Down-expression of the NLRP3 inflammasome delays the progression of diabetic retinopathy.

The investigation aimed to evaluate the effects of Mcc950, an inhibitor of the NLRP3 inflammasome, on diabetic retinopathy (DR) mice. The general physiological condition of each group of mice was recorded. Retinal blood vessels were stained for observation of the density of blood vessels, and retinas were used for further morphological examination and fluorescent staining after the intravitreal injection of Mcc950. Mcc950 partially reversed hyperglycemia-induced vascular damage and had reduced histological changes compared to DR mice. IL-1ß production in mice retinas in the diabetic model (DM) group increased, but pretreatment with Mcc950 significantly reversed these changes. Additionally, Mcc950 engineered reduced FITC dextran extravasation and vascular leakage. Therefore, it played an apparent protective role in DR and could be a new treatment strategy for DR.

Knockout of NRAGE promotes autophagy-related gene expression and the periodontitis process in mice.

BACKGROUND AND OBJECTIVE: Neurotrophin receptor-interacting MAGE homologue (NRAGE) plays a crucial role in the regulation of bone metabolism. The present study investigated the regulation role of NRAGE on autophagy activation and periodontitis process during experimental periodontitis. MATERIALS AND METHODS: Six-week-old wild-type (WT) and NRAGE-/- mice were randomly divided into three time points in the periodontitis groups (0, 2, and 4 weeks). Histopathological changes were determined using the tooth mobility, hematoxylin and eosin (H&E) staining, and micro-computed tomography (micro-CT). Osteoclasts activation and number were investigated using tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry, and real-time quantitative PCR (RT-PCR). The level of autophagy-related gene expression was measured using immunohistochemistry, immunofluorescence, and RT-PCR. RESULTS: H&E staining and Micro-CT showed that the destruction of the alveolar bone was considerably more severe in the NRAGE-/- group than the WT group after ligation. Tooth mobility in the NRAGE-/- group was obviously higher than that in the WT group. The activation and number of osteoclasts and the level of autophagy-related gene expression in NRAGE-/- group were significantly higher than that in WT group. CONCLUSIONS: The present study showed that knockout of NRAGE induced autophagy-related gene expression and accelerated the process of periodontitis disease via increasing the activity and differentiation of osteoclast.

LINC01315 Impairs microRNA-211-Dependent DLG3 Downregulation to Inhibit the Development of Oral Squamous Cell Carcinoma.

Recent studies have revealed that long non-coding RNAs (lncRNAs) involve in the progression of oral squamous cell carcinoma (OSCC). These lncRNAs have emerged as biomarkers or therapeutic targets for OSCC. We here aimed to investigate the role of lncRNA LINC01315 in OSCC and the related mechanisms. LINC01315 and DLG3 were determined to be poorly expressed while microRNA-211 (miR-211) was highly expressed in OSCC tissues and cells using RT-qPCR and western blot analysis. Based on the results obtained from dual-luciferase reporter gene, RIP, and FISH assays, LINC01315 was found to upregulate DLG3 expression by competitively binding to miR-211. Upon altering the expression of LINC01315, and/or miR-211 in OSCC cells with shRNA, mimic, or an inhibitor, we assessed their effects on OSCC cell proliferation, migration, invasion, and apoptosis. LINC01315 knockdown enhanced OSCC cell proliferation, migration and invasion, but dampened their apoptosis, all of which could be reversed by miR-211 inhibition. Elevation of DLG3, a target gene of miR-211, activated the Hippo signaling pathway, whereby suppressing OSCC progression in vitro. Finally, their roles in tumor growth were validated in vivo. These findings suggest that LINC01315 elevates DLG3 expression by competitively binding to miR-211, thereby suppressing OSCC progression.

Bearing capacity of ceramic crowns before and after cyclic loading: An in vitro study.

The objective of this study was to compare the resistance to failure of three types of all-ceramic crowns under static and cyclic contact loading. Three types of crown specimens were fabricated (N = 14 per group) including: i) sintered bi-layer crowns (SBC) made of IPS e.max CAD veneers fused on Lava zirconia core ceramics, ii) adhesive bi-layer crowns (ABC) made of IPS e.max CAD veneers bonded onto Lava zirconia core ceramics, and iii) monolith ceramics crown (MCC) made of IPS e.max CAD. All were bonded onto a compliant substrate of resin composite with commercial adhesive. Eight specimens were selected from each group for monotonic loading to failure via 6 mm diameter ball to obtain the initial load capacity (Pinitial) of the crowns. The remaining six crown specimens were subjected to cyclic contact loading to 5 million cycles, and then loaded monotonically to fracture to obtain residual load capacity after fatigue (Presidual). A finite element analysis (FEA) was used to analyze the stress distributions within the three types of crowns and estimate the crack origins from the maximum stress. The initial load to failure (Pinitial) for the SBC, ABC, and MCC groups were 1120 ±â€¯170 N, 970 ±â€¯150 N, and 950 ±â€¯60 N, respectively, and significantly different (p = 0.027). The residual load to failure after fatigue (Presidual) for the crown types were 890 ±â€¯240 N, 680 ±â€¯240 N, and 1050 ±â€¯120 N, respectively, and also significantly different (p = 0.012). For SBC and MCC, failure occurred predominantly by bulk fracture, whereas the ABC failed primarily by chipping. The FEA suggested that failure of SBC and ABC would originate in the cement layers, and MCC has a more reasonable stress allocation than that in bi-layer crowns (SBC and ABC), which agreed with the observed failure modes. The SBC crowns had superior load to failure, whereas the bi-layer systems (SBC and ABC) had inferior fatigue resistance compared with the monolith crowns (MCC). The cement interface was the weak-link of the bi-layer systems, especially for ABC. Considering their use in clinical practice, the ranking in resistance to failure is SBC>MCC>ABC.

Animal Models Used for Testing Hydrogels in Cartilage Regeneration.

Local cartilage or osteochondral lesions are painful and harmful. Besides pain and limited function of joints, cartilage defect is considered as one of the leading extrinsic risk factors for osteoarthritis (OA). Thus, clinicians and scientists have paid great attention to regenerative therapeutic methods for the early treatment of cartilaginous defects. Regenerative medicine, showing great hope for regenerating cartilage tissue, relies on the combination of biodegradable scaffolds and particular biological factors, such as growth factors, genetic cues. Among all biomaterials, hydrogels have become a promising type of scaffolds for simultaneous cell growth and drug delivery in cartilage tissue engineering. A wide range of animal models have been applied in testing repair with hydrogels in cartilage defects. This review summarized the current animal models used to test hydrogels technologies for the regeneration of cartilage. Advantages and disadvantages in the establishment of the cartilage defect animal models among different species were emphasized, as well as the feasibility of replication of diseases in animals.

The Formation Mechanism of Hydrogels.

Hydrogels are degradable polymeric networks, in which cross-links play a vital role in structure formation and degradation. Cross-linking is a stabilization process in polymer chemistry that leads to the multi-dimensional extension of polymeric chains, resulting in network structures. By crosslinking, hydrogels are formed into stable structures that differ from their raw materials. Generally, hydrogels can be prepared from either synthetic or natural polymers. Based on the types of cross-link junctions, hydrogels can be categorized into two groups: the chemically cross-linked and the physically cross-linked. Chemically cross-linked gels have permanent junctions, in which covalent bonds are present between different polymer chains, thus leading to excellent mechanical strength. Although chemical cross-linking is a highly resourceful method for the formation of hydrogels, the cross-linkers used in hydrogel preparation should be extracted from the hydrogels before use, due to their reported toxicity, while, in physically cross-linked gels, dissolution is prevented by physical interactions, such as ionic interactions, hydrogen bonds or hydrophobic interactions. Physically cross-linked methods for the preparation of hydrogels are the alternative solution for cross-linker toxicity. Both methods will be discussed in this review.

[Research on the mechanical differences of machinable lithium disilicate all-ceramic crowns].

Due to the superior pigment and high flexural strength, machinable lithium disilicate ceramics can be used as a monolithic crown or veneering porcelains on the zirconia core to form the all-ceramic crowns by sintering or bonding procedures. This paper reports the research on the differences in stress distributions amongst these three types of all-ceramic crowns under typical loading conditions. Three-dimensional numerical models of the restored crown based on the first mandibular molar were developed. The vertical concentrated load and 8-point uniformly distributed load were applied, respectively. The maximum stress and stress distribution were resulted from finite element evaluation. It was found that the maximum tensile stress in 3 types of restored crowns subjected to the concentrate load was less than the flexural strength of IPS e.max. The stress distributions in the sintered and bonded double layered crowns were basically identical, and different from the monolithic crown. The stress magnitude in veneer porcelain of the bonded crown was greater than that in the sintered crown. The use of IPS e.max computer aided design monolithic crown as molar restorations should be careful to avoid high stress as the cyclic stress is a concern of fatigue which may influence the longevity of the restored crown. The bonded double layer crowns bear greater risks of veneer chipping compared with the sintered crowns. The conclusions of this study provide helpful guidelines in clinical applications for preparation of computer aided design/computer aided manufacture lithium disilicate all-ceramic restorations.

The properties of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) and its applications in tissue engineering.

Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) is a member of the polyhydroxyalkanoate (PHA) family. It is the designation of molecules consisting of random co-polymers of 3-hydroxybutyrate and 3- hydroxyhexanoate. PHBHHx plays a significant role in the field of biomedical materials. It has good physical, chemical and mechanical properties, making it potentially useful for a wide range of biomaterials applications. In addition, it has also shown better biocompatibility with different cell types. This paper will introduce the physical, chemical and biological properties of PHBHHx, including biodegradation, hydrophilicity, surface properties and cytocompatibility. The development of PHBHHx in tissue-engineering applications will be discussed. PHBHHx used to repair bone, cartilage, tendons, nerves and vessels will be the focus of discussion.