Exploration of alternative test methods to evaluate phototoxicity of ophthalmic agents by using Statens Seruminstitut Rabbit Cornea cell lines and 3D human reconstituted cornea models.

Many chemicals have been reported to induce phototoxicity. The absorbance of light energy within the sunlight range is a common characteristic of phototoxicity. The 3T3 NRU phototoxicity test (PT) in 3T3 mouse skin fibroblasts has been used to identify the phototoxic potential induced by excited chemicals after exposure to ultra violet (UV). However, as phototoxicity may occur in ocular cells, it is necessary to develop a more suitable test for cornea-derived cells. In this study, we attempted to establish a new in vitro PT method in rabbit corneal cell lines (SIRC). We evaluated five ophthalmic agents, ciprofloxacin, levofloxacin, lomefloxacin, norfloxacin, and tetracycline, for their cytotoxic potential and in vitro phototoxicity. The results obtained using 3D human corneal models revealed that the UV-induced eye tissue toxicity by the test substances showed good correlation with those obtained using the in vitro phototoxicity test. However, the results from the 3D PT for ciprofloxacin, norfloxacin, and tetracycline in the 3D human cornea model were only partially comparable. Therefore, we suggest the SIRC cell line as a new phototoxicity test model; however, a sequential testing strategy, such as 3D PT, was also proposed to obtain relevant information for topical eye agents

Protective Effect of Octylmethoxycinnamate against UV-Induced Photoaging in Hairless Mouse via the Regulation of Matrix Metalloproteinases

Ultraviolet (UV) irradiation damages skin and produces symptoms of photoaging, such as thickening, rough texture, wrinkles, and pigmentation. However, the cellular and molecular mechanisms underlying photoaging induced by chronic UV irradiation are not yet fully understood. Matrix metalloproteinases (MMPs) have been reported to be involved in the response to UV irradiation. In this study, we examined the effects of the sunscreen agent Octylmethoxycinnamate (OMC) on photoaging of the skin induced by chronic UV exposure in hairless albino Crl:SKH1-Hrhr (SKH-1) mice. We demonstrated that the expression of MMPs was elevated by UV irradiation, whereas the topical application of OMC inhibited the upregulation of MMPs. Furthermore, UV-induced wrinkle formation was decreased by OMC treatment. These results suggest that OMC is a potential agent for the prevention and treatment of skin photoaging

Exploration of alternative test methods to evaluate phototoxicity of ophthalmic agents by using Statens Seruminstitut Rabbit Cornea cell lines and 3D human reconstituted cornea models - Fig 4

<p>Hematoxylin and eosin staining of 3D human cornea models (HCE) of the ophthalmic agent, with and without UV irradiation of 6 J/cm²: A) chlorpromazine (positive control), B) ciprofloxacin, C) norfloxacin, D) tetracycline, E) L-histidine (negative control), and F) sodium lauryl sulfate (negative control).</p

Spectral properties of chlorpromazine (positive control), ciprofloxacin, levofloxacin, lomefloxacin, norfloxacin, and tetracycline (test substances), and L-histidine and sodium lauryl sulfate (negative controls).

<p>Spectral properties of chlorpromazine (positive control), ciprofloxacin, levofloxacin, lomefloxacin, norfloxacin, and tetracycline (test substances), and L-histidine and sodium lauryl sulfate (negative controls).</p

Artificial Intelligence-based Prediction of Diabetes and Prediabetes Using Health Checkup Data in Korea

The economic burden of Type 2 Diabetes (T2D) on society has increased over time. Early prediction of diabetes and prediabetes can reduce treatment cost and improve intervention. The development of (pre)diabetes is associated with various health conditions that can be monitored by routine health checkups. This study aimed to develop amachine learning-based model for predicting (pre)diabetes. Our frameworks were based on 22,722 patient samples collected from 2013 to 2020 in ageneral hospital in Korea. The disease progression was divided into three categories based on fasting blood glucose: normal, prediabetes, and T2D. The risk factors at each stage were identified and compared. Based on the area under the curve, the support vector machine appeared to have optimal performance. At the normal and prediabetes stages, fasting blood glucose and HbA1c are prevalent risk features for the suggested models. Interestingly, HbA1c had the highest odds ratio among the features even in the normal stage (FBG is less than 100). In addition, factors related to liver function, such as gamma-glutamyl transpeptidase can be used to predict progression from normal to prediabetes, while factors related to renal function, such as blood urea nitrogen and creatinine, are prediction factors of T2D development

Phototoxicity criteria in NRU test.

<p>Phototoxicity criteria in NRU test.</p

Exploration of alternative test methods to evaluate phototoxicity of ophthalmic agents by using Statens Seruminstitut Rabbit Cornea cell lines and 3D human reconstituted cornea models - Fig 3

<p>Phototoxicity evaluation of the ophthalmic agents in SIRC cells: A) chlorpromazine (positive control), B) ciprofloxacin, C) levofloxacin, D) lomefloxacin, E) norfloxacin, F) tetracycline, G) L-histidine (negative control), and H) sodium lauryl sulfate (negative control). The closed circle and open circle represent data from the nonirradiated groups and UV-irradiated groups, respectively. Phototoxic chemicals induced dose-response curve shift with UV-irradiation. Fitting of the curve to the data was performed by a non-linear regression method (n = 6).</p

Irradiation sensitivity of SIRC cells.

<p>Cell viability showed a dose-dependent response to irradiation, with 85.2%±4.9% after irradiation at 5 J/cm², 73.8%±3.4% after irradiation at 10 J/cm², and 66.4%±2.9% after irradiation at 20 J/cm². The data are expressed as the mean ± S.E. (n = 5).</p

Comparison of phototoxicity test results from in vitro SIRC, 3D human model and 3T3 NRU phototoxicity test.

<p>Comparison of phototoxicity test results from in vitro SIRC, 3D human model and 3T3 NRU phototoxicity test.</p