A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Background: The purpose of this study was to identify the prevalence of posttraumatic embitterment disorder (PTED) among soldiers, and examine its relation to stress, depression, self-esteem, impulsiveness, and suicidal ideation. Methods: The subjects of this study were 200 soldiers and 197 control subjects, a total of 397 persons. Measurement tools used included the PTED self-rating scale, Stress Response Inventory, Beck Depression Inventory, Rosenberg Self-Esteem Inventory, Barratt Impulsiveness Scale, and Beck Scale of Suicide Ideation.Result: The major findings of the analysis are as follows: first, 11.5% of the soldiers were in the risk group for PTED, and 4% of them had PTED. Second, PTED in the soldiers was significantly associated with a number of variables such as their educational background, stress, depression, self-esteem, impulsiveness, and suicidal ideation, while it was not significantly associated with age. Third, through the hierarchical multiple regression analysis, it was found that academic background, stress, and depression had a statistically significant positive effect on the incidence of PTED in the soldiers. Conclusion In order to prevent and effectively intervene in PTED in soldiers, there is a need for interventional efforts focused on depression and stress related to negative life events.

The general linear model (GLM) describes the dependent variable as a linear combination of independent variables and an error term. The GLM procedure of SAS® and the “car” package in R calculate the type I, II, or III ANOVA (analysis of variance) tables. In this study, we validated the newly-developed R package, “sasLM,” which is compatible with the GLM procedure of SAS®. The “sasLM” package was validated by comparing the output with SAS®, which is the current gold standard for statistical programming. Data from ten books and articles were used for validation. The results of the “sasLM” and “car” packages were compared with those in SAS® using 194 models. All of the results in “sasLM” were identical to those of SAS®, whereas more than 20 models in “car” showed different results from those of SAS®. As the results of the “sasLM” package were similar to those in SAS® PROC GLM, the “sasLM” package could be a viable alternative method for calculating the type II and III sum of squares. The newly-developed “sasLM” package is free and open-source, therefore it can be used to develop other useful packages as well. We hope that the “sasLM” package will enable researchers to conveniently analyze linear models.

Objectives: ：Loneliness and poor sleep quality are common phenomena in old age and are associated with negative physical and mental health. However, little is known regarding the relation between loneliness and sleep quality. The aim of this study was to examine the association of loneliness and sleep quality among the elderly living alone. Methods: ：This is a cross-sectional study that enrolled 1,090 subjects who are the community-residing elderly living alone. Sociodemographic status, medical condition, cognition, mood disorder, sleep quality and levels of loneliness were collected using a self-administered questionnaire and a specific semi-structured interview con-ducted by trained nurses. Descriptive statistics were used to analyze data regarding sociodemographic variable and loneliness. Univariate and Multivariate regression analyses were applied to examine the association between loneliness and sleep quality after adjustment for multiple confounding variables. Results: ：The Pittsburgh Sleep Quality Index (PSQI) mean score of “lonely group” (9.2±4.2) was signifi-cantly higher than that of “not lonely group” (7.3±3.7) (student-t test, p<0.001). Loneliness was significantly as-sociated with PSQI (standardized β= 0.065, p=0.025), sleep disturbance (standardized β=0.086, p=0.005), use of sleep medication (standardized β= 0.065, p=0.034) after adjustment for possible confounding variables including sex and mood disorder. Conclusions ：Loneliness was associated with sleep disturbance and this finding implied negative impact of loneliness on sleep quality of older adults. Public health promotion efforts to reduce loneliness may improve sleep quality and mental health in the elderly living alone.

Objectives: ：Loneliness and poor sleep quality are common phenomena in old age and are associated with negative physical and mental health. However, little is known regarding the relation between loneliness and sleep quality. The aim of this study was to examine the association of loneliness and sleep quality among the elderly living alone. Methods: ：This is a cross-sectional study that enrolled 1,090 subjects who are the community-residing elderly living alone. Sociodemographic status, medical condition, cognition, mood disorder, sleep quality and levels of loneliness were collected using a self-administered questionnaire and a specific semi-structured interview con-ducted by trained nurses. Descriptive statistics were used to analyze data regarding sociodemographic variable and loneliness. Univariate and Multivariate regression analyses were applied to examine the association between loneliness and sleep quality after adjustment for multiple confounding variables. Results: ：The Pittsburgh Sleep Quality Index (PSQI) mean score of “lonely group” (9.2±4.2) was signifi-cantly higher than that of “not lonely group” (7.3±3.7) (student-t test, p<0.001). Loneliness was significantly as-sociated with PSQI (standardized β= 0.065, p=0.025), sleep disturbance (standardized β=0.086, p=0.005), use of sleep medication (standardized β= 0.065, p=0.034) after adjustment for possible confounding variables including sex and mood disorder. Conclusions ：Loneliness was associated with sleep disturbance and this finding implied negative impact of loneliness on sleep quality of older adults. Public health promotion efforts to reduce loneliness may improve sleep quality and mental health in the elderly living alone.

PURPOSE: Chronic rhinosinusitis (CRS) is a complex immunological condition, and novel experimental modalities are required to explore various clinical and pathophysiological endotypes; mere evaluation of nasal polyp (NP) status is inadequate. Therefore, we collected patient nasal secretions on filter paper and characterized the proteomes. METHODS: We performed liquid chromatography-mass spectrometry (MS)/MS in the data-dependent acquisition (DDA) and data-independent acquisition (DIA) modes. Nasal secretions were collected from 10 controls, 10 CRS without NPs (CRSsNP) and 10 CRS with NPs (CRSwNP). We performed Orbitrap MS-based proteomic analysis in the DDA (5 controls, 5 CRSsNP and 5 CRSwNP) and the DIA (5 controls, 5 CRSsNP and 5 CRSwNP) modes, followed by a statistical analysis and a hierarchical clustering to identify differentially expressed proteins in the 3 groups. RESULTS: We identified 2,020 proteins in nasal secretions. Canonical pathway analysis and gene ontology (GO) evaluation revealed that interleukin (IL)-7, IL-9, IL-17A and IL-22 signaling and neutrophil-mediated immune responses like neutrophil degranulation and activation were significantly increased in CRSwNP compared to control. The GO terms related to the iron ion metabolism that may be associated with CRS and NP development. CONCLUSIONS: Collection of nasal secretions on the filter paper is a practical and non-invasive method for in-depth study of nasal proteomics. Our proteomic signatures also support that Asian NPs could be characterized as non-eosinophilic inflammation features. Therefore, the proteomic profiling of nasal secretions from CRS patients may enhance our understanding of CRS endotypes.
Asian Continental Ancestry Group ; Gene Ontology ; Humans ; Inflammation ; Interleukin-17 ; Interleukin-9 ; Interleukins ; Iron ; Metabolism ; Methods ; Nasal Polyps ; Neutrophils ; Proteome ; Proteomics ; Sinusitis ; Spectrum Analysis

IL-18 is a crucial pro-inflammatory cytokine that mediates chronic intestinal inflammation. Metformin, an anti-diabetic drug, was reported to have ameliorative effects on inflammatory bowel disease. Recently, the mechanism of action of metformin was explained as a modulation of gut microbiota. In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet. Further, FMT downregulated the expression of the inflammatory cytokine IL-18. Within the genera Akkermansia, Bacteroides, and Butyricimonas, which were promoted by metformin therapy, Butyricimonas was found to be consistently abundant following FMT. Our findings suggest that modulation of gut microbiota is a key factor for the anti-inflammatory effects of metformin which is used for the treatment of hyperglycemia.
Animals ; Bacteroides ; Diet, High-Fat ; Down-Regulation ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Glucagon-Like Peptide 1 ; Hyperglycemia ; Inflammation ; Inflammatory Bowel Diseases ; Interleukin-18 ; Metformin ; Mice ; Toll-Like Receptors

BACKGROUND: Over the last decade, the incidence of ultraviolet B (UVB)-related skin problems has increased. Oxidative stress caused by UVB induces the secretion of melanocyte growth and activating factors from keratinocytes, which results in the formation of cutaneous hyperpigmentation. Therefore, increasing the antioxidant abilities of skin cells is thought to be a beneficial strategy for the development of sunscreen agents. Superoxide dismutase 1 (SOD1) is an antioxidant enzyme that is known to exhibit antioxidant properties. OBJECTIVE: The purpose of this study was to investigate the effect of SOD1 on alpha-melanocyte stimulating hormone (alpha-MSH) and UVB-induced melanogenesis in B16F10 melanoma cells and HRM-2 melanin-possessing hairless mice. METHODS: The inhibitory effect of SOD1 on tyrosinase activity was evaluated in a cell-free system. Additional experiments were performed using B16F10 melanoma cells to demonstrate the effects of SOD1 in vitro, and HRM-2 melanin-possessing hairless mice were used to evaluate the antimelanogenic effects of SOD1 in vivo. RESULTS: We found that SOD1 inhibited melanin production in a dose-dependent manner without causing cytotoxicity in B16F10 melanoma cells. SOD1 did not inhibit tyrosinase activity under cell-free conditions. The results indicate that SOD1 may reduce pigmentation by an indirect, nonenzymatic mechanism. We also found that SOD1 decreased UVB-induced melanogenesis in HRM-2 melanin-possessing hairless mice, as visualized through hematoxylin and eosin staining and Fontana-Masson staining. CONCLUSION: Our results indicate that SOD1 has an inhibitory effect on alpha-MSH and UVB-induced melanogenesis, indicating that SOD1 may be a promising sunscreen agent.
alpha-MSH ; Animals ; Cell-Free System ; Eosine Yellowish-(YS) ; Hematoxylin ; Hyperpigmentation ; Incidence ; Keratinocytes ; Melanins ; Melanocytes ; Melanoma ; Mice ; Mice, Hairless ; Monophenol Monooxygenase ; Oxidative Stress ; Pigmentation ; Skin Pigmentation ; Skin* ; Superoxide Dismutase*