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1.
J Pharm Pharmacol ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836550

RESUMO

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.

2.
Adv Healthc Mater ; : e2400297, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877613

RESUMO

The close relationship between bacteria and tumors has recently attracted increasing attention, and an increasing number of resources are being invested in the research and development of biomedical materials designed for the treatment of both. In this study, prefabricated TiN nanodots (NDs) and Fe(CO)5 nanoparticles are combined into sodium alginate (ALG) hydrogels to create a biomedical material for the topical treatment of breast cancer and subcutaneous abscesses, and a pseudocatalytic hydrogel with intrinsic photothermal and antibacterial activities is synthesized. TiN+Fe(CO)5+ALG hydrogels are used to determine the ability of Fe(CO)5 to promote CO production. Moreover, TiN NDs catalyze the production of reactive oxygen species (ROS) from hydrogen peroxide in tumor microenvironments and exhibit excellent photothermal conversion properties. After local injection of the TiN+Fe(CO)5+ALG hydrogel into subcutaneous tumors and subcutaneous abscesses, and two-zone near-infrared (NIR-II) irradiation, tumor cells and methicillin-resistant Staphylococcus aureus are effectively removed by the hydrogel, the mouse epidermis exhibiting complete recovery within 8 d, indicating that this hydrogel exhibits better antibacterial efficacy than the small-molecule antibiotic penicillin. This study demonstrates the potential of novel hydrogels for antitumor and antimicrobial combination therapy and aims to provide design ideas for the research and development of multifunctional antitumor and antimicrobial drug combinations.

3.
Imeta ; 3(3): e197, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38898992

RESUMO

Engineering bacteria are considered as a potential treatment for cardiovascular diseases and related risk factors. Oral bacteria are closely related to the occurrence and development of cardiovascular diseases, and their engineering has broad prospects and potential in the treatment of cardiovascular diseases. Oral pathogenic bacteria undergo protein and genetic engineering, including the incorporation of exogenous plasmids to yield therapeutic effects; genetically engineered oral probiotics can be harnessed to secrete cytokines and reactive oxygen species, offering novel therapeutic avenues for cardiovascular diseases.

4.
Int J Oral Sci ; 16(1): 24, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38472176

RESUMO

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.


Assuntos
Microbiota , Neoplasias , Humanos , Microambiente Tumoral , Bactérias , Neoplasias/tratamento farmacológico , Boca
5.
Data Brief ; 52: 110010, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38287952

RESUMO

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.

6.
Eur J Med Res ; 29(1): 84, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287445

RESUMO

OBJECTIVE: To use deep learning to segment the mandible and identify three-dimensional (3D) anatomical landmarks from cone-beam computed tomography (CBCT) images, the planes constructed from the mandibular midline landmarks were compared and analyzed to find the best mandibular midsagittal plane (MMSP). METHODS: A total of 400 participants were randomly divided into a training group (n = 360) and a validation group (n = 40). Normal individuals were used as the test group (n = 50). The PointRend deep learning mechanism segmented the mandible from CBCT images and accurately identified 27 anatomic landmarks via PoseNet. 3D coordinates of 5 central landmarks and 2 pairs of side landmarks were obtained for the test group. Every 35 combinations of 3 midline landmarks were screened using the template mapping technique. The asymmetry index (AI) was calculated for each of the 35 mirror planes. The template mapping technique plane was used as the reference plane; the top four planes with the smallest AIs were compared through distance, volume difference, and similarity index to find the plane with the fewest errors. RESULTS: The mandible was segmented automatically in 10 ± 1.5 s with a 0.98 Dice similarity coefficient. The mean landmark localization error for the 27 landmarks was 1.04 ± 0.28 mm. MMSP should use the plane made by B (supramentale), Gn (gnathion), and F (mandibular foramen). The average AI grade was 1.6 (min-max: 0.59-3.61). There was no significant difference in distance or volume (P > 0.05); however, the similarity index was significantly different (P < 0.01). CONCLUSION: Deep learning can automatically segment the mandible, identify anatomic landmarks, and address medicinal demands in people without mandibular deformities. The most accurate MMSP was the B-Gn-F plane.


Assuntos
Imageamento Tridimensional , Mandíbula , Humanos , Imageamento Tridimensional/métodos , Reprodutibilidade dos Testes , Mandíbula/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/métodos , Pontos de Referência Anatômicos/diagnóstico por imagem
7.
J Nanobiotechnology ; 22(1): 17, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172992

RESUMO

There is a growing body of evidence indicating a close association between inflammatory bowel disease (IBD) and disrupted intestinal homeostasis. Excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with an increase in M1 proinflammatory macrophage infiltration during the activation of intestinal inflammation, plays a pivotal role in disrupting intestinal homeostasis in IBD. The overabundance of ROS/RNS can cause intestinal tissue damage and the disruption of crucial gut proteins, which ultimately compromises the integrity of the intestinal barrier. The proliferation of M1 macrophages contributes to an exaggerated immune response, further compromising the intestinal immune barrier. Currently, intestinal nanomaterials have gained widespread attention in the context of IBD due to their notable characteristics, including the ability to specifically target regions of interest, clear excess ROS/RNS, and mimic biological enzymes. In this review, we initially elucidated the gut microenvironment in IBD. Subsequently, we delineate therapeutic strategies involving two distinct types of nanomedicine, namely inorganic nanoparticles and natural product nanomaterials. Finally, we present a comprehensive overview of the promising prospects associated with the application of nanomedicine in future clinical settings for the treatment of IBD (graphic abstract). Different classes of nanomedicine are used to treat IBD. This review primarily elucidates the current etiology of inflammatory bowel disease and explores two prominent nanomaterial-based therapeutic approaches. First, it aims to eliminate excessive reactive oxygen species and reactive nitrogen species. Second, they focus on modulating the polarization of inflammatory macrophages and reducing the proportion of pro-inflammatory macrophages. Additionally, this article delves into the treatment of inflammatory bowel disease using inorganic metal nanomaterials and natural product nanomaterials.


Assuntos
Produtos Biológicos , Doenças Inflamatórias Intestinais , Nanopartículas , Humanos , Espécies Reativas de Oxigênio/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Espécies Reativas de Nitrogênio/metabolismo
8.
Adv Sci (Weinh) ; 10(36): e2303946, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37897313

RESUMO

Macrophage efferocytosis of apoptotic osteoblasts (apoOBs) is a key osteoimmune process for bone homeostasis. However, apoOBs frequently accumulate in aged bone marrow, where they may mount proinflammatory responses and progressive bone loss. The reason why apoOBs are not cleared during aging remains unclear. In this study, it is demonstrated that aged apoOBs upregulate the immune checkpoint molecule CD47, which is controlled by SIRT6-regulated transcriptional pausing, to evade clearance by macrophages. Using osteoblast- and myeloid-specific gene knockout mice, SIRT6 is further revealed to be a critical modulator for apoOBs clearance via targeting CD47-SIRPα checkpoint. Moreover, apoOBs activate SIRT6-mediated chemotaxis to recruit macrophages by releasing apoptotic vesicles. Two targeting delivery strategies are developed to enhance SIRT6 activity, resulting in rejuvenated apoOBs clearance and delayed age-related bone loss. Collectively, the findings reveal a previously unknown linkage between immune surveillance and bone homeostasis and targeting the SIRT6-regulated mechanism can be a promising therapeutic strategy for age-related bone diseases.


Assuntos
Antígeno CD47 , Sirtuínas , Camundongos , Animais , Eferocitose , Osteoblastos , Camundongos Knockout , Envelhecimento
9.
Eur J Med Res ; 28(1): 287, 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37592356

RESUMO

OBJECTIVE: To explore the forewarning immunological indicators during periodontal attachment loss progression in American adults. METHODS: A total of 5744 participants with periodontal attachment loss were enrolled from the National Health and Nutrition Examination Surveys (NHANES) 2009-2014. In which, dependent variable was the counts of teeth with severe attachment loss (depth of periodontal probing was above 5 mm). Independent variables were circulatory immunological indexes, including counts of white blood cells (WBC), Lymphocytes, Monocytes, Neutrophils, Eosinophils, and Basophils. The association among variables was examined using multivariable linear regression models, fitting with smoothing curves, and generalizing additive models. RESULTS: Based on the indicators of 5744 subjects, we found that severe attachment loss tended to occur in the elderly or males and was accompanied by higher WBC, Monocytes, and Neutrophils, as well as lower poverty-income ratio and educational qualification. WBC (above the inflection point: 6200 cells/µL) and Neutrophils (above the inflection point: 3300 cells/µL) counts were positively associated with attachment loss progression in each multivariable linear regression model. On subgroup analyses, stratified by sex and race, the positive correlation of WBC or Neutrophils with severe attachment loss was stable in both men and women, as well as in all races except blacks (WBC ß = - 0.0576, 95% CI - 0.1945 to 0.0793, Neutrophils ß = - 0.0527, 95% CI - 0.2285 to 0.1231). CONCLUSION: Increasing WBC (above 6200 cells/µL) and Neutrophils (above 3300 cells/µL) counts were risk indicators of severe periodontal attachment loss among all races, except in blacks.


Assuntos
Leucócitos , Neutrófilos , Adulto , Idoso , Masculino , Humanos , Feminino , Inquéritos Nutricionais , Perda da Inserção Periodontal , Monócitos
10.
Chemosphere ; 337: 139405, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37399997

RESUMO

OBJECTIVE: To explore the relationship between oral restoration count, blood lead (PbB) level, and renal function as potential heavy metal releases, and the related toxicity of dental restorative materials. METHODS: A total of 3682 participants from the National Health and Nutrition Examination Survey (January 2017 to March 2020) were included in this cross-sectional analysis. We utilized multivariable linear regression models to investigate the associations between the number of oral restorations and PbB levels or renal function. The mediating effect of PbB on renal function indicators was analyzed using the R mediation package. RESULTS: Based on the indicators of 3682 participants, we found that the elderly, females, and whites were fit with more oral restoration, which was accompanied by increased PbB levels and decreased renal function. Meanwhile, oral restoration count was positively associated with PbB level (ß = 0.023, 95% CI: -0.020 to 0.027), renal function-related urine albumin creatinine ratio (ß = 1.541, 95% CI: 0.615-2.468), serum uric acid level (ß = 0.012, 95% CI: 0.007 to 0.017), and serum creatinine level, and negatively associated with estimated glomerular filtration rate (eGFR) (ß = -0.804, 95% CI: -0.880 to -0.728). Furthermore, the mediation effect test confirmed that PbB played a mediating role in the relationship between restoration count and serum uric acid or eGFR, with mediation effects accounting for 98.0% and 71.0%, respectively. CONCLUSIONS: Oral restoration negatively affects renal function. Oral restoration-related PbB level is a potential mediating factor.


Assuntos
Chumbo , Ácido Úrico , Feminino , Humanos , Idoso , Inquéritos Nutricionais , Estudos Transversais , Chumbo/toxicidade , Taxa de Filtração Glomerular , Rim/fisiologia
11.
Clin Oral Investig ; 27(8): 4727-4733, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37291391

RESUMO

OBJECTIVES: Periodontitis is accompanied by attachment loss and alveolar bone resorption. Vitamin D (VD) deficiency was closely associated with bone loss or osteoporosis. The study aims to investigate the potential relationship between different VD levels and severe periodontal attachment loss in American adults. METHODS: A cross-sectional analysis was conducted including 5749 participants in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014. The association of periodontal attachment loss progression with total VD, vitamin D3 (VD3), and vitamin D2 (VD2) levels was assessed using multivariable linear regression models, hierarchical regression, fitted smoothing curves, and generalized additive models. RESULTS: Based on the indicators of 5749 subjects, we found that severe attachment loss tended to occur in the elderly or males and was accompanied by less total VD levels, or VD3 levels, as well as a lower poverty-income ratio (PIR). Total VD (below the inflection point: 111 nmol/L) or VD3 were negatively associated with the progression of attachment loss in each multivariable regression model. In threshold analysis, VD3 is linearly correlated with the progression of attachment loss (ß = - 0.0183, 95% CI: - 0.0230 to - 0.0136). The relationship between VD2 and attachment loss progression was an S-shaped curve (inflection point: 5.07 nmol/L). CONCLUSION: Increasing total VD (below 111 nmol/L) and VD3 levels may be beneficial to periodontal health. VD2 levels above 5.07 nmol/L were a risk factor for severe periodontitis. CLINICAL RELEVANCE: The present study reports that different vitamin D levels may serve as different associations with periodontal attachment loss progression.


Assuntos
Perda do Osso Alveolar , Periodontite , Deficiência de Vitamina D , Masculino , Adulto , Humanos , Idoso , Vitamina D , Inquéritos Nutricionais , Perda da Inserção Periodontal , Estudos Transversais , Vitaminas , Periodontite/etiologia , Deficiência de Vitamina D/complicações
12.
BMC Oral Health ; 23(1): 303, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198606

RESUMO

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).


Assuntos
Fibras na Dieta , Vitamina K , Masculino , Feminino , Humanos , Adulto , Estados Unidos , Idoso , Inquéritos Nutricionais , Perda da Inserção Periodontal , Estudos Transversais
13.
Environ Sci Pollut Res Int ; 29(39): 58698-58702, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35366725

RESUMO

The aim of this study is to examine the environmental exposure to perchlorate, nitrate, and thiocyanate and their associations with oral health-related productivity loss (PL) in general population. A total of 13,554 participants were enrolled from the National Health and Nutrition Examination Survey. Urinary perchlorate, nitrate, and thiocyanate were measured using ion chromatography coupled with electrospray tandem mass spectrometry. Multivariable linear and logistic regressions were performed to explore the associations between urinary perchlorate, nitrate, and thiocyanate with the prevalence of PL. Restricted cubic splines were used to explore the nonlinearity. There are 636 PL cases. There was higher urinary level of thiocyanate in PL group. We found that compared with the lowest quartile, thiocyanate was associated with PL (odds ratio 0.72, 95% confidence interval [0.53, 0.98]; p = 0.039) in the highest quartile. Restricted cubic spines reveled that urinary thiocyanate was L-shaped associated with PL with the infection point of 1.35. Urinary thiocyanate was L-shaped associated with PL with the infection point of 1.35.


Assuntos
Percloratos , Tiocianatos , Adulto , Exposição Ambiental , Humanos , Nitratos , Inquéritos Nutricionais , Saúde Bucal
14.
Front Public Health ; 10: 829466, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35356020

RESUMO

Aim: To examine the human exposure to perchlorate, nitrate, and thiocyanate, and their associations with oral pain (OP) in the general population from the U.S. Methods: A total of 13,554 participants were enrolled in the National Health and Nutrition Examination Survey. The urinary perchlorate, nitrate, and thiocyanate were measured using ion chromatography coupled with an electrospray tandem mass spectrometry. The multivariable linear and logistic regressions were performed to explore the associations of the urinary perchlorate, nitrate, and thiocyanate, with the prevalence of oral pain. Restricted cubic splines were used to explore the non-linearity. Results: There are 3,129 OP cases. There was a higher urinary level of perchlorate, nitrate, and thiocyanate in OP. We found that urinary thiocyanate was positively associated with OP (odds ratio [OR] = 1.06; [1, 1.13]; p = 0.049). Restricted cubic spines revealed that urinary thiocyanate was in a U-shape association with OP. Conclusions: Urinary thiocyanate was in a U-shape association with OP, suggesting that we should keep the exposure of thiocyanate under a reasonable range.


Assuntos
Boca , Nitratos , Dor , Percloratos , Tiocianatos , Exposição Ambiental/efeitos adversos , Humanos , Boca/fisiopatologia , Nitratos/urina , Inquéritos Nutricionais , Dor/epidemiologia , Percloratos/urina , Tiocianatos/urina , Estados Unidos/epidemiologia
15.
Cell Death Differ ; 29(2): 351-365, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34497381

RESUMO

Aged bone marrow mesenchymal stem cells (BMSCs) exhibit aberrant self-renewal and lineage specification, which contribute to imbalanced bone-fat and progressive bone loss. In addition to known master regulators of lineage commitment, it is crucial to identify pivotal switches governing the specific differentiation fate of aged BMSCs. Here, we profiled differences in epigenetic regulation between adipogenesis and osteogenesis and identified super-enhancer associated lncRNA nuclear-enriched abundant transcript 1 (NEAT1) as a key bone-fat switch in aged BMSCs. We validated that NEAT1 with high enhancer activity was transcriptionally activated by ATF2 and directed aged BMSCs to a greater propensity to differentiate toward adipocytes than osteoblasts by mediating mitochondrial function. Furthermore, we confirmed NEAT1 as a protein-binding scaffold in which phosphorylation modification of SOX2 Ser249/250 by CDK2 impaired SOX2/OCT4 complex stability and dysregulated downstream transcription networks of pluripotency maintenance. In addition, by sponging miR-27b-3p, NEAT1 upregulated BNIP3L, BMP2K, and PPARG expression to shape mitochondrial function and osteogenic/adipogenic differentiation commitment, respectively. In extracellular communication, NEAT1 promoted CSF1 secretion from aged BMSCs and then strengthened osteoclastic differentiation by extracellular vesicle delivery. Notably, Neat1 small interfering RNA delivery induced increased bone mass in aged mice and decreased fat accumulation in the bone marrow. These findings suggest that NEAT1 regulates the lineage fates of BMSCs by orchestrating mitochondrial function and pluripotency maintenance, and might be a potential therapeutic target for skeletal aging.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , RNA Longo não Codificante , Adipogenia/genética , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Diferenciação Celular/genética , Epigênese Genética , Células-Tronco Mesenquimais/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Osteogênese/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
16.
Theranostics ; 11(11): 5491-5510, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859759

RESUMO

Rationale: Postmenopausal-induced bone loss is mainly caused by declining core transcription factors (TFs) of bone mesenchymal stem cells (BMSCs), but little is known about how miRNAs regulate chromatin structure remodeling of TFs gene to maintain BMSCs function in bone homeostasis. Methods: We examined the serum, salivary and bone samples from Pre- and Post-menopause women by paired analysis and confirmed canonical ceRNA role of MIR143HG and miR-143/145 complexes in cytoplasm and noncanonical role for SOX2 transcription in nucleus (FISH, qRT-PCR, immunostaining, Luciferase assays and ChIP). Moreover, we took advantage of transgenic mice under OVX-induced osteoporosis, studying the in vitro and in vivo effect of miR-143/145 deletion on BMSCs function and bone homeostasis. Last, using miRNA antagonism, antagomiR-143/145 were delivered into bone marrow to treat estrogen-deficient bone loss. Results: Here, we identified miR-143/145 as potential diagnostic candidates for postmenopausal osteoporosis, and miR-143/145 overexpression impaired BMSCs self-renewing and differentiation function. Mechanistically, we confirmed that cytoplasmic miR-143/145 and LncRNA MIR143HG, that controlled by ERß, cooperatively regulated pluripotency genes translation via canonical ceRNA pathway, and MIR143HG cooperates with miR­143 to nuclear translocation for co-activation of SOX2 transcription via opening promoter chromatin. Meanwhile, miR­143/145 were shuttled into osteoclasts in extracellular vesicles and triggered osteoclastic activity by targeting Cd226 and Srgap2. Furthermore, miR-143/145-/- mice or using chemically­modified antagomiR-143/145 significantly alleviated estrogen-deficient osteoporosis. Conclusions: Our findings reveal a canonical and noncanonical role of miR-143/145 in controlling BMSCs pluripotency and unfold their dual effect on bone formation and bone resorption, suggesting miR-143/145 as promising therapeutic targets for treating estrogen-deficient bone loss.


Assuntos
Doenças Ósseas Metabólicas/genética , Estrogênios/deficiência , Estrogênios/genética , MicroRNAs/genética , Osteoporose Pós-Menopausa/genética , Adulto , Idoso , Animais , Doenças Ósseas Metabólicas/metabolismo , Células da Medula Óssea/metabolismo , Reabsorção Óssea/genética , Osso e Ossos/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Vesículas Extracelulares/genética , Feminino , Células HEK293 , Humanos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese/genética , Osteoporose/genética , RNA Longo não Codificante/genética
17.
Sci Rep ; 10(1): 18437, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116221

RESUMO

Marginal bone loss (MBL) is one of the leading causes of dental implant failure. This study aimed to investigate the feasibility of machine learning (ML) algorithms based on trabeculae microstructure parameters to predict the occurrence of severe MBL. Eighty-one patients (41 severe MBL cases and 40 normal controls) were involved in the current study. Four ML models, including support vector machine (SVM), artificial neural network (ANN), logistic regression (LR), and random forest (RF), were employed to predict severe MBL. The area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity were used to evaluate the performance of these models. At the early stage of functional loading, severe MBL cases showed a significant increase of structure model index and trabecular pattern factor in peri-implant alveolar bone. The SVM model exhibited the best outcome in predicting MBL (AUC = 0.967, sensitivity = 91.67%, specificity = 100.00%), followed by ANN (AUC = 0.928, sensitivity = 91.67%, specificity = 93.33%), LR (AUC = 0.906, sensitivity = 91.67%, specificity = 93.33%), RF (AUC = 0.842, sensitivity = 75.00%, specificity = 86.67%). Together, ML algorithms based on the morphological variation of trabecular bone can be used to predict severe MBL.


Assuntos
Reabsorção Óssea/patologia , Implantes Dentários , Mandíbula/patologia , Falha de Prótese/etiologia , Máquina de Vetores de Suporte , Osso Esponjoso/patologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Redes Neurais de Computação
18.
Aging (Albany NY) ; 12(3): 2084-2100, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32017705

RESUMO

The dysfunction of bone marrow stromal cells (BMSCs) may be a core factor in Type 2 diabetes mellitus (T2DM) associated osteoporosis. However, the underlying mechanism is not well understood. Here, we delineated the critical role of insulin impeding osteogenesis of BMSCs in T2DM. Compared with BMSCs from healthy people (H-BMSCs), BMSCs from T2DM patient (DM-BMSCs) showed decreased osteogenic differentiation and autophagy level, and increased senescent phenotype. H-BMSCs incubated in hyperglycemic and hyperinsulinemic conditions similarly showed these phenotypes of DM-BMSCs. Notably, enhanced TGF-ß1 expression was detected not only in DM-BMSCs and high-glucose and insulin-treated H-BMSCs, but also in bone callus of streptozocin-induced diabetic rats. Moreover, inhibiting TGF-ß1 signaling not only enhanced osteogenic differentiation and autophagy level of DM-BMSCs, but also delayed senescence of DM-BMSCs, as well as promoted mandible defect healing of diabetic rats. Finally, we further verified that it was TGF-ß receptor II (TßRII), not TßRI, markedly increased in both DM-BMSCs and insulin-treated H-BMSCs. Our data revealed that insulin impeded osteogenesis of BMSCs by inhibiting autophagy and promoting premature senescence, which it should be responsible for T2DM-induced bone loss, at least in part. These findings suggest that inhibiting TGF-ß1 pathway may be a potential therapeutic target for T2DM associated bone disorders.


Assuntos
Autofagia/fisiologia , Senescência Celular/fisiologia , Diabetes Mellitus Tipo 2/metabolismo , Insulina/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osteogênese/fisiologia , Osteoporose/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Autofagia/efeitos dos fármacos , Calo Ósseo/metabolismo , Estudos de Casos e Controles , Senescência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hiperglicemia , Hiperinsulinismo , Insulina/farmacologia , Masculino , Mandíbula/cirurgia , Fraturas Mandibulares/diagnóstico por imagem , Fraturas Mandibulares/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Pessoa de Meia-Idade , Osteogênese/efeitos dos fármacos , Osteoporose/complicações , Ratos , Receptor do Fator de Crescimento Transformador beta Tipo II/efeitos dos fármacos , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores
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