•Compositionally equivalent liquid versus solid cocoa butter emulsion droplets were produced.•Particle size, shape, charge, melting, and polymorphism were similar with BC.•Degradation of encapsulated ...BC was similar between solid and liquid droplets.•Early in vitro digestive lipolysis and BC bioaccessibility were higher for the liquid droplets.
The impacts of lipid crystallinity on in vitro digestive lipolysis and bioaccessibility of encapsulated (0.1 wt%) beta-carotene (BC) were investigated for a 15 wt% cocoa butter emulsion prepared as crystalline (i.e. solid emulsions, SE & SE-BC) or undercooled (liquid emulsions, LE & LE-BC) droplets at 25 °C. Particle size distributions (D4,3 ∼0.7 μm), morphology (spherical), polymorphism (beta-V), thermal behavior (peak melting ∼30 °C), zeta potential (∼−44 mV) and BC degradation under accelerated lighting conditions were similarly extensive. Following exposure to simulated gastric conditions, duodenal hydrolysis and BC bioaccessibility were lower for SE-BC up to 2 h (P < 0.05). Ultimately, samples with both solid and liquid droplets were hydrolyzed extensively and BC bioaccessibility did not differ (P > 0.05). Therefore, for compositionally equivalent emulsions, lipid droplet solid state delayed digestive lipolysis and bioactive solubilization. These results help to clarify the role of lipid physical state on dietary lipid digestion and bioactive release.
Near 70% of hepatocellular carcinoma (HCC) recurrence is early recurrence within 2-year post surgery. Long non-coding RNAs (lncRNAs) are intensively involved in HCC progression and serve as ...biomarkers for HCC prognosis. The aim of this study is to construct a lncRNA-based signature for predicting HCC early recurrence.
Data of RNA expression and associated clinical information were accessed from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database. Recurrence associated differentially expressed lncRNAs (DELncs) were determined by three DEG methods and two survival analyses methods. DELncs involved in the signature were selected by three machine learning methods and multivariate Cox analysis. Additionally, the signature was validated in a cohort of HCC patients from an external source. In order to gain insight into the biological functions of this signature, gene sets enrichment analyses, immune infiltration analyses, as well as immune and drug therapy prediction analyses were conducted.
A 4-lncRNA signature consisting of AC108463.1, AF131217.1, CMB9-22P13.1, TMCC1-AS1 was constructed. Patients in the high-risk group showed significantly higher early recurrence rate compared to those in the low-risk group. Combination of the signature, AFP and TNM further improved the early HCC recurrence predictive performance. Several molecular pathways and gene sets associated with HCC pathogenesis are enriched in the high-risk group. Antitumor immune cells, such as activated B cell, type 1 T helper cell, natural killer cell and effective memory CD8 T cell are enriched in patients with low-risk HCCs. HCC patients in the low- and high-risk group had differential sensitivities to various antitumor drugs. Finally, predictive performance of this signature was validated in an external cohort of patients with HCC.
Combined with TNM and AFP, the 4-lncRNA signature presents excellent predictability of HCC early recurrence.
Early recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are deeply involved in HCC prognosis. In this study, we aimed to establish a ...prognostic lncRNA signature for HCC early recurrence.
The lncRNA expression profile and corresponding clinical data were retrieved from total 299 HCC patients in TCGA database. LncRNA candidates correlated to early recurrence were selected by differentially expressed gene (DEG), univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. A 25-lncRNA prognostic signature was constructed according to receiver operating characteristic curve (ROC). Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the performance of this signature. ROC and nomogram were used to evaluate the integrated models based on this signature with other independent clinical risk factors. Gene set enrichment analysis (GSEA) was used to reveal enriched gene sets in the high-risk group. Tumor infiltrating lymphocytes (TILs) levels were analyzed with single sample Gene Set Enrichment Analysis (ssGSEA). Immune therapy response prediction was performed with TIDE and SubMap. Chemotherapeutic response prediction was conducted by using Genomics of Drug Sensitivity in Cancer (GDSC) pharmacogenomics database.
Compared to low-risk group, patients in high-risk group showed reduced disease-free survival (DFS) in the training (p < 0.0001) and validation cohort (p = 0.0132). The 25-lncRNA signature, AFP, TNM and vascular invasion could serve as independent risk factors for HCC early recurrence. Among them, the 25-lncRNA signature had the best predictive performance, and combination of those four risk factors further improves the prognostic potential. Moreover, GSEA showed significant enrichment of "E2F TARGETS", "G2M CHECKPOINT", "MYC TARGETS V1" and "DNA REPAIR" pathways in the high-risk group. In addition, increased TILs were observed in the low-risk group compared to the high-risk group. The 25-lncRNA signature negatively associates with the levels of some types of antitumor immune cells. Immunotherapies and chemotherapies prediction revealed differential responses to PD-1 inhibitor and several chemotherapeutic drugs in the low- and high-risk group.
Our study proposed a 25-lncRNA prognostic signature for predicting HCC early recurrence, which may guide postoperative treatment and recurrence surveillance in HCC patients.
Currently, peripheral tissue distribution of cannabinoids after treatment is poorly understood. This pilot study sought to examine the early tissue distribution of major cannabinoids 30 minutes ...following an intraperitoneal injection of vehicle (1:9 Tween 80/SAL), and doses of THC (1 mg/kg) and CBD (5 mg/kg) that are feasible for human consumption in serum, adipose, brain, lung, liver, jejunum, and muscle of male Sprague-Dawley rats. The jejunum and adipose were most enriched in THC. Similarly, CBD was enriched in the jejunum and adipose but also the liver. In contrast, the brain had the lowest concentration of cannabinoids relative to other tissues. The liver had the greatest concentration of the THC metabolites, 11-OH-THC and COOH-THC, compared to all other tissues. Overall, these findings highlight broad tissue distribution and marked differences in tissue concentration not previously appreciated. Thus, as cannabinoid research continues to rapidly grow, consideration of the potential bioactive effects of these molecules in peripheral tissues is warranted in future studies.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Due to the lack of potent diagnosis and prognosis biomarkers and effective therapeutic targets, the ...overall prognosis of survival is poor in HCC patients. Circular RNAs (circRNAs) are a class of novel endogenous non-coding RNAs with covalently closed loop structures and implicated in diverse physiological processes and pathological diseases. Recent studies have demonstrated the involvement of circRNAs in HCC diagnosis, prognosis, development, and drug resistance, suggesting that circRNAs may be a class of novel targets for improving HCC diagnosis, prognosis, and treatments. In fact, some artificial circRNAs have been engineered and showed their therapeutic potential in treating HCV infection and gastric cancer. In this review, we introduce the potential of circRNAs as biomarkers for HCC diagnosis and prognosis, as therapeutic targets for HCC treatments and discuss the challenges in circRNA research and chances of circRNA application.
Metformin (MET), the most common medicine for type 2 diabetes (T2DM), improves insulin sensitivity by targeting the liver, intestine and other organs. Its impact on expression of the solute carrier (
...) transporter genes have not been reported in the mechanism of insulin sensitization. In this study, we examined
gene expression in the liver and colon of diet-induced obese (DIO) mice treated with MET by transcriptomic analysis. There were 939 differentially expressed genes (DEGs) in the liver of DIO mice
lean mice, which included 34
genes. MET altered 489 DEGs in the liver of DIO mice, in which 23 were
genes. Expression of 20 MET-responsive
DEGs was confirmed by qRT-PCR, in which 15
genes were altered in DIO mice and their expressions were restored by MET, including
,
,
,
,
,
,
,
,
,
,
,
,
and
. While, there were only 97 DEGs in the colon of DIO mice with 5
genes, whose expression was not restored by MET. The data suggest that more genes were altered in the liver over the colon by the high fat diet (HFD). There were 20
genes with alteration confirmed in the liver of DIO mice and 15 of them were restored by MET, which was associated with improvement of insulin sensitivity and obesity. The restoration may improve the uptake of glucose, amino acids, mannose, fructose, 1,5-anhydro-D-glucitol and bumetanide in hepatocytes of the liver of DIO mice. The study provides new insight into the mechanism of metformin action in insulin sensitization and obesity.
Type 2 transmembrane serine protease (TMPRSS2) is a new member of the serine proteases, and studies have shown that TMPRSS2 plays a role in the occurrence of prostate malignancies and is closely ...related to the occurrence of the coronavirus disease 2019 (COVID-19). However, the role of TMPRSS2 in prostatic adenocarcinoma (PRAD) remains largely unclear. To better explore its function in PRAD, we examined the expression level of TMPRSS2 in the GEO, tumor immune assessment resource (TIMER), as well as Oncomine databases and studied the association between TMPRSS2 and overall survival (OS) rates in the UALCAN and gene expression profiling interactive analysis (GEPIA) databases. In addition, we studied the correlation of the level of immune infiltration and markers of immune cell type in the TIMER database, analyzed the prognosis based on the expression level of TMPRSS2 in the related immune cell subsets, and determined the methylation profile of TMPRSS2 promoter by UALCAN database. Subsequently, we conducted a survival analysis and gene ontology (GO) pathway analysis in the TISID database and detected the expression of TMPRSS2 in the Human Protein Atlas (HPA) database. We also studied the protein-protein interaction (PPI) network of TMPRSS2 in the GENEMANIA database. Additionally, we used the microarray GSE56677 and GSE52920 to illustrate changes in TMPRSS2 expression in vivo and in vitro after severe acute respiratory syndrome-coronavirus (SARS-COV) infection, finding that expression of TMPRSS2 decreased after SARS-COV infection in vitro. The function of TMPRSS2 in the dataset was further verified by gene set enrichment analysis (GSEA). In conclusion, the expression of TMPRSS2 is significantly increased in PRAD, elevated TMPRSS2 is associated with immune infiltration, and prognosis is positively correlated. In addition, tumor tissue from COVID-19 patients with PRAD may be more susceptible to infection with SARS-COV-2, which may render the prognosis gets worse.
Systemic low-grade inflammation mechanistically links obesity to impairments in the metabolic processes central to the development of type 2 diabetes and cardiovascular disease. This phenomenon is ...promoted by digestion of a high-fat meal, whereas whole foods with proposed anti-inflammatory actions, such as apples, may be beneficial. Thus, the current studies aimed to assess the effects of acute and chronic consumption of whole apples on biomarkers of inflammation in overweight and obese adults.
Overweight or obese adults in otherwise good health were recruited. With n = 26 (17 female/9 male; mean age 45.5 ± 3.1 y; mean BMI 34.1 ± 0.2 kg/m2), a randomized, crossover trial was conducted to assess the effects of acute (one time) consumption of 3 whole Gala apples (∼200 g) on the 6 h postprandial inflammatory response (e.g., plasma gut-derived lipopolysaccharide (LPS), cytokines) to an oral fat tolerance test (1 g fat/kg body weight). Fasting and 4 h postprandial peripheral blood mononuclear cells (PBMCs) were also isolated from whole blood and stimulated with 10 ng/mL LPS for 24 h to measure secreted cytokines. With n = 46 (32 female/14 male; mean age, 46.2 ± 2.2 y; mean BMI 33.5 ± 0.8 kg/m2), a parallel-arm, randomized, controlled trial was conducted to assess the effects of chronic (6 week) consumption of 3 whole Gala apples per day (∼200 g) on fasting inflammatory markers.
Acute apple consumption decreased 4 h postprandial unstimulated (IL-1β, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein (MIP)-1β, TNF-α) and LPS-stimulated (IL-6, TNF-α) PBMC-secreted inflammatory cytokines (P < 0.05, n = 18). Similarly, chronic apple consumption decreased fasting unstimulated (IL-6) and LPS-stimulated (IL-6, INF-γ, TNF-α) PBMC-secreted inflammatory cytokines (P < 0.05; n = 16–18/group), as well as plasma IL-6 (P < 0.05, n = 22/group).
Both acute and chronic whole apple consumption may be an effective dietary strategy to mitigate the obesity-associated inflammation that precedes and exacerbates metabolic disease risk.
Ontario Ministry of Agriculture, Food & Rural Affairs; Ontario Apple Growers.
Long-chain omega-3 polyunsaturated fatty acids (LC-ω3 PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play key roles in physiological functions and disease prevention. ...The nutrient gap in meeting LC-ω3 intake recommendations in the U.S. and globally can be addressed by alternative sources of LC-ω3. This randomized, placebo-controlled, seamless phase I/II study evaluated the pharmacokinetics, safety, and efficacy of a transgenic LC-ω3-rich canola oil in healthy adults. Participants (
= 33/group) were randomized to receive low-, mid-, or high-dose of the LC-ω3-rich oil (providing 285, 570, or 1,140 mg LC-ω3 PUFA, respectively) or placebo (corn oil). After one dose, plasma ω3 (primary outcome) levels were assessed over a 72 h pharmacokinetic period. Whole blood and red blood cells (RBC) ω3 and serum cardiovascular biomarkers were assessed during a 16-week continuation period with daily supplementation. Compared to low-dose and placebo, high-dose group showed greater DHA AUC
and C
. A linear response was observed for DHA and EPA AUC
. Compared to placebo, high- and mid-dose groups showed increased whole blood DHA, EPA, α-linolenic acids (ALA) (high-dose only), omega-3 score, and omega-3 index after 4 weeks, and increased DHA and EPA in RBC after 16 weeks (
< 0.05). No changes in cardiovascular biomarkers were seen. Overall, this LC-ω3-rich oil demonstrated good DHA bioavailability and significantly improved short and long-term blood LC-ω3 profiles. Sixteen weeks of daily supplementation of the LC-ω3-rich oil was safe and well-tolerated.
In the previous work, a typical recurrent neural network termed Zhang neural network (ZNN) has been developed for various time-varying problems solving. Based on the previous work, by exploiting a ...special activation function (i.e., Li activation function), the resultant ZNN model is presented and investigated in this paper for online solution of time-varying linear matrix inequality (TVLMI). For such a Li-function activated ZNN (LFAZNN) model, theoretical results are provided to show its excellent computational performance on solving the TVLMI. That is, the presented LFAZNN model has the property of finite-time convergence. Comparative simulation results with two illustrative examples further substantiate the efficacy of the presented LFAZNN model for TVLMI solving.
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