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Chemodynamic therapy based on the Fenton reaction has been developed as an extremely promising modality for cancer therapeutics. In this study, a core-shell structure nanoplatform was constructed by a Au nanorod externally encapsulating Ce/Zn-based composites (ACZO). The nanoparticles can catalyze the generation of reactive oxygen species (ROS) under acidic conditions and effectively consume existing glutathione (GSH) to destroy the redox balance within the tumor. Moreover, the decomposition of the nanocomplexes under acidic conditions releases large amounts of zinc ions, leading to zinc overload in cancer cells. The photothermal effect generated by the Au nanorods not only provides photothermal therapy (PTT) but also augments the catalytic reaction and ions action mentioned above. This facile strategy to improve the efficacy of chemodynamic therapy by the photothermal enhancement of catalytic activity and zinc ion release provides a promising perspective for potential tumor treatment.
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Nanopartículas , Nanotubos , Neoplasias , Humanos , Catálise , Glutationa , Zinco/farmacologia , Íons , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Peróxido de Hidrogênio , Microambiente TumoralRESUMO
This study aimed to determine if air pollution affected the risk of periodontitis outpatient visits. We collected the records of 56,456 periodontitis outpatient visits in Hefei, China, from January 1ï¼2014 to December 31ï¼2021. The relationship between air pollution and periodontitis outpatient visits was evaluated using distributed lag nonlinear and generalized linear models. Additional analyses were performed, stratifying the data by age, season, and sex. Subgroup analyses showed a significantly higher risk of periodontitis outpatient visits due to NO2 exposure during the warm season compared with the cold season. Moreover, O3 exposure was associated with a lower risk of periodontitis outpatient visits in the cold season. The findings suggest that NO2 exposure is associated with an increased risk of periodontitis outpatient visits, whereas O3 exposure is associated with a decreased risk of periodontitis outpatient visits. Season is found to be an effect modifier in these associations.
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BACKGROUND: Periodontitis-related attachment loss is accompanied by mucosal bleeding and inflammatory lesions. Dietary vitamin K and fibre intake are known to be correlation factors of haemostasis and anti-inflammation, respectively. OBJECTIVE: To explore the association between severe periodontal attachment loss and vitamin K or fibre intake in American adults. METHODS: A cross-sectional analysis was conducted including 2747 males and 2218 females in the National Health and Nutrition Examination Surveys (NHANES) from 2009 to 2014. The number of teeth with severe periodontal attachment loss (above 5 mm attachment loss) was used as the dependent variable. The main independent variables included the intake of vitamin K and dietary fibre. The association among variables was examined using multivariable linear regression models, hierarchical regression, fitted smoothing curves, and generalized additive models. RESULTS: Based on the indicators of 4965 subjects, we found that severe attachment loss tended to occur in elderly individuals or males and was accompanied by less intake of vitamin K or dietary fibre, as well as lower educational qualification. Vitamin K intake was stably negatively associated with attachment loss progression in each multivariable linear regression model. In subgroup analyses, a negative association between fibre intake and attachment loss progression was identified in all races except blacks (ß = 0.0005, 95% CI: -0.0005 to 0.0016). The relationship between fibre intake and attachment loss progression was a broad U-shaped curve (inflection point: 753.4 mg), which especially manifested in males (inflection point: 967.5 mg). CONCLUSION: There was an inverse association between vitamin K intake and the progression of periodontal attachment loss in American adults, while dietary fibre should be moderate in intake (below 753.4 mg), especially in males (below 967.5 mg).
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Fibras na Dieta , Vitamina K , Masculino , Feminino , Humanos , Adulto , Estados Unidos , Idoso , Inquéritos Nutricionais , Perda da Inserção Periodontal , Estudos TransversaisRESUMO
BACKGROUND: Tooth loss may be a surrogate for systemic health and aging. However, no previous studies have systematically assessed multiple outcomes relevant to aging trajectory in this area, and many important confounders were not adjusted in most previous studies. This study aims to prospectively evaluate the associations of complete tooth loss (edentulism) with broad markers of sarcopenia, cognitive impairment and mortality. METHODS: Data were derived from the China Health and Retirement Longitudinal Study, a nationally representative household study of the Chinese population aged 45 years and older. Multivariate Weibull proportional hazards regression was used to assess the association between edentulism with sarcopenia and all-cause mortality. Average changes in cognitive function by edentulism was estimated by mixed-effects linear regression models. RESULTS: During the 5-year follow-up, the prevalence of edentulism among adults aged 45 and over was 15.4%. Participants with edentulism had a greater decline in cognitive function compared to those without (ß=-0.70, 95%CI:-1.09, -0.31, P < 0.001). The association of edentulism and all-cause mortality for 45-64 age group (HR = 7.50, 95%CI: 1.99, 28.23, P = 0.003), but not statistically significant for the ≥ 65 age group (HR = 2.37, 95%CI: 0.97, 5.80, P = 0.057). Effects of edentulism on sarcopenia are statistically significant for all age groups (45-64 age group: HR = 2.15, 95%CI: 1.27, 3.66, P = 0.005; ≥65 age group: HR = 2.15, 95%CI: 1.27, 3.66, P = 0.002). CONCLUSIONS: These findings could have important clinical and public health implications, as tooth loss is a quick and reproducible measurement that could be used in clinical practice for identifying persons at risk of accelerated aging and shortened longevity, and who may benefit most from intervention if causality is established.
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Disfunção Cognitiva , Mortalidade , Sarcopenia , Perda de Dente , Idoso , Humanos , Pessoa de Meia-Idade , Disfunção Cognitiva/complicações , Disfunção Cognitiva/epidemiologia , População do Leste Asiático , Estudos Longitudinais , Sarcopenia/complicações , Sarcopenia/epidemiologia , Perda de Dente/complicações , Perda de Dente/epidemiologiaRESUMO
Background: Oral lichen planus (OLP) is an infrequent autoimmune disease of the oral mucosa, which affects up to 2% of the world population. An investigation of Tripterygium wilfordii's mechanism of action for treating OLP was conducted, and a theoretical basis was provided for improving current treatment regimens. Materials and Methods: We used a network pharmacological approach to gain insight into the molecular mechanism of Tripterygium wilfordii in the treatment of OLP. Then, potential protein targets between Tripterygium wilfordii and OLP were analyzed through a drug-target network. This was followed by KEGG enrichment analysis and Gene Ontology (GO) classification. Finally, for molecular docking, AutoDock Vina was used. Results: A protein-protein interaction (PPI) network was constructed by analyzing the common targets of a total of 51 wilfordii-OLP interactions from different databases. The GO and KEGG enrichment analyses showed that the treatment of OLP with Tripterygium wilfordii mainly involves lipopolysaccharide response, bacterial molecular response, positive regulation of cytokine production, and leukocyte proliferation, and the signaling pathways mainly include the AGE-RAGE, NF-κB, Toll-like receptor, IL-17, HIF-1, and TNF signaling pathways. The molecular docking results showed that ß-sitosterol, kaempferol, hederagenin, and triptolide have a higher affinity for AKT1, TNF, CASP3, and PTGS2, respectively. Based on the CytoNCA analysis of common targets, 19 key targets, including AKT1, TNF, VEGFA, STAT3, CXCL8, PTGS2, TP53, and CASP3, and their connections were identified. Conclusions: Preliminarily, this study reveals that Tripterygium wilfordii interferes with OLP by interacting with multiple targets through multiple accesses, as validated by molecular docking.
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Líquen Plano Bucal , Tripterygium , Humanos , Simulação de Acoplamento Molecular , Caspase 3 , Farmacologia em Rede , Ciclo-Oxigenase 2 , Líquen Plano Bucal/tratamento farmacológicoRESUMO
Evidence that common beverage consumption is associated with oral ecosystem. However, little is known about the effect of sugar-sweetened beverages (SSBs) on composition and functional potential of childhood oral microbiota. We aim to examine associations between SSBs consumption with oral microbiota diversity and function among school-aged children. Oral microbiota in buccal swab samples was collected from 180 children (11.3 ± 0.6 years) from an ongoing child growth and development cohort established in 2016, using 16S rDNA gene sequencing. Higher SSBs consumption (≥1 serving/day) was associated with lower oral microbiota richness and diversity. Children with higher SSBs consumption showed decreased abundance of genus Fusobacterium, Lachnoanaerobaculum, Soonwooa, Tannerella and Moraxella (p < 0.05). However, more SSBs intake selectively increases the dominance of aciduric bacteria (Neisseria and Streptococcus), which can lead to dental caries and other oral problems. Furthermore, PICRUSt analysis illustrated that oral microbiota was more conducive to the pathway activated of protein export (p = 0.020), D-glutamine and D-glutamate metabolism (p = 0.013), and pantothenate and CoA biosynthesis (p = 0.004), indicating vigorous microbial metabolism in oral bacterial community in higher SSBs intake groups. Overall, our finding suggests that higher SSBs consumption may disturb oral microecology and reduce diversity of microbiota during childhood, stimulating an increase in cariogenic genera, which contributes to increased susceptibility of SSBs-related oral diseases.
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Cárie Dentária , Microbiota , Bebidas Adoçadas com Açúcar , Bebidas/análise , Criança , Cárie Dentária/etiologia , Humanos , Instituições AcadêmicasRESUMO
Accumulating evidence indicates that the brain natriuretic peptide (BNP) and its receptor (natriuretic peptide receptor, NPR) are widely distributed in a variety of tissues including trigeminal ganglion (TG). Furthermore, recent studies support the involvement of the BNP-NPR-A pathway in acute and chronic pain. To investigate the role of this pathway in chronic pain, an infraorbital nerve-chronic constriction injury (ION-CCI) model of trigeminal neuralgia (TN) was produced in the rat. The time course of changes in mechanical pain threshold was examined. We observed an upregulation of BNP and NPR-A and a downregulation of large-conductance Ca2+-activated K+ (BKCa) mRNA and protein in rats subjected to ION-CCI. Patch clamping experiments in vitro found that BKCa currents were significantly reduced in rats subjected to ION-CCI. BNP increased BKCa currents in ION-CCI rats. These results suggest that BNP and NPR-A might serve as endogenous pain relievers in ION-CCI rats. Modulation of the BNP/NPR-A/BKCa channel pathway in TG may be a viable strategy for the treatment of TN.NEW & NOTEWORTHY BNP has been known to activate its receptor, NPR-A, to modulate inflammatory pain. However, the potential modulatory roles of BNP in TN have not been investigated in detail. We established an ION-CCI model of TN in the rat and observed an upregulation of BNP and NPR-A and a downregulation of BKCa in rats subjected to ION-CCI. Moreover, BNP can increase BKCa currents in ION-CCI rats. Thus, BNP and NPR-A might have inhibitory effects on trigeminal neuralgia through activating the BNP/NPR-A/BKCa channel pathway.
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Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Neuralgia/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Receptores do Fator Natriurético Atrial/metabolismo , Gânglio Trigeminal/metabolismo , Neuralgia do Trigêmeo/metabolismo , Animais , Doença Crônica , Constrição , Modelos Animais de Doenças , Regulação para Baixo , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVES: To evaluate the clinical significance of cyclin-dependent kinase 1 (CDK1) in 77 oral squamous cell carcinomas (OSCC) using immunohistochemical methods. STUDY DESIGN: Immunohistochemical expression of CDK1 was compared with various clinicopathological features in 77 OSCC and 60 controlled epithelia adjacent to the tumours. In addition, correlation of CDK1 expression and prognostic and the 5-year accumulative survival rate of OSCC were investigated. RESULTS: The CDK1 protein was expressed in 52 cases of 77 tumor tissues (67.5%), compared with 21 cases of 60 controlled (35.0%). The expression of CDK1 was significantly correlated with the histological grade of OSCC (P<0.05). The CDK1 protein was over-expressed in recurrent tumors or in those with lymph node metastasis. Statistical analysis showed a significant reduction in the 5-year accumulative survival rate in CDK1 positive cases compared with CDK1 negative cases (P<0.05). Namely, the CDK1 positive patients had poor prognosis. CONCLUSIONS: The expression of CDK1 might serve as malignant degree and prognostic markers for the survival of OSCC.
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Proteína Quinase CDC2/biossíntese , Carcinoma de Células Escamosas/enzimologia , Neoplasias Bucais/enzimologia , Proteína Quinase CDC2/análise , Carcinoma de Células Escamosas/química , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/química , Taxa de SobrevidaRESUMO
Despite decades of research, cancer continues to be a major global health concern. The human mouth appears to be a multiplicity of local environments communicating with other organs and causing diseases via microbes. Nowadays, the role of oral microbes in the development and progression of cancer has received increasing scrutiny. At the same time, bioengineering technology and nanotechnology is growing rapidly, in which the physiological activities of natural bacteria are modified to improve the therapeutic efficiency of cancers. These engineered bacteria were transformed to achieve directed genetic reprogramming, selective functional reorganization and precise control. In contrast to endotoxins produced by typical genetically modified bacteria, oral flora exhibits favorable biosafety characteristics. To outline the current cognitions upon oral microbes, engineered microbes and human cancers, related literatures were searched and reviewed based on the PubMed database. We focused on a number of oral microbes and related mechanisms associated with the tumor microenvironment, which involve in cancer occurrence and development. Whether engineering oral bacteria can be a possible application of cancer therapy is worth consideration. A deeper understanding of the relationship between engineered oral bacteria and cancer therapy may enhance our knowledge of tumor pathogenesis thus providing new insights and strategies for cancer prevention and treatment.
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Microbiota , Neoplasias , Humanos , Microambiente Tumoral , Bactérias , Neoplasias/tratamento farmacológico , BocaRESUMO
We aimed to investigate the role and mechanism of LSP1 in the progression of acute myelogenous leukemia. In this study, we established shLSP1 cell line to analyze the function of LSP1 in AML. We observed high expression of LSP1 in AML patients, whereas it showed no expression in normal adults. Furthermore, we found that LSP1 expression was associated with disease prognosis. Our results indicate that LSP1 plays a crucial role in mediating proliferation and survival of leukemia cells through the KSR/ERK signaling pathway. Additionally, LSP1 promotes cell chemotaxis and homing by enhancing cell adhesion and migration. We also discovered that LSP1 confers chemotactic ability to leukemia cells in vivo. Finally, our study identified 12 genes related to LSP1 in AML, which indicated poor survival outcome in AML patients and were enriched in Ras and cell adhesion signaling pathways. Our results revealed that the overexpression of LSP1 is related to the activation of the KSR/ERK signaling pathway, as well as cell adhesion and migration in AML patients. Reducing LSP1 expression impair AML progression, suggesting that LSP1 may serve as a potential drug therapy target for more effective treatment of AML.
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Leucemia Mieloide Aguda , Transdução de Sinais , Adulto , Humanos , Movimento Celular , Linhagem Celular , Leucemia Mieloide Aguda/genética , Proliferação de Células , Linhagem Celular Tumoral , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismoRESUMO
BACKGROUND: Trigeminal neuralgia (TN) is a common and difficult-to-treat neuropathic pain disorder in clinical practice. Previous studies have shown that Toll-like receptor 4 (TLR4) modulates the activation of the NF-κB pathway to affect neuropathic pain in rats. Voltage-gated sodium channels (VGSCs) are known to play an important role in neuropathic pain electrical activity. OBJECTIVE: To investigate whether TLR4 can regulate Nav1.3 through the TRAF6/NF-κB p65 pathway after infraorbital nerve chronic constriction injury (ION-CCI). STUDY DESIGN: ION-CCI modeling was performed on SD (Sprague Dawley) rats. To verify the success of the modeling, we need to detect the mechanical pain threshold and ATF3. Then, detecting the expression of TLR4, TRAF6, NF-κB p65, p-p65, and Nav1.3 in rat TG. Subsequently, investigate the role of TLR4/TRAF6/NF-κB pathway in ION-CCI model by intrathecal injections of LPS-rs (TLR4 antagonist), C25-140 (TRAF6 inhibitor), and PDTC (NF-κB p65 inhibitor). RESULTS: ION-CCI surgery decreased the mechanical pain threshold of rats and increased the expression of ATF3, TLR4, TRAF6, NF-κB p-p65 and Nav1.3, but there was no difference in NF-κB p65 expression. After inject antagonist or inhibitor of the TLR4/TRAF6/NF-κB pathway, the expression of Nav1.3 was decreased and mechanical pain threshold was increased. CONCLUSION: In the rat model of ION-CCI, TLR4 in the rat trigeminal ganglion regulates Nav1.3 through the TRAF6/NF-κB p65 pathway, and TLR4 antagonist alleviates neuropathic pain in ION-CCI rats.
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Canal de Sódio Disparado por Voltagem NAV1.3 , Ratos Sprague-Dawley , Transdução de Sinais , Fator 6 Associado a Receptor de TNF , Receptor 4 Toll-Like , Animais , Receptor 4 Toll-Like/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Masculino , Canal de Sódio Disparado por Voltagem NAV1.3/metabolismo , Transdução de Sinais/fisiologia , NF-kappa B/metabolismo , Neuralgia do Trigêmeo/metabolismo , Ratos , Modelos Animais de Doenças , Fator de Transcrição RelA/metabolismo , Fator 3 Ativador da Transcrição/metabolismo , Limiar da Dor/fisiologiaRESUMO
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with approximately 600,000 new cases each year. A small number of HNSCCs are caused by human papillomavirus (HPV) infection. Frizzled related protein (FRZB) has been reported in many inflammatory diseases and cancers, but it is yet unclear how FRZB affects HNSCC, as well as its role and underlying mechanism. TIMER2 database was utilized to evaluate FRZB expression in cancer tissues, and FRZB expression in HNSCC tissues was confirmed by samples obtained from Gene Expression Omnibus. To identify whether FRZB could be used as a prognostic predictor, we performed univariate and multivariate Cox regression analyses. FRZB co-expression profile was explored using the LinkedOmics database, then Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed for these FRZB-related genes in HNSCC samples. Lasso regression analysis was subsequently used to screen for prognostic variables, and we determined the infiltration of immune cells in HNSCC patients to clarify the influence of FRZB on tumor immune microenvironment. At last, we assessed the association between FRZB expression and immune checkpoint gene, and compared the sensitivity of common chemotherapeutic agents. In this study, we found that FRZB was dysregulated in HNSCC tumor tissues and had a relationship with clinical parameters. The reliability and independence of FRZB as a factor in determining a patient's prognosis for HNSCC was also established. Additional investigation revealed that FRZB was linked to common immune checkpoint genes and may be implicated in immune infiltration.
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Biomarcadores Tumorais , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Neoplasias de Cabeça e Pescoço/genética , Masculino , Feminino , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral , Pessoa de Meia-IdadeRESUMO
This article describes an ensemble of datasets used to understand the relationship between generalized severe periodontitis and hematological parameters. This dataset combines public periodontal examination data, hematological parameters data, and demographic data from the National Center for Health Statistics from 2009 to 2014. The stage of periodontitis was identified by attachment loss conducted by dental examiners, who were dentists (D.D.S./ D.M.D.) licensed in at least one U.S. state, while matching current classification criteria from the American Academy of Periodontology and the European Federation of Periodontology. Based on the NHANES database, information on age, gender, education level (< 9th grade, 9-11th grade, high school, college, graduate), race/ethnicity (Mexican American, Hispanic, non-Hispanic White, non-Hispanic Black, and other races), PIR (poverty income ratio) were acquired from the demographic data. Hematological parameters (including HB, HCT, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, red cell distribution width, platelet count, mean platelet volume, and red blood cell count) and glucose data had been obtained from laboratory data. Smoking data had been obtained from questionnaire data.
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Background: An evident association between mood disorders and TMJ dysfunction has been demonstrated in previous studies. This study observed both the behavioral changes and the pathological changes in hippocampal tissue of rats in an animal model of TMJ-OA by injecting MIA into TMJ. Methods: Eighteen SD rats were randomly assigned to the NC group and the MIA groups. A TMJ-OA model was established to assess the HWT in the TMJ region, and the rats were subjected to the OFT and EPM. HE, O-fast green staining, qRT-PCR and immunofluorescence were used to detect condylar damage. Serum and hippocampal oxidative stress levels were detected. Functions of genes obtained by RNA-Seq were investigated using H2O2, ZnCl2 and transfection of siRNA on HT22 cells. Results: Injection of MIA resulted in disorganization of the chondrocyte layer on the condylar surface of rats, with reduced synthesis and increased degradation of the condylar cartilage matrix and reduced HWT. The results of the OFT and EPM showed that the rats in the MIA group developed anxiety-like behavior during the sixth week of MIA injection. Increased Nox4 expression, decreased SOD2 expression, elevated MDA level, and reduced GSH level were detected in serum and hippocampal neurons in the MIA group, with nuclear pyknosis and reduced Nissl bodies observed in neurons. The expression of Slc39a12 in hippocampal neurons of rats in the MIA group decreased. Slc39a12 knockdown in HT22 cells induced increased Nox4 expression, decreased SOD2 expression, increased MDA level, and reduced GSH and intracellular Zn2+. Oxidative stress in HT22 cells after transfection and H2O2 stimulation was reversed when ZnCl2 was added. Conclusion: Loss of Slc39a12 in hippocampal neurons results in cellular oxidative stress, further leading to neuronal damage. This may potentially explain how TMJ-OA triggers anxiety-like behavior in rats.
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Patients with head and neck squamous cell carcinoma (HNSCC) have a poor prognosis because of their high recurrence and metastasis rates. Cuproptosis is a novel type of copper-dependent cell death that differs from apoptosis, necroptosis, and cytosolic scorch death. We designed and validated an individualized cuproptosis-related gene (CRG) signature for risk evaluation and prognostic prediction in HNSCC patients. Ninety differentially expressed CRGs were found in HNSCC. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses were performed to investigate the functional involvement of CRGs in the Cancer Genome Atlas (TCGA) HNSCC cohort. A CRG signature was created using 10 genes after univariate and multivariate analysis. Kaplan Meier (KM) analysis showed that the survival rate of the high-risk group was significantly lower than that of the low-risk group. Multivariate regression analysis identified risk scores based on prognostic characteristics as independent prognostic indicators of HNSCC. Moreover, risk models are related to tumor mutational burden (TMB), tumor-infiltrating immune cells (TICs), immune checkpoints, clinical characteristics, and antitumor drug susceptibility. Furthermore, we found that CuCl2 treatment promoted cuproptosis in HNSCC cells, and that the expression levels of cuproptosis-related genes were altered by different doses of CuCl2. In summary, understanding the detailed molecular mechanisms of cuproptosis and its impact on overall survival (OS), and identifying potential therapeutic targets for HNSCC will provide potential insights for treatment.Communicated by Ramaswamy H. Sarma.
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Chemodynamic therapy (CDT) involving the use of metal nanozymes presents new opportunities for the treatment of deep-seated tumors. However, the lower ROS catalytic rate and dependence on high H2O2 concentrations affect therapeutic efficacy. To address this issue, a hydrogel was constructed for the treatment of osteosarcoma by combining Cu-Fe3O4 nanozymes (NCs) and artemisinin (AS) coencapsulated in situ with sodium alginate (ALG) and calcium ions. This hydrogel can release nanoparticles and AS within tumor tissue for an extended period of time, utilizing the multienzyme activity of NCs to achieve ROS accumulation. The carbon radicals (â¢C) generated from the interaction of Fe2+/Cu2+ with AS amplify oxidative stress, leading to tumor cell damage. Simultaneously, the NCs activate ferroptosis via the GPX4 pathway by depleting GSH and activate cuproptosis via the DLAT pathway by causing intracellular copper overload, enhancing therapeutic efficacy. In vitro experiments confirmed that the NCs-AS-ALG hydrogel has an excellent tumor cell killing effect, while in vivo experimental results demonstrated that it can effectively eliminate tumors with excellent biocompatibility, providing a new approach for osteosarcoma treatment.
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Cobre , Ferroptose , Hidrogéis , Osteossarcoma , Estresse Oxidativo , Ferroptose/efeitos dos fármacos , Hidrogéis/química , Cobre/química , Cobre/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Humanos , Linhagem Celular Tumoral , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Camundongos , Alginatos/química , Camundongos Nus , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Tongue squamous cell carcinoma (TSCC) exhibits an aggressive biological behavior of lymph node and distant metastasis, which contributes to poorer prognosis and results in tongue function loss or death. In addition to known regulators and pathways of cell migration in TSCC, it is important to uncover pivotal switches governing tumor metastasis. METHODS: Cancer cell migration-associated transcriptional and epigenetic characteristics were profiled in TSCC, and the specific super-enhancers (SEs) were identified. Molecular function and mechanism studies were used to investigate the pivotal switches in TSCC metastasis. RESULTS: Ameboidal-type cell migration-related genes accompanied by transcriptional and epigenetic activity were enriched in TSCC. Meanwhile, the higher-ranked SE-related genes showed significant differences between 43 paired tumor and normal samples from the TCGA TSCC cohort. In addition, key motifs were detected in SE regions, and transcription factor-related expression levels were significantly associated with TSCC survival status. Notably, BATF and ATF3 regulated the expression of ameboidal-type cell migration-related MMP14 by switching the interaction with the SE region. CONCLUSION: SEs and related key motifs transcriptional regulate tumor metastasis-associated MMP14 and might be potential therapeutic targets for TSCC.
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Caries is a destructive condition caused by bacterial infection that affects the hard tissues of the teeth, significantly reducing the quality of life for individuals. Photothermal therapy (PTT) offers a noninvasive and painless treatment for caries, but the use of unsafe laser irradiance limits its application. To address this challenge, we prepared nanoparticles of silver ion-doped Prussian blue (AgPB), which was encased within cationic guar gum (CG) to form the antibacterial PTT hydrogel CG-AgPB with a photothermal conversion efficiency of 34.4%. When exposed to an 808 nm laser at a power density of 0.4 W/cm2, the hydrogel readily reached a temperature of over 50 °C in just 3 min, synchronized by the discharge of Ag+ ions from the interstitial sites of AgPB crystals, resulting in broad-spectrum and synergistic antibacterial activities (>99%) against individual oral pathogens (Streptococcus sanguinis, Streptococcus mutans, and Streptococcus sobrinus) and pathogen-induced biofilms. In vivo, CG-AgPB-mediated PTT demonstrated a capability to profoundly reduce the terminal number of cariogenic bacteria to below 1% in a rat model of caries. Given the outstanding biocompatibility, injectability, and flushability, this CG-AgPB hydrogel may hold promise as a next-generation oral hygiene adjunct for caries management in a clinical setting.
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Antibacterianos , Cárie Dentária , Ferrocianetos , Hidrogéis , Prata , Prata/química , Prata/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Cárie Dentária/terapia , Cárie Dentária/tratamento farmacológico , Cárie Dentária/microbiologia , Animais , Ratos , Ferrocianetos/química , Ferrocianetos/farmacologia , Terapia Fototérmica , Biofilmes/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Humanos , Ratos Sprague-DawleyRESUMO
Critical-size bone defects are a common and intractable clinical problem that typically requires filling in with surgical implants to facilitate bone regeneration. Considering the limitations of autologous bone and allogeneic bone in clinical applications, such as secondary damage or immunogenicity, injectable microhydrogels with osteogenic and angiogenic effects have received considerable attention. Herein, polydopamine (PDA)-functionalized strontium alginate/nanohydroxyapatite (Sr-Alg/nHA) composite microhydrogels loaded with vascular endothelial growth factor (VEGF) were prepared using microfluidic technology. This composite microhydrogel released strontium ions stably for at least 42 days to promote bone formation. The PDA coating can release VEGF in a controlled manner, effectively promote angiogenesis around bone defects, and provide nutritional support for new bone formation. In in vitro experiments, the composite microhydrogels had good biocompatibility. The PDA coating greatly improves cell adhesion on the composite microhydrogel and provides good controlled release of VEGF. Therefore, this composite microhydrogel effectively promotes osteogenic differentiation and vascularization. In in vivo experiments, composite microhydrogels were injected into critical-size bone defects in the skull of rats, and they were shown by microcomputed tomography and tissue sections to be effective in promoting bone regeneration. These findings demonstrated that this novel microhydrogel effectively promotes bone formation and angiogenesis at the site of bone defects.
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Indóis , Osteogênese , Polímeros , Fator A de Crescimento do Endotélio Vascular , Ratos , Animais , Fator A de Crescimento do Endotélio Vascular/farmacologia , Alginatos/farmacologia , Microtomografia por Raio-X , Angiogênese , Regeneração Óssea , Crânio , Hidroxiapatitas/farmacologia , Estrôncio/farmacologiaRESUMO
The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration. Adequate energy production forms the cornerstone supporting new bone formation. ETS variant 2 (ETV2) has been identified as a transcription factor that promotes energy metabolism reprogramming and facilitates the coordination between osteogenesis and angiogenesis. In vitro molecular experiments have demonstrated that ETV2 enhances osteogenic differentiation of dental pulp stem cells (DPSCs) by regulating the ETV2- prolyl hydroxylase 2 (PHD2)- hypoxia-inducible factor-1α (HIF-1α)- vascular endothelial growth factor A (VEGFA) axis. Notably, ETV2 achieves the rapid reprogramming of energy metabolism by simultaneously accelerating mitochondrial aerobic respiration and glycolysis, thus fulfilling the energy requirements essential to expedite osteogenic differentiation. Furthermore, decreased α-ketoglutarate release from ETV2-modified DPSCs contributes to microcirculation reconstruction. Additionally, we engineered hydroxyapatite/chitosan microspheres (HA/CS MS) with biomimetic nanostructures to facilitate multiple ETV2-DPSC functions and further enhanced the osteogenic differentiation. Animal experiments have validated the synergistic effect of ETV2-modified DPSCs and HA/CS MS in promoting the critical-size bone defect regeneration. In summary, this study offers a novel treatment approach for vascularized bone tissue regeneration that relies on energy metabolism activation and the maintenance of a stable local hypoxia signaling state.