Cellular Adaptation of Macrophages to Anthrax Lethal Toxin-Induced Pyroptosis via Epigenetic Mechanisms

Cellular adaptation to microbial stresses has been demonstrated in several cell types. Macrophages (MФ) are sentinel immune cells fending off invading microbes. Anthrax lethal toxin (LeTx) is a key virulence factor released by Bacillus anthracis that causes rapid cell death, pyroptosis. A small number of RAW246.7 macrophages (~4%) exposed to a non-lethal dose of LeTx become resistant to LeTx-induced pyroptosis for ~ 4 weeks, termed “toxin-induced resistance (TIR)”. Here, I showed that high levels of DNA methyl transferase1 (DNMT1) expression were maintained although global genomic methylation levels were not high in TIR. TIR cells treated with the DNMT inhibitor 5-azacitidine or (si)RNA targeting DNMT1 became susceptible to LeTx-induced pyroptosis. Knocking down DNMT1 also increased expression of the mitochondrial cell death proteins Bnip3 and Bnip3L involved in pyroptosis. However, DNA methylation of CpG islands in Bnip3 and Bnip3L were not different between wild type and TIR cells. Among histone modification genes examined, histone deacetylase (HDAC) 8 was up-regulated in TIR cells. The HDAC inhibitor panobinostat or siRNAs against HDAC8 rendered TIR cells sensitive to LeTx-induced pyroptosis and induced Bnip3 and Bnip3L expression. Acetylation of histone H3 lysine 27 (H3K27Ac) leads to binding of BNIP3 to H3, but this association was decreased in TIR cells. Also treatments of panobinostat or 5-azacitidine enhanced the levels of H3K27Ac in TIR cells. Collectively, these results suggest that TIR was maintained by multiple epigenetic mechanisms through up-regulating expression of DNMT1 and HDAC8. This resulted in decrease of H3K27Ac and subsequently suppressed the expression of BNIP3

Extraskeletal chondroma of the fallopian tube.

Extraskeletal chondroma can occur in the hands, feet, head and neck. This tumor usually presents as a small solitary nodule. The histogenesis of the tumor is controversial, but some have suggested a metaplastic origin. Chondroma of the fallopian tube is very rare. There is only one report in English literature. The origin of this tumor can be subcoelomic mesenchyme of the tubal serosa or mesenchyme of the myosalpinx. We describe a case of chondroma arising from the serosal surface of the fallopian tube with a review of literature. A 30-yr-old woman visited hospital due to left adnexal mass. On operating finding, 2 x 3 cm sized nodular mass was noted on the left tubal serosal area. The excised mass showed multilobulated appearance covered with thin fibrous membrane. The cut surface was solid, grayish yellow, and myxoid with a focal gelatinous area. The microscopic finding showed islands and elongated lobules of mature benign cartilage without cytologic atypia

Development and validation of the digestive function assessment instrument for traditional korean medicine: Sasang digestive function inventory

Objective. This study was conducted for development and validation of the Sasang Digestive Function Inventory (SDFI) with type-specific digestive function-related symptoms for identification of Sasang type and pathological pattern. Methods and Materials. We selected questionnaire items for pathophysiological symptoms using internal consistency analysis and examined construct validity using 193 healthy participants. Test-retest reliability with a four-week interval as well as convergent validity was examined using the Nepean Dyspepsia Index-Korean (NDIK), Functional Dyspepsia-Related Quality of Life (FDQOL), Dutch Eating Behavior Questionnaire (DEBQ), and Body Mass Index (BMI). Results. The 21-item SDFI showed satisfactory internal consistency (Cronbach’s alpha = 0.743) and test-retest reliability (, ). Three extracted subscales, SDFI-Digestion, SDFI-Appetite, and SDFI-Eating pattern, explained 56.02% of the total variance. The SDFI showed significant () correlation with total symptom score of NDIK, FDRQOL-Eating status, DEBQ-External Eating scale, and BMI. The SDFI score of the Tae-Eum () type was significantly () larger than that of the So-Eum () type. Conclusion. Current results demonstrated the reliability and validity of the SDFI and its subscales, which can be utilized as an objective instrument for diagnosis of Sasang types and assessment of the type-specific digestive function

Anti-obesity effects of Yerba Mate (Ilex Paraguariensis): a randomized, double-blind, placebo-controlled clinical trial

Dietary assessment parameters of the Yerba Mate and placebo groups measured at 0, 6 and 12 weeks. (DOC 37.5 kb