Introduction: Neurodegeneration resulting from pathogen invasion or tissue damage has been associated with activation of microglia, and exacerbated by the release of neurotoxic mediators such as pro-inflammatory cytokines, chemokines and reactive oxygen species. Activation of microglia stimulated by lipopolysaccharide is mediated in part by GSK-3 signaling molecule. Induced IL-10 expression via GSK-3 inhibition is noteworthy since IL-10 has been remarkably shown to suppress inflammation. Objectives: We aimed to inactivate microglia through inhibition of GSK-3 signaling and to determine its effects on the production of pro- and anti-inflammatory mediators. Methods: LPS-stimulated BV-2 cells were treated with a GSK-3 inhibitor (LiCl, NP12, SB216763 or CHIR99021). Inhibition of GSK-3 was determined by the phosphorylation status of GSK-3β. The effects of GSK-3 inhibition on microglial inflammatory response were investigated by examining various mediators and CD200R marker. Production of nitric oxide (NO), glutamate and pro- and anti-inflammatory cytokines were measured using flow cytometry, Griess assay, glutamate assay and Cytometric Bead Array (CBA) respectively. Results: GSK-3β signaling in LPS-stimulated microglia was blocked by GSK-3 inhibitor through increased phosphorylation at Serine 9 residue. GSK-3 inhibitors had also led to reducing in microglia activity via increased expression of CD200R. Inhibition of GSK-3 also diminished inflammatory mediators such as nitric oxide (NO), glutamate, pro-inflammatory cytokines (TNF-α and IL-6) and chemokine, MCP-1. Reduction of pro-inflammatory mediators by GSK-3 inhibitor was coincided with increased IL-10 production. Conclusions: Suppression of microglia-mediated inflammatory response was facilitated by GSK-3 inhibition with associated increased in IL-10 production.
Microglia

Introduction: Glycogen synthase kinase-3 (GSK-3) is an important immune regulator that controls inflammation via inhibition of its protein kinase activities. Persistent inflammatory responses through the activation of immune cells and excessive production of immune mediators may cause tissue destruction and implicated in the development of chronic inflammatory diseases. The objective of this study was to examine the role of Tideglusib, a GSK-3 inhibitor, in inflammatory responses elicited through macrophage activation by investigating the expression of cell surface biomarkers and inflammatory molecule levels. Method: The effects of GSK-3 inhibition by Tideglusib on the expression of CD11b and CD40 and secretion of pro-inflammatory cytokines in the lipopolysaccharide (LPS)-activated macrophage-derived RAW 264.7 cells were determined by flow cytometry, while the presence of nitric oxide (NO) was determined by Griess assay. Results: Stimulation of RAW 264.7 cells with LPS increased substantial levels of CD11b and CD40 expressions, and secretion of NO, TNF-α, and MCP-1. However, the expression of these molecules was suppressed through inhibition of GSK-3. Conclusion: These findings suggest the significant role of Tideglusib to limit the upregulation of immune responses in activated macrophages, and as a potential anti-inflammatory drug for the intervention and treatment of inflammatory diseases.

Objective: This study aimed to determine prevalence of latent tuberculosis infection among medical students and tuberculosis exposure at the health facilities. Methods: A cross-section of study year 1 (n=68) and year 5 (n=75) medical students in a local university were recruited for latent tuberculosis infection testing using QuantiFERON-TB Gold Plus and a questionnaire analyzed for multivariate risk. Results: The majority of the study were vaccinated with BCG. None of year 1 medical students were positive for latent tuberculosis infection, however, six (8.0%) year 5 students were tested positive for latent tuberculosis infection. A higher incidence of year 5 medical students claimed to be exposed to tuberculosis at health facility (65.3% vs. 4.4%) and a higher percentage reported contact with tuberculosis case over the preceding year compared to year 1 students (30.7% vs. 8.8%). Conclusion: We observed a higher incidence of latent tuberculosis infection and higher exposure to tuberculosis in health facilities among year 5 medical students. Baseline screening and monitoring for progression to tuberculosis infection may benefit tuberculosis management programs.

Introduction: Ultraviolet (UV) A is the longest wavelength of UV radiation, accounts for approximately 95% of the radiation reaching the earth's surface. It can penetrate deeply into the skin layer and able to induce photoaging and photocarcinogenesis through the activation of reactive oxygen species (ROS). Polysaccharides-containing Pleurotus flabellatus (known as a pink oyster mushroom) has antioxidative properties and may inhibit free radical activities generated from UV radiation. Hence, this present study was to evaluate the antioxidative and photoprotective properties of exopolysaccharides (ExPFE) and exopolysaccharides (EnPFE) of Pleurotus flabellatus extracts on UVA irradiated human dermal fibroblast (HS-27) cell line. Methods: The antioxidant level of ExPFE and EnPFE was determined using 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging assay, while both cytotoxicity and photoprotective effects of the extracts on the HS-27 cell line were determined using CellTiter-Blue® cell viability assay. The effects of ExPFE and EnPFE on the HS-27 cell migration was evaluated using the scratch assay. Results: Both ExPFE and EnPFE exhibited respectable antioxidant and scavenging activity in DPPH. The extracts also demonstrated a non-cytotoxicity, but photoprotective effects to the HS-27 cells by increasing the percentage of cell viability and enhancing cell migration activity upon UVA exposure. Conclusion: The ExPFE and EnPFE exhibit antioxidative and photoprotective effects on UVA irradiated HS-27 cell line. This study suggests that pink oyster polysaccharides could be a potential natural bioactive compound for skin protection against UVA radiation.