In this study, we found that the natural antisense transcript (NAT) of FcεRIα (FCER1A-AS) is co-expressed with the sense transcript (FCER1A-S) in both interleukin (IL)-3-induced FcεRIα-expressing cells and in the high FcεRIα-expressing cell line MC/9. When FCER1A-AS is selectively knocked down by the CRISPR/RfxCas13d (CasRx) approach in MC/9 cells, the expression of both FCER1A-S mRNA and proteins is markedly decreased. Furthermore, FCER1A-AS deficiency was also found to be associated with a lack of FCER1A-S expression in vivo. Correspondingly, homozygous mice deficient in FCER1A-AS demonstrated a similar phenotype to FCER1A knockout mice in Schistosoma japonicum infection and in IgE-FcεRIα-mediated cutaneous anaphylaxis. Thus, we uncovered a novel pathway for the control of FcεRIα expression by its co-expressed natural antisense transcript. IMPORTANCE FcεRIα is responsible for high-affinity binding with the Fc portion of IgE, which is critical for IgE-dependent disease responses such as allergy responses and anti-parasite immunity. FcεRIα is expressed on a few cell types, including mast cells and basophils. Although the expression of FcεRIα is known to be promoted by the IL-3-GATA-2 pathway during its differentiation, the mechanism by which FcεRIα expression is maintained remains unknown. In this study, we discovered that a natural antisense transcript, FCER1A-AS, is co-expressed with the sense transcript. The presence of FCER1A-AS is essential for sense transcript expression in mast cells and basophils, but not for the differentiation of these cells through cis-regulation. Like FcεRIα knockout mice, mice lacking FCER1A-AS also exhibit reduced survival after Schistosoma japonicum infection and a lack of IgE-mediated cutaneous anaphylaxis. Thus, a novel pathway for regulating IgE-mediated allergic diseases through noncoding RNAs has been revealed.


Subject(s)
Anaphylaxis , RNA, Antisense , Receptors, IgE , Schistosomiasis japonica , Animals , Mice , Immunoglobulin E , Mice, Knockout , Receptors, IgE/genetics , Receptors, IgE/metabolism , RNA, Antisense/genetics , RNA, Antisense/metabolism
8.
Curr Res Food Sci ; 6: 100424, 2023.
Article in English | MEDLINE | ID: mdl-36618100

ABSTRACT

Lipase is a very important digestive enzyme for triglyceride absorption in vivo. The inhibitory activities of 26 dietary flavonoids, including flavone, flavanone, isoflavone and flavanol, on lipase were determined. Flavone exhibited stronger inhibitory activity than other types of flavonoids. Among them, luteolin exhibited the strongest inhibitory activity with IC50 value of 99 ± 11 µM, followed by quercetin and baicalein. The binding affinity of these flavonoids with lipase was investigated by fluorescence titration method. The binding affinity of flavones was stronger than flavanones, and was linearly positively correlated with their inhibitory activity. The binding of flavones on lipase caused the blue-shift of fluorescence, while flavanones caused red-shift. The analysis of structure-activity relationship of flavonoids on lipase revealed that the structure of C ring is very crucial. The hydrogenation of C2=C3 bond and the absence of C=O group in C ring both caused significant decrease of inhibitory activity. Besides, the hydroxylation on ring A and B of flavones increased the activity, while glycosylation weakened the activity. Molecular docking analysis confirmed that C2=C3 bond in C ring of flavones increases the π-conjugation and contributes to maintaining the planarity of flavonoid structure, which favour its Pi-Pi interaction with lipase.

9.
Crit Rev Food Sci Nutr ; 63(28): 9506-9518, 2023.
Article in English | MEDLINE | ID: mdl-35442837

ABSTRACT

Astilbin is a dihydroflavanol found in many plants and processed foods. Astilbin possesses multiple health-beneficial bioactivities and has received great attention. Hence, the natural source, physicochemical properties, biological activities and metabolism of astilbin are summarized in the present article. Engelhardia roxburghiana Wall. and Smilax glabra Roxb. are the main resource for astilbin purification because of high content. Because of chemical instability, astilbin amount in foods is dependent on the processing and storage conditions. The degradation of astilbin includes isomerization and decomposition. The interconversion of astilbin and its isomers occurs through a chalcone intermediates, which significantly affects the taste of wine during storage. Many factors such as temperature, pH, metal ions and food additives could affect the chemical stability of astilbin. Astilbin exhibits very novel selective immunosuppressive activity, which is not found in other compounds. The rhamnose moiety of astilbin is essential for this bioactivity. After digestion, astilbin was mainly absorbed and transported in circulatory blood in its intact form, and only one metabolite, 3'-O-methylastilbin, was found. Although having many bioactivities, astilbin faces the challenge of poor bioavailability. Some promising strategies were developed for improving its bioavailability, particularly through fabrication the zein nanoparticles.


Subject(s)
Flavonols , Nanoparticles , Isomerism , Biological Availability , Nanoparticles/chemistry , Food
10.
Molecules ; 27(21)2022 Nov 04.
Article in English | MEDLINE | ID: mdl-36364410

ABSTRACT

Chalcone-1-deoxynojirimycin heterozygote (DC-5), a novel compound which was designed and synthesized in our laboratory for diabetes treatment, showed an extremely strong in vitro inhibitory activity on α-glucosidase in our previous studies. In the current research, its potential in vivo anti-diabetic effects were further investigated by integration detection and the analysis of blood glucose concentration, blood biochemical parameters, tissue section and gut microbiota of the diabetic rats. The results indicated that oral administration of DC-5 significantly reduced the fasting blood glucose and postprandial blood glucose, both in diabetic and normal rats; meanwhile, it alleviated the adverse symptoms of elevated blood lipid level and lipid metabolism disorder in diabetic rats. Furthermore, DC-5 effectively decreased the organ coefficient and alleviated the pathological changes of the liver, kidney and small intestine of the diabetic rats at the same time. Moreover, the results of 16S rDNA gene sequencing analysis suggested that DC-5 significantly increased the ratio of Firmicutes to Bacteroidetes and improved the disorder of gut microbiota in diabetic rats. In conclusion, DC-5 displayed a good therapeutic effect on the diabetic rats, and therefore had a good application prospect in hypoglycemic drugs and foods.


Subject(s)
Chalcone , Chalcones , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Rats , Animals , Blood Glucose , Diabetes Mellitus, Experimental/pathology , 1-Deoxynojirimycin/pharmacology , 1-Deoxynojirimycin/therapeutic use , Chalcones/pharmacology , Chalcones/therapeutic use , Chalcone/pharmacology , Heterozygote , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Diabetes Mellitus, Type 2/drug therapy
11.
Biomed Pharmacother ; 150: 112959, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35430392

ABSTRACT

The metabolism, tissue distribution and excretion of taxifolin in rat after oral administration of taxifolin encapsulated zein-caseinate Nanoparticles (TZP) were studied. The isomerization of taxifolin in rat small intestine and colon was found. Besides isomers, 16 metabolites of taxifolin were identified in rat feces, plasma and urine by UPLC-QTOF-MS. In colon, taxifolin underwent the metabolism of hydration, dehydration and ring-fission through the gut microflora. The main metabolites of taxifolin found in plasma and urine were its sulfated, glucuronidated, and/or methylated products. The dynamic variation of taxifolin and its metabolites in tissues and urine were quantified by UPLC-QqQ-MS/MS. Taxifolin and its metabolites could be quickly absorbed and distributed in the tissues, and relatively low concentrations were found in the heart and brain. The feces excretion of taxifolin was determined by HPLC. The total excretion during 24 h was 2.83 ± 0.80% to its given does, and the maximum excretion was found during 8-10 h post administration. Compared with feces, the excretion of taxifolin and its metabolites in urine was much faster, and the total excretion was 1.96 ± 0.23% during 12 h.


Subject(s)
Quercetin , Tandem Mass Spectrometry , Administration, Oral , Animals , Chromatography, High Pressure Liquid , Quercetin/analogs & derivatives , Rats , Tissue Distribution
12.
Food Sci Biotechnol ; 31(1): 49-59, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35059229

ABSTRACT

Slowly digestible gorgon nut starch (GN-SDS) was prepared by heating-cooling treatment (HCT), meanwhile its morphological and structural features were characterized in detail by SEM, DSC, XRD and IR detection. The optimized parameters of GN-SDS processing were as following: starch milk (20%) was heated at 100 °C for 20 min, and then cooled under 4 °C for 24 h. Under the optimized parameters, the SDS content increased from 20.49 to 61.74%. GN-SDS showed typical SDS characteristics in in vivo digestion with a low postprandial blood glucose. SEM images suggested that GN-S particles changed from uniform regular polyhedron with smooth surface to irregular gravel-like particles with coarse surface and obvious layered structure inside after HCT. The results of SEM, DSC, XRD and IR determination indicated that HCT changed the granule morphology, interior structure, gelatinization temperature and crystal type (A to B-type) of GN-S, and therefore made it hard to be digested accordingly. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-01007-6.

13.
J Sci Food Agric ; 102(4): 1598-1608, 2022 Mar 15.
Article in English | MEDLINE | ID: mdl-34409603

ABSTRACT

BACKGROUND: Taxifolin is a natural dihydroflavonol found in many plants and health products. In the present study, its anti-obesity and gut microbiota modulating effects were studied. C57BL/6J mice were fed with a high-fat diet (HFD) supplemented with taxifolin (0, 0.5 and 1 mg mL-1 , respectively) in drinking water for 15 weeks. RESULTS: Taxifolin supplementation showed no influence on food and water intake. However, it decreased body weight gain, inhibited fat accumulation, and decreased total cholesterol and triacylglycerol level in mice liver. Taxifolin enhanced superoxide dismutase (SOD) activity in mice liver, which in turn protected the liver from lipid peroxidation damage. It also improved insulin resistance in obese mice. Metagenomic analysis of bacterial 16S rRNA demonstrated that HFD decreased gut microbiota diversity and caused dysbiosis. However, taxifolin improved the gut microbiota diversity and decreased the Firmicutes/Bacteroidetes ratio. In particular, it inhibited Proteobacteria from blooming, this being a signature of dysbiosis in gut microbiota. CONCLUSION: Taxifolin ameliorated the symptoms of obesity, hepatic steatosis, lipid peroxidation, insulin resistance, and gut microbiota dysbiosis in HFD fed C57BL/6J mice. © 2021 Society of Chemical Industry.


Subject(s)
Diet, High-Fat , Gastrointestinal Microbiome , Animals , Diet, High-Fat/adverse effects , Mice , Mice, Inbred C57BL , Obesity/drug therapy , Quercetin/analogs & derivatives , RNA, Ribosomal, 16S
14.
Mol Nutr Food Res ; 66(4): e2101002, 2022 02.
Article in English | MEDLINE | ID: mdl-34932880

ABSTRACT

SCOPE: Alzheimer's disease (AD) is a neurodegenerative disease with phenomena of cognitive impairments. Oxidative stress and cholinergic system dysfunction are two widely studied pathogenesis of AD. Dihydromyricetin (DMY) is a natural dihydroflavonol with many bioactivities. In this study, it is aimed to investigate the effects of DMY on cognitive impairment in d-galactose (d-gal) induced aging mice. METHODS AND RESULTS: Mice are intraperitoneally injected with d-gal for 16 weeks, and DMY is supplemented in drinking water. The results show that DMY significantly improves d-gal-induced cognitive impairments in novel object recognition and Y-maze studies. H&E and TUNEL staining show that DMY could improve histopathological changes and cell apoptosis in mice brain. DMY effectively induces the activities of catalase, superoxide dismutase and glutathione peroxidase, and reduces malondialdehyde level in mice brain and liver. Furthermore, DMY reduces cholinergic injury by inhibiting the activity of Acetylcholinesterase (AChE) in mice brain. In vitro studies show that DMY is a non-competitive inhibitor of AChE with IC50 value of 161.2 µg mL-1 . CONCLUSION: DMY alleviates the cognitive impairments in d-gal-induced aging mice partly through regulating oxidative stress and inhibition of acetylcholinesterase.


Subject(s)
Cognitive Dysfunction , Neurodegenerative Diseases , Acetylcholinesterase/adverse effects , Acetylcholinesterase/metabolism , Aging , Animals , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Flavonols , Galactose/adverse effects , Mice , Oxidative Stress
15.
Food Funct ; 12(20): 9784-9792, 2021 Oct 19.
Article in English | MEDLINE | ID: mdl-34533153

ABSTRACT

Three shell materials, lecithin (ZNP-L), chitosan (ZNP-CH) and sodium caseinate (ZNP-SC), were used to prepare core-shell zein nanoparticles. Astilbin was encapsulated as a model flavonoid to compare the influence of the shell materials on zein nanoparticles both in vitro and in vivo. The particle size was moderately increased by lecithin and sodium caseinate, but notably increased by chitosan. All the shell materials provided good redispersibility for the nanoparticles and significantly improved the colloidal stability. Chitosan and sodium caseinate significantly delayed and decreased the feces excretion of astilbin in rats, while lecithin exhibited a very weak effect. The results may be attributed to the difference in mucoadhesive properties between the shell materials. As a consequence, the bioavailability values of astilbin in rats were 18.2, 9.3 and 1.89 times increased through ZNP-CH, ZNP-SC and ZNP-L compared with that of free astilbin, respectively.


Subject(s)
Flavonoids/pharmacology , Flavonols/pharmacology , Nanocapsules/chemistry , Animals , Biological Availability , Caseins/chemistry , Chitosan/chemistry , Female , Flavonoids/chemistry , Flavonols/chemistry , Lecithins/chemistry , Rats , Rats, Sprague-Dawley
16.
Food Funct ; 12(16): 7440-7447, 2021 Aug 21.
Article in English | MEDLINE | ID: mdl-34195734

ABSTRACT

Bambusa multiplex cv Fernleaf (B. multiplex) is a species of bamboo. In the present study, B. multiplex leaf extract was prepared through the resin absorption/desorption procedure and analyzed by HPLC. C-Glycosyl flavonoids are the main constituents of B. multiplex extract, and the content of isoorientin and vitexin was 51.8 and 23.1 mg g-1, respectively. Besides, the extract exhibited inhibitory activities on pancreatic lipase and α-glucosidase with IC50 values of 0.91 and 1.16 mg mL-1, respectively. The extract could bind to pancreatic lipase and showed mixed-type inhibition. An in vivo study showed that pre-administration of B. multiplex extract significantly reduced the fat absorption in rats and increased fat excretion through feces. The change in the C-glycosyl flavonoid content in feces was the same as that in the triglyceride content. The inhibitory activity of B. multiplex leaf extract on pancreatic lipase was confirmed both in vitro and in vivo.


Subject(s)
Bambusa , Lipase/drug effects , Pancreas/drug effects , Plant Extracts/pharmacology , Animals , Chromatography, High Pressure Liquid , Flavonoids/pharmacology , Models, Animal , Rats
17.
J Sci Food Agric ; 101(9): 3862-3869, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33336364

ABSTRACT

BACKGROUND: Dihydromyricetin (DMY) is a natural dihydroflavonol with many bioactive effects. However, the physicochemical properties of DMY related to its bioavailability, especially its stability, are unclear. RESULTS: The effects of pH, temperature, metal ions and ascorbic acid (AA) on the stability of DMY were studied using high-performance liquid chromatography (HPLC). The bioavailability of DMY in the presence and absence of AA was compared. Dihydromyricetin was unstable in weak alkaline solutions, and the degradation was significantly accelerated in the presence of Cu2+ and Fe3+ . The degradation process followed the first-order kinetic model. The degradation rate constant (k) increased with increasing pH and temperature. The remaining DMY was only 49% of its initial concnentration after 4 h in simulated intestinal fluid (SIF) at 37 °C. However, by supplementing with AA, the degradation of DMY was rarely occured within 6 h. The solubility of DMY at pH 3-5 was about 750 µg mL-1 , slightly increasing to 853 µg mL-1 at pH 6. Pharmacokinetic studies showed that the bioavailability of DMY increased from 0.122% to 0.341% by supplementing with AA (10% of DMY). CONCLUSION: The degradation of DMY is one reason for its poor bioavailability. The presence of AA could significantly improve the stability of DMY, and further improve its bioavailability in rats. © 2020 Society of Chemical Industry.


Subject(s)
Ascorbic Acid/chemistry , Flavonols/chemistry , Flavonols/pharmacokinetics , Animals , Biological Availability , Chromatography, High Pressure Liquid , Drug Stability , Female , Flavonols/administration & dosage , Kinetics , Rats , Rats, Sprague-Dawley , Solubility
18.
Molecules ; 25(20)2020 Oct 15.
Article in English | MEDLINE | ID: mdl-33076319

ABSTRACT

Astilbin and neoastilbin are two flavonoid stereoisomers. In the present study, their solubility, stability, and bioavailability were compared in a rat. The results revealed that the water solubility of astilbin and neoastilbin was 132.72 µg/mL and 217.16 µg/mL, respectively. The oil-water distribution coefficient (log P) of astilbin and neoastilbin in simulated gastric fluid (SGF) was 1.57 and 1.39, and in simulated intestinal fluid (SIF) was 1.09 and 0.98, respectively. In SIF, about 78.6% astilbin remained after 4 h of incubation at 37 °C, while this value was 88.3% for neoastilbin. Most of the degraded astilbin and neoastilbin were isomerized into their cis-trans-isomer, namely neoisoastilbin and isoastilbin, respectively, and the decomposed parts were rare. For bioavailability comparison in a rat, an HPLC method for trace amounts of astilbin and neoastilbin determination in plasma was developed, and the pretreatment of plasma was optimized. A pharmacokinetic study showed that the absolute bioavailability of astilbin and neoastilbin in a rat showed no significant difference with values of 0.30% and 0.28%, respectively.


Subject(s)
Drugs, Chinese Herbal/chemistry , Flavonoids/chemistry , Flavonols/chemistry , Smilax/chemistry , Biological Availability , Drugs, Chinese Herbal/pharmacology , Humans , Solubility/drug effects
19.
Food Chem ; 330: 127245, 2020 Nov 15.
Article in English | MEDLINE | ID: mdl-32521399

ABSTRACT

Dihydromyricetin (DMY) encapsulated zein-caseinate nanoparticles (DZP) were fabricated by antisolvent method. The encapsulation and loading efficiency of DMY in DZP were 90.2% and 22.6% as determined by HPLC. DZP is spherical with particle size and ζ potential of 206.4 nm and -29.6 mV, respectively. Physicochemical characterization showed that DMY existed in amorphous form in DZP and its interaction with proteins was found. The fabrication of DZP significantly improved the stability of DMY. Besides, the diffusion rate of DMY in DZP was faster than its suspensions in both simulated gastric and intestinal fluid. The adhesion of DMY in mice gastrointestinal tract was also improved. Besides DMY itself, its methylated metabolites with further sulfation and glucuronide were identified in rat plasma by UPLC-QTOF-MS. UPLC-QqQ-MS/MS quantitative analysis showed that the oral bioavailability of DMY was 1.95 times enhanced. Besides, the concentration of DMY metabolites in plasma were all increased.


Subject(s)
Caseins/chemistry , Flavonols/chemistry , Nanoparticles/chemistry , Zein/chemistry , Animals , Biological Availability , Caseins/metabolism , Chromatography, High Pressure Liquid , Female , Flavonols/metabolism , Mice , Particle Size , Rats , Tandem Mass Spectrometry , Zein/metabolism
20.
Aging (Albany NY) ; 12(12): 12187-12205, 2020 06 16.
Article in English | MEDLINE | ID: mdl-32544882

ABSTRACT

Recent studies demonstrate that immune checkpoint inhibitor (ICI) therapy has achieved success in many types of advanced cancers including advanced hepatocellular carcinoma (HCC). However, ICI therapy is beneficial in only some HCC patients, suggesting that immune-responses are highly variable in HCCs. Therefore, understanding the immune status in HCC microenvironment will facilitate ICI immunotherapy and guide patient selection for the therapy. In this study, we first analyzed the expression profile of immune-modulating genes and their relationship with survival of HCC patients using the data downloaded from The Cancer Genome Atlas - Liver Hepatocellular Carcinoma (TCGA-LIHC) database, and found that the higher expressions of CD276 (B7-H3) and CD47 were significantly associated with poor survival. Then we identified 4 immune subtypes of HCCs with different survivals by using the combination expression of B7-H3 (or CD47) and CD8. Patients with B7-H3low/CD8high or CD47low/CD8high have the best survival while ones with B7-H3high/CD8low or CD47high/CD8low have the worst survival. The 4 immune subtypes were validated in another 72 HCC patients obtained from South China. In conclusion, our findings suggest that HCC patient prognosis is associated with immunophenotypes by T cell infiltration (CD8 expression) and the expression of the adaptive immune resistance gene (B7-H3 or CD47), and this immune classification system will facilitate HCC patient selection for ICI immunotherapy.


Subject(s)
B7 Antigens/metabolism , CD47 Antigen/metabolism , Carcinoma, Hepatocellular/immunology , Liver Neoplasms/immunology , T-Lymphocytes/metabolism , Adult , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , China/epidemiology , Datasets as Topic , Disease Progression , Female , Hepatectomy , Humans , Immunotherapy , Kaplan-Meier Estimate , Liver/immunology , Liver/pathology , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Male , Middle Aged , Patient Selection , Prognosis , RNA-Seq , Retrospective Studies , T-Lymphocytes/immunology , Tumor Microenvironment/immunology
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