An integrative approach for exploring the nature of fibroepithelial neoplasms.

BACKGROUND: Malignant phyllodes tumour (MPT) is a rare breast malignancy with epithelial and mesenchymal features. Currently, there are no appropriate research models or effective targeted therapeutic approaches for MPT. METHODS: We collected fresh frozen tissues from nine patients with MPT and performed whole-exome and RNA sequencing. Additionally, we established patient-derived xenograft (PDX) models from patients with MPT and tested the efficacy of targeting dysregulated pathways in MPT using the PDX model from one MPT. RESULTS: MPT has unique molecular characteristics when compared to breast cancers of epithelial origin and can be classified into two groups. The PDX model derived from one patient with MPT showed that the mouse epithelial component increased during tumour growth. Moreover, targeted inhibition of platelet-derived growth factor receptor (PDGFR) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) by imatinib mesylate and PKI-587 showed in vivo tumour suppression effects. CONCLUSIONS: This study revealed the molecular profiles of MPT that can lead to molecular classification and potential targeted therapy, and suggested that the MPT PDX model can be a useful tool for studying the pathogenesis of fibroepithelial neoplasms and for preclinical drug screening to find new therapeutic strategies for MPT

Quick Compact Model Development Through Slow Transient Simulation: An Alternative Approach to Table Models for Emerging Nanodevices

A transient simulation which proceeds slowly, compared to all dynamic processes, can be designed to generate a multi-dimensional quasistationary dataset. In order to characterize an electrical device/circuit, in this work we explore a simulation design based on frequency-nested cosine functions where before an array of quasistationary voltage sweeps was necessary. We present an example of 3 terminal voltages, each in the range of (–1V, 1V), to demonstrate how to plan granularity of a data set. Then we apply this example setup to a novel semiconductor device. Lastly, we present a method to verify if data from the respective transient simulation can indeed be interpreted as quasistationary data. The proposed methods are described in a generic mathematical way to allow transfer to other dynamic systems incorporating fluidic, mechanic or thermic processes

Hypouricemic Effects of Chrysanthemum indicum L. and Cornus officinalis on Hyperuricemia-Induced HepG2 Cells, Renal Cells, and Mice

Hyperuricemia, abnormally excess accumulation of uric acid, is caused by an imbalance between the production and excretion of uric acid and is a major cause of gout. We compared the effects of extracts from Chrysanthemum indicum L. (Ci) and Cornus officinalis Siebold and Zucc. (Co) on hyperuricemia, both individually and in combination (FSU-CC), using hypoxanthine-treated human liver cancer (HepG2) cells, primary mouse renal proximal tubule cells, and potassium oxonate induced hyperuricemic mice. The Ci contained 7.62 mg/g luteolin and 0 mg/g loganin, Co contained 0 mg/g luteolin and 4.90 mg/g loganin, and FSH-CC contained 3.95 mg/g luteolin and 2.48 mg/g loganin. We found that treatment with Ci, Co, and FSU-CC suppressed the activity of xanthine oxidase and mRNA expression of xanthine dehydrogenase while inducing an increase in the expression levels of the organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) proteins and a decrease in the expression levels of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) proteins. Particularly, treatment and supplementation with FSU-CC showed stronger effects than those of supplementation with either Ci or Co alone. We observed that the excretion of creatinine and uric acid in the combination of Ci and Co was higher than that observed in their individual supplementations and was similar to that of the normal group. Therefore, our data suggest that a combination of Ci and Co may potentially be used for the development of effective natural anti-hyperuricemic functional foods

Gastro-Protective Effect of Fermented Soybean (Glycine max (L.) Merr.) in a Rat Model of Ethanol/HCl-Induced Gastric Injury

The present research purposed to examine the gastro-protective effect of Glycine max (L.) Merr. fermented using Lactobacillus delbrueckii ssp. delbrueckii Rosell-187 (Gastro-AD®) on ethanol/HCl-induced gastric damage, specifically on gastric acid secretion. After oral supplementation of Gastro-AD® to Sprague–Dawley (SD) rats with ethanol/HCl-induced gastric damage, we determined that Gastro-AD® attenuated the gastric mucosal lesion, hemorrhage and gastric acid secretion induced by ethanol/HCl. In addition, we observed that the Gastro-AD® treatment increased the serum prostaglandin E2 level and decreased the levels of gastric acid secretion-related receptors in both gastric tissues and primary gastric parietal cells. Furthermore, it decreased the levels of inflammatory factors, including serum histamine and expression of p-IκB, p-p65, iNOS and COX-2 and the activity of apoptotic signaling pathways, including those involving p-JNK, Bcl2/Bax, Fas, FADD, caspase-8 and caspase-3, in the stomach of the ethanol/HCl-treated rats. Thus, we suggest that Gastro-AD® supplementation may reduce ethanol/HCl-induced gastric acid secretion and prevent gastric injury

Zingiber mioga Extract Improves Moisturization and Depigmentation of Skin and Reduces Wrinkle Formation in UVB-Irradiated HRM-2 Hairless Mice

Here, we investigated the effects of Zingiber mioga extracts (FSH-ZM) on the moisturization and depigmentation of skin as well as wrinkle formation in UVB-irradiated HRM-2 hairless mice. The mice were divided into six groups as follows: normal control (NC), UVB-irradiated control (C), positive control 1 (PC1, L-ascorbic acid 200 mg/kg b.w.), positive control 2 (PC2, Arbutin 200 mg/kg b.w.), Z100 (FSH-ZM 100 mg/kg b.w.), and Z200 (FSH-ZM 200 mg/kg b.w.). The experiment spanned a period of 6 weeks. We found that FSH-ZM led to an increase in the expression of hyaluronan synthase 2, fibrillin-1, and elastin mRNAs, and showed improved skin hydration in HRM-2 hairless mice compared to that in the UVB-irradiated control group. Furthermore, FSH-ZM also inhibited the expression of inflammatory cytokines and wrinkle forming factors generated by UVB and reduced the formation of wrinkles in the test group relative to that in the control group by increasing collagen synthesis. Moreover, we found that FSH-ZM decreased the expression of melanogenesis factors, which improved depigmentation in UVB-irradiated hairless mice. These results suggest that Zingiber mioga can potentially be utilized to develop products aimed at improving skin moisturization and depigmentation and reducing wrinkle formation

Antarctic Krill Oil Ameliorates Monosodium Iodoacetate-Induced Irregularities in Articular Cartilage and Inflammatory Response in the Rat Models of Osteoarthritis

The aim of this study was to examine the effects of Antarctic krill oil (FJH-KO) in a rat model of monosodium iodoacetate (MIA) induced osteoarthritis. The effect of FJH-KO on the development and severity of MIA-induced osteoarthritis was assessed using hematoxylin and eosin (H&E) staining and micro-CT. The expression of PGE2, pro-inflammatory cytokines (IL-1β, TNF-α), and arthritics related genes in osteoarthritic rats in response to FJH-KO supplementation was investigated using real time PCR. FJH-KO supplementation in the arthritic rat model reduced tissue damage, cartilage degeneration, and reduced the MIA-induced irregularities in articular cartilage surface. Serum PGE2, IL-1β, IL-6, and TNF-α levels were higher in MIA treated animals, but these levels decreased upon FJH-KO supplementation. When FJH-KO was provided at a dose of 150 mg/kg b.w to MIA-treated animals, it significantly increased the mRNA expression of anabolic factors. The mRNA expression of catabolic factors was significantly decreased MIA-treated animals that were provided FJH-KO at a dose of 100 and 150 mg/kg b.w. Moreover, the mRNA expression of inflammatory mediators was significantly decreased MIA-treated animals supplemented with FJH-KO. These results suggest supplementation with FJH-KO ameliorates the irregularities in articular cartilage surface and improves the inflammatory response in the osteoarthritis. Thus, FJH-KO could serve as a potential therapeutic agent for osteoarthritis treatment

Glucocerebroside-Containing Milk Concentrated Powder Suppresses Oxidative Stress and Photoaging in the Skin of Hairless Mice

This study investigated the protective effects of glucocerebroside-containing buttermilk concentrated powder (GCBM) on oxidative stress and photoaging in ultraviolet B (UVB)-irradiated hairless mice. We measured antioxidant enzyme activities, collagen synthesis-related pathways, and moisturizing-related factors in the dorsal skin of mice. We observed that dietary supplementation with GCBM increased antioxidant enzyme activity and decreased pro-inflammatory cytokine expression in the UVB-irradiated dorsal skin. Furthermore, dietary supplementation with GCBM inhibited wrinkle formation by suppressing the JNK/c-FOS/c-Jun/MMP pathway and stimulating the TGF-βRI/Smad3/procollagen type I pathway. Dietary supplementation with GCBM also increased skin moisturization by stimulating hyaluronic acid and ceramide synthesis in the dorsal skin. Therefore, buttermilk powder supplementation helps prevent photoaging and can be used as an effective component in developing anti-photoaging products

The Effects of 3-Dimensional Bioprinting Calcium Silicate Cement/Methacrylated Gelatin Scaffold on the Proliferation and Differentiation of Human Dental Pulp Stem Cells

A calcium silicate cement/methacrylated gelatin (GelMa) scaffold has been applied in tissue engineering; however, the research on its applications in dental tissue regeneration remains lacking. We investigate the effect of this scaffold on human dental pulp stem cells (hDPSCs). hDPSCs were cultured in 3D-printed GelMa and MTA-GelMa scaffolds. Cell adhesion was evaluated using scanning electron microscopy images. Cells were cultured in an osteogenic differentiation medium, which contained a complete medium or α-MEM containing aqueous extracts of the 3D-printd GelMa or MTA-GelMa scaffold with 2% FBS, 10 mM β-glycerophosphate, 50 μg/mL ascorbic acid, and 10 nM dexamethasone; cell viability and differentiation were shown by WST-1 assay, Alizarin Red S staining, and alkaline phosphatase staining. Quantitative real-time PCR was used to measure the mRNA expression of DSPP and DMP-1. One-way analysis of variance followed by Tukey’s post hoc test was used to determine statistically significant differences, identified at p < 0.05. hDPSCs adhered to both the 3D-printed GelMa and MTA-GelMa scaffolds. There was no statistically significant difference between the GelMa and MTA-GelMa groups and the control group in the cell viability test. Compared with the control group, the 3D-printed MTA-GelMa scaffold promoted the odontogenic differentiation of hDPSCs. The 3D-printed MTA-GelMa scaffold is suitable for the growth of hDPSCs, and the scaffold extracts can better promote odontoblastic differentiation

Krill Oil Inhibits Cholesterol Synthesis and Stimulated Cholesterol Excretion in Hypercholesterolemic Rats

The present study aimed to investigate the antihypercholesterolemic effects of krill oil supplementation in high-cholesterol diet-induced hypercholesterolemic rats, and the mechanisms underlying these effects. Rats were divided into five groups: normal control, control (high-cholesterol diet), krill oil 100 mg/kg b.w. (high-cholesterol diet with Krill oil 100 mg/kg b.w.), and krill oil 200 mg/kg b.w. (high-cholesterol diet with Krill oil 200 mg/kg b.w.). After 12 weeks, the rats were sacrificed to observe the effects of krill oil on cholesterol synthesis and excretion. We found that krill oil supplementation suppressed total triglycerides, total cholesterol, and LDL-cholesterol levels, as well as HMG-CoA reductase activity. It stimulated AMPK phosphorylation, LDL receptor and ACAT2 expression in the liver, and the fecal output of cholesterol. Furthermore, it decreased the levels of P-selectin, sVCAM-1, and NO, as well as aortic wall thickness, demonstrating its role in the prevention of atherosclerosis. Thus, we suggest that krill oil supplementation can reduce LDL-cholesterol levels in the blood during hypercholesterolemia by stimulating the uptake of LDL-cholesterol into tissue and cholesterol excretion, as well as inhibition of cholesterol synthesis