Apigenin (4',5,7-trihydroxyflavone, flavonoid) is a phenolic compound that is known to reduce the risk of chronic disease owing to its low toxicity. The first study on apigenin analyzed its effect on ...histamine release in the 1950s. Since then, anti-mutation and antitumor properties of apigenin have been widely reported. In the present study, we evaluated the apigenin-mediated amelioration of skin disease and investigated its applicability as a functional ingredient, especially in cosmetics. The effect of apigenin on RAW264.7 (murine macrophage), RBL-2H3 (rat basophilic leukemia), and HaCaT (human immortalized keratinocyte) cells were analyzed. Apigenin (100 μM) significantly inhibited nitric oxide (NO) production, cytokine expression (interleukin (IL)-1β, IL6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase iNOS), and phosphorylation of mitogen-activated protein kinase (MAPK) signal molecules, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) in RAW264.7 cells. Apigenin (30 M) also inhibited the phosphorylation of signaling molecules (Lyn, Syk, phospholipase Cγ1, ERK, and JNK) and the expression of high-affinity IgE receptor FcεRIα and cytokines (tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-6, IL-13, and COX-2) that are known to induce inflammation and allergic responses in RBL-2H3 cells. Further, apigenin (20 μM) significantly induced the expression of filaggrin, loricrin, aquaporin-3, hyaluronic acid, hyaluronic acid synthase (HAS)-1, HAS-2, and HAS-3 in HaCaT cells that are the main components of the physical barrier of the skin. Moreover, it promoted the expression of human β-defensin (HBD)-1, HBD-2, HBD-3, and cathelicidin (LL-37) in HaCaT cells. These antimicrobial peptides are known to play an important role in the skin as chemical barriers. Apigenin significantly suppressed the inflammatory and allergic responses of RAW264.7 and RBL cells, respectively, and would, therefore, serve as a potential prophylactic and therapeutic agent for immune-related diseases. Apigenin could also be used to improve the functions of the physical and chemical skin barriers and to alleviate psoriasis, acne, and atopic dermatitis.
Aquaponics is known to be one of the most efficient agriculture production systems by far; however, limited quantitative data are available on the level of efficiency, particularly in comparison to ...its counterpart, hydroponics. This study compared aquaponics with hydroponics to assess nitrogen (N) and phosphorus (P) distributions, N- and P-use efficiency (NUE and PUE), and potential environmental impacts. Cherry tomato, basil, and lettuce were cultured in recirculating tilapia (Oreochromis niloticus)-based aquaponic or stand-alone hydroponic systems over a 3-month period. N and P mass balances were developed by using N and P concentrations in fish feed, solid waste, wastewater, fish biomass, and plant biomass for aquaponic systems, and chemical fertilizer, wastewater, and plant biomass for hydroponic systems, which were to estimate N and P loss from each system via denitrification and P precipitations, respectively. In aquaponics, 59–70% of total N input was estimated to be lost via denitrification (45–50%), wastewater (14–20%), and solid waste (0.7–2%) and 30–41% was assimilated into biomass (21–24% fish; 9–17% plants). In hydroponics, 76–87% was estimated to be lost via denitrification (69–78%) and wastewater (7–15%), and only 14–24% was assimilated into biomass. Similarly, 38–54% of total P input in aquaponics was lost via wastewater (22–28%), precipitations (8–25%), and solid waste (2–7%) and 46–62% was assimilated into biomass (35–45% fish; 11–25% plants). In hydroponics, 79–89% of total P input was lost via wastewater (52–74%) and precipitations (15–27%), and only 11–21% was assimilated into plant biomass. Plant species had a significant impact on N and P distribution, and tomato was most effective in removing N from wastewater and reducing denitrification via higher biomass production compared to basil and lettuce. NUE was lower for aquaponics than for hydroponics when only edible plant parts were taken into consideration, but 71–114% higher when both fish and plant biomass were considered. Meanwhile, PUE was higher for aquaponics than for hydroponics even only when edible parts were considered and 336–369% higher when the biomass of both crops was considered. Our N and P mass balance analyses demonstrated for the first time that aquaponics is more efficient than hydroponics. Greater N and P losses in hydroponics were mainly due to higher N and P inputs, causing 2 times higher N loss via gas emission and up to 3 times higher P loss via inorganic P in wastewater compared to aquaponics. Therefore, reducing nutrient inputs is critical in improving NUE and PUE for both aquaponics and hydroponics, which should be combined with proper crop choice, operation conditions, and management practices to further improve the efficiency of the systems.
•N and P mass balances were compared between aquaponics and hydroponics.•Aquaponics decreases N, P loss by 21 and 49% respectively compared to hydroponics.•N-, P-use efficiency (NUE; PUE) was respectively 2, 4 times higher in aquaponics.•Tomato-based aquaponics has higher NUE and PUE than other plant-based systems.•High N and P inputs were the major cause of reduced efficiency in both systems.
Cumulative studies have indicated that high-dose vitamin C has antitumor effects against a variety of cancers. However, the molecular mechanisms underlying these inhibitory effects against ...tumorigenesis and metastasis, particularly in relation to pancreatic cancer, are unclear. Here, we report that vitamin C at high concentrations impairs the growth and survival of pancreatic ductal adenocarcinoma (PDAC) cells by inhibiting glucose metabolism. Vitamin C was also found to trigger apoptosis in a caspase-independent manner. We further demonstrate that it suppresses the invasion and metastasis of PDAC cells by inhibiting the Wnt/β-catenin-mediated epithelial-mesenchymal transition (EMT). Taken together, our results suggest that vitamin C has therapeutic effects against pancreatic cancer.
Recurrence and chemoresistance in colorectal cancer remain important issues for patients treated with conventional therapeutics. Metformin and phenformin, previously used in the treatment of ...diabetes, have been shown to have anticancer effects in various cancers, including breast, lung and prostate cancers. However, their molecular mechanisms are still unclear. In this study, we examined the effects of these drugs in chemoresistant rectal cancer cell lines. We found that SW837 and SW1463 rectal cancer cells were more resistant to ionizing radiation and 5‐fluorouracil than HCT116 and LS513 colon cancer cells. In addition, metformin and phenformin increased the sensitivity of these cell lines by inhibiting cell proliferation, suppressing clonogenic ability and increasing apoptotic cell death in rectal cancer cells. Signal transducer and activator of transcription 3 and transforming growth factor‐β/Smad signaling pathways were more activated in rectal cancer cells, and inhibition of signal transducer and activator of transcription 3 expression using an inhibitor or siRNA sensitized rectal cancer cells to chemoresistant by inhibition of the expression of antiapoptotic proteins, such as X‐linked inhibitor of apoptosis, survivin and cellular inhibitor of apoptosis protein 1. Moreover, metformin and phenformin inhibited cell migration and invasion by suppression of transforming growth factor β receptor 2‐mediated Snail and Twist expression in rectal cancer cells. Therefore, metformin and phenformin may represent a novel strategy for the treatment of chemoresistant rectal cancer by targeting signal transducer and activator of transcription 3 and transforming growth factor‐β/Smad signaling.
Metformin and phenformin decreased the expression of pro‐apoptotic proteins by inhibiting STAT3 phosphorylation at Ser‐727 and suppressed invasion and migration by inhibiting TGFBR2‐mediated signaling
Eutectic gallium–indium alloy (EGaIn) liquid metal is highly conductive, moldable, and extremely deformable and has attracted significant attention for many applications, ranging from stretchable ...electronics to drug delivery. Even though EGaIn liquid metal is generally known to have low toxicity, the toxicity of the metal, rather than a salt form of Ga or In, has not been systematically studied yet. In this paper, we investigate the time-dependent concentration of the ions released from EGaIn liquid metal in an aqueous environment and their cytotoxicity to human cells. It is observed that only the Ga ion is dominantly released from EGaIn when no external agitation is applied, whereas the concentration of the In ion drastically increases with sonication. The cytotoxicity study reveals that all human cells tested are viable in the growth media with naturally released EGaIn ions, but the cytotoxicity becomes significant with sonication-induced EGaIn releasates. On the basis of the comparative study with other representative toxic elements, that is, Hg and Cd, it could be concluded that EGaIn is reasonably safe to use in an aqueous environment; however, it should be cautiously handled when any mechanical agitation is applied.
Based on problem behavior theory and interpersonal acceptance–rejection theory, this study aimed to examine the mediating roles of self-esteem and fear of missing out (FoMO) on the influence of ...parental support on adolescents’ problematic smartphone use. This study is a cross-sectional and descriptive study. A total of 260 Korean adolescents from two public middle schools were selected through convenience sampling (female, 50.4%; mean age, 13.16 ± 0.84; range age, 12~15). Participants completed self-report questionnaires assessing sociodemographic characteristics, parental support, self-esteem, FoMO, and problematic smartphone use. The collected data were analyzed using descriptive statistics, t-test, ANOVA, Pearson’s correlation coefficients, and mediation analysis. The findings show that self-esteem and FoMO play a serial mediating role in the relationship between parental support and adolescents’ problematic smartphone use. Specifically, parental support had a negative effect on adolescents’ problematic smartphone use by increasing self-esteem but decreasing FoMO. These results provide further guidance in the prevention of and intervention of adolescent problematic smartphone use.
Keratin (KRT) 19 is a poor prognostic marker for hepatocellular carcinoma (HCC); however, regulatory mechanisms underlying its expression remain unclear. We have previously reported the presence of ...fibrous tumor stroma in KRT19-positive HCC, suggesting that cross-talk between cancer-associated fibroblasts (CAF) and tumor epithelial cells could regulate KRT19 expression. This was investigated in this study using an
model of paracrine interaction between HCC cell lines (HepG2, SNU423) and hepatic stellate cells (HSC), a major source of hepatic myofibroblasts. HSCs upregulated transcription and translation of KRT19 in HCC cells via paracrine interactions. Mechanistically, hepatocyte growth factor (HGF) from HSCs activated c-MET and the MEK-ERK1/2 pathway, which upregulated KRT19 expression in HCC cells. Furthermore, AP1 (JUN/FOSL1) and SP1, downstream transcriptional activators of ERK1/2, activated KRT19 expression in HCC cells. In clinical specimens of human HCC (
= 339), HGF and KRT19 protein expression correlated with CAF levels. In addition, HGF or MET protein expression was associated with FOSL1 and KRT19 expression and was found to be a poor prognostic factor. Analysis of data from The Cancer Genome Atlas also revealed KRT19 expression was closely associated with CAF and MET-mediated signaling activities. These results provide insights into the molecular background of KRT19-positive HCC that display an aggressive phenotype.
These findings reveal KRT19 expression in hepatocellular carcinoma is regulated by cross-talk between cancer-associated fibroblasts and HCC cells, illuminating new therapeutic targets for this aggressive disease.
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Nitrate in fruits and vegetables Colla, Giuseppe; Kim, Hye-Ji; Kyriacou, Marios C. ...
Scientia horticulturae,
07/2018, Letnik:
237
Journal Article
Recenzirano
•Scientific advances on nitrate accumulation in plant tissues are reviewed.•Genetic, agroenvironmental and postharvest factors are critically examined.•Horticultural commodities are classified based ...on nitrate level of edible product.•The physiological and developmental role of nitrate as osmoticum is examined.•Nitrate management practices and future research warranted are highlighted.
The current article provides an updated review of scientific advances regarding nitrate accumulation in plant tissues and a critical examination of the genetic, agroenvironmental and postharvest factors that can modulate nitrate levels in a wide range of horticultural crops, including herbs, roots and tubers, inflorescences, buds, seeds, stems, and leafy vegetables, fungi as well as fruits. A refined classification of horticultural crops is presented according to the nitrate content of their edible product. The role of plant cultivar/morphotype and tissue age in nitrate accumulation is discussed along with the physiological role of nitrate as osmoticum in maintaining turgor and driving leaf expansion under conditions of variable photosynthetic capacity. Nitrate accumulation is examined in respect to key cultural practices, such as the timing-rate-form of N application and the use of plant biostimulants (natural substances and microbial inoculants), as well as the potential interaction with other nutrients (e.g., P, Ca, Mo and Cl). The influence of environmental conditions during plant growth (light intensity, spectral quality, photoperiod, air and root-zone temperature and atmospheric CO2 concentration), harvest stage and diurnal timing of harvest is assessed. Postharvest storage conditions (temperature, light, and duration) are discussed in respect to their effects on the putative endogenous conversion of nitrate residues to nitrites. Several approaches that may be adopted to reduce nitrate content in vegetables, fruits and herbs are analysed and warranted future research subjects are identified.
The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆
-tetrahydrocannabinol (∆
-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of ...the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆
-THC is known to bring about the 'high' associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing these receptors and in C57BL/6 mice in an attempt to better understand their pharmacodynamics. Specifically, ∆
-THC, ∆
-tetrahydrocannabinolic acid (∆
-THCa), ∆
-tetrahydrocannabivarin (THCV), CBD, cannabidiolic acid (CBDa), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC) were evaluated. Compounds were assessed for their affinity to receptors, ability to inhibit cAMP accumulation, βarrestin2 recruitment, receptor selectivity, and ligand bias in cell culture; and cataleptic, hypothermic, anti-nociceptive, hypolocomotive, and anxiolytic effects in mice. Our data reveal partial agonist activity for many phytocannabinoids tested at CB1R and/or CB2R, as well as in vivo responses often associated with activation of CB1R. These data build on the growing body of literature showing cannabinoid receptor-dependent pharmacology for these less-abundant phytocannabinoids and are critical in understanding the complex and interactive pharmacology of Cannabis-derived molecules.
Abstract
Yeast is an integral part of mammalian microbiome, and like commensal bacteria, has the potential of being harnessed to influence immunity in clinical settings. However, functional ...specificities of yeast-derived immunoregulatory molecules remain elusive. Here we find that while under steady state, β-1,3-glucan-containing polysaccharides potentiate pro-inflammatory properties, a relatively less abundant class of cell surface polysaccharides, dubbed mannan/β-1,6-glucan-containing polysaccharides (MGCP), is capable of exerting potent anti-inflammatory effects to the immune system. MGCP, in contrast to previously identified microbial cell surface polysaccharides, through a Dectin1-Cox2 signaling axis in dendritic cells, facilitates regulatory T (Treg) cell induction from naïve T cells. Furthermore, through a TLR2-dependent mechanism, it restrains Th1 differentiation of effector T cells by suppressing IFN-γ expression. As a result, administration of MGCP display robust suppressive capacity towards experimental inflammatory disease models of colitis and experimental autoimmune encephalomyelitis (EAE) in mice, thereby highlighting its potential therapeutic utility against clinically relevant autoimmune diseases.
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