Pyropia yezoensis peptide promotes collagen synthesis by activating the TGF-ß/Smad signaling pathway in the human dermal fibroblast cell line Hs27.

Pyropia yezoensis (P. yezoensis) is a marine algae that exhibits antioxidant, anti-inflammatory, antitumor and anti-aging activities. In this study, we investigated the effects of the P. yezoensis peptide, PYP1­5, on collagen synthesis in the human dermal fibroblast cell line Hs27. Skin aging is related to reduced collagen production and the activities of multiple enzymes, including matrix metalloproteinases (MMPs), which degrade collagen structure in the dermis, and tissue inhibitor of tissue inhibitor of metalloproteinases (TIMPs), which inhibit the action of MMPs. While collagen synthesis is associated with a number of signaling pathways, we examined the increased collagen synthesis via the upregulation of the transforming growth factor-ß (TGF-ß)/Smad signaling pathway. Using MTS assay, we found that PYP1­5 did not affect cell viability. Moreover, we confirmed that PYP1­5 increased type 1 collagen expression using enzyme-linked immunosorbent assay (ELISA), western blot analysis and quantitative PCR. In addition, we identified changes in various enzymes, as well as the mechanisms behind the PYP1­5-induced collagen synthesis. PYP1­5 decreased the MMP-1 protein and mRNA levels, and increased the TIMP-1 and TIMP-2 protein and mRNA levels. In addition, PYP1­5 activated the TGF-ß/Smad signaling pathway, which increased TGF-ß1, p-Smad2 and p-Smad3 expression, while inhibiting Smad7, an inhibitor of the TGF-ß/Smad pathway. Furthermore, PYP1­5 upregulated transcription factor specificity protein 1 (Sp1) expression, which is reportedly involved in type 1 collagen expression. These findings indicate that PYP1­5 activates the TGF-ß/Smad signaling pathway, which subsequently induces collagen synthesis in Hs27 cells.

Ischemia Reperfusion Injury Triggers TNFα Induced-Necroptosis in Rat Retina.

PURPOSE: A recent study revealed a novel form of cell death, termed necroptosis, or programmed necrosis. Previous research indicated that after ischemia-reperfusion (IR) injury to the retina, Tumor Necrosis Factor α (TNFα) is increased, which may activate necroptosis. This study observed macroglial cell activation, and in particular, astrocyte activation, after the release of TNFα and other necroptosis factors in the rat retina due to IR. MATERIALS AND METHODS: IR was induced in the retinas of adult male Sprague-Dawley rats by increasing the intraocular pressure to 160 mmHg and then allowing reperfusion. In addition, to inhibit necroptosis, Nec-1 (necrostatin-1) was injected intravitreally after IR. Rats were sacrificed after reperfusion at 12 hours, 1, 3, and 5 days, and 1 and 2 weeks. Retinas from each time point were analyzed by immunohistochemistry (IHC) and Western blotting (WB) to identify the initiator of necroptosis, TNFα, the expression of necroptosis factors, such as receptor interacting protein (RIP) 1, 3, and inactive caspase 8, and Brn3a. RESULTS: Cell death in the IR-injured retinas was identified by cell counting. We found decreased retinal cell numbers in the inner and outer nuclear layers (INL and ONL), as well as in the ganglion cell layer (GCL). Increased glial cell activation was detected by using glial fibrillary acidic protein (GFAP) IHC. TNFα, RIP1, RIP3, and inactive caspase 8 were mainly expressed in the GCL after IR, as determined by IHC and WB. Nec-1 inhibited RIP1, a necroptosis factor, indicating protection against retinal cell loss after IR injury. CONCLUSIONS: We showed that IR injury triggered increases in both activation of astrocytes and the expression of TNFα. In addition, TNFα, which was activated by IR, triggered the release of necroptosis factors, particularly, in GCL. Inhibition of necroptosis using Nec-1 decreased the level of RIP1 and retinal cell loss in IR-injured retinas.

Responsive Surface Methodology Optimizes Extraction Conditions of Industrial by-products, Camellia japonica Seed Cake.

BACKGROUND: The central nervous system is easily damaged by oxidative stress due to high oxygen consumption and poor defensive capacity. Hence, multiple studies have demonstrated that inhibiting oxidative stress-induced damage, through an antioxidant-rich diet, might be a reasonable approach to prevent neurodegenerative disease. OBJECTIVE: In the present study, response surface methodology was utilized to optimize the extraction for neuro-protective constituents of Camellia japonica byproducts. MATERIALS AND METHODS: Rat pheochromocytoma cells were used to evaluate protective potential of Camellia japonica byproducts. RESULTS: Optimum conditions were 33.84 min, 75.24%, and 75.82°C for time, ethanol concentration and temperature. Further, we demonstrated that major organic acid contents were significantly impacted by the extraction conditions, which may explain varying magnitude of protective potential between fractions. CONCLUSIONS: Given the paucity of information in regards to defatted C. japonica seed cake and their health promoting potential, our results herein provide interesting preliminary data for utilization of this byproduct from oil processing in both academic and industrial applications. SUMMARY: Neuro-protective potential of C. japonica seed cake on cell viability was affected by extraction conditionsExtraction conditions effectively influenced on active constituents of C. japonica seed cakeBiological activity of C. japonica seed cake was optimized by the responsive surface methodology. Abbreviations used: GC-MS: Gas chromatography-mass spectrometer, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, PC12 cells: Pheochromocytoma, RSM: Response surface methodology.

Cinnamomum loureirii Extract Inhibits Acetylcholinesterase Activity and Ameliorates Trimethyltin-Induced Cognitive Dysfunction in Mice.

The pathogenesis of Alzheimer's disease (AD) has been linked to the deficiency of neurotransmitter acetylcholine (ACh) in the brain, and the main treatment strategy for improving AD symptoms is the inhibition of acetylcholinesterase (AChE) activity. In the present study, we aimed to identify potent AChE inhibitors from Cinnamomum loureirii extract via bioassay-guided fractionation. We demonstrated that the most potent AChE inhibitor present in the C. loureirii extract was 2,4-bis(1,1-dimethylethyl)phenol. To confirm the antiamnesic effects of the ethanol extract of C. loureirii, mice were intraperitoneally injected with the neurotoxin trimethyltin (2.5 mg/kg) to induce cognitive dysfunction, and performance in the Y-maze and passive avoidance tests was assessed. Treatment with C. loureirii extract significantly improved performance in both behavioral tests, suggesting that this extract may be neuroprotective and therefore beneficial in preventing or ameliorating the degenerative processes of AD, potentially by restoring cholinergic function.

Effect of Chaenomeles sinensis Extract on Choline Acetyltransferase Activity and Trimethyltin-Induced Learning and Memory Impairment in Mice.

The aim of this study was to search for a novel choline acetyltransferase (ChAT) activator from plants traditionally grown in Korea. An ethanol extract from Chaenomeles sinensis Koehne showed the highest ChAT-activating effect in vitro in an assay that used human neuroblastoma cells and [(14)C]acetyl-CoA. The active compound was speculated to be stearic acid methyl ester (SAME). In an in vivo experiment, C. sinensis extract and SAME improved trimethyltin (TMT)-induced deficits in learning and memory in mice as assessed by a Y-maze behavioral test and a passive avoidance test. The C. sinensis extract might attenuate the TMT-induced brain disorder. This study suggests that SAME from C. sinensis might be useful in the treatment of Alzheimer's disease.

Factors Associated with Fatigue in Korean Gastric Cancer Survivors.

BACKGROUND: Gastric cancer is the second most common cancer in Korea. Fatigue is a common symptom among cancer survivors. The aim of this study was to identify factors associated with fatigue in gastric cancer survivors. METHODS: Data were analyzed from 199 gastric cancer survivors who visited a cancer survivor outpatient clinic from July 2013 to June 2014. Patients were surveyed using a questionnaire containing a fatigue severity scale (FSS) and questions regarding associated symptoms. Participants were divided into fatigue (FSS) and non-fatigue groups based on FSS scores (≥4 and <4, respectively). Age, sex, weight, body mass index, cancer stage, pathology, surgery type, chemotherapy, radiotherapy, comorbid disease, family history of cancer, smoking, alcohol consumption, exercise, and laboratory results were investigated. RESULTS: The fatigue and non-fatigue groups contained 42 and 157 survivors, respectively. Their mean age was 58 years, and the mean post-operative period was 6.58 years. Arthralgia (odds ratio [OR], 12.95; 95% confidence interval [CI], 3.21-52.34), dyspnea (OR, 10.54; 95% CI, 2.94-37.80), dyspepsia (OR, 8.26; 95% CI, 2.63-25.96), changed bowel habits (OR, 4.56; 95% CI, 1.09-19.11), anemia (OR, 3.18; 95% CI, 1.26-8.05), and regular exercise (OR, 0.31; 95% CI, 0.12-0.77) were significantly associated with fatigue in gastric cancer survivors, while weight, treatment, and depressive mood were not. CONCLUSION: Arthralgia, dyspnea, dyspepsia, bowel habit change, anemia, and regular exercise are associated with fatigue in gastric cancer survivors.

Quality evaluation on use of camellia oil as an alternative method in dried seaweed preparation.

The fatty acid and volatile compound compositions of camellia oil were analyzed in this study. The impacts of the replacement of conventional vegetable oil with camellia oil on the sensory attributes of dried seaweed were also determined. C18:1 (83.59%), followed by C16:0 and C18:2, were the most abundant fatty acids in camellia oil. A total of 11 and 32 volatile compounds were identified in camellia oil and sesame oil, respectively. In the preference test, the camellia oil samples received a higher, although insignificant, liking rating in overall acceptability of appearance. Overall, there were no differences between the sensory attributes of camellia oil and sesame oil. This finding, combined with the unique fatty acid composition, thermal stability, and health benefits of camellia oil indicate that further study into the use of camellia oil in foods is warranted.

Ligularia fischeri extract protects against oxidative-stress-induced neurotoxicity in mice and PC12 cells.

Alzheimer's disease (AD) is pathologically characterized by the presence of amyloid plaques in brain and the overproduction of amyloid beta (Aß), leading to learning and memory impairment and intense oxidative stress. In this study, the protective effect of Ligularia fischeri extract was investigated using PC12 cells. L. fischeri extract attenuated hydrogen-peroxide-induced DNA fragmentation in cells. In vivo behavioral tests were performed to examine the effects of the extract on amyloid-ß peptide1-42-induced impairment of learning and memory in mice. A diet containing the extract increased alternation behaviors in the Y-maze test and step-through latency of passive avoidance task. Moreover, we found that consumption of the extract decreased lipid peroxidation in a biochemical study of brain tissue in mice. High-performance liquid chromatography was used to identify the active compounds in the extract. These results suggest that L. fischeri extract could be protective against Aß-induced neurotoxicity, possibly due to the antioxidative capacity of its constituent, 3-O-caffeoylquinic acid.

Surface coated Eu(OH)3 nanorods: a facile synthesis, characterization, MR relaxivities and in vitro cytotoxicity.

The water-soluble and biocompatible D-glucuronic acid coated Eu(OH)3 nanorods (average thickness x average length = 9.0 x 118.3 nm) have been prepared in one-pot synthesis. The D-glucuronic acid coated Eu(OH)3 nanorods showed a strong fluorescence at approximately 600 nm with a narrow emission band width. A cytotoxicity test by using DU145 cells showed that D-glucuronic acid coated Eu(OH)3 nanorods are not toxic up to 100 microM, making them a promising candidate for biomedical applications such as fluorescent imaging. The minimum Eu concentration needed for a conventional confocal imaging was estimated to be approximately 0.1 mM. Therefore, D-glucuronic acid coated Eu(OH)3 nanorods can be applied to fluorescent imaging. However, a very tiny magnetization of approximately 1.2 emu/g at room temperature and at an applied field of 5 tesla was observed. As a result, very small r1 and r2 water proton relaxivities were estimated, implying that surface coated Eu(OH)3 nanorods are not sufficient for MRI contrast agents.

Mixed lanthanide oxide nanoparticles as dual imaging agent in biomedicine.

There is no doubt that the molecular imaging is an extremely important technique in diagnosing diseases. Dual imaging is emerging as a step forward in molecular imaging technique because it can provide us with more information useful for diagnosing diseases than single imaging. Therefore, diverse dual imaging modalities should be developed. Molecular imaging generally relies on imaging agents. Mixed lanthanide oxide nanoparticles could be valuable materials for dual magnetic resonance imaging (MRI)-fluorescent imaging (FI) because they have both excellent and diverse magnetic and fluorescent properties useful for dual MRI-FI, depending on lanthanide ions used. Since they are mixed nanoparticles, they are compact, robust, and stable, which is extremely useful for biomedical applications. They can be also easily synthesized with facile composition control. In this study, we explored three systems of ultrasmall mixed lanthanide (Dy/Eu, Ho/Eu, and Ho/Tb) oxide nanoparticles to demonstrate their usefulness as dual T2 MRI-FI agents.

Effects of brussels sprouts and their phytochemical components on oxidative stress-induced neuronal damages in PC12 cells and ICR mice.

In this study, the protective effects of Brussels sprouts extract and its major constituents against oxidative stress-induced damages were investigated in rat pheochromocytoma cells and Institute of Cancer Research mice. The major constituents of Brussels sprouts (3,4',5,7-tetrahydroxyflavone (kaempferol), indole-3-carbinol, and phenethyl isothiocyanate) were selectively tested. Of these, the flavonoid compound, kaempferol exhibited the highest potency in radical scavenging activity (1,1-diphenyl-2-picryl hydrazyl assay and oxygen radical absorbance capacity assay) and was most protective against oxidative stress in neuronal cell assays (measurement of intracellular oxidative stress levels and cell viability). In mice, after 4 weeks of kaempferol administration, significant protection against amyloid beta (Aß) peptide-induced neurotoxicity was also observed, as assessed through the passive avoidance test. Taken together, the results suggest that Brussels sprouts could be protective against Aß-induced neurotoxicity, possibly due to the antioxidative capacity of its major constituent, kaempferol.

Antioxidant Activities of Ribes diacanthum Pall Extracts in the Northern Region of Mongolia.

Ribes diacanthum Pall (RDP) is a member of the Saxifragaceae family. The plant is traditionally used in Mongolia for the treatment of various ailments associated with kidney and bladder's diseases, cystitis, kidney stone, and edema. This study was aimed to investigate antioxidant activities of different solvent extracts of whole Pall plants, based on ferric-reducing antioxidant potential (FRAP), 2,2'-azinobis(3-ethybenzothiazoline-6-sulfonic acid) (ABTS· +) radical scavenging activity, 1,1-diphenyl-2-picrydrazyl (DPPH·), and hydroxyl (·OH) radical scavenging activities. Additionally, total flavonoids and phenolic contents (TPC) were also determined. The ethyl acetate extract of RDP (EARDP) had a remarkable radical scavenging capacity with an IC50 value of 0.1482 mg/mL. In addition, EARDP was shown to be higher in total phenolic and flavonoid contents than the methanol extract of RDP (MRDP). Moreover, the EARDP had the predominant antioxidant capacity, DPPH, hydroxyl, and ABTS radical scavenging activities and ferric reducing power. These results suggest a potential for R. diacanthum Pall extract as a functional medicinal material against free-radical-associated oxidative damage.

Effects of methoxsalen from Poncirus trifoliata on acetylcholinesterase and trimethyltin-induced learning and memory impairment.

Previously, we identified methoxsalen (8-methoxy-2',3',6,7-furocoumarin) as the bioactive compound probably responsible for acetylcholinesterase (AchE) inhibition achieved by feeding crude extract of Poncirus trifoliate. To confirm the activity of methoxsalen, Institute of Cancer Research (ICR) mice were fed a control or a methoxsalen-supplemented diet for 4 weeks, and then learning and memory enhancing effects with respect to trimethyltin (TMT)-induced neurotoxicity were evaluated. The brain tissues of ICR mice were dissected after completion of the behavioral tests for biochemical analysis. Methoxsalen effectively reversed TMT-induced memory impairment on both Y-maze and passive avoidance tests. Brain AchE activity was inhibited by the oral consumption of all concentrations of methoxsalen. Moreover, the level of oxidative stress was significantly ameliorated in the groups on methodsalen containing diets. This is the first in vivo study conducted with methoxsalen in the field of AD research, and it indicates that further investigation of methoxsalen is warranted.