Interfacial adsorption of soybean phosphatidylethanolamine in different oil phase and the stability of water-in-oil emulsion.

Water-in-oil (W/O) emulsion holds great potential in designing fat-reduced foods. However, due to the lack of W/O-type surfactant, formation of all-natural W/O emulsion is challenged. This study aimed to investigate the effect of oil phase on interfacial adsorption of soybean phosphatidylethanolamine (SP) and stability of W/O emulsion. Five oils, including medium chain triglycerides oil (MO), coconut oil (CO), palm kernel oil (PKO), sunflower oil (SO) and rapeseed oil (RO), were selected. Results showed that diffusion rate of SP to the interface ranked as MO > CO > PKO > SO ≈ RO, increasing interfacial adsorption from 50.2 % to 85.3 %. Higher interfacial adsorption improved the deformation resistance of interfacial layer, causing more significant decrease in interfacial tension (3.54 mN/m). So, the largest water fraction (65 %) was stabilized by SP with MO and CO, and exhibited smaller droplet sizes and better stability. Consequently, shorter-chain oil was more suitable for preparing W/O emulsions.

Evaluating the distinct pleiotropic effects of omega-3 fatty acids on type 2 diabetes mellitus: a mendelian randomization study.

BACKGROUND: Observational studies and conventional Mendelian randomization (MR) studies showed inconclusive evidence to support the association between omega-3 fatty acids and type 2 diabetes. We aim to evaluate the causal effect of omega-3 fatty acids on type 2 diabetes mellitus (T2DM), and the distinct intermediate phenotypes linking the two. METHODS: Two-sample MR was performed using genetic instruments derived from a recent genome-wide association study (GWAS) of omega-3 fatty acids (N = 114,999) from UK Biobank and outcome data obtained from a large-scale T2DM GWAS (62,892 cases and 596,424 controls) in European ancestry. MR-Clust was applied to determine clustered genetic instruments of omega-3 fatty acids that influences T2DM. Two-step MR analysis was used to identify potential intermediate phenotypes (e.g. glycemic traits) that linking omega-3 fatty acids with T2DM. RESULTS: Univariate MR showed heterogenous effect of omega-3 fatty acids on T2DM. At least two pleiotropic effects between omega-3 fatty acids and T2DM were identified using MR-Clust. For cluster 1 with seven instruments, increasing omega-3 fatty acids reduced T2DM risk (OR: 0.52, 95%CI 0.45-0.59), and decreased HOMA-IR (ß = - 0.13, SE = 0.05, P = 0.02). On the contrary, MR analysis using 10 instruments in cluster 2 showed that increasing omega-3 fatty acids increased T2DM risk (OR:1.10; 95%CI 1.06-1.15), and decreased HOMA-B (ß = - 0.04, SE = 0.01, P = 4.52 × 10-5). Two-step MR indicated that increasing omega-3 fatty acid levels decreased T2DM risk via decreasing HOMA-IR in cluster 1, while increased T2DM risk via decreasing HOMA-B in cluster 2. CONCLUSIONS: This study provides evidence to support two distinct pleiotropic effects of omega-3 fatty acids on T2DM risk influenced by different gene clusters, which could be partially explained by distinct effects of omega-3 fatty acids on insulin resistance and beta cell dysfunction. The pleiotropic feature of omega-3 fatty acids variants and its complex relationships with T2DM need to be carefully considered in future genetic and clinical studies.

Self-Assembled pH-Sensitive Polymeric Nanoparticles for the Inflammation-Targeted Delivery of Cu/Zn-Superoxide Dismutase.

The use of superoxide dismutase (SOD) is currently limited by its short half-life, rapid plasma clearance rate, and instability. We synthesized a small library of biofriendly amphiphilic polymers that comprise methoxy poly(ethylene glycol)-poly(cyclohexane-1,4-diyl acetone dimethyleneketal) (mPEG-PCADK) and mPEG-poly((cyclohexane86.7%, 1,5-pentanediol13.3%)-1,4-diyl acetone dimethylene ketal) (PK3) for the targeted delivery of SOD. The novel polymers could self-assemble into micellar nanoparticles with favorable hydrolysis kinetics, biocompatibility, long circulation time, and inflammation-targeting effects. These materials generated a better pH-response curve and exhibited better hydrolytic kinetic behavior than PCADK and PK3. The polymers showed good biocompatibility with protein drugs and did not induce an acidic microenvironment during degradation in contrast to materials such as PEG-block-poly(lactic-co-glycolic acid) (PLGA) and PLGA. The SOD that contained reverse micelles based on mPEG2000-PCADK exhibited good circulation and inflammation-targeting properties. Pharmacodynamic results indicated exceptional antioxidant and anti-inflammatory activities in a rat adjuvant-induced arthritis model and a rat peritonitis model. These results suggest that these copolymers are ideal protein carriers for targeting inflammation treatment.

Comparative Transcriptome Analysis Reveals Differentially Expressed Genes and Signaling Pathways Between Male and Female Red-Tail Catfish (Mystus wyckioides).

Sexual dimorphism is widespread in fish species. The red-tail catfish (Mystus wyckioides) is a commercially important catfish in the lower reaches of the Lancang River and the Mekong basin, and it shows a growth advantage in males. Here, RNA-seq was for the first time used to explore the gene expression difference between the sexes in the hypothalamus and pituitary of red-tail catfish, respectively. In the hypothalamus, 5732 and 271 unigenes have significantly higher and lower expressions, respectively, in males compared with females. KEGG analysis showed that 212 DEGs were annotated to 216 signaling pathways, and enrichment analysis suggested different levels of cAMP and glutamatergic synapse signaling between male and female hypothalami and some of the DEGs appear involved in gonad development and growth. In the pituitary, we found only 19 differentially expressed unigenes, which were annotated to 32 signaling pathways, most of which play important roles in gonad development.

Clinical phenotype, in silico and biomedical analyses, and intervention for an East Asian population-specific c.370G>A (p.G124S) COQ4 mutation in a Chinese family with CoQ10 deficiency-associated Leigh syndrome.

COQ4 mutations have recently been shown to cause a broad spectrum of mitochondrial disorders in association with CoQ10 deficiency. Herein, we report the clinical phenotype, in silico and biochemical analyses, and intervention for a novel c.370 G > A (p.G124S) COQ4 mutation in a Chinese family. This mutation is exclusively present in the East Asian population (allele frequency of ~0.001). The homozygous mutation caused CoQ10 deficiency-associated Leigh syndrome with an onset at 1-2 months of age, presenting as respiratory distress, lactic acidosis, dystonia, seizures, failure to thrive, and detectable lesions in the midbrain and basal ganglia. No renal impairment was involved. The levels of CoQ10 and mitochondrial respiratory chain complex (C) II + III activity were clearly lower in cultured fibroblasts derived from the patient than in those from unaffected carriers; the decreased CII + III activity could be increased by CoQ10 treatment. Follow-up studies suggested that our patient benefitted from the oral supplementation of CoQ10, which allowed her to maintain a relatively stable health status. Based on the genetic testing, preimplantation and prenatal diagnoses were performed, confirming that the next offspring of this family was unaffected. Our cases expand the phenotypic spectrum of COQ4 mutations and the genotypic spectrum of Leigh syndrome.

Dual-functional lipid polymeric hybrid pH-responsive nanoparticles decorated with cell penetrating peptide and folate for therapy against rheumatoid arthritis.

Methotrexate (MTX), as a disease modifying antirheumatic drug (DMARD), was first line drug to treat rheumatoid arthritis. However, the severe side effect during long term and high dosage usage limit its application. The aim of this study was to develop dual-functional lipid polymeric hybrid pH-responsive nanoparticles to deliver MTX to inflamed joints selectively. The designed MTX loaded stearic acid-octa-arginine and folic acid decorated poly lactic-co-glycolic acid (PLGA) -PK3-based lipid polymeric hybrid nanoparticles (Sta-R8-FA-PPLPNs/MTX) were composed of PK3, Folate-PEG-PLGA, egg PC, and Sta-R8. The nanoparticles exhibited smooth spherical morphology and particle size of 100-150 nm. The in vitro release study indicated that MTX was released faster in phosphate buffered solution (PBS) of pH 5.0 than that in PBS of pH 7.4 from Sta-R8-FA-PPLPNs/MTX. The cellular uptake study revealed that Sta-R8-FA-PPLPNs/MTX were internalized through folate receptor mediated endocytosis into activated macrophages. Therapeutic effects on adjuvant-induced arthritis (AIA) rats further confirm that Sta-R8-FA-PPLPNs/MTX could be promising against rheumatoid arthritis.

Investigation of hypoglycemic, hypolipidemic and anti­nephritic activities of Paecilomyces tenuipesN45 in diet/streptozotocin­induced diabetic rats.

Due to its pharmacological activities, Paecilomyces tenuipes has previously been used as a folk medicine in Asia. The primary aim of the present study was to investigate the hypoglycemic, hypolipidemic and anti­nephritic effects of P. tenuipes N45 aqueous extracts (PTNE) in a high fat diet/streptozotocin­induced diabetic rat model. The rats were treated with 120 mg/kg of metformin or 0.04, 0.2 or 1.0 g/kg PTNE for 4 weeks. The hypoglycemic activity of PTNE was confirmed by the observation of reduced fasting blood glucose level and by partially normalized oral glucose tolerance. PTNE reduced total cholesterol and triglyceride content, and balanced the levels of low­density and high­density lipoproteins. The suppressive effects of PTNE on creatinine, blood urea nitrogen, interleukin (IL)­2, IL­6 and nuclear factor­κB levels indicated its ability to provide protection against diabetic nephropathy. PTNE treatment increased superoxide dismutase, malondialdehyde and glutathione peroxidase levels, suggesting that its anti­diabetic and anti­nephropathic activities may be associated with the prevention of oxidative damage during type 2 diabetic mellitus. The findings of the present study provided experimental evidence for the application of Paecilomyces tenuipes N45 on the treatment of type 2 diabetic mellitus.

A comparative transcriptome and proteomics analysis reveals the positive effect of supplementary Ca(2+) on soybean sprout yield and nutritional qualities.

UNLABELLED: Effects of Ca(2+) on yield and nutritional qualities of soybean sprout were investigated. Ca-treated sprouts had higher yield than water-treated ones. Metabolism of selected storage materials and bioactive substances in soybean sprouts was strengthened by Ca(2+). The phytic acid and saponin content of Ca-treated soybean sprouts were lower than those of control. Supplemental Ca(2+) increased content of gamma-aminobutyric acid, isoflavones, phenolics, and vitamins, respectively. These findings indicate that supplemental Ca(2+) can increase soybean sprout yield and improve its nutritional qualities. The comparative transcriptome and proteomics between water-treated and Ca-treated soybean sprouts were studied. As consequence 1912 genes and 460 proteins were up- or down-regulated after 4days of Ca(2+) treatment. The functional classification of these differentially expressed genes and proteins indicated their connection with primary/secondary metabolic pathways, ion transport, signal transduction, and transcriptional regulation. The results obtained here will enable to understand how changes in yield and nutritional quality are regulated by extra Ca(2+) in soybean sprouts. BIOLOGICAL SIGNIFICANCE: In this study, a total of 1912 genes and 460 proteins involved in the growth, storage material decomposition, and bioactive substance synthesis in soybean sprouts after treated with Ca(2+) were identified. This is the first report of a comprehensive transcriptomic and proteomic analysis of soybean sprout in response to supplemental Ca(2+).

Anti-diabetic activities of Paecilomyces tenuipes N45 extract in alloxan-induced diabetic mice.

Due to the limitations of existing anti-diabetic drugs, the treatment of diabetes mellitus remains a significant challenge. The present study aimed to investigate the hypoglycemic, hypolipidemic and antioxidant effects of Paecilomyces tenuipes N45 extracts on alloxan-induced type I diabetes mellitus in mice. Diabetic Kunming mice were orally administered with water extract (WE) at doses of 2.50, 0.25 and 0.05 g/kg) or alcohol extract (AE) at doses of 2.00, 0.20 and 0.04 g/kg, for 3 weeks, following which the levels of factors associated with blood glucose, lipids and free radicals were determined. The anti-diabetic activities of AE and WE were further confirmed via an oral glucose tolerance test. Similar to the effects of metformin, Paecilomyces tenuipes N45 extracts led to a significant reduction in blood glucose levels, increase in serum insulin concentration and normalization in the densities of low-density lipoprotein cholesterol and high density lipoprotein cholesterol. The Paecilomyces tenuipes N45 extracts exerted antioxidative effects, indicated by regulation in the levels of superoxide dismutase, malondialdehyde and glutathione peroxidase. Taken together, the results of the present study demonstrated that Paecilomyces tenuipes N45 extract, a safe pharmaceutical agent, exerted anti-diabetic and anti-nephropathic activities and, thus, offers potential as a novel therapeutic agent in the treatment of diabetes.

Investigation of the antidepressant effects of exopolysaccharides obtained from Marasmius androsaceus fermentation in a mouse model.

Marasmius androsaceus, a well­known medical fungus, possesses antihypertensive, analgesic and antioxidant effects. Exopolysaccharide (EPS), produced by microorganism secretion, exerts various types of biological activities. The present study aimed to investigate the antidepressant­like effect of the EPS produced during Marasmius androsaceus submerge fermentation (MEPS). Based on the assessment of acute toxicity and behavior, a forced swimming test (FST), tail suspension test (TST), 5­hydroxytryptophan­induced head­twitch assessment and reserpine­induced hypothermia assessment were performed. The administration of MEPS for 7 days enhanced mouse locomotor and balance ability in the mice. Similar to the results following treatment with fluoxetine, which was used as positive control drug, MEPS significantly decreased the duration of immobility in the FST and TST, increased head twitches in the 5­HTP­induced head­twitch test and enhanced rectal temperature in resperpine­induced hypothermia. MEPS altered the abnormal concentrations of 5­hydroxytryptamine, 5­hydroxyindoleacetic acid, dopamine and norepinephrine in the hypothalamus in the resperine­induced mouse model. Additionally, an increase in the expression of tyrosine hydroxylase and a reduction in the level of dopamine transporter in the hypothalamus were noted following 7 days of MEPS administration. Taken together, the EPS produced during MEPS exhibited antidepressant­like effects, which may be associated with its regulation on the dopaminergic system. The results of the present study provide experimental evidence supporting the clinical use of MEPS as an effective agent against depression.

Acute and subchronic toxicity studies on safety assessment of Paecilomyces tenuipes N45 extracts.

Paecilomyces tenuipes, one of the commonly used Chinese medicinal fungus, has received much attention over the world, which possesses various active compounds and biological activities. However, little toxicological information is available. Therefore, the present study evaluated the potential toxicity of aqueous and ethanol extracts of Paecilomyces tenuipes N45 via acute and subchronic administration in mouse and rat, respectively. For improving the extraction rate of aqueous extract, response surface methodology (RSM) was employed to optimize the extraction condition first in this paper. The obtained optimal extract conditions were temperature 80 °C, liquid-solid ratio 50 mL·g-1 and time 3 h. In the acute toxicity test, aqueous and ethanol extracts caused neither mortality nor toxicological signs, and the maximum tolerance dose was estimated over 15 g/kg. No mortality or adverse effects was observed in subchronic toxicity studies. No significant difference in bodyweight, relative organ weight or hematological parameters was noted during the experiment. Comparing with nontreated rats, ALT, K and BUN levels were changed in experimental group detecting via biochemical analysis. No abnormality of internal organs was noted between treatment and control groups in gross and histopathological examinations. Our present study suggested that the tolerance dose of the Paecilomyces tenuipes N45 extracts were more than 15 g/kg and no-observed-adverse-effect level (NOAEL) of the extracts for both male and female rats after 90-day adminstation. Additionally, the extracts may possess renal-protective and hepato-protective effects.

Studies on the regulatory effect of Peony-Glycyrrhiza Decoction on prolactin hyperactivity and underlying mechanism in hyperprolactinemia rat model.

Clinical trials have demonstrated the beneficial effects of Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL) in schizophrenic patients. In previous experiment, PGD suppressed prolactin (PRL) level in MMQ cells, involving modulating the expression of D2 receptor (DRD2) and dopamine transporter (DAT). In the present study, hyperPRL female rat model induced by dopamine blocker metoclopramide (MCP) was applied to further confirm the anti-hyperpPRL activity of PGD and underlying mechanism. In MCP-induced hyperPRL rats, the elevated serum PRL level was significantly suppressed by either PGD (2.5-10 g/kg) or bromocriptine (BMT) (0.6 mg/kg) administration for 14 days. However, in MCP-induced rats, only PGD restored the under-expressed serum progesterone (P) to control level. Both PGD and BMT administration restore the under-expression of DRD2, DAT and TH resulted from MCP in pituitary gland and hypothalamus. Compared to untreated group, hyperPRL animals had a marked reduction on DRD2 and DAT expression in the arcuate nucleus. PGD (10 g/kg) and BMT (0.6 mg/kg) treatment significant reversed the expression of DRD2 and DAT. Collectively, the anti-hyperPRL activity of PGD associates with the modulation of dopaminergic neuronal system and the restoration of serum progesterone level. Our finding supports PGD as an effective agent against hyperPRL.

Parenteral thermo-sensitive organogel for schizophrenia therapy, in vitro and in vivo evaluation.

Novel biodegradable in situ forming organogel, obtained via the self-assembly of long chain fatty acid in pharmaceutical oil, was prepared and characterized. Different from traditional organogels, the use of organic solvent was avoided in this gel system, in consideration of its tissue irritation. Four kinds of fatty acids were employed as organogelators, which could successfully gel with injectable soybean oil. The gelation procedure was thermo-reversible. Phase transition temperature and time were depended on carbon chain length and concentration of gelators. Optimized formulations containing drug were then injected subcutaneously in rats for pharmacokinetic study. Results showed the steady drug release for one week with the well-controlled burst, which fitted well with the drug release mechanism of both drug diffusion and frame erosion. In vivo imaging of the organogel with fluorescence in live animals suggested that the organogel matrix was gradually absorbed and completely up-taken in nine days. Histopathological analysis of the surrounding tissues was carried out and revealed an overall good biocompatibility property of the implants over drug release period. This research demonstrates that this thermo-sensitive in situ forming organogel system represents a potentially promising platform for sustained drug delivery.

Development of a novel niosomal system for oral delivery of Ginkgo biloba extract.

BACKGROUND: The aim of this study was to develop an optimal niosomal system to deliver Ginkgo biloba extract (GbE) with improved oral bioavailability and to replace the conventional GbE tablets. METHODS: In this study, the film dispersion-homogenization method was used to prepare GbE niosomes. The resulting GbE niosome suspension was freeze-dried or spray-dried to improve the stability of the niosomes. GbE-loaded niosomes were formulated and characterized in terms of their morphology, particle size, zeta potential, entrapment efficiency, and angle of repose, and differential scanning calorimetry analysis was performed. In vitro release and in vivo distribution studies were also carried out. RESULTS: The particle size of the optimal delivery system prepared with Tween 80, Span 80, and cholesterol was about 141 nm. There was a significant difference (P < 0.05) in drug entrapment efficiency between the spray-drying method (about 77.5%) and the freeze-drying method (about 50.1%). The stability study revealed no significant change in drug entrapment efficiency for the GbE niosomes at 4°C and 25°C after 3 months. The in vitro release study suggested that GbE niosomes can prolong the release of flavonoid glycosides in phosphate-buffered solution (pH 6.8) for up to 48 hours. The in vivo distribution study showed that the flavonoid glycoside content in the heart, lung, kidney, brain, and blood of rats treated with the GbE niosome carrier system was greater than in the rats treated with the oral GbE tablet (P < 0.01). No flavonoid glycosides were detected in the brain tissue of rats given the oral GbE tablets, but they were detected in the brain tissue of rats given the GbE niosomes. CONCLUSION: Niosomes are a promising oral system for delivery of GbE to the brain.