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Objective: This study was conducted to evaluate the effects of feed processing and particle size on growth performance, nutrient digestibility, carcass characteristics, and gastric health in growing-finishing pigs.Methods: A total of 360 growing pigs (22.64±0.014 kg initial body weight [BW]) were allocated to 1 of 6 treatments with 6 replicates by BW and sex, and 10 pigs were housed in one pen in a randomized complete block design. The BW and feed intake were recorded to calculate growth performance. For the digestibility trial, a total of 24 barrows with an initial BW of 33.65±0.372 kg were split into 6 treatments with a completely randomized design. Dietary treatments were designed by a 2×3 factorial arrangement of treatments based on two main factors, particle size (600, 750, 900 μm) and feed form (mash and pellet) of diet. Experimental diets were formulated to contain the requirements of the NRC (2012).Results: The BW and average daily gain were not changed by dietary treatments, and the feed intake of finishing pigs (wks 6 to 12) was increased when the pigs were fed a mash diet (p

Given the increasing global trend toward unhealthy lifestyles and dietary decisions, such as "over-consumption of alcohol, and high sugar and fat diets" (ACHSFDs), it is not surprising that metabolic hypertension (MH) is now the most common type of hypertension. There is an urgent, global need for effective measures for the prevention and treatment of MH. Improper diet leads to decreased short-chain fatty acid (SCFA) production in the gut, leading to decreased gastrointestinal function, metabolism, and blood pressure as a result of signaling through G-protein-coupled receptors (GPCRs), ultimately causing MH. Previous studies have suggested that Dendrobium officinale (DO) may improve gastrointestinal function, lower blood pressure, and regulate metabolic abnormalities, but it is not clear whether it acts on MH by increasing SCFA and, if so, how. In this research, it was observed that Dendrobium officinale ultrafine powder (DOFP) could lower blood pressure and improve lipid abnormalities in ACHSFD-induced MH model rats. Moreover, DOFP was found to improve the intestinal flora and increased the SCFA level in feces and serum, as well as increased the expressions of GPCR43/41 and eNOS and the nitric oxide (NO) level. An experiment on isolated aorta rings revealed that DOFP improved the vascular endothelial relaxation function in MH rats, and this effect could be blocked by the eNOS inhibitor l-NAME. These experimental results suggest that DOFP improved the intestinal flora and increased the production, transportation, and utilization of SCFA, activated the intestinal-vascular axis SCFA-GPCR43/41 pathway, improved vascular endothelial function, and finally lowered blood pressure in MH model rats. This research provides a new focus for the mechanism of the effect of DOFP against MH by triggering the enteric-origin SCFA-GPCR43/41 pathway.

Background As a result of similar appearances between edible and poisonous plants, 42 patients have ingested poisonous plants from 2013 to 2017 in Korea. We have developed species-specific primer sets of three of edible and poisonous plants sets (Ligularia fischeri & Caltha palustris, Artemisia annua & Ambrosia artemisiifolia and Hemerocallis fulva & Veratrum maackii) for distinguishing both plants using a real-time polymerase chain reaction assay. Results The efficiencies of the developed primer sets ranged from 87.8% to 102.0%. The developed primer sets have significant correlation coefficient values between the Ct values and the log DNA concentration for their target species (r2 > 0.99). The cut-off lines as the crossing point values of the limit of quantitation of the target species were determined, and all non-target species were amplified later than the cut-off cycles. Then, the effectiveness of the developed primer sets was evaluated using commercial food products and digested samples with simulated gastric juice. Conclusion All of the developed species-specific primer sets were able to detect target DNA successfully in commercial food products and the digested samples. Therefore, the developed species-specific primer sets in the present study would be useful tools for distinguishing between poisonous plants and edible plants. © 2020 Society of Chemical Industry.

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.

Angiogenesis plays important roles in pathological conditions such as cancer and inflammation as well as normal tissue development and homeostasis. Here, we investigated the effects and molecular mechanisms of α-viniferin, an oligostilbene isolated from Caragana sinica, on human umbilical vein endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. α-viniferin treatment inhibited mitogen-induced HUVEC proliferation by retinoblastoma protein hypophosphorylation. In addition, α-viniferin suppressed mitogen-induced HUVEC adhesion, migration, invasion, and microvessel outgrowth. These anti-angiogenic activities of α-viniferin might be mediated through downregulation of cell cycle-related proteins, vascular endothelial growth factor receptor-2 (VEGFR-2), and matrix metalloproteinase-2. Furthermore, inactivation of VEGFR-2/p70 ribosomal S6 kinase signaling pathway was found to be involved in α-viniferin-mediated modulation of endothelial cell responses. Our results demonstrate the pharmacological functions and molecular mechanisms of α-viniferin in regulating angiogenesis, suggesting the therapeutic potential of α-viniferin to treat and prevent various angiogenesis-related diseases.

Aim and Objective: Hypertension-induced stroke and coronary artery disease are significant causes of global morbidity and mortality. Metabolic hypertension has recently become the leading cause of hypertension. Flos Chrysanthemi Indici (CIF) has a long history as a treatment of hypertension as part of traditional Chinese medicine. However, its mechanisms of activity remain largely unknown. This study was aimed to uncover the potential anti-hypertensive mechanisms of CIF based on network pharmacology. Materials and Methods: In this research, a systems pharmacology approach integrating the measurement of active compounds, target fishing, gene screening, Gene Ontology (GO) pathway analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology Based Annotation System (KOBAS) database analysis, and compound-target network construction were performed to explore the anti-hypertensive mechanisms of CIF. Results: These studies revealed that 12 bioactive compounds in CIF had good druggability, 5 of which were flavonoids. After screening, 8 of those 12 bioactive compounds interacted with 118 hypertensionrelated target genes, which were mapped to 218 signal pathways. Network analysis showed that these targets were associated with improving insulin resistance, improving vascular function, inhibiting renninangiotensin- aldosterone system (RAAS), inhibiting the sympathetic nervous system (SNS) and regulating other physiological processes. Conclusion: In summary, CIF is predicted to target multiple proteins and pathways to form a network that exerts systematic pharmacological effects in order to regulate blood pressure and metabolic disorder.

The objective of this study was to determine the interactive effects of dietary fiber solubility and lipid source on growth performance, visceral organ weights, gut histology, and gut microbiota composition of weaned pigs. A total of 280 nursery pigs [initial body weight (BW) = 6.84 kg] weaned at 21 d were housed in 40 pens (7 pigs/pen). The pigs were fed four diets (10 pens/diet) in a randomized complete block design in two phases: Phase 1 from 0 to 2 wk and Phase 2 from 2 to 5 wk. The diets were corn-soybean meal-based with either sugar beet pulp (SBP) or soybean hulls (SBH) as a fiber source and either soybean oil (SBO) or choice white grease (CWG) as a lipid source in a 2 × 2 factorial arrangement. The BW and feed intake were determined by phase, whereas visceral organ weights, intestinal histology, and gut microbial composition were determined at the end of the trial. Dietary fiber solubility and lipid source did not interact (P > 0.05) on average daily feed intake and average daily gain across all phases. However, the gain to feed ratio (G:F) for CWG-containing diets was lower (P < 0.05) than that for SBO-containing diets for Phase 1. Also, G:F for SBP-containing diets was lower (P < 0.05) than that for SBH-containing diets for Phase 1 and for the entire study period. Pigs fed SBP-containing diets had greater (P < 0.05) stomach weight, and tended to have greater (P < 0.10) small and large intestine weights relative to BW than those fed SBH-containing diets. Duodenal villous height to crypt depth ratio for CWG-based diets tended to be greater (P = 0.09) than that for SBO-based diets. Fiber solubility and lipid source interacted (P < 0.05) on relative abundance of Bacteroides in the colon such that the relative abundance of the Bacteroides for CWG was greater (P < 0.05) than that for the SBO in SBP-based diet, but not in SBH-based diet. Relative abundance of Butyricicoccus in the colon for SBH-based diet was greater (P < 0.05) than that for SBP-based diet. In conclusion, inclusion of SBH instead of SBP in corn-soybean meal-based diets for weaned pigs can result in increased feed efficiency and relative abundance of Butyricicoccus in the colon, which is associated with improved gut health. Also, inclusion of SBO instead of CWG in the diets for weaned pigs can result in improved feed efficiency during Phase 1 feeding; however, the pigs may recover from the low feed efficiency induced by dietary inclusion of CWG instead of SBO after Phase 1 feeding.

As the number of patients with metabolic hypertension (MH) is increasing, there is an essential require for global measures to prevent and treat MH. Flavonoids such as buddleoside (BUD) from Chrysanthemum indicum L. are the main pharmacological components of cardiovascular activities. Previous studies have suggested that the buddleoside-rich Chrysanthemum indicum L. extract (BUDE) can reduce blood pressure in spontaneously hypertensive rats (SHR). However, its effect on MH and how it works remains to be researched. In this study, it was observed that BUDE could lower blood pressure, improve dyslipidemia, and decrease the level of plasma LPS in MH rats. Moreover, BUDE improved intestinal flora and increased the expression of occludin and claudin-1 in the colon, and improved the pathological injury of the colon. Western bolt and qRT-PCR experiments showed that BUDE could down-regulate TLR4 and MyD88 protein and mRNA expression and inhibit phosphorylation of IKKβ, IκBα and NF-κB p65 in vessels of MH rats. These results showed that BUDE could regulate intestinal flora, improve intestinal barrier function, reduce the production and penetration of LPS, thereby inhibiting the vascular TLR4/MyD88 pathway, improving vascular endothelial function, and ultimately lowering blood pressure in MH rats. This study provides a new mechanism of BUDE against MH by inhibiting the enteric-origin LPS/TLR4 pathway.

This study was conducted to evaluate the effects of lysine cell mass (LCM) as an alternative lysine source in diets for weaning pigs on growth performance, diarrhea incidence, and blood profiles. In experiment 1, a total of 200 weaning pigs, with an average body weight (BW) of 6.89 ± 1.04 kg, were allotted into one of five treatments with four replicates of 10 pigs per pen in a randomized complete block design (RCBD). The dietary treatments were composed of LCM supplementation (0, 0.25, 0.5, 0.75, or 1.0%) with partial replacement of L-lysine·HCl (0 to 0.8% for phase 1 diets and 0 to 0.07% for phase 2 diets). The BW and feed intake were recorded at the end of each phase (d 0 to 14 for phase 1, d 14 to 35 for phase 2), and diarrhea incidence was checked daily throughout the experimental period. Blood samples were taken from the jugular vein of pigs at 2 weeks and 5 weeks to determine the blood profiles of weaning pigs. In experiment 2, a total of 144 weaning pigs with an average BW of 6.44 ± 1.19 kg were allotted into one of six treatments with six replicates of four pigs per pen in RCBD. The dietary treatments were composed of LCM supplementation (0 to 3.5% for phase 1 diets and 0 to 2.2% for phase 2 diets) with replacement of L-lysine·HCl from 0 to 100%. In experiment 1, partial replacement of L-lysine·HCl with 0 to 1% LCM did not affect growth performance and diarrhea incidence of pigs. An increase in the LCM supplementation from 0 to 1% with partial replacement of L-lysine·HCl had no influence on the blood urea nitrogen concentrations, whereas it resulted in a linear decrease (p &lt, 0.05) in the serum IgG concentrations for 5 weeks. In experiment 2, increasing the dietary level of LCM with replacement of L-lysine·HCl quadratically decreased (p &lt, 0.05) ADG and G–F ratio for phase 2 and G–F ratio for the overall period such that 100% replacement of L-lysine·HCl with LCM decreased ADG and G–F ratio of weaning pigs. An increase in the LCM supplementation with replacement of L-lysine·HCl tended to decrease linearly (p &lt, 0.10) the diarrhea incidence of weaning pigs for the overall period and linearly decrease (p &lt, 0.05) the serum IgG concentrations for 2 weeks. In conclusion, partial replacement of L-lysine·HCl with LCM from 0 to 1% had no negative impacts on the growth performance, but 100% replacement of L-lysine·HCl with LCM decreased the growth performance of weaning pigs. Therefore, LCM could be included in the diets for weaning pigs up to 2.8% and 1.76% for phase 1 and phase 2, respectively, as a substitute for L-lysine·HCl without detrimental effects on the performance of weaning pigs.

This study was performed to evaluate the effects of dietary vitamin levels on physiological responses, blood profiles, and reproductive performance in gestating sows. A total of 52 F1 multiparous sows (Yorkshire × Landrace) with an average body weight of 223.5 ± 31.7 kg, an average parity of 6.4 ± 2.7, and an average backfat thickness of 18.5 ± 4.9 mm were divided into four treatment groups considering body weight, backfat thickness, and parity in a completely randomized design with 13 replicates. The treatments were 100% (V1), 300% (V3), 600% (V6) and 900% (V9) of the National Research Council (NRC) Nutrient Requirements of Swine. The gestation diet was formulated based on corn-soybean meal (SBM) and contained 3,265 kcal of metabolizable energy (ME)/kg and 12.00% crude protein. During the lactation period, all sows were fed the same commercial lactation diet. There was no significant difference in body weight of gestating sows. However backfat thickness tended to increase when higher levels of vitamins were provided to gestating sows (p < 0.10). When high levels of dietary vitamins were provided, the body weight change of lactating sows increased (p < 0.01). When sows were fed higher levels of vitamins, the feed intake of lactating sows tended to decrease (p = 0.06). There were no treatment differences in the number of total born, born alive, stillbirth piglets, or the body weight of piglets according to different dietary vitamin level. As dietary vitamin level increased, the serum concentration of 25(OH)D3 in sows at 90 days of gestation linearly increased (p < 0.01). Furthermore, the serum vitamin E level of gestating sows was linearly increased with increasing dietary vitamin level (p < 0.05). The current NRC vitamin requirements are sufficient for gestating sows and higher levels of vitamins in the gestation diet did not show any beneficial effects for gestating and lactating sows.

Purpose In order to identify the molecular characteristics and improve the efficacy of early diagnosis of mucinous epithelial ovarian cancer (mEOC), here, the transcriptome profiling by weighted gene co-expression network analysis (WGCNA) has been proposed as an effective method. Methods The gene expression dataset GSE26193 was reanalyzed with a systematical approach, WGCNA. mEOC-related gene co-expression modules were detected and the functional enrichments of these modules were performed at GO and KEGG terms. Ten hub genes in the mEOC-related modules were validated using two independent datasets GSE44104 and GSE30274. Results 11 co-expressed gene modules were identified by WGCNA based on 4917 genes and 99 epithelial ovarian cancer samples. The turquoise module was found to be significantly associated with the subtype of mEOC. KEGG pathway enrichment analysis showed genes in the turquoise module significantly enriched in metabolism of xenobiotics by cytochrome P450 and steroid hormone biosynthesis. Ten hub genes (LIPH, BCAS1, FUT3, ZG16B, PTPRH, SLC4A4, MUC13, TFF1, HNF4G and TFF2) in the turquoise module were validated to be highly expressed in mEOC using two independent gene expression datasets GSE44104 and GSE30274. Conclusion Our work proposed an applicable framework of molecular characteristics for patients with mEOC, which may help us to obtain a precise and comprehensive understanding on the molecular complexities of mEOC. The hub genes identified in our study, as potential specific biomarkers of mEOC, may be applied in the early diagnosis of mEOC in the future.

(E)-3,4-Dihydroxybenzylideneacetone (compound 1) inhibited receptor activator of NF-κB ligand-induced osteoclastogenesis of C57BL/6 bone marrow monocyte/macrophages with IC50 of 7.8 μM (IC50 of alendronate, 3.7 μM) while stimulating the differentiation of MC3T3-E1 osteoblastic cells, accompanied by the induction of Runt-related transcription factor 2, alkaline phosphatase, and osteocalcin. (E)-4-(3-Hydroxy-4-methoxyphenyl)-3-buten-2-one (compound 2c) showed a dramatically increased osteoclast-inhibitory potency with IC50 of 0.11 μM while sustaining osteoblast-stimulatory activity. (E)-4-(4-Hydroxy-3-methoxyphenyl)-3-buten-2-one (compound 2g) stimulated alkaline phosphatase production 2-fold at 50 μM without changing osteoclast-inhibitory activity, compared with compound 1. Oral administration of compounds 1, 2c, and 2g prevented ovariectomy-induced osteoporosis in ddY mice to a degree proportional to their osteoclastogenesis-inhibitory potencies. The administration of 1 (mg/kg)/d compound 2c ameliorated histomorphometry of osteoporotic bone to a degree comparable with 10 (mg/kg)/d alendronate. Conclusively, the in vitro capacity of a few benzylideneacetone derivatives to inhibit osteoclastogenesis supported by independent osteoblastogenesis activation was convincingly reflected in in vivo management of osteoporosis, suggesting a potential novel therapeutics for osteopenic diseases.

The ethanolic extract obtained from the stems of Glycosmis pentaphylla was found to suppress antigen-mediated degranulation of rat basophilic leukemia (RBL-2H3) cells. Four new geranylated 2-quinolone alkaloids, named glycopentanolones A–D (1–4), and 12 known metabolites (5–16) were isolated from the ethanolic extract from the stems of G. pentaphylla using bioassay-guided fractionation. Their structures were elucidated by a combination of 1D and 2D NMR, and HRESI-MS. The inhibitory effects of the isolated constituents on β-hexosaminidase release from RBL-2H3 cells were examined, and compounds 1, 5, 8 and 11 exhibited potent inhibitory activity with IC50 values between 0.05 and 4.28 μM.

The supplementation level of barley was limited because of high contents of fiber in monogastric animals. Barley contained high soluble fiber, thus it could prevent to diarrhea of weaning pigs. Moreover, as the barley break down by enzymes, free sugars come out from the barley, which could be used as an energy source in weaning pigs and replace milk by-products in weaning pig’s diet. Therefore, present study was conducted to investigate the influence of barley to replace milk by-product in weaning pig’s diet on growth performance, blood profile, nutrient digestibility, diarrhea incidence, and economic analysis in weaning pigs. A total of 112 crossbred ([York-shire × Landrace] × Duroc, weaned at 28 days of age) piglets were allotted to 4 treatments in a randomized complete block (RCB) design. Each treatment has 7 replications with 4 pigs per pen. Pigs were fed each treatment diet which containing different levels of barley (0%, 10%, 20%, and 30%) at the expense of whey powder and lactose. Three phase feeding programs were used for 6 weeks of growth trial (phase 1: 0–2 weeks; phase 2: 3–4 weeks; phase 3: 5–6 weeks). During 0–2 week, body weight (BW), average daily gain (ADG) and G:F ratio were decreased as barley level increased in the diet (linear response, p < 0.01). In blood profile, blood urea nitrogen was decreased as the barley level increased in the diet (linear, p < 0.01). However, no significant differences were observed in blood glucose level. In nutrient digestibility, crude fat digestibility was linearly increased as barley increased (linear, p < 0.01). The incidence of diarrhea was improved as increasing barley contents in all phases (linear, p < 0.01). These results demonstrated that supplementation of barley to replace milk by-product influenced negatively on growth performance during 0–2 week. However, the incidence of diarrhea and later growth performance from 3 week postweaning were improved as dietary barley level increased.

We extracted 15 pterosin derivatives from Pteridium aquilinum that inhibited β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and cholinesterases involved in the pathogenesis of Alzheimer’s disease (AD). (2R)-Pterosin B inhibited BACE1, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with an IC50 of 29.6, 16.2 and 48.1 µM, respectively. The Ki values and binding energies (kcal/mol) between pterosins and BACE1, AChE, and BChE corresponded to the respective IC50 values. (2R)-Pterosin B was a noncompetitive inhibitor against human BACE1 and BChE as well as a mixed-type inhibitor against AChE, binding to the active sites of the corresponding enzymes. Molecular docking simulation of mixed-type and noncompetitive inhibitors for BACE1, AChE, and BChE indicated novel binding site-directed inhibition of the enzymes by pterosins and the structure−activity relationship. (2R)-Pterosin B exhibited a strong BBB permeability with an effective permeability (Pe) of 60.3×10−6 cm/s on PAMPA-BBB. (2R)-Pterosin B and (2R,3 R)-pteroside C significantly decreased the secretion of Aβ peptides from neuroblastoma cells that overexpressed human β-amyloid precursor protein at 500 μM. Conclusively, our study suggested that several pterosins are potential scaffolds for multitarget-directed ligands (MTDLs) for AD therapeutics., Alzheimer’s disease: Promising therapeutic compounds found in plants Compounds extracted from bracken fern block the activity of three enzymes associated with Alzheimer’s disease (AD). Because AD is a complex and multifactorial disease, a multitarget-directed approach is an attractive strategy for the development of disease-modifying therapeutics. A study led by Gil Hong Park, Korea University, Seoul, and Nam Sook Kang, Chungnam National University, Daejon, revealed that pterosin derivatives could reduce the activity of β-site amyloid precursor protein cleaving enzyme 1, acetylcholinesterase and butyrylcholinesterase in a concentration-dependent manner. Furthermore, the fern-extracted compounds did not cause cellular toxicity and were able to cross the blood–brain barrier, which is impermeable to most drugs, to reach the brain. Future studies will determine whether they can be developed into drugs to simultaneously engage various AD targets in animal models of the disease.

Prostate cancer (PC) progressed to castration resistance (CRPC) is a fatal disease. CRPC tumors develop resistance to new-generation antiandrogen enzalutamide through lineage plasticity, characterized by epithelial-mesenchymal transition (EMT) and a basal-like phenotype. FOXA1 is a transcription factor essential for epithelial lineage differentiation. Here, we demonstrate that FOXA1 loss leads to remarkable upregulation of transforming growth factor beta 3 (TGFB3), which encodes a ligand of the TGF-β pathway. Mechanistically, this is due to genomic occupancy of FOXA1 on an upstream enhancer of the TGFB3 gene to directly inhibit its transcription. Functionally, FOXA1 downregulation induces TGF-β signaling, EMT, and cell motility, which is effectively blocked by the TGF-β receptor I inhibitor galunisertib (LY2157299). Tissue microarray analysis confirmed reduced levels of FOXA1 protein and a concordant increase in TGF-β signaling, indicated by SMAD2 phosphorylation, in CRPC as compared with primary tumors. Importantly, combinatorial LY2157299 treatment sensitized PC cells to enzalutamide, leading to synergistic effects in inhibiting cell invasion in vitro and xenograft CRPC tumor growth and metastasis in vivo. Therefore, our study establishes FOXA1 as an important regulator of lineage plasticity mediated in part by TGF-β signaling, and supports a novel therapeutic strategy to control lineage switching and potentially extend clinical response to antiandrogen therapies.

The β-adrenergic-like octopamine receptor (OA2B2), which binds the biogenic amine octopamine, belongs to the class of G-protein coupled receptors and significantly regulates many physiological and behavioral processes in insects. In this study, the putative open reading frame sequence of the MsOA2B2 gene in Mythimna separata was cloned, the full-length complementary DNA was 1191 bp and it encoded a 396-amino acid protein (GenBank accession number MN822800). Orthologous sequence alignment, phylogenetic tree analysis, and protein sequence analysis all showed that the cloned receptor belongs to the OA2B2 protein family. Real-time quantitative polymerase chain reaction of spatial and temporal expression analysis revealed that the MsOAB2 gene was expressed in all developmental stages of M. separata and was most abundant in egg stages and second and fourth instars compared with other developmental stages, while the expression level during the pupal stage was much lower than that at the other stages. Further analysis with sixth instar M. separata larvae showed that the MsOA2B2 gene was expressed 1.81 times higher in the head than in integument and gut tissues. Dietary ingestion of dsMsOA2B2 significantly reduced the messenger RNA level of MsOA2B2 and decreased mortality following amitraz treatment. This study provides both a pharmacological characterization and the gene expression patterns of OA2B2 in M. separata, facilitating further research for insecticides using MsOA2B2 as a target.

Amomum tsao-ko (Zingiberaceae), an important traditional medicinal herb, possesses many biological activities, including anti-inflammatory effects. Though the anti-obesity properties of the crude ethanol extract of A. tsao-ko fruits have been reported, the anti-adipogenic properties of its phytochemical constituents have not been reported. Therefore, in the present study, we isolated the active constituents of A. tsao-ko and investigated their anti-adipogenic effects. The bioassay-guided isolation of the phytochemicals from the ethanol extract of A. tsao-ko fruits identified four bioactive compounds, comprising one fatty acid (1), one sesquiterpene alcohol (2), and two phenolic compounds (3 and 4). Their structures were elucidated by a combination of 1D and/or 2D nuclear magnetic resonance and mass spectrometry. The anti-adipogenic activities of the four compounds evaluated by Oil Red O staining in 3T3-L1 cells revealed that the treatment with the isolated compounds 1 and 3 reduced the lipid accumulation in 3T3-L1 adipocytes more strongly than the compounds 2 and 4, in a dose-dependent manner.

Chronic inflammation can cause oviduct mucosal damage and immune dysfunction, leading to infertility, early pregnancy loss, ectopic pregnancy, tumors, and a decrease in reproductive capacities in female animals. Estrogen can suppress immune responses in different tissues and oviducts, and regulate the oviduct immune balance; however, the underlying mechanisms remain unclear. The objective of this study was to explore the mechanism of estrogen-regulated oviduct mucosal immunity and discover new estrogen targets for regulating oviduct mucosal immune homeostasis. Sheep oviduct epithelial cells (SOECs) were treated with 17-β estradiol (E2). Transcriptome sequencing and analysis showed differentially expressed S100 calcium-binding protein A (S100A) genes that may participate in the oviduct mucosa immunoregulation of estrogen. Quantitative polymerase chain reaction and immunocytochemistry analysis showed thatS100A8expression changed dynamically in E2-treated SOECs and peaked after 7 h of treatment. Estrogen nuclear receptors and G protein-coupled membrane receptors promoted E2-dependentS100A8upregulation. TheS100A8gene was disrupted using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 method. Levels of inflammatory factors interleukin (IL)-1β and IL-4 were significantly upregulated inS100A8-knockdown SOECs, whereas those of the anti-inflammatory factor IL-10 was downregulated. Following S100A8 knockdown in SOECs treated with E2 for 7 h, IL-10 levels increased significantly. Estrogen affected oviduct mucosa immune function and dynamically regulated S100A8 in SOECs. S100A8 knockdown caused an excessive immune response, indicating that S100A8 is beneficial for maintaining immune homeostasis in the oviduct mucosa. Moreover, estrogen can compensate for the effect of S100A8 knockdown by upregulating IL-10.

Dendrobium officinale (DOF) is a traditional Chinese edible and officinal plant. Ultrafine DOF powder (DOFP) can regulate lipids and histopathology in the liver, but the underlying mechanisms of hepatic fatty acid (FA) metabolism, which is generally correlated with the development of nonalcoholic fatty liver disease (NAFLD), remain unclear. The purpose of the present study was to investigate whether DOFP treatment alters hepatic FA metabolism in NAFLD mice by using multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) and analyse the underlying mechanisms. A 3-week DOFP treatment prevented lipid deposition and improved hepatic histopathology in NAFLD mice after withdrawal from the high-sucrose, high-fat (HSHF) diet, and it decreased triglyceride and FA content in the liver. Furthermore, the C16 : 0/C14 : 0 and C18 : 1/18 : 0 ratios in FAs were significantly decreased in the DOFP treatment group, and the C20 : 4/C20 : 3 and C22 : 4/C22 : 3 ratios were increased, and saturated FA was inhibited. Additionally, DOFP treatment significantly increased the content of two FA β-oxidation-related proteins (carnitine palmitoyltransferase 1-α and acyl-coenzyme A oxidase 1). It also decreased the content of a FA synthesis-related protein (fatty acid synthase), a FA desaturation-related protein (stearoyl-coenzyme A desaturase-1), and a FA uptake-related protein (fatty acid transport protein 2). Moreover, DOFP treatment improved dysregulated levels of major phospholipids in the livers of model mice. The results of this study confirm that DOFP treatment in NAFLD mice has liver recovery effects by regulating FA metabolism.

Background. Yeju Jiangya decoction (CIF) is an herbal formula from traditional Chinese medicine (TCM) for the treatment of hypertension. Materials and Methods. Based on the analysis of network pharmacology, combined with in animal experiments, the network pharmacology was used to explore the potential proteins and mechanisms of CIF against hypertension. The bioactive compounds of CIF were screened by using the platform, and the targets of hypertension and CIF were collected. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction network (PPI) core targets were carried out, and the useful proteins were found by molecular docking technology. Finally, we used N-nitro-L-arginine (L-NNA) induced hypertension model rats to confirm the effect and mechanism of CIF on hypertension. Results. 14 bioactive compounds of CIF passed the virtual screening criteria, and 178 overlapping targets were identified as core targets of CIF against hypertension. The CIF-related target network with 178 nodes and 344 edges is constructed. The topological results show that quercetin and luteolin are the key components in the network. The key targets NOS3 (nitric oxide synthase 3) and NOS2 (nitric oxide synthase 2) were screened by the protein-protein interaction network. The analysis of target protein pathway enrichment showed that the accumulation pathway is related to the vascular structure of CIF regulation of hypertension. Further verification based on molecular docking results showed that NOS3 had the good binding ability with quercetin and luteolin. On the other hand, NOS3 has an important relationship with the composition of blood vessels. Furthermore, the animal experiment indicated that after the L-NNA-induced hypertension rat model was established, CIF intervention was given by gavage for 3 weeks, and it can decrease serum concentrations of endothelin-1 (ET-1) and thromboxane B2 (TXB2), increase the expression of nitric oxide (NO) and prostacyclin 2 (PGI2), and improve renal, cardiac, and aortic lesions. At the same time, it can reduce blood pressure and shorten vertigo time. Western blot (WB) and immunohistochemistry (IHC) analyses indicated that CIF may downregulate the expression of NOS3, guanylyl cyclase-alpha 1 (GC-α1), guanylyl cyclase-alpha 2 (GC-α2), and protein kinase CGMP-dependent 1 (PRKG1). These results suggest that CIF may play an antihypertensive role by inhibiting the activation of the NOS3/PRKG1 pathway. Conclusions. The results of this study indicate that CIF has the ability to improve target organs, protect endothelial function, and reduce blood pressure and that CIF might be a potential therapeutic drug for the prevention of hypertension. It provides new insight into hypertension and the potential biological basis and mechanism for CIF clinical research.

Many studies have demonstrated that cancer stem cells (CSCs) or tumor-initiating cells (TICs) are responsible for tumor cell proliferation, chemotherapy resistance, metastasis, and relapse in various cancers. We, and others, have previously shown that the signal transducer and activator of transcription 3 (STAT3) signaling pathway is responsible for CSCs and TICs growth. Recent reports have indicated that the heat shock protein 90 (Hsp90) is also essential for the survival of CSCs and TICs. SNX-2112 is an Hsp90 inhibitor. However, it remains unclear whether proliferation of esophageal cancer stem-like cells (ECSLCs) is suppressed by SNX-2112 with knockdown of STAT3 (shSTAT3). Here, we explored the association between SNX-2112 with shSTAT3 and the suppression of ECSLCs growth. We found that the expression level of both STAT3 and p-STAT3 was higher in clinical esophageal cancer tissue than in the adjacent normal tissue, using western blot and qPCR analysis. Furthermore, differential expression analysis demonstrated that STAT3 was overexpressed in clinical specimens. We demonstrated that SNX-2112 inhibited cancer cell proliferation, decreased ABCB1 and ABCG2 gene expression levels and reduced the colony formation capacity of ECSLCs, which was enhanced by STAT3 silencing. Flow cytometry analysis revealed that the combination of SNX-2112 and shSTAT3 significantly induced apoptosis and cell cycle arrest at G2/M phase in ECSLCs. Levels of proliferation pathway proteins, including p38, c-Jun N-terminal kinase (JNK), and extracellular signal–regulated kinase (ERK) which were also client proteins of Hsp90, were also reduced. In addition, SNX-2112 with shSTAT3 inhibited the proliferation of ECSLCs in vivo. Finally, STAT3 overexpression eliminated the apoptotic and antiproliferative effects of SNX-2112 on ECSLCs. Hence, these results provide a rationale for the therapeutic potential of the combination of SNX-2112 with shSTAT3 in esophageal cancer, and may indicate new targets for clinical intervention in human cancer.

Effects of dietary solvent-extracted canola meal (SECM) on growth performance, blood thyroid hormones, and immune parameters of nursery pigs were investigated. A total of 200 weaned pigs (initial body weight = 7.00 kg) were obtained in 2 batches of 100 pigs each. Pigs in each batch were housed in 25 pens (4 pigs/pen) and fed 5 diets in a randomized complete block design. The 5 diets were corn-soybean meal-based diet with 0, 10, 20, 30, or 40% SECM. The diets were fed in 3 phases; Phase 1: d 0 to 7, Phase 2: d 7 to 21, and Phase 3: d 21 to 42. Growth performance was determined by phase. Blood parameters were determined at the end of Phases 1 and 2. Increasing dietary SECM from 0 to 40% resulted in a quadratic increase (P=0.007) in overall (d 0-42) average daily gain (ADG) such that an increase in dietary level of SECM from 0 to 20% resulted in an increase (P< 0.05) in ADG by 14.1%, but an increase in level of SECM from 20 to 40% resulted in a decrease (P< 0.05) in ADG by 11.4 %. Dietary SECM tended to linearly reduce (P=0.05) Phase 2 serum tetraiodothyronine level. An increase in dietary level of SECM from 0 to 20% did not affect the serum IgA level, but an increase in level of dietary level of SECM from 20 to 40% resulted in a decrease (P< 0.05) in the serum IgA level. Serum IgG and TNF-α levels were unaffected by diet. In conclusion, increasing dietary SECM level from 0 to 20% increased growth performance of weaned pigs. However, increasing dietary SECM level from 20 to 40% reduced growth performance and increased immune response. Thus, SECM can be included in diets for nursery pigs at 20% to improve performance.

Aralia continentalis (A. continentalis) is a medicinal plant belonging to Araliaceae, it has been reported to exert anti-cancer, anti-bacterial, anti-inflammatory, anti-platelet and anti-oxidative activities. But the potential mechanism for the anti-inflammatory effect of compounds isolated from the roots of A. continentalis is still insufficient. So, we evaluated whether compounds isolated from the roots of A. continentalis exert anti-inflammatory effects and elucidated its potential mechanism in RAW264.7 cells. The concentrated residue was subsequently suspended in H2O and partitioned with n-hexane, methylene chloride (CH2Cl2), ethyl acetate (EtOAc) and n-butanol (n-BuOH). The fractions were subjected to sequential column chromatography over silica-gel, RP-18, MPLC, recycling and preparative HPLC to isolated the novel compound. The novel compound was identified as 18-nor-ent-pimara-9(11),15-diene-4β-ol and confirmed anti-inflammatory activity. The 18-nor-ent-pimara-9(11),15-diene-4β-ol dose-dependently blocked NO production and inhibited iNOS, COX-2, TNF-α and IL-1β expression in LPS-stimulated RAW264.7 cells. The 18-nor-ent-pimara-9(11),15-diene-4β-ol inhibited LPS-stimulated degradation of IκB-α and nuclear accumulation of p65, which resulted in the suppression of NF-κB activation in RAW264.7 cells. Also, the 18-nor-ent-pimara-9(11),15-diene-4β-ol attenuated the phosphorylation of p38 and ERK1/2 in LPS-induced RAW264.7 cells. These results suggest that the nor-ent-pimara-9(11),15-diene-4β-ol isolated from the roots of A. continentalis may have grate potential for the development of anti-inflammatory drugs.

Turmeric, or Curcuma longa, is commonly consumed in the South East Asian countries as a medical product and as food due to its therapeutic properties. However, with increasing demand for turmeric powder, adulterated turmeric powders mixed with other cheap starch powders, such as from corn or cassava, are being distributed by food suppliers for economic benefit. Here, we developed molecular markers using quantitative real-time PCR to identify adulteration in commercial turmeric powder products. Chloroplast genes, such as matK, atpF, and ycf2, were used to design species-specific primers for C. longa and Zea mays. Of the six primer pairs designed and tested, the correlation coefficients (R2) were higher than 0.99 and slopes were &minus, 3.136 to &minus, 3.498. The efficiency of the primers was between 93.14 and 108.4%. The specificity of the primers was confirmed with ten other species, which could be intentionally added to C. longa powders or used as ingredients in complex turmeric foods. In total, 20 blind samples and 10 commercial C. longa food products were tested with the designed primer sets to demonstrate the effectiveness of this approach to detect the addition of Z. mays products in turmeric powders. Taken together, the real-time PCR assay developed here has the potential to contribute to food safety and the protection of consumer&rsquo, s rights.

This study was conducted to evaluate the effects of L-arginine supplementation levels during late gestation on reproductive performance and piglet uniformity in high prolific sows. A total of 60 F1 multiparous sows (Yorkshire &times, Landrace), with an average body weight of 238.2 kg, were allotted to one of three treatment groups in a completely randomized design. The dietary treatments were divided by the supplementation level of arginine during the late-gestation period, from day 70 to farrowing, as follows&mdash, (1) CON: corn-soybean meal-based basal diet (Arg 0.72%), (2) Arg10: basal diet + L-Arg 0.28% (Arg 1.0%), and (3) Arg15: basal diet + L-Arg 0.79% (Arg 1.5%). The same lactation diet was provided ad libitum to sows during the lactation period. There were no significant differences in body weight and backfat thickness in sows during late-gestation and lactation. Dietary arginine levels had no significant influences on the number of total born, stillbirth, and born alive. However, increasing inclusion level of L-arginine supplementation tended to increase (p &lt, 0.10) alive litter weight linearly, and also linearly increased (p &lt, 0.05) the piglet weight gain and litter weight gain during the lactation period. In piglet uniformity, the standard deviation of piglet birth weight (p &lt, 0.05) and the coefficient of variation for piglet birth weight (p &lt, 0.10) increased linearly, as dietary arginine levels increased in the late gestation period. Increasing L-arginine supplementation to late gestating sows linearly increased (p &lt, 0.05) the blood concentrations of arginine and ornithine at day 90 and day 110 of gestation. On the other hand, dietary arginine levels in late gestation did not affect the blood parameters related to the nitrogen utilization. Increasing dietary arginine levels for the late gestating sows did not affect the milk composition for colostrum and milk at day 21 of lactation. In conclusion, the inclusion level of arginine in the diet for late gestating sows, by up to 1.5%, could improve the alive litter weight at birth and litter weight gain during lactation, whereas the piglet uniformity at birth was decreased due to the increase of survival for fetuses with light birth weight.

Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare (C. quadrangulare) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.

Background Aberrant AKT activation contributes to cancer stem cell (CSC) traits in hepatocellular carcinoma (HCC). We previously reported that CD73 activated AKT signaling via the Rap1/P110β cascade. Here, we further explored the roles of CD73 in regulating CSC characteristics of HCC. Methods CD73 expression modulations were conducted by lentiviral transfections. CD73+ fractions were purified by magnetic-based sorting, and fluorescent-activated cell sorting was used to assess differentiation potentials. A sphere-forming assay was performed to evaluate CSC traits in vitro, subcutaneous NOD/SCID mice models were generated to assess in vivo CSC features, and colony formation assays assessed drug resistance capacities. Stemness-associated gene expression was also determined, and underlying mechanisms were investigated by evaluating immunoprecipitation and ubiquitylation. Results We found CD73 expression was positively associated with sphere-forming capacity and elevated in HCC spheroids. CD73 knockdown hindered sphere formation, Lenvatinib resistance, and stemness-associated gene expression, while CD73 overexpression achieved the opposite effects. Moreover, CD73 knockdown significantly inhibited the in vivo tumor propagation capacity. Notably, we found that CD73+ cells exhibited substantially stronger CSC traits than their CD73– counterparts. Mechanistically, CD73 exerted its pro-stemness activity through dual AKT-dependent mechanisms: activating SOX9 transcription via c-Myc, and preventing SOX9 degradation by inhibiting glycogen synthase kinase 3β. Clinically, the combined analysis of CD73 and SOX9 achieved a more accurate prediction of prognosis. Conclusions Collectively, CD73 plays a critical role in sustaining CSCs traits by upregulating SOX9 expression and enhancing its protein stability. Targeting CD73 might be a promising strategy to eradicate CSCs and reverse Lenvatinib resistance in HCC.

Objectives. The incidence of hyperuricemia (HUA) is increasing year by year, and there are no ideal drugs for the treatment; the existing ones can cause serious liver and kidney damage. We have confirmed that the water extract of Dendrobium candidum leaves could reduce the level of uric acid in rats, but the active ingredients remain unknown, and the mechanism is not well understood. This research investigated the therapeutic effect of the macroporous resin extract of the Dendrobium candidum leaf (DLE) on hyperuricemia. In this study, hyperuricemia was induced in rats by a 5-week high-purine diet. After that, DLE was administered continuously for 9 weeks. The result showed that biochemical parameters of liver and kidney function, especially serum uric acid (UA) levels, were significantly improved with DLE, which may relate to the reduction of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the liver. Moreover, DLE could significantly prevent kidney and liver from damage, and intestinal injury and reduce inflammation in hyperuricemic rats by inhibiting the expression of both NF-κB and TLR4 proteins. These results showed that the macroporous resin extract of the Dendrobium candidum leaves may be effective for the treatment of hyperuricemia in rats by inhibiting uric acid production and decreasing inflammation.

Nω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension and liver injury. This study aimed at investigating the changes of liver lipometabonomics and exploring the underlying mechanisms of liver injury in the L-NAME-treated rats. The male Sprague-Dawley (SD) rats were treated with L-NAME (40 mg/kg, p.o.) for 8 weeks. After that, the liver, aorta, fecal, and serum were collected for analysis. The results showed that L-NAME induced hypertension and disordered the endothelial nitric oxide synthase (eNOS)-NO pathway in the treated rats. L-NAME could also increase the levels of serum total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), and aspartate transaminase (AST). The multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) analysis showed that L-NAME could induce significant changes of the total hepatic lipids and most hepatic triglycerides, as well as fatty acid (FA). A positive correlation was found between the blood pressure and TAG. Immunofluorescence and Western-Blot experiments indicated that the L-NAME treatment significantly influenced some FA β-oxidation, desaturation, and synthesis-related proteins. The increase of intestinal inflammation, decrease of microcirculation and tight junction proteins, as well as alterations of microbial communities were observed in the L-NAME induced hypertensive rats, as well as alterations of microbial communities were notable correlation to TAG and FA species. This study demonstrated that the L-NAME-induced hypertensive rats exhibiting liver injury were the joint action of hepatic abnormal fatty acid metabolism and microcirculation disorder. Furthermore, the gut microflora, as well as the changes of FA β-oxidation (ACOX, CPT1α), desaturation (SCD-1), and synthesis (FAS) may be the potential mechanisms for abnormal fatty acid metabolism.

In the course of screening for cosmetic ingredients by measuring antioxidant and antiwrinkle and whitening and anti-inflammatory activities, skin-related activity was tested using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 2,2 ′ -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, elastase inhibition, tyrosinase inhibition, and nitric oxide assay. Several Polygonaseae extracts were found to show potent activity. The results showed that the Persicaria senticosa methanolic extract has the 1,1­diphenyl-2­picrylhydrazyl (DPPH) and ABTS radical scavenging activities (IC50 61.0 and 17.5 μg/mL). In the elastase inhibition assay and nitric oxide assay, the IC50 of methanolic extract of Persicaria senticosa was 739.7 μg/mL and 71.8 μg/mL. The Persicaria senticosa 70% ethanolic extract partitioned with n-hexane, CH2Cl2, EtOAc, n-BuOH, and aqueous fractions. The purification of EtOAc soluble layer was by column chromatography separation and MPLC analysis of Compounds 1-7. It was identified as loliolide (1), quercetin-3-O-glucoside (2), quercetin-3-O-glucuronide (3), 4-methoxy caftraric acid (4), kaempferol-3-(6-methylglucuronide) (5), quercetin-3-(6-methylglucuronide) (6), and quercetin (7). Structure was elucidated by a combination of 1D and 2D NMR and MS spectrometry as well as comparison with reported literatures. Radical scavenging effect on DPPH, tyrosinase inhibition, and nitric oxide assay on several compounds from Persicaria senticosa was found to show potent activity. The results showed that Compound 7 has the NO assay (IC5029.7 μM). For DPPH, the IC50 of Compounds 2, 3, 5, and 7 was 39.6, 31.2, 37.0, and 22.7 μM. In tyrosinase inhibitory activity, the IC50 of Compound 7 was 14.3 μM.

Two new compounds, including a nor-pimarane diterpenoid (continentanol, 1) and a phenolic derivative (aralianic acid, 2), along with the known diterpenoids (3–11), polyacetylenes (12–15), phenolic components (16–28), and phytosterols (29 and 30), were isolated from roots of Aralia continentalis. The structures of the new compounds were established by spectroscopic data interpretation, particularly HRESIMS, 1 D and 2 D NMR data including HSQC and HMBC. Also, those of the known compounds were identified by spectral comparison with those of the reported values.

Bioassay-guided fractionation of the ethanolic extract from the whole plants of Pteridium aquilinum has resulted in the isolation of a new pterosin glycoside, (‒)-pteroside N (1), and a new seco-illudoid sesquiterpene, pterosinone (2). Their structures were identified by analysis of the spectroscopic data including extensive 2D NMR. All of the isolates were evaluated for the anti-Alzheimer disease (anti-AD) activity through enzyme inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). (‒)-Pteroside N (1) showed moderate BACE1 inhibitory activity (IC50 value: 30.6 μM), but exhibited potent inhibitory activity against AChE and BChE (IC50 values: 4.47 and 7.39 μM, respectively). On the other hand, pterosinone (2) showed mild AChE and BChE inhibitory activity (IC50 value: 87.7 and 72.9 μM), but exhibited potent inhibitory activity against BACE1 (IC50 value: 19.4 μM). The results of the present study demonstrate that sesquiterpenoids from P. aquilinum might be beneficial in the treatment of AD.

The adequate intake of energy and lysine for primiparous sows are necessary for maternal growth of sows and growth of their progeny. This study was conducted to evaluate the effects of dietary energy and lysine levels on primiparous sows and their progeny. A total of 48 gilts (Yorkshire × Landrace), with an initial body weight (BW) of 168.1 ± 9.71 kg and at day 35 of gestation, were allotted to eight treatment groups with a 2 × 4 factorial arrangement. The first factor was metabolizable energy levels in diet (3,265 or 3,365 kcal of ME/kg), and the second factor was lysine levels in diet (gestation 0.55%, 0.65%, 0.75%, 0.85%, lactation 0.70%, 0.85%, 1.00%, 1.15%). The BW gain (p = 0.07) and backfat thickness (p = 0.09) in the gestation period showed a tendency to be increased in sows fed the high-energy diets. In the lactation period, sows fed the high-energy diets tended to be greater BW (p = 0.09) and less BW loss (p = 0.05) than those of sows fed the low-energy diets. Sows fed high-energy diets had a tendency of greater piglet weight at day 21 of lactation and greater piglet weight gain (p = 0.08 and p = 0.08, respectively). Although the blood urea nitrogen (BUN) was increased linearly as dietary lysine level increased at day 110 of gestation (Linear, p = 0.03), the BUN was decreased linearly as dietary lysine level increase at day 21 of lactation (Linear, p < 0.01). In the composition of colostrum, sows fed high-energy diets had greater casein, protein, total solid, solid not fat, and free fatty acid concentrations than those of sows fed low-energy diets (p < 0.05). Supplementation of total lysine 0.75% for gestation and 1.00% for lactation with 3,365 kcal of ME/kg energy level could be applied to the primiparous sows’ diet to improve performance of sows and growth of their progeny.

Background: Tumor microenvironment (TME) cells is one of the important elements, constitute the tumor tissues and in predicting tumor clinical results and treatment effect has the important significance of clinical pathology. However, a detailed map for prognostic landscape of TME in Luminal B breast cancer is still lacking. Methods: ownloaded the expression profile and clinical follow-up information of luminal B breast cancer from TCGA and GEO, and used CIBERSORT to evaluate the infiltration mode of TME in 209 patients, and constructed the molecular subtype of luminal B breast cancer based on TME, further evaluated the relationship between molecular subtype and prognosis. DESeq2 was used to analyze the differentially expressed genes among molecular subtypes of luminal B breast cancer, and cox multivariate regression analysis was used for feature selection to construct TME signature. Results: ased on the median value of TMEscore, the samples were divided into High TMEscore and Low TMEscroe, and the relationship with prognosis, clinical features, immune gene expression and genomic variation was further evaluated. Different TME cells have significant correlation in luminal B breast cancer. These TME cells stratified different clinical results of luminal B breast cancer, and further TMEscore was established by Cox regression analysis. High TME score is associated with poor prognosis. Meanwhile, this study showed that CXCL10, CXCL9, GZMB and other immune activation genes and PDCD1LG2 and other immune checkpoint genes have higher expression levels in high TME score, and the mutation frequency of TP53 gene was lower in risk-H than that in risk-L. Conclusion: In this study, we systematically evaluated the TME infiltration patterns of 209 TCGA luminal B breast cancer patients and developed the TME score approach. It was found that TME score is a powerful prognostic biomarker and predictor of response to immunocheckpoint inhibitors and provides a new strategy for luminal B breast cancer immunotherapy.

OBJECTIVE This experiment was to evaluate the effects of the dietary energy levels on the physiological parameters and reproductive performance during gestation over three parities in sows. METHODS A total of 52 F1 gilts (Yorkshire×Landrace) were allotted to one of four dietary treatments using a completely randomized design. The treatments contained 3,100, 3,200, 3,300, or 3,400 kcal of metabolizable energy (ME)/kg diet but feed was provided at 2.0, 2.2, and 2.4 kg/d in the first, second and third parity, respectively. RESULTS The body weight and body weight gain during gestation increased as the dietary energy level increased (p

The main purpose of this study was to evaluate the antioxidant and neuroprotective activities in the aerial parts of seven Eragrostis species (Poaceae) and to find antioxidant or neuroprotective compounds from the most active species. The total phenolic content (TPC), total flavonoid content (TFC), 1,1-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH RSA), total antioxidant capacity (TAC), and neuroprotective activity against amyloid beta peptide induced toxicity in PC12 cells were measured in the methanol extracts of the aerial parts of E. ferruginea, E. cilianensis, E. minor, E. multicaulis, E. pilosa, E. japonica, and E. curvula collected from June to August 2013. All species showed antioxidant or neuroprotective activities and, among them, E. japonica was the most active species to isolate antioxidant or neuroprotective compounds, because it was found to show both the highest TPC (10.63 ± 0.31 mg/g) and TFC (2.83 ± 0.06 mg/g) values, as well as TAC (11.34 ± 0.80 mg/g) and DPPH RSA (47.07 ± 2.81 µg/mL), with the second-highest neuroprotective value (23.0 µg/mL). Three known compounds were isolated from E. japonica by the bioassay guided approach and these were identified as isoorientin, isovitexin, and caffeic acid that have antioxidant and neuroprotective activities.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy that is often resistant to therapy. Nowadays, chemotherapy is still one of the main methods for the treatment of ESCC. However, the multidrug resistance (MDR)-mediated chemotherapy resistance is one of the leading causes of death. Exploring agents able to reverse MDR, which thereby increase the sensitivity with clinical first-line chemotherapy drugs, could significantly improve cancer treatment. Cepharanthine hydrochloride (CEH) has the ability to reverse the MDR in ESCC and the mechanism involved have not been reported. The aim of the study was to investigate the potential of CEH to sensitize chemotherapeutic drugs in ESCC and explore the underlying mechanisms by in vitro and in vivo studies. Our data demonstrated that CEH significantly inhibited ESCC cell proliferation in a dose-dependent manner, induced G2/M phase cell cycle arrest and apoptosis, and increased the sensitivity of cell lines resistant to cisplatin (cDDP). Mechanistically, CEH inhibited ESCC cell growth and induced apoptosis through activation of c-Jun, thereby inhibiting the expression of P-gp, and enhancing p21 expression via activation of the p53 signaling pathway. In this study, we observed that growth of xenograft tumors derived from ESCC cell lines in nude mice was also significantly inhibited by combination therapy. To our knowledge, we demonstrate for the first time that CEH is a potentially effective MDR reversal agent for ESCC, based on downregulation of the mRNA expression of MDR1 and P-gp. Together, these results reveal emphasize CEH putative role as a resistance reversal agent for ESCC.

Background: Fresh pine needles, which evergreen, renewable and can be collected at any time, have abundant essential oil. The pine needle essential oil possess various biological activities, including antimicrobial, antioxidant, anti-inflammatory, cardioprotective properties etc., and can be widely used as medicine or medical raw materials, fragrances etc. So in order to make full use of pine needle plant resources, especially essential oil, the identification and quantification of essential oil were investigated. Materials and Methods: GC-MS was used to identified compounds in pine needle essential oil of Pinus massoniana Lamb. from Zhejiang, and GC method was developed for determining 5 compounds (namely α-pinene, β-pinene, limonene, bornyl acetate, β-caryophyllene) in pine needle essential oil from different habitats of Pinus massoniana Lamb. and different species (Pinus koraiensis Sieb. et Zucc., Pinus sylvestris var. mongolica Litv., Abies holophylla Maxim.). Hierarchical clustering analysis (HCA) was used to evaluate homogeneity of pine needles in China. Results: 42 compounds(monoterpenes and sesquiterpenes) were identified by GC-MS, which accounted for 99.62% of total essential oil, particularly contained α-and β-pinene (45.23%). Quantification results showed content of bornyl acetate were the lowest, while content of α-pinene, β-pinene were all high except Sichuan, among them α-pinene were higher than β-pinene except for Shandong and Jiangsu, and total content of essential oil in Guangxi is the highest, Jiangsu was the lowest within Pinus massoniana from different habitats. Within pine needle from different species, the highest total content was Pinus koraiensis, the lowest was Pinus sylvestris, Interestingly, the highest content of bornyl acetate was Abies holophylla. By HCA, samples were sorted into two clusters, Abies holophylla and the other, that is Abies holophylla is different from Pinus massoniana, Pinus koraiensis and Pinus sylvestris. Pinus massoniana from Sichuan is different from other Pinus, in which limonene was the highest in all samples. Conclusions: Compounds of pine needle essential oil vary greatly between genus, while smaller between species, so composition differences among pine needle essential oil was related with genus and species. Abies holophylla is different from other pinus species, and Pinus massoniana from Sichuan is different from other habitats. Pine needle essential oil contains abundant α-and β-pinene, which can be used as an alternative raw materials source of pinene. And Abies holophylla and Pinus massoniana from Sichuan can become bornyl acetate and limonene alternative source of raw materials.

Objective This study was conducted to evaluate various levels of milk by-product in weaning pig diet on growth performance, blood profiles, carcass characteristics and economic performance for weaning to finishing pigs. Methods A total of 160 weaning pigs ([Yorkshire×Landrace]×Duroc), average 7.01±1.32 kg body weight (BW), were allotted to four treatments by BW and sex in 10 replications with 4 pigs per pen in a randomized complete block design. Pigs were fed each treatment diet with various levels of milk by-product (Phase 1: 0%, 10%, 20%, and 30%, Phase 2: 0%, 5%, 10%, and 15%, respectively). During weaning period (0 to 5 week), weaning pigs were fed experimental diets and all pigs were fed the same commercial feed during growing-finishing period (6 to 14 week). Results In the growth trial, BW, average daily gain (ADG), and average daily feed intake (ADFI) in the nursery period (5 weeks) increased as the milk by-product level in the diet increased (linear, p

Saringosterol, a steroid isolated from Sargassum muticum, a brown edible alga widely distributed on the seashores of southern and eastern Korea, has been shown to exhibit anti-obesity effect. In this study, we investigated the anti-obesity activity of saringosterol through various experiments. The inhibitory effect of saringosterol on adipogenesis was evaluated via Oil Red O staining in 3T3-L1 preadipocytes. After confirming that saringosterol is not cytotoxic to these cells by using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, the effect of saringosterol on the expression of various adipogenesis-related genes was analyzed via quantitative real-time polymerase chain reaction and western blotting. We demonstrated that saringosterol dose dependently inhibited adipocyte differentiation and expression of adipogenic marker genes such as adipocyte fatty acid-binding protein, adiponectin, resistin, and fatty acid synthase in 3T3-L1 cells. In addition, saringosterol significantly inhibited the mRNA and protein expression of peroxisome proliferator-activated receptor γ and CCAAT enhancer-binding protein α in 3T3-L1 cells. Collectively, these findings indicate that saringosterol isolated from S. muticum exhibits anti-obesity effect by inhibiting the expression of adipogenic transcription factors and marker genes and that it may be developed as a drug to suppress adipogenesis. Copyright © 2017 John Wiley & Sons, Ltd.

Background To reduce use of main feed ingredient like corn, soy bean meal (SBM) and wheat, alternative ingredients has been studied like copra meal (CM). Production amount of CM which has been high makes CM to be an alternative feed stuff. However, low digestibility on AA and low energy content by high fiber content can be an obstacle for using CM. This experiment was conducted to evaluate the effects of CM supplementation with β-mannanase on growth performance, blood profile, nutrient digestibility, pork quality and economic analysis in growing-finishing pigs. Methods A total of 100 growing pigs ([Yorkshire × Landrace] × Duroc) averaging 31.22 ± 2.04 kg body weight were allotted to 5 different treatments by weight and sex in a randomized complete block (RCB) design in 5 replicate with 4 pigs per pen. Treatments were 1) Control (corn-SBM based diet + 0.1% of β-mannanase (800 IU)), 2) CM10 (10% copra meal + 0.1% β-mannanase (800 IU)), 3) CM15 (15% copra meal + 0.1% β-mannanase (800 IU)), 4) CM20 (20% copra meal + 0.1% β-mannanase (800 IU)) and 5) CM25 (25% copra meal + 0.1% β-mannanase (800 IU)). Four phase feeding program was used: growing I (week 1–3), growing II (week 4–6), finishing I (week 7–9) and finishing II (week 10–12). Results In growth performance, there was no significant difference among treatments during whole experimental period. In growingI phase, G:F ratio tended to increase when CM was increased (P = 0.05), but ADG and ADFI tended to decrease in finishingII phase (linear, P = 0.08). Also, increasing CM reduced ADG (linear, P = 0.02) and feed efficiency (linear, P = 0.08) during the whole finishing period. In blood profiles, BUN was linearly increased as CM increased (linear, P = 0.02) at growingII period. In digestibility trial, there was no significant difference in dry matter, crude fat, crude ash and nitrogen digestibility. However, crude protein digestibility was decreased linearly (linear, P = 0.02). In economic analysis, feed cost per weight gain and total feed cost per pig were reduced in overall period when CM was provided by 25% (linear, P = 0.02). Conclusion CM with 0.1% of β-mannanase (800 IU) could be supplemented instead of corn and SBM up to 25% without detrimental effects on growth performance and pork quality of growing-finishing pigs.

Two new flavonoid glycosides, excavaside A ( 1 ) and B ( 2 ), together with 14 known compounds, myricetin 3- O -β- d -rutinoside ( 3 ), myricetin 3,3′-di-α- l -rhamnopyranoside ( 4 ), myricetin 3′-α- l -rhamnopyranoside ( 5 ), myricitrin ( 6 ), myricetin ( 7 ), quercitrin ( 8 ), clauslactone B ( 9 ), clauslactone A ( 10 ), murrayacoumarin C ( 11 ), clauslactone E ( 12 ), triphasiol ( 13 ), clauslactone P ( 14 ), seseline ( 15 ), and 5-geranyloxy-7-hydroxycoumarin ( 16 ) have been isolated from the ethanol extract of the leaves and twigs of Clausena excavata . Among them, compounds 3 – 5 and 13 were isolated and identified from this plant for the first time. The structures of the new compounds were established by spectroscopic data interpretation, particularly HRESIMS, 1D and 2D NMR data including HSQC and HMBC. Also, those of the known compounds were identified by spectral comparison with those of the reported values.

Hyperuricemia is a clinical condition characterized by an elevated level of serum uric acid and is a key risk factor for the development of gout and metabolic disorders. The existing urate-lowering therapies are often impractical for certain patient populations, providing a rationale to explore new agents with improved safety and efficacy. Here, we discovered that Salvia plebeia extract inhibited the enzyme activity of xanthine oxidase, which is a key enzyme generating uric acid in the liver. In an animal model of hyperuricemia, S. plebeia extract reduced serum urate to the levels observed in control animals. The urate-lowering effect of S. plebeia extract in vivo was supported by the identification of compounds that inhibit xanthine oxidase enzyme activity in vitro. Nepetin, scutellarein, and luteolin contributed significantly to S. plebeia bioactivity in vitro. These compounds showed the highest potency against xanthine oxidase with IC50 values of 2.35, 1.74, and 1.90 µM, respectively, and were present at moderate quantities. These observations serve as a basis for further elaboration of the S. plebeia extracts for the development of new therapeutics for hyperuricemia and related diseases.

This study was conducted to investigate the effects of gestating sows housed in groups with electronic sow feeding (ESF) system over three consecutive parities. A total of 83 pregnant gilts [Yorkshire×Landrace] were housed into ST: gilts housed in individual stalls, and ESF: gilts housed in groups with ESF system on the basis of body weight (BW) and backfat thickness (BFT) in a completely randomized design. Rice hulls were used as bedding material on the group housing floor. The same commercial gestating diet was provided daily at 2.0 kg, 2.2 kg and 2.4 kg/day in the first, second and third parity, respectively, in both treatments. All sows introduced farrowing crates five days before expected farrowing. BW and BFT of the sows were measured at d 35, and 110 of gestation as well as at 12 h and d 21 postpartum. Parturition time was recorded during farrowing. Reproductive performance, including total born, stillborn, mummy, born alive, mortality, weaning pigs as well as litter and piglet weight were recorded. Scratch incidence and locomotion scores in sows were assessed at d 36, 70, and 110, respectively. Ten sows in each treatment were randomly selected for blood sampling. Serum samples were analyzed for cortisol and oxytocin levels. In the gestation period, ESF tended to increase BW gain in the second parity (P=0.08), and consistently showed significance during the third parity (P

A new oligostilbene, caragasinin C (1), and seven known compounds, betulinic acid (2), 4-hydroxybenzaldehyde (3), (‒)-medicarpin (4), wistin (5), (2E,4S)-4-hydroxy-2-nonenoic acid (6), pallidol (7), and (+)-α-viniferin (8), were isolated from the roots of Caragana sinica. The structure of caragasinin C was established on the basis of spectroscopic techniques, including HRESIMS, 1D and 2D-NMR.