The Emerging Regulatory Role of Circular RNAs in Periodontal Tissues and Cells

Periodontitis is a chronic complex inflammatory disease associated with a destructive host immune response to microbial dysbiosis, leading to irreversible loss of tooth-supporting tissues. Regeneration of functional periodontal soft (periodontal ligament and gingiva) and hard tissue components (cementum and alveolar bone) to replace lost tissues is the ultimate goal of periodontal treatment, but clinically predictable treatments are lacking. Similarly, the identification of biomarkers that can be used to accurately diagnose periodontitis activity is lacking. A relatively novel category of molecules found in oral tissue, circular RNAs (circRNAs) are single-stranded endogenous, long, non-coding RNA molecules, with covalently circular-closed structures without a 5’ cap and a 3’ tail via non-classic backsplicing. Emerging research indicates that circRNAs are tissue and disease-specific expressed and have crucial regulatory functions in various diseases. CircRNAs can function as microRNA or RNA binding sites or can regulate mRNA. In this review, we explore the biogenesis and function of circRNAs in the context of the emerging role of circRNAs in periodontitis pathogenesis and the differentiation of periodontal cells. CircMAP3K11, circCDK8, circCDR1as, circ_0062491, and circ_0095812 are associated with pathological periodontitis tissues. Furthermore, circRNAs are expressed in periodontal cells in a cell-specific manner. They can function as microRNA sponges and can form circRNA–miRNA–mRNA networks during osteogenic differentiation for periodontal-tissue (or dental pulp)-derived progenitor cells.     

Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications

Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, their therapeutic application remains debated: the TE construct often fails to completely restore the biomechanical properties of the native tissue, leading to poor clinical outcomes in the long term. Pulsed electromagnetic fields (PEMFs) are currently used as a safe and non-invasive treatment to enhance bone healing and to provide joint protection. PEMFs enhance both osteogenic and chondrogenic differentiation of MSCs. Here, we provide extensive review of the signaling pathways modulated by PEMFs during MSCs osteogenic and chondrogenic differentiation. Particular attention has been given to the PEMF-mediated activation of the adenosine signaling and their regulation of the inflammatory response as key player in TE approaches. Overall, the application of PEMFs in tissue repair is foreseen: (1) in vitro: to improve the functional and mechanical properties of the engineered construct; (2) in vivo: (i) to favor graft integration, (ii) to control the local inflammatory response, and (iii) to foster tissue repair from both implanted and resident MSCs cells.     

Biomimetic Lamellar Chitosan Scaffold for Soft Gingival Tissue Regeneration

Mucogingival surgery has become a common procedure for soft gingival tissue reparation in dental clinical practice, which mainly relies on autograft or commercial collagen membranes (CM). However, the autograft faces grand challenges in source availability and long-term post-surgery pain management, and the CM is restricted by its poor mechanical properties in an aqueous environment. Here, it is reported that a bio-inspired lamellar chitosan scaffold (LCS) with long range ordered porous structure, manufactured through a bidirectional freezing method, can serve as a promising gingival tissue engineering material. The LCS not only exhibits excellent mechanical properties in the hydrated state but also accelerates vessel formation and soft tissue regeneration in vivo. Most interestingly, the LCS is found to be capable of inducing macrophage differentiation to M2 macrophages, which is thought to play an important role in tissue regeneration. These advantages combined with its easy and low-cost preparation process make the LCS a promising candidate for dental clinical applications.     

Healing Pattern Analysis for Dental Implants Using the Mechano-Regulatory Tissue Differentiation Model

(1) Background: Our aim is to reveal the influence of the geometry designs on biophysical stimuli and healing patterns. The design guidelines for dental implants can then be provided. (2) Methods: A two-dimensional axisymmetric finite element model was developed based on mechano-regulatory algorithm. The history of tissue differentiation around eight selected implants can be predicted. The performance of the implants was evaluated by bone area (BA), bone-implant contact (BIC); (3) Results: The predicted healing patterns have very good agreement with the experimental observation. Many features observed in literature, such as soft tissues covering on the bone-implant interface; crestal bone loss; the location of bone resorption bumps, were reproduced by the model and explained by analyzing the solid and fluid biophysical stimuli and (4) Conclusions: The results suggested the suitable depth, the steeper slope of the upper flanks, and flat roots of healing chambers can improve the bone ingrowth and osseointegration. The mechanism related to solid and fluid biophysical stimuli were revealed. In addition, the model developed here is efficient, accurate and ready to extend to any geometry of dental implants. It has potential to be used as a clinical application for instant prediction/evaluation of the performance of dental implants.     

High tunability in (1 1 0)-oriented BaZr0.2Ti0.8O3 (BTZ) lead-free thin films fabricated by pulsed laser deposition

Using a pulsed laser deposition method the BaZr_0.2Ti_0.8 O₃ (BTZ) lead–free thin films with a thickness of ~250 nm were grown on FTO, ITO and Pt–Si substrates, respectively. The analysis results of microstructural, dielectric properties and leakage current reveal that the thin films deposited on Pt–Si substrates are oriented growth along the (1 1 0) direction and exhibit the optimal performance characteristics. Calculations of figure of merit (FoM) and dielectric tunability display a maximum value of ~42.8 and ~68.5% at E = 400 kV/cm at room temperature, respectively. The excellent tunable properties, high dielectric constant (~635@ 100 kHz) and low leakage current density of (9.3 × 10^–8 A/cm² at 400 kV/cm) make the (1 1 0)–oriented BaZr_0.2Ti_0.8 O₃ thin film to be an attractive material for applications of tunable devices.     

A2B Adenosine Receptors: When Outsiders May Become an Attractive Target to Treat Brain Ischemia or Demyelination

Adenosine is a signaling molecule, which, by activating its receptors, acts as an important player after cerebral ischemia. Here, we review data in the literature describing A_2BR-mediated effects in models of cerebral ischemia obtained in vivo by the occlusion of the middle cerebral artery (MCAo) or in vitro by oxygen-glucose deprivation (OGD) in hippocampal slices. Adenosine plays an apparently contradictory role in this receptor subtype depending on whether it is activated on neuro-glial cells or peripheral blood vessels and/or inflammatory cells after ischemia. Indeed, A_2BRs participate in the early glutamate-mediated excitotoxicity responsible for neuronal and synaptic loss in the CA1 hippocampus. On the contrary, later after ischemia, the same receptors have a protective role in tissue damage and functional impairments, reducing inflammatory cell infiltration and neuroinflammation by central and/or peripheral mechanisms. Of note, demyelination following brain ischemia, or autoimmune neuroinflammatory reactions, are also profoundly affected by A_2BRs since they are expressed by oligodendroglia where their activation inhibits cell maturation and expression of myelin-related proteins. In conclusion, data in the literature indicate the A_2BRs as putative therapeutic targets for the still unmet treatment of stroke or demyelinating diseases.     

Prevention of breast cancer by dietary polyphenols—role of cancer stem cells

Abstract

Breast cancer is a common malignancy with poor prognosis. Cancer cells are heterogeneous and cancer stem cells (CSCs) are primarily responsible for tumor relapse, treatment-resistance and metastasis, so for breast cancer stem cells (BCSCs). Diets are known to be associated with carcinogenesis. Food-derived polyphenols are able to attenuate the formation and virulence of BCSCs, implying that these compounds and their analogs might be promising agents for preventing breast cancer. In the present review, we summarized the origin and surface markers of BCSCs and possible mechanisms responsible for the inhibitory effects of polyphenols on BCSCs. The suppressive effects of common dietary polyphenols against BCSCs, such as curcumin, epigallocatechin gallate (EGCG) and related polyphenolic compounds were further discussed.     

Ex post demand information sharing between differentiated suppliers and a common retailer

We consider ex post demand information sharing in a two-echelon supply chain in which two suppliers sell differentiated products through a common retailer. We model three scenarios of information sharing to characterise the conditions under which information sharing may benefit or hurt different players: (1) no supplier is informed; (2) only one supplier is informed; and (3) both suppliers are informed. We find that the retailer may voluntarily share the low demand information when the product differentiation and demand magnitude satisfy certain conditions. In contrast, the retailer has no incentive to share the high demand information, even though this information benefits the suppliers. To achieve information sharing, we propose a side payment mechanism, which allows benefitted players to subsidise hurtful players. Finally, we extend our model by considering a situation where the suppliers have limited capacity and may invest to ramp up production capacity to satisfy a high demand.