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.

Surfactin reduces particulate matter-induced VCAM-1-dependent monocyte adhesion in human gingival fibroblasts by increasing Nrf2-dependent HO-1 expression.

BACKGROUND AND OBJECTIVES: The mechanisms of particulate matter (PM) toxicity involve the generation of ROS and upregulation of proinflammatory molecules. Nrf2 is a multifunctional cytoprotective transcription factor that regulates the expression of various antioxidant, anti-inflammatory, and detoxifying molecules, such as HO-1. As surfactin has potential to induce Nrf2 activation and HO-1 expression, this study aimed to investigate the anti-inflammatory effects of surfactin on PM-exposed human gingival fibroblasts (HGFs) and signaling pathways engaged by surfactin. MATERIALS AND METHODS: Human gingival fibroblasts were challenged by PM with or without surfactin pretreatment. The expression of Nrf2, HO-1, VCAM-1, and other molecules was determined by western blot, real-time PCR, or ELISA. Human monocytic THP-1 cells labeled with fluorescent reagent were added to HGFs, and the cell adhesion was assessed. ROS generation and NADPH oxidase activity were also measured. The involvement of Nrf2/HO-1 and ROS signaling pathways was investigated by treating HGFs with specific pathway interventions, genetically or pharmacologically. One dose of surfactin was given to mice before PM treatment to explore its in vivo effect on VCAM-1 expression in gingival tissues. RESULTS: Particulate matter led to VCAM-1-dependent monocyte adhesion in HGFs, which was regulated by PKCα/NADPH oxidase/ROS/STAT1/IL-6 pathway. Surfactin could attenuate monocyte adhesion by disrupting this VCAM-1-dependent pathway. Additionally, surfactin promoted Nrf2-dependent HO-1 expression in HGFs, mitigating VCAM-1 expression. PM-treated mice exhibited the lower expression of IL-6 and VCAM-1 in gingival tissues if they previously received surfactin. CONCLUSION: Surfactin exerts anti-inflammatory effects against PM-induced inflammatory responses in HGFs by inhibiting VCAM-1-dependent pathway and inducing Nrf2/HO-1 axis.

Surfactin attenuates particulate matter-induced COX-2-dependent PGE2 production in human gingival fibroblasts by inhibiting TLR2 and TLR4/MyD88/NADPH oxidase/ROS/PI3K/Akt/NF-κB signaling pathway.

OBJECTIVE: To evaluate the anti-inflammatory effects of surfactin and underlying mechanisms against particulate matter (PM)-induced inflammatory responses in human gingival fibroblasts (HGFs). BACKGROUND: PM, a major air pollutant, may associate with certain oral diseases possibly by inducing inflammation and oxidative stress. Surfactin, a potent biosurfactant, possesses various biological properties including anti-inflammatory activity. However, the underlying mechanisms are unclear. Also, there is no study investigating the effects of surfactin on PM-induced oral inflammatory responses. As an essential constituent of human periodontal connective tissues which involves immune-inflammatory responses, HGFs serve as useful study models. METHODS: HGFs were pretreated with surfactin prior to PM incubation. The PGE2 production was determined by ELISA, while the protein expression and mRNA levels of COX-2 and upstream regulators were measured using Western blot and real-time PCR, respectively. The transcriptional activity of COX-2 and NF-κB were determined using promoter assay. ROS generation and NADPH oxidase activity were identified by specific assays. Co-immunoprecipitation assay, pharmacologic inhibitors, and siRNA transfection were applied to explore the interplay of molecules. Mice were given one dose of surfactin or different pharmacologic inhibitors, then PM was delivered into the gingiva for three consecutive days. Gingival tissues were obtained for analyzing COX-2 expression. RESULTS: PM-treated HGFs released significantly higher COX-2-dependent PGE2 , which were regulated by TLR2 and TLR4/MyD88/NADPH oxidase/ROS/PI3K/Akt/NF-κB pathway. PM-induced COX-2/PGE2 increase was effectively reversed by surfactin through the disruption of regulatory pathway. Similar inhibitory effects of surfactin was observed in mice. CONCLUSION: Surfactin may elicit anti-inflammatory effects against PM-induced oral inflammatory responses.

Dental education changed by COVID-19: Student's perceptions and attitudes.

BACKGROUND: Dental students have encountered changes in the teaching format amid the SARS CoV-2 pandemic. This study aims to evaluate the attitudes of dental students of one medical university toward online courses and compare them with those of non-dental students amid the SARS CoV-2 pandemic. METHODS: A cross-sectional survey with a self-report online questionnaire was conducted at the medical university in May 2020 in Taipei. Students from the School of Dentistry, School of Dental Technology, and School of Oral Hygiene Study were enrolled in our survey. RESULTS: In total, 473 students responded to the survey, 318 (67.2%) of whom were dental students. Overall, 366 (77%) students agreed with the change to online learning. Only 10.4% of students thought that dental professional courses with a laboratory format could be changed to online courses. Dental students were significantly more worried than non-dental students about being infected with COVID-19 and about the COVID-19 pandemic continuing. CONCLUSIONS: In conclusion, changing to online learning seems to be perceived as feasible by students. However, more discussion about changing dental professional courses with a laboratory format to online courses considering the attitudes from students is needed.

The impact of COVID-19 on knowledge, attitude, and infection control behaviors among dentists.

BACKGROUND: This study seeks to elucidate the impact of COVID-19 on knowledge, attitude, and infection control behaviors among dentists. METHODS: Changes in knowledge, attitude, and infection control behaviors reported in 2020 (COVID-19 period) were compared to the historical control of the non-COVID-19 period in 2018. A proportional random sampling method was used to select the study samples from 400 dental institutions. The response rate was 69% in 2018 and 62.8% in 2020. A total of 276 dentists in 2018 and 251 dentists in 2020 responded to this questionnaire. Multiple logistic regression was used to assess the associations between factors and recommended infection control practices. RESULTS: High rates of correct COVID-19 knowledge (94.76%), fears of being infected with the virus (94%) and use of personal protective equipment (mask, glove and protection gown; 95%) were reported. We found that knowledge regarding environmental infection control, HIV transmission, and the window of HIV transmission were significantly higher in the post-COVID-19 period compared with the pre-COVID-19 period. High compliance rates of wearing mask, gloves and protection were reported. The number of dentists wearing a hair cap and a protective eye mask/face shield during the pandemic significantly increased compared with that noted before the COVID-19 pandemic. Factors associated with the use of a hair cap and an eye mask/face shield differed between the pre- and post-COVID-19 periods. The factors associated with compliance regarding environment infection control also differed between the pre- and post-COVID-19 periods. CONCLUSION: The significant impact of COVID-19 on the knowledge, attitude, and infection control behaviors among dental care workers was observed in the current study. In particular, the use of hair caps and protective eye mask or face shields as well as environmental disinfection protocols has significantly improved. Trial registration TMU-JIRB: N201804006.

Highly Expressed FOXF1 Inhibit Non-Small-Cell Lung Cancer Growth via Inducing Tumor Suppressor and G1-Phase Cell-Cycle Arrest.

Cancer pathogenesis results from genetic alteration-induced high or low transcriptional programs, which become highly dependent on regulators of gene expression. However, their role in progressive regulation of non-small-cell lung cancer (NSCLC) and how these dependencies may offer opportunities for novel therapeutic options remain to be understood. Previously, we identified forkhead box F1 (FOXF1) as a reprogramming mediator which leads to stemnesss when mesenchymal stem cells fuse with lung cancer cells, and we now examine its effect on lung cancer through establishing lowly and highly expressing FOXF1 NSCLC engineered cell lines. Higher expression of FOXF1 was enabled in cell lines through lentiviral transduction, and their viability, proliferation, and anchorage-dependent growth was assessed. Flow cytometry and Western blot were used to analyze cellular percentage in cell-cycle phases and levels of cellular cyclins, respectively. In mice, tumorigenic behavior of FOXF1 was investigated. We found that FOXF1 was downregulated in lung cancer tissues and cancer cell lines. Cell proliferation and ability of migration, anchorage-independent growth, and transformation were inhibited in H441-FOXF1H and H1299-FOXF1H, with upregulated tumor suppressor p21 and suppressed cellular cyclins, leading to cell-cycle arrest at the gap 1 (G1) phase. H441-FOXF1H and H1299-FOXF1H injected mice showed reduced tumor size. Conclusively, highly expressing FOXF1 inhibited NSCLC growth via activating tumor suppressor p21 and G1 cell-cycle arrest, thus offering a potentially novel therapeutic strategy for lung cancer.

Effect of nonextraction and extraction orthodontic treatments on smile esthetics for different malocclusions.

INTRODUCTION: Smile esthetics is a critical factor for evaluating orthodontic treatment outcomes. In this study, we evaluated the differences in esthetic perceptions and smile variables between extraction and nonextraction treatments for different malocclusions. METHODS: Ninety participants were divided into 3 groups according to their pretreatment overjet (group I, 0-4 mm; group II, >4 mm; group III, <0 mm), with 15 extraction participants and 15 nonextraction participants in each group. Posttreatment frontal smiling photographs were evaluated by 30 raters (10 orthodontists, 10 general dentists, 10 laypeople), and 9 smile variables were measured. RESULTS: Smile perception for the group II extraction subjects was higher than for the nonextraction subjects by the orthodontists and general dentists. Regardless of the type of treatment, group III subjects were rated lower than those in groups I and II. The arch form index, maxillary incisor show, and smile arc were greater in the extraction participants. In multiple regression analysis, nonextraction and group III correlated negatively with the esthetic score. Maxillary incisor show, tooth number display, and buccal corridor ratio correlated positively with the esthetic score. CONCLUSIONS: Group II extraction subjects were rated higher than the nonextraction subjects by dental professionals. A smile with greater maxillary incisor show, number of displayed teeth, and buccal corridor ratio was considered more esthetic.

Effect of maternal use of chewing gums containing xylitol on transmission of mutans streptococci in children: a meta-analysis of randomized controlled trials.

BACKGROUND: Mutans streptococci (MS) are the major causative bacteria involved in human dental decay. Habitual consumption of xylitol has been proved to reduce MS levels in saliva and plaque. AIM: To evaluate the effect of the maternal use of xylitol gum on MS reduction in infants. DESIGN: A structured literature review and meta-analysis. A random effects model was used to assess the relative risks of the incidence of MS in the saliva or plaque of children who were 6, 9, 12, 18, and 24 months old. RESULTS: We reviewed 11 RCTs derived from 5 research teams that included 601 mothers. Our results indicated that the incidence of MS in the saliva or plaque of the infants was significantly reduced in the xylitol group (risk ratio: 0.54; 95% confidence interval: 0.39-0.73, at 12-18 months) and (risk ratio: 0.56; 95% confidence interval: 0.40-0.79, at 36 months) compared with the control groups. The long-term effect of maternal xylitol gum exposure on their children's dental caries was controversial. CONCLUSION: Habitual xylitol consumption by mothers with high MS levels was associated with a significant reduction in the mother-child transmission of salivary MS.

Organic light-emitting diode therapy promotes longevity through the upregulation of SIRT1 in senescence-accelerated mouse prone 8 mice.

Phototherapy has been extensively used to prevent and treat signs of aging and stimulate wound healing, and phototherapy through light-emitting diodes (LEDs). In contrast to LED, organic LED (OLED) devices are composed of organic semiconductors that possess novel characteristics. We investigated the regenerative potential of OLED for restoring cellular potential from senescence and thus delaying animal aging. Bone marrow-derived stem cells (BMSCs) and adipose-derived stem cells (ADSCs) were isolated from the control and OLED- treated groups to evaluate their proliferation, migration, and differentiation potentials. Cellular senescence was evaluated using a senescence-associated ß-galactosidase (SA-ß-gal) activity assay and gene expression biomarker assessment. OLED treatment significantly increased the cell proliferation, colony formation, and migration abilities of stem cells. SA-ß-gal activity was significantly decreased in both ADSCs and BMSCs in the OLED-treated group. Gene expression biomarkers from treated mice indicated a significant upregulation of IGF-1 (insulin growthfactor-1). The upregulation of the SIRT1 gene inhibited the p16 and p19 genes then to downregulate the p53 expressions for regeneration of stem cells in the OLED-treated group. Our findings indicated that the survival rates of 10-month aging senescence-accelerated mouse prone 8 mice were prolonged and that their gross appearance improved markedly after OLED treatment. Histological analysis of skin and brain tissue also indicated significantly greater collagen fibers density, which prevents ocular abnormalities and ß-amyloid accumulation. Lordokyphosis and bone characteristics were observed to resemble those of younger mice after OLED treatment. In conclusion, OLED therapy reduced the signs of aging and enhanced stem-cell senescence recovery and then could be used for tissue regeneration.

Factors affecting infection control measures performed by dental workers.

Background/purpose: An understanding of self-protection related factors is important for dental infection control. This study aimed to investigate factors associated with personal self-protection in infection control among dental care workers. Materials and methods: A cross-sectional survey with self-report questionnaire was conducted between Jan and Dec, 2018.275 dentists and 298 dental assistants were enrolled from randomly selected dental care settings. Results: Compliance with wearing hair caps, facial masks, and hand washing is not as high as oral masks and gloves (over 90%). For dentists, the level of clinical setting (aOR = 3.1, P < 0.001) and the correct use of disinfectants for impression materials (aOR = 2.0, P < 0.05) were associated with hair cap wearing. Gender (aOR = 0.15, P < 0.05) and correct use of indicator during sterilization (aOR = 2.9, P < 0.05) were associated with facial mask wearing. The correct use of indicator during sterilization (aOR = 2.4, P < 0.05) and disinfection for impression materials (aOR = 2.2, P < 0.05) were associated with hand washing. For dental assistants, longer work experience (aOR = 1.05, P < 0.05), working days (aOR = 1.82, P < 0.05), the correct use of disinfectants for impression materials (aOR = 2.4, P < 0.001), and the frequent use of gloves (aOR = 8.0, P < 0.05) were associated with facial mask wearing. The surface disinfection of working tables (aOR = 2.8, P < 0.001) and the frequent changing of gloves (aOR = 5.96, P < 0.05) were associated with hand washing. Conclusion: Gender, the length of work practice, and correct techniques for sterilization use were identified as major factors associated with compliance with self-protection in infection control among dental care workers.

Dental scaling and lower risk of spontaneous intracranial hemorrhage.

Background: -Spontaneous intracranial hemorrhage (ICH) has high fatality while has few proven treatments. We aim at investigating the association between dental scaling (DS) and the risk of ICH. Methods: -In this cohort study, two cohorts were matched by propensity score based on potential confounders. Data from ICH between January 2008 and December 2014 in Taiwan were analyzed. The subjects underwent DS at least 6 times between January 1, 2002, and December 31, 2007, while the matched controls did not undergo any DS during the same period. Cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing confounders. Results: -Each cohort consisted of 681,126 subjects. Compared with the non-DS cohort, the regular-DS cohort had a significantly lower incidence of ICH (0.8% vs 1.2%; P < 0.0001), and the adjusted hazards ratio (aHR) of 7-year ICH was 0.61 (95% confidence interval, CI, 0.59-0.63; P < 0.0001). The 30-39-year age group of the regular-DS cohort had the lowest HR (0.57; 95% CI, 0.52-0.61; P < 0.0001) of 7-year ICH when compared with similar controls. Compared with the controls, the regular-DS cohort also had significantly lower HR (0.82; 95% CI, 0.81-0.82; P < 0.0001) of 7-year hypertension. Compared with those without DS, the lowest risk of intracerebral hemorrhage was observed in the male participants with regular DS (0.43; 95% CI, 0.40-0.47; P < 0.0001). Conclusions: -Regular DS was consistently associated with lower ICH risk in subjects aged 30-59 years, which may benefit from the decreased HBP risk. DS had a potential role in the prophylaxis for ICH, a condition with a high disability or mortality.

Identification of the perpetrator imperatorin in Xin-yi-san-theophylline interaction: observed and predicted herb-drug interaction in rats.

OBJECTIVES: Theophylline is a bronchodilator with a narrow therapeutic index and primarily metabolised by cytochrome P450 (CYP) 1A2. Xin-yi-san (XYS) is a herbal formula frequently used to ameliorate nasal inflammation. This study aimed to investigate the effects of XYS and its ingredient, imperatorin, on theophylline pharmacokinetics in rats. METHODS: The kinetics of XYS- and imperatorin-mediated inhibition of theophylline oxidation were determined. Pharmacokinetics of theophylline were analysed. Comparisons were made with the CYP1A2 inhibitor, fluvoxamine. KEY FINDINGS: XYS extract and its ingredient, imperatorin, non-competitively inhibited theophylline oxidation. Fluvoxamine (50 and 100 mg/kg) and XYS (0.5 and 0.9 g/kg) significantly prolonged the time to reach the maximum plasma concentration (tmax) of theophylline by 3-10 fold. In a dose-dependent manner, XYS and imperatorin (0.1-10 mg/kg) treatments significantly decreased theophylline clearance by 27-33% and 19-56%, respectively. XYS (0.9 g/kg) and imperatorin (10 mg/kg) significantly prolonged theophylline elimination half-life by 29% and 142%, respectively. Compared with the increase (51-112%) in the area under curve (AUC) of theophylline by fluvoxamine, the increase (27-57%) by XYS was moderate. CONCLUSIONS: XYS decreased theophylline clearance primarily through imperatorin-suppressed theophylline oxidation. Further human studies are essential for the dose adjustment in the co-medication regimen.

The performance of the two-year postgraduate year dentist training program in Taiwan.

Background/purpose: The postgraduate year dentist training program (PGYD) officially implemented in 2010. This study aimed to assess PGYD trainees' subjective satisfaction perception and objective competence performance according to different training institutions (either dental clinics or hospitals). Materials and methods: A nationwide cross-sectional survey was conducted in 2018. Subjective satisfaction questionnaires from 222 PGYD trainees and 166 PGYD trainees' scores of objective structured clinical examinations (OSCEs) were collected for analysis. The t-test and logistic regression were used to compare differences between two groups. Results: In subjective satisfaction, PGYD trainees in hospitals revealed less positive perceptions on teachers (odds ratios [ORs] range: 0.33-0.7) and on training plans and auxiliary facilities (ORs range: 0.23-0.69), but they had more opportunities to attend and present at professional meetings than those in clinics. In PGYD trainees' opinion, the optimal training period allocation was 25% in hospitals and 75% in clinics. Overall, trainees in hospitals had better OSCE scores than those in clinics (OR [95% confidence interval, CI]: 3.12 [1.68-5.79]), except for the item of "the relation between physical condition and dental treatment outcome" (0.3 [0.1-0.97]). Conclusion: PGYD trainees in dental clinics have more positive perceptions on teachers and on training plans and auxiliary facilities, but PGYD trainees in hospitals have better OSCE scores. PGYD trainees prefer to be trained in clinics for a better connection with future careers, while hospitals can offer better training for PGYD trainees to become independent dentists because they have better training environment and more educational resources.

Carbon monoxide releasing molecule-2 attenuates angiotensin II-induced IL-6/Jak2/Stat3-associated inflammation by inhibiting NADPH oxidase- and mitochondria-derived ROS in human aortic smooth muscle cells.

Abdominal aortic aneurysm (AAA) is a common inflammatory vascular disease. Angiotensin II (Ang II) involves in AAA progression by promoting the proliferation and migration of vascular smooth muscle cells, the degradation of extracellular matrices, and the generation of ROS to lead to vascular inflammation. Carbon monoxide releasing molecule-2 (CORM-2) is known to exert anti-inflammatory and antioxidant activities. However, it remains unclear whether CORM-2 can suppress Ang II-induced vascular inflammation to prevent AAA progression. Therefore, this study aimed to investigate the vasoprotective effects of CORM-2 against Ang II-induced inflammatory responses of human aortic smooth muscle cells (HASMCs) and the underlying mechanisms of those effects. The results showed that Ang II induced inflammatory responses of HASMCs via NADPH oxidase- and mitochondria-derived ROS/NF-κB/IL-6/Jak2/Stat3 pathway which was attenuated by the pretreatment with CORM-2. Additionally, CORM-2 further exhibited anti-inflammatory activities in Ang II-stimulated HASMCs, as indicated by the reduction of monocyte adhesion to HASMCs and migration of HASMCs via the suppression of ICAM-1 and VCAM-1 as well as MMP-2 and MMP-9 levels, respectively. Moreover, Ang II-induced COX-2-mediated PGE2 secretion was also inhibited by the pretreatment with CORM-2. Importantly, our data demonstrated that CORM-2 reversed Ang II-induced IL-6 overexpression dependent on Nrf2 activation and HO-1 expression. Taken together, the present study indicates that CORM-2-induced Nrf2/HO-1 alleviates IL-6/Jak2/Stat3-mediated inflammatory responses to Ang II by inhibiting NADPH oxidase- and mitochondria-derived ROS, suggesting that CORM-2 is a promising pharmacologic candidate to reverse the pathological changes involved in the inflammation of vessel wall for the prevention and treatment of AAA.

WSG, a glucose-enriched polysaccharide from Ganoderma lucidum, suppresses tongue cancer cells via inhibition of EGFR-mediated signaling and potentiates cisplatin-induced apoptosis.

Tongue cancer, a kind of oral cancer, is common in Southeast Asian countries because of dietary habits. However, there is no specific targeted drug that could effectively inhibit oral cancer. WSG, as a water soluble glucose-enriched polysaccharide from Ganoderma lucidum, exerts excellent pharmacological efficacy of anti-lung cancer. However, its anticancer functions and mechanisms in human tongue cancer need to be further explored. Herein, we showed that WSG dramatically reduced cell viability and colony formation of tongue cancer cells. WSG increased subG1 and G2/M populations as well as induced apoptotic responses. In parallel, WSG enhanced apoptosis-related Bax/Bcl2 ratio. Mechanistic studies showed that WSG reduced phosphorylation of EGFR and AKT. In addition, we found a synergistic effect of WSG with cisplatin in inhibition of cell viability and induction of apoptosis. WSG significantly reduced the inhibition concentration 50% (IC50) of cisplatin. More importantly, WSG ameliorated cisplatin-induced cytotoxicity in normal human oral epithelial SG cells. In conclusion, our findings provided important insights into the anti-tongue cancer effects of WSG via inhibition of EGFR/AKT axis and induction of apoptosis, which indicated that WSG could be a promising supplement for tongue cancer treatment.

Comparison of Dental Surface Image Registration and Fiducial Marker Registration: An In Vivo Accuracy Study of Static Computer-Assisted Implant Surgery.

This study compared the accuracy of static computer-assisted implant surgery (sCAIS) planned through dental surface image registration and fiducial marker registration. Stone models of 30 patients were converted into digital dental casts by using a desktop scanner. Cone-beam computed tomography (CBCT) was performed and superimposed to the digital dental casts with two methods: matching the dental surface images or matching the fiducial markers on a stereolithographic radiographic template. Following the implant planning, stereolithographic surgical guides were fabricated, and 56 fully guided implants were inserted by the same doctor. Deviations between planned and inserted implants were measured and compared using postoperative CBCT images. After adjustment for other potential influencing factors, compared with the fiducial marker registration group, significantly larger mean lateral deviations were noted in the dental surface registration group at both the implant platform and apex (p = 0.0188 and 0.0371, respectively). However, the mean lateral deviations for the dental surface registration (0.83 ± 0.51 mm at implant platform and 1.24 ± 0.68 mm at implant apex) were comparable to the literature. In conclusion, our findings indicate that although sCAIS planned using dental surface image registration was not statistically as accurate as that using fiducial marker registration, its accuracy was satisfactory for clinical use.

The potentials of carbon monoxide-releasing molecules in cancer treatment: An outlook from ROS biology and medicine.

Carbon monoxide (CO) is now well recognized a pivotal endogenous signaling molecule in mammalian lives. The proof-of-concept employing chemical carriers of exogenous CO as prodrugs for CO release, also known as CO-releasing molecules (CO-RMs), has been appreciated. The major advantage of CO-RMs is that they are able to deliver CO to the target sites in a controlled manner. There is an increasing body of experimental studies suggesting the therapeutic potentials of CO and CO-RMs in different cancer models. This review firstly presents a short but crucial view concerning the characteristics of CO and CO-RMs. Then, the anticancer activities of CO-RMs that target many cancer hallmarks, mainly proliferation, apoptosis, angiogenesis, and invasion and metastasis, are discussed. However, their anticancer activities are varying and cell-type specific. The aerobic metabolism of molecular oxygen inevitably generates various oxygen-containing reactive metabolites termed reactive oxygen species (ROS) which play important roles in both physiology and pathophysiology. Although ROS act as a double-edged sword in cancer, both sides of which may potentially have been exploited for therapeutic benefits. The main focus of the present review is thus to identify the possible signaling network by which CO-RMs can exert their anticancer actions, where ROS play the central role. Another important issue concerning the potential effect of CO-RMs on the aerobic glycolysis (the Warburg effect) which is a feature of cancer metabolic reprogramming is given before the conclusion with future prospects on the challenges of developing CO-RMs into clinically pharmaceutical candidates in cancer therapy.

Melatonin rescues cerebral ischemic events through upregulated tunneling nanotube-mediated mitochondrial transfer and downregulated mitochondrial oxidative stress in rat brain.

BACKGROUND: Cerebral ischemic events, comprising of excitotoxicity, reactive oxygen production, and inflammation, adversely impact the metabolic-redox circuit in highly active neuronal metabolic profile which maintains energy-dependent brain activities. Therefore, we investigated neuro-regenerative potential of melatonin (Mel), a natural biomaterial secreted by pineal gland. METHODS: We specifically determined whether Mel could influence tunneling nanotubes (TNTs)-mediated transfer of functional mitochondria (Mito) which in turn may alter membrane potential, oxidative stress and apoptotic factors. In vitro studies assessed the effects of Mito on levels of cytochrome C, mitochondrial transfer, reactive oxygen species, membrane potential and mass, which were all further enhanced by Mel pre-treatment, whereas in vivo studies examined brain infarct area (BIA), neurological function, inflammation, brain edema and integrity of neurons and myelin sheath in control, ischemia stroke (IS), IS + Mito and IS + Mel-Mito group rats. RESULTS: Results showed that Mel pre-treatment significantly increased mitochondrial transfer and antioxidants, and inhibited apoptosis. Mel-pretreated Mito also significantly reduced BIA with improved neurological function. Apoptotic, oxidative-stress, autophagic, mitochondrial/DNA-damaged biomarkers indices were also improved. CONCLUSION: Conclusively, Mel is a potent biomaterial which could potentially impart neurogenesis through repairing impaired metabolic-redox circuit via enhanced TNT-mediated mitochondrial transfer, anti-oxidation, and anti-apoptotic activities in ischemia.

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.

The Adverse Impact of Incense Smoke on Human Health: From Mechanisms to Implications.

Incense burning is a very popular activity in daily life among many parts all over the world. A growing body of both epidemiological and experimental evidences has reported the negative effects of incense use on human well-being, posing a potential threat at public significance. This work is a comprehensive review that covers the latest findings regarding the adverse impact of incense smoke on our health, providing a panoramic visualization ranging from mechanisms to implications. The toxicities of incense smoke come directly from its harmful constituents and deposition capacity in the body. Besides, reactive oxygen species-driven oxidative stress and associated inflammation seem to be plausible underlying mechanisms, eliciting various unfavorable responses. Although our current knowledge remains many gaps, this issue still has some important implications.