Characteristics of novel Ti-40Nb-xCu alloy and surface treatment with superior antibacterial property and biocompatibility using micro-arc oxidation for dental implants.

Peri-implantitis and insufficient osseointegration are the principal challenges faced by dental implants at present. In order to fabricate dual-function dental implant materials possessing both antibacterial and osteogenic capabilities, this study incorporates the antimicrobial element Cu into the Ti40Nb alloy, developing a novel Ti40Nb-xCu alloy with antibacterial properties. Among them, Ti40Nb3Cu has the best overall performance. Compared to Ti40Nb, the tensile strength increased by 27.97%, reaching 613 MPa. Although the elongation rate has decreased from 23% to 13.5%, the antibacterial rates against S. aureus and P. gingivalis both exceed 85%. Furthermore, the surface of Ti40Nb-xCu alloy was then treated with micro-arc oxidation to enhance its bioactivity, thereby accelerating osseointegration. The results indicated that the MAO treatment retains the antibacterial properties of the Ti40Nb3Cu alloy while significantly promoting bone formation through its introduced porous coating, thus heralding it as a propitious candidate material for dental implant applications.

Multifunctional role of oral bacteria in the progression of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders of varying severity, ultimately leading to fibrosis. This spectrum primarily consists of NAFL and non-alcoholic steatohepatitis. The pathogenesis of NAFLD is closely associated with disturbances in the gut microbiota and impairment of the intestinal barrier. Non-gut commensal flora, particularly bacteria, play a pivotal role in the progression of NAFLD. Notably, Porphyromonas gingivalis, a principal bacterium involved in periodontitis, is known to facilitate lipid accumulation, augment immune responses, and induce insulin resistance, thereby exacerbating fibrosis in cases of periodontitis-associated NAFLD. The influence of oral microbiota on NAFLD via the "oral-gut-liver" axis is gaining recognition, offering a novel perspective for NAFLD management through microbial imbalance correction. This review endeavors to encapsulate the intricate roles of oral bacteria in NAFLD and explore underlying mechanisms, emphasizing microbial control strategies as a viable therapeutic avenue for NAFLD.

Periosteum Containing Implicit Stem Cells: A Progressive Source of Inspiration for Bone Tissue Regeneration.

The periosteum is known as the thin connective tissue covering most bone surfaces. Its extrusive bone regeneration capacity was confirmed from the very first century-old studies. Recently, pluripotent stem cells in the periosteum with unique physiological properties were unveiled. Existing in dynamic contexts and regulated by complex molecular networks, periosteal stem cells emerge as having strong capabilities of proliferation and multipotential differentiation. Through continuous exploration of studies, we are now starting to acquire more insight into the great potential of the periosteum in bone formation and repair in situ or ectopically. It is undeniable that the periosteum is developing further into a more promising strategy to be harnessed in bone tissue regeneration. Here, we summarized the development and structure of the periosteum, cell markers, and the biological features of periosteal stem cells. Then, we reviewed their pivotal role in bone repair and the underlying molecular regulation. The understanding of periosteum-related cellular and molecular content will help enhance future research efforts and application transformation of the periosteum.

Porphyromonas gingivalis as a promotor in the development of the alcoholic liver disease via ferroptosis.

Alcoholic liver disease (ALD) is a liver disease caused by heavy drinking. Porphyromonas gingivalis (P.g), a major cause of periodontitis, whose antibodies are elevated in severe ALD patients in the plasma. The purpose of this study is to further study the role and the molecular mechanism of P.g in the progress of ALD. In this study, saliva of patients with ALD was collected. Then, an animal model of ALD with oral P.g administration was established, pathology of liver and spleen, intestinal microorganisms and metabolites were analyzed. The molecular mechanism of P.g on ALD was analyzed in vitro. ALD and intestinal microflora and metabolite changes were observed more serious in the alcohol and P.g groups than the alcohol group. Moreover, ferroptosis was aggravated by P.g in the liver. Meanwhile, P.g promoted ferroptosis accomplication with alcohol in vitro, which can be reversed by ferroptosis inhibitors. In conclusion, P.g aggravates ALD through exacerbation gut microbial metabolic disorder in mice with alcohol, which maybe depend on ferroptosis activation in hepatocytes. The study provides a new strategy for prevention and treatment of ALD by improving the oral micro-environment.

Effect of Aging on Tendon Biology, Biomechanics and Implications for Treatment Approaches.

Tendon aging is associated with an increasing prevalence of tendon injuries and/or chronic tendon diseases, such as tendinopathy, which affects approximately 25% of the adult population. Aged tendons are often characterized by a reduction in the number and functionality of tendon stem/progenitor cells (TSPCs), fragmented or disorganized collagen bundles, and an increased deposition of glycosaminoglycans (GAGs), leading to pain, inflammation, and impaired mobility. Although the exact pathology is unknown, overuse and microtrauma from aging are thought to be major causative factors. Due to the hypovascular and hypocellular nature of the tendon microenvironment, healing of aged tendons and related injuries is difficult using current pain/inflammation and surgical management techniques. Therefore, there is a need for novel therapies, specifically cellular therapy such as cell rejuvenation, due to the decreased regenerative capacity during aging. To augment the therapeutic strategies for treating tendon-aging-associated diseases and injuries, a comprehensive understanding of tendon aging pathology is needed. This review summarizes age-related tendon changes, including cell behaviors, extracellular matrix (ECM) composition, biomechanical properties and healing capacity. Additionally, the impact of conventional treatments (diet, exercise, and surgery) is discussed, and recent advanced strategies (cell rejuvenation) are highlighted to address aged tendon healing. This review underscores the molecular and cellular linkages between aged tendon biomechanical properties and the healing response, and provides an overview of current and novel strategies for treating aged tendons. Understanding the underlying rationale for future basic and translational studies of tendon aging is crucial to the development of advanced therapeutics for tendon regeneration.

Porphyromonas gingivalis triggers inflammation in hepatocyte depend on ferroptosis via activating the NF-κB signaling pathway.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive fat deposition in hepatocytes caused by non-alcoholic liver injury. Porphyromonas gingivalis (P.g) is the main pathogen causing periodontitis, which can aggravate the progression of NAFLD in our previously study. The objective of this study was to further investigate the pathogenesis and moleculer michanisma of NAFLD aggravated by P.g. METHODS: A mouse model of NAFLD was established, and the changes of inflammatory factors and NF-κB signaling pathway in liver tissue and L-02 cells were analyzed by transcriptome sequencing, Western blot, IHC and RT-PCR. In addition, the NF-κB signaling pathway inhibitor QNZ and ferroptosis inhibitor Fer-1 were used to analyze the relationship between NF-κB signaling pathway and ferroptosis in vitro. RESULTS: In vivo and in vitro experiments, P.g can induce liver inflammation and activate NF-κB signaling pathway. At the same time, P.g promotes ferroptosis and inflammation in L-02 in vitro. QNZ alleviates ferroptosis and inflammatory activation in L-02. Fer-1 can relieve the L-02 inflammation caused by P.g products. CONCLUSION: Porphyromonas gingivalis can induce ferroptosis and inflammation in hepatocytes and further worsen liver lesions. The mechanism of ferroptosis in hepatocytes depends on NF-κB signaling pathway, which provides a new strategy for clinical treatment and prevention of NAFLD.

Porphyromonas gingivalis is a risk factor for the development of nonalcoholic fatty liver disease via ferroptosis.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease that can eventually lead to liver cirrhosis and hepatocellular carcinoma. Porphyromonas gingivalis (P.g) is the main pathogen that causes periodontal disease, which participates in the development of NAFLD. The purpose of our study was to further study the direct role of P.g in NAFLD and the underlying molecular mechanism. An animal model of oral P.g administration was established, and liver function and pathology in this model were evaluated. The gut microbiome and metabolic products were analysed. Furthermore, the Th17/Treg balance in the spleen and liver was assessed. In our study, NAFLD was observed in all the mice that were orally administered P.g. The gut microbiome and metabolic products were altered after oral P.g administration. P.g and ferroptosis were observed in the livers of the mice after oral P.g administration. Additionally, ferroptosis was observed in hepatocytes in vitro, but it was reversed by ferroptosis inhibitors. In addition, P.g triggered an imbalance in the Th17/Treg ratio in the liver and spleen in vivo. These findings suggest that oral P.g administration directly induced NAFLD in mice, which may be dependent on the ferroptosis of liver cells that occurs through the Th17/Treg imbalance induced by disordered microbial metabolism. Therefore, improving the periodontal environment is a novel treatment strategy for preventing NAFLD.

Ultrafine particles exposure is associated with specific operative procedures in a multi-chair dental clinic.

Air quality in dental clinics is critical, especially in light of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, given that dental professionals and patients are at risk of regular exposure to aerosols and bioaerosols in dental clinics. High levels of ultrafine particles (UFP) may be produced by dental procedures. This study aimed to quantify ultrafine particles (UFP) concentrations in a real multi-chair dental clinic and compare the levels of UFP produced by different dental procedures. The efficiency of a high-volume evacuator (HVE) in reducing the UFP concentrations during dental procedures was also assessed. UFP concentrations were measured both inside and outside of a dental clinic in Shanghai, China during a 12-day period from July to September 2020. Dental activities were recorded during working hours. The mean (±standard deviation) concentrations of indoor and outdoor UFP during the sampling period were 8,209 (±4,407) counts/cm3 and 15,984 (±7,977) counts/cm3, respectively. The indoor UFP concentration was much higher during working hours (10,057 ± 5,725 counts/cm3) than during non-working hours (7,163 ± 2,972 counts/cm3). The UFP concentrations increased significantly during laser periodontal treatment, root canal filling, tooth drilling, and grinding, and were slightly elevated during ultrasonic scaling or tooth extraction by piezo-surgery. The highest UFP concentration (241,136 counts/cm3) was observed during laser periodontal treatment, followed by root canal filling (75,034 counts/cm3), which showed the second highest level. The use of an HVE resulted in lower number concentration of UFP when drilling and grinding teeth with high-speed handpieces, but did not significantly reduce UFP measured during laser periodontal therapy. we found that many dental procedures can generate high concentration of UFP in dental clinics, which may have a great health impact on the dental workers. The use of an HVE may help reduce the exposure to UFP during the use of high-speed handpieces.

Short-Term Administration of HIV Protease Inhibitor Saquinavir Improves Skull Bone Healing with Enhanced Osteoclastogenesis.

BACKGROUND: Using immunomodulatory methods to address the challenging issue of craniofacial bone repair may be a potentially effective approach. The protease inhibitor saquinavir has been shown to inhibit the inflammatory response by targeting the toll-like receptor 4/myeloid differentiation primary response complex. Independently, inhibition of toll-like receptor 4 or myeloid differentiation primary response led to enhanced skull bone repair. Therefore, the authors aimed to investigate the effects of saquinavir on skull bone healing. METHODS: The effects of saquinavir on skull bone healing were assessed by means of gene expression, histology, immunohistochemistry, and tomography in a mouse calvarial defect model. Subsequently, the role of saquinavir in cell viability, migration, and osteogenic and osteoclastogenic differentiation was also evaluated in vitro. RESULTS: One-week saquinavir administration improved skull bone healing based on micro-computed tomographic and histomorphometric analyses. Compared to the vehicle control, 1-week saquinavir treatment (1) enhanced osteoclast infiltration (tartrate-resistant acid phosphatase staining) at day 7, but not at days 14 and 28; (2) induced more CD206 + M2 macrophage infiltration, but not F4/80 + M0 macrophages at days 7, 14, and 28; and (3) elevated osteoclastogenic gene RANKL (quantitative polymerase chain reaction) expression and other osteogenic and cytokine expression. Furthermore, in vitro data showed that saquinavir administration did not influence MC3T3-E1 cell migration or mineralization, whereas higher concentrations of saquinavir inhibited cell viability. Saquinavir treatment also enhanced the osteoclastic differentiation of bone marrow-derived precursors, and partially reversed high-mobility group box 1-driven osteoclastogenesis inhibition and elevated proinflammatory cytokine expression. CONCLUSION: The improved skull bone repair following short-term saquinavir treatment may involve enhanced osteoclastogenesis and modulated inflammatory response following skull injury. CLINICAL RELEVANCE STATEMENT: The authors' work demonstrates improved skull bone healing by short-term application of saquinavir, a drug traditionally used in the treatment of acquired immunodeficiency syndrome. As such, saquinavir may be repurposed for skeletal repair.

Tocopherol attenuates the oxidative stress of BMSCs by inhibiting ferroptosis through the PI3k/AKT/mTOR pathway.

Oxidative stress can induce bone tissue damage and the occurrence of multiple diseases. As a type of traditional medicine, tocopherol has been reported to have a strong antioxidant effect and contributes to osteogenic differentiation. The purpose of this study was to investigate the protective effect of tocopherol on the oxidative stress of rat bone marrow-derived mesenchymal stem cells (BMSCs) and the underlying mechanisms. By establishing an oxidative stress model in vitro, the cell counting kit-8 (CCK-8), reactive oxygen species (ROS) analysis, Western blot (WB), real-time PCR (RT-PCR), alkaline phosphatase (ALP) staining, and Alizarin Red staining (ARS) evaluated the effects of tocopherol on the cell viability, intracellular ROS levels, and osteogenic differentiation in BMSCs. In addition, ferroptosis-related markers were examined via Western blot, RT-PCR, and Mito-FerroGreen. Eventually, the PI3K/AKT/mTOR signaling pathway was explored. We found that tocopherol significantly maintained the cell viability, reduced intracellular ROS levels, upregulated the levels of anti-oxidative genes, promoted the levels of osteogenic-related proteins, and the mRNA of BMSCs stimulated by H2O2. More importantly, tocopherol inhibited ferroptosis and upregulated the phosphorylation levels of PI3K, AKT, and mTOR of BMSCs upon H2O2 stimulation. In summary, tocopherol protected BMSCs from oxidative stress damage via the inhibition of ferroptosis through the PI3K/AKT/mTOR pathway.

Evaluation of antibacterial property and biocompatibility of Cu doped TiO2 coated implant prepared by micro-arc oxidation.

In order to enhance osteogenic differentiation and antibacterial property of dental implants, volcano-shaped microporous TiO2 coatings doped with Cu were fabricated via micro-arc oxidation (MAO) on Ti. Cu-doped coating with different mass ratios of Cu were obtained by changing the concentration of copper acetate in the electrolyte. The structure of Cu-TiO2 coatings were systematically investigated. Element Copper was uniformly distributed throughout the coating. Compared with TiO2 coating, the Cu-doped can further improved proliferation of bone mesenchymal stem cells (BMSCs), facilitated osteogenic differentiation. The bacteriostasis experiments demonstrated that Cu-doped TiO2 coating possess excellent antibacterial property against Staphylococcus aureus (S. aureus) and Porphyromonas gingivalis (P. gingivalis).

Quercetin protects rat BMSCs from oxidative stress via ferroptosis.

Quercetin has been shown to have a wide range of beneficial effects, such as anti-inflammation, anti-oxidation and immunomodulation. The study was designed to explore the role and molecular mechanisms of quercetin on the protective effect of bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress in vitro. BMSCs were isolated from 4-week-old male Sprague-Dawley rats. Upon H2O2 stimulation in vitro, the effects of quercetin on the proliferation, anti-oxidation and osteogenic differentiation of BMSCs were evaluated by Cell Counting Kit-8, reactive oxygen species analysis, Western blot (WB), real-time PCR (RT-PCR), alkaline phosphatase staining and alizarin red staining. Additionally, ferroptosis-related markers were examined by WB, RT-PCR and Mito-FerroGreen. Finally, PI3K/AKT/mTOR signaling pathway was explored in these processes. We found that quercetin significantly maintained BMSCs viability upon H2O2 stimulation. Quercetin upregulated protein (ALP, OPN and RUNX2) and mRNA (Alp, Opn, Ocn and Runx2) levels of osteogenic markers, downregulated ROS levels and upregulated antioxidative gene expressions (Nrf2, Cat, Sod-1 and Sod-2) compared with the H2O2 group. The ferroptosis in BMSCs was activated after H2O2 stimulation, and the phosphorylation level of PI3K, AKT and mTOR was upregulated in H2O2-stimulated BMSCs. More importantly, quercetin inhibited ferroptosis and the phosphorylation level of PI3K, AKT and mTOR were downregulated after quercetin treatment. We conclude that quercetin maintained the viability and the osteoblastic differentiation of BMSCs upon H2O2 stimulation, potentially via ferroptosis inhibition by PI3K/AKT/mTOR pathway.

Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway.

Osteoporosis bears an imbalance between bone formation and resorption, which is strongly related to oxidative stress. The function of leonurine on bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress is still unclear. Therefore, this study was aimed at identifying the protective effect of leonurine on H2O2 stimulated rat BMSCs. We found that leonurine can alleviate cell apoptosis and promote the differentiation ability of rat BMSCs induced by oxidative stress at an appropriate concentration at 10 µM. Meanwhile, the intracellular ROS level and the level of the COX2 and NOX4 mRNA decreased after leonurine treatment in vitro. The ATP level and mitochondrial membrane potential were upregulated after leonurine treatment. The protein level of PINK1 and Parkin showed the same trend. The mitophage in rat BMSCs blocked by 3-MA was partially rescued by leonurine. Bioinformatics analysis and leonurine-protein coupling provides a strong direct combination between leonurine and the PI3K protein at the position of Asp841, Glu880, Val882. In conclusion, leonurine protects the proliferation and differentiation of BMSCs from oxidative stress by activating mitophagy, which depends on the PI3K/Akt/mTOR pathway. The results showed that leonurine may have potential usage in osteoporosis and bone defect repair in osteoporosis patients.

Berberine ameliorates the LPS-induced imbalance of osteogenic and adipogenic differentiation in rat bone marrow-derived mesenchymal stem cells.

Lipopolysaccharide (LPS) from oral pathogenic bacteria is an important factor leading to alveolar bone absorption and the implant failure. The present study aimed to evaluate the modulation of berberine hydrochloride (BBR) on the LPS-mediated osteogenesis and adipogenesis imbalance in rat bone marrow-derived mesenchymal stem cells (BMSCs). Cell viability, osteoblastic and adipogenic differentiation levels were measured using the Cell Counting Kit-8 assay, alkaline phosphatase (ALP) staining and content assay, and oil red O staining, respectively. Reverse transcription-quantitative PCR and immunoblotting were used to detect the related gene and protein expression levels. In undifferentiated cells, BBR increased the mRNA expression levels of the osteoblastic genes (Alp, RUNX family transcription factor 2, osteocalcin and secreted phosphoprotein 1) but not the adipogenic genes (fatty acid binding protein 4, Adipsin and peroxisome proliferator-activated receptorγ). LPS-induced osteoblastic gene downregulation, adipogenic gene enhancement and NF-κB activation were reversed by BBR treatment. In osteoblastic differentiated cells, decreased ALP production by LPS treatment was recovered with BBR co-incubation. In adipogenic differentiated cells, LPS-mediated lipid accumulation was decreased by BBR administration. The mRNA expression levels of the pro-inflammatory factors (MCP-1, TNF-α, IL-6 and IL-1ß) were increased by LPS under both adipogenic and osteoblastic conditions, which were effectively ameliorated by BBR. The actions of BBR were attenuated by compound C, suggesting that the role of BBR may be partly due to AMP-activated protein kinase activation. The results demonstrated notable pro-osteogenic and anti-adipogenic actions of BBR in a LPS-stimulated inflammatory environment. This indicated a potential role of BBR for bacterial infected-related peri-implantitis medication.

Leonurine Promotes the Osteoblast Differentiation of Rat BMSCs by Activation of Autophagy via the PI3K/Akt/mTOR Pathway.

BACKGROUND: Leonurine, a major bioactive component from Herba leonuri, has been shown to exhibit anti-inflammatory and antioxidant effects. The aim of this study was to investigate the effect of leonurine on bone marrow-derived mesenchymal stem cells (BMSCs) as a therapeutic approach for treating osteoporosis. MATERIALS AND METHODS: Rat bone marrow-derived mesenchymal stem cells (rBMSCs) were isolated from 4-weeks-old Sprague-Dawley rats. The cytocompatibility of leonurine on rBMSCs was tested via CCK-8 assays and flow cytometric analyses. The effects of leonurine on rBMSC osteogenic differentiation were analyzed via ALP staining, Alizarin red staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. Additionally, autophagy-related markers were examined via qRT-PCR and Western blot analyses of rBMSCs during osteogenic differentiation with leonurine and with or without 3-methyladenine (3-MA) as an autophagic inhibitor. Finally, the PI3K/Akt/mTOR signaling pathway was evaluated during rBMSC osteogenesis. RESULTS: Leonurine at 2-100 µM promoted the proliferation of rBMSCs. ALP and Alizarin red staining results showed that 10 µM leonurine promoted rBMSC osteoblastic differentiation, which was consistent with the qRT-PCR and Western blot results. Compared with those of the control group, the mRNA and protein levels of Atg5, Atg7, and LC3 were upregulated in the rBMSCs upon leonurine treatment. Furthermore, leonurine rescued rBMSC autophagy after inhibition by 3-MA. Additionally, the PI3K/AKT/mTOR pathway was activated in rBMSCs upon leonurine treatment. CONCLUSION: Leonurine promotes the osteoblast differentiation of rBMSCs by activating autophagy, which depends on the PI3K/Akt/mTOR pathway. Our results suggest that leonurine may be a potential treatment for osteoporosis.

SPRC Suppresses Experimental Periodontitis by Modulating Th17/Treg Imbalance.

Object: The aims of the study were to explore the protective effects of S-propargyl-cysteine (SPRC) on periodontitis and to determine the underlying mechanisms. Methods: A rat periodontitis model was constructed by injecting LPS and SPRC (0, 25, and 50 mg/kg/d) was administered intraperitoneally. H2S and CSE level were detected. The alveolar bone level was evaluated by micro-CT, HE staining and methylene blue staining analysis. Inflammation-related factors, Treg and Th17 cells were detected by immunohistochemistry, RT-PCR, immunofluorescence, Western blot and flow cytometry. Phosphorylation levels of ERK1/2 and CREB were analysed. Results: The administration of SPRC significantly increased the expression of CSE in the gingival tissue and the concentration of endogenous H2S in the peripheral blood. Simultaneously, SPRC significantly inhibited the resorption of alveolar bone based on the H&E staining, micro-CT and methylene blue staining analysis. Compared with the periodontitis group, the levels of IL-17A, IL-10 were downregulated and IL-6,TGF-ß1 were upregulated in the SPRC groups. In the SPRC group, the percentage of TH17 cells and the expression of ROR-γt were downregulated, while the percentage of Tregs and the expression of Foxp3 were upregulated accompanied with inhibition of phosphorylation ERK1/2 and CREB. Conclusion: SPRC can prevent the progression of periodontitis by regulating the Th17/Treg balance by inhibition of the ERK/CREB signalling pathway.

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.

In vitro anti­bacterial activity of diosgenin on Porphyromonas gingivalis and Prevotella intermedia.

Diosgenin (Dios), a natural steroidal sapogenin, is a bioactive compound extracted from dietary fenugreek seeds. It has a wide range of applications, exhibiting anti­oxidant, anti­inflammatory and anti­cancer activities. However, whether the extracts have beneficial effects on periodontal pathogens has so far remained elusive. The aim of the present study was to investigate the anti­bacterial effects of Dios on Porphyromonas gingivalis (P. gingivalis) and Prevotella intermedia (P. intermedia) in vitro. The anti­microbial effect of Dios on P. gingivalis and P. intermedia was assessed by a direct contact test (DCT) and the Cell Counting Kit (CCK)­8 assay at 60, 90 and 120 min. In addition, counting of colony­forming units (CFU) and live/dead cell staining were used to evaluate the anti­bacterial effects. The results of the DCT and CCK­8 assays indicated that Dios had beneficial dose­dependent inhibitory effects on P. gingivalis and P. intermedia. The CFU counting results also indicated that Dios had dose­dependent anti­bacterial effects on P. gingivalis and P. intermedia. Of note, Dios had significant anti­bacterial effects on the biofilms of P. gingivalis and P. intermedia in vitro as visualized by the live/dead cell staining method. In conclusion, the present results demonstrated that Dios had a marked anti­bacterial activity against P. gingivalis and P. intermedia in vitro, both in suspension and on biofilms. The present study highlighted the potential applications of Dios as a novel natural agent to prevent and treat periodontitis through its anti­bacterial effects.

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.

Precision Medicine in Tissue Engineering on Bone.

With the rapidly development of clinical treatments, precision medicine has come to people eyes with the requirement according to different people and different disease situation. So precision medicine is called personalized medicine which is a new frontier of healthcare. Bone tissue engineering developed from traditional bone graft to precise medicine era. So scientists seek approaches to harness stem cells, scaffolds, growth factors, and extracellular matrix to promise enhanced and more reliable bone formation. This review provides an overview of novel developments on precision medicine in tissue engineering of bone hoping it can open new perspectives of strategies on bone treatment.