Association of Corticosteroid Use With Incidence of Central Serous Chorioretinopathy in South Korea.

Importance: Information on the incidence of central serous chorioretinopathy (CSC) in individuals who receive corticosteroids is scarce but clinically important because these agents are useful and widely used. Objective: To estimate the annual and 5-year incidence of CSC in South Korea in the overall population and in those who have used corticosteroid medications. Design, Setting, and Participants: A cohort study of a population-based random sample included East Asian adults for whom records are held in the Korean National Health Insurance Service database for calendar years 2011 through 2015. The data analysis was performed from July 1, 2017 to January 5, 2018. Exposures: Any type of corticosteroid use from 2002 through 2015. Main Outcomes and Measures: Incidence of CSC. Results: The data set contained data from 868 939 adults (4 117 768 person-years). From 2011 through 2015, 1423 individuals (among whom the mean [SD] age was 46.8 [16.4] years and 1091 [76.7%] were male) with newly diagnosed CSC were identified. From 2002 to 2015, 783 099 individuals in the data set (90.1%) had ever used corticosteroids. The incidence of CSC per 10 000 person-years was 3.5 (5.4 in men; 1.6 in women) among the total population, 2.5 (3.0 in men; 1.2 in women) in those who had never used corticosteroids, and 3.6 (5.7 in men; 1.6 in women) among those who had ever used corticosteroids. The risk of CSCR with individuals who had ever used corticosteroids was estimated as an adjusted hazard ratio of 1.81 (95% CI, 1.47-2.23) compared with those who have never used these drugs. Current or recent corticosteroid use showed a positive association with the incidence of CSC (depending on duration of use, adjusted hazard ratio ranged from 1.54 to 2.15). Corticosteroid use in 2006 through 2009 was associated with an increased incidence of CSC after 2011 (adjusted hazard ratio 1.57 [95% CI, 1.13-2.18]). Conclusions and Relevance: In 2002 through 2015, 90.1% of adults in Korea received corticosteroids at least once. Although there was a clear difference in relative risk, this data analysis could not replicate the more than 30-fold increase in the risk ratio of CSC that has been reported previously. The incidence of CSC in the most vulnerable group, middle-aged men, was estimated to be approximately 1 case per 1000 corticosteroid users in the year following medication use. The overall incidence among those who had ever used corticosteroids and those who had never used these drugs was 2.5 and 3.6 per 10 000 person-years, respectively. This study provides additional evidence to support the potential role of corticosteroids in CSC.

Prevention of azoxymethane/dextran sodium sulfate-induced mouse colon carcinogenesis by processed Aloe vera gel.

The preventive effect of a processed Aloe vera gel (PAG) on colon carcinogenesis was examined using an azoxymethane (AOM)-initiated and dextran sodium sulfate (DSS)-promoted mouse colon carcinogenesis model. Oral administration of PAG (200, or 400mg/kg/day) significantly reduced the multiplicity of colonic adenomas and adenocarcinomas compared with the AOM/DSS only-treated mice. In the mice treated with 400mg/kg of PAG, adenoma and adenocarcinoma development was reduced to 80% and 60%, respectively, compared to 100% in the PAG-untreated AOM/DSS-treated mice. Western blot analysis using colon extracts showed that PAG reduced the activation of nuclear factor kappa B (NF-κB), resulting in the inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression. PAG appeared to inhibit the NF-κB activation through the activation of peroxisome proliferator-activated receptor gamma. PAG also inhibited the expression and phosphorylation of signal transducer and activator of transcription 3, which is known to connect inflammation and cancer. In addition, PAG inhibited cell cycle progression-inducing cellular factors, such as extracellular signal-regulated kinases 1/2, cyclin-dependent kinase 4, and cyclin D1. On the other hand, PAG increased the expression of Caudal-related homeobox transcription factor 2, which is known to be a tumor suppressor in colorectal cancer. These findings show that PAG suppresses colitis-related colon carcinogenesis by inhibiting both chronic inflammation and cell cycle progression in the colon.

Panaxydol, a component of Panax ginseng, induces apoptosis in cancer cells through EGFR activation and ER stress and inhibits tumor growth in mouse models.

We reported previously that panaxydol, a component of Panax ginseng roots, induced mitochondria-mediated apoptosis preferentially in transformed cells. This study demonstrates that EGFR activation and the resulting ER stress mediate panaxydol-induced apoptosis, and that panaxydol suppresses in vivo tumor growth in syngeneic and xenogeneic mouse tumor models. In addition, we elucidated that CaMKII and TGF-ß-activated kinase (TAK1) participate in p38/JNK activation by elevated cytoplasmic Ca(2+) concentration ([Ca(2+)]c). In MCF-7 cells, EGFR was activated immediately after exposure to panaxydol, and this activation was necessary for induction of apoptosis, suggesting that panaxydol might be a promising anticancer candidate, especially for EGFR-addicted cancer. Activation of PLCγ followed EGFR activation, resulting in Ca(2+) release from the endoplasmic reticulum (ER) via inositol triphosphate and ryanodine receptors. ER Ca(2+) release triggered mitochondrial Ca(2+) uptake indirectly through oxidative stress and ensuing ER stress. Elevated [Ca(2+)]c triggered sequential activation of calmodulin/CaMKII, TAK1 and p38/JNK. As shown previously, p38 and JNK activate NADPH oxidase. Here, it was shown that the resulting oxidative stress triggered ER stress. Among the three signaling branches of the unfolded protein response, protein kinase R-like ER kinase (PERK), but not inositol-requiring enzyme 1 or activating transcription factor 6, played a role in transmitting the apoptosis signal. PERK induced C/EBP homologous protein (CHOP), and CHOP elevated Bim expression, initiating mitochondrial Ca(2+) uptake and apoptosis. In summary, we identified roles of EGFR, the CAMKII-TAK1-p38/JNK pathway, and ER stress in panaxydol-induced apoptosis and demonstrated the in vivo anticancer effect of panaxydol.

Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like skin lesions via suppression of NF-κB and STAT1 and activation of Nrf2/ARE-mediated heme oxygenase-1.

PURPOSE: The consequences of precipitously rising allergic skin inflammation rates worldwide have accelerated the risk of atopic dermatitis (AD). Natural product-based agents with good efficacy and low risk of side effects offer promising prevention and treatment strategies for inflammation-related diseases. We have already reported that Platycodon grandiflorum root-derived saponins (Changkil saponins, CKS) have many pharmacological effects, including anti-inflammatory and anti-allergic effects, but its influence on AD remains unclear. Therefore, we evaluated the inhibitory effect of CKS, mainly platycodin D, on AD-like skin symptoms in mice and the possible mechanisms in cells. METHODS: Mice were sensitized and challenged with 2,4-dinitrochlorobenzene (DNCB). Four weeks after challenge, mice were treated with oral administration of CKS for 4 weeks. In addition, cells were used to evaluate the effect of CKS, mainly platycodin D, on the TARC expression regulated mechanism. RESULTS: CKS attenuated DNCB-induced dermatitis severity, serum levels of IgE and TARC, and mRNA expression of TARC, TNF-α, IFN-γ, IL-4, IL-5, and IL-13 in mice. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells and mast cells in the ears. Moreover, CKS and platycodin D inhibited TNF-α/IFN-γ-induced TARC expression through the suppression of NF-κB and STAT1 and induction of Nrf2/ARE-mediated hemeoxygenase-1 (HO-1) expression in cells. CONCLUSION: We suggest that CKS and platycodin D inhibited the development of AD-like skin symptoms by regulating cytokine mediators and may be an effective alternative therapy for AD-like skin symptoms.