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Fidelity estimation is an important technique for evaluating prepared quantum states in noisy quantum devices. A recent theoretical work proposed a frugal approach called neural quantum fidelity estimation (NQFE) [X. Zhang et al., Phys. Rev. Lett. 127, 130503 (2021).PRLTAO0031-900710.1103/PhysRevLett.127.130503]. While this requires a much smaller number of measurement operators than full quantum state tomography, it uses a weight-based floating measurement strategy that predetermines the top global Pauli operators that contribute the most to the fidelity and uses discrete fidelity intervals as predictions. In this Letter, we develop a measurement-fixed NQFE based on a transformer model which requires less measurement cost and can output continuous estimates of fidelity. Here we further experimentally apply the NQFE in a realistic situation using a nuclear spin quantum processor. We prepare the ground states of local Hamiltonians and arbitrary states and investigate how to estimate their fidelity with reference states, and we compare the fidelity estimation strategy with our and the original NQFE to conventional tomography. It is shown that NQFE can estimate the fidelity with comparable accuracy to the tomography approach. In the future, NQFE will become an important tool for benchmarking quantum states ahead of the advent of well-trusted fault-tolerant quantum computers.
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We report a voltage-tunable reflective gold wire grid metasurface on vanadium dioxide thin film, which consists of a metal-insulator-metal (MIM) structure. We excite surface plasmon polariton (SPP) modes on the gold surface by fabricating a one-dimensional structured gold wire grid. Joule heating of laser-induced graphene (LIG) can be controlled by the voltage at the bottom, allowing vanadium dioxide in the structure to complete the transition from the insulating state to the metallic state. The phase transition of vanadium dioxide strongly disrupts the plasmon modes excited by the gold wire grid above, thereby realizing a huge change in the reflection spectrum. This acts as a tunable metasurface optical switch with a maximum modulation depth (MD) of over 20â dB. We provide a more effective and simple method for creating tunable metasurfaces in the near-infrared band, which can allow metasurfaces to have wider applications in optical signal processing, optical storage, and holography.
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The Keratoconus (KC) is a corneal ectatic disease with unclear etiology. There are increasing studies that reported its association with a variety of inflammatory mechanisms. Vitamin A(VA) is an important nutrient related to inflammation regulation, and its deficiency may cause abnormalities of the ocular surface. However, the proportion of Vitamin A deficiency(VAD) was found surprisingly high among KC patients in our clinic practice. The aim of this study is to explore the effects of VAD on the transcriptome of corneas with the help of the VAD murine model and transcriptomics techniques. Blood samples of KC patients and non-KC controls (NC) were collected and the serum VA concentrations were measured and analyzed. A total of 52 NC and 39 KC were enrolled and the comparison of serum VA showed that the proportion of VAD in KC patients was 48.7% versus 1.9% in NC group. The further analysis of gender differences showed the proportion of VAD in female KC was 88.9% versus 36.7% in KC male patients. To explore the influence of VAD on cornea, the VAD mice fed with VAD diets were used. The RNA sequencing was employed to compare the corneal transcriptomic characteristics between the VAD female mice, NC female mice, VAD male mice and NC male mice. The transcriptome analysis revealed that the upregulated differential genes were mainly enriched in the immune response related pathways in VAD female mice versus NC female mice, especially the genes of JAK-STAT signaling pathway. The downstream molecules of JAK-STAT pathway were also significant after corneal mechanical scratching in female VAD mice. While, the differential genes between VAD male mice and NC male mice were estrogen signaling pathway instead of JAK-STAT pathway. This study indicates that VAD affects the transcriptomics of murine cornea with gender differences, which specifically affects the inflammatory status of the female murine cornea.
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Ceratocone , Vitamina A , Humanos , Masculino , Animais , Feminino , Camundongos , Janus Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Córnea/metabolismo , Ceratocone/genética , Ceratocone/metabolismoRESUMO
BACKGROUND: Polarity is necessary for epithelial cells to perform distinct functions at their apical and basal surfaces. Oral epithelial cell-derived ameloblasts at secretory stage (SABs) synthesize large amounts of enamel matrix proteins (EMPs), largely amelogenins. EMPs are unidirectionally secreted into the enamel space through their apical cytoplasmic protrusions, or Tomes' processes (TPs), to guide the enamel formation. Little is known about the transcriptional regulation underlying the establishment of cell polarity and unidirectional secretion of SABs. RESULTS: The higher-order chromatin architecture of eukaryotic genome plays important roles in cell- and stage-specific transcriptional programming. A genome organizer, special AT-rich sequence-binding protein 1 (SATB1), was discovered to be significantly upregulated in ameloblasts compared to oral epithelial cells using a whole-transcript microarray analysis. The Satb1-/- mice possessed deformed ameloblasts and a thin layer of hypomineralized and non-prismatic enamel. Remarkably, Satb1-/- ameloblasts at the secretory stage lost many morphological characteristics found at the apical surface of wild-type (wt) SABs, including the loss of Tomes' processes, defective inter-ameloblastic adhesion, and filamentous actin architecture. As expected, the secretory function of Satb1-/- SABs was compromised as amelogenins were largely retained in cells. We found the expression of epidermal growth factor receptor pathway substrate 8 (Eps8), a known regulator for actin filament assembly and small intestinal epithelial cytoplasmic protrusion formation, to be SATB1 dependent. In contrast to wt SABs, EPS8 could not be detected at the apical surface of Satb1-/- SABs. Eps8 expression was greatly reduced in small intestinal epithelial cells in Satb1-/- mice as well, displaying defective intestinal microvilli. CONCLUSIONS: Our data show that SATB1 is essential for establishing secretory ameloblast cell polarity and for EMP secretion. In line with the deformed apical architecture, amelogenin transport to the apical secretory front and secretion into enamel space were impeded in Satb1-/- SABs resulting in a massive cytoplasmic accumulation of amelogenins and a thin layer of hypomineralized enamel. Our studies strongly suggest that SATB1-dependent Eps8 expression plays a critical role in cytoplasmic protrusion formation in both SABs and in small intestines. This study demonstrates the role of SATB1 in the regulation of amelogenesis and the potential application of SATB1 in ameloblast/enamel regeneration.
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Ameloblastos/fisiologia , Amelogênese , Polaridade Celular , Esmalte Dentário/crescimento & desenvolvimento , Proteínas de Ligação à Região de Interação com a Matriz/genética , Animais , Diferenciação Celular , Humanos , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , CamundongosRESUMO
PURPOSE: The purpose of this study was to evaluate the long-term incidence, risk factors, and the management of corneal melt following Boston type I keratoprosthesis (B-KPro I) implantation. METHODS: This is a retrospective observational case series. Data were collected regarding demographics, preoperative characteristics, incidence, and outcomes of corneal melt in 102 patients who underwent B-KPro I in the Chinese PLA General Hospital between 2011 and 2018, with a follow-up period ranging from 4 to 11 years. RESULTS: Chemical burn was the most common indication for B-KPro I (n = 56; 53.8%), followed by ocular trauma (n = 26; 25.0%). During the follow-up period (107 ± 25.7 months), corneal melt occurred in 60 cases among 37 eyes (35.6%), with an incidence of 20.2% at 1 year after surgery. Fourteen cases presented with recurrent corneal melt. Patients with multiple corneal allograft failures had a higher risk of corneal melt. Thermal burns, compared with alkali burns, significantly elevated the odds ratio (OR) of corneal melt (OR, 5.11; 95% confidence interval, 1.05-24.86; P = 0.043). CONCLUSIONS: Corneal melt significantly reduced the retention time of KPro ( P < 0.01), and its coexistence with other complications further shortened the retention time. A specific pattern of corneal melt occurrence was identified, with a peak incidence at 1 year postoperatively. Our findings suggest variations in the risk of corneal melt among different indications, with thermal burns carrying the highest OR. Moreover, each previous failed keratoplasty doubled the risk of corneal melt after B-KPro I.
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Doenças da Córnea , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Doenças da Córnea/cirurgia , Incidência , Idoso , Fatores de Risco , Córnea , Acuidade Visual/fisiologia , China/epidemiologia , Seguimentos , Complicações Pós-Operatórias , Órgãos Artificiais , Hospitais Gerais , Implantação de Prótese , Queimaduras Oculares/cirurgia , Adulto Jovem , Próteses e Implantes , Adolescente , Hospitais Militares , População do Leste AsiáticoRESUMO
OBJECTIVE: All-trans retinoic acid (ATRA) has been demonstrated to inhibit tumor growth by restoration of gap junctional intercellular communication (GJIC) via upregulation of connexin (Cx) expression in some solid tumors. However, the relationship between ATRA and GJIC remains unclear in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the effect of ATRA on the GJIC function of OSCC. STUDY DESIGN: We measured the effects of ATRA on the viability and cell cycle distribution of SCC9 and Tca8113 OSCC cells. The GJIC function was observed using the scrape-loading dye transfer technique, and the mRNA and protein levels of Cx32 and Cx43 were detected by qRT-PCR, Western blot, and immunofluorescence assays. RESULTS: ATRA inhibited the growth of OSCC cells in a dose- and time-dependent manner (P <0.05) and caused cell cycle arrest. ATRA-treated cells showed a 2.69-fold and 2.06-fold enhancement of GJIC in SCC9 and Tca8113 cells, respectively (P <0.05). Moreover, ATRA induced upregulation of Cx32 and Cx43 at both the mRNA and protein levels in OSCC cells. CONCLUSION: Our results indicated that restoration of GJIC via enhanced Cx32 and Cx43 expression might serve as a novel mechanism for the anti-tumor effect of ATRA in OSCC.
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Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Comunicação Celular/efeitos dos fármacos , Conexina 43/biossíntese , Conexinas/biossíntese , Junções Comunicantes/efeitos dos fármacos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Tretinoína/farmacologia , Regulação para Cima , Regulação Neoplásica da Expressão Gênica , Humanos , RNA Mensageiro/biossíntese , Células Tumorais Cultivadas , Proteína beta-1 de Junções ComunicantesRESUMO
PURPOSE: To assess the levels of oral health-related quality of life (OHRQoL) in orthodontic patients both during the suspension of dental services caused by COVID-19 and after a year of dental service reinstatement, and to evaluate the associated factors for OHRQoL in those patients during the suspension period. MATERIALS AND METHODS: A cross-sectional online study was conducted both during the suspension of dental service due to COVID-19 (T1) and after a year of dental service reinstatement (T2). The questionnaire - consisting of personal information, subjective complaints, OHIP-14 and oral health conditions - was completed by the participants at T1 and T2. Data were evaluated by the Χ2 test, the Wilcoxon rank-sum test, and multivariate logistic regression analysis. RESULTS: 324 participants were ultimately included in the study sample. The participants reported higher OHIP-14 total scores at T1 than T2 (p < 0.001). Statistically significant differences were detected in the domains psychological discomfort, psychological disability, social disability and handicap (p < 0.001). The multivariate logistic regression analysis showed that wearing fixed appliances, being over 18 years old, having delayed orthodontic treatment and poor oral hygiene habits were statistically significantly associated with higher OHIP-14 total scores at T1 (p < 0.05). CONCLUSION: The OHRQoL in orthodontic patients was negatively impacted by the suspension of dental services during COVID-19, which was reflected in all the psychosocial domains. Types of appliances, ages, delays in follow-up visits and oral hygiene habits seemed to be the factors associated with OHRQoL in orthodontic patients during the suspension.
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COVID-19 , Qualidade de Vida , Humanos , Adolescente , Qualidade de Vida/psicologia , Saúde Bucal , Estudos Transversais , Pandemias , COVID-19/epidemiologia , Assistência Odontológica , Inquéritos e QuestionáriosRESUMO
We propose a heat-reconfigurable metasurface composed of the silicon-based gold grating. The asymmetric Fano-like line shape is formed due to the mutual coupling of the local surface plasmon (LSP) in the gap between the two layers of Au gratings and the surface propagating plasmon (SPP) on the surface of the Au gratings. Then, we effectively regulate the Fano resonance by applying a bias voltage to laser-induced graphene (LIG), to generate Joule heat, so that the resonant dip of one mode of the Fano resonance can shift up to 28.5 nm. In contrast, the resonant dip of the other mode barely changes. This effectively regulates the coupling between two resonant modes in Fano resonance. Our study presents a simple and efficient method for regulating Fano-like interference in the near-infrared band.
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Enamel development is a process in which extracellular matrix models from a soft proteinaceous matrix to the most mineralized tissue in vertebrates. Patients with mutant NCKX4, a gene encoding a K+-dependent Na+/Ca2+-exchanger, develop a hypomineralized and hypomature enamel. How NCKX4 regulates enamel protein removal to achieve an almost protein-free enamel is unknown. We characterized the upregulation pattern of Nckx4 in the progressively differentiating enamel-forming ameloblasts by qPCR, and as well as confirmed NCKX4 protein to primarily localize at the apical surface of wild-type ruffle-ended maturation ameloblasts by immunostaining of the continuously growing mouse incisors, posing the entire developmental trajectory of enamel. In contrast to the normal mature enamel, where ECM proteins are hydrolyzed and removed, we found significant protein retention in the maturation stage of Nckx4 -/- mouse enamel. The Nckx4 -/- enamel held less Ca2+ and K+ but more Na+ than the Nckx4 +/+ enamel did, as measured by EDX. The alternating acidic and neutral pH zones at the surface of mineralizing Nckx4 +/+ enamel were replaced by a largely neutral pH matrix in the Nckx4 -/- enamel. In situ zymography revealed a reduced kallikrein-related peptidase 4 (KLK4) activity in the Nckx4 -/- enamel. We showed that KLK4 took on 90% of proteinase activity in the maturation stage of normal enamel, and that recombinant KLK4 as well as native mouse enamel KLK4 both performed less effectively in a buffer with increased [Na+] and pH, conditions found in the Nckx4 -/- developing enamel. This study, for the first time to our knowledge, provides evidence demonstrating the impaired in situ KLK4 activity in Nckx4 -/- enamel and suggests a novel function of NCKX4 in facilitating KLK4-mediated hydrolysis and removal of ECM proteins, warranting the completion of enamel matrix modeling.
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Metasurface has attracted massive interest owing to its ability to control light arbitrarily in a wide range of applications, such as high-speed imaging, optical interconnection, and spectroscopy. Here we propose a free space light modulator combined with a gold grating metasurface based on lithium niobate (LiNbO3). The quasi-bound states in the continuum (quasi-BIC) are achieved in the metasurface. In addition, the plasmonic quasi-BIC and the guided-mode resonance (GMR) can be modulated by controlling the polarization of the incident light without any geometric adjustment. Thus, the working wavelength range from 1480 nm to 1620 nm was achieved, and the maximum resonance depth reached about 51% at the resonant wavelength. In addition, the insertion loss of the device was -2.8 dB at a wavelength of 1510 nm. Furthermore, the dynamic modulation speed reached up to 190 MHz and the highest signal-to-noise ratio (SNR) could reach about 49 dB at a frequency of 65 MHz. The data showed potential for the material for applications such as near-infrared imaging, beam steering, and free-space optical communication links.
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Amelogenins containing exons 8 and 9 are alternatively spliced variants of amelogenin. Some amelogenin spliced variants have been found to promote pulp regeneration following pulp exposure. The function of the amelogenin spliced variants with the exons 8 and 9 remains unknown. In this study, we synthesized recombinant leucine rich amelogenin peptide (LRAP, A-4), LRAP plus exons 8 and 9 peptide (LRAP 8, 9) or exons 8 and 9 peptide (P89), to determine their effects on odontoblasts. In vivo analyses were completed following the insertion of agarose beads containing LRAP or LRAP 8, 9 into exposed cavity preparations of rat molars. After 8, 15 or 30 days' exposure, the pulp tissues were analyzed for changes in histomorphometry and cell proliferation by PCNA stainings. In vitro analyses included the effects of the addition of the recombinant proteins or peptide on cell proliferation, differentiation and adhesion of postnatal human dental pulp cells (DPCs). These studies showed that in vivo LRAP 8, 9 enhanced the reparative dentin formation as compared to LRAP. In vitro LRAP 8, 9 promoted DPC proliferation and differentiation to a greater extent than LRAP. These data suggest that amelogenin exons 8 and 9 may be useful in amelogenin-mediated pulp repair.
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Amelogenina/genética , Proteínas do Esmalte Dentário/genética , Polpa Dentária/fisiologia , Éxons , Odontoblastos/metabolismo , Animais , Processos de Crescimento Celular/genética , Polpa Dentária/metabolismo , Polpa Dentária/patologia , Modelos Animais de Doenças , Humanos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: The chemokine receptor CXCR4 and its ligand CXCL12 have been suggested to play important roles in the initiation or progression of cancers. The goal of the present study was to investigate alterations of CXCL12/CXCR4 in oral premalignant lesions and oral squamous cell carcinoma (OSCC). METHODS: In 13 normal oral epithelia, 24 dysplastic oral leukoplakia (OLK), and 40 OSCC specimens, expressions of CXCL12 and CXCR4 were evaluated by immunohistochemistry. RESULTS: CXCR4 was expressed in 37.5% of OLK and 60% of OSCC. CXCL12 was detected in 50% of OLK and 62.5% of OSCC. In OLK, CXCR4 positive ratio showed no significant difference from normal epithelia, but the CXCL12 positive ratio was significantly higher. Significant relationship between CXCL12 and CXCR4 was found both in OLK and OSCC. CONCLUSION: Our results indicated that CXCL12/CXCR4 axis may play roles from early steps of oral malignant transformation and contribute to the progress of oral carcinogenesis.
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Carcinoma de Células Escamosas/metabolismo , Quimiocina CXCL12/metabolismo , Neoplasias Bucais/metabolismo , Lesões Pré-Cancerosas/metabolismo , Receptores CXCR4/metabolismo , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Leucoplasia Oral/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
INTRODUCTION: As important effector cells of the innate immune system, neutrophils are involved in rejection of solid organ and/or tissue transplants. But their role in rejection of oral mucosa transplantation (OMT) remains unclear. The aim of this study is to observe the spatial-temporal change of neutrophils during acute rejection of OMT. METHODS: In a rat model of oral mucosal xenotransplantation, myeloperoxidase (MPO), an indicator of influx of neutrophils was detected by technique of ELISA on day 7 and 30 (D7, D30) of posttransplantation. RESULTS: On D7, MPO level (6.183±0.416, x102 ng/mg) in the OMT group was significantly higher than in trauma (0.681±0.073, x102 ng/mg) and normal controls (0.262±0.043, x102 ng/mg) (P<0.001, respectively), and this level was found to correlate with the index of submandibular lymph nodes (ILN), an indicator of inflammation of rejection (r=0.909, P<0.05). Moreover, this level was decreased significantly under FK506 treatment (2.103±0.146, x102 ng/mg, P=0.005). On D30, MPO in the OMT group (1.063±0.096, x102 ng/mg) was lower significantly than that on D7 (P<0.001), although this level was still higher that of normal controls on D30 (0.532±0.112, x102 ng/mg, P=0.042). CONCLUSION: Neutrophils infiltration was an early event of OMT, which may play important roles on acute rejection of OMT.
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Mucosa Bucal/transplante , Infiltração de Neutrófilos , Animais , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Ratos , Ratos Wistar , Fatores de Tempo , Transplante HeterólogoRESUMO
Amelogenins, the principal proteins in the developing enamel microenvironment, self-assemble into supramolecular structures to govern the remodeling of a proteinaceous organic matrix into longitudinally ordered hydroxyapatite nanocrystal arrays. Extensive in vitro studies using purified native or recombinant proteins have revealed the potential of N-terminal amelogenin on protein self-assembly and its ability to guide the mineral deposition. We have previously identified a 14-aa domain (P2) of N-terminal amelogenin that can self-assemble into amyloid-like fibrils in vitro. Here, we investigated how this domain affects the ability of amelogenin self-assembling and stability of enamel matrix protein scaffolding in an in vivo animal model. Mice harboring mutant amelogenin lacking P2 domain had a hypoplastic, hypomineralized, and aprismatic enamel. In vitro, the mutant recombinant amelogenin without P2 had a reduced tendency to self-assemble and was prone to accelerated hydrolysis by MMP20, the prevailing metalloproteinase in early developing enamel matrix. A reduced amount of amelogenins and a lack of elongated fibrous assemblies in the development enamel matrix of mutant mice were evident compared with that in the wild-type mouse enamel matrix. Our study is the first to demonstrate that a subdomain (P2) at the N-terminus of amelogenin controls amelogenin's assembly into a transient protein scaffold that resists rapid proteolysis during enamel development in an animal model. Understanding the building blocks of fibrous scaffold that guides the longitudinal growth of hydroxyapatites in enamel matrix sheds light on protein-mediated enamel bioengineering. © 2021 American Society for Bone and Mineral Research (ASBMR).
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Amelogênese , Proteínas do Esmalte Dentário , Amelogenina/metabolismo , Animais , Camundongos , Domínios Proteicos , Proteólise , Proteínas Recombinantes/metabolismoRESUMO
Biomaterials as bone substitutes are always considered as foreign bodies that can trigger host immune responses. Traditional designing principles have been always aimed at minimizing the immune reactions by fabricating inert biomaterials. However, clinical evidence revealed that those methods still have limitations and many of which were only feasible in the laboratory. Currently, osteoimmunology, the very pioneering concept is drawing more and more attention-it does not simply regard the immune response as an obstacle during bone healing but emphasizes the intimate relationship of the immune and skeletal system, which includes diverse cells, cytokines, and signaling pathways. Properties of biomaterials like topography, wettability, surface charge, the release of cytokines, mediators, ions and other bioactive molecules can impose effects on immune responses to interfere with the skeletal system. Based on the bone formation mechanisms, the designing methods of the biomaterials change from immune evasive to immune reprogramming. Here, we discuss the osteoimmunomodulatory effects of the new modification strategies-adjusting properties of bone biomaterials to induce a favorable osteoimmune environment. Such strategies showed potential to benefit the development of bone materials and lay a solid foundation for the future clinical application.
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BACKGROUND: Label-retaining cells (LRCs), the presumptive stem cells, have been detected in the mouse and hamster oral epithelia, but the data on LRCs in rat oral epithelia have not been available yet. The aim of this study was to identify LRCs in oral squamous epithelia of rat. METHODS: Fifty-four two-week-old Sprague-Dawley rats were injected intraperitoneally with BrdU twice daily for four consecutive days. The BrdU-labeled rats were sacrificed at 2 h, week 2, 4, 6, 8, 10, 12, 14 and 16 after the last BrdU injection. The tissues of cheek, tongue and palate were analyzed by techniques of fluorescence-activated cell sorting (FACS) and immunohistochemistry. RESULTS: The number of BrdU-labeled cells quantified by FACS increased within 2 weeks after labeling, then, decreased gradually until week 10. After week 10, the BrdU-labeled cells were found to locate mainly in basal layer and their number kept consistent at 3-7% of total oral epithelial cells. The number of BrdU-labeled epithelial cells in palate was statistically higher than that in cheek or tongue at the same time point. CONCLUSIONS: This study showed that the number and the distribution of BrdU-labeled epithelial cells stabilized from 10 weeks after labeling. Therefore, these BrdU-labeled cells after a 10-week chase were considered oral epithelial LRCs.
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Células-Tronco Adultas/citologia , Células Epiteliais/citologia , Boca/citologia , Nicho de Células-Tronco/citologia , Células-Tronco Adultas/metabolismo , Animais , Biomarcadores/metabolismo , Bromodesoxiuridina/metabolismo , Contagem de Células , Proliferação de Células , Células Epiteliais/metabolismo , Imuno-Histoquímica , Estudos Longitudinais , Boca/metabolismo , Ratos , Ratos Sprague-Dawley , Coloração e Rotulagem/métodos , Nicho de Células-Tronco/metabolismo , Fatores de Tempo , Distribuição TecidualRESUMO
Background: We previously demonstrated that Proline rich 11 (PRR11) gene is associated with the development and progression of tongue squamous cell carcinoma (TSCC), but the underlying mechanism is unknown. This study aimed to investigate the molecular mechanism underlying oncogenic potential of PRR11 in TSCC cells. Methods: Overexpression and knockdown of PRR11 were performed by plasmid transfection into SCC15 and HSC3 human TSCC cells. Expressions of mRNA and protein were assessed by qRT-PCR and Western blot, respectively. Cell proliferation and invasion were determined by CCK-8 and Transwell assay, respectively. In vivo tumor growth and cell cycle were determined by a nude mice model of subcutaneous tumorigenesis and flow cytometry, respectively. Results: Overexpression of PRR11 significantly enhanced TSCC cells proliferation and the invasive ability of TSCC cells, whereas PRR11 knockdown in TSCC cells exhibited a reverse trend. In addition, the in vivo subcutaneous tumorigenicity assay showed that PRR11 knockdown significantly reduced tumor size and the Ki67 (a proliferation marker)expression in the tumor tissue. Flow cytometry analysis revealed that PRR11 overexpression significantly decreased the proportion of cells in S phase, whereas PRR11 knockdown in TSCC cells exhibited a reverse trend. Furthermore, PRR11 overexpression simultaneously down-regulated two cyclin-dependent kinase inhibitors (CKIs), p21 and p27 and up-regulated CDK2 and Cyclin A2 in TSCC cells. PRR11 knockdown again exhibited reverse trends of expressions of the above proteins.Conclusion: These results suggested that PRR11 promoted cell proliferation by regulating the expressions of p21, p27, CDK2 and Cyclin A to facilitate S/G phase transition in TSCC cells.
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Oral squamous cell carcinoma (OSCC) is the most common and aggressive epithelial tumor in the head and neck region with a rising incidence. Despite the advances in basic science and clinical research, the overall survival rate of OSCC remains low. Thus finding novel effective therapeutic agents for OSCC is necessary. In this study, we investigated the effects and mechanisms of combined metformin and 4SC-202 in OSCC. Our results showed that metformin and 4SC-202 synergistically suppressed the proliferation and promoted the intrinsic apoptosis of OSCC cells in vitro and in vivo. Importantly, the proteasome inhibitor MG132 impeded the ΔNp63-decreasing effects after metformin and 4SC-202 treatment, indicating that metformin and 4SC-202 could promote the degradation of ΔNp63 protein. Moreover, ubiquitination level of ΔNp63 increased after metformin or/and 4SC-202 administration. Furthermore, we revealed that ΔNp63 mediated anticancer effects of metformin and 4SC-202, as overexpression or suppression of ΔNp63 could attenuate or facilitate the apoptosis rate of OSCC under metformin or/and 4SC-202 treatment. Collectively, metformin and 4SC-202 synergistically promote intrinsic apoptosis through accelerating ubiquitin-mediated degradation of ΔNp63 in OSCC, and this co-treatment can serve as a potential therapeutic scheme for OSCC.
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Apoptose/efeitos dos fármacos , Benzamidas/farmacologia , Carcinoma de Células Escamosas/metabolismo , Metformina/farmacologia , Neoplasias Bucais/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Feminino , Humanos , Camundongos , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , UbiquitinaçãoRESUMO
Intact and stable bone reconstruction is ideal for the treatment of periodontal bone destruction but remains challenging. In research, biomaterials are used to encapsulate stem cells or bioactive factors for periodontal bone regeneration, but, to the best of our knowledge, using a supramolecular hydrogel to encapsulate bioactive factors for their sustained release in bone defect areas to promote periodontal bone regeneration has not been reported. Herein, we used a well-studied hydrogelator, NapFFY, to coassemble with SDF-1 and BMP-2 to prepare a supramolecular hydrogel, SDF-1/BMP-2/NapFFY. In vitro and in vivo results indicated that these two bioactive factors were ideally, synchronously, and continuously released from the hydrogel to effectively promote the regeneration and reconstruction of periodontal bone tissues. Specifically, after the bone defect areas were treated with our SDF-1/BMP-2/NapFFY hydrogel for 8 weeks using maxillary critical-sized periodontal bone defect model rats, a superior bone regeneration rate of 56.7% bone volume fraction was achieved in these rats. We anticipate that our SDF-1/BMP-2/NapFFY hydrogel could replace bone transplantation in the clinic for the repair of periodontal bone defects and periodontally accelerated osteogenic orthodontics in the near future.
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Regeneração Óssea/efeitos dos fármacos , Hidrogéis/farmacologia , Osteogênese/efeitos dos fármacos , Periodonto/crescimento & desenvolvimento , Animais , Materiais Biocompatíveis/farmacologia , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/farmacologia , Regeneração Óssea/genética , Diferenciação Celular/efeitos dos fármacos , Preparações de Ação Retardada/farmacologia , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/genética , Periodonto/efeitos dos fármacos , Periodonto/patologia , Ratos , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/farmacologiaRESUMO
Targeted delivery of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system to the receptor cells is essential for in vivo gene editing. Exosomes are intensively studied as a promising targeted drug delivery carrier recently, while limited by their low efficiency in encapsulating of large nucleic acids. Here, a kind of hybrid exosomes with liposomes is developed via simple incubation. Different from the original exosomes, the resultant hybrid nanoparticles efficiently encapsulate large plasmids, including the CRISPR-Cas9 expression vectors, similarly as the liposomes. Moreover, the resultant hybrid nanoparticles can be endocytosed by and express the encapsulated genes in the mesenchymal stem cells (MSCs), which cannot be transfected by the liposome alone. Taken together, the exosome-liposome hybrid nanoparticles can deliver CRISPR-Cas9 system in MSCs and thus be promising in in vivo gene manipulation.