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1.
Eur J Radiol ; 176: 111496, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38733705

RESUMO

PURPOSE: To develop a deep learning (DL) model for classifying histological types of primary bone tumors (PBTs) using radiographs and evaluate its clinical utility in assisting radiologists. METHODS: This retrospective study included 878 patients with pathologically confirmed PBTs from two centers (638, 77, 80, and 83 for the training, validation, internal test, and external test sets, respectively). We classified PBTs into five categories by histological types: chondrogenic tumors, osteogenic tumors, osteoclastic giant cell-rich tumors, other mesenchymal tumors of bone, or other histological types of PBTs. A DL model combining radiographs and clinical features based on the EfficientNet-B3 was developed for five-category classification. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate model performance. The clinical utility of the model was evaluated in an observer study with four radiologists. RESULTS: The combined model achieved a macro average AUC of 0.904/0.873, with an accuracy of 67.5 %/68.7 %, a macro average sensitivity of 66.9 %/57.2 %, and a macro average specificity of 92.1 %/91.6 % on the internal/external test set, respectively. Model-assisted analysis improved accuracy, interpretation time, and confidence for junior (50.6 % vs. 72.3 %, 53.07[s] vs. 18.55[s] and 3.10 vs. 3.73 on a 5-point Likert scale [P < 0.05 for each], respectively) and senior radiologists (68.7 % vs. 75.3 %, 32.50[s] vs. 21.42[s] and 4.19 vs. 4.37 [P < 0.05 for each], respectively). CONCLUSION: The combined DL model effectively classified histological types of PBTs and assisted radiologists in achieving better classification results than their independent visual assessment.

2.
J Econ Entomol ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579138

RESUMO

Metarhizium anisopliae is an important class of entomopathogenic fungi used for the biocontrol of insects, but its virulence is affected by insect immunity. We identified a novel FK506 binding protein gene that was differentially expressed between control and Metarhizium-treated Locusta migratoria manilensis. We hypothesized that this protein played an important role in Metarhizium infection of L. migratoria and could provide new insights for developing highly efficient entomopathogenic fungi. We, therefore, cloned the specific gene and obtained its purified protein. The gene was then named FKBP52, and its dsRNA (dsFKBP52) was synthesized and used for gene interference. Bioassay results showed that the mortality of L. migratoria treated with dsFKBP52 + Metarhizium was significantly lower than that of other treatments. Furthermore, immune-related genes (MyD88, Dorsal, Cactus, and Defensin) in L. migratoria treated with dsFKBP52 + Metarhizium showed significant upregulation compared to that treated with Metarhizium only. However, the activities of peroxidase (POD), superoxide dismutase (SOD), and calcineurin (CaN) showed fluctuations. These results suggest that the FKBP52 gene may play a crucial role in the innate immunity of L. migratoria. The effect of its silencing indicated that this immunity-related protein might be a potential target for insect biocontrol.

3.
Insights Imaging ; 15(1): 93, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530554

RESUMO

OBJECTIVE: To develop a deep learning (DL) model for segmenting fat metaplasia (FM) on sacroiliac joint (SIJ) MRI and further develop a DL model for classifying axial spondyloarthritis (axSpA) and non-axSpA. MATERIALS AND METHODS: This study retrospectively collected 706 patients with FM who underwent SIJ MRI from center 1 (462 axSpA and 186 non-axSpA) and center 2 (37 axSpA and 21 non-axSpA). Patients from center 1 were divided into the training, validation, and internal test sets (n = 455, 64, and 129). Patients from center 2 were used as the external test set. We developed a UNet-based model to segment FM. Based on segmentation results, a classification model was built to distinguish axSpA and non-axSpA. Dice Similarity Coefficients (DSC) and area under the curve (AUC) were used for model evaluation. Radiologists' performance without and with model assistance was compared to assess the clinical utility of the models. RESULTS: Our segmentation model achieved satisfactory DSC of 81.86% ± 1.55% and 85.44% ± 6.09% on the internal cross-validation and external test sets. The classification model yielded AUCs of 0.876 (95% CI: 0.811-0.942) and 0.799 (95% CI: 0.696-0.902) on the internal and external test sets, respectively. With model assistance, segmentation performance was improved for the radiological resident (DSC, 75.70% vs. 82.87%, p < 0.05) and expert radiologist (DSC, 85.03% vs. 85.74%, p > 0.05). CONCLUSIONS: DL is a novel method for automatic and accurate segmentation of FM on SIJ MRI and can effectively increase radiologist's performance, which might assist in improving diagnosis and progression of axSpA. CRITICAL RELEVANCE STATEMENT: DL models allowed automatic and accurate segmentation of FM on sacroiliac joint MRI, which might facilitate quantitative analysis of FM and have the potential to improve diagnosis and prognosis of axSpA. KEY POINTS: • Deep learning was used for automatic segmentation of fat metaplasia on MRI. • UNet-based models achieved automatic and accurate segmentation of fat metaplasia. • Automatic segmentation facilitates quantitative analysis of fat metaplasia to improve diagnosis and prognosis of axial spondyloarthritis.

4.
Eur Radiol ; 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38127073

RESUMO

OBJECTIVES: To develop an ensemble multi-task deep learning (DL) framework for automatic and simultaneous detection, segmentation, and classification of primary bone tumors (PBTs) and bone infections based on multi-parametric MRI from multi-center. METHODS: This retrospective study divided 749 patients with PBTs or bone infections from two hospitals into a training set (N = 557), an internal validation set (N = 139), and an external validation set (N = 53). The ensemble framework was constructed using T1-weighted image (T1WI), T2-weighted image (T2WI), and clinical characteristics for binary (PBTs/bone infections) and three-category (benign/intermediate/malignant PBTs) classification. The detection and segmentation performances were evaluated using Intersection over Union (IoU) and Dice score. The classification performance was evaluated using the receiver operating characteristic (ROC) curve and compared with radiologist interpretations. RESULT: On the external validation set, the single T1WI-based and T2WI-based multi-task models obtained IoUs of 0.71 ± 0.25/0.65 ± 0.30 for detection and Dice scores of 0.75 ± 0.26/0.70 ± 0.33 for segmentation. The framework achieved AUCs of 0.959 (95%CI, 0.955-1.000)/0.900 (95%CI, 0.773-0.100) and accuracies of 90.6% (95%CI, 79.7-95.9%)/78.3% (95%CI, 58.1-90.3%) for the binary/three-category classification. Meanwhile, for the three-category classification, the performance of the framework was superior to that of three junior radiologists (accuracy: 65.2%, 69.6%, and 69.6%, respectively) and comparable to that of two senior radiologists (accuracy: 78.3% and 78.3%). CONCLUSION: The MRI-based ensemble multi-task framework shows promising performance in automatically and simultaneously detecting, segmenting, and classifying PBTs and bone infections, which was preferable to junior radiologists. CLINICAL RELEVANCE STATEMENT: Compared with junior radiologists, the ensemble multi-task deep learning framework effectively improves differential diagnosis for patients with primary bone tumors or bone infections. This finding may help physicians make treatment decisions and enable timely treatment of patients. KEY POINTS: • The ensemble framework fusing multi-parametric MRI and clinical characteristics effectively improves the classification ability of single-modality models. • The ensemble multi-task deep learning framework performed well in detecting, segmenting, and classifying primary bone tumors and bone infections. • The ensemble framework achieves an optimal classification performance superior to junior radiologists' interpretations, assisting the clinical differential diagnosis of primary bone tumors and bone infections.

5.
Oral Dis ; 29(4): 1692-1705, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35152542

RESUMO

OBJECTIVE: Exosomes secreted by stem cells are recognized as a critical component in tissue regeneration during stem cell-based therapy. Considering the limited sources and bone regeneration efficiency of human periodontal ligament cells (hPDLCs), we explored whether exosomes secreted by stem cells from human exfoliated deciduous teeth (SHED-exo) could improve the pluripotency and regenerative potential of hPDLCs. METHODS AND MATERIALS: In hPDLCs, cell proliferation, migration, cell cycle, apoptosis, and osteogenic differentiation were detected after cells were exposed to SHED-exo (SHED-exo group), blank (control group), or control supernatant without exo (Csup group), via CCK-8, scratch analysis, flow cytometric, real-time PCR, and so on. Exosomes sequencing was performed to compare and analyze miRNAs contented in SHED-exo and hPDLC-exo. RESULTS: As compared to control or Csup, SHED-exo significantly increased migration, apoptosis, and proliferation, promoted cell cycle transition from G1 to S phase in hPDLCs, and enhanced Runx2 expression and mineralization. In addition, it may be explained by the significant differences in miRNA contented in SHED-exo and hPDLC-exo. CONCLUSION: Exosomes from SHED can improve cell proliferation, migration, cell cycle, apoptosis, and osteogenic differentiation of hPDLCs, which highlights the therapeutic value of this bioactive component in the regeneration of periodontal tissues using hPDLCs in clinical practice.


Assuntos
Exossomos , MicroRNAs , Humanos , Osteogênese/genética , Ligamento Periodontal , Exossomos/metabolismo , Células Cultivadas , Diferenciação Celular , MicroRNAs/metabolismo , Proliferação de Células
6.
Bioact Mater ; 15: 482-494, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35386341

RESUMO

Local drug delivery has received increasing attention in recent years. However, the therapeutic efficacy of local delivery of drugs is still limited under certain scenarios, such as in the oral cavity or in wound beds after resection of tumors. In this study, we introduce a bioinspired adhesive hydrogel derived from the skin secretions of Andrias davidianus (SSAD) as a wound dressing for localized drug elution. The hydrogel was loaded with aminoguanidine or doxorubicin, and its controlled drug release and healing-promoting properties were verified in a diabetic rat palatal mucosal defect model and a C57BL/6 mouse melanoma-bearing model, respectively. The results showed that SSAD hydrogels with different pore sizes could release drugs in a controllable manner and accelerate wound healing. Transcriptome analyses of the palatal mucosa suggested that SSAD could significantly upregulate pathways linked to cell adhesion and extracellular matrix deposition and had the ability to recruit keratinocyte stem cells to defect sites. Taken together, these findings indicate that property-controllable SSAD hydrogels could be a promising biofunctional wound dressing for local drug delivery and promotion of wound healing.

7.
Eur J Pharmacol ; 891: 173731, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33220275

RESUMO

Metformin has protective effects on diabetic nephropathy. However, the mechanism underlying the renoprotective action of metformin in spontaneously hypertensive rats (SHR) is not completely understood. We determined the role of metformin in proteinuria and investigated the mechanism. We measured the urinary protein concentration (mg/day) in 48-week-old SHR. Matched control animals were of the same genetic strain, Wistar-Kyoto (WKY). The rats received metformin (100 mg/kg/day) or vehicle for 10 months. Metformin improved renal function and reduced the proteinuria (urine protein: 48.4 ± 3.7 vs. 25.4 ± 1.8 mg, P < 0.01) induced by long-term high blood pressure. Metformin increased the production of vascular endothelial growth factor (VEGF)-A in rat kidneys and cultured rat podocytes. Metformin activated hypoxia-inducible factor-2α (Hif-2α) in response to VEGF but did not affect Hif-1α in rat kidneys and cultured rat podocytes. Metformin reduced the proteinuria induced by long-term high blood pressure in vivo and increased the VEGF-A production in rat kidneys and cultured rat podocytes, probably by activating the Hif-2α-VEGF signaling pathway. These findings provide a new mechanism for the renoprotective effects of metformin.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Hipertensão/tratamento farmacológico , Rim/efeitos dos fármacos , Metformina/farmacologia , Proteinúria/prevenção & controle , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Pressão Sanguínea , Células Cultivadas , Modelos Animais de Doenças , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Rim/metabolismo , Rim/fisiopatologia , Masculino , Fosforilação , Proteinúria/metabolismo , Proteinúria/fisiopatologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Transdução de Sinais
8.
Differentiation ; 111: 1-11, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31630077

RESUMO

The exosomes from human exfoliated deciduous teeth (SHED-Exos) have exhibited potential therapeutic role in dental and oral disorders. The biological effects of exosomes largely depend on cellular origin and physiological status of donor cell. In the present study, we explored the influence of conditioned exosomes from SHED with osteogenic induction on periodontal ligament stem cells (PDLSCs) in vitro. Conditioned SHED-Exos from a 3-day osteogenic supernatant were applied during PDLSCs osteogenic differentiation. We found that conditioned SHED-Exos had no cytotoxicity on PDLSCs viability assessed by CCK-8 assay. These SHED-Exos promoted PDLSCs osteogenic differentiation with deep Alizarin red staining, high alkaline phosphatase (ALP) activity and upregulated osteogenic gene expression (RUNX2, OPN and OCN). We further found BMP/Smad signaling and Wnt/ß-catenin were activated by enhanced Smad1/5/8 phosphorylation and increased nuclear ß-catenin protein expression. Inhibiting these two signaling pathways with specific inhibitors (cardamonin and LDN193189) remarkably weakened the enhanced osteogenic differentiation. Furthermore, Wnt3a and BMP2 were upregulated in SHED and SHED-Exos. Silencing Wnt3a and BMP2 in SHED-Exos partially counteracts the enhanced osteogenic differentiation. Our findings indicate that conditioned SHED-Exos-enhanced PDLSCs osteogenic differentiation was partly due to its carrying Wnt3a and BMP2. These data provide new insights into the use of SHED-Exos in periodontitis-induced bone defects therapy.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Exossomos/metabolismo , Osteogênese , Ligamento Periodontal/citologia , Células-Tronco/citologia , Dente Decíduo/citologia , Via de Sinalização Wnt , Proteína Morfogenética Óssea 2/genética , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Humanos , Ligamento Periodontal/metabolismo , Células-Tronco/metabolismo , Esfoliação de Dente , Dente Decíduo/metabolismo
9.
Stem Cell Res Ther ; 10(1): 216, 2019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358056

RESUMO

OBJECTIVES: Temporomandibular joint osteoarthritis (TMJOA) is an inflammatory joint disease. This study investigated whether exosomes (Exos) of stem cells from human exfoliated deciduous teeth (SHEDs) have a therapeutic effect on TMJ inflammation and elucidated the underlying mechanisms. MATERIALS AND METHODS: SHEDs were verified by flow cytometry. SHED-Exos were identified by western blotting, nanoparticle tracking analysis, and transmission electron microscopy. Western blot and RT-qPCR were performed to verify the anti-inflammatory effects of SHED-Exos. MicroRNA (miRNA) array analysis was conducted to determine the miRNA expression profiles of SHED-Exos, and the key pathways were analyzed. After chondrocytes were treated with an miR-100-5p mimic or rapamycin, relative expression of genes was measured by RT-qPCR and western blotting. A luciferase reporter assay was performed to reveal the molecular role of the exosomal miR-100 target, mTOR. RESULTS: MiR-100-5p was enriched in the SHED-Exos. Treatment with SHED-Exos suppressed the expression of interleukin-6 (IL-6), IL-8, matrix metalloproteinase 1 (MMP1), MMP3, MMP9, MMP13, and disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5). Chondrocytes treated with the miR-100 mimic showed lower expression of MMP1, MMP9, MMP13, ADAMTS5, and mTOR. In contrast, miR-100 downregulation upregulated the MMPs and mTOR. Rapamycin treatment upregulated miR-100 and downregulated MMPs and ADAMTS5. Furthermore, the luciferase reporter assay demonstrated that miR-100-5p directly targeted the mTOR 3' untranslated region and that SHED-Exos miR-100-5p repressed mTOR expression. CONCLUSIONS: This study demonstrated that SHED-Exos suppress inflammation in TMJ chondrocytes and may thus be a novel therapeutic agent for TMJ inflammation.


Assuntos
Condrócitos/citologia , Exossomos/metabolismo , MicroRNAs/metabolismo , Células-Tronco/metabolismo , Articulação Temporomandibular/citologia , Dente Decíduo/citologia , Western Blotting , Criança , Pré-Escolar , Condrócitos/metabolismo , Condrócitos/fisiologia , Humanos , Inflamação/metabolismo , Inflamação/terapia , Microscopia Eletrônica de Transmissão , Osteoartrite/metabolismo , Osteoartrite/terapia
10.
Pain Med ; 20(4): 840-845, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30602000

RESUMO

OBJECTIVE: The present study aimed to validate the Centrality of Pain Scale (COPS) for use in Chinese patients with painful temporomandibular disorders (TMDs). METHODS: The Centrality of Pain Scale was firstly translated and cross-culturally adapted following international guidelines. In total, 166 patients with TMD were recruited to complete the Chinese version of the COPS (COPS-C). In addition to the COPS-C, the patients were also administered the Pain Catastrophizing Scale (PCS) and the Pain Self-Efficacy Questionnaire (PSEQ). The reliability of the COPS-C was evaluated using internal consistency and test-retest methods. The construct validity of the COPS-C was evaluated using exploratory factor analysis (EFA). Convergent validity was determined by analyzing the correlations between COPS-C scores and the scores of the PCS and PSEQ. RESULTS: Cronbach's alpha for the total COPS-C score was 0.942. The interitem correlations ranged from 0.356 to 0.901. The intraclass correlation coefficient values of the COPS-C ranged between 0.815 and 0.929. The results of the EFA indicated a one-factor solution for the measure, accounting for 70.4% of the total observed variance. The factor loadings of all items ranged from 0.713 to 0.917. Regarding convergent validity, the COPS-C had moderate correlations with the PCS and the PSEQ. CONCLUSIONS: The results provide initial evidence that the COPS-C is a reliable and valid measure. It can be used as a suitable instrument for Chinese patients with TMD.


Assuntos
Medição da Dor/métodos , Psicometria/instrumentação , Transtornos da Articulação Temporomandibular/complicações , Adulto , Povo Asiático , Feminino , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Tradução
11.
Neurol Res ; 41(1): 9-18, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30281408

RESUMO

Objectives: In this study, we aim to determine how CUG-expansion and the abundance of Celf1 regulates normal myocyte differentiation and reveal the role ofmiR-206 in myotonic dystrohy and explore a possible gene therapy vector. Methods: we set up CUG-expansion and Celf1 overexpression C2C12 cell models to imitate the myocyte differentiation defects of DM1, then transfected AdvmiR-206 into cell models, tested the level of myogenic markers MyoD, MyoG, Mef2c, Celf1 by RT-PCRand Western Blotting, detected myotube formation by myosin heavy chain immunostaining. Result: 3'-UTR CUG-expansion leads to myotube defects and impaired myoblasts differentiation. Overexpression of Celf1 inhibits myoblast differentiation and impairs differentiation. Knockdown of Celf1 partially rescues differentiation defects of myoblasts harboring CUG-expansion. miR-206 incompletely reverses myoblast differentiation inhibition induced by CUG-expansion and partially recuses myoblast differentiation defects induced by Celf1 overexpression. Conclusions: Ectopic miR-206 mimicking the endogenous temporal patterns specifically drives a myocyte program that boosts myoblast lineages, likely by promoting the expression of MyoD to rectify the myogenic deficiency by stimulating the accumulation of Celf1. Abbreviations: DMPK: (dystrophia myotonica protein kinase); 3'-UTR: (3'-untranslated region); MBNL1: (muscleblind-like [Drosophila]); DM1: (myotonic dystrophy type 1); GFP: (green fluorescent protein); RT-PCR: (quantitative reverse transcriptase-polymerase chain reaction); shRNA: (short hairpin RNA).


Assuntos
Proteínas CELF1/antagonistas & inibidores , MicroRNAs/metabolismo , Desenvolvimento Muscular/fisiologia , Mioblastos/metabolismo , Distrofia Miotônica/metabolismo , Animais , Diferenciação Celular/fisiologia , Linhagem Celular , Camundongos , Miotonina Proteína Quinase/genética , Miotonina Proteína Quinase/metabolismo
12.
Int J Mol Med ; 42(3): 1436-1444, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29845292

RESUMO

The mechanism underlying the anti­inflammatory or antifibrotic activity of erythropoietin (EPO) in myocardial fibrosis (MF) remains elusive. In the current study, abdominal aortic constriction (AAC) was performed on rats and EPO and/or Toll­like receptor (TLR)4 were overexpressed in rat hearts through intramyocardial administration of lentivirus expressing the EPO and TLR4 genes. Hematoxylin and eosin staining and Masson's trichrome staining were performed on tissue sections from rat hearts for histopathological examination. ELISA was used to determine the levels of inflammatory mediators in serum. Gene expression levels were determined by quantitative polymerase chain reaction analysis and protein expression levels were determined by western blot analysis and immunofluorescence staining. The results indicated that EPO overexpression improved MF in rat hearts, by inhibiting the release of transforming growth factor (TGF)­ß1, tumor necrosis factor (TNF)­α, interleukin (IL)­6, IL­1ß, IL­17A, matrix metalloproteinase (MMP)­9 and MMP­2. Moreover, EPO overexpression suppressed the expression of TLR4, while promoting phosphoinositide 3­kinase (PI3K) and phosphorylated AKT serine/threonine kinase 1 (Akt) expression levels. However, the beneficial effects of EPO were attenuated by overexpression of TLR4. In addition, inhibition of PI3K/Akt signaling activity by treatment with LY294002 markedly reversed the protective effect of EPO on the AAC­induced MF. Taken together, the present study demonstrated that EPO may have a critical role against MF by activating PI3K/Akt signaling and by downregulating TLR4 expression, thereby inhibiting the release of TGF­ß1, TNF­α, IL­6, IL­1ß, IL­17A, MMP­9 and MMP­2. These findings suggest that the PI3K/Akt/TLR4 signaling pathway is associated with the anti­inflammatory effects of EPO and may play a role in attenuating AAC­induced MF.


Assuntos
Eritropoetina/farmacologia , Inflamação/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Receptor 4 Toll-Like/metabolismo , Animais , Cardiomegalia/patologia , Citocinas/sangue , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismo
13.
Genesis ; 55(12)2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29193599

RESUMO

The Hippo- yes-associated protein (YAP) pathway is essential for controlling organ size and tumorigenesis. Previous studies have demonstrated that the primary outcome of YAP signaling in the nucleus is achieved by interaction with the transcription factor TEA domain transcription factor (TEAD1). The YAP/TEAD1 complex binds to DNA element and regulates the expression of genes involved in cell growth. However, constitutive knockout of TEAD1 leads to early embryonic lethality in mice. Thus, generation of a floxed TEAD1 mouse becomes crucial for further understanding mid- to late-gestation and post-natal role of TEAD1. Herein, we created and characterized a mouse model that allows for conditional disruption of TEAD1. Embryonic fibroblasts derived from the floxed TEAD1 mice enabled the Cre-mediated deletion of TEAD1 in vitro using virally delivered Cre recombinase. Furthermore, crossing the floxed TEAD1 mouse with a ubiquitously expressing Cre mouse resulted in efficient ablation of the floxed allele in vivo, and the animals recapitulated early embryonic lethality defects. In conclusion, our data demonstrate an important role of TEAD1 in early development in mice, and the floxed TEAD1 mouse model will be a valuable genetic tool to determine the temporal and tissue-specific functions of TEAD1.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Ligação a DNA/genética , Desenvolvimento Embrionário/genética , Fosfoproteínas/genética , Fatores de Transcrição/genética , Alelos , Animais , Proteínas de Ciclo Celular , Proliferação de Células/genética , Regulação da Expressão Gênica no Desenvolvimento , Genes Letais , Integrases/genética , Camundongos , Transdução de Sinais , Fatores de Transcrição de Domínio TEA , Proteínas de Sinalização YAP
14.
Acta Otolaryngol ; 137(5): 482-484, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27841099

RESUMO

CONCLUSIONS: Patients with BPPV comorbid with hypertension (h-BPPV) tend to receive a delayed diagnosis of BPPV. Comorbidity with hypertension did not influence the efficacy of the repositioning maneuver; however, comorbidity with hypertension was associated with an increased recurrence rate of BPPV. OBJECTIVES: To determine the clinical characteristics and outcomes of h-BPPV, as well as the clinical differences between h-BPPV and idiopathic BPPV (i-BPPV). METHODS: The authors reviewed the medical records of 41 consecutive patients with h-BPPV (the h-BPPV group) from March to December 2014 and 47 patients with i-BPPV (the i-BPPV group) during the same period. RESULTS: There were no significant differences in age, sex ratio, or the affected side between the h-BPPV and i-BPPV groups. The proportion of patients reporting an initial episode of positional vertigo was significantly lower in the h-BPPV group (51.22% vs 74.47%; p = .024). Patients in the h-BPPV group reported a longer median episode duration than did those in the i-BPPV group (60 days vs 15 days; p = .017). The results of treatment using repositioning maneuvers were similar between the two groups. At follow-up, 13 patients in the h-BPPV group were diagnosed with recurrent BPPV compared with six in the i-BPPV group (p = .031).


Assuntos
Vertigem Posicional Paroxística Benigna/complicações , Vertigem Posicional Paroxística Benigna/terapia , Hipertensão/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
Orthop Surg ; 8(4): 496-502, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28032714

RESUMO

OBJECTIVE: Complex cobalt-chromium alloys, bearing surfaces of the second-generation metal-on-metal (MoM) hip prostheses, are subject to wear and generate cobalt nanoparticles (CoNPs). CoNPs could reduce cellular viability, activate the mitogen-activated protein kinase (MAPK) pathway and increase cell apoptosis via reactive oxygen species (ROS). However, the detailed mechanisms of ROS functioning on CoNP-mediated signaling molecules and cytotoxicity has not yet been fully demonstrated. The present study investigated the functional role of N-acetylcysteine (NAC) in reversing the activation of ROS signaling pathways triggered by CoNPs in normal mice kidney cells (TCMK-1 cells). METHODS: After being pretreated with NAC, TCMK-1 cells were treated with 300-700 µmol/L CoNPs, then, CCK-8 assay was used to verify the survival of TCMK-1 cells. Annexin V/PI staining was performed to investigate the apoptosis of TCMK-1 cells after NAC and different concentrations of CoNP treatments. In addition, western blot was performed to identify the cytokine (p-ERK, p-p38, and p-JNK) expression of the ROS-related MAPK signaling pathway. RESULTS: Apoptosis rate of TCMK-1 cells was increased obviously after different concentrations of CoNP treatment. However, TCMK-1 cells, pretreated with NAC, exhibited a significantly decreased apoptosis rate. In addition, p-ERK, p-p38, and p-JNK expressions were increased with CoNP treatment, which indicated that CoNPs could activate the MAPK pathway. Interestingly, this entire stimulated phenomenon by CoNPs was reversed with NAC treatment. CONCLUSIONS: These findings indicated that NAC could reverse CoNP-induced cytotoxicity by inhibiting ROS-induced cell death and cytokine expression. To our knowledge, this is the first report that describes how CoNP-induced cytotoxicity in TCMK-1 cells could be attenuated by anti-oxidative agents (NAC), which may function through inhibition of cell death and ROS.


Assuntos
Acetilcisteína/farmacologia , Apoptose/efeitos dos fármacos , Cobalto/toxicidade , Citocinas/metabolismo , Sequestradores de Radicais Livres/farmacologia , Nanopartículas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Animais , Biomarcadores/metabolismo , Western Blotting , Linhagem Celular , Prótese de Quadril/efeitos adversos , Próteses Articulares Metal-Metal/efeitos adversos , Camundongos , Transdução de Sinais/efeitos dos fármacos
16.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 30(6): 739-741, 2016 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-29786266

RESUMO

OBJECTIVE: To explore the effectiveness of preperitoneal herniorrhaphy with Ultrapro Plug (UPP) mesh for umbilical hernia repair in adults. METHODS: Between September 2011 and June 2015, 71 patients with umbilical hernia underwent preperitoneal herniorrhaphy with UPP mesh. There were 26 males and 45 females, aged 19-92 years (mean, 54.3 years). The disease duration was 45 days to 30 years (median, 18 months). Umbilical hernia was diagnosed through physical examination, ultrasound, and other relevant auxiliary examination. According to American Society of Anesthesiologists (ASA) classification, 12 cases were rated as grade Ⅰ, 34 cases as grade Ⅱ, 21 cases as grade Ⅲ, and 4?cases as grade Ⅳ. The operation time, postoperative hospitalization time, complication, and recurrence were recorded. RESULTS: The diameter of hernia ring ranged 0.5-3.0 cm (mean, 1.8 cm). There was no vessel or intestine injury. The operation time was 12-35 minutes (mean, 22.4 minutes); postoperative hospitalization time was 12-48 hours (mean, 16.3 hours). Fat liquefaction of incision occurred in 2 cases, and primary healing of incision was obtained in the other cases. Sixty-nine patients were followed up 8-51 months (median, 28 months). Hernia recurrence and patch infection occurred in 1 case respectively during follow-up. No postoperative foreign body sensation and chronic pain occurred. CONCLUSIONS: Repairing umbilical hernia in adults with UPP mesh should be safe and reliable, because it has the advantages of short operation time, short hospital stay, less complication, and lower incidence of recurrence.

17.
Int J Clin Exp Med ; 8(4): 6224-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26131229

RESUMO

OBJECTIVE: To assess the association between coronary heart disease (CHD) and vitamin D receptor (VDR) gene polymorphisms in Han Chinese adults. METHODS: A total of 215 CHD patients and 67 controls were recruited. In both groups, the VDR gene single nucleotide polymorphisms (SNP) of Tru9I (rs757343), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) were detected, and the frequencies of VDR genotypes were compared between patients and controls. The relationship between VDR FokI genotype and risk for CHD was assessed by logistic regression analysis after adjusting for age and sex. In addition, the clinical parameters and biochemical characteristics of CHD subgroups were compared according to the VDR FokI polymorphism. RESULTS: The frequencies of FokI genotypes in CHD patients were 23.7% for AA, 47.9% for AG, and 28.4% for GG. The frequency of FokI-GG genotype significantly decreased in CHD patients as compared to control group (P = 0.039). No significant differences were observed in other VDR SNPs (rs7975232, rs731236 and rs757343) (P > 0.05) between groups. FokI-A allele carriers had a 2.61-fold increase in the odds (95% CI: 1.116-6.102, P = 0.027) as compare to CHD subjects with FokI mutation. In CHD subgroup, patients with GG genotype had a significantly higher concentration of high-density lipoprotein cholesterol than those with AG genotype or A* genotype (P = 0.001, respectively). CONCLUSION: VDR FokI polymorphisms appear to be associated with CHD. GG genotype predicts a higher HDL-cholesterol in CHD adults.

18.
Int J Clin Exp Med ; 8(10): 18629-37, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26770476

RESUMO

To study the relationship between human 8-oxoguanine glycosylase (hOGG1) Ser326Cys gene polymorphism and coronary artery lesions in patients with diabetes mellitus, we analyzed 323 patients with diabetic mellitus, who underwent coronary angiography. Using PCR-RFLP, these patients were grouped into three genotypes: Cys/Cys (n=85), Ser/Ser (n=121), and Ser/Cys (n=117). Several clinical data, including history of diseases and biochemical indices were recorded. hOGG1 mRNA expression and 8-hydroxy deoxyguanosine (8-OHdG) were measured by RT-PCR and ELISA, respectively. The quantities and severity of coronary artery with lesions were analyzed from coronary angiography. The Gensini and SYNTAX scores were detected by the unitary criteria. The 8-OHdG levels showed statistical difference among the three genotypes (F=21.56, P<0.05). Also, 8-OHdG in Cys/Cys genotype was higher than Ser/Ser and Ser/Cys genotype (q=2.32, q=3.12, P<0.05). In terms of the expression of hOGGl mRNA, the measure of hOGGl/ß-actin showed significant difference among the three groups (F=12.56, P<0.05). On comparing two groups, hOGGl/ß-actin in Cys/Cys genotype was higher thanSer/Ser and Ser/Cys genotypes (q=2.32, q=3.12, P<0.05). Percentage of 3-vessel lesions was high in Cys/Cys genotype and percentage of 1-vessel lesions was low in Ser/Cys genotype. Gensini and SYNTAX scores and ratio of complex lesions were significantly higher in the Cys/Cys genotype than the other two genotypes (FGensini=47.16, FSYNTAX=55.12; P<0.05). hOGG1 Ser326Cys polymorphism showed correlation with coronary artery lesions in patients with diabetes mellitus, and Cys/Cys genotype may have more impact on the severity of lesions.

19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 32(6): 1207-11, 2015 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-27079088

RESUMO

Pulse waves contain abundant physiological and pathological information of human body. Research of the relationship between pulse wave and human cardiovascular physiological parameters can not only help clinical diagnosis and treatment of cardiovascular diseases, but also contribute to develop many new medical instruments. Based on the traditional double elastic cavity model, the human cardiovascular system was established by using the electric network model in this paper. The change of wall pressure and blood flow in artery was simulated. And the influence of the peripheral resistance and vessel compliance to the distribution of blood flow in artery was analyzed. The simulation results were compared with the clinical monitoring results to predict the physiological and pathological state of human body. The result showed that the simulation waveform of arterial wall pressure and blood flow was stabile after the second cardiac cycle. With the increasing of peripheral resistance, the systolic blood pressure of artery increased, the diastolic blood pressure had no significant change, and the pulse pressure of artery increased gradually. With the decreasing of vessel compliance, the vasoactivity became worse and the pulse pressure increased correspondingly. The simulation results were consistent with the clinical monitoring results. The increasing of peripheral resistance and decreasing of vascular compliance indicated that the incidence of hypertension and atherosclerosis was increased.


Assuntos
Coração/fisiologia , Modelos Cardiovasculares , Resistência Vascular , Aorta , Artérias/fisiologia , Aterosclerose , Pressão Sanguínea , Doenças Cardiovasculares , Eletricidade , Hemodinâmica , Humanos , Hipertensão
20.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 32(4): 378-81, 2014 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-25241541

RESUMO

OBJECTIVE: To examine the oral health status among the orphan children and adolescents of Chongqing and assist in planning of the oral health programs. METHODS: According to the third national oral health investigation of epidemiology, the dental caries, gingival bleeding and calculus was examined among 317 orphan living in Chongqing, by cluster sampling. The statistical software SPSS 17.0 was used for the data analysis. RESULTS: In primary and permanent teeth, the prevalence of dental caries and mean DMFT (dmft) were found to be 50.00%, 1.94 +/- 2.81 and 39.53%, 0.90 +/- 1.38. There were no significant difference between female and male (P>0.05). But there was significant difference of the prevalence of permanent tooth caries between the age group under 12 (include 12) and above 12 (P < 0.05). It was also found that 35.25% of the orphan children and adolescents had caries in the first permanent molar, and there was significant difference between female and male (P < 0.05). Neither of the caries teeth above was treated nor the healthy teeth were sealed. The prevalence rate of gingival bleeding was 78.22%, and the calculus rate was 67.66%. CONCLUSION: The oral status of the orphan is poor, and this community has experienced a low utilization of preventive or therapeutic oral health services. In the future work, orphans should be considered as a priority group when make plans for oral health care.


Assuntos
Índice CPO , Cárie Dentária , Adolescente , Criança , Pré-Escolar , China , Dentição Permanente , Feminino , Nível de Saúde , Humanos , Masculino , Dente Molar , Saúde Bucal , Prevalência
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