Transcriptional regulator CTR9 promotes hepatocellular carcinoma progression and metastasis via increasing PEG10 transcriptional activity.

Cln Three Requiring 9 (CTR9), a scaffold protein of the polymerase-associated factor-1 (PAF1) complex (PAF1c), is primarily localized in the nucleus of cells. Recent studies show that CTR9 plays essential roles in the development of various human cancers and their occurrence; however, its regulatory roles and precise mechanisms in hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the roles of CTR9 using in vitro assays and a xenograft mouse model. We found that CTR9 protein is upregulated in tumor tissues from HCC patients. Knockdown of CTR9 substantially reduced HCC cell proliferation, invasion, and migration, whereas its overexpression promoted these activities. In addition, in vitro results revealed that CTR9 silencing dramatically increased cell cycle regulators, p21 and p27, but markedly decreased matrix metalloproteinases, MMP2 and MMP9, with these outcomes reversed upon CTR9 overexpression. Furthermore, the underlying molecular mechanism suggests that CTR9 promoted the oncogene paternally expressed gene 10 (PEG10) transcription via its promoter region. Finally, the oncogenic roles of CTR9 were confirmed in a xenograft mouse model. This study confirms that CTR9, an oncoprotein that promotes HCC cell proliferation, invasion, and migration, increases tumor growth in a xenograft mouse model. CTR9 could be a novel therapeutic target. Further investigation is warranted to verify CTR9 potential in novel therapies for HCC.

Procyanidins and Their Therapeutic Potential against Oral Diseases.

Procyanidins, as a kind of dietary flavonoid, have excellent pharmacological properties, such as antioxidant, antibacterial, anti-inflammatory and anti-tumor properties, and so they can be used to treat various diseases, including Alzheimer's disease, diabetes, rheumatoid arthritis, tumors, and obesity. Given the low bioavailability of procyanidins, great efforts have been made in drug delivery systems to address their limited use. Nowadays, the heavy burden of oral diseases such as dental caries, periodontitis, endodontic infections, etc., and their consequences on the patients' quality of life indicate a strong need for developing effective therapies. Recent years, plenty of efforts are being made to develop more effective treatments. Therefore, this review summarized the latest researches on versatile effects and enhanced bioavailability of procyanidins resulting from innovative drug delivery systems, particularly focused on its potential against oral diseases.

ANP32A promotes the proliferation, migration and invasion of hepatocellular carcinoma by modulating the HMGA1/STAT3 pathway.

Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) has been reported to play an essential role in the development and progression of various human cancers. However, its expression pattern and possible mechanism in human hepatocellular carcinoma (HCC) remain to be elucidated. In this study, we used western blot and immunohistochemical staining to detect protein expression. The effects of ANP32A on the proliferation, migration and invasion of HCC cells were examined using 5-ethynyl-20-deoxyuridine (EdU), colony formation, CCK-8, and transwell assays. RT-qPCR was performed to detect mRNA expression. The interaction between ANP32A and the high mobility group A1 (HMGA1) mRNA was assessed using RNA immunoprecipitation (RIP). The tumorigenicity of ANP32A was assessed by establishing a xenograft tumor model in Balb/c nude mice. We found that the ANP32A protein was expressed at high levels in patients with HCC, which was associated with a poor prognosis. Functional experiments revealed that the silencing of ANP32A inhibited the proliferation, migration, and invasion of HCC cells, whereas overexpression of ANP32A promoted these processes. Further investigations indicated that ANP32A bound the HMGA1 mRNA and maintained its stability to promote the expression of HMGA1, thereby increasing the expression and activation of STAT3. Finally, a xenograft tumor model of Balb/c nude mice confirmed the tumorigenicity of ANP32A. This study found that ANP32A is up-regulated in patients with HCC and may accelerate the proliferation, migration and invasion of HCC cells by modulating the HMGA1/STAT3 pathway.

Association between diabetes and dental implant complications: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to explore the possible association between diabetes mellitus and dental implant complications. MATERIAL AND METHODS: A systematic literature review was conducted to answer the following PICO (Participants, Intervention, Comparison, and Outcome) question: Is there association between diabetes mellitus and dental implant complications? Two independent searchers performed a literature search of the PubMed/MEDLINE, Web of Science, Cochrane Library and EMBASE databases for studies published until February 2020, focussing on studies including continuous outcomes, marginal bone loss (primary outcome), probing depth, and bleeding upon probing (secondary outcomes). RESULTS AND CONCLUSIONS: A final total of 10 published studies were included in this systematic review. There were statistically significant differences between the groups with regard to marginal bone loss (p < .00001), probing depth (p < .00001) and bleeding around dental implants (p < .00001), and subjects without diabetes had lower complication rates. Additionally, in the subgroup analysis performed with loading time and HbA1c levels, a more evident association was found in immediate loading for probing depth. Moreover, the analysis results of bleeding around dental implants suggested that as HbA1c level increases, the bleeding of the tissues surrounding the implant will also increase. With regard to dental implant complications, there were statistically significant differences favouring patients without diabetes mellitus.

Synthesis, characterization, and aging resistance of the polyurethane dimethacrylate layer for dental restorations.

In this study, polyurethane dimethacrylate (PUDMA) was synthetized from different components and incorporated into a direct resin composite restoration system with the aim to buffer tooth-resin interfacial stresses and maintain the marginal adaptation. The tensile strength, elongation at fracture (ε), and thermal stability of the PUDMA layer were characterized, showing a tensile strength of 22 MPa, an ε of 112%, and a thermal decomposition temperature of about 282°C. In addition, the degree of conversion, water sorption/solubility, hydrophobicity, microtensile bond strength (µTBS), marginal leakage, and cytotoxicity in vitro were evaluated for the PUDMA layer. The data were analyzed using one-way ANOVA, except for leakage depths (which were analyzed using the Wilcoxon paired-rank test). The level of significance was set at 0.05. Compared with dental adhesives, PUDMA displayed a higher degree of conversion, lower water sorption/solubility, and improved hydrophobicity and biocompatibility in vitro. After thermocycling, the µTBS of the restoration system containing PUDMA had increased compared with the µTBS at 24 h. Restorations containing PUDMA showed lower leakage depths than those which did not contain PUDMA. In conclusion, because of its hydrophobic and elastic nature, the PUDMA layer, when used as an intermediate between tooth and resin restoratives, may buffer interfacial stresses, improve the stability and durability of the bonding interface, and reduce microleakage.

TSG101 promotes the proliferation, migration and invasion of hepatocellular carcinoma cells by regulating the PEG10.

The tumour susceptibility gene 101 (TSG101) is reported to play important roles in the development and progression of several human cancers. However, its potential roles and underlined mechanisms in human hepatocellular carcinoma (HCC) are still needed to be further clarified. In the present study, we reported that knock down of TSG101 suppressed the proliferation, migration and invasion of HCC cells, while overexpression of TSG101 facilitated them. Molecularly, the results revealed that knock down of TSG101 significantly decreased the cell cycle related regulatory factor p53 and p21. In another point, knock down of TSG101 also obviously decreased the level of metallopeptidase inhibitor TIMP1 (Tissue inhibitors of metalloproteinases 1), which results in inhibition of MMP2, MMP7 and MMP9. In contrast, overexpression of TSG101 had opposite effects. The iTRAQ proteomics analysis identified that oncogenic protein PEG10 (Paternally expressed gene 10) might be a potential downstream target of TSG101. Further investigation showed that TSG101 interacted with PEG10 and protected it from proteasomal degradation thereby regulating the expression of p53, p21 and MMPs. Finally, we found that both TSG101 and PEG10 proteins are up-regulated and presented a direct correlation in HCC patients. In conclusion, these results suggest that TSG101 is up-regulated in human HCC patients, which may accelerate the proliferation, migration and invasion of HCC cells through regulating PEG10.

PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway.

PHAP1 (Putative HLA-DR-associated protein 1), also termed acidic leucine-rich nuclear phosphoprotein 32A (ANP32A), Phosphoprotein 32 (pp32) or protein phosphatase 2A inhibitor (I1PP2A), is a multifunctional protein aberrantly expressed in multiple types of human cancers. However, its expression pattern and clinical relevance in human glioma remain unknown. In this study, Western blotting and immunohistochemistry analysis demonstrated PHAP1 protein was highly expressed in glioma patients, especially in those with high-grade disease. Publicly available data also revealed high levels of PHAP1 were associated with poor prognosis in glioma patients. The functional studies showed that knock-down of PHAP1 suppressed the proliferation of glioma cells, while overexpression of PHAP1 facilitated it. The iTRAQ proteomic analysis suggested that stathmin might be a potential downstream target of PHAP1. Consistently, PHAP1 knock-down significantly decreased the expression of stathmin, while overexpression of PHAP1 increased it. Also, the upstream negative regulator, p27, expression levels increased upon PHAP1 knock-down and decreased when PHAP1 was overexpressed. As a result, the phosphorylated Akt (S473), an upstream regulator of p27, expression levels decreased upon silencing of PHAP1, but elevated after PHAP1 overexpression. Importantly, we demonstrate the p27 down-regulation, stathmin up-regulation and cell proliferation acceleration induced by PHAP1 overexpression were dependent on Akt activation. In conclusion, the above results suggest that PHAP1 expression is elevated in glioma patients, which may accelerate the proliferation of glioma cells by regulating the Akt/p27/stathmin pathway.

Triclosan to Improve the Antimicrobial Performance of Universal Adhesives.

To solve the proble ms of composite restoration failure caused by secondary caries, this study reports a light curable antibacterial triclosan derivative (TCS-IH), which was synthesized and added to the existing commercial universal adhesive to achieve a long-term antibacterial effect The effect of mixing different mass percentages of TCS-IH on the bond strength of dentin was also investigated.TCS-IH was synthesized by solution polymerization and characterized by nuclear magnetic resonance hydrogen spectroscopy (1H NMR) and Fourier transform infrared (FTIR) spectroscopy. Two commercial universal adhesives, Single Bond Universal and All Bond Universal, were selected and used as the control group, and universal adhesives with different mass percentages (1 wt%, 3 wt%, 5 wt% and 7 wt%) of TCS-IH were used as the experimental group. The antibacterial properties were analysed by means of colony count experiments, biofilm formation detection, plotting of growth curves, biofilm metabolic activity detection, insoluble extracellular polysaccharide measurements and observations by confocal laser scanning microscopy and scanning electron microscopy (SEM). The effect of adhesives on biofilm formation, metabolism, extracellular matrix production, distribution of live and dead bacteria, and bacterial morphology of Streptococcus mutans (S. mutans) was analysed. The mechanical properties were evaluated by the degree of conversion and microtensile bonding strength under different conditions. Its biosafety was tested. We found that the addition of TCS-IH significantly improved the antibacterial performance of the universal adhesive, with the 5 wt% and 7 wt% groups showing the best antibacterial effect and effectively inhibiting the formation of biofilm. In addition, the adhesive strength test results showed that there was no statistical difference (p < 0.05) in the microtensile bond strength measured under various factors in all experimental groups except for the 7 wt% group in the self-etch bonding mode, and all of them had good biosafety. In summary, the 5 wt% group of antibacterial monomer TCS-IH was selected as the optimum addition to the universal adhesive to ensure the antimicrobial properties of the universal adhesive and the stability and durability of the adhesive interface. This study provides a reference for the clinical application of adhesives with antimicrobial activity to improve the stability and durability of adhesive restorations.

Effect of collagen cross-linkers on dentin bond strength: A systematic review and network meta-analysis.

Objective: This study aimed to evaluate the role of collagen cross-linkers in the bonding performance of the resin-dentin interface through a systematic review and a network meta-analysis. Sources: The literature search was conducted in several databases like PubMed, EMBASE, Cochrane, Scopus and Web of Science from their inception till 30 April 2022. Study selection: The inclusion criteria consisted of in vitro studies evaluating the micro-tensile and micro-shear bond strengths of different cross-linkers acting on dentin. Bayesian network meta-analysis was conducted using RStudio. Data: Out of the 294 studies evaluated in the full-text analysis, 40 were included in the systematic review and meta-analysis. Most studies have used cross-linkers as primer (65.1%), followed by incorporating them into in adhesives and acid etching agents. The application methods of the adhesive system were classified as "etch-and-rinse (ER) adhesives" (77%) and "self-etching (SE) adhesives". Moreover, there were six types of cross-linkers in this presented review, of which the most numerous were polyphenols. Conclusion: Different application methods of cross-linkers, the long-term results showed that were only effective when used for longer durations, the immediate results were not statistically different. According to immediate and long-term results, etch-and-rinse (ER) adhesives showed a greater bonding performance than the control groups (p ≤ 0.05), whereas self-etching (SE) adhesives showed similar bond strength values (p ≥ 0.05). The result of network meta-analysis (NMA) showed that Dope like compound showed higher long-term bonding performance than other cross-linkers. Clinical significance: Long-term clinical studies may be needed to determine the effect of the cross-linkers on the bonding properties.

Biomimetic Mineralized Hydrophilic Polyurethane Primers for Inducing Dentin Tubule Fillings.

This experiment aimed to synthesize a biomimetic mineralized hydrophilic polyurethane dentin primer containing DDDEEKC peptide (DDDEEKC-PU) to fill dentin tubules and induce mineralization. The degree of conversion (DC) was tested. Dentin samples were acid-etched and treated with DDDEEKC-PU. They were immersed in stimulated human fluid (SBF) for 7, 14 and 28 days. Dentin permeability, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and Vickers hardness were measured. After 28 days, regenerated minerals were deposited on resin tags which were confirmed to be hydroxyapatite (HAp). The minerals reduced the dentin permeability and improved the microhardness. DDDEEKC-PU was able to fill dental tubules immediately and induce mineralization simultaneously.

A novel resin cement to improve bonding interface durability.

Bonding failure is one of the main causes of failure of dental restorations. The bonding strength, aging resistance, and polymerization shrinkage of cement can affect the stability of the bonding interface and lead to marginal microleakage. To reduce the bonding failure rate of restorations, a novel polyurethane (PU) cement was designed to improve the mechanical properties, hydrophobicity, degree of conversion (DC), polymerization shrinkage, bond strength and aging resistance of cement by introducing isophorone diisocyanate (IPDI) and hydroxyethyl methacrylate (HEMA) and adjusting the polyester : polyether ratio to increase the degree of cross-linking. Experimental results verified that the novel PU could increase the mechanical properties and thermal stability of the cement, reduce polymerization shrinkage during the curing reaction, improve the bonding performance and DC, endow the cement with hydrophobic properties, and improve its ability to resist aging in the salivary environment to maintain the long-term stability of interfacial bonding under the influence of comprehensive factors. The results of this study provide a new direction and insights to reduce microleakage and improve the success rate of restorations.

A novel dental adhesive containing Ag/polydopamine-modified HA fillers with both antibacterial and mineralization properties.

OBJECTIVES: To evaluate the antibacterial and mineralization properties of a dental adhesive containing Ag/polydopamine-modified HA (HA, hydroxyapatite) fillers. METHODS: First, an HA-polydopamine-Ag-polydopamine (HA-PDA-Ag-PDA) filler was prepared and characterized using SEM, TEM, XPS, XRD and FTIR. Then, the HA-PDA-Ag-PDA filler was mixed into an adhesive at different mass fractions (0 wt%, 0.5 wt%, 1 wt%, 2 wt%) to prepare a functional adhesive. Antibacterial and mineralization tests were carried out, and the cytotoxicity of the functional adhesive against L929 fibroblasts was also examined. RESULTS: The SEM, TEM, XPS, XRD and FTIR characterizations confirmed the successful preparation of the HA-PDA-Ag filler. The 1 wt% and 2 wt% functional adhesives showed the strongest bacterial inhibition effect among all the samples (p < 0.05). Obvious apatite crystals were observed in the SEM micrograph of the surface of the functional adhesive sample after immersion in artificial saliva for predetermined times (1 d, 7 d, 14 d and 28 d). There was no significant difference between the experimental group and the control group in terms of cell proliferation activity (p > 0.05). CONCLUSIONS: The 1 wt% and 2 wt% functional adhesives demonstrated good antibacterial and mineralization properties, as well as good biocompatibility. CLINICAL SIGNIFICANCE: Functional adhesives containing Ag/polydopamine-modified HA fillers with antibacterial and mineralization capabilities might have excellent potential to enhance the stability and durability of hybrid layers and prolong the service life of dental restorations. Our study on bifunctional adhesives has paved the way for future clinical applications to increase restoration longevity.

Enhancement performance of application mussel-biomimetic adhesive primer for dentin adhesives.

In this study, we evaluated bioinspired adhesive primers for durable adhesion between dentin and composite resins. N-3,4-Dihydroxyphenethyl methacrylamide (DMA) primer monomer (small bifunctional group molecules containing catechol and acrylic groups at opposite ends) was prepared to mimic the interaction between the catechol group and the mineral interface of marine mussels. The shear bonding strength, microleakage, degree of conversion, contact angle, and compatibility were tested. The shear bond strength was significantly improved, and microleakage was diminished after the application of the DMA primer. However, the degree of conversion was decreased. The wettability of the dentin was enhanced, and the DMA primer showed no negative influence on cell proliferation. The results of this study showed the possibility of using DMA primers in clinical practice. This may provide a new strategy for improving adhesion durability.

[Effects of scaffold microstructure and mechanical properties on regeneration of tubular dentin].

Tubular dentin is of great significance in the process of tooth tissue and tooth regeneration, because it is not only the structural feature of primary dentin, but also can affect the tooth sensory function, affect the differentiation of dental pulp cells and provide strong mechanical support for teeth. Scaffold is one of the three elements of tissue engineering dentin regeneration. Most experiments on dentin regeneration involve the study of the microstructure and mechanical properties of the scaffold. The microstructure and mechanical characteristics of scaffold materials have important effects on the differentiation and adhesion of odontoblast, it can directly affect the tissue structure of regenerated dentin.

The functions of hydrophobic elastic polyurethane combined with an antibacterial triclosan derivative in the dentin restoration interface.

Dentin restoration produces weak interfaces because of the effects of bacterial microflora, biofilms, and mechanical, thermal, and shrinkage stresses. This results in secondary caries. Therefore, hydrophobic elastic polyurethane (PU) containing different concentrations of triclosan derivatives was synthesized and applied to solve this problem. The antibacterial PU was characterized according to its tensile strength (TS) and elasticity (ε) via a universal testing machine, and water sorption (Wsp) and solubility testing (Wsl) was performed according to ISO 4049: 2009. Additionally, this study evaluated the antibacterial properties of PU against Streptococcus mutans (ATCC35668) and Escherichia coli (ATCC25922). A marginal leakage test was performed to evaluate the leakage prevention property. As a result, the antibacterial PU showed high TS (>17 MPa), high elasticity (ε > 65%), and low Wsp (>81.06 µg/mm3) and Wsl (>11.22 µg/mm3). The PU exhibited antibacterial effects against both Streptococcus mutans and Escherichia coli. The antibacterial rates were over 90% and >99% for the 3% and 5% groups, respectively. Moreover, the marginal level of leakage was 0. Based on the mechanical properties, Wsp and Wsl values and the antibacterial properties, the 3% group exhibited satisfactory performance and has been deemed a possible solution to reduce the occurrence of secondary caries.