Virtual simulation (VS) as an emerging interactive pedagogical strategy has been paid more and more attentions in the undergraduate medical education. Because of the fast development of modern computer simulation technologies, more and more advanced and emerging VS-based instructional practices are constantly increasing to promote medical education in diverse forms. In order to describe an overview of the current trends in VS-based medical teaching and learning, this scoping review presented a worldwide analysis of 92 recently published articles of VS in the undergraduate medical teaching and learning. The results indicated that 98% of included articles were from Europe, North America, and Asia, suggesting a possible inequity in digital medical education. Half (52%) studies reported the immersive virtual reality (VR) application. Evidence for educational effectiveness of VS in medical students’ knowledge or skills was sufficient as per Kirkpatrick’s model of outcome evaluation. Recently, VS has been widely integrated in surgical procedural training, emergency and pediatric emergency medicine training, teaching of basic medical sciences, medical radiation and imaging, puncture or catheterization training, interprofessional medical education, and other case-based learning experiences. Some challenges, such as accessibility of VS instructional resources, lack of infrastructure, “decoupling” users from reality, as well as how to increase students’ motivation and engagement, should be addressed.

Background: Acrylamide (ACR) formed during heating of tobacco and carbohydrate-rich food as well as widely applied in industries has been known as a well-established neurotoxic pollutant. Although the precise mechanism is unclear, enhanced apoptosis, oxidative stress and inflammation have been demonstrated to contribute to the ACR-induced neurotoxicity. In this study, we assessed the possible anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin, the most active component in a popular spice known as turmeric, on the neurotoxicity caused by ACR in rats. Methods: Curcumin at the dose of 50 and 100 mg/kg was orally given to ACR- intoxicated Sprague-Dawley rats exposed by ACR at 40 mg/kg for 4 weeks. All rats were subjected to behavioral analysis. The HE staining and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) staining were used to detect histopathological changes and apoptotic cells, respectively. The mRNA and protein expressions of apoptosis-related molecule telomerase reverse transcriptase (TERT) were detected using real-time PCR and immunohistochemistry, respectively. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as the indicators for evaluating the level of oxidative stress in brain. The levels of pro-inflammatory cytokinestumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the cerebral homogenates were detected using ELISA assay. Results: ACR-induced weigh loss, deficits in motor function as well as pathological alterations in brains were significantly improved in rats administrated with 50 and 100 mg/kg curcumin. TUNEL-positive apoptotic cells in curcumin-treated ACR intoxicated brains were less than those in the ACR model group. Curcumin administration especially at the dose of 100 mg/kg upregulated the TERT mRNA expression and enhanced the number of TERT-positive cells in ACR-intoxicated cortex tissues. Moreover, curcumin treatment reduced the concentrations of TNF-α, IL-1β and MDA, while increased the GSH contents as well as the SOD and GSH-Px activities in the cerebral homogenates, in comparison to ACR control group. Conclusions: These data suggested the anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on ACR-induced neurotoxicity in rats. Maintaining TERT-related anti-apoptotic function might be one mechanism underlying the protective effect of curcumin on ACR-intoxicated brains.

Ulcerative colitis (UC) has closely been associated with an increased risk of colorectal cancer. However, the exact mechanisms underlying colitis-associated cancer (CAC) development remain unclear. As a classic pattern-recognition receptor, Toll like receptor (TLR)4 is a canonical receptor for lipopolysaccharide of Gram-negative bacteria (including two CAC-associated pathogens Fusobacterium nucleatum and Salmonella), and functions as a key bridge molecule linking oncogenic infection to colonic inflammatory and malignant processes. Accumulating studies verified the overexpression of TLR4 in colitis and CAC, and the over-expressed TLR4 might promote colitis-associated tumorigenesis via facilitating cell proliferation, protecting malignant cells against apoptosis, accelerating invasion and metastasis, as well as contributing to the creation of tumor-favouring cellular microenvironment. In recent years, considerable attention has been focused on the regulation of TLR4 signaling in the context of colitis-associated tumorigenesis. MicroRNA (miR)-155 and TLR4 exhibited a similar dynamic expression change during CAC development and shared similar CAC-promoting properties. The available data demonstrated an interplay between TLR4 and miR-155 in the context of different disorders or cell lines. miR-155 could augment TLR4 signaling through targeting negative regulators SOCS1 and SHIP1; and TLR4 activation would induce miR-155 expression via transcriptional and post-transcriptional mechanisms. This possible TLR4-miR-155 positive feedback loop might result in the synergistic accelerating effect of TLR4 and miR-155 on CAC development.

The anti-cancer activities of brown algae and some active extracts or components from brown algae have been demonstrated. But the anti-tumor activities of eckol, a new natural phlorotannin derived from marine brown algae, are poorly understood. In order to investigate the in vivo anti-tumor effect and its potential mechanisms of eckol in a sarcoma 180 (S180) xenograft-bearing animal model, S180 xenograft-bearing mice were randomly divided into 4 groups: model control, and eckol low-dose (0.25 mg kg⁻¹), middle-dose (0.5 mg kg⁻¹) and high-dose (1.0 mg kg⁻¹) groups. After eckol administration, the tumor inhibition, tumor tissue histology, thymus index and spleen index were measured. The apoptotic tumor cells were detected using the terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) assay. The protein expression levels of cleaved Caspase-3 and Caspase-9 (two key apoptotic proteins), Bcl-2 and Bax (two key anti-apoptosis-related genes), as well as epidermal growth factor receptor (EGFR, a well-known cell proliferation-stimulating molecule in tumorigenesis) and p-EGFR in tumor tissues were determined by western blot. A carbon particle clearance test, measurement of serum cytokine levels, a splenic T lymphocyte proliferation test, and T lymphocyte subpopulation analysis were used to evaluate the effect of eckol on the immune function of tumor-bearing mice. Moreover, CD11c⁺-dendritic cell (DC) infiltration in tumor tissues was detected by immunohistochemistry, and the surface molecules on bone marrow-derived DCs were analyzed using flow cytometry. The pro-apoptosis and anti-proliferation activities of eckol were manifested by the increased TUNEL-positive apoptotic cells, the upregulated Caspase-3 and Caspase-9 expression, and the downregulated expression of Bcl-2, Bax, EGFR and p-EGFR in eckol-treated transplanted S180 tumors. Most importantly, eckol stimulated the mononuclear phagocytic system, recruited and activated DCs, promoted the tumor-specific Th1 responses, increased the CD4+/CD8+ T lymphocyte ratio, and enhanced cytotoxic T lymphocyte responses in the eckol-treated animals, suggesting its potent stimulatory property on innate and adaptive immune responses. This study suggested that eckol might act as a functional food constituent derived from marine brown algae with a potential in vivo anti-tumor effect achieved by improving the immune response.