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1.
Foods ; 10(2)2021 Feb 03.
Article in English | MEDLINE | ID: mdl-33546232

ABSTRACT

Microwave assisted thermal sterilization (MATS) is a novel microwave technology currently used in the commercial production of ready-to-eat meals. It combines surface heating of high-temperature circulation water with internal microwave heating in cavities. The heating pattern inside the food packages in a MATS process depends heavily on the electric field distribution formed by microwaves from the top and bottom windows of the microwave heating cavities. The purpose of this research was to study the effect of the electric field on 922 MHz microwave heating of ready-to-eat meals as they moved through the microwave chamber of a pilot-scale MATS system using the finite-difference time-domain (FDTD) method. A three-dimensional numerical simulation model was developed as a digital twin of the MATS process of food moving through the microwave chamber. The simulation showed that the electric field intensity of the MATS microwave cavity was greatest on the surface and side edge of the cavity and of the food. There was a strong similarity of the experimental heating pattern with that of the electric field distribution simulated by a computer model. The digital twin modeling approach can be used to design options for improving the heating uniformity and throughput of ready-to-eat meals in MATS industrial systems.

2.
Cancer Res Treat ; 53(1): 104-111, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33017882

ABSTRACT

PURPOSE: As the aging of society progresses, the proportion of extremely older lung cancer patients has also increased; However, studies of these patients with non-small cell lung cancer are limited. Therefore, we investigated the initial treatment modalities and survival outcomes for patients aged 80 years or over. MATERIALS AND METHODS: We included a multicenter retrospective cohort from the Korean Association for Lung Cancer Registry, which surveys 10% of the newly diagnosed lung cancer patients across 52 hospitals in Korea. We analyzed and compared the 2014-2016 data of the non-small cell lung cancer patients aged ≥ 80 years and those aged < 80 years. RESULTS: Of the 6,576 patients reviewed, 780 patients were aged ≥ 80 years, and 5,796 patients were aged < 80 years. In the patients aged ≥ 80 years, surgery and radiation therapy resulted in longer patient survival among those with a resectable tumor (stage I-II) than the best supportive care (median survival, not reached [surgery] vs. 32.2 months [radiation therapy] vs. 11.43 months [best supportive care]). The duration of survival in patients with advanced-stage (IV) lung cancers was higher after chemotherapy than after the best supportive care (median survival, 8.63 months vs. 2.5 months). Patients with stage IV adenocarcinoma who received targeted therapy had better survival than those who did not (median survival, 9.0 months vs. 4.3 months). CONCLUSION: Even in extremely older patients, active treatments, such as surgery, radiation therapy, and chemotherapy, can result in better survival outcomes than the best supportive care.


Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Cohort Studies , Female , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Retrospective Studies , Survival Analysis
3.
Food Res Int ; 119: 584-595, 2019 05.
Article in English | MEDLINE | ID: mdl-30884692

ABSTRACT

A mathematical model for predicting electromagnetic power dissipation within a rectangular dielectric slab heated by equal intensity 915 MHz plane waves from top and bottom was developed. A dimensionless parameter (J-T number) which is a combination of the loss factor (εr″), dielectric constant (εr') and food thickness (L) was proposed. This unique number provided direct insight into the relationship between food dielectric properties, thickness, product temperature, and thermal lethality. For the validation tests, mashed potatoes, peas and rice samples with 0-2% salt content were processed in a pilot scale microwave assisted thermal sterilization (MATS) system. In each food, the combination of dielectric properties and thickness which gave J-T number of 1.8-2.2 at 100-121°C, provided the highest lethalities. MATS is a novel commercial technology being adapted in the food industry. A qualitative assessment of the combined effect of food properties on lethalities using this model will be helpful in process development for MATS systems.


Subject(s)
Electromagnetic Phenomena , Heating , Microwaves , Oryza , Pisum sativum , Sodium Chloride , Solanum tuberosum , Cooking , Food , Food Handling , Food Industry , Models, Theoretical , Sodium Chloride, Dietary , Temperature
4.
Biochem Biophys Res Commun ; 496(4): 1134-1140, 2018 02 19.
Article in English | MEDLINE | ID: mdl-29410178

ABSTRACT

The nuclear receptor-binding SET domain protein gene (NSD) family encodes a group of highly conserved SET domain-containing histone lysine methyltransferases that are important in multiple aspects of development in various organisms. The association of NSD1 duplications has been reported with growth retardation diseases in humans. In this study, to gain insight into the molecular mechanisms by which the overexpression of NSD1 influences the disease progression, we analyzed the gain-of-function mutant phenotypes of the Drosophila NSD using the GAL4/UAS system. Ubiquitous overexpression of NSD in the fly caused developmental delay and reduced body size at the larval stage, resulting in pupal lethality. Moreover, targeted overexpression in various developing tissues led to significant phenotype alterations, and the gain-of-function phenotypes were rescued by NSD RNAi knockdown. We also demonstrated that NSD overexpression not only enhanced the transcription of pro-apoptotic genes but also activated caspase. The atrophied phenotype of NSD-overexpressing wing was strongly suppressed by a loss-of-function mutation in hemipterous, which encodes a Drosophila Jun N-terminal kinase. Taken together, our findings suggest that NSD induces apoptosis via the activation of JNK, and thus contributes to the understanding of the molecular mechanisms involved in NSD1-related diseases in humans.


Subject(s)
Apoptosis/physiology , Drosophila Proteins/metabolism , Drosophila/physiology , Histone-Lysine N-Methyltransferase/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Metabolic Networks and Pathways/physiology , Up-Regulation/physiology , Animals , Body Size/physiology , Enzyme Activation , Histone Methyltransferases
5.
Am J Chin Med ; 44(7): 1325-1347, 2016.
Article in English | MEDLINE | ID: mdl-27776428

ABSTRACT

Alzheimer's disease (AD), the most common neurodegenerative disease, has a complex and widespread pathology that is characterized by the accumulation of amyloid [Formula: see text]-peptide (A[Formula: see text]) in the brain and various cellular abnormalities, including increased oxidative damage, an amplified inflammatory response, and altered mitogen-activated protein kinase signaling. Based on the complex etiology of AD, traditional medicinal plants with multiple effective components are alternative treatments for patients with AD. In the present study, we investigated the neuroprotective effects of an ethanol extract of Coriandrum sativum (C. sativum) leaves on A[Formula: see text] cytotoxicity and examined the molecular mechanisms underlying the beneficial effects. Although recent studies have shown the benefits of the inhalation of C. sativum oil in an animal model of AD, the detailed molecular mechanisms by which C. sativum exerts its neuroprotective effects are unclear. Here, we found that treatment with C. sativum extract increased the survival of both A[Formula: see text]-treated mammalian cells and [Formula: see text]42-expressing flies. Moreover, C. sativum extract intake suppressed [Formula: see text]-induced cell death in the larval imaginal disc and brain without affecting A[Formula: see text]42 expression and accumulation. Interestingly, the increases in reactive oxygen species levels and glial cell number in AD model flies were reduced by C. sativum extract intake. Additionally, C. sativum extract inhibited the epidermal growth factor receptor- and A[Formula: see text]-induced phosphorylation of extracellular signal-regulated kinase (ERK). The constitutively active form of ERK abolished the protective function of C. sativum extract against the [Formula: see text]-induced eye defect phenotype in Drosophila. Taken together, these results suggest that C. sativum leaves have antioxidant, anti-inflammatory, and ERK signaling inhibitory properties that are beneficial for patients with AD.


Subject(s)
Alzheimer Disease/drug therapy , Anti-Inflammatory Agents , Antioxidants , Cell Proliferation/drug effects , Coriandrum/chemistry , Neuroglia/cytology , Neuroglia/metabolism , Neuroprotective Agents , Phytotherapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Reactive Oxygen Species/metabolism , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Animals , Brain/cytology , Brain/metabolism , Cells, Cultured , Disease Models, Animal , Drosophila , Drosophila Proteins/metabolism , ErbB Receptors/metabolism , MAP Kinase Signaling System/drug effects , Peptide Fragments/metabolism , Phosphorylation/drug effects , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Leaves/chemistry , Receptors, Invertebrate Peptide/metabolism , Rutin/isolation & purification , Rutin/pharmacology , Rutin/therapeutic use
6.
Yonsei Med J ; 57(4): 928-35, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27189287

ABSTRACT

PURPOSE: Roflumilast is the only oral phosphodiesterase 4 inhibitor approved to treat chronic obstructive pulmonary disease (COPD) patients [post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted] with chronic bronchitis and a history of frequent exacerbations. This study evaluated the efficacy and safety of roflumilast in Korean patients with COPD and compared the efficacy based on the severity of airflow limitation. MATERIALS AND METHODS: A post-hoc subgroup analysis was performed in Korean COPD patients participating in JADE, a 12-week, double-blinded, placebo-controlled, parallel-group, phase III trial in Asia. The primary efficacy endpoint was the mean [least-squares mean adjusted for covariates (LSMean)] change in post-bronchodilator FEV1 from baseline to each post-randomization visit. Safety endpoints included adverse events (AEs) and changes in laboratory values, vital signs, and electrocardiograms. RESULTS: A total of 260 Korean COPD patients were recruited, of which 207 were randomized to roflumilast (n=102) or placebo (n=105) treatment. After 12 weeks, LSMean post-bronchodilator FEV1 increased by 43 mL for patients receiving roflumilast and decreased by 60 mL for those taking placebo. Adverse events were more common in the roflumilast group than in the placebo group; however, the types and frequency of AEs were comparable to those reported in previous studies. CONCLUSION: Roflumilast significantly improved lung function with a tolerable safety profile in Korean COPD patients irrespective of the severity of airflow limitation.


Subject(s)
Aminopyridines/therapeutic use , Asian People , Benzamides/therapeutic use , Phosphodiesterase 4 Inhibitors/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/ethnology , Aged , Cyclopropanes/therapeutic use , Double-Blind Method , Female , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/physiopathology , Republic of Korea , Respiratory Function Tests , Treatment Outcome
7.
Dis Model Mech ; 9(3): 295-306, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26659252

ABSTRACT

Expression of the Down syndrome critical region 1 (DSCR1) protein, an inhibitor of the Ca(2+)-dependent phosphatase calcineurin, is elevated in the brains of individuals with Down syndrome (DS) or Alzheimer's disease (AD). Although increased levels of DSCR1 were often observed to be deleterious to neuronal health, its beneficial effects against AD neuropathology have also been reported, and the roles of DSCR1 on the pathogenesis of AD remain controversial. Here, we investigated the role of sarah (sra; also known as nebula), a Drosophila DSCR1 ortholog, in amyloid-ß42 (Aß42)-induced neurological phenotypes in Drosophila. We detected sra expression in the mushroom bodies of the fly brain, which are a center for learning and memory in flies. Moreover, similar to humans with AD, Aß42-expressing flies showed increased Sra levels in the brain, demonstrating that the expression pattern of DSCR1 with regard to AD pathogenesis is conserved in Drosophila. Interestingly, overexpression of sra using the UAS-GAL4 system exacerbated the rough-eye phenotype, decreased survival rates and increased neuronal cell death in Aß42-expressing flies, without modulating Aß42 expression. Moreover, neuronal overexpression of sra in combination with Aß42 dramatically reduced both locomotor activity and the adult lifespan of flies, whereas flies with overexpression of sra alone showed normal climbing ability, albeit with a slightly reduced lifespan. Similarly, treatment with chemical inhibitors of calcineurin, such as FK506 and cyclosporin A, or knockdown of calcineurin expression by RNA interference (RNAi), exacerbated the Aß42-induced rough-eye phenotype. Furthermore, sra-overexpressing flies displayed significantly decreased mitochondrial DNA and ATP levels, as well as increased susceptibility to oxidative stress compared to that of control flies. Taken together, our results demonstrating that sra overexpression augments Aß42 cytotoxicity in Drosophila suggest that DSCR1 upregulation or calcineurin downregulation in the brain might exacerbate Aß42-associated neuropathogenesis in AD or DS.


Subject(s)
Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Calcineurin Inhibitors/metabolism , Disease Models, Animal , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Peptide Fragments/metabolism , Animals , Brain/metabolism , Brain/pathology , Calcium-Binding Proteins , Cell Death , Hydrogen Peroxide/metabolism , Larva/metabolism , Longevity , Mitochondria/metabolism , Mushroom Bodies/metabolism , Nerve Degeneration/metabolism , Nerve Degeneration/pathology , Neuroglia/metabolism , Neurons/metabolism , Nitric Oxide/metabolism , Oxidative Stress , Phenotype , Photoreceptor Cells, Invertebrate/metabolism , RNA Interference , Reactive Oxygen Species/metabolism , Up-Regulation
8.
Biol Pharm Bull ; 38(12): 1891-901, 2015.
Article in English | MEDLINE | ID: mdl-26458335

ABSTRACT

Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by progressive neuronal loss with amyloid ß-peptide (Aß) plaques. Despite several drugs currently used to treat AD, their beneficial effects on AD progress remains under debate. Here, we established a rapid in vivo screening system using Drosophila AD models to assess the neuroprotective activities of medicinal plants that have been used in traditional Chinese medicine. Among 23 medicinal plants tested, the extracts from five plants, Coriandrum sativum, Nardostachys jatamansi, Polygonum multiflorum (P. multiflorum), Rehmannia glutinosa, and Sorbus commixta (S. commixta), showed protective effects against the Aß42 neurotoxicity. We further characterized the neuroprotective activity of ethanol extracts from P. multiflorum and S. commixta. Aß42-expressing flies that we used showed AD neurological phenotypes, such as decreased survival and motility and increased cell death and reactive oxygen species level. However, feeding these flies extracts from P. multiflorum or S. commixta showed strong suppression of such phenotypes. Similar results were observed in human cells, so that the treatment of P. multiflorum and S. commixta extracts increased the viability of Aß-treated SH-SY5Y cells. Moreover, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside, one of the main constituents of P. multiflorum, also showed similar protective activity against Aß42 cytotoxicity in both Drosophila and human cells. Taken together, our results suggest that both P. multiflorum and S. commixta have therapeutic potential for the treatment of neurodegenerative diseases, such as AD.


Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Protein Precursor/metabolism , Drugs, Chinese Herbal/pharmacology , Magnoliopsida/chemistry , Neuroprotective Agents/pharmacology , Alzheimer Disease/drug therapy , Animals , Coriandrum/chemistry , Disease Models, Animal , Drosophila , Drug Evaluation, Preclinical , Fallopia multiflora/chemistry , Medicine, Chinese Traditional , Nardostachys/chemistry , Phytotherapy , Plants, Medicinal/chemistry , Rehmannia/chemistry , Sorbus/chemistry
9.
J Food Sci ; 79(4): E546-61, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24689882

ABSTRACT

The high-temperature sous-vide (HTSV) method was developed to prepare carrots with a soft texture at the appropriate degree of pasteurization. The effect of heating conditions, such as temperature and time, was investigated on various package sizes. Heating temperatures of 70, 80, and 90 °C and heating times of 10 and 20 min were used to evaluate the HTSV method. A 3-dimensional conduction model and numerical simulations were used to estimate the temperature distribution and the rate of heat transfer to samples with various geometries. Four different-sized packages were prepared by stacking carrot sticks of identical size (9.6 × 9.6 × 90 mm) in a row. The sizes of the packages used were as follows: (1) 9.6 × 86.4 × 90, (2) 19.2 × 163.2 × 90, (3) 28.8 × 86.4 × 90, and (4) 38.4 × 86.4 × 90 mm. Although only a moderate change in color (L*, a*, and b*) was observed following HTSV cooking, there was a significant decrease in carrot hardness. The geometry of the package and the heating conditions significantly influenced the degree of pasteurization and the final texture of the carrots. Numerical simulations successfully described the effect of geometry on samples at different heating conditions.


Subject(s)
Cooking/methods , Daucus carota , Food Packaging/methods , Hardness , Hot Temperature , Pasteurization , Vegetables , Color , Humans , Plant Roots
10.
J Food Sci ; 79(6): M1168-74, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24754226

ABSTRACT

UNLABELLED: The aim of this study was to determine the growth kinetics of Listeria monocytogenes, with and without cold-adaption, on fresh-cut cantaloupe under different storage temperatures. Fresh-cut samples, spot inoculated with a 4-strain cocktail of L. monocytogenes (∼3.2 log CFU/g), were exposed to constant storage temperatures held at 10, 15, 20, 25, or 30 °C. All growth curves of L. monocytogenes were fitted to the Baranyi, modified Gompertz, and Huang models. Regardless of conditions under which cells grew, the time needed to reach 5 log CFU/g decreased with the elevated storage temperature. Experimental results showed that there were no significant differences (P > 0.05) in the maximum growth rate k (log CFU/g h(-1) ) and lag phase duration λ (h) between the cultures of L. monocytogenes with or without previous cold-adaption treatments. No distinct difference was observed in the growth pattern among 3 primary models at various storage temperatures. The growth curves of secondary modeling were fitted on an Arrhenius-type model for describing the relationship between k and temperature of the L. monocytogenes on fresh-cut cantaloupe from 10 to 30 °C. The root mean square error values of secondary models for non- and cold-adapted cells were 0.018, 0.021, and 0.024, and 0.039, 0.026, and 0.017 at the modified Gompertz, Baranyi, and Huang model, respectively, indicating that these 3 models presented the good statistical fit. This study may provide valuable information to predict the growth of L. monocytogenes on fresh-cut cantaloupes at different storage conditions. PRACTICAL APPLICATION: Listeriosis has occurred and increased along with the increased demand of fresh and fresh-cut fruits and vegetables. This study was conducted to predict the growth of non- and cold-adapted L. monocytogenes on fresh-cut cantaloupe at different temperature using mathematical model. These results can be helpful for risk assessments of L. monocytogenes in fresh-cut cantaloupe. This study provides valuable information to food handlers to choose proper storage temperatures for extending the shelf-life of fresh-cut cantaloupe.


Subject(s)
Cucumis melo/microbiology , Food Microbiology , Fruit/microbiology , Listeria monocytogenes/growth & development , Temperature , Adaptation, Physiological , Cold Temperature , Colony Count, Microbial , Consumer Product Safety , Food Handling/methods , Humans , Kinetics , Models, Biological
11.
PLoS Genet ; 9(4): e1003412, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23593018

ABSTRACT

DJ-1, a Parkinson's disease (PD)-associated gene, has been shown to protect against oxidative stress in Drosophila. However, the molecular mechanism underlying oxidative stress-induced phenotypes, including apoptosis, locomotive defects, and lethality, in DJ-1-deficient flies is not fully understood. Here we showed that Daxx-like protein (DLP), a Drosophila homologue of the mammalian Death domain-associated protein (Daxx), was upregulated under oxidative stress conditions in the loss-of-function mutants of Drosophila DJ-1ß, a Drosophila homologue of DJ-1. DLP overexpression induced apoptosis via the c-Jun N-terminal kinase (JNK)/Drosophila forkhead box subgroup O (dFOXO) pathway, whereas loss of DLP increased resistance to oxidative stress and UV irradiation. Moreover, the oxidative stress-induced phenotypes of DJ-1ß mutants were dramatically rescued by DLP deficiency, suggesting that enhanced expression of DLP contributes to the DJ-1ß mutant phenotypes. Interestingly, we found that dFOXO was required for the increase in DLP expression in DJ-1ß mutants and that dFOXO activity was increased in the heads of DJ-1ß mutants. In addition, subcellular localization of DLP appeared to be influenced by DJ-1 expression so that cytosolic DLP was increased in DJ-1ß mutants. Similarly, in mammalian cells, Daxx translocation from the nucleus to the cytosol was suppressed by overexpressed DJ-1ß under oxidative stress conditions; and, furthermore, targeted expression of DJ-1ß to mitochondria efficiently inhibited the Daxx translocation. Taken together, our findings demonstrate that DJ-1ß protects flies against oxidative stress- and UV-induced apoptosis by regulating the subcellular localization and gene expression of DLP, thus implying that Daxx-induced apoptosis is involved in the pathogenesis of DJ-1-associated PD.


Subject(s)
Adaptor Proteins, Signal Transducing , Drosophila Proteins , Forkhead Transcription Factors , Nerve Tissue Proteins , Nuclear Proteins , Oxidative Stress , Parkinson Disease , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Animals , Apoptosis/radiation effects , Drosophila/genetics , Drosophila/metabolism , Drosophila Proteins/deficiency , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Humans , JNK Mitogen-Activated Protein Kinases/metabolism , Mutation , Nerve Tissue Proteins/deficiency , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neurons/cytology , Neurons/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Oxidative Stress/genetics , Oxidative Stress/radiation effects , Parkinson Disease/genetics , Parkinson Disease/metabolism , Parkinson Disease/physiopathology , Radiation Tolerance/genetics , Ultraviolet Rays
12.
Int J Food Microbiol ; 160(3): 239-44, 2013 Jan 01.
Article in English | MEDLINE | ID: mdl-23290230

ABSTRACT

The aim of this study was to determine survival or growth of unadapted, acid-adapted and cold-stressed Salmonella spp., and natural microbiota on fresh-cut dragon fruits at different storage temperatures. Dragon fruits were sliced and spot inoculated with five-strain cocktail of Salmonella spp. at two inoculum levels (2.5 or 5.5 log CFU/g). Inoculated fruits were stored at 28°C for 48h and at 4°C and 12°C for 96 h. Salmonella population significantly increased by 2.4 to 3.0 log CFU/g at low inoculum level, whereas the numbers increased by 0.4 to 0.7 log CFU/g at the high inoculum level on fruits held at 28°C for 48h. Only unadapted and acid-adapted cells grew with 0.7 to 0.9log increase at the low inoculum level at 12°C for 96h. No significant growth was observed at both inoculum levels during storage at 4°C. Overall, acid, starved and cold adaptation of Salmonella spp. did not show significant difference in survival or growth on fresh-cut dragon fruits during storage compared to unadapted control cells. For natural microbiota on the fruit, mesophilic bacterial counts reached to 5-log CFU/g at 28 and 12°C by 9.9 and 52.9h. Similar with Salmonella spp. there was no growth of natural microbiota at 4°C. These results showed that Salmonella spp. could grow on fresh-cut dragon fruits under inappropriate storage conditions, indicating that fresh-cut dragon fruits could be a potential vehicle for salmonellosis. Thus, this study suggests that fresh-cut dragon fruits should be stored at 4°C to ensure the safety as well as to extend the shelf life of fresh-cut dragon fruits.


Subject(s)
Food Handling/methods , Food Handling/standards , Food Microbiology , Fruit/microbiology , Salmonella/physiology , Temperature , Colony Count, Microbial , Consumer Product Safety , Metagenome/physiology , Salmonella/growth & development , Salmonella/isolation & purification , Time Factors
13.
Biol Pharm Bull ; 36(3): 390-8, 2013.
Article in English | MEDLINE | ID: mdl-23238278

ABSTRACT

SuHeXiang Wan (SHXW), a Chinese traditional medicine, has been used to treat infantile convulsions, seizures and strokes. Previously, we reported that modified SHXW, called KSOP1009, suppressed the hyper-activation of c-Jun N-terminal kinase (JNK) and Alzheimer's disease (AD)-like phenotypes in amyloid-ß42 (Aß42)-expressing Drosophila AD models. In the present study, we, further, investigated the detailed mechanism by which KSOP1009 suppresses the AD-like phenotypes of the model flies. As seen in the brains of AD patients, pan-neuronal expression of Aß42 in Drosophila increased activation of extracellular signal-regulated kinase (ERK), which was monitored by its phosphorylation level, and the number of glial cells in the brain. Suppression of caspase activity did not affect these phenomena, suggesting that Aß42 induces ERK activation and glial cell proliferation independently of apoptotic processes. KSOP1009 intake significantly reduced the level of ERK activation and the number of glial cells. Moreover, KSOP1009 intake also effectively decreased the defects in the wing vein formation induced by Epidermal growth factor receptor (Egfr) overexpression in fly wings, suggesting that it may contain an inhibitory substance that inhibits the EGFR/ERK signaling pathway. In addition, the Aß42-induced locomotive defect was partially rescued by inhibition of the elevated ERK activity through its antagonistic drug treatment. Taken together, these results suggest that KSOP1009 exerts its therapeutic effect by inhibiting the EGFR/ERK pathway and glial cell proliferation and by suppressing the JNK pathway and apoptosis.


Subject(s)
Alzheimer Disease/drug therapy , Amyloid beta-Peptides/toxicity , Drugs, Chinese Herbal/pharmacology , Extracellular Signal-Regulated MAP Kinases/metabolism , Neuroglia/drug effects , Neuroprotective Agents/pharmacology , Animals , Animals, Genetically Modified , Cell Proliferation/drug effects , Disease Models, Animal , Drosophila , ErbB Receptors/physiology , Humans , Phosphorylation
14.
FEBS Lett ; 586(22): 4031-7, 2012 Nov 16.
Article in English | MEDLINE | ID: mdl-23068610

ABSTRACT

The metastasis suppressor KAI1/CD82 has been implicated in various cellular processes; however, its function in development is not fully understood. Here, we generated and characterized mutants of Tsp66E and Tsp74F, which are Drosophila homologues of KAI1/CD82 and Tspan11, respectively. These mutants exhibited egg elongation defects along with disturbed integrin localization and actin polarity. Moreover, the defects were enhanced by mutation of inflated, an αPS2 integrin gene. Mutant ovaries had elevated αPS2 integrin levels and reduced endocytic trafficking. These results suggest that Drosophila KAI1/CD82 affects the polarized localization and the level of integrin, which may contribute to epithelial cell polarity.


Subject(s)
Drosophila Proteins/physiology , Integrin alpha Chains/physiology , Integrins/metabolism , Ovarian Follicle/growth & development , Tetraspanins/physiology , Wings, Animal/growth & development , Actins/metabolism , Animals , Blotting, Western , Dextrans/metabolism , Dextrans/pharmacokinetics , Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/growth & development , Drosophila melanogaster/metabolism , Endocytosis , Female , Humans , Immunohistochemistry , Integrin alpha Chains/genetics , Kangai-1 Protein/genetics , Kangai-1 Protein/physiology , Male , Microscopy, Confocal , Mutation , Ovarian Follicle/cytology , Ovarian Follicle/metabolism , Ovum/growth & development , Ovum/metabolism , Tetraspanins/genetics , Wings, Animal/metabolism
15.
J Hazard Mater ; 237-238: 153-60, 2012 Oct 30.
Article in English | MEDLINE | ID: mdl-22954598

ABSTRACT

In this study, Pt/Fe/ZSM5 catalysts were applied to oxidation of ammonia, where the catalysts showed good low-temperature activity (≤ 200°C) for converting ammonia into nitrogen. With 1.5% Pt/0.5% Fe/ZSM5 catalyst, we could obtain 81% NH(3) conversion and 93% N(2) selectivity at 175°C at the short contact-time of w/f=0.00012 g min/mL. Through the characterization studies using high-resolution transmission electron microscopy (HRTEM) and X-ray spectroscopies (XRD, XPS), we could find that the active species was collaborating Pt/Fe species, which structure and activity were largely influenced by support material - in a positive way by ZSM5, rather than by Al(2)O(3) and SiO(2). When using ZSM5 as the support material, Pt was highly dispersed exclusively on the Fe oxide, and the valence state and dispersion of Pt changed according to Fe loading amount.


Subject(s)
Ammonia/chemistry , Iron/chemistry , Platinum/chemistry , Zeolites/chemistry , Catalysis , Nitrogen/chemistry , Oxidation-Reduction , Temperature
16.
Biochem Biophys Res Commun ; 419(1): 49-53, 2012 Mar 02.
Article in English | MEDLINE | ID: mdl-22326868

ABSTRACT

Amyloid-ß-42 (Aß42) has been implicated in the pathogenesis of Alzheimer's disease (AD). Neuronal Aß42 expression induces apoptosis and decreases survival and locomotive activity in Drosophila. However, the mechanism by which Aß42 induces these neuronal impairments is unclear. In this study, we investigated the underlying pathway in theses impairments. JNK activity was increased in Aß42-expressing brains, and the Aß42-induced defects were rescued by reducing JNK or caspase activity through genetic modification or pharmacological treatment. In addition, these impairments were restored by Drosophila forkhead box subgroup O (dFOXO) deficiency. These results suggest that the JNK/dFOXO pathway confers a therapeutic potential for AD.


Subject(s)
Alzheimer Disease/enzymology , Amyloid beta-Peptides/metabolism , Brain/enzymology , Caspases/metabolism , Drosophila Proteins/metabolism , Drosophila melanogaster/enzymology , Forkhead Transcription Factors/metabolism , MAP Kinase Kinase 4/metabolism , Peptide Fragments/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/pharmacology , Animals , Anthracenes/pharmacology , Apoptosis , Brain/drug effects , Brain/pathology , Disease Models, Animal , Drosophila melanogaster/cytology , Drosophila melanogaster/physiology , MAP Kinase Kinase 4/antagonists & inhibitors , Neurons/drug effects , Neurons/enzymology , Neurons/pathology , Peptide Fragments/pharmacology , Protein Kinase Inhibitors/pharmacology , Signal Transduction
17.
J Ethnopharmacol ; 134(3): 1028-32, 2011 Apr 12.
Article in English | MEDLINE | ID: mdl-21333721

ABSTRACT

AIM OF THE STUDY: SuHeXiang Wan (SHXW) is a Chinese traditional medicinal prescription that consists of 15 crude herbs. SHXW has been used to treat central nervous depression, seizures, infantile convulsion and stroke, and its essential oil has been shown to have anticonvulsant and antioxidative activity. The goal of this study was to investigate the beneficial effects of SHXW on the neurological phenotypes of Drosophila AD models. MATERIALS AND METHODS: We evaluated the effects of a modified SHXW (called KSOP1009) intake on the AD-like phenotypes of Drosophila AD models, which express human Aß42 in their developing eyes or neurons. RESULTS: When the flies were kept on the media containing 5 µg/ml of KSOP1009 extract, Aß42-induced eye degeneration, apoptosis, and the locomotive dysfunctions were strongly suppressed. However, Aß42 fibril deposits in the Aß42 overexpressing model were not affected by treatment with KSOP1009 extract. Conversely, KSOP1009 extract intake significantly suppressed the constitutive active form of hemipterous, a JNK activator, while it induced eye degeneration and JNK activation, which has been recognized as an important mediator of Aß42-associated neuro-cytotoxicity. CONCLUSIONS: In conclusion, the results of this study suggest that KSOP1009 confers a therapeutic potential to AD-like pathology of Aß42 overexpressing Drosophila model via suppression of the hyperactivation of JNK activity and apoptosis.


Subject(s)
Alzheimer Disease/drug therapy , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Neuroprotective Agents/therapeutic use , Alzheimer Disease/enzymology , Alzheimer Disease/pathology , Animals , Apoptosis , Drosophila , Humans , Immunohistochemistry , MAP Kinase Kinase 4/metabolism
18.
Mol Cells ; 31(4): 337-42, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21331775

ABSTRACT

Hempseed is rich in polyunsaturated fatty acids (PUFAs), which have potential as therapeutic compounds for the treatment of neurodegenerative and cardiovascular disease. However, the effect of hempseed meal (HSM) intake on the animal models of these diseases has yet to be elucidated. In this study, we assessed the effects of the intake of HSM and PUFAs on oxidative stress, cytotoxicity and neurological phenotypes, and cholesterol uptake, using Drosophila models. HSM intake was shown to reduce H(2)O(2) toxicity markedly, indicating that HSM exerts a profound antioxidant effect. Meanwhile, intake of HSM, as well as linoleic or linolenic acids (major PUFA components of HSM) was shown to ameliorate Aß42-induced eye degeneration, thus suggesting that these compounds exert a protective effect against Aß42 cytotoxicity. On the contrary, locomotion and longevity in the Parkinson's disease model and eye degeneration in the Huntington's disease model were unaffected by HSM feeding. Additionally, intake of HSM or linoleic acid was shown to reduce cholesterol uptake significantly. Moreover, linoleic acid intake has been shown to delay pupariation, and cholesterol feeding rescued the linoleic acid-induced larval growth delay, thereby indicating that linoleic acid acts antagonistically with cholesterol during larval growth. In conclusion, our results indicate that HSM and linoleic acid exert inhibitory effects on both Aß42 cytotoxicity and cholesterol uptake, and are potential candidates for the treatment of Alzheimer's disease and cardiovascular disease.


Subject(s)
Antioxidants/chemistry , Cannabis , Drosophila melanogaster/physiology , Hypercholesterolemia/diet therapy , Linoleic Acid/pharmacology , Neurodegenerative Diseases/diet therapy , Seeds , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/biosynthesis , Animals , Animals, Genetically Modified , Antioxidants/metabolism , Cardiovascular Diseases/diet therapy , Cholesterol/metabolism , Compound Eye, Arthropod/drug effects , Compound Eye, Arthropod/metabolism , Compound Eye, Arthropod/pathology , Drosophila melanogaster/embryology , Drosophila melanogaster/genetics , Hydrogen Peroxide/toxicity , Lipid Metabolism/drug effects , Motor Activity/drug effects , Peptide Fragments/antagonists & inhibitors , Peptide Fragments/biosynthesis , alpha-Linolenic Acid/pharmacology
19.
Mol Cells ; 30(1): 29-36, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20652493

ABSTRACT

Hempseed, a rich source of polyunsaturated fatty acids (PUFAs) and phytosterols, has been recognized as a potential therapeutic food used for cardioprotection, preventing platelet aggregation, and improving atopic dermatitis. Although several studies have revealed the physiological benefits of hempseed on a variety of animals, the effects of dietary hempseed intake on animal development are currently unknown. In this study, we evaluated the developmental effects of the addition of hempseed meal (HSM) to the diet of Drosophila. Interestingly, dietary HSM intake was shown to increase the body size of flies by increasing cell numbers, and also truncated the larval period without affecting survival rate or longevity. The oviposition of female flies was also increased by dietary HSM supplementation. Interestingly, the levels of sterols, which are precursors of ecdysone, a molting hormone, were found to be elevated in the larvae fed on HSM. Additionally, the hexane extracts of hempseed mimicked the effects of HSM on growth, developmental timing, and reproduction. Moreover, among the major nonpolar components of HSM, feeding on cholesterol but not PUFA mix or campesterol accelerated pupariation and increased body size. These results indicate that the dietary intake of HSM accelerates both body growth and developmental rates in Drosophila via the stimulation of cell growth and ecdysone synthesis. Additionally, nonpolar components of hempseed, such as cholesterol, might be responsible for the effects of HSM on development and reproduction.


Subject(s)
Cannabis , Drosophila melanogaster/physiology , Fatty Acids, Unsaturated/administration & dosage , Seeds , Sterols/metabolism , Animals , Cannabis/chemistry , Cell Growth Processes/physiology , Cholesterol/biosynthesis , Diet , Drosophila melanogaster/growth & development , Drosophila melanogaster/metabolism , Eating , Female , Larva , Male , Platelet Aggregation/drug effects , Seeds/chemistry , Survival Analysis , Up-Regulation
20.
Mol Cells ; 29(6): 575-80, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20496123

ABSTRACT

Parkin is the most prevalent genetic factor in the onset of autosomal recessive juvenile parkinsonism (AR-JP), and mutations in parkin has been reported to cause motor defects, which result from dopamine deficiency caused by dopaminergic neuronal cell death. Activation of c-Jun N-terminal kinase (JNK) has also been implicated in neuronal cell death in Parkinson's disease (PD). Moreover, Drosophila models for AR-JP, loss of function mutants of Drosophila parkin, also show dopaminergic neural degeneration associated with hyperactivation of JNK, increased apoptosis, and mitochondrial defects. However, the molecular mechanism by which Parkin protects cells from apoptosis remains unclear. In the present study, we tested whether Drosophila Parkin suppressed the JNK signaling pathway in developing tissues. Ectopically expressed parkin strongly suppressed the constitutively active form of Hemipterous (Hep(CA)), a Drosophila JNK kinase that induces an eye degeneration phenotype and apoptosis in the eye imaginal disc. Moreover, parkin also suppressed extra vein formation induced by Basket (Bsk), a Drosophila JNK. Interestingly, the bsk mRNA level was markedly reduced by parkin over-expression, suggesting that the effect of parkin on the phenotype induced by activation of JNK signaling was achieved by transcriptional regulation. Furthermore, we found that the expression level of JNK target genes was reduced by parkin over-expression. Taken together, these results suggest that Drosophila Parkin suppresses JNK signaling by reducing bsk transcription.


Subject(s)
Apoptosis/genetics , Drosophila Proteins/metabolism , Neurons/metabolism , Parkinsonian Disorders/metabolism , Receptor, EphA5/biosynthesis , Ubiquitin-Protein Ligases/metabolism , Animals , Disease Models, Animal , Drosophila , Drosophila Proteins/genetics , Eye/blood supply , Eye/embryology , Eye/growth & development , Gene Expression Regulation, Developmental/genetics , Humans , Mitogen-Activated Protein Kinase Kinases/genetics , Mitogen-Activated Protein Kinase Kinases/metabolism , Mutation/genetics , Neovascularization, Physiologic/genetics , Neurons/pathology , Parkinsonian Disorders/genetics , Receptor, EphA5/genetics , Signal Transduction/genetics , Ubiquitin-Protein Ligases/genetics
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