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Temporomandibular joint (TMJ) supports chewing, talking or other daily oral activities. So far, it still remains a great challenge to treat the defected TMJ condyle cartilage through tissue engineering technology. Herein, a bilayered scaffold is designed to fully reconstruct the different cartilage matrices of TMJ condyle under same induction condition. The bilayered scaffold with segregated hydrophobicity-hydrophilicity in top and bottom layer is prepared from a low and high content of polyethylene glycol (PEG) crosslinked poly (L-glutamic acid)-g-polycaprolactone (PLGA-g-PCL). The hydrophobic aggregates in top layer support the adhesion and spread of bone mesenchymal stem cells (BMSCs), thus inducing the differentation towards fibrocartilage; while aggregates (spheroids) are formed on the hydrophlic bottom layer, showing a preferable hyaline differentiation pathway under same chondrogenic induction in vitro. After 14 d in vitro induction, the scaffold/BMSCs construct is implanted in goat TMJ condyle defects. The post-operative outcome after 2 months demonstrates that the defects are fully covered by neo-cartilage. And the regenerated hierarchical TMJ condyle cartilage perfectly consist of ordered fibrocartilage and hyaline cartilage, which is same as natural condyle cartilage. These results corroborate that this bilayered scaffold with segregated hydrophilicity-hydrophobicity carrying induced BMSCs is a promising for treatment of TMJ condyle cartilage defects.Controlled delivery of human growth factors is still a challenge in tissue engineering protocols, and poly-lactic acid and poly-lactic-co-glycolic acid carriers have been recently proposed for this purpose. Here, the microencapsulation of two human growth factors, namely Growth Differentiation Factor -5 (hGDF-5) and Transforming Growth Factor β1 (hTGF-β1) was tested, by processing different emulsions with Supercritical Emulsion Extraction (SEE) technology. Polymer molecular weight, co-polymer ratio and surfactant amount in aqueous phases as well as phases mixing rate were varied to fabricate carriers with suitable size and loadings. Carriers with different mean sizes from 0.4 ± 0.09 μm up to 3 ± 0.9 μm were obtained by SEE technology when processing emulsions with different formulations; carriers were loaded with 3 μg/g and 7 μg/g for hGDF-5 and hTGF-β1 with controlled growth factor release over 25 days. Carriers displayed extremely low cytotoxicity when evaluated in Chinese Hamster Ovary cells (CHO-K1). Further, they also exhibited reduced cytotoxicity with respect to carriers obtained by conventional evaporation techniques, and low reactivity on human peripheral blood mononuclear cells (hPBMCs), suggesting their safety and potential use in tissue engineering protocols.

Radiation therapy (RT) is widely used in the treatment of cancer. Unfortunately, RT alone is insufficient to control the disease in most cases, as regrowth after irradiation still occur. Thus, it would be meaningful to explore the underlying mechanism of tumor regrowth after irradiation. Myeloid-derived suppressor cells (MDSCs) contribute to the immunosuppressive tumor microenvironment and hinder the therapeutic efficacy of RT. However, it is unclear whether MDSCs-mediated immune suppression contributes to local relapse after irradiation. In this article, we tried to figure out how MDSCs sabotage the therapeutic effect of RT, and tried to determine the potential synergistic effect of combination between targeting MDSCs and RT.

A syngeneic murine model of Lewis lung cancer was used. selleckchem The abundance of tumor infiltrating MDSCs and tumor growth after irradiation was assessed. The percentage and functional state of CD8

T cells were measured by flow cytometry, with or without polymorphonuclear (PMN)-MDSCs depl immunity, which provides a new alternative to delay tumor recurrence after RT.

Our results have suggested that PMN-MDSCs participate in the irradiation-induced immune suppression through ARG1 activation. We have also found that sildenafil has the potential to facilitate antitumor immunity, which provides a new alternative to delay tumor recurrence after RT.The upper respiratory tract (URT) is the main entrance point for many viral and bacterial pathogens, and URT infections are among the most common infections in the world. Recent evidences by our own group and others imply the importance of lactobacilli as gatekeepers of a healthy URT. However, the benefits of putting health-promoting microbes or potential probiotics, such as these URT lactobacilli, in function of URT disease control and prevention is underestimated, among others because of the absence of adequate formulation modalities. Therefore, this study entails important aspects in probiotic nasal spray development with a novel URT-derived probiotic strain by spray drying. We report quantitative and qualitative analysis of several spray-dried formulations, i.e. powders for reconstitution, based on disaccharide or sugar alcohol combinations with a polymer, including their long-term stability. Four formulations with the highest survival of >109 (Colony Forming Units) CFU/g after 28 weeks were further examined upon reconstitution which confirmed sufficiency of one bottle/dosage form during 7 days and rheological properties of shear-thinning. Tests also demonstrated maintained viability and cell morphology overall upon spraying through a nasal spray bottle in all 4 formulations. Lastly, application suitability in terms of high adherence to Calu-3 cells and antimicrobial activity against common URT pathogens was demonstrated and was not impacted neither by powder production process nor by spraying of reconstituted powder through a nasal spray device.Rigid, repetitive behaviors (RRBs) as a part of autism spectrum disorder (ASD) are perplexing and challenging to treat effectively. First, how is it that they associate with deficits in social communication and social interaction to create a strong symptomatic association for the DSM-5 diagnosis of ASD?1 Deficits in social communication make sense in how they define a developmental disorder, but what is the mechanism by which social interaction and RRBs connect to define the classification of ASD? Perhaps it is that, rather than by neurotransmitters or linked structural brain regions, ASD is a neural systems condition mediated by abnormalities in regionally distributed cortical networks.2.

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