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.     

Application of whey protein isolate in bone regeneration: Effects on growth and osteogenic differentiation of bone-forming cells

Recently, milk-derived proteins have attracted attention for applications in the biomedical field such as tissue regeneration. Whey protein isolate (WPI), especially its main component β-lactoglobulin, can modulate immunity and acts as an antioxidant, antitumor, antiviral, and antibacterial agent. There are very few reports of the application of WPI in tissue engineering, especially in bone tissue engineering. In this study, we tested the influence of different concentrations of WPI on behavior of human osteoblast-like Saos-2 cells, human adipose tissue-derived stem cells (ASC), and human neonatal dermal fibroblasts (FIB). The positive effect on growth was apparent for Saos-2 cells and FIB but not for ASC. However, the expression of markers characteristic for early osteogenic cell differentiation [type-I collagen (COL1) and alkaline phosphatase (ALP)] as well as ALP activity, increased dose-dependently in ASC. Importantly, Saos-2 cells were able to deposit calcium in the presence of WPI, even in a proliferation medium without other supplements that support osteogenic cell differentiation. The results indicate that, depending on the cell type, WPI can act as an enhancer of cell proliferation and osteogenic differentiation. Therefore, enrichment of biomaterials for bone regeneration with WPI seems a promising approach, especially due to the low cost of WPI.     

Calf massager: Intervention for body muscle discomfort during prolonged standing

Many occupations require workers to stand for long periods of time without proper interventions, which causes discomfort in the back and lower limbs. Therefore, this study aims to assess the effectiveness in alleviating body muscle discomfort during prolonged standing through the use of a calf massager. This study was conducted among male workers at a manufacturer with production line workers and the list was obtained from the HR Department and simple random sampling was done by number categorization. A total of 100 respondents (50 respondents for both the control and the experimental groups) participated in this study. The experiment took place in a room with a similar setup for the production line. Each respondent was requested to perform the simulated task for 2 hr. For the experimental group, the calf massager was turned on every 15 min. At every 15‐min interval after turning on the calf massager, respondents from both groups were required to evaluate their discomfort level on a Borg's scale CR‐10 questionnaire. The results showed that the level of body discomfort among respondents in the experimental group reduced (20–30%) compared with that of the control group. Multivariate analysis results revealed that the discomfort rating for the lower back, knees, thighs, calves, and feet was significantly lower (p < .05) among the experimental group compared with the control group. For lower body parts, the lower back region was statistically significant (p < .05) at the 90th, 105th, and 120th min; the thigh region was statistically significant (p < .05) at the 120th min; the knee region was statistically significant (p < .05) at the 105th and 120th min; the calf region was statistically significant (p < .05) at all minute intervals except the 15th and 45th min, while the feet region, was statistically significant at the 105th and 120th min. Therefore, this study indicates that calf massage treatment is capable of reducing body muscle discomfort during prolonged standing and highlights the significance of calf massage.     

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.