Surfactin induces autophagy, apoptosis, and cell cycle arrest in human oral squamous cell carcinoma.

OBJECTIVES: To investigate the anticancer effects and underlying mechanisms of surfactin on human oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The capacity of surfactin to induce apoptosis, autophagy, and cell cycle arrest of two different human OSCC cell lines was investigated by cell viability, acridine orange staining, and cell cycle regulatory protein expression, respectively. The signaling network underlying these processes were determined by the analysis of reactive oxygen species (ROS) generation, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, endoplasmic reticulum (ER) stress-related protein levels, calcium release, mitogen-activated protein kinases activation, and cell cycle regulatory protein expression through corresponding reagents and experiments under various experimental conditions using specific pharmaceutical inhibitors or small interfering RNAs. RESULTS: Surfactin was able to induce apoptosis through NADPH oxidase/ROS/ER stress/calcium-downregulated extracellular signal-regulated kinases 1/2 pathway. Surfactin could also lead to autophagy that shared the common regulatory signals with apoptosis pathway until calcium node. Cell cycle arrest at G2 /M phase caused by surfactin was demonstrated through p53 and p21 accumulation combined p34cdc2 , phosphorylated p34cdc2 , and cyclin B1 inhibition, which was regulated by NADPH oxidase-derived ROS. CONCLUSION: Surfactin could induce apoptosis, autophagy, and cell cycle arrest in ROS-dependent manner, suggesting a multifaced anticancer agent for OSCC.

The association between the severity of periodontitis and osteonecrosis of the jaw in patients with different cancer locations: a nationwide population-based study.

OBJECTIVES: To determine the relation between the severity of periodontitis and osteonecrosis of the jaw (ONJ) occurrence among different cancer locations and estimate the effect of dental care on ONJ prevention in cancer patients. MATERIALS AND METHODS: This population-based cross-sectional study was conducted through the Longitudinal Health Insurance Database, Taiwan. Patients with malignancies were collected and subdivided into groups according to their different cancer locations, the severity of periodontitis, and dental care. Multivariable logistic regression analysis was performed to assess the associations between ONJ and ONJ-related factors. RESULTS: A total of 8,234 ONJ patients and 32,912 control patients were investigated. Lip, oral cavity, and pharynx malignancies had the highest ONJ risk among all cancer locations (OR from 3.07 to 9.56, P < 0.01). There is a linear relationship between different severities of periodontitis and ONJ. Patients with radiotherapy and severe periodontitis had the highest ONJ risk (adjusted OR, 9.56; 95% CI, 5.34-17.1). Patients with good dental care had a lower ONJ risk. CONCLUSIONS: The periodontal condition and cancer location showed a significant impact on the risk of developing ONJ after adjusting for bisphosphonate use. Good dental care could decrease the risk of ONJ in cancer patients. The severity of periodontitis might be a target to predict the potency of ONJ. CLINICAL RELEVANCE: Dentists must be vigilant about the increased risk of ONJ in cancer patients with periodontitis, especially in the head and neck cancer population. Good dental care is advised for cancer patients with severe periodontitis.

Protective mechanisms of Taiwanese green propolis toward high glucose-induced inflammation via NLRP3 inflammasome signaling pathway in human gingival fibroblasts.

OBJECTIVE: To investigate protective effects of Taiwanese green propolis (TGP) against high glucose-induced inflammatory responses in human gingival fibroblasts (HGFs) through NLRP3 inflammasome signaling pathway. BACKGROUND: NLRP3 inflammasome has been implicated in the progression of both diabetes mellitus and periodontitis, suggesting a common potential therapeutic target for these diseases. Propolis is renowned for various biological activities, particularly anti-inflammation and antioxidant, representing a promising therapy for many conditions. However, underlying mechanisms remain unclear. METHODS: The cytotoxicity of TGP was evaluated by cell viability assay. The mRNA levels and protein expression or secretion of various inflammatory molecules and NLRP3 inflammasome-related molecules in high glucose-exposed HGFs with or without pretreatment of TGP (5 µg/ml) were determined by real-time PCR and western blot or specific kits, respectively. Intracellular and mitochondrial ROS measurements, NADPH oxidase activity determination, and subcellular fractions were performed to assess ROS generation. The transcriptional activity of NF-κB was measured by luciferase reporter kit. The signaling components were further differentiated using pharmacological inhibitors of ROS and small interfering RNAs of TLR2, TLR4, or NF-κB. RESULTS: High glucose could induce IL-1ß-driven inflammatory responses in HGFs via the activation of NLRP3 inflammasome regulated by TLR2/TLR4 coupled ROS in NF-κB-dependent manner. TGP had no adverse impact on the cell viability of HGFs at concentrations no greater than 10 µg/ml, and could exert inhibitory effects on high glucose-induced inflammatory responses via the interruption of NLRP3 inflammasome signaling pathway. CONCLUSION: Taiwanese green propolis could elicit protective effects against IL-1ß-driven inflammation in high glucose-exposed HGFs through TLR2/TLR4 combined ROS/NF-κB/NLRP3 inflammasome pathway.

Risk of dementia in patients with periodontitis and related protective factors: A nationwide retrospective cohort study.

AIM: We aimed to evaluate the long-term risk of dementia in patients with periodontitis and its associated factors. MATERIALS AND METHODS: Using Taiwan's National Health Insurance Database, we identified 56,018 patients aged ≥50 years with newly diagnosed periodontitis in 2000-2008. A cohort of 56,018 adults without periodontitis was selected for comparison, with matching by age and sex. Both cohorts were followed from 2000 to the end of 2013, and incident dementia was identified during the follow-up period. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of dementia associated with periodontitis were calculated in the multivariate regressions. RESULTS: Periodontitis was associated with dementia risk (HR: 1.79, 95% CI: 1.67-1.93), and the association between periodontitis and dementia risk was significant in men, women, and people aged more than 60 years. Among patients with periodontitis, the use of statins (HR: 0.78, 95% CI: 0.71-0.87), metformin (HR: 0.53, 95% CI: 0.44-0.62), and influenza vaccination (HR: 0.67, 95% CI: 0.61-0.74) were associated with a reduced risk of dementia, while diabetes, mental disorders, and stroke were major significant risk factors. CONCLUSIONS: Periodontitis was a risk factor for dementia, while the use of statins and metformin may reduce the risk of dementia.

Slug mediates myofibroblastic differentiation to promote fibrogenesis in buccal mucosa.

Epithelial-mesenchymal transition (EMT) has been implicated in fibrogenesis and carcinogenesis; however, the exact role of EMT-inducer Slug in the progression of precancerous oral submucous fibrosis (OSF) has not been investigated. In the current study, we showed that the expression of Slug was upregulated in OSF tissues and associated with various myofibroblast markers. After silence of Slug in fibrotic buccal mucosal fibroblasts (fBMFs), the elevated myofibroblast activities and fibrosis markers were all downregulated. Our data revealed that arecoline, an areca nut alkaloid, increased the expression of Slug in normal BMFs, and inhibition of Slug successfully prevented the arecoline-induced myofibroblast activation. Additionally, overexpression of Slug in BMFs stimulated the activities of myofibroblasts, indicating that upregulation of Slug by arecoline contributes to the myofibroblast transdifferentiation. Most importantly, Slug was able to bind to the E-box of type I collagen, leading to increased expression of type I collagen. Altogether, this study demonstrated the abnormal elevation of Slug in OSF and its significance in arecoline-induced fibrogenesis. Moreover, downregulation of Slug could be a potential target for OSF remedy via suppression of myofibroblast activities and type I collagen.

LncRNA LINC00974 activates TGF-ß/Smad signaling to promote oral fibrogenesis.

BACKGROUND: Oral submucous fibrosis (OSF) is a progressive scarring disease and has been considered as a premalignant condition of the oral cavity. However, the detailed molecular mechanisms underlying the pathogenesis of OSF are still unclear. METHOD: Here, we examined the expression of a novel long non-coding RNA LINC00974 in OSF and investigated its function role in myofibroblast transdifferentiation. Phenotypic analyses, including collagen gel contraction, migration, invasion and wound healing assays, were used to assess the myofibroblast activities following overexpression or inhibition of LINC00974. RESULTS: We found that the expression of LINC00974 in OSF tissues or myofibroblasts was aberrantly upregulated, and there was a positive correlation between LINC00974 and myofibroblast markers. Our results showed that inhibition of LINC00974 suppressed the myofibroblast activities, while overexpression of LINC00974 increased the activation. We demonstrated that the expression levels of α-SMA, α-1 type I collagen, fibronectin were downregulated in the LINC00974-inhibited myofibroblasts. Additionally, the TGF-ß secretion and phosphorylated Smad2 expression were also repressed in the LINC00974-inhibited myofibroblasts. We further demonstrated that silence of LINC00974 prevented the arecoline-induced myofibroblast activation, and LINC00974-increased myofibroblast activities were via TGF-ß pathway. CONCLUSION: Altogether, these findings suggested that arecoline-increased myofibroblast transdifferentiation was via LINC00974-mediated activation of TGF-ß signaling.

Antimetastatic potentials of salvianolic acid A on oral squamous cell carcinoma by targeting MMP-2 and the c-Raf/MEK/ERK pathway.

The metastasis of oral squamous cell carcinoma (OSCC) is one of the most important causes of cancer-related deaths. Thus, various therapeutic strategies have been developed to prevent the metastasis of OSCC. Salvianolic acid A (SAA), a traditional Chinese medicine, has antithrombosis, antiplatelet, anti-inflammation, and antitumor activities. Here, we provide molecular evidence indicating that SAA exerts its antimetastatic effects by markedly inhibiting the invasion and migration of oral squamous SCC-9 and SCC-25 cells. SCC-9 and SCC-25 cells were treated with various concentrations of SAA to further investigate the precise involvement of SAA in cancer metastasis. The results of zymography, and Western blotting indicated that SAA treatment may decrease matrix metallopoteinase-2 (MMP-2) expression. SAA also inhibited p-c-Raf, p-MEK1/2, and p-ERK1/2 protein expression. In addition, treating SCC-9 cells with U0126, a MEK-specific inhibitor, decreased MMP-2 expression and concomitantly inhibited cell migration. Our findings suggested that SAA inhibits the invasion and migration of OSCC by inhibiting the c-Raf/MEK/ERK pathways that control MMP-2 expression. Our findings provide new insights into the molecular mechanisms that underlie the antimetastatic effect of SAA and are thus valuable for the development of treatment strategies for metastatic OSCC.

Effect of systemic administration of lipopolysaccharides derived from Porphyromonas gingivalis on gene expression in mice kidney.

Although an association between periodontitis and chronic kidney disease (CKD) has been suggested, the mechanism involved remains unclear. Herein, we examined the global gene expression profile in a mouse model that showed no acute inflammation in the kidney following stimulation with lipopolysaccharides (LPS) derived from Porphyromonas gingivalis (PG-LPS). The mice were injected with PG-LPS at a concentration of 5 mg/kg intraperitoneally, every 3 days, for 1 month. Microarray analysis was used to identify 10 genes with the highest expression levels in the kidney stimulated with PG-LPS. Among them, the functions of five genes (Saa3, Ticam2, Reg3b, Ocxt2a, and Xcr1) were known. The upregulation of these genes was confirmed by quantitative polymerase chain reaction assay. Furthermore, we examined whether the expression of these upregulated genes were altered in endothelial cells derived from the kidney, in vitro. The mRNA expression levels of all five genes were significantly higher in the experimental group than in the controls (no LPS stimulation; *p < 0.05). In conclusion, the responses noted in the kidney may have arisen mainly from the endothelial cells. Moreover, upregulation of the expression levels of Saa3, Ticam2, Reg3b, Ocxt2a, and Xcr1 may be associated with the pathogenesis of CKD.

PCL/Graphene Scaffolds for the Osteogenesis Process.

This study aims to characterize the osteoconductivity, optimal bioresorbable, biodegradability, biocompatibility, and mechanical properties of Poly-ε-caprolactone (PCL)/graphene (G) scaffolds at concentrations of 0.5, 1, 1.5, 2, 2.5, and 3 wt%, which are used to support bone regeneration through solvent casting and particulate leaching. The water contact angle measurement revealed a transition from a hydrophobic to a hydrophilic surface after incorporating various G concentrations. The scaffolds with 0.5 wt% G had smaller pores compared to those produced using 3 wt% G. Furthermore, numerous pores were connected, particularly those with larger diameters in the 2 and 3 wt% G samples. The proportion of water absorption varied between 50% and 350% for 4 months, with large percentages of scaffolds containing high G concentrations. Raman spectroscopy and X-ray diffraction, which were used to confirm the presence of nanofiller by increasing the ratios of ID/IG, I2D/IG, and band 2θ = 26.48°. The mechanical properties were improved by the addition of G, with a Young's modulus of 3 wt% G, four times that of PCL. Measuring cell biocompatibility, adhesion, proliferation, and differentiation with osteoblast-like (MG-63) cells revealed that PCL/G scaffolds with higher concentrations were more biocompatible than PCL as well as those with lower concentrations.

In silico repurposing of midostaurin as a therapeutic candidate for head and neck cancer via targeting SPARC/MMP9/CD44 Cancer-Associated Fibroblasts (CAFs) oncogenic signature.

Head and neck squamous carcinoma (HNSCC) affects more than half a million individuals and ranks the ninth leading cause of death globally each year. Many patients develop treatment resistance leading to poor clinical outcomes. The poor treatment responses are in part due to the heterogeneity of HNSCC tumor and tumor microenvironment (TME). The interaction of tumor cells with their TME has been studied vigorously in recent years because of their pivotal roles in tumorigenesis and determining the treatment response. Cancer-associated fibroblasts (CAFs) are one of the most abundant tumor-infiltrating cells, which have been shown to associate with the aggressive behavior of HNSCC. Hence, targeting and disrupting the tumor-CAFs interactions represents a rational therapeutic approach. To develop targeted therapeutic drugs against CAFs, the identification of CAF-associated gene signature is essential. Here, we analyzed multiple sequencing databases including microarrays and single-cell RNA-sequencing databases and identified SPARC/MMP9/CD44 as HNSCC targetable gene signatures encompassing cancer-associated fibroblasts (CAFs). We found SPARC/MMP9CD44 signature was highly expressed in HNSC tissues compared to adjacent normal tissues. Increased SPARC/MMP9/CD44 signature levels strongly correlated with tumor-infiltrating CAFs, suggesting the functional importance of this signature for HNSCC-CAFs interaction and progression. Subsequently, we utilized a genomics approach and identified midostaurin as the top-ranking drug candidate for targeting SPARC/MMP9/CD44 signature. For validation, we performed molecular docking of midostaurin in complex with SPARC/MMP9/CD44 and demonstrated midostaurin's high binding affinities compared to their respective standard inhibitors. In summary, our study provided a rapid genomics approach for identifying targetable gene signature and drug candidate for HNSCC.

MXD3 as an onco-immunological biomarker encompassing the tumor microenvironment, disease staging, prognoses, and therapeutic responses in multiple cancer types.

MAX dimerization (MXD) protein 3 (MXD3) is a member of the MXD family of basic-helix-loop-helix-leucine-zipper (bHLHZ) transcription factors that plays pivotal roles in cell cycle progression and cell proliferation. However, there is insufficient scientific evidence on the pathogenic roles of MXD3 in various cancers and whether MXD3 plays a role in the immuno-oncology context of the tumor microenvironment, pathogenesis, prognosis, and therapeutic response of different tumors through certain common molecular mechanisms; thus, we saw a need to conduct the present in silico pan-cancer study. Using various computational tools, we interrogated the role of MXD3 in tumor immune infiltration, immune evasion, tumor progression, therapy response, and prognosis of cohorts from various cancer types. Our results indicated that MXD3 was aberrantly expressed in almost all The Cancer Genome Atlas (TCGA) cancer types and subtypes and was associated with the tumor stage, metastasis, and worse prognoses of various cohorts. Our results also suggested that MXD3 is associated with tumor immune evasion via different mechanisms involving T-cell exclusion in different cancer types and by tumor infiltration of immune cells in thymoma (THYM), liver hepatocellular carcinoma (LIHC), and head and neck squamous cell carcinoma (HNSC). Methylation of MXD3 was inversely associated with messenger (m)RNA expression levels and mediated dysfunctional T-cell phenotypes and worse prognoses of cohorts from different cancer types. Finally, we found that genetic alterations and oncogenic features of MXD3 were concomitantly associated with deregulation of the DBN1, RAB24, SLC34A1, PRELID1, LMAN2, F12, GRK6, RGS14, PRR7, and PFN3 genes and were connected to phospholipid transport and ion homeostasis. Our results also suggested that MXD3 expression is associated with immune or chemotherapeutic outcomes in various cancers. In addition, higher MXD3 expression levels were associated with decreased sensitivity of cancer cell lines to several mitogen-activated protein kinase kinase (MEK) inhibitors but led to increased activities of other kinase inhibitors, including Akt inhibitors. Interestingly, MXD3 exhibited higher predictive power for response outcomes and overall survival of immune checkpoint blockade sub-cohorts than three of seven standardized biomarkers. Altogether, our study strongly suggests that MXD3 is an immune-oncogenic molecule and could serve as a biomarker for cancer detection, prognosis, therapeutic design, and follow-up.

Carbon Monoxide-Releasing Molecule-2 Ameliorates Particulate Matter-Induced Aorta Inflammation via Toll-Like Receptor/NADPH Oxidase/ROS/NF-κB/IL-6 Inhibition.

Particulate matter (PM), a major air pollutant, may be associated with adverse cardiovascular effects. Reactive oxygen species- (ROS-) dependent proinflammatory cytokine production, such as interleukin-6 (IL-6), is a possible underlying mechanism. Carbon monoxide- (CO-) releasing molecule-2 (CORM-2) which liberates exogenous CO can exert many beneficial effects, particularly anti-inflammation and antioxidant effects. The purpose of this study was to explore the protective effects and underpinning mechanisms of CORM-2 on PM-induced aorta inflammation. Here, human aortic vascular smooth muscle cells (HASMCs) were utilized as in vitro models for the assessment of signaling pathways behind CORM-2 activities against PM-induced inflammatory responses, including Toll-like receptors (TLRs), NADPH oxidase, ROS, nuclear factor-kappa B (NF-κB), and IL-6. The modulation of monocyte adherence and HASMC migration, that are two critical cellular events of inflammatory process, along with their regulators, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and matrix metalloproteinase-2 (MMP-2) and MMP-9, in response to PM by CORM-2, were further evaluated. Finally, mice experiments under different conditions were conducted for the in vivo evaluation of CORM-2 benefits on the expression of inflammatory molecules including IL-6, ICAM-1, VCAM-1, MMP-2, and MMP-9. Our results found that PM could induce aorta inflammation in vitro and in vivo, as evidenced by the increase of IL-6 expression that was regulated by the TLR2 and TLR4/NADPH oxidase/ROS/NF-κB signaling pathway, thereby promoting ICAM-1- and VCAM-1-dependent monocyte adhesion and MMP-2- and MMP-9-dependent HASMC migration. Importantly, our experimental models demonstrated that CORM-2-liberated CO effectively inhibited the whole identified PM-induced inflammatory cascade in HASMCs and tissues. In conclusion, CORM-2 treatment may elicit multiple beneficial effects on inflammatory responses of aorta due to PM exposure, thereby providing therapeutic value in the context of inflammatory diseases of the cardiovascular system.

Ex Vivo Expanded Circulating Tumor Cells for Clinical Anti-Cancer Drug Prediction in Patients with Head and Neck Cancer.

The advanced-stage head and neck cancer (HNC) patients respond poorly to platinum-based treatments. Thus, a reliable pretreatment method for evaluating platinum treatment response would improve therapeutic efficiency and outcomes. This study describes a novel strategy to predict clinical drug responses in HNC patients by using eSelect, a lab-developed biomimetic cell culture system, which enables us to perform ex vivo expansion and drug sensitivity profiling of circulating tumor cells (CTCs). Forty liquid biopsies were collected from HNC patients, and the CTCs were expanded ex vivo using the eSelect system within four weeks. Immunofluorescence staining confirmed that the CTC-derived organoids were positive for EpCAM and negative for CD45. Two illustrative cases present the potential of this strategy for evaluating treatment response. The statistical analysis confirmed that drug sensitivity in CTC-derived organoids was associated with a clinical response. The multivariant logistic regression model predicted that the treatment accuracy of chemotherapy responses achieved 93.75%, and the area under the curves (AUCs) of prediction models was 0.8841 in the whole dataset and 0.9167 in cisplatin specific dataset. In summary, cisplatin sensitivity profiles of patient-derived CTCs expanded ex vivo correlate with a clinical response to cisplatin treatment, and this can potentially underpin predictive assays to guide HNC treatments.

Potential effects of noxious chemical-containing fine particulate matter on oral health through reactive oxygen species-mediated oxidative stress: Promising clues.

Nowadays, air pollution which is dominated by fine particulate matter with aerodynamic diameter less than or equal to 2.5 µm resulting from rapid industrialization and urbanization combined with population explosion has become more and more severe problem to mankind and the whole planet because of its diversity of deleterious effects. The latest data estimated that exposure to fine particulate matter, or PM2.5, contributes to approximately 4 million deaths worldwide due to cardiopulmonary conditions such as heart disease and stroke, respiratory infections, chronic lung disease and lung cancer. During recent years, there has been growing concern about the adverse effects of this global threat on oral health which is one of key components of general health and quality of life. Although a few studies have reported such possible association, the findings are still far from conclusion. Moreover, the underlying mechanisms remain unclear. To our knowledge, the analysis of literature regarding this scope has yet been published. Thus, current work systematically assesses existing evidences on the potential association between exposure to PM2.5 and the development of various oral diseases as well as figures out the plausible paradigm of PM2.5-induced damages in the oral cavity through its toxic chemical constituents along with its ability to induce oxidative stress via reactive oxygen species production. This might partially provide the clues for new research ideas and progression in the field of oral health.

Surfactin from Bacillus subtilis induces apoptosis in human oral squamous cell carcinoma through ROS-regulated mitochondrial pathway.

Recently, ambient air particulate matter (PM) has been shown to increase the risk of oral cancer. The most common malignant tumor in the oral cavity is oral squamous cell carcinoma (OSCC). Recent studies have revealed that surfactin, a cyclic lipopeptide generated by Bacillus subtilis, has anti-inflammatory and anti-cancer properties. However, the exact anti-cancer effects of surfactin on human OSCC and underlying molecular mechanisms remain largely unknown. In the present study, we found that treatment of SCC4 and SCC25 cells (human OSCC cell lines) with surfactin reduced the viability of SCC4 and SCC25 cells by induction of apoptosis. Surfactin-induced apoptosis was associated with caspase activation and poly(ADP-ribose) polymerase (PARP) cleavage and was regulated by the mitochondrial pathway, exemplified by mitochondrial depolarization, mitochondrial-derived reactive oxidative species (ROS) production, cytochrome c release, up-regulation of Bad and Bax, and down-regulation of Bcl-2. Surfactin induced NADPH oxidase-dependent ROS generation, which appeared essential for the activation of the mitochondrial pathway. Surfactin-induced mitochondrial-derived ROS generation was associated with JNK1/2 activation. After treatment with surfactin, ROS caused JNK1/2-dependent cell death of SCC4 and SCC25 cells. Taken together, our findings suggest that surfactin induces mitochondria associated apoptosis of human OSCC cell lines, and surfactin may be a potential chemotherapeutic agent for future OSCC treatment.

Fully Digital Workflow for Planning Static Guided Implant Surgery: A Prospective Accuracy Study.

The accuracy of static guided implant surgery (sGIS) using conventional planning workflow has been extensively examined; however, more information is required to justify the application of fully digital planning protocol. The purpose of this study was to investigate the clinical accuracy of sGIS with a fully digital planning workflow. Twenty-one partially edentulous patients were enrolled in this prospective study. Cone-beam computed tomography (CBCT) and intraoral scans were taken and superimposed by matching the dental surface images directly (surface registration protocol) or by matching fiducial markers on a stereolithographic (SLA) radiographic template fabricated from the digital data of the intraoral scan (fiducial marker registration protocol). Virtual implant treatment plans were then determined, and tooth-supported SLA surgical guides were fabricated according to the plans. Twenty-six implant surgeries were performed via the surgical guide by one surgeon. Pre- and post-operative CBCT images were superimposed, and the positional and angular deviations between placed and planned implants were measured with metrology software. A total of 43 fully guided implants were placed, in which 25 implants were planned with the surface registration protocol. Implants planned based on the surface registration protocol had a larger mean angular deviation than the fiducial marker registration protocol. No significant differences were found for any deviations of the examined variables. Within the limits of this study, we concluded that the clinical accuracy of the sGIS planned with a fully digital workflow was consistent with the conventional workflow for partially edentulous patients.

The Inducible Role of Ambient Particulate Matter in Cancer Progression via Oxidative Stress-Mediated Reactive Oxygen Species Pathways: A Recent Perception.

Cancer is one of the leading causes of premature death and overall death in the world. On the other hand, fine particulate matter, which is less than 2.5 microns in aerodynamic diameter, is a global health problem due to its small diameter but high toxicity. Accumulating evidence has demonstrated the positive associations between this pollutant with both lung and non-lung cancer processes. However, the underlying mechanisms are yet to be elucidated. The present review summarizes and analyzes the most recent findings on the relationship between fine particulate matter and various types of cancer along with the oxidative stress mechanisms as its possible carcinogenic mechanisms. Also, promising antioxidant therapies against cancer induced by this poison factor are discussed.

Surfactin from Bacillus subtilis attenuates ambient air particulate matter-promoted human oral cancer cells metastatic potential.

Recently, many studies have indicated that ambient air particulate matter (PM) can increase the risk of oral cancer. The most common malignant tumor in the oral cavity is oral squamous cell carcinoma (OSCC). Usually, cancer cell migration/invasion is the most important cause of cancer mortality. Matrix metalloproteinase-2 (MMP-2) and MMP-9 have been shown to play important roles in regulating metastasis and the tumor microenvironment. Here, we studied the anti-cancer effects of surfactin, a cyclic lipopeptide generated by Bacillus subtilis, on cancer cell migration and invasion. Surfactin suppressed PM-promoted cell migration and invasion and colony formation of SCC4 and SCC25 human oral squamous cell carcinoma cell lines. We observed that PM induced MMP-2 and MMP-9 expression, which was inhibited by surfactin. Transfection with p65, p50, c-Jun, c-Fos, p85, p110, Akt, mammalian target of rapamycin (mTOR), or interleukin-6 (IL-6) siRNA markedly inhibited PM-induced MMP-2 and MMP-9 expression. Moreover, surfactin could reduce Akt, mTOR, p65, and c-Jun activation and IL-6 secretion induced by PM. Finally, we proved that transfection with Akt, p65, or c-Jun siRNA significantly inhibited PM-induced IL-6 release. Taken together, these results suggest that surfactin functions as a suppressor of PM-induced MMP2/9-dependent oral cancer cell migration and invasion by inhibiting the activation of phosphoinositide 3-kinase (PI3K)/Akt/mTOR and PI3K/Akt/nuclear factor-κB (NF-κB) and activator protein-1 (AP-1)/IL-6 signaling pathways.

Analysis on Characteristics of ZnO Surface Acoustic Wave with and without Micro-Structures.

In this paper, we fabricate a surface acoustic wave (SAW) device with micro-structures on a zinc oxide (ZnO) thin film and measure its signal response. The manufacturing processes of the SAW device include the fabrication of micro-structures of a SAW element and its interdigital transducer by silicon micro-machining and the fabrication of a thin film of ZnO by RF magnetron sputtering. We, then, measure the SAW properties. This research investigates the properties of sputtered thin films for various amounts of O2/(Ar + O2) using Zn and ZnO targets. Regardless of target, the growth rate of the ZnO thin film decreases as the oxygen content increases. When the SAW is sputtered ZnO thin film using 30% oxygen, the digital signal of the SAW has better performance. The measurement signal of the SAW with micro-structures is similar to that without micro-structures.

Protective Effects of Oral Astaxanthin Nanopowder against Ultraviolet-Induced Photokeratitis in Mice.

PURPOSE: Astaxanthin (AST) has a strong antioxidant cellular membrane chaperone protective effect. Recently, a water-soluble nanosized AST (nano-AST) form was produced, which is expected to improve the efficacy of oral intake effects. The purpose of this study was to examine whether oral nano-AST has therapeutic effects on UV-induced photokeratitis in mice. METHODS: C57BL/6 mice were administered twice with either nano-AST, AST oil, lutein, or bilberry extracts 3 hours before and shortly before UV irradiation (dose: 400 mJ/cm2). The corneas were collected 24 hours after irradiation and stained with H&E and TUNEL. NF-κB, dihydroethidium (DHE), COX-2, p-IκB-α, TNFα, and CD45 expression were evaluated through immunohistochemistry, Western blot analysis, and qPCR. RESULTS: Corneal epithelium was significantly thicker in mice orally administered with nano-AST than in the others (p < 0.01), with significantly less NF-κB nucleus translocation (p < 0.001), and significantly fewer TUNEL cells (p < 0.01). Weaker DHE signals were detected in the nano-AST group (p < 0.05) relative to the others. Furthermore, reduced inflammation and decreased cell death in corneal tissue were observed in the nano-AST group, as indicated by a reduction in the expression of COX-2, p-IκB-α, TNFα, and CD45. CONCLUSIONS: Oral administration of nano-AST demonstrated a protective effect on UV-induced photokeratitis via antioxidative, anti-inflammatory, and antiapoptotic activity.