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Epigenetic regulation, mainly involving DNA methylation, histone modification, and noncoding RNAs (ncRNAs), is essential for the regulation of multiple cellular processes. Dental-derived mesenchymal stem cells (DMSCs), a kind of multipotent cells derived from dental tissues, are impactful in regenerative medicine. Recent studies have shown that epigenetic regulation plays a major role in DMSCs. Therefore, exploring how epigenetic regulation is involved in DMSCs may be of guiding significance for tissue repair and regeneration or for exploring more effective treatments. A number of research of ncRNAs in DMSCs have been reported. However, little is known about the roles of DNA methylation and histone modifications in DMSCs. In this review, we summarize the important roles of DNA methylation and histone modifications of the fate of DMSCs.

AimsMicroRNA-183 ( miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 in OA pain and to investigate the underlying mechanisms.MethodsClinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 ( CCL2), proinflammatory cytokines (interleukin (IL)-6, IL-1β, and tumour necrosis factor-α ( TNF-α)), and pain-related factors (transient receptor potential vanilloid subtype-1 ( TRPV1), voltage-gated sodium 1.3, 1.7, and 1.8 ( Nav1.3, Nav1.7, and Nav1.8)). Expression of miR-183 in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 ( CCR2) levels were examined by immunoblot analysis and interaction between miR-183 and TGFα, determined by luciferase reporter assay. The extent of pain in mice was measured using a behavioural assay, and OA severity assessed by Safranin O and Fast Green staining. Immunofluorescent staining was conducted to examine the infiltration of macrophages in mouse DRG.ResultsmiR-183 was downregulated in tissue samples from patients and mice with OA. In DMM mice, overexpression of miR-183 inhibited the expression of proinflammatory cytokines ( IL-6, IL-1β, TNF-α) and pain-related factors ( TRPV1, Nav1.3, Nav1.7, Nav1.8) in DRG. OA pain was relieved by miR-183-mediated inhibition of macrophage infiltration, and dual luciferase reporter assay demonstrated that miR-183 directly targeted TGFα.ConclusionOur data demonstrate that miR-183 can ameliorate OA pain by inhibiting the TGFα- CCL2/ CCR2 signalling axis, providing an excellent therapeutic target for OA treatment. Cite this article: Bone Joint Res 2021;10(8):548–557.

Osteoarthritis (OA) represents a progressive degenerative disorder that predominantly affects the synovial membranes of joints. Recent studies have highlighted the significant role played by microRNAs (miRNAs) in OA development. The current study aimed to elucidate the underlying modulatory role of miR-27b-3p in the development of OA. The expression of miR-27b-3p in the OA patients and rat models post anterior cruciate ligament transection operation was measured using reverse transcription quantitative polymerase chain reaction, through which overexpressed miR-27b-3p was found in both of the samples. To further explore the miR-27b-3p functions in OA, western blot analysis, enzyme-linked immunosorbent assay, and β-galactosidase activity assay were conducted with the results showing that knockdown of miR-27b-3p promoted expression of the osteogenic differentiation markers while inhibiting expression of the adipogenic differentiation markers, inflammatory factors, and cellular senescence of bone marrow mesenchymal stem cells (BMSCs). After that, the interactions between miR-27b-3p, lysine Demethylase 4B (KDM4B), and Distal-Less Homeobox 5 (DLX5) identified using dual-luciferase reporter gene assay and ChIP assay revealed that miR-27b-3p inhibited KDM4B and further reduced expression of DLX5. Finally, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were assessed in rat models, and increased PWT and PWL were detected after miR-27b-3p silencing. In conclusion, suppression of miR-27b-3p could enhance KDM4B and DLX5 to alleviate OA pain, shedding light on a new potential therapeutic target for OA.

The potential energy surface for the reductive repair of thymidine glycol (dTg) via electron transfer in aqueous solution has been mapped out in the present study employing a hybrid function of BH&HLYP in conjunction with the 6-311+G(d,p) basis set. Two types of repair mechanisms have been explored, including the reductive modification of the base portion and the excision of the base. The results indicate that thymidine (dT) is the most energetically feasible reductive product of dTg and also is the feasible degradation product of 5-hydroxy-5,6-dihydrothymidin-6-yl radical. The latter, however, has not been characterized in the previous experimental investigation. The insights explored in this paper help shed light on the interaction between low-energy electron and DNA base.

Melanin is the pigment responsible for the color of human skin and hair. Melanin serves as a double-edge sword which can exert both protective and spot-causing effects on skin. Although melanin has an important role in protecting the skin against UV damage, an excessive or uneven melanin production can lead to the formation of freckles and age spots. Isoliquiritigenin (ISL) has been reported to inhibit melanin synthesis; however, its role in melanin degradation remains unclear. In the present study, we evaluated the detailed function of ISL in melanin degradation in human epidermal keratinocytes. Since autophagy has been reported to be related to melanin degradation, we also examined the activation of autophagy by ISL treatment in keratinocytes by measurement of autophagy-related proteins, ATG7, LC3 and p62. Moreover, si-ATG7-induced ATG7 knockdown and autophagy inhibitor 3-MA decreased LC3 II protein levels and increased PMEL17, p62 and melanin levels in HaCaT cells, which could be partially reversed by ISL treatment, indicating that autophagy participated in melanin degradation. The decreased p-AKT and p-mTOR proteins upon ISL treatment indicated the involvement of PI3K/AKT/mTOR signaling in ISL-induced melanin degradation. Taken together, we demonstrated that autophagy participates in ISL-induced melanin degradation in human epidermal keratinocytes through PI3K/AKT/mTOR signaling.

We report an interfacially active system based on an informational peptide surfactant mixed with an oppositely charged polyelectrolyte. The 21-residue cationic peptide, AM1, has previously been shown to respond reversibly to pH and metal ions at fluid interfaces, forming elastic films that can be rapidly switched to collapse foams or emulsions on demand. Here we report the reversible association of AM1 with the methacrylate-based anionic polymer Eudragit S-100. The strength of the association, in bulk aqueous solution, is modulated by added metal ions and by ionic strength. Addition of zinc ions to the peptide-polymer system promotes complex formation and phase separation, while addition of a chelating agent reverses the association. The addition of salt weakens peptide-polymer interactions in the presence or absence of zinc. At the air-water interface, Eudragit S-100 forms an elastic mixed film with AM1 in the absence of metal, under conditions where the peptide alone does not show interfacial elasticity. When zinc is present, the elasticity of the mixed film is increased, but the rate of interfacial adsorption slows due to formation of peptide-polymer complexes in bulk solution. An understanding of these interactions can be used to identify favorable foam-forming conditions in the mixed system.

To evaluate the efficacy of health education on patients with hip replacement based on the Internet, and to establish a new health education model through modern technology.A total of 300 patients with hip replacement from March to August, 2015 were enrolled in this study. The participants were divided into a control group and an experimental group according to months surgeries performed. Traditional education was applied in the control group while the multimedia source material plus the Internet platform of Joint Registration System were applied in the experimental group. Levels of anxiety, degree of satisfaction, and postoperative complications were analyzed.The levels of knowledge, attitude and behavior compliance in the patients of the experimental group were significantly improved, while the levels of postoperative anxiety were decreased compared with those in the control group (P0.05).Education based on the Internet platform of Joint Registration System and the computer video could improve patients' knowledge, attitude, and behavior, which is worthy of clinical spread.