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Staphylococcus aureus is an important pathogenic bacterium that causes various infectious diseases. Extracellular vesicles (EVs) released from S. aureus contain bacterial proteins, nucleic acids, and lipids. These EVs can induce immune responses leading to similar symptoms as during staphylococcal infection condition and have the potential as vaccination agent. Here, we show that active immunization (vaccination) with S. aureus-derived EVs induce adaptive immunity of antibody and T cell responses. In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells. Moreover, vaccination with S. aureus EVs conferred protection against lethality induced by airway challenge with lethal dose of S. aureus and also pneumonia induced by the administration of sub-lethal dose of S. aureus. These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice. Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17. Together, the study herein suggests that S. aureus EVs are a novel vaccine candidate against S. aureus infections, mainly via Th1 cellular response.

In this study, we assessed the biocompatibility and bioactivity of various pulp capping materials—ProRoot MTA (Dentsply Tulsa Dental Specialties), Biodentine (Septodont), TheraCal LC (Bisco), and Dycal (Dentsply Caulk)—on human dental pulp stem cells (hDPSCs). Experimental disks (diameter, 7 mm; height, 4 mm) were stored in a humified incubator at 37 °C for 48 h. Then, the pulp capping materials were tested for cytotoxic effects by methyl-thiazoldiphenyl-tetrazolium and scratch wound healing assays, and for mineralization potential by Alizarin red S (ARS) staining assay and alkaline phosphatase enzyme (ALP) activity. Cell viability and cell migration did not significantly differ between ProRoot MTA, Biodentine, and control (p > 0.05). TheraCal LC exhibited slower cell migration on days 2–4 compared to control (p < 0.05), and Dycal showed no cell migration. ALP activity was highest with Biodentine on days 10 and 14, and was lowered with TheraCal LC and Dycal (p < 0.05). In the ARS assay, hDPSCs grown in ProRoot MTA and TheraCal LC eluates showed significantly increased mineralized nodule formation on day 21 compared to Biodentine, Dycal, and control (p < 0.05). These findings indicate that ProRoot MTA, Biodentine, and TheraCal LC exhibit better biocompatibility and bioactivity than Dycal.

Gut microbes might influence host metabolic homeostasis and contribute to the pathogenesis of type 2 diabetes (T2D), which is characterized by insulin resistance. Bacteria-derived extracellular vesicles (EVs) have been suggested to be important in the pathogenesis of diseases once believed to be non-infectious. Here, we hypothesize that gut microbe-derived EVs are important in the pathogenesis of T2D. In vivo administration of stool EVs from high fat diet (HFD)-fed mice induced insulin resistance and glucose intolerance compared to regular diet (RD)-fed mice. Metagenomic profiling of stool EVs by 16S ribosomal DNA sequencing revealed an increased amount of EVs derived from Pseudomonas panacis (phylum Proteobacteria) in HFD mice compared to RD mice. Interestingly, P. panacis EVs blocked the insulin signaling pathway in both skeletal muscle and adipose tissue. Moreover, isolated P. panacis EVs induced typical diabetic phenotypes, such as glucose intolerance after glucose administration or systemic insulin injection. Thus, gut microbe-derived EVs might be key players in the development of insulin resistance and impairment of glucose metabolism promoted by HFD.

Atopic dermatitis is an inflammatory dermatological disease characterized by persistent scratching and recurrent eczema. Due to the influence of environmental variables on the cause of this disease, there remains an ongoing interest in the development of therapeutic interventions. Previous studies have shown that various plants of the genus Aster and its derived phytochemicals possess efficacy in treating inflammatory-mediated diseases, including atopic dermatitis. Therefore, the present study investigated a potential compound with anti-atopic dermatitis properties derived from Aster koraiensis leaves, specifically targeting HaCaT keratinocyte cells. First, we isolated eleven compounds with three unknown compounds, including two polyacetylenes (1 and 3) and a benzoic acid derivative (4). The chemical structures of the isolates were elucidated by 1D and 2D NMR, specific rotation, acid hydrolysis, and quantum chemical calculations. Next, we treated an A. koraiensis extract and all isolates to HaCaT keratinocyte, followed by stimulation with TNF-α/IFN-γ. Among bioactive compounds, astersaponin J (7) exhibited a significant reduction in the levels of inflammatory cytokines associated with atopic dermatitis at a concentration of 2.5 μM. These findings suggest that chemicals obtained from an A. koraiensis 95% ethanol extract and derived compounds are potential therapeutics to help reduce the immunological response driven by atopic dermatitis.

Skin barrier disruption and dermal inflammation are key phenotypes of atopic dermatitis (AD). Staphylococcus aureus secretes extracellular vesicles (EVs), which are involved in AD pathogenesis. Here, we evaluated the role of EVs-associated α-hemolysin derived from S. aureus in AD pathogenesis. α-hemolysin production from S. aureus was detected using western blot analyses. The cytotoxic activity of α-hemolysin on HaCaT keratinocytes was evaluated by measuring cell viability after treating cells with soluble and EVs-associated α-hemolysin. To determine the type of cell death, HaCaT keratinocytes were stained with annexin V and 7-AAD. The in vivo effects of α-hemolysin were evaluated by application of soluble and EV-associated α-hemolysin on the mouse skin. The present study showed that increased α-hemolysin was produced by S. aureus colonized on AD patients compared to healthy subjects. α-hemolysin production was also related to AD severity. In addition, EV-associated α-hemolysin was more cytotoxic to HaCaT keratinocytes than soluble α-hemolysin, and α-hemolysin-negative EVs did not induce keratinocyte death. EV-associated α-hemolysin induced necrosis, but soluble α-hemolysin induced apoptosis of keratinocytes. In vivo, skin barrier disruption and epidermal hyperplasia were induced by soluble and EV-associated α-hemolysin. However, AD-like dermal inflammation was only caused by EV-associated α-hemolysin. Moreover, neither skin barrier disruption nor AD-like skin inflammation was induced by α-hemolysin-negative EVs. Taken together, α-Hemolysin secreted from S. aureus, particularly the EV-associated form, induces both skin barrier disruption and AD-like skin inflammation, suggesting that EV-associated α-hemolysin is a novel diagnostic and therapeutic target for the control of AD.

Oleanolic acid (OA) is a pentacyclic triterpenoid, abundantly found in plants of the Oleaceae family, and is well known for its beneficial pharmacological activities. Previously, we reported the inhibitory effect of OA on mast cell-mediated allergic inflammation. In this study, we investigated the effects of OA on atopic dermatitis (AD)-like skin lesions and its underlying mechanism of action. We evaluated the inhibitory effect of OA on AD-like responses and the possible mechanisms using a 1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD animal model and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT keratinocytes. We found that OA has anti-atopic effects, including histological alterations, on DNCB-induced AD-like lesions in mice. Moreover, it suppressed the expression of Th2 type cytokines and chemokines in the AD mouse model and TNF-α/IFN-γ-induced HaCaT keratinocytes by blocking the activation of serine-threonine kinase Akt, nuclear factor-κB, and the signal transducer and activator of transcription 1. The results demonstrate that OA inhibits AD-like symptoms and regulates the inflammatory mediators; therefore, it may be used as an effective and attractive therapeutic agent for allergic disorders, such as AD. Moreover, the findings of this study provide novel insights into the potential pharmacological targets of OA for treating AD.

The characteristics of retrograde filling material are important factors that can affect the long-term success of apical microsurgery. Various calcium silicate-based cements (CSC) were introduced to overcome drawbacks of mineral trioxide aggregate (MTA), while Emdogain is known to be effective in the regeneration of periodontal tissues. The aim of this study is to evaluate the biocompatibility and osteogenic potential of various CSCs combined with Emdogain on human bone marrow-derived mesenchymal stem cells. Experimental groups were classified into eight groups depending on the material and the presence of Emdogain. In the cell-counting kit test, all experimental groups combined with Emdogain showed higher cell viability compared with those without Emdogain at days 1 and 2. In the wound-healing assay, cell migration increased significantly over time, with or without Emdogain. In the alkaline phosphatase assay, all groups treated with Emdogain showed higher activity compared with those without Emdogain at day 3 (p < 0.05). Using alizarin red S staining, all groups treated with Emdogain showed greater calcium nodule formation compared with those without Emdogain at days 7 and 14 (p < 0.05). In conclusion, using CSCs as retrograde filling materials and the application of additional Emdogain will increase bone regeneration and improve the prognosis of apical microsurgery.

Anaphylaxis is the most severe form of radiocontrast media (RCM) induced hypersensitivity and can be life-threatening if profound hypotension is combined. With increased use of iodine based RCM, related hypersensitivity is rapidly growing. However, the clinical characteristics and risk factors of RCM induced anaphylaxis accompanied by hypotension (anaphylactic shock) are not clearly defined. This study was performed to investigate the risk factors of RCM induced anaphylactic shock and the clinical value of RCM skin testing to identify causative agents in affected patients. We analyzed the data of RCM induced anaphylaxis monitored by an inhospital pharmacovigilance center at a tertiary teaching hospital from January 2005 to December 2012 and compared the clinical features and skin test results according to the accompanying hypotension. Among total of 104 cases of RCM induced anaphylaxis, 34.6% of patients, developed anaphylaxis on their first exposure to RCM. Anaphylactic patients presenting with shock were older (57.4 vs. 50.1 years, p = 0.026) and had a history of more frequently exposure to RCM (5.1±7.8 vs. 1.9±3.3, p = 0.004) compared to those without hypotension. Among RCMs, hypotension was more frequent in anaphylaxis related to iopromide compared to other agents (85.0% vs. 61.4%, p = 0.011). Skin tests were performed in 51 patients after development of RCM induced anaphylaxis. Overall skin test positivity to RCM was 64.7% and 81.8% in patients with anaphylactic shock. RCM induced anaphylactic shock is related to multiple exposures to RCM and most patients showed skin test positivity to RCM.

Contrary to many reports that antiplatelet agents inhibit cancer growth and metastasis, new solid tumors have been reported in patients receiving long-term antiplatelet therapy. We investigated the effects of these agents directly on cancer cells in the absence of platelets to mimic the effects of long-term therapy. When four antiplatelet agents (aspirin, clopidogrel, prasugrel, and ticagrelor) were administered to colon cancer cells, cancer cell proliferation was inhibited similarly to a previous study. However, surprisingly, when cells were treated with a purinergic P2Y12 inhibitor (purinergic antiplatelet agent), the motility of the cancer cells was significantly increased. Therefore, gene expression profiles were identified to investigate the effect of P2Y12 inhibitors on cell mobility, and Serpin family 1 (SERPINE1) was identified as a common gene associated with cell migration and cell death in three groups. Antiplatelet treatment increased the level of SERPINE1 in cancer cells and also promoted the secretion of SERPINE1 into the medium. Increased SERPINE1 was found to induce MMP1 and, thus, increase cell motility. In addition, an increase in SERPINE1 was confirmed using the serum of patients who received these antiplatelet drugs. With these results, we propose that SERPINE1 could be used as a new target gene to prevent the onset and metastasis of cancer in patients with long-term antiplatelet therapy.