Clinical Features of Re-Emerging Hepatitis A: An Analysis of Patients Hospitalized during an Urban Epidemic in Korea

From April 2008 to November 2008, many cases of hepatitis A were reported in Seoul and Gyeonggi Province in Korea. Furthermore, the rate of severe or fulminant hepatitis have significantly increased during the latest epidemic (13.4% vs. 5.2%, p=0.044). Therefore, widespread use of vaccine is warranted to reduce the burden of hepatitis A in Korea

Effect of Ginseng Sapogenin Protopanaxadiol-Enriched Rice (DJ-PPD) on Immunomodulation

Protopanaxadiol (PPD), a gut microbiome-induced ginseng metabolite, has positive immune effects. We previously reported the immune-boosting and anti-inflammatory effects of PPD-enricshed rice seed extracts in normal and inflammatory cell environments, respectively. In the present study, the immunomodulatory activity of PPD-enriched transgenic rice seed extract (DJ-PPD), which exhibited the highest immune-related activity among all available extracts, was compared with that of commercially synthesized 20s-PPD (S-PPD) and naturafigure s ginseng root extract (GE), in RAW264.7 cells. Compared with S-PPD and GE treatment, DJ-PPD treatment (i) significantly promoted NF-κB p65 and c-Jun N-terminal protein kinase (JNK) phosphorylation; (ii) upregulated IL-1β, IL-6, COX-2, TLR-4, and TNF-α expression; (iii) and increased prostaglandin E2 (PGE2) production. However, there were no significant differences in the effects of the three treatments containing PPD-type sapogenin or saponins on nitric oxide (NO) production and phagocytic activity. In the inflammatory cell environment, DJ-PPD treatment markedly decreased the production of LPS-induced inflammatory factors, including NO and PGE2, as well as proinflammatory cytokine expression, by decreasing phosphorylated (p-)NF-κB p65, p-p38 MAPK, and p-JNK levels. Thus, DJ-PPD that does not require complex intestinal microbial processes to exert higher anti-inflammatory effects compared with S-PPD and GE. However, DJ-PPD exerted similar or higher immune-boosting effects (depending on inflammatory biomarkers) than S-PPD and GE. These findings indicate the potential of PPD-enriched transgenic rice as an alternative immunomodulatory agent

Anti-Inflammatory Efficacy of Resveratrol-Enriched Rice Callus Extract on Lipopolysaccharide-Stimulated RAW264.7 Macrophages

Resveratrol and its derivative piceid exhibit a wide spectrum of health-promoting bioactivities. A resveratrol-enriched variety of Dongjin rice (DJ526) has been developed by transfection of a resveratrol biosynthesis gene, and increased resveratrol content has been confirmed in seeds following germination. In the current study, these resveratrol-enriched seeds were induced to produce callus, and callus extracts were evaluated for in vitro anti-inflammatory activity. Callus cultures contained greater amounts of resveratrol and piceid than DJ526 seeds, and treatment with DJ526 callus extract significantly reduced the lipopolysaccharide (LPS)-induced production of proinflammatory mediators nitric oxide and prostaglandin E2 by RAW264.7 macrophages. The inflammation-related nuclear factor kappa B and mitogen-activated protein kinase pathways were also inhibited in DJ526 callus extract-treated RAW264.7 cells, resulting in downregulation of proinflammatory factor genes COX-2, iNOS, IL-1β, IL-6, and TNF-α. Expression of the LPS-binding toll-like receptor-4 was also markedly reduced in DJ526 callus extract-treated cells compared to DJ callus extract-treated cells. These findings demonstrate increased resveratrol and piceid content by callus culture of DJ526 rice seeds and the potent anti-inflammatory activity of resveratrol-enriched callus extract

Genetically Engineered Resveratrol-Enriched Rice Inhibits Neuroinflammation in Lipopolysaccharide-Activated BV2 Microglia Via Downregulating Mitogen-Activated Protein Kinase-Nuclear Factor Kappa B Signaling Pathway

Resveratrol, a natural stilbenoid, is produced by several plants, especially grape vines. Its strong potency against obesity, metabolic disorders, vascular disease, inflammation, and various cancers has already been reported. Large amounts of wine or grapes need to be consumed to obtain the amount of resveratrol required for biological activity. Pure resveratrol at concentrations as low as 10 μM induces cytotoxicity to normal cells. To overcome these limitations, we prepared genetically modified resveratrol-enriched rice (RR). We previously reported the strong antiaging potential of RR against ultraviolet B/reactive oxygen species-induced toxicity in normal human dermal fibroblasts (NHDF). As aging is characterized by neuroinflammation and neurodegeneration, we further evaluated the role of RR against LPS-induced neuroinflammation. RR inhibited nitric oxide production and the expression of inflammatory proteins such as iNOS and COX-2. RR significantly modulated mitogen-activated protein kinase signaling, activator protein AP-1 signaling, and nuclear factor kappa B (NF-κB) mediated transcription of inflammatory proteins via inhibition of NF-κB translocation, IkB phosphorylation, and proinflammatory cytokine productions such as interleukin IL-6, IL-1β, tumor necrosis factor alpha (TNF-α), and prostaglandin E2 (PGE2). These findings show that the strong antineuroinflammatory effects of RR can be beneficial for aging-mediated neurodegenerative conditions as well as disorders of the central nervous system caused by neuroinflammation

Transgenic Rice Seed Extracts Exert Immunomodulatory Effects by Modulating Immune-Related Biomarkers in RAW264.7 Macrophage Cells

Protopanaxadiol (PPD), a native active triterpenoid present in Panax ginseng, has been reported to exert immune-related effects. We previously created PPD-producing transgenic rice by introducing the P. ginseng protopanaxadiol synthase and dammarenediol-II synthase genes into Dongjin rice. In the present study, the seeds of the T4 generation of this transgenic rice were tested for their immunomodulatory effects in RAW264.7 macrophage cells. Treatment with transgenic rice seed extract in RAW264.7 cells (i) significantly enhanced nitric oxide (NO) production in a dose-dependent manner without any cytotoxicity (up to 100 µg/mL), (ii) upregulated the expression of immune-related genes and increased production of the inflammation mediator prostaglandin E2 (PGE2), and (iii) activated nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) by promoting the phosphorylation of NF-κB p65, p38 MAPK, and c-Jun N-terminal protein kinase (JNK). In lipopolysaccharide (LPS)-treated RAW264.7 cells used to mimic the inflammation condition, treatment with transgenic rice seed extract significantly reduced NO production, proinflammatory cytokine expression, and PGE2 production, all of which are LPS-induced inflammation biomarkers, by inhibiting the phosphorylation of NF-κB p65, p38 MAPK, and JNK. Collectively, these results indicate that PPD-producing transgenic rice has immunomodulatory effects

Enhancing Resveratrol Bioproduction and Anti-Melanogenic Activities through Elicitation in DJ526 Cell Suspension

Resveratrol, a secondary plant metabolite, and its derivatives, including piceid, show several potential health-related biological activities. However, resveratrol production is uncommon in plants; thus, resveratrol-enriched rice (DJ526) is produced for its nutritional and therapeutic value. Here, a DJ526 cell suspension was treated with various elicitors to determine its resveratrol-production potential and elicit its biological activity. Treatments with most elicitors produced more piceid than resveratrol; as elicitation periods increased, the average piceid levels were 75-fold higher than resveratrol levels. This increase is associated with glycosylation during growth and development. The duration of exposure and concentrations of elicitors were crucial factors affecting resveratrol synthase expression. Of all the elicitors tested, jasmonic acid and methyl jasmonate (MeJA) were strong elicitors; they increased resveratrol production to ≤115.1 μg g−1 (total resveratrol and piceid content). Moreover, 5 μM of MeJA increased total resveratrol production by >96.4% relative to the control production. In addition, the extract of cell suspension treated with 5 μM of MeJA significantly reduced melanin content and cellular tyrosinase activity (24.2% and 21.5% relative to the control, respectively) in melan-a cells without disturbing cell viability. Overall, elicitation can enhance resveratrol production and elicit the biological activity of the compound, in this case, its anti-melanogenic activities, in DJ526 cell suspension

Effect of Ginseng Sapogenin Protopanaxadiol-Enriched Rice (DJ-PPD) on Immunomodulation

Protopanaxadiol (PPD), a gut microbiome-induced ginseng metabolite, has positive immune effects. We previously reported the immune-boosting and anti-inflammatory effects of PPD-enricshed rice seed extracts in normal and inflammatory cell environments, respectively. In the present study, the immunomodulatory activity of PPD-enriched transgenic rice seed extract (DJ-PPD), which exhibited the highest immune-related activity among all available extracts, was compared with that of commercially synthesized 20s-PPD (S-PPD) and natural ginseng root extract (GE), in RAW264.7 cells. Compared with S-PPD and GE treatment, DJ-PPD treatment (i) significantly promoted NF-κB p65 and c-Jun N-terminal protein kinase (JNK) phosphorylation; (ii) upregulated IL-1β, IL-6, COX-2, TLR-4, and TNF-α expression; (iii) and increased prostaglandin E2 (PGE2) production. However, there were no significant differences in the effects of the three treatments containing PPD-type sapogenin or saponins on nitric oxide (NO) production and phagocytic activity. In the inflammatory cell environment, DJ-PPD treatment markedly decreased the production of LPS-induced inflammatory factors, including NO and PGE2, as well as proinflammatory cytokine expression, by decreasing phosphorylated (p-)NF-κB p65, p-p38 MAPK, and p-JNK levels. Thus, DJ-PPD that does not require complex intestinal microbial processes to exert higher anti-inflammatory effects compared with S-PPD and GE. However, DJ-PPD exerted similar or higher immune-boosting effects (depending on inflammatory biomarkers) than S-PPD and GE. These findings indicate the potential of PPD-enriched transgenic rice as an alternative immunomodulatory agent

Enhanced Anti-Skin-Aging Activity of Yeast Extract-Treated Resveratrol Rice DJ526

Resveratrol is a powerful antioxidant that defends against oxidative stress in cells but is not found in large quantities in plants. Resveratrol-enriched rice DJ526, which was developed as a functional crop, shows a diverse range of biological activities. Resveratrol production is measured as total resveratrol and its glycoside, piceid, which is mainly found in plant-derived resveratrol. In the present study, elicitation using yeast extract (YE), methyl jasmonate, and jasmonic acid increased resveratrol production in DJ526 rice seeds. DJ526 seeds elicited using 1 g/L (YE1) and 5 g/L yeast extract (YE5) showed enhanced resveratrol production and antioxidant activity. YE5-treated DJ526 seeds showed decreased melanin content by 46.1% and 37.0% compared with the negative control and DJ526 (non-elicitation), respectively. Both YE1 and YE5 efficiently improved the wound-healing activity by reducing the wound gap faster than in untreated cells, with a maximum rate of 60.2% at 24 h and complete closure at 48 h. YE1 and YE5 significantly decreased the levels of proinflammatory cytokine, TNF-α, and enhanced collagen synthesis in inflammatory cells. These findings indicate that YE-treated resveratrol rice DJ526 may improve resveratrol production and could be an active antiaging ingredient for cosmetic and skin therapy applications

Protopanaxadiol-Enriched Rice Extracts Suppressed Oxidative and Melanogenic Activities in Melan-a Cells

Concerns about hyperpigmentation and skin appearance have led to increasing research into the prevention and altering of skin pigmentation. Natural compounds may be of interest in the search for skin-lightening actives. Protopanaxadiol (PPD), a gut microbiome-induced ginseng metabolite, has been reported to have anti-melanogenic effects. This study aimed to evaluate the antioxidative and anti-melanogenic effects of PPD-enriched rice seed extracts on melan-a cells. The antioxidant and cytotoxicity activities of the extracts were investigated in melan-a cells before measuring their responses to melanogenic activities. The extracts significantly enhanced the antioxidant potency compared with normal rice seed extract. PPD-enriched rice seed extracts (i) significantly downregulated microphthalmia-associated transcription factor, which led to a reduction in tyrosinase and tyrosinase-related protein-1 and -2, (ii) decrease in the cellular tyrosinase activity and melanin content, (iii) reduction in the number of melanin-containing cells, (iv) promotion of melanogenesis downregulators, phosphorylation of extracellular signal-regulated kinase 1/2 and protein kinase B, and (v) downregulation of the phosphorylated p38 mitogen-activated protein kinase and melanin synthesis. These results indicate the feasibility of PPD-enriched rice seed extracts as a novel agent for suppressing melanogenesis and controlling hyperpigmentation