Identification of CD5/SOX11 double-negative pleomorphic mantle cell lymphoma.

Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(-) cyclin D1(+) SOX11(-), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1-rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1-rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1-rearranged cases were similar to MCL, whereas CCND1-non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1-rearranged cases had a notable trend (P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement.

Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19.

INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) and AXL tyrosine kinase receptor are known to be involved in the SARS-CoV-2 entry of the host cell. Therefore, targeting ACE2 and AXL should be an effective strategy to inhibit virus entry into cells. However, developing agents that can simultaneously target ACE2 and AXL remains a formidable task. The natural compound quercetin has been shown to inhibit AXL expression. MATERIALS AND METHODS: In this study, we employed PLGA nanoparticles to prepare nanoparticles encapsulated with quercetin, coated with ACE2-containing cell membranes, or encapsulated with quercetin and then coated with ACE-2-containing cell membranes. These nanoparticles were tested for their abilities to neutralize or inhibit viral infection. RESULTS: Our data showed that nanoparticles encapsulated with quercetin and then coated with ACE2-containing cell membrane inhibited the expression of AXL without causing cytotoxic activity. Nanoparticles incorporated with both quercetin and ACE2-containing cell membrane were found to be able to neutralize pseudo virus infection and were more effective than free quercetin and nanoparticles encapsulated with quercetin at inhibition of pseudo virus and SARS-CoV-2 infection. CONCLUSIONS: We have shown that the biomimetic nanoparticles incorporated with both ACE-2 membrane and quercetin showed the most antiviral activity and may be further explored for clinical application.

Arecoline Induces ROS Accumulation, Transcription of Proinflammatory Factors, and Expression of KRT6 in Oral Epithelial Cells.

Areca nut is a major contributor to the high prevalence of oral cancer in Asia. The precise mechanisms by which areca nut stimulates mucosal cells and contributes to the progression of oral cancer urgently require clarification. The current study aimed to assess the effects of arecoline on the normal human gingival epithelium cell line S-G. Cell viability, levels of reactive oxygen species (ROS), protein expression, cellular morphology, and gene expression were evaluated using the MTT test, flow cytometry, Western blot analysis, optical or confocal microscopy, and RT-qPCR. Keratin (KRT6) analysis involved matched normal and cancer tissues from clinical head and neck specimens. The results demonstrated that 12.5 µg/mL of arecoline induced ROS production, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) mRNA expression in S-G cells. This activation of the MAPK/ERK pathway increased KRT6 expression while limiting cell migration. In head and neck cancer tissues, KRT6B gene expression exceeded that of normal tissues. This study confirms that arecoline induces ROS accumulation in normal cells, leading to the secretion of proinflammatory factors and KRT6 expression. This impedes oral mucosal healing, thereby promoting the progression of oral cancer.

Corylin Attenuates CCl4-Induced Liver Fibrosis in Mice by Regulating the GAS6/AXL Signaling Pathway in Hepatic Stellate Cells.

Liver fibrosis is reversible when treated in its early stages and when liver inflammatory factors are inhibited. Limited studies have investigated the therapeutic effects of corylin, a flavonoid extracted from Psoralea corylifolia L. (Fabaceae), on liver fibrosis. Therefore, we evaluated the anti-inflammatory activity of corylin and investigated its efficacy and mechanism of action in ameliorating liver fibrosis. Corylin significantly inhibited inflammatory responses by inhibiting the activation of mitogen-activated protein kinase signaling pathways and the expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha in human THP-1 and mouse RAW264.7 macrophages. Furthermore, corylin inhibited the expression of growth arrest-specific gene 6 in human hepatic stellate cells (HSCs) and the activation of the downstream phosphoinositide 3-kinase/protein kinase B pathway. This inhibited the activation of HSCs and the expression of extracellular matrix proteins, including α-smooth muscle actin and type I collagen. Additionally, corylin induced caspase 9 and caspase 3 activation, which promoted apoptosis in HSCs. Moreover, in vivo experiments confirmed the regulatory effects of corylin on these proteins, and corylin alleviated the symptoms of carbon tetrachloride-induced liver fibrosis in mice. These findings revealed that corylin has anti-inflammatory activity and inhibits HSC activation; thus, it presents as a potential adjuvant in the treatment of liver fibrosis.

Caffeic Acid Phenethyl Ester and Caffeamide Derivatives Suppress Oral Squamous Cell Carcinoma Cells.

Caffeic acid phenethyl ester (CAPE) contains antibiotic and anticancer activities. Therefore, we aimed to investigate the anticancer properties and mechanisms of CAPE and caffeamide derivatives in the oral squamous cell carcinoma cell (OSCC) lines SAS and OECM-1. The anti-OSCC effects of CAPE and the caffeamide derivatives (26G, 36C, 36H, 36K, and 36M) were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Cell cycle and total reactive oxygen species (ROS) production were analyzed using flow cytometry. The relative protein expression of malignant phenotypes was determined via Western blot analysis. The results showed that 26G and 36M were more cytotoxic than the other compounds in SAS cells. After 26G or 36M treatment for 48 h, cell cycle S phase or G2/M phase arrest was induced, and cellular ROS increased at 24 h, and then decreased at 48 h in both cell lines. The expression levels of cell cycle regulatory and anti-ROS proteins were downregulated. In addition, 26G or 36M treatment inhibited malignant phenotypes through mTOR-ULK1-P62-LC3 autophagic signaling activated by ROS generation. These results showed that 26G and 36M induce cancer cell death by activating autophagy signaling, which is correlated with altered cellular oxidative stress.

PM2.5 promotes lung cancer progression through activation of the AhR-TMPRSS2-IL18 pathway.

Particulate matter 2.5 (PM2.5) is a risk factor for lung cancer. In this study, we investigated the molecular mechanisms of PM2.5 exposure on lung cancer progression. We found that short-term exposure to PM2.5 for 24 h activated the EGFR pathway in lung cancer cells (EGFR wild-type and mutant), while long-term exposure of lung cancer cells to PM2.5 for 90 days persistently promoted EGFR activation, cell proliferation, anchorage-independent growth, and tumor growth in a xenograft mouse model in EGFR-driven H1975 cancer cells. We showed that PM2.5 activated AhR to translocate into the nucleus and promoted EGFR activation. AhR further interacted with the promoter of TMPRSS2, thereby upregulating TMPRSS2 and IL18 expression to promote cancer progression. Depletion of TMPRSS2 in lung cancer cells suppressed anchorage-independent growth and xenograft tumor growth in mice. The expression levels of TMPRSS2 were found to correlate with nuclear AhR expression and with cancer stage in lung cancer patient tissue. Long-term exposure to PM2.5 could promote tumor progression in lung cancer through activation of EGFR and AhR to enhance the TMPRSS2-IL18 pathway.

Effects of Temoporfin-Based Photodynamic Therapy on the In Vitro Antibacterial Activity and Biocompatibility of Gelatin-Hyaluronic Acid Cross-Linked Hydrogel Membranes.

This study was performed to design a hydrogel membrane that exhibits antibacterial properties and guides different tissues. Gelatin and hyaluronic acid were used as the main structures, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) was used as a cross-linker, and temoporfin was used as an antibacterial agent. The results revealed that the hydrogel membrane impregnated with temoporfin (HM-T) had a fixation index of >89%. Temoporfin was used in conjunction with a diode laser and did not significantly affect EDC-induced cross-linking. The inhibitory activity of temoporfin showed that HM-T15 and HM-T30 (light exposure for 15 and 30 min, respectively) had remarkable antibacterial properties. The cell survival rate of HM-T15 was 73% of that of the control group, indicating that temoporfin exposure for 15 min did not exert cytotoxic effects on L-929 cells. HM and HM-T15 hydrogel membranes showed good cell adhesion and proliferation after 14 days of dark incubation. However, the hydrogel membrane containing temoporfin significantly reduced pro-inflammatory gene expression. In summary, the HM-T15 group showed potential as a biodegradable material for biocompatible tissue-guarded regeneration membranes with antibacterial properties. This study demonstrated the potential of temoporfin for innovative biomaterials and delivery systems applied to new regenerative periodontal therapies.

Association of rs9679162 Genetic Polymorphism and Aberrant Expression of Polypeptide N-Acetylgalactosaminyltransferase 14 (GALNT14) in Head and Neck Cancer.

The polypeptide N-Acetylgalactosaminyltransferase 14 (GALNT14) rs9679162 and mRNA expression were associated with treatment outcome in various cancers. However, the relation of GALNT14 and head and neck cancer were nuclear. A total of 199 patients with head and neck squamous cell carcinoma (HNSCC) were collected in this study, including oral SCC (OSCC), oropharyngeal SCC (OPSCC), laryngeal SCC (LSCC), and others. The DNA and RNA of cancer tissues were extracted using the TRI Reagent method. The rs9679162 was analyzed using polymerase chain reaction (PCR) and sequencing methods in 199 DNA specimens, and the mRNA expression was analyzed using quantitative reverse transcription PCR (RT-qPCR) methods in 68 paired RNA specimens of non-cancerous matched tissues (NCMT) and tumor tissues. The results showed that the genotype of TT, TG, and GG appeared at 30%, 44%, and 26%, respectively. Non-TT genotype or G alleotype were associated with alcohol, betel nut, and cigarette using among patients with OSCC, and it also affected the treatment and survival of patients with OSCC and LSCC. High GALNT14 mRNA expression levels increased lymphatic metastasis of patients with HNSCC, and treatment and survival in patients with OPSCC. Overall, the GALNT14-rs9679162 genotype and mRNA expression level can be used as indicators of HNSCC treatment prognosis.

Deep Learning-Based Nuclear Morphometry Reveals an Independent Prognostic Factor in Mantle Cell Lymphoma.

Blastoid/pleomorphic morphology is associated with short survival in mantle cell lymphoma (MCL), but its prognostic value is overridden by Ki-67 in multivariate analysis. Herein, a nuclear segmentation model was developed using deep learning, and nuclei of tumor cells in 103 MCL cases were automatically delineated. Eight nuclear morphometric attributes were extracted from each nucleus. The mean, variance, skewness, and kurtosis of each attribute were calculated for each case, resulting in 32 morphometric parameters. Compared with those in classic MCL, 17 morphometric parameters were significantly different in blastoid/pleomorphic MCL. Using univariate analysis, 16 morphometric parameters (including 14 significantly different between classic and blastoid/pleomorphic MCL) emerged as significant prognostic factors. Using multivariate analysis, Biologic MCL International Prognostic Index (bMIPI) risk group (P = 0.025), low skewness of nuclear irregularity (P = 0.020), and high mean of nuclear irregularity (P = 0.047) emerged as independent adverse prognostic factors. Additionally, a morphometric score calculated from the skewness and mean of nuclear irregularity (P = 0.0038) was an independent prognostic factor in addition to bMIPI risk group (P = 0.025), and a summed morphometric bMIPI score was useful for risk stratification of patients with MCL (P = 0.000001). These results demonstrate, for the first time, that a nuclear morphometric score is an independent prognostic factor in MCL. It is more robust than blastoid/pleomorphic morphology and can be objectively measured.

In Vitro Antimicrobial Potential of CAPE and Caffeamide Derivatives against Oral Microbes.

Caffeic acid phenethyl ester (CAPE) is a natural component isolated from propolis and used in traditional medicine. We aimed to investigate the antimicrobial properties and action mechanism of CAPE and caffeamide derivatives (26G and 36M) against oral disease microbes. We resolved the minimum inhibitory and bactericidal concentrations of 26G and 36M and their stability at different temperatures and pH. We also evaluated their effect on biofilm formation and antibiotic resistance gene expression in methicillin-resistant Staphylococcus aureus (MRSA). Our results revealed that 26G and 36M showed the best anticancer and antimicrobial activities, respectively, compared with the other four caffeamide derivatives. Both 26G and 36M showed heat-dependent decreases in antimicrobial activity. The 36M derivative was stable irrespective of pH, whereas 26G was not stable under high pH conditions. Biofilm formation and antibiotic resistance-related gene expression were consistent with their respective phenotypes. This study provides evidence for the potential application of CAPE and caffeamide derivatives in dental medicine to cure or prevent oral diseases.

The flavonoid corylin exhibits lifespan extension properties in mouse.

In the long history of traditional Chinese medicine, single herbs and complex formulas have been suggested to increase lifespan. However, the identification of single molecules responsible for lifespan extension has been challenging. Here, we collected a list of traditional Chinese medicines with potential longevity properties from pharmacopeias. By utilizing the mother enrichment program, we systematically screened these traditional Chinese medicines and identified a single herb, Psoralea corylifolia, that increases lifespan in Saccharomyces cerevisiae. Next, twenty-two pure compounds were isolated from Psoralea corylifolia. One of the compounds, corylin, was found to extend the replicative lifespan in yeast by targeting the Gtr1 protein. In human umbilical vein endothelial cells, RNA sequencing data showed that corylin ameliorates cellular senescence. We also examined an in vivo mammalian model, and found that corylin extends lifespan in mice fed a high-fat diet. Taken together, these findings suggest that corylin may promote longevity.

Psorachromene induces apoptosis and suppresses tumor growth in NSCLC cells harboring EGFR L858R/T790M/C797S.

The extracts from Psoralea corylifolia Linn. (P. corylifolia) seeds have been shown to display antitumor activity. To date, the prospects of this plant and its active compounds in the treatment of non-small-cell lung cancer (NSCLC) have not been thoroughly studied. In this study, we identified a novel psorachromene compound that displays selective cytotoxic effects on all NSCLC cells tested, including NSCLC cells harboring epidermal growth factor receptor (EGFR) activation mutants (H1975L858R/T790M and H1975-MS35L858R/T790M/C797S ). Psorachromene induces G1 arrest in NSCLC cells harboring wild-type EGFR but induces apoptosis in NSCLC cells harboring activating EGFR mutations. Psorachromene inhibits activated EGFR signaling and kinase activity and suppresses tumor growth of implanted H1975-MS35L858R/T790M/C797S cells in nude mice. Molecular docking analysis revealed that psorachromene could form stronger bonds with mutant EGFR than wild-type EGFR, which might account for the greater cytotoxic effects observed in NSCLC cells harboring activating EGFR mutations (H1975 and H1975-MS35) than wild-type EGFR (A549). In conclusion, it is suggested that psorachromene is an attractive agent to be further explored for its use in the treatment of NSCLC patients harboring EGFR L858R/T790M/C797S.

The relation between NEAT1 expression level and survival rate in patients with oral squamous cell carcinoma.

BACKGROUND/PURPOSE: Numerous studies have shown that long noncoding RNAs (lncRNAs) are involved in cancer progression and chemotherapy resistance. Nuclear enriched abundant transcript 1 (NEAT1) is an lncRNA. It affects tumor cell progression and drug resistance in various tumors. However, the relation of NEAT1 and survival rate in oral squamous cell carcinoma (OSCC) requires further study. MATERIALS AND METHODS: One normal gingival epithelium cell line, SG, three oral cancer cell lines (HSC3, OEC-M1, and SAS), 34 paired non-cancerous matched tissues (NCMT), and OSCC tissues were used in this study. Tri-reagent was used for total RNA extraction. NEAT1 expression was assessed by reverse transcription-quantitative PCR (RT-qPCR). RESULTS: NEAT1 expression in oral cancer cell lines was lower than that in normal cells and was significantly downregulated in OSCC. NEAT1 upregulation reduced the survival rate of patients with OSCC. NEAT1 upregulation also reduced the survival rate of OSCC patients treated with chemotherapy and radiotherapy. CONCLUSION: These results indicate that NEAT1 expression is a valuable biomarker for the prediction and prognosis of oral cancer.

In Vitro Assessment of the Cell Metabolic Activity, Cytotoxicity, Cell Attachment, and Inflammatory Reaction of Human Oral Fibroblasts on Polyetheretherketone (PEEK) Implant-Abutment.

The purpose of this research is to compare the cytotoxicity of polyetheretherketone (PEEK) and polyetherketoneketone (PEKK) with conventional dental implant-abutment materials, namely titanium alloy (Ti-6Al-4V) and yttria-stabilized tetragonal zirconia polycrystal (Y-TZP), to evaluate the cell metabolic activity, cytotoxicity, and inflammation potential of human oral fibroblasts (HOF) on these materials. Disk-shaped specimens were designed and prepared via a dental computer-aided manufacturing technology system. Surface topography, roughness, and free energy were investigated by atomic force microscope and contact angle analyzer; cell metabolic activity and cytotoxicity by MTT assay; and morphological changes by scanning electron microscopy (SEM). The effect of pro-inflammatory gene expression was evaluated by RT-qPCR. The obtained data were analyzed with one-way analysis of variance and post-hoc Tukey's honest significant difference tests. PEEK and PEKK exhibited higher submicron surface roughness (0.04 µm) and hydrophobicity (>80°) than the control. Although the cell activity of PEEK was lower than that of Ti-6Al-4V and Y-TZP for the first 24 h (p < 0.05), after 48 h there was no difference (p > 0.05). According to the cell cytotoxicity and the pro-inflammatory cytokine gene expression assays, there was no difference between the materials (p > 0.05). SEM observations indicated that HOF adhered poorly to PEKK but properly to Ti-6Al-4V, Y-TZP, and PEEK. PEEK and PEKK show comparable epithelial biological responses to Ti-6Al-4V and Y-TZP as implant-abutment materials. Between the two polymeric materials, the PEEK surface, where the HOF showed better cell metabolic activity and cytotoxicity, was a more promising implant-abutment material.

Growth Suppression in Lung Cancer Cells Harboring EGFR-C797S Mutation by Quercetin.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are approved treatments for non-small-cell lung cancer (NSCLC) patients harboring activating EGFR mutations. The EGFR C797S mutation is one of the known acquired-resistance mutations to the latest third-generation TKIs. At present, there are no clear options for treating patients who acquire resistance to third-generation TKIs. The acquisition of the EGFR C797S mutation was shown to upregulate the expression of AXL, a receptor tyrosine kinase of the TAM (TYRO3-AXL-MER) family, and the suppression of AXL is effective in reducing the growth of NSCLC cells harboring EGFR C797S. As quercetin was recently shown to inhibit AXL, quercetin may be effective in treating NSCLC cells harboring the EGFR C797S mutation. In this work, the cytotoxic effects of quercetin and its ability to inhibit tumor growth were examined in TKI-resistant NSCLC cells harboring the EGFR C797S mutation. We demonstrated that quercetin exhibited potent cytotoxic effects on NSCLC cells harboring the EGFR C797S mutation by inhibiting AXL and inducing apoptosis. Quercetin inhibited the tumor growth of xenografted NSCLC cells harboring the EGFR C797S mutation and appeared to act synergistically with brigatinib to inhibit of tumor growth in vivo. In summary, herein, we revealed that quercetin is an effective inhibitor for the treatment of non-small-cell lung cancer harboring the EGFR C797S mutation.

Hydroxygenkwanin Increases the Sensitivity of Liver Cancer Cells to Chemotherapy by Inhibiting DNA Damage Response in Mouse Xenograft Models.

Molecules involved in DNA damage response (DDR) are often overexpressed in cancer cells, resulting in poor responses to chemotherapy and radiotherapy. Although treatment efficacy can be improved with the concomitant use of DNA repair inhibitors, the accompanying side effects can compromise the quality of life of patients. Therefore, in this study, we identified a natural compound that could inhibit DDR, using the single-strand annealing yeast-cell analysis system, and explored its mechanisms of action and potential as a chemotherapy adjuvant in hepatocellular carcinoma (HCC) cell lines using comet assay, flow cytometry, Western blotting, immunofluorescence staining, and functional analyses. We developed a mouse model to verify the in vitro findings. We found that hydroxygenkwanin (HGK) inhibited the expression of RAD51 and progression of homologous recombination, thereby suppressing the ability of the HCC cell lines to repair DNA damage and enhancing their sensitivity to doxorubicin. HGK inhibited the phosphorylation of DNA damage checkpoint proteins, leading to apoptosis in the HCC cell lines. In the mouse xenograft model, HGK enhanced the sensitivity of liver cancer cells to doxorubicin without any physiological toxicity. Thus, HGK can inhibit DDR in liver cancer cells and mouse models, making it suitable for use as a chemotherapy adjuvant.

Identification of nodal micrometastasis in colorectal cancer using deep learning on annotation-free whole-slide images.

Detection of nodal micrometastasis (tumor size: 0.2-2.0 mm) is challenging for pathologists due to the small size of metastatic foci. Since lymph nodes with micrometastasis are counted as positive nodes, detecting micrometastasis is crucial for accurate pathologic staging of colorectal cancer. Previously, deep learning algorithms developed with manually annotated images performed well in identifying micrometastasis of breast cancer in sentinel lymph nodes. However, the process of manual annotation is labor intensive and time consuming. Multiple instance learning was later used to identify metastatic breast cancer without manual annotation, but its performance appears worse in detecting micrometastasis. Here, we developed a deep learning model using whole-slide images of regional lymph nodes of colorectal cancer with only a slide-level label (either a positive or negative slide). The training, validation, and testing sets included 1963, 219, and 1000 slides, respectively. A supercomputer TAIWANIA 2 was used to train a deep learning model to identify metastasis. At slide level, our algorithm performed well in identifying both macrometastasis (tumor size > 2.0 mm) and micrometastasis with an area under the receiver operating characteristics curve (AUC) of 0.9993 and 0.9956, respectively. Since most of our slides had more than one lymph node, we then tested the performance of our algorithm on 538 single-lymph node images randomly cropped from the testing set. At single-lymph node level, our algorithm maintained good performance in identifying macrometastasis and micrometastasis with an AUC of 0.9944 and 0.9476, respectively. Visualization using class activation mapping confirmed that our model identified nodal metastasis based on areas of tumor cells. Our results demonstrate for the first time that micrometastasis could be detected by deep learning on whole-slide images without manual annotation.

Biofilm Formation on the Surface of (Poly)Ether-Ether-Ketone and In Vitro Antimicrobial Efficacy of Photodynamic Therapy on Peri-Implant Mucositis.

Poly-ether-ether-ketone (PEEK) is an aesthetically pleasing natural material with good biocompatibility and shock absorption characteristics. The application of PEEK as a dental implant or abutment is expected to reduce the risk of failure and enhance aesthetics. Given that approximately one in 15 patients have allergic reactions to antibiotics, photodynamic therapy (PDT) has been gaining attention as an alternative treatment. Herein, the applicability of PEEK dental implants or abutments was investigated using material analyses, biofilm formation assay, and cell viability tests. The possible use of PDT for peri-implant mucositis was evaluated with the biofilm removal assay. The obtained data were analyzed based on the multivariate analysis of variance, paired t-tests, and the Pearson correlation coefficient (α = 0.05). The results revealed that PEEK was significantly less conducive to the formation of biofilms with S. mutans and A. actinomycetemcomitan (p < 0.001) but exhibited comparable MG-63 (human osteoblast-like) osteoblast cell viability (p > 0.05) to the other materials. PDT had similar antimicrobial efficacy and yielded similar biofilm removal effects to antibiotics. Altogether, these findings suggest that PEEK has attractive features and can serve as an alternative material for dental implants or abutments. In cases where peri-implant mucositis occurs, PDT can be used as an accessible therapeutic approach.

Effects of melatonin to arecoline-induced reactive oxygen species production and DNA damage in oral squamous cell carcinoma.

BACKGROUND/PURPOSE: Arecoline, the major alkaloid of areca nut, is known to induce reactive oxygen species (ROS) and DNA damage during oral cancer progression. This study aim to evaluate whether melatonin, an antioxidant, supported or repressed the arecoline-induced carcinogenesis phenotypes in oral squamous cell carcinoma (OSCC). METHODS: The cytotoxicity of arecoline or melatonin treatment alone and their co-treatment in the OSCC cell line OEC-M1 were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cell cycle, cell death, and total ROS production were analyzed using flow cytometer. The protein expression was determined using western blot analysis. The genotoxicity and mutation rate were determined using micronucleus assay and hypoxanthine phosphoribosyl transferase (HPRT) forward mutation assay, respectively, in CHO-K1 cells. The ataxia telangiectasia mutated (ATM) promoter activity and DNA repair ability were determined through reporter assay. RESULTS: The result showed that both the arecoline and melatonin induced ROS production and antioxidant enzymes expression. Melatonin treatment enhanced arecoline-induced ROS production, cytotoxicity, G2/M phase arrest, and cell apoptosis in OSCC cells. On the other hand, melatonin treatment activated DNA repair activity to reverse arecoline-induced DNA damage and mutation. CONCLUSION: These results indicated that melatonin is a potential chemopreventive agent for betel quid chewers to prevent OSCC initiation and progression.

In vitro antimicrobial and antipro-inflammation potential of honokiol and magnolol against oral pathogens and macrophages.

BACKGROUND/PURPOSE: Honokiol and magnolol are natural components isolated from Magnolia bark that is used in traditional Chinese and Japanese herbal medicine. These two isomers are used as a component of dietary supplements and cosmetic products. In this study, we investigated the antimicrobial effect of honokiol and magnolol on pathogens causing oral diseases, their mechanism of action in biofilm formation and drug resistance of oral pathogens, and inflammatory regulation in mammalian cells. METHODS: We determined the minimum inhibitory concentration and minimum bactericidal concentration of honokiol and magnolol, and their stability at different temperatures and pH. We also evaluated their effect on biofilm formation, antibiotic-resistance gene expression in MRSA, and pro-inflammatory gene expression in mammalian cells. RESULTS: Honokiol showed better antimicrobial activity than magnolol. Both honokiol and magnolol showed stable bacterial inhibitory activity over a wide range of temperature and pH, reduced biofilm formation, and antibiotic resistance in oral pathogens. The biofilm formation- and antibiotic resistance-related gene expression was consistent with the respective phenotypes. Furthermore, these two isomers repressed the expression of pro-inflammatory genes in RAW264.7 cells. CONCLUSION: Our study provides evidence of the potential application of honokiol and magnolol in dental medicine to cure or prevent oral diseases.