Melatonin Inhibits Reactive Oxygen Species-Driven Proliferation, Epithelial-Mesenchymal Transition, and Vasculogenic Mimicry in Oral Cancer.

Globally, oral cancer is the most common type of head and neck cancers. Melatonin elicits inhibitory effects on oral cancer; however, the biological function of melatonin and underlying mechanisms remain largely unknown. In this study, we found that melatonin impaired the proliferation and apoptosis resistance of oral cancer cells by inactivating ROS-dependent Akt signaling, involving in downregulation of cyclin D1, PCNA, and Bcl-2 and upregulation of Bax. Melatonin inhibited the migration and invasion of oral cancer cells by repressing ROS-activated Akt signaling, implicating with the reduction of Snail and Vimentin and the enhancement of E-cadherin. Moreover, melatonin hampered vasculogenic mimicry of oral cancer cells through blockage of ROS-activated extracellular-regulated protein kinases (ERKs) and Akt pathways involving the hypoxia-inducible factor 1α. Consistently, melatonin retarded tumorigenesis of oral cancer in vivo. Overall, these findings indicated that melatonin exerts antisurvival, antimotility, and antiangiogenesis effects on oral cancer partly by suppressing ROS-reliant Akt or ERK signaling.

The relationship between toll like receptor 4 gene rs4986790 and rs4986791 polymorphisms and sepsis susceptibility: A meta-analysis.

Accumulating evidences have demonstrated that lipopolysaccharide (LPS) represents the important etiologic factor for sepsis. Some previous studies have reported the relationship between common polymorphisms rs4986790 and rs4986791 in the coding gene for this receptor and the susceptibility to sepsis, but there were distinct divergences between those findings. We therefore designed this meta-analysis incorporated 28 published articles containing 6,537 sepsis patients and 8,832 controls for a more comprehensive conclusion on this matter. Odds ratios (ORs) and 95% confidence interval (95% CIs) were calculated to evaluate the association of toll like receptor 4 gene polymorphisms rs4986790 and rs4986791 with sepsis risk. Heterogeneity between included studies was inspected using Q test, and sensitivity analysis was implemented via sequential deletion of each included study to investigate the stability of overall estimates. Funnel plot and Egger's test were adopted to examine publication bias across selected studies. We found no significant association for either the polymorphism rs4986790 or rs4986791 with sepsis susceptibility in total analysis under any genetic models. Neither did we after combining these two polymorphisms. The results of this meta-analysis suggest that the rs4986790 and rs4986791 polymorphisms in toll like receptor 4 gene may have no statistically significant influence on sepsis susceptibility.

Innovative strategies for tissue engineered skin based on multiple growth factors gene transfection.

Tissue engineering combines the principles of cell biology, engineering and materials science to develop three-dimensional tissues to replace or restore tissue function. Tissue engineered skin (TE-skin) is one of most advanced tissue constructs. However, much clinical providence demonstrates the TE-skin may not be viewed as the equal of skin grafts, the contributions to accelerate the closure of wound were come mainly from various growth factor. These growth factors respond to its environment to bring about the desired effect. In our hypothesis, this three-dimensional skin substitute could be genetically modified with various growth factor and transplanted in order to deliver therapeutic proteins locally and systemically for the treatment of trauma. The likelihood of transgened TE-skin plays function as a pharmacological agent suggests a wide range of therapeutic applications. In future, the TE-skin could be design as gene delivery to enhance potential capacity for treatment of burns, chronic wounds and even systemic diseases.

[Fluoride preconditioning attenuates sensitivity induced by tooth bleaching: a scanning electron microscopy study].

OBJECTIVE: To evaluate the effects of fluorid on morphology change in enamel and dentin during tooth bleaching. METHODS: The study population consisted of twelve patients who required the extraction of first premolars for orthodontic reasons. Twelve participants were divided into three groups: bleaching with NaF-treated group, bleaching-treated group and control group. Immediately after bleaching treatment, all teeth were extracted and prepared for scanning electron microscope (SEM). Morphologic observations were carried out with SEM. RESULTS: In the bleaching-treated group, mild demineralization was observed on the surface of enamel and collapse of collagen scaffold was also observed on the longitudinal section of dentine. The diameter of dentinal tubule was not uniform due to peritubular dentine was demineralized. In the bleaching with NaF-treated group, the demineralization of enamel and dentin were reduced and some diameter of dentinal tubule were smaller than bleaching-treated group. CONCLUSION: Fluoride can reduced the demineralization of enamel and dentine obviously, which may be applied as a therapeutic tool for sensitivity induced by tooth bleaching.

[The positive effect of transforming growth factor beta on ectomesenchymal stem cells of embryonic facial processes differentiating to smooth muscle cells].

OBJECTIVE: To investigate the effect of transforming growth factor beta (TGF-beta) on ectomesenchymal stem cells differentiating to smooth muscle cells. METHODS: 60 pmol/L TGF-beta was added to the ectomesenchymal stem cells of embryonic facial processes. Immunohistochemistry assay and image analysis were used to value the expression extent of a smooth muscle actin (alpha-SMA) and quantitative RT-PCR was used to value the quantity of alpha-SMA. RESULTS: 2 days later, about 95% cells in TGF-beta group and 65% cells in control group without differentiation inhibitor expressed alpha-SMA. Expression of alpha-SMA in TGF-beta group was stronger than that of control group after one and two days. Quantitative RT-PCR showed the quantity of alpha-SMA mRNA in treated group cells was more than that of in control group. CONCLUSION: Quantity of alpha-SMA in TGF-beta group is more than that of spontaneous differentiation group. TGF-beta has positive effect on ectomesenchymal stem cells differentiating to smooth muscle cells.

[Identification of ectomesenchymal stem cells of human fetal facial processes and spontaneous differentiation to smooth muscle cells].

OBJECTIVE: To investigate the characteristic and phenotype of ectomesenchymal stem cells of human fetal facial processes and the procedure of spontaneous differentiation to smooth muscle cells. METHODS: The primary ectomesenchymal cells of E 50 human fetal facial processes were isolated by 2.5 g/L trypsin and cultured with DMEM/F 12 with 10(-6) U/L leukemia inhibitor factor(LIF). The morphology and growth rate were observed by inverted microscop. After being withdrawn LIF, the characteristic of cells were identified by immunohistochemistry and RT-PCR. Ultrastructure was observed by transmission electron microscope. RESULTS: The cultured cells displayed monolayer growth and were fibroblast-like with 2-4 processes. The cells were stainely positived for anti-human natural killer cell marker-1, Vimentin, S-100, neuron specific enolase, myoglobin and VIII factor, but negatively for glial fibrillary acidic protein, neural fiblament, alpha-SMA and cytokeratin in immunohistochemistry. Two days after being withdrawn the LIF, cells expressed alpha-SMA in protein and mRNA levels. The cells were rich in muscular filament-like structure and dense bodies under transmission electron microscope. CONCLUSION: Cultured cells are undifferentiated ectomesenchymal stem cells. The cells have the potential for differentiating spontaneously to smooth muscle cell.