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Background: Morinda citrifolia (Noni) is a plant that has long been used in various products such as foods and cosmetics. Although noni has been known to have immunostimulatory activity, detailed mechanism at the cellular level has not been fully elucidated yet. In this study, we focused on understanding as to how noni fruit can positively stimulate body's immune responses. Methods: To do this, an ethanol extract of noni fruit (Mc-fEE) was prepared and administered for 30 days to male C57BL/6 mice for in vivo experiment. NK cell activity and cytokine production level from Mc-fEE-treated mice were analyzed by flowcytometry, real-time PCR, and ELISA. Mc-fEE-triggered molecular events were detected from RAW264.7 cells and splenocytes using Western blotting and real-time PCR analyses. Results: The mRNA expression levels of cytokines such as interleukin families, interferon (IFN)-β, and tumor necrosis factor (TNF)-α were increased by Mc-fEE treatment in vitro and in vivo. Western blotting analysis showed that the phosphorylation levels of nuclear factor (NF)-κB and activator protein (AP)-1 subunits these were enhanced in Mc-fEE-treated RAW264.7 cells. In addition, according to in vivo experiments, it was considered that Mc-fEE can increase the population of splenic NK cells and subsequent upregulation of their cytotoxic activity against YAC-1 cells, a T- cell lymphoma. Conclusion: In this paper, we could confirm that Mc-fEE has remarkable immunostimulatory effects by activation and increase of the NK cell population. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of Clean-DM1 (C-DM1), a polyherbal formulation of Radix Scrophulariae, Radix Astragali, Rhizoma Atractylodis, and Radix Salviae Miltiorrhizae, on high-fat diet (HFD)-induced diabetes mice. Methods: The information about active components of C-DM1 extract and molecular mechanism was obtained from network pharmacology analysis. Main compounds of C-DM1 extract by high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis were conducted for quality control. For in vivo study, mice were induced diabetes by HFD for 12 weeks. The mice in the normal group (Nor) were maintained with a regular diet and treated with saline by gavage. The HFD model mice were randomly divided into 3 groups, including a HFD diabetic model group, a C-DM1 extract-administered group (C-DM1, 500 mg/kg), and metformin-administered groups (Met, 500 mg/kg), 8 mice in each group. Food intake, body weight (BW), and fasting blood glucose (FBG) levels were recorded weekly for 4 weeks. After 4 weeks of treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood glucose, low-density lipoprotein cholesterol (LDL-C) were determined using an automated clinical chemistry analyzer, and homeostatic model for assessing insulin resistance (HOMA-IR) levels and oral glucose tolerance test (OGTT) were detected. The histopathological changes of liver and pancreatic tissues were observed by hematoxylin-eosin staining. Insulin receptor substrate (IRS)/phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT) and adenosine 5′-monophosphate-activated protein kinase (AMPK) expressions in liver and pancreas tissues were detected by Western blot analysis. Results: HPLC-MS identified dihydroisotanshinone, dihydroisotanshinone I, cryptotanshinone, harpagoside, and atractyloside A in C-DM1 extract. The administration of C-DM1 extract significantly decreased body weight, calorie intake, and the levels of blood glucose and insulin in the diabetic mice (P<0.05 or P<0.01). The C-DM1 extract administration improved the impaired glucose tolerance and insulin resistance in the diabetic mice and significantly decreased the levels of LDL-C, ALT and AST (P<0.01). The C-DM1 extract inhibited the histopathological changes of fatty liver and hyperplasia of pancreatic islets in the diabetic mice. The C-DM1 extract significantly increased the phosphorylation of IRS, AKT, and AMPK and the expression of PI3K in pancreas and liver tissues (P<0.05 or P<0.01), which was consistent with the analysis results of network pharmacology. Conclusion: C-DM1 extract improved diabetes symptoms in long-term HFD-induced mice by regulation of IRS/PI3K/AKT and AMPK expressions in pancreas and liver tissues, suggesting that C-DM1 formulation may help prevent the progression of T2DM. [ABSTRACT FROM AUTHOR]

Carcinogenicity tests predict the tumorigenic potential of various substances in the human body by studying tumor induction in experimental animals. There is a need for studies that explore the use of FVB/N-Trp53em2Hwl/Korl (FVB-Trp53+/-) mice, created by TALEN-mediated gene targeting in Korea, in carcinogenicity tests. This study was performed to determine whether FVB-Trp53+/- mice are a suitable model for short-term carcinogenicity studies. To compare the carcinogenicity at different concentrations, 25, 50, and 75 mg/kg of N-methyl-N-nitrosourea (MNU), a known carcinogen, were administered intraperitoneally to FVB-Trp53+/- and wild-type male mice. After 26 weeks, the survival rate was significantly reduced in FVB-Trp53+/- mice compared to the wild-type mice in the 50 and 75 mg/kg groups. The incidence of thymic malignant lymphoma (TML) in the 50 and 75 mg/kg groups was 54.2 and 59.1% in FVB-Trp53+/- male mice, respectively. TML metastasized to the lungs, spleen, lymph nodes, liver, kidney, and heart in FVB-Trp53+/- male mice. Furthermore, the incidence of primary lung tumors, such as adenomas and adenocarcinomas, was 65.4, 62.5, and 45.4% in the FVB-Trp53+/- mice of the 25, 50, and 75 mg/kg groups, respectively. The main tumor types in FVB-Trp53+/- mice were TML and primary lung tumors, regardless of the dose of MNU administered. These results suggest that systemic tumors may result from malfunctions in the p53 gene and pathway, which is an important factor in the pathogenesis of human cancers. Therefore, FVB-Trp53 heterozygous mice are suitable for short-term carcinogenicity tests using positive carcinogens, and that the best result using MNU, a positive carcinogen, might have a single dose of 50 mg/kg. [ABSTRACT FROM AUTHOR]

Simple Summary: Experimental mice are the most commonly used laboratory animals for biomedical research and comparative studies. However, microbial infection may alter the mouse phenotype and confound interpretation results. The genus Corynebacterium, Gram-positive diphtheroid rod-shaped bacteria, induces severe diseases, such as hyperkeratosis and pseudotuberculosis, in immunodeficient mice. In this report, we described the population of Corynebacterium spp. isolated from laboratory mice in Korea using different approaches, comparing the accuracy and problems associated with each method. When identified based on molecular methods such as 16S rRNA and rpoB gene sequence analysis, the main Corynebacterium species were C. mastitidis (44.8%), C. bovis (25.5%), C. lowii (21.2%), and C. amycolatum (8.5%). In addition, matrix-assisted laser desorption/ionization–time of flight mass spectrometry (MALDI-TOF MS) yielded results that were 77.9% identical to the molecular results, whereas biochemical methods showed only 15.5% identical to molecular identification. Collectively, our findings indicate that the different results may be obtained depending on the method used to identify Corynebacterium isolated from experimental mice, highlighting the importance of selecting an appropriate Corynebacterium identification method in obtaining accurate identification results. This result will help to increase the reliability of Corynebacterium diagnosis result from experimental mice. The genus Corynebacterium, composed of Gram-positive diphtheroid rod-shaped bacteria, induces severe diseases, such as Corynebacterium-associated hyperkeratosis and pseudotuberculosis, in immunodeficient mice. We isolated and identified a total of 165 strains of Corynebacterium species from experimental mice in Korean laboratories, diagnosed using several methods. When identified based on molecular methods, namely, 16S rRNA and rpoB gene sequence analysis, the main Corynebacterium species isolated in Korean laboratory mice were C. mastitidis (44.8%, n = 74), C. bovis (25.5%, n = 42), C. lowii (21.2%, n = 35), and C. amycolatum (8.5%, n = 14). Diagnoses were also performed using matrix-assisted laser desorption/ionization–time of flight mass spectrometry (MALDI-TOF MS) and biochemical methods. MALDI-TOF MS yielded results that were 77.9% identical to the molecular identification results, whereas biochemical methods showed only 15.5% identical to molecular identification, partly owing to difficulties in distinguishing among C. mastitidis strains. Collectively, our findings indicate that molecular biological methods are better suited for detecting and identifying Corynebacterium species candidates isolated from mice than biochemical methods. Because of limitations associated with the use of MALDI-TOF MS, more precise results will be obtained by complementing this approach with other methods when used for rapid identification testing. [ABSTRACT FROM AUTHOR]

Chrysanthemum morifolium Ramatuelle and Scutellaria baicalensis Georgi (skullcap) have been used as safe raw materials for drinking or as traditional medicines in Korea. In this study, we investigated the potential therapeutic effects of ovalbumin-induced asthma in a mouse model. After establishing the model, mice were treated with a mixture of chrysanthemum and skullcap extracts at different mixing ratios (6 : 4, 7 : 3, and 8 : 2). Immune cell counts and the production of various inflammatory cytokines were measured using biochemical tests. Among the mixtures tested, the 7 : 3 ratio (CS73) showed the most pronounced effects. CS73 significantly reduced the levels of the inflammatory cytokines interleukin- (IL-) 1β, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-17F, and IL-17E in the serum and bronchoalveolar lavage fluid of asthmatic mice. In addition, CS73 treatment significantly increased the production of IL-2 and interferon-γ and decreased the production of immunoglobulin E, histamine, and thymic stromal lymphopoietin in asthmatic mice compared to the control group. Our results suggest that the combination of chrysanthemum and skullcap extracts, especially at a 7 : 3 ratio, can be used to improve bronchial health and contribute to improved public health. [ABSTRACT FROM AUTHOR]