Influence of the Hawthorne effect on spatiotemporal parameters, kinematics, ground reaction force, and the symmetry of the dominant and nondominant lower limbs during gait.

The Hawthorne effect is a change in behavior resulting from awareness of being observed or evaluated. This study aimed to determine whether awareness of being evaluated or presence of an observer influence gait. Twenty-one young women were asked to walk in three conditions. In the first condition (unawareness of evaluation; UE), participants were aware that it was a practice trial, and there was no observer. In the second condition (awareness of evaluation; AE), participants were aware that their gait was being evaluated. The third condition (AE + researcher observation; RO) was similar to the second condition except that an additional researcher observed the participant' gait. The spatiotemporal, kinematic, ground reaction forces, and ratio index (symmetry of both lower limbs) were compared among the three conditions. A higher ratio index indicated a relative increase in the value on left versus right. Gait speed (P = 0.012) and stride length (right and left; P = 0.006 and 0.007, respectively) were significantly increased in the AE + RO than in UE. Range of motion of the right hip and left ankle was significantly greater in AE than in UE (P = 0.039 and 0.012, respectively). The ratio index of ground reaction force during push-off was significantly higher in AE and AE + RO conditions than in UE (P < 0.001 and P = 0.004, respectively). The Hawthorne effect (awareness of being evaluated or presence of an observer) potentially influences gait. Thus, factors that influence gait analysis should be considered when evaluating normal gait.

MsrB1-regulated GAPDH oxidation plays programmatic roles in shaping metabolic and inflammatory signatures during macrophage activation.

Classically activated pro-inflammatory macrophages are generated from naive macrophages by pro-inflammatory cues that dynamically reprogram their fuel metabolism toward glycolysis. This increases their intracellular reactive oxygen species (ROS) levels, which then activate the transcription and release of pro-inflammatory mediators. Our study on mice that lack methionine sulfoxide reductase (Msr)-B1 shows that the resulting partial loss of protein methionine reduction in pro-inflammatory macrophages creates a unique metabolic signature characterized by altered fuel utilization, including glucose and pyruvate. This change also associates with hyper-inflammation that is at least partly due to sustained oxidation of an exposed methionine residue (M44) on glyceraldehyde 3-phosphate dehydrogenase (GAPDH), thereby inducing GAPDH aggregation, inflammasome activation, and subsequent increased interleukin (IL)-1ß secretion. Since MsrB1-knockout mice exhibit increased susceptibility to lipopolysaccharide (LPS)-induced sepsis, the MsrB1-GAPDH axis may be a key molecular mechanism by which protein redox homeostasis controls the metabolic profile of macrophages and thereby regulates their functions.

Examination of Microcystin Adsorption by the Type of Plastic Materials Used during the Procedure of Microcystin Analysis.

The incidence of eutrophication is increasing due to fertilizer abuse and global warming. Eutrophication can induce the proliferation of cyanobacteria such as Microcystis, which produces microcystins. Microcystins are toxic to specific organs such as the liver and the heart. Thus, monitoring of microcystins is strongly required to control drinking water and agricultural product qualities. However, microcystins could be adsorbed by plastic materials during sample storage and preparation, hindering accurate analysis. Therefore, the current study examined the recovery rate of microcystins from six plastics used for containers and eight plastics used for membrane filters. Among the six plastics used for containers, polyethylene terephthalate showed the best recovery rate (≥81.3%) for 48 h. However, polypropylene, polystyrene, and high- and low-density polyethylenes showed significant adsorption after exposure for 1 hr. For membrane materials, regenerated cellulose (≥99.3%) showed the highest recovery rate of microcystins, followed by polyvinylidene fluoride (≥94.1%) and polytetrafluoroethylene (≥95.7%). The adsorption of microcystins appeared to be strongly influenced by various molecular interactions, including hydrophobic interaction, hydrogen bonding, and electrostatic interaction. In addition, microcystins' functional residues seemed to be critical factors affecting their adsorption by plastic materials. The present study demonstrates that polyethylene terephthalate and regenerated cellulose membrane are suitable plastic materials for the analysis of microcystins.

Polygonum cuspidatum Extract (Pc-Ex) Containing Emodin Suppresses Lung Cancer-Induced Cachexia by Suppressing TCF4/TWIST1 Complex-Induced PTHrP Expression.

Cachexia, which is characterised by the wasting of fat and skeletal muscles, is the most common risk factor for increased mortality rates among patients with advanced lung cancer. PTHLH (parathyroid hormone-like hormone) is reported to be involved in the pathogenesis of cancer cachexia. However, the molecular mechanisms underlying the regulation of PTHLH expression and the inhibitors of PTHLH have not yet been identified. The PTHLH mRNA levels were measured using quantitative real-time polymerase chain reaction, while the PTHrP (parathyroid hormone-related protein) expression levels were measured using Western blotting and enzyme-linked immunosorbent assay. The interaction between TCF4 (Transcription Factor 4) and TWIST1 and the binding of the TCF4-TWIST1 complex to the PTHLH promoter were analysed using co-immunoprecipitation and chromatin immunoprecipitation. The results of the mammalian two-hybrid luciferase assay revealed that emodin inhibited TCF4-TWIST1 interaction. The effects of Polygonum cuspidatum extract (Pc-Ex), which contains emodin, on cachexia were investigated in vivo using A549 tumour-bearing mice. Ectopic expression of TCF4 upregulated PTHLH expression. Conversely, TCF4 knockdown downregulated PTHLH expression in lung cancer cells. The expression of PTHLH was upregulated in cells ectopically co-expressing TCF4 and TWIST1 when compared with that in cells expressing TCF4 or TWIST1 alone. Emodin inhibited the interaction between TCF4 and TWIST1 and consequently suppressed the TCF4/TWIST1 complex-induced upregulated mRNA and protein levels of PTHLH and PTHrP. Meanwhile, emodin-containing Pc-Ex significantly alleviated skeletal muscle atrophy and downregulated fat browning-related genes in A549 tumour-bearing mice. Emodin-containing Pc-Ex exerted therapeutic effects on lung cancer-associated cachexia by inhibiting TCF4/TWIST1 complex-induced PTHrP expression.

Oat (Avena sativa) Extract against Oxidative Stress-Induced Apoptosis in Human Keratinocytes.

Oat (Avena sativa) is well known for its various health benefits. The protective effect of oat extract against oxidative stress-induced apoptosis in human keratinocytes HaCaT was determined. First, extracts of two varieties of oat, Daeyang and Choyang, were analyzed for fat-soluble antioxidants such as α-tocotrienol, γ-oryzanols, lutein and zeaxanthin using an UPLC system and for antioxidant activity using a DPPH assay. Specifically, an 80% ethanol extract of Daeyang oat (Avena sativa cv. Daeyang), which had high amounts of antioxidants and potent radical scavenging activity, was further evaluated for protective effect against oxidative stress-induced cell death, intracellular reactive oxygen species levels, the phosphorylation of DNA damage mediating genes such as H2AX, checkpoint kinase 1 and 2, and p53 and the activation of apoptotic genes such as cleaved caspase-3 and 7 and poly (ADP-ribose) polymerase in HaCaT cells. The Daeyang and Choyang oat 80% ethanol extracts had 26.9 and 24.1 mg/100 g γ-oryzanols, 7.69 and 8.38 mg/100 g α-tocotrienol, 1.25 and 0.34 mg/100 g of lutein and 1.20 and 0.17 mg/100 g of zeaxanthin, respectively. The oat 80% ethanol extract treatment (Avena sativa cv. Daeyang) had a protective effect on oxidative stress-induced cell death in HaCaT cells. In addition, the oat 80% ethanol extracts led to a significant decrease in the intracellular ROS level at a concentration of 50-200 µg/mL, the attenuation of DNA damage mediating genes and the inhibition of apoptotic caspase activities in a dose dependent manner (50-200 µg/mL). Thus, the current study indicates that an oat (Avena sativa cv. Daeyang) extract rich in antioxidants, such as polyphenols, avenanthramides, γ-oryzanols, tocotrienols and carotenoids, has a protective role against oxidative stress-induced keratinocyte injuries and that oat may a useful source for oxidative stress-associated skin damage.

PGC1α Loss Promotes Lung Cancer Metastasis through Epithelial-Mesenchymal Transition.

PGC1α oppositely regulates cancer metastasis in melanoma, breast, and pancreatic cancer; however, little is known about its impact on lung cancer metastasis. Transcriptome and in vivo xenograft analysis show that a decreased PGC1α correlates with the epithelial-mesenchymal transition (EMT) and lung cancer metastasis. The deletion of a single Pgc1α allele in mice promotes bone metastasis of KrasG12D-driven lung cancer. Mechanistically, PGC1α predominantly activates ID1 expression, which interferes with TCF4-TWIST1 cooperation during EMT. Bioinformatic and clinical studies have shown that PGC1α and ID1 are downregulated in lung cancer, and correlate with a poor survival rate. Our study indicates that TCF4-TWIST1-mediated EMT, which is regulated by the PGC1α-ID1 transcriptional axis, is a potential diagnostic and therapeutic target for metastatic lung cancer.

Effects of gamma-aminobutyric acid and piperine on gene regulation in pig kidney epithelial cell lines.

OBJECTIVE: Gamma-aminobutyric acid (GABA) and piperine (PIP) are both nutritional supplements with potential use in animal diets. The purpose of this study is to investigate the effect of GABA and/or PIP treatment on the gene expression pattern of a pig kidney epithelial cell line. METHODS: LLCPK1 cells were treated with GABA, PIP, or both, and then the gene expression pattern was analyzed using microarray. Gene ontology analysis was done using GeneOntology (Geneontology.org), and validation was performed using quantitative real-time polymerase chain reaction. RESULTS: Gene ontology enrichment analysis was used to identify key pathway(s) of genes whose expression levels were regulated by these treatments. Microarray results showed that GABA had a positive effect on the transcription of genes related to regulation of erythrocyte differentiation and that GABA and PIP in combination had a synergistic effect on genes related to immune systems and processes. Furthermore, we found that effects of GABA and/or PIP on these selected genes were controlled by JNK/p38 MAPK pathway. CONCLUSION: These results can improve our understanding of mechanisms involved in the effect of GABA and/or PIP treatment on pig kidney epithelial cells. They can also help us evaluate their potential as a clinical diagnosis and treatment.

Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis.

Several reports have shown that thymoquinone (TQ) effectively attenuates angiogenesis in cancer cells, resulting in suppression of tumor growth. However, it is not yet clear whether TQ reduces hypoxia-inducible factor-1α (HIF-1α) expression in hypoxic cancer cells. Here, we found that TQ was a novel HIF-1α inhibitor through hypoxia response element (HRE)-luciferase assay-based large screening by using 502 natural compounds containing chemical library. TQ reduced HIF-1α protein levels in renal cancer cells; however, it did not affect the HIF-1α protein levels in the presence of proteasome inhibitor, MG132, indicating that the reduction effects of TQ on HIF-1α protein are mediated via the ubiquitination-proteasome dependent pathway. TQ boosted HIF-1α protein degradation, and the mechanism was revealed by inhibiting interaction between HSP90 and HIF-1α. TQ suppressed downstream genes of HIF-1α, indicating negative impact of TQ on HIF-1α transcriptional activities. In addition, TQ altered glucose, lactate, and ATP levels, leading to anaerobic metabolic disturbance. TQ induced apoptosis in hypoxic cancer cells as determined by crystal violet staining and flow cytometry for annexin V-stained cells. Taken together, we suggested that TQ is a potential anticancer agent targeting HIF-1α.

The graviola impact on human astroglioma cells: functional significance of MUDENG.

Graviola (Annona muricate) is a coveted tropical plant that has been found to be effective against many human cancers. Malignant glioblastoma multiformes are the most common and aggressive malignant forms of astrocytoma in the central nervous system. MUDENG (Mu-2-related death-inducing gene, MuD) is involved in cell death signaling. In this study, we investigated the impact of extracts from graviola leaves (from Korea and Africa), fruits and seeds against human astroglioma cells. Interestingly, graviola leaf extract-Korea (GLE-K), graviola leaf extract-Africa (GLE-A) and graviola fruit extract-Africa (GFE-A) exhibited significant cytotoxic effects on the cell proliferation in a dose-dependent manner and altered the MuD expression pattern. Cell cycle analyses revealed that GLE-A and GLE-K triggered no significant induction of apoptosis at concentrations up to 5% in U251-MG cells, while in GLE-K treated cells at 10% concentrations, there were much fewer apoptotic cells (33.64%) compared to those in GLE-A (73.55%) treated cells. In the case of GFE-A treated cells, 5% graviola extract (GE) concentration resulted in predominant cells entering the apoptotic phase (59.31%), whereas almost no significant increase in apoptotic cells was observed in GSE-A treated cells (1.38%) even up to 25% of graviola extract (GE) concentration. While using stable transfectants knock-out (KO)(-)-and overexpressing (OE)-MuD(+), significant and consistent differences in the cell viability (enhanced anti-astroglioma effect of GEs) were observed in KO-MuD(-) cells. This validated the functional consequence of MuD in the anti-astroglioma activity of GEs. Our results confirmed that GFE-A possesses the highest anti-astroglioma activity followed by the leaf extracts (GLE-A/K). This is the first report that highlights the MuD aspect of GEs.

Black soybeans protect human keratinocytes from oxidative stress-induced cell death.

Black soybeans are functional foods containing a variety of bioactives such as isoflavones, carotenoids, tocopherols, phenolic acid as well as anthocyanins. Here, we examined whether Cheongja#3 black soybean extract has a protective effect on oxidative stress-induced cell death in human keratinocytes HaCaT. First, we identified fat-soluble bioactives in three varieties of soybean extracts (Saedanbaek, Daechan, and Cheongja#3). In particular, black soybean Cheongja#3 had high amounts of lutein than other varieties. We demonstrated that Cheongja#3 extract reduced intracellular reactive oxygen species levels in HaCaT cells. Furthermore, Cheongja#3 protected cells from hydrogen peroxide (H2O2)-induced oxidative stress and triggered cell death determined by cell viabilities and apoptotic caspase activities. Next, we identified the underlying mechanism is due to increased Nrf2 antioxidant system by Cheongja#3, thus increasing the expression of heme oxygenases (HO)-1. These results indicated that Cheongja#3 soybean extract has protective role against oxidative stress by upregulating the Nrf-2 antioxidant system in human keratinocyte HaCaT cells.

Induction of functional erythropoietin and erythropoietin receptor gene expression by gamma-aminobutyric acid and piperine in kidney epithelial cells.

AIMS: The aim of this study was to evaluate gamma-aminobutyric acid (GABA)- and piperine-induced erythropoietin (EPO) and EPO-receptor expression. MATERIALS AND METHODS: The effect of GABA and piperine on cell viability was examined using kidney epithelial cells. Expression levels of EPO and EPO-R mRNA and protein were evaluated in response to GABA and piperine treatments. GABA- and piperine-mediated activation of the mitogen-activated protein kinase (MAPK) signaling pathway was investigated. Additionally, EPO function was evaluated using conditioned media containing EPO. The GABA receptor type involved in this process was identified. KEY FINDINGS: Messenger RNA and protein expression levels of EPO and EPO-R significantly increased in response to treatment with GABA, piperine, or the combination of both, compared with control. GABA plus piperine synergistically enhanced EPO and EPO-R expression through p38 and c-Jun N-terminal kinase (JNK) MAPK signaling pathways, but not through the extracellular signal-regulated kinase (ERK) MAPK pathway. SB203580 and SP600125 (p38 and JNK pathway inhibitors, respectively) attenuated GABA plus piperine-induced EPO and EPO-R expression. Treatment of macrophages with EPO-containing conditioned media induced mRNA expression of interleukin (IL)-10 and nuclear factor (NF)-κB due to the interaction between EPO and EPO-R. Interestingly, GABA-induced EPO and EPO-R expression was mediated through GABAA, not GABAB, receptor activation. SIGNIFICANCE: These findings demonstrate that GABA plus piperine-mediated p38 and JNK MAPK activation increases EPO and EPO-R expression, resulting in up-regulation of IL-10 and NF-κB.

Emodin Sensitizes Hepatocellular Carcinoma Cells to the Anti-Cancer Effect of Sorafenib through Suppression of Cholesterol Metabolism.

Reduced therapeutic efficacy of sorafenib, a first-generation multikinase inhibitor, is often observed during the treatment of advanced hepatocellular carcinoma (HCC). Emodin is an active component of Chinese herbs, and is effective against leukemia, lung cancer, colon cancer, pancreatic cancer, and HCC; however, the sensitizing effect of emodin on sorafenib-based HCC therapy has not been evaluated. Here, we demonstrate that emodin significantly improved the anti-cancer effect of sorafenib in HCC cells, such as HepG2, Hep3B, Huh7, SK-HEP-1, and PLC/PRF5. Mechanistically, emodin inhibits sterol regulatory element-binding protein-2 (SREBP-2) transcriptional activity, which suppresses cholesterol biosynthesis and oncogenic protein kinase B (AKT) signaling. Additionally, attenuated cholesterol synthesis and oncogenic AKT signaling inactivated signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. Furthermore, emodin synergistically increased cell cycle arrest in the G1 phase and apoptotic cells in the presence of sorafenib. Animal models xenografted with HepG2 or SK-HEP-1 cells also showed that the combination of emodin and sorafenib was sufficient to inhibit tumor growth. Overall, these results suggested that the combination of emodin and sorafenib may offer a potential therapy for patients with advanced HCC.

Zerumbone, a Tropical Ginger Sesquiterpene of Zingiber officinale Roscoe, Attenuates α-MSH-Induced Melanogenesis in B16F10 Cells.

Zerumbone (ZER), an active constituent of the Zingiberaceae family, has been shown to exhibit several biological activities, such as anti-inflammatory, anti-allergic, anti-microbial, and anti-cancer; however, it has not been studied for anti-melanogenic properties. In the present study, we demonstrate that ZER and Zingiber officinale (ZO) extract significantly attenuate melanin accumulation in α-melanocyte-stimulating hormone (α-MSH)-stimulated mouse melanogenic B16F10 cells. Further, to elucidate the molecular mechanism by which ZER suppresses melanin accumulation, we analyzed the expression of melanogenesis-associated transcription factor, microphthalmia-associated transcription factor (MITF), and its target genes, such as tyrosinase, tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2), in B16F10 cells that are stimulated by α-MSH. Here, we found that ZER inhibits the MITF-mediated expression of melanogenic genes upon α-MSH stimulation. Additionally, cells treated with different concentrations of zerumbone and ZO showed increased extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation, which are involved in the degradation mechanism of MITF. Pharmacological inhibition of ERK1/2 using U0126 sufficiently reversed the anti-melanogenic effect of ZER, suggesting that increased phosphorylation of ERK1/2 is required for its anti-melanogenic activity. Taken together, these results suggest that ZER and ZO extract can be used as active ingredients in skin-whitening cosmetics because of their anti-melanogenic effect.

Isotopic labelling for the characterisation of HNE-sequestering agents in plant-based extracts and its application for the identification of anthocyanidins in black rice with giant embryo.

Reactive carbonyl species (RCS) are cytotoxic molecules that originate from lipid peroxidation and sugar oxidation. Natural derivatives can be an attractive source of potential RCS scavenger. However, the lack of analytical methods to screen and identify bioactive compounds contained in complex matrices has hindered their identification. The sequestering actions of various rice extracts on RCS have been determined using ubiquitin and 4-hydroxy-2-nonenal (HNE) as a protein and RCS model, respectively. Black rice with giant embryo extract was found to be the most effective among various rice varieties. The identification of bioactive compounds was then carried out by an isotopic signature profile method using the characteristic isotopic ion cluster generated by the mixture of HNE: 2H5-HNE mixed at a 1:1 stoichiometric ratio. An in-house database was used to obtain the structures of the possible bioactive components. The identified compounds were further confirmed as HNE sequestering agents through HPLC-UV analysis.

Enhanced Antioxidant Activity of Bioactives in Colored Grains by Nano-Carriers in Human Lens Epithelial Cells.

The use of phytochemicals for preventing chronic diseases associated with oxidative stress such as cataracts is hindered by their low bioavailability. The effects of nano-carriers on the antioxidant activities of extracts of black rice with giant embryo (BRGEx) and soybeans (SBx) have been determined in human lens epithelial B3 cells. Scanning (SEM) and transmission electron microscopy (TEM) demonstrated that rGO (reduced graphene oxide) has a flat surface unlike GO (graphene oxide), which has a distinctive wrinkled structure with defects. UPLC analysis revealed 41.9 µg/100 g of γ-oryzanols in water extract of BRGE, and 111.8 µg /100 g of lutein, 757.7 µg/100 g of γ-tocotrienol, 4071.4 µg/100 g of γ-tocopherol in 40% ethanol extract of soybeans, respectively. Even though a low concentration of BRGEx alone did not show any antioxidant activity in B3 cells, co-treatment of BRGEx with rGO together substantially reduced hydrogen peroxide and methylglyoxal-induced DNA damage, as determined by phosphorylated γH2AX. In addition, SBx with rGO also attenuated DNA damage. Furthermore, intracellular reactive oxygen species were significantly decreased by combining extracts of these colored grains with rGO. These results suggest a potential application of nanocarriers for enhancing the bioavailability of phytochemicals.

Silver nanoparticle-induced hormesis of astroglioma cells: A Mu-2-related death-inducing protein-orchestrated modus operandi.

Hormesis is a dose-response phenomenon that, when applied to nanomaterial-biological interactions, refers to growth stimulation at low doses and growth inhibition at high doses. MUDENG (Mu-2-related death-inducing gene, MuD) is involved in cell death signaling. Astrocytes, the major glial cell type in the central nervous system, are a major source of brain tumors. In this study, we investigated whether silver nanoparticles (AgNPs) induce hormesis in astroglioma cells and the possible involvement of MuD in AgNP-induced hormesis. AgNPs exhibited cytotoxic effects on cell proliferation in a dose-dependent manner and increased MuD expression was observed during AgNP-induced astroglioma hormesis. Studies using MuD-knockout cells and MuD siRNA transfection showed that MuD might influence cell viability upon AgNP treatment. In addition, apoptotic cell population and production of reactive oxygen species in the absence of MuD were significantly increased. The phosphorylation of two mitogen-activated protein kinases, p38 and extracellular signal-regulated kinase (ERK), but not c-Jun N-terminal kinases (JNK), was observed upon AgNP stimulation. In summary, AgNPs at low doses induced hormesis of human astroglioma cells, and MuD and p38/ERK mediators are involved in AgNP-induced astroglioma hormesis, resulting in beneficial effects from the cellular point of view.

Dietary Anthocyanins against Obesity and Inflammation.

Chronic low-grade inflammation plays a pivotal role in the pathogenesis of obesity, due to its associated chronic diseases such as type II diabetes, cardiovascular diseases, pulmonary diseases and cancer. Thus, targeting inflammation is an attractive strategy to counter the burden of obesity-induced health problems. Recently, food-derived bioactive compounds have been spotlighted as a regulator against various chronic diseases due to their low toxicity, as opposed to drugs that induce severe side effects. Here we describe the beneficial effects of dietary anthocyanins on obesity-induced metabolic disorders and inflammation. Red cabbage microgreen, blueberry, blackcurrant, mulberry, cherry, black elderberry, black soybean, chokeberry and jaboticaba peel contain a variety of anthocyanins including cyanidins, delphinidins, malvidins, pelargonidins, peonidins and petunidins, and have been reported to alter both metabolic markers and inflammatory markers in cells, animals, and humans. This review discusses the interplay between inflammation and obesity, and their subsequent regulation via the use of dietary anthocyanins, suggesting an alternative dietary strategy to ameliorate obesity and obesity associated chronic diseases.

Fascaplysin Exerts Anti-Cancer Effects through the Downregulation of Survivin and HIF-1α and Inhibition of VEGFR2 and TRKA.

Fascaplysin has been reported to exert anti-cancer effects by inhibiting cyclin-dependent kinase 4 (CDK4); however, the precise mode of action by which fascaplysin suppresses tumor growth is not clear. Here, we found that fascaplysin has stronger anti-cancer effects than other CDK4 inhibitors, including PD0332991 and LY2835219, on lung cancer cells that are wild-type or null for retinoblastoma (RB), indicating that unknown target molecules might be involved in the inhibition of tumor growth by fascaplysin. Fascaplysin treatment significantly decreased tumor angiogenesis and increased cleaved-caspase-3 in xenografted tumor tissues. In addition, survivin and HIF-1α were downregulated in vitro and in vivo by suppressing 4EBP1-p70S6K1 axis-mediated de novo protein synthesis. Kinase screening assays and drug-protein docking simulation studies demonstrated that fascaplysin strongly inhibited vascular endothelial growth factor receptor 2 (VEGFR2) and tropomyosin-related kinase A (TRKA) via DFG-out non-competitive inhibition. Overall, these results suggest that fascaplysin inhibits TRKA and VEGFR2 and downregulates survivin and HIF-1α, resulting in suppression of tumor growth. Fascaplysin, therefore, represents a potential therapeutic approach for the treatment of multiple types of solid cancer.

Inhibition of NAT10 Suppresses Melanogenesis and Melanoma Growth by Attenuating Microphthalmia-Associated Transcription Factor (MITF) Expression.

N-acetyltransferase 10 (NAT10) has been considered a target for the treatment of human diseases such as cancer and laminopathies; however, its functional role in the biology of melanocytes is questionable. Using a small molecule or small interfering RNA targeting NAT10, we examined the effect of NAT10 inhibition on melanogenesis and melanoma growth in human and mouse melanoma cells. Genetic silencing or chemical inhibition of NAT10 resulted in diminished melanin synthesis through the suppression of melanogenesis-stimulating genes such as those encoding dopachrome tautomerase (DCT) and tyrosinase in B16F10 melanoma cells. In addition, NAT10 inhibition significantly increased cell cycle arrest in S-phase, thereby suppressing the growth and proliferation of malignant melanoma cells in vitro and in vivo. These results demonstrate the potential role of NAT10 in melanogenesis and melanoma growth through the regulation of microphthalmia-associated transcription factor (MITF) expression and provide a promising strategy for the treatment of various skin diseases (melanoma) and pigmentation disorders (chloasma and freckles).

Implications of red Panax ginseng in oxidative stress associated chronic diseases.

The steaming process of Panax ginseng has been reported to increase its major known bioactive components, ginsenosides, and, therefore, its biological properties as compared to regular Panax ginseng. Biological functions of red Panax ginseng attenuating pro-oxidant environments associated with chronic diseases are of particular interest, since oxidative stress can be a key contributor to the pathogenesis of chronic diseases. Additionally, proper utilization of various biomarkers for evaluating antioxidant activities in natural products, such as ginseng, can also be important to providing validity to their activities. Thus, studies on the effects of red ginseng against various diseases as determined in cell lines, animal models, and humans were reviewed, along with applied biomarkers for verifying such effects. Limitations and future considerations of studying red ginseng were been discussed. Although further clinical studies are warranted, red ginseng appears to be beneficial for attenuating disease-associated symptoms via its antioxidant activities, as well as for preventing oxidative stress-associated chronic diseases.