Burden of oral disorders, 1990-2019: estimates from the Global Burden of Disease Study 2019.

Introduction: The aim of this study was to understand the global incidence and disability-adjusted life years (DALY) of oral disorders by age, gender, region, and Sociodemographic Index (SDI) from 1990 to 2019. Material and methods: The estimated annual percentage change (EAPC) and 95% confidence intervals (CIs) were used to assess the trends in age-standardized incidence and DALY rates from 1990 to 2019. Results: The global age-standardized incidence rate (EAPC = 0.01) of oral disorders increased slightly from 1990 to 2019. From 1990 to 2019, the age-standardized DALY rate decreased in high-SDI (EAPC = -0.43) and high-middle-SDI (EAPC = -0.14) regions, but it showed increasing trends in low-SDI (EAPC = 0.22), low-middle-SDI (EAPC = 0.36), and middle-SDI (EAPC = 0.17) regions. The EAPC in the age-standardized DALY rate was negatively correlated with the regional SDI value (ρ = -0.402, p = 0.001). From 1990 to 2019, the region with the largest increase in age-standardized DALY rate was South Asia (EAPC = 0.67), while the country with the greatest increase in age-standardized DALY rate was India (EAPC = 0.82). Conclusions: From 1990 to 2019, the global age-standardized incidence rate of oral disorders showed a slight increasing trend. It is necessary to control the increase in DALY and the disease burden associated with oral disorders in low-, low-middle-, and middle-SDI regions, such as South Asia, particularly in India.

Mitochondrial impairment and downregulation of Drp1 phosphorylation underlie the antiproliferative and proapoptotic effects of alantolactone on oral squamous cell carcinoma cells.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent and fatal oral cancers. Mitochondria-targeting therapies represent promising strategies against various cancers, but their applications in treating OSCC are limited. Alantolactone (ALT) possesses anticancer properties and also regulates mitochondrial events. In this study, we explored the effects of ALT on OSCC and the related mechanisms. METHODS: The OSCC cells were treated with varying concentrations and duration of ALT and N-Acetyl-L-cysteine (NAC). The cell viability and colony formation were assessed. The apoptotic rate was evaluated by flow cytometry with Annexin V-FITC/PI double staining. We used DCFH-DA and flow cytometry to detect reactive oxygen species (ROS) production and DAF-FM DA to investigate reactive nitrogen species (RNS) level. Mitochondrial function was reflected by mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP levels. KEGG enrichment analyses determined the mitochondrial-related hub genes involved in OSCC progression. Dynamin-related protein 1 (Drp1) overexpression plasmids were further transfected into the cells to analyze the role of Drp1 in OSCC progression. Immunohistochemistry staining and western blot verified the expression of the protein. RESULTS: ALT exerted anti-proliferative and pro-apoptosis effects on OSCC cells. Mechanistically, ALT elicited cell injury by promoting ROS production, mitochondrial membrane depolarization, and ATP depletion, which were reversed by NAC. Bioinformatics analysis showed that Drp1 played a crucial role in OSCC progression. OSCC patients with low Drp1 expression had a higher survival rate. The OSCC cancer tissues presented higher phosphorylated-Drp1 and Drp1 levels than the normal tissues. The results further showed that ALT suppressed Drp1 phosphorylation in OSCC cells. Moreover, Drp1 overexpression abolished the reduced Drp1 phosphorylation by ALT and promoted the cell viability of ALT-treated cells. Drp1 overexpression also reversed the mitochondrial dysfunction induced by ALT, with decreased ROS production, and increased mitochondrial membrane potential and ATP level. CONCLUSIONS: ALT inhibited proliferation and promoted apoptosis of oral squamous cell carcinoma cells via impairment of mitochondrial homeostasis and regulation of Drp1. The results provide a solid basis for ALT as a therapeutic candidate for treating OSCC, with Drp1 being a novel therapeutic target in treating OSCC.

SI ATRP for the Surface Modifications of Optically Transparent Paper Films Made by TEMPO-Oxidized Cellulose Nanofibers.

Applications of cellulose nanofibers currently match the demands of biodegradable and renewable constituent biocomposites. In this study, we studied the process of preparing TEMPO-oxidized cellulose nanofibers (TOCNs). These nano-sized cellulose fibers (ca. 11 nm) can be fabricated to high transmittance and optically transparent paper (OP) films. Then the OP films can be facilely immobilized initiating sites for the subsequent surface-initiated atom transfer radical polymerization (SI ATRP). We investigated SI ATRP with styrene (St) kinetics and monitored chemical structure changes of the OP surfaces. The obtained OP-g-PSt significantly led to enhance thermal stability and alter the OP surface with hydrophobic compared to that of pristine OP film. Characterization was studied by Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), UV-Vis spectroscopy, thermogravimetric analyzer (TGA), and water contact angle (WCA) measurements.

Effect of fibrin glue on the healing efficacy of deproteinized bovine bone and autologous bone in critical-sized calvarial defects in rats.

OBJECTIVES: In order to verify the hypothesis that fibrin glue (FG) is able to seal the area of bone grafting and facilitate bone regeneration. MATERIALS AND METHODS: Twenty-one Sprague-Dawley rats with critical-sized calvarial bone defects were randomly assigned to three groups: (A) co-administrated deproteinized bovine bone (DBB) and autologous bone grafts with FG [fibrin ( +)], (B) co-administrated DBB and autologous bone grafts without FG [fibrin ( -)], and (C) no graft as control. Four weeks and 8 weeks later, micro-CT analysis and histomorphometric analysis were carried out to evaluate following parameters: bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp), percentage of new bone area (Pe.NB), average thickness of bone defect (Th.BD), average thickness of basal bone (Th.BB), and percentage of new bone in center of the skull defect (Pe.NBc). RESULTS: BV/TV, Tb.Th, and Tb.N in fibrin ( -) group were significantly higher than that of fibrin ( +) group (p = 0.008, 0.000, 0.007, respectively) and control group (p = 0.004, 0.001, and 0.007, respectively) at 8 weeks. Pe.NB in fibrin ( -) group (33.67 ± 11.72%) was significantly higher than that of fibrin ( +) group (12.33 ± 3.21%) (p = 0.038) and control group (9.66 ± 8.50%) (p = 0.045) at 8 weeks. Pe.NBc in fibrin ( -) group (12.05 ± 3.91%) was significantly higher than that of fibrin ( +) group (4.79 ± 1.21%) (p = 0.005) and control group (0.00 ± 0.00%) (p = 0.000) at 4 weeks. CONCLUSIONS: Administration of both DBB and autograft stimulates calvarial bone defect regeneration, while combination of FG does not additionally accelerate new bone formation. CLINICAL RELEVANCE: The use of fibrin to cement traditional bone graft materials in oral clinical practice requires caution.

Miktoarm Star Copolymers Prepared by Transformation from Enhanced Spin Capturing Polymerization to Nitroxide-Mediated Polymerization (ESCP-T-NMP) toward Nanomaterials.

Reversible-deactivation radical polymerization (RDRP) serves as a powerful tool nowadays for the preparations of unique linear and non-linear macromolecules. In this study, enhanced spin capturing polymerizations (ESCPs) of styrene (St) and tert-butyl acrylate (tBA) monomers were, respectively, conducted in the presence of difunctional (1Z,1'Z)-1,1'-(1,4-phenylene) bis (N-tert-butylmethanimine oxide) (PBBN) nitrone. Four-arm (PSt)4 and (PtBA)4 star macroinitiators (MIs) can be afforded. By correspondingly switching the second monomer (i.e., tBA and St), miktoarm star copolymers (µ-stars) of (PSt)2-µ-(PtBA-b-PSt)2 and (PtBA)2-µ-(PSt-b-PtBA)2) were thus obtained. We further conducted hydrolysis of the PtBA segments to PAA (i.e., poly(acrylic acid)) in µ-stars to afford amphiphilic µ-stars of (PSt)2-µ-(PAA-b-PSt)2 and (PAA)2-µ-(PSt-b-PAA)2. We investigated each polymerization step and characterized the obtained two sets of "sequence-isomeric" µ-stars by FT-IR, 1H NMR, differential scanning calorimeter (DSC), and thermogravimetric analysis (TGA). Interestingly, we identified their physical property differences in the case of amphiphilic µ-stars by water contact angle (WCA) and atomic force microscopy (AFM) measurements. We thus proposed two microstructures caused by the difference of polymer chain sequences. Through this polymerization transformation (T) approach (i.e., ESCP-T-NMP), we demonstrated an interesting and facile strategy for the preparations of µ-stars with adjustable/switchable interior and exterior polymer structures toward the preparations of various nanomaterials.

Preparations of Tough and Conductive PAMPS/PAA Double Network Hydrogels Containing Cellulose Nanofibers and Polypyrroles.

To afford an intact double network (sample abbr.: DN) hydrogel, two-step crosslinking reactions of poly(2-acrylamido-2-methylpropanesulfonic acid) (i.e., PAMPS first network) and then poly(acrylic acid) (i.e., PAA second network) were conducted both in the presence of crosslinker (N,N'-methylenebisacrylamide (MBAA)). Similar to the two-step processes, different contents of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) oxidized cellulose nanofibers (TOCN: 1, 2, and 3 wt.%) were initially dispersed in the first network solutions and then crosslinked. The TOCN-containing PAMPS first networks subsequently soaked in AA and crosslinker and conducted the second network crosslinking reactions (TOCN was then abbreviated as T for DN samples). As the third step, various (T-)DN hydrogels were then treated with different concentrations of FeCl3(aq) solutions (5, 50, 100, and 200 mM). Through incorporations of ferric ions into (T-)DN hydrogels, notably, three purposes are targeted: (i) strengthen the (T-)DN hydrogels through ionic bonding, (ii) significantly render ionic conductivity of hydrogels, and (iii) serve as a catalyst for the forth step to proceed with in situ chemical oxidative polymerizations of pyrroles to afford polypyrrole-containing (sample abbr.: Py) hydrogels [i.e., (T-)Py-DN samples]. The characteristic functional groups of PAMPS, PAA, and Py were confirmed by FT-IR. Uniform microstructures were observed by cryo scanning electron microscopy (cryo-SEM). These results indicated that homogeneous composites of T-Py-DN hydrogels were obtained through the four-step process. All dry samples showed similar thermal degradation behaviors from the thermogravimetric analysis (TGA). The T2-Py5-DN sample (i.e., containing 2 wt.% TOCN with 5 mM FeCl3(aq) treatment) showed the best tensile strength and strain at breaking properties (i.e., σTb = 450 kPa and εTb = 106%). With the same compositions, a high conductivity of 3.34 × 10-3 S/cm was acquired. The tough T2-Py5-DN hydrogel displayed good conductive reversibility during several "stretching-and-releasing" cycles of 50-100-0%, demonstrating a promising candidate for bioelectronic or biomaterial applications.

Nobiletin inhibits cell growth through restraining aerobic glycolysis via PKA-CREB pathway in oral squamous cell carcinoma.

BACKGROUND/AIM: Nobiletin is a polymethoxylated flavone enriched in Citrus and is used as an important drug in traditional Chinese medicine for various kinds of diseases. Among its multiple functions, it has shown that nobiletin inhibits proliferation of various cancer cells. However, it is unclear whether nobiletin inhibits the growth of oral squamous cell carcinoma (OSCC) cells. MATERIALS AND METHODS: We explored the antitumor effects of nobiletin in TCA-8113 and CAL-27 oral squamous cells. The Cell Counting Kit-8 (CCK8) assay was used to measure cell vitality. Flow cytometry was performed to measure the number of cells in the various phases of the cell cycle. PCR and Western blot were applied to determine mRNA and protein expression, respectively. RESULTS: Nobiletin inhibited proliferation of TCA-8113 and CAL-27 cells via inducing cell cycle arrest at the G1 phase. In addition, the levels of phosphorylated-PKA and phosphorylated-CREB were reduced in nobiletin-treated TCA-8113 and CAL-27 cells. Importantly, our results showed that nobiletin treatment resulted in impaired mitochondrial function and altered glucose consumption, and pyruvate and lactate production. Lastly, nobiletin was found to inhibit the generation of xenografts in vivo. Interestingly, administration of 50 µmol/L Sp-cAMP, a potent PKA activator, rescued all phenotypes caused by nobiletin. CONCLUSIONS: Nobiletin inhibits OSCC cell proliferation in a mitochondria-dependent manner, indicating that it may have a promising role in cancer treatment and attenuation of drug resistance.

Heat Transfer of Semicrystalline Nylon Nanofibers.

Polymers are generally regarded as thermal insulators. The efficient heat transfer observed in the low-dimensional polymers in the literature mainly result from the larger crystallinity or improved polymer chain orientation in the low-dimensional polymers. However, the role of the amorphous domain on heat transfer in polymers remains unexplored. In this work, we report that the semicrystalline nylon polymer nanofibers can exhibit a very large thermal conductivity of 59.1 ± 3.1 W m-1 K-1 and the heat transfer in the semicrystalline polymer nanofibers was time-dependent. The thermal conductivity of the nanofibers could be modulated to span 3 orders of magnitude from being nearly insulated (∼0.27 ± 0.02 W m-1 K-1) to being highly thermal conductive after annealing (∼59.1 ± 3.1 W m-1 K-1). The time-dependent thermal conductivity was observed at a temperature lower than the gamma transition temperature of the polymer and was a result of the physical aging of the semicrystalline polymer. A phenomenological model was adopted to explain the time-dependent heat transfer of the semicrystalline nanofibers. The physical aging reduced the configuration disorder in the polymer and caused the heat transfer of the semicrystalline polymer to increase during the annealing process.

Surface-Initiated Initiators for Continuous Activator Regeneration (SI ICAR) ATRP of MMA from 2,2,6,6-tetramethylpiperidine-1-oxy (TEMPO) Oxidized Cellulose Nanofibers for the Preparations of PMMA Nanocomposites.

An effective method of oxidation from paper pulps via 2,2,6,6-tetramethylpiperidine-1-oxy (TEMPO) compound to obtain TEMPO-oxidized cellulose nanofibers (TOCNs) was demonstrated. Following by acylation, TOCN having an atom transfer radical polymerization (ATRP) initiating site of bromoisobutyryl moiety (i.e., TOCN-Br) was successfully obtained. Through a facile and practical technique of surface-initiated initiators for continuous activator regeneration atom transfer radical polymerization (SI ICAR ATRP) of methyl methacrylate (MMA) from TOCN-Br, controllable grafting polymer chain lengths (Mn = ca. 10k-30k g/mol) with low polydispersity (PDI < 1.2) can be achieved to afford TOCN-g-Poly(methyl methacrylate) (PMMA) nanomaterials. These modifications were monitored by Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), electron spectroscopy for chemical analysis (ESCA), and water contact angle analysis. Eventually, TOCN-g-PMMA/PMMA composites were prepared using the solvent blending method. Compared to the pristine PMMA (Tg = 100 °C; tensile strength (σT) = 17.1 MPa), the composites possessed high transparency with enhanced thermal properties and high tensile strength (Tg = 110 °C and σT = 37.2 MPa in 1 wt% TOCN containing case) that were investigated by ultraviolet-visible spectroscopy (UV-Vis), thermogravimetric analysis (TGA), dynamic mechanical analysis (DMA), and tensile tests. We demonstrated that minor amounts of TOCN-g-PMMA nanofillers can provide high efficacy in improving the mechanical and thermal properties of PMMA matrix.

Size effect of nano-hydroxyapatite on proliferation of odontoblast-like MDPC-23 cells.

Nano-hydroxyapatite (nano-HAP) is supposed to be a promising candidate for apatite substitute in hard tissue engineering. We aimed to investigate the effect of nano-HAP particles on the proliferation of odontoblast-like MDPC-23 cells compared with conventional hydroxyapatite (c-HAP). HAP in diameter of ~20 nm (np20), ~70 nm (np70) and ~200 nm (c-HAP) were synthesized and characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM). Inverted microscope and MTT assay were used to detect the morphology and proliferation rate of MDPC-23 cells; TEM was used to reveal the internalization of HAP. We found that nano-HAP (np20 and np70), especially np20 expressed obvious growth-promoting effect on MDPC-23 cells compared with c-HAP, which caused the most vacuole in MDPC-23 cells. These results suggest that nano-HAP may be an optimal choice of apatite substitute for MDPC-23 cells on the aspect of cell proliferation.

Curcumin analog EF24 induces apoptosis and downregulates the mitogen activated protein kinase/extracellular signal-regulated signaling pathway in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide. Diphenyldifluoroketone (EF24) is a curcumin analog that has been demonstrated to improve anticancer activity; however, its therapeutic potential and mechanisms in oral cancer remain unknown. In the present study, the effect of EF24 on apoptosis induction and its potential underlying mechanism in the CAL­27 human OSCC cell line was investigated. To achieve this, various concentrations of cisplatin or EF24 were administrated to CAL­27 cells for 24 h, and cell viability, apoptotic DNA fragmentation, and cleaved caspase 3 and 9 levels were evaluated. To investigate the potential underlying mechanism, the levels of mitogen­activated protein kinase kinase 1 (MEK1) and extracellular signal­regulated kinase (ERK), two key proteins in the mitogen­activated protein kinase/ERK signaling pathway, were additionally examined. The results indicated that EF24 and cisplatin treatment decreased cell viability. EF24 treatment increased the levels of activated caspase 3 and 9, and decreased the phosphorylated forms of MEK1 and ERK. Sequential treatments of EF24 and 12­phorbol­13­myristate acetate, a MAPK/ERK activator, resulted in a significant increase of activated MEK1 and ERK, and reversed cell viability. These results suggested that EF24 has potent anti­tumor activity in OSCC via deactivation of the MAPK/ERK signaling pathway. Further analyses using animal models are required to confirm these findings in vivo.

Tunable mesoporous lamellar silicas prepared using poly(ethylene oxide-b-L-lactide) and poly(ethylene-b-ethylene oxide-b-L-lactide) block copolymers as templates.

In this study, we synthesized poly(ethylene oxide-b-L-lactide) (PEO-PLLA) diblock copolymers and poly(ethylene-b-ethylene oxide-b-L-lactide) (PE-PEO-PLLA) triblock terpolymers as templates for the preparation of mesoporous lamellar silicas, possessing single, bimodal, or trimodal pore size distributions, through an evaporation-induced self-assembly (EISA) approach. As templates, we synthesized the diblock copolymers EO114LLA26 and EO114LLA130 and the triblock terpolymers E13EO42LLA26 and E13EO42LLA35 using simple ring-opening polymerization. Small-angle X-ray scattering, transmission electron microscopy, and N2 sorption measurements revealed that the mesoporous silicas displayed the morphologies of either lamellar silica walls featuring a distribution of many short cylindrical mesopores or pure lamellar structures. The morphology was greatly affected by the nature of the template (diblock or triblock copolymer) and the molecular weight of the PLLA segment in the block copolymer.