ABSTRACT
The loss of vitamin D3 upregulated protein 1 (VDUP1) has been implicated in the pathogenesis of various inflammation-related diseases. Notably, reduced expression of VDUP1 has been observed in clinical specimens of ulcerative colitis (UC). However, the role of VDUP1 deficiency in colitis remains unclear. In this study, we investigated the role of VDUP1 in dextran sulfate sodium (DSS)-induced experimental colitis in mice. VDUP1-deficient mice were more susceptible to DSS-induced colitis than their wild-type (WT) littermates after 2% DSS administration. VDUP1-deficient mice exhibited an increased disease activity index (DAI) and histological scores, as well as significant colonic goblet cell loss and an increase in apoptotic cells. These changes were accompanied by a significant decrease in MUC2 mRNA expression and a marked increase in proinflammatory cytokines and chemokines within damaged tissues. Furthermore, phosphorylated NF-κB p65 expression was significantly upregulated in damaged tissues in the context of VDUP1 deficiency. VDUP1 deficiency also led to significant infiltration of macrophages into the site of ulceration. An in vitro chemotaxis assay confirmed that VDUP1 deficiency enhanced bone marrow-derived macrophage (BMDM) chemotaxis induced by CCL2. Overall, this study highlights VDUP1 as a regulator of UC pathogenesis and a potential target for the future development of therapeutic strategies.
Subject(s)
Colitis, Ulcerative , Colitis , Animals , Mice , Chemotaxis , Colitis/chemically induced , Colitis/genetics , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/genetics , MacrophagesABSTRACT
Recent studies have reported that small double-strand RNAs (dsRNAs) can activate endogenous genes via an RNA-based promoter targeting mechanism termed RNA activation (RNAa). In the present study, we showed that dsVDUP1-834, a novel small activating RNA (saRNA) targeting promoter of vitamin D3 up-regulated protein 1 (VDUP1) gene, up-regulated expression of VDUP1 at both mRNA and protein levels in A549 lung cancer cells. We also demonstrated that dsVDUP1-834 inhibited cell proliferation in A549 lung cancer cells. Further studies showed that dsVDUP1-834 induced cell-cycle arrest by increasing p27 and p53 and decreasing cyclin A and cyclin B1. In addition, knockdown of VDUP1 abrogated dsVDUP1-834-induced up-regulation of VDUP1 gene expression and related effects. The activation of VDUP1 by dsVDUP1-834 was accompanied by an increase in dimethylation of histone 3 at lysine 4 (H3K4me2) and acetylation of histone 3 (H3ac) and a decrease in dimethylation of histone 3 at lysine 9 (H3K9me2) at the target site of VDUP1 promoter. Moreover, the enrichment of Ago2 was detected at the dsVDUP1-834 target site, and Ago2 knockdown significantly suppressed dsVDUP1-834-mediated inhibition of cell proliferation and modulation of cell-cycle regulators. Taken together, the results presented in this report demonstrate that dsVDUP1-834 induces VDUP1 gene expression by epigenetic changes, resulting in cell growth inhibition and cell-cycle arrest. Our results suggest that targeted induction of VDUP1 by dsVDUP1-834 might be a promising therapeutic strategy for the treatment of lung cancer.
Subject(s)
Carrier Proteins/metabolism , Lung Neoplasms , Histones/metabolism , Humans , Lung Neoplasms/genetics , Lysine/genetics , RNA, Double-StrandedABSTRACT
Scytonemin is a yellow-green ultraviolet sunscreen pigment present in different genera of aquatic and terrestrial blue-green algae, including marine cyanobacteria. In the present study, the anti-inflammatory activities of scytonemin were evaluated in vitro and in vivo. Topical application of scytonemin inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear swelling in BALB/c mice. The expression of tumor necrosis factor-a (TNF-a) and inducible nitric oxide synthase (iNOS) was also suppressed by scytonemin treatment in the TPA-treated ear of BALB/c mice. In addition, scytonemin inhibited lipopolysaccharide (LPS)-induced production of TNF-a and nitric oxide (NO) in RAW 264.7 cells, a murine macrophage-like cell line, and the mRNA expressions of TNF-a and iNOS were also suppressed by scytonemin in LPS-stimulated RAW 264.7 cells. Further study demonstrated that LPS-induced NF-kB activity was significantly suppressed by scytonemin treatment in RAW 264.7 cells. Our results also showed that the degradation of IkBa and nuclear translocation of the p65 subunit were blocked by scytonemin in LPS-stimulated RAW 264.7 cells. Collectively, these results suggest that scytonemin inhibits skin inflammation by blocking the expression of inflammatory mediators, and the anti-inflammatory effect of scytonemin is mediated, at least in part, by down-regulation of NF-kB activity. Our results also suggest that scytonemin might be used as a multi-function skin care ingredient for UV protection and anti-inflammation.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Indoles/pharmacology , Phenols/pharmacology , Sunscreening Agents/pharmacology , Animals , Lipopolysaccharides , Mice , Mice, Inbred BALB C , NF-KappaB Inhibitor alpha , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , RAW 264.7 Cells , Tetradecanoylphorbol Acetate/analogs & derivatives , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Contamination of fresh vegetables and berries with human enteric viruses is a major cause of food poisoning. The aim of this study was to investigate the prevalence of norovirus GI, norovirus GII, hepatitis A virus (HAV), adenovirus, astrovirus, rotavirus, and male-specific coliphage systematically in fresh fruit and vegetables and associated agricultural environmental samples, including irrigation water, soil, and worker's gloves. Enteric viruses were detected by international standard methods (ISO/TS 15216), and male-specific coliphages were isolated using US EPA Method 1601. For the study, 773 samples were collected from June 2016 to April 2017, including Chinese cabbage (n = 244), cucumber (n = 98), lettuce (n = 73), strawberry (n = 120), soil (n = 191), irrigation water (n = 14), and gloves (n = 27). Two cucumber and two irrigation water samples were positive for norovirus GI, and one cucumber and two irrigation water samples were positive for norovirus GII. HAV was detected in one strawberry sample and one glove sample. The other tested foodborne viruses were not detected in any of the samples. Sixteen male-specific coliphages were isolated from Chinese cabbage, cucumber, lettuce, cherry tomato, soil, and irrigation water. The isolation of male-specific coliphage would be more practical to investigate the fecal contamination in produce rather than pathogenic viruses.
Subject(s)
Food Microbiology , Fruit/virology , Vegetables/virology , Viruses/isolation & purification , Agricultural Irrigation , Demography , Enterovirus/isolation & purification , Food Contamination , Hepatitis A virus/isolation & purification , Humans , Norovirus/isolation & purification , Republic of Korea , Rotavirus/isolation & purificationABSTRACT
Black phosphorus (BP) has attracted increasing attention due to its unique electrical properties. In addition, the outstanding optical nonlinearity of BP has been demonstrated in various ways. Its functionality as a saturable absorber, in particular, has been validated in demonstrations of passive mode-locked lasers. However, normally, the performance of BP is degraded eventually by both thermal and chemical damage in ambient conditions. The passivation of BP is the critical issue to guarantee a stable performance of the optical devices. We quantitatively characterized the mode-locked lasers operated by BP saturable absorbers with diversified passivation materials such as polydimethylsiloxane (PDMS) or Al2O3, considering the atomic structure of the materials, and therefore the hydro-permeability of the passivation layers. Unlike the BP layers without passivation, we demonstrated that the Al2O3-passivated BP layer was protected from the surface oxidation reaction in the long-term, and the PDMS-passivated one had a short-term blocking effect. The quantitative analysis showed that the time-dependent characteristics of the pulsed laser without passivation were changed with respect to the pulse duration, spectral width, and time-bandwidth product displaying 550 fs, 2.8 nm, and 0.406, respectively. With passivation, the changes were limited to <43 fs, <0.3 nm, and <0.012, respectively.
ABSTRACT
Estimating the actual occurrence of foodborne illness is challenging because only a small proportion of foodborne illnesses are confirmed and reported. Many studies have attempted to accurately estimate the overall number of cases of foodborne illness, but none have attempted to estimate the burden of foodborne disease in South Korea. This study used data from the Health Insurance Review and Assessment Service (HIRA), a public health surveillance system in South Korea, to calculate the number of cases and hospitalizations due to 18 specific pathogens and unspecified agents commonly transmitted through contaminated food between 2008 and 2012 in South Korea while accounting for uncertainty in the estimate. The estimated annual occurrences of foodborne illness were 336,138 (90% credible interval [CrI]: 258,379-430,740), with inpatient stays (hospitalizations), outpatient visits (foodborne disease infections), and patients' experiences (without visiting physicians) accounting for 2.3% (n=7809 [90% CrI: 7016-8616]), 14.4% (n=48,267 [90% CrI: 45,883-50,695]) and 83.3% (n=280,062 [90% CrI: 201,795-374,091]), respectively. Escherichia coli, including enterohemorrhagic E. coli, caused most illnesses, followed by nontyphoidal Salmonella spp., Staphylococcus aureus, hepatitis A virus, and norovirus. These results will be useful to food safety policymakers for the prevention and control of foodborne pathogens in South Korea.
Subject(s)
Enterohemorrhagic Escherichia coli/pathogenicity , Food Contamination/prevention & control , Foodborne Diseases/epidemiology , Cost of Illness , Food Safety , Hepatitis A virus/pathogenicity , Hospitalization , Humans , Norovirus/pathogenicity , Outpatients , Republic of Korea/epidemiology , Salmonella/pathogenicity , Staphylococcus aureus/pathogenicityABSTRACT
Because of global warming, the quantity of naturally generated mercury (Hg) will increase, subsequently methylation of Hg existing in seawater may be enhanced, and the content of metal in marine products rise which consequently results in harm to human health. Studies of the effects of temperatures on Hg absorption have not been adequate. In this study, in order to observe the effects of temperature changes on Hg absorption, inorganic Hg or methylmercury (MeHg) was added to water tanks containing loaches. Loach survival rates decreased with rising temperatures, duration, and exposure concentrations in individuals exposed to inorganic Hg and MeHg. The MeHg-treated group died sooner than the inorganic Hg-exposed group. The total Hg and MeHg content significantly increased with temperature and time in both metal-exposed groups. The MeHg-treated group had higher metal absorption rates than inorganic Hg-treated loaches. The correlation coefficients for temperature elevation and absorption were significant in both groups. The results of this study may be used as basic data for assessing in vivo hazards from environmental changes such as climate warming.
Subject(s)
Cypriniformes/metabolism , Environmental Exposure/analysis , Mercury/pharmacokinetics , Methylmercury Compounds/pharmacokinetics , Water Pollutants, Chemical/pharmacokinetics , Animals , Environment , Seawater/chemistry , TemperatureABSTRACT
In the present study, we investigated the effect of agelasine D (AD) on osteoclastogenesis. Treatment of bone marrow macrophages (BMMs) with receptor activator of nuclear factor κB ligand (RANKL) resulted in a differentiation of BMMs into osteoclasts as evidenced by generation of tartrate-resistant acid phosphatase (TRAP)-positive, multinucleated cells and formation of pits in calcium phosphate-coated plates. However, RANKL-induced osteoclastogenesis was significantly suppressed by AD treatment. We also confirmed the increased mRNA and protein expression of osteoclastic markers, such as TRAP, cathepsin K and matrix metalloproteinase-9, during RANKL-induced osteoclast differentiation and this was down-regulated by AD treatment. Moreover, AD treatment significantly suppressed RANKL-induced mRNA expression of DC-STAMP and OC-STAMP and cell fusion of TRAP-positive mononuclear osteoclast precursors. In addition, AD suppressed RANKL-induced expression of transcription factors, c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are important transcription factors involved in differentiation of BMMs into osteoclasts. Furthermore, RANKL-induced phosphorylation of extracellular signal-related kinase (ERK) and activation of NF-κB were also inhibited by AD treatment. Collectively, these results suggest that AD inhibits RANKL-induced osteoclastogenesis by down-regulation of multiple signaling pathways involving c-Fos, NFATc1, NF-κB and ERK. Our results also suggest that AD might be a potential therapeutic agent for prevention and treatment of osteoporosis.
Subject(s)
Acid Phosphatase/metabolism , Isoenzymes/metabolism , Osteoclasts/drug effects , Purines/pharmacology , RANK Ligand/administration & dosage , Animals , Bone Marrow Cells/cytology , Down-Regulation , Female , Macrophages/drug effects , Macrophages/metabolism , Mice , Mice, Inbred C57BL , NF-kappa B/genetics , NFATC Transcription Factors/genetics , Osteoclasts/metabolism , Proto-Oncogene Proteins c-fos/genetics , RANK Ligand/metabolism , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Signal Transduction/drug effects , Tartrate-Resistant Acid PhosphataseABSTRACT
A facile and sensitive analytical method that uses gold-coated magnetic nanoparticle clusters (Au/MNCs) and magnetophoretic chromatography with a precision pipet has been developed for the detection of Salmonella bacteria. Antibody-conjugated Au/MNCs are used to capture the Salmonella bacteria in milk and are then separated from the milk by applying an external magnetic field. The Salmonella-containing solution is sucked into a precision pipet tip to which a viscous polymer solution is then added. Once the magnetophoretic chromatography process has been carried out for 10 min, the presence of 100 cfu/mL Salmonella bacteria can be detected with the naked eye because the bacteria have become concentrated at the narrow pipet tip. The performance of this method was evaluated by using dynamic light scattering and light absorption spectroscopy.
Subject(s)
Chromatography/methods , Magnetic Phenomena , Salmonella/isolation & purification , Gold/chemistry , Magnetite Nanoparticles/chemistryABSTRACT
The influence of temperature on the development and embryonation of Ascaris suum eggs was studied using coarse sand medium in an environmental chamber with 50% humidity. The time required for development and embryonation of eggs was examined under 3 different temperature conditions, 5°C, 25°C, and 35°C. A. suum eggs did not develop over 1 month at the temperature of 5°C. However, other temperature conditions, 25°C and 35°C, induced egg development to the 8-cell-stage at days 5-6 after incubation. All eggs examined developed to the 8-cell stage at day 6 after incubation in the sand medium at 25°C. The higher temperature, 35°C, slightly accelerated the A. suum egg development compared to 25°C, and the development to the 8-cell stage occurred within day 5 after incubation. The formation of larvae in A. suum eggs at temperatures of 35° and 25°C appeared at days 17 and 19 after incubation, respectively. These findings show that 35° condition shortens the time for the development of A. suum eggs to the 8-cell-stage in comparison to 25°C, and suggest the possibility of accelerated transmission of this parasite, resulting from global warming and ecosystem changes.
Subject(s)
Ascaris suum/embryology , Ascaris suum/radiation effects , Animals , Ascaris suum/growth & development , Culture Media , Eggs/radiation effects , Humidity , Larva/growth & development , Larva/radiation effects , Silicon Dioxide , TemperatureABSTRACT
Tumor necrosis factor alpha (TNF-alpha) is a major inflammatory cytokine that plays an important role in the development of various inflammatory diseases. TNF-alpha has been considered as a potential therapeutic target for the treatment of chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease. In this study, we report that cyclopropyl-{4-[4-(4-fluorophenyl)-2-piperidin-4-yl-thiazol-5-yl]pyrimidin-2-yl}amine (DBM1285) is a novel inhibitor of TNF-alpha production. DBM1285 concentration-dependently inhibited lipopolysaccharide (LPS)-induced TNF-alpha secretion in various cells of macrophage/monocyte lineage, including mouse bone marrow macrophages, THP-1 cells, and RAW 264.7 cells. However, LPS-induced mRNA expression of TNF-alpha was not affected by DBM1285 in these cells. Further studies demonstrated that the inhibitory effect of DBM1285 on TNF-alpha production might be mediated by post-transcriptional regulation through the modulation of the p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein kinase 2 (MK2) signaling pathway. We also confirmed that DBM1285 directly inhibits p38 MAPK enzymatic activity. In vivo administration of DBM1285 inhibited LPS-induced increase in the plasma level of TNF-alpha in mice. Whole-blood in vivo target inhibition assay also revealed that DBM1285 attenuates p38 MAPK activity after oral administration in mice. Moreover, DBM1285 suppressed zymosan-induced inflammation and adjuvant-induced arthritis in murine models. Collectively, these results suggest that DBM1285 inhibits TNF-alpha production, at least in part, by blocking the p38 MAPK/MK2 pathway. Furthermore, in vivo results suggest that DBM1285 might be a possible therapeutic candidate for the treatment of TNF-alpha-related chronic inflammatory diseases.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Intracellular Signaling Peptides and Proteins/physiology , Protein Serine-Threonine Kinases/physiology , Pyrimidines/pharmacology , Thiazoles/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/physiology , Animals , Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid/drug therapy , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Cell Lineage , In Vitro Techniques , Inflammation/drug therapy , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Mice , RNA, Messenger/biosynthesis , Signal Transduction , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/genetics , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitorsABSTRACT
This study aimed to investigate the prevalence of foodborne viruses in reservoirs (an important resource of irrigation water) and its correlation with environmental and weather factors. From May 2017 to November 2018, we visited ten reservoirs and a river in the Anseong region of South Korea and collected a total of 192 samples in accordance with the environment protection agency guidelines. We recorded the weather factors (temperature, humidity, and accumulated precipitation) and investigated the surrounding environment factors (livestock, fishing site, the catchment area of reservoirs, etc.). Our research results show that from the river and reservoirs, the detection rates of human norovirus GII, adenovirus, rotavirus, human norovirus GI, and astrovirus were 27.1, 10.4, 10.4, 4.16, and 3.1%, respectively. Their viral load ranged from -1.48 to 1.55 log10 genome copies/l. However, hepatitis A virus was not detected in any irrigation water sample. Although no sampling was performed in winter, foodborne viruses and male-specific coliphages were frequently found during spring (40.78%) and autumn (39.47%). Interestingly, the significant correlation between the accumulative precipitation and the number of detected norovirus and adenovirus was confirmed by linear regression analysis. Furthermore, when the accumulative precipitation ranged from 20 to 60 mm, it significantly affected the viral load and prevalence. Among the environmental factors, recreational facilities such as fishing sites and bungalow fishing spots were identified as contamination sources by correlation analysis. Our research results confirmed the correlations between environmental contamination factors in the reservoir and weather factors with the prevalence of foodborne viruses in the reservoir. These facilitates the assessment of potential foodborne virus contamination during crop irrigation. In addition, predictive models including environmental and weather factors should be developed for monitoring and controlling the safety of irrigation waters in reservoirs.
ABSTRACT
In this study, a total of 195 samples including fresh produce and farming environments was used to perform the microbial risk assessment. Levels of total aerobic bacteria ranged from 2.77 to 5.99, 6.28 to 7.81, and 1.31 to 2.74 log10 CFU/g, whereas levels of coliforms were ≤ 2.48, ≤ 3.35, and ≤ 0.85 log10 CFU/g, levels of Escherichia coli were ≤ 1.04, ≤ 0.12, and ≤ 1.69 log10 CFU/g in fresh produce, soil, and irrigation water, respectively. When the presence of pathogenic bacteria was detected, only Bacillus cereus and Staphylococcus aureus were isolated from 14 (7.2%) and 7 (3.6%) samples out of 195 samples, respectively. From the results, it was difficult to find a strong correlation between microbial contamination of fresh produce and their farming environments. However, continuous monitoring of agricultural products and related environments should be undertaken in order to ensure the microbial safety of fresh produce.
ABSTRACT
Climatic factors can affect the incidence of foodborne diseases (FBDs). Moreover, microbial network inference is useful for predicting the interrelationships between the incidence of FBDs and climatic factors. However, the interrelationships between FBD pathogens and most climatic factors are unknown. Using principal component analysis (PCA) and partial correlation coefficient matrices (PCCMs), we determined the intra-ecosystem interrelationship network of the multiple combined effects of 5 climatic factors (temperature, relative humidity, rainfall, insolation, and cloudiness) and the monthly incidences of 12 bacterial FBDs. Many FBD pathogens are interrelated with multiple combined factors. Salmonellosis has strong positive interrelationships with Vibrio parahaemolyticus and enterohemorrhagic Escherichia coli, and the interrelationships between Staphylococcus aureus/enteropathogenic E. coli/enterotoxigenic E. coli exhibits a typical triangular pattern with the combined effects of all 5 climatic factors. Meanwhile, campylobacteriosis and Clostridium perfringens infections are negatively interrelated with insolation and cloudiness. Enteroinvasive E. coli, Bacillus cereus, Listeria spp., and Yersinia enterocolitica are significantly interrelated with any climatic factor combination. The interrelationships or higher-order interrelationships among these climatic factors play an important role in the incidence of FBDs, although the underlying mechanisms remain unclear. Our results will serve as a foundation for more sophisticated models of future FBD patterns with regard to climate change.
Subject(s)
Bacteria , Bacterial Infections/epidemiology , Climate Change , Foodborne Diseases/epidemiology , Bacterial Infections/microbiology , Foodborne Diseases/microbiology , Humans , Incidence , TemperatureABSTRACT
Information regarding the relationship between the incidence of foodborne diseases (FBD) and climatic factors is useful in designing preventive strategies for FBD based on anticipated future climate change. To better predict the effect of climate change on foodborne pathogens, the present study investigated the combined influence of multiple climatic factors on bacterial FBD incidence in South Korea. During 2011-2015, the relationships between 8 climatic factors and the incidences of 13 bacterial FBD, were determined based on inpatient stays, on a monthly basis using the Pearson correlation analyses, multicollinearity tests, principal component analysis (PCA), and the seasonal autoregressive integrated moving average (SARIMA) modeling. Of the 8 climatic variables, the combination of temperature, relative humidity, precipitation, insolation, and cloudiness was significantly associated with salmonellosis (P<0.01), vibriosis (P<0.05), and enterohemorrhagic Escherichia coli O157:H7 infection (P<0.01). The combined effects of snowfall, wind speed, duration of sunshine, and cloudiness were not significant for these 3 FBD. Other FBD, including campylobacteriosis, were not significantly associated with any combination of climatic factors. These findings indicate that the relationships between multiple climatic factors and bacterial FBD incidence can be valuable for the development of prediction models for future patterns of diseases in response to changes in climate.
Subject(s)
Bacterial Infections/epidemiology , Climate , Foodborne Diseases/epidemiology , Seasons , Climate Change , Humans , Incidence , Republic of Korea , TemperatureABSTRACT
Recent studies have reported that chemically synthesized double-stranded RNAs (dsRNAs), also known as small activating RNA (saRNAs), can specifically induce gene expression by targeting promoter sequences by a mechanism termed RNA activation (RNAa). In the present study, we designed 4 candidate saRNAs targeting the Von Hippel-Lindau (VHL) gene promoter. Among these saRNAs, dsVHL-821 significantly inhibited cell growth by up-regulating VHL at both the mRNA and protein levels in renal cell carcinoma 769-P cells. Functional analysis showed that dsVHL-821 induced apoptosis by increasing p53, decreasing Bcl-xL, activating caspase 3/7 and poly-ADP-ribose polymerase in a dose-dependent manner. Chromatin immunoprecipitation analysis revealed that dsVHL-821 increased the enrichment of Ago2 and RNA polymerase II at the dsVHL-821 target site. In addition, Ago2 depletion significantly suppressed dsVHL-821-induced up-regulation of VHL gene expression and related effects. Single transfection of dsVHL-821 caused long-lasting (14 days) VHL up-regulation. Furthermore, the activation of VHL by dsVHL-821 was accompanied by an increase in dimethylation of histone 3 at lysine 4 (H3K4me2) and acetylation of histone 4 (H4ac) and a decrease in dimethylation of histone 3 at lysine 9 (H3K9me2) and lysine 27 (H3K27me2) in the dsVHL-821 target region. Taken together, these results demonstrate that dsVHL-821, a novel saRNA for VHL, induces the expression of the VHL gene by epigenetic changes, leading to inhibition of cell growth and induction of apoptosis, and suggest that targeted activation of VHL by dsVHL-821 may be explored as a novel treatment of renal cell carcinoma.
Subject(s)
Carcinoma, Renal Cell/metabolism , Epigenesis, Genetic/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Kidney Neoplasms/metabolism , RNA, Double-Stranded/pharmacology , Von Hippel-Lindau Tumor Suppressor Protein/biosynthesis , Apoptosis/drug effects , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Von Hippel-Lindau Tumor Suppressor Protein/geneticsABSTRACT
As part of the aging process, multiple oral physiologic changes occur and these changes may cause individuals to reduce food intake or switch the types of food texture. Thus, the need to develop food products for the elderly has increased. To evaluate the suitability of the food products for the elderly, the evaluation method should be verified and it is important to identify the parameters of mastication and swallowing. Therefore, the purpose of this study was to compare the differences of mastication and swallowing parameters between the young adults and the elderly depending on the varying hardness of rice food product. Subjects included 20 young adults and 40 elderly and bolus transit times of video-fluoroscopic swallowing study (VFSS) were used. Four types of rice products with different hardness were provided including cooked rice, soft-boiled rice, rice gruel and thin rice gruel. In the elderly group, the chewing number, oral processing time, post-faucial aggregation time, valleculae aggregation time (VAT), first subsequence duration and total duration were significantly different according to the changes in food hardness. Of the bolus transit times, the VAT and the second subsequence duration (S-S2) were significantly different between the two groups. These results suggest that VAT and S-S2, key VFSS parameters, as well as the chewing number and total duration are useful tools for evaluating the effect of aging on mastication and swallowing of solid foods. PRACTICAL APPLICATIONS: In Korea, the aging population is rapidly increasing. According to recent surveys, a large number of elderly Koreans have reported chewing difficulties and many of them are in the state of under-nutrition. As aging progresses, multiple physiologic changes occur in mastication and swallowing functions. These changes may cause individuals to reduce their food intake or switch to soft food products. Therefore, the development of texture-modified food products for the elderly is needed and they should be developed based on the understandings of the physiology of mastication and swallowing according to different rheological properties of food products consumed in Korea, which are quite different from those of the western countries. In this study, we compared the differences of mastication and swallowing parameters between the young adults and the elderly depending on the varying hardness of rice food product.
Subject(s)
Deglutition/physiology , Food , Hardness , Mastication/physiology , Oryza/chemistry , Adult , Age Factors , Aged , Aged, 80 and over , Biomechanical Phenomena , Female , Fluoroscopy , Food/classification , Humans , Male , Republic of Korea , Starch/chemistry , Surface Properties , Video Recording , Young AdultABSTRACT
The effectiveness of sanitizing treatments was investigated on reducing pathogens inoculated in whole or cut fresh vegetables, including Brussels sprouts, carrots, cherry tomatoes, paprika, and lettuce. These products were inoculated with Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, and Listeria monocytogenes and then treated with chlorine and alcohol sanitizers, followed by the subsequent washing procedure in sterile distilled water at 25°C for 5min. Alcohol sanitizer was the most effective in inhibiting E. coli O157:H7, S. Typhimurium, and L. monocytogenes on cut Brussels sprouts, showing bacterial reductions of 4.16, 3.60, and 3.26 log CFU/g, respectively. Interestingly, the effects of sanitizing treatments were significantly lower for fresh cut produce than those for whole products (p<0.05), indicating that the effectiveness of sanitizers would be different, depending on fresh produce and the pre-cut process. Therefore, further information should be obtained to develop an effective sanitizing treatment for fresh produce.
ABSTRACT
Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by autoantibody production. Mesenchymal stem cells (MSCs) ameliorate SLE symptoms by targeting T cells, whereas the mechanisms of their efficacy remain incompletely understood. In this study, we show that transfer of human MSCs increased MRL.Faslpr mouse survival, decreased T cell infiltration in the kidneys, and reduced T cell cytokine expression. In vitro, allogeneic mouse MSCs inhibited MRL.Faslpr T cell proliferation and cytokine production. Time-lapse imaging revealed that MSCs recruited MRL.Faslpr T cells establishing long-lasting cellular contacts by enhancing T cell VCAM-1 expression in a CCL2-dependent manner. In contrast, CCL2 deficient MSCs did not induce T cell migration and VCAM-1 expression, resulting in insufficient cell-cell contact. Consequently, CCL2 deficient MSCs did not inhibit IFN-γ production by T cells and upon transfer no longer prolonged survival of MRL.Faslpr mice. Taken together, our imaging study demonstrates that CCL2 enables the prolonged MSC-T cell interactions needed for sufficient suppression of autoreactive T cells and helps to understand how MSCs ameliorate symptoms in lupus-prone MRL.Faslpr mice.
Subject(s)
Cell Communication , Chemokine CCL2/deficiency , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/pathology , Mesenchymal Stem Cells/metabolism , T-Lymphocytes/metabolism , Animals , Cell Movement , Humans , Mice, Inbred C57BL , Mice, Inbred MRL lpr , Solubility , Vascular Cell Adhesion Molecule-1/metabolismABSTRACT
The risk of Staphylococcus aureus in ready-to-eat kimbab (rice rolled in laver) sold in Korea was evaluated by a mathematical modeling approach. Four nodes were constructed from preparation at retail to consumption. A predictive microbial growth model and survey data were combined with probabilistic modeling to simulate the level of S. aureus in a single kimbab at the time of consumption. We estimated the mean level of S. aureus to be 2.92 log CFU/g for a typical kimbab (150 to 200 g each) at the time of consumption. Our model also showed that 29.73% of the kimbabs had > or = 100,000 S. aureus CFU/g, which poses some risk of illness, since some level of enterotoxin would be expected from toxigenic strains. However, because of the lack of dose-response models for staphylococcal enterotoxin, the final level of S. aureus in the kimbabs could not be used to estimate how many people would become ill from eating them. Correlation sensitivity results showed that consumer eating patterns and initial contamination levels at retail stores were the most significant risk factors for illness and that temperature control under 10 degrees C was a critical control point in kimbab retail establishments to prevent the growth of S. aureus.