RESUMO
Even though it is very important, it is still rather difficult to detect minuscule levels of the bacterial pathogen in clinical practice, such as samples from dental implants. We construct here an efficient scaffold for label-free and sensitive Staphylococcus aureus (S. aureus) detection. The precise recognition of target bacteria by the detection scaffold leads to the self-assembly of Chain i and DNAzyme based cleavage of Chain iii. In detail, active DNAzyme conformation is formed based on the hybridization of Chain iii and Chain ii, and a nicking site is generated in Chain iii, making it possible to form a self-primer in Chain i. With the assistance of DNA polymerase, a single-strand DNA chain is added to the 3' terminal of Chain i, in which process the bacteria is released for the complex to bind with a next detection scaffold, forming a signal recycle. Following DNAzyme-based cleavage, the liberated sequences unroll MB and release G-rich sequences that can specifically bind with the fluorescent dye Thioflavin T (ThT), initiating ThT's fluorescence signal production. The approach demonstrates a wide detection range of 102 CFU/mL and 106 CFU/mL with a low limit of detection of 45 CFU/mL based on the developed detection scaffold, offering good prospects in the diagnosis of bacterial illnesses.
Assuntos
Técnicas Biossensoriais , DNA Catalítico , DNA Catalítico/metabolismo , Staphylococcus aureus/genética , DNA/genética , DNA de Cadeia Simples , Hibridização de Ácido Nucleico , Limite de Detecção , Técnicas de Amplificação de Ácido NucleicoRESUMO
PURPOSE: To investigate the clinical characteristics of oral and maxillofacial tumors in children and adolescents. METHODS: This is a retrospective study of patients who had oral and maxillofacial tumors under the age of 18 years and were treated at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from January 1990 to July 2021 (31 y). Their general conditions, pathological diagnosis, gender, age, and anatomical location were counted to analyze their morbidity and composition characteristics. RESULTS: This study contained 5405 cases, including 2903 male patients and 2502 female patients, with a median age of 9 years. Peak incidence was observed in the 14 to 18 years age group. The mandible (22.15%), maxilla (11.75%), and tongue (9.25%) were the most common sites of incidence. Malignant and intermediate type tumors accounted for 13.04%, benign tumors and tumor-like lesions for 55.67%, most often occurs in the maxillofacial bone, of which fibro-osseous lesions constitute an important part. Cysts accounted for 31.29%. Among the tumors occurring in the jaws, the most common malignant type was sarcoma, and ameloblastoma was the most common benign tumor. Malignant jaw tumors were mostly treated by resection, 10.64% by fibular flap reconstruction. While benign jaw tumors and tumor-like lesions were mostly treated by resection or curettage. CONCLUSIONS: The distribution of anatomical location and pathological types of oral and maxillofacial tumors in children has certain characteristics, so that the selection of their treatment options is different from that of adults due to the consideration of the growth and developmental characteristics of children.
Assuntos
Ameloblastoma , Neoplasias Maxilomandibulares , Neoplasias de Tecidos Moles , Cirurgia Bucal , Adulto , Humanos , Criança , Masculino , Feminino , Adolescente , Estudos Retrospectivos , Neoplasias Maxilomandibulares/epidemiologia , Neoplasias Maxilomandibulares/cirurgia , Neoplasias Maxilomandibulares/diagnóstico , Ameloblastoma/epidemiologia , Ameloblastoma/cirurgiaRESUMO
Primary hepatocellular carcinoma (HCC) is a common malignant tumor. Surgery is the main treatment, but HCC patients have a potential risk of tumor recurrence. Besides, many limitations arise during the application of single first-line antitumor drugs. Here, we selected Pluronic F-127 and sodium alginate (SA) to prepare a thermosensitive gel (Gel). The optimal synergistic ratio of PTX and DOX on the SMMC-7721 cells was 1: 2 (w/w), calculated by the Chou-Talalay analysis. Then, PTX and DOX coloaded liposomes (PD-LPs) with such drugs ratios presented enhanced anticancer ability in vitro. Upon local injection, the PD-LPs Gel formed a nanoparticles reservoir at tumor via sol-gel transformation, while exhibiting a long-term effective anti-tumor ability in vivo. The relative tumor volume after the PD-LPs Gel treatment was reduced over 62%. Effective mitochondria related apoptosis induction was observed. Therefore, the local delivery of PD-LPs Gel can be a promising alternative method for the HCC therapy.
Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular , Doxorrubicina , Neoplasias Hepáticas Experimentais , Mitocôndrias Hepáticas , Nanocompostos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Humanos , Lipossomos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/patologia , Nanocompostos/química , Nanocompostos/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Phototherapy is a promising treatment method for cancer therapy. However, the various factors have greatly restricted phototherapy development, including the poor accumulation of photosensitizer in tumor, hypoxia in solid tumor tissue and systemic phototoxicity. Herein, a mitochondrial-targeted multifunctional dye-anchored manganese oxide nanoparticle (IR808@MnO NP) is developed for enhancing phototherapy of cancer. In this nanoplatform, IR808 as a small molecule dye acts as a tumor targeting ligand to make IR808@MnO NPs with capacity to actively target tumor cells and relocate finally in the mitochondria. Meanwhile, continuous production of oxygen (O2 ) and regulation of pH induced by the high reactivity and specificity of MnO NPs toward mitochondrial endogenous hydrogen peroxide (H2 O2 ) could effectively modulate tumor hypoxia and lessen the tumor subacid environment. Large amounts of reactive oxide species (ROS) are generated during the reaction process between H2 O2 and MnO NPs. Furthermore, under laser irradiation, IR808 in IR808@MnO NPs turns O2 into a highly toxic singlet oxygen (1 O2 ) and generates hyperthermia. The results indicate that IR808@MnO NPs have the high efficiency of specific targeting of tumors, relieving tumor subacid environment, improving the tumor hypoxia environment, and generating large amounts of ROS to kill tumor cells. It is expected to have a wide application in treating cancer.
Assuntos
Neoplasias da Mama/terapia , Corantes/química , Compostos de Manganês/química , Mitocôndrias/metabolismo , Nanopartículas/química , Óxidos/química , Fototerapia , Animais , Materiais Biocompatíveis/química , Neoplasias da Mama/patologia , Sobrevivência Celular , Feminino , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A sensitive and selective method for separating fluoroquinolones (FQs) from bovine milk samples was successfully developed using montmorillonite magnetic molecularly imprinted polymers (MMMIPs) as adsorbents. MMMIPs were prepared using montmorillonite as carrier, fleroxacin (FLE) as template molecule, and Fe3O4 magnetite as magnetic component. MMMIPs possessed high adsorption capacity of 46.3 mg g(-1) for FLE. A rapid and convenient magnetic solid-phase extraction procedure coupled with capillary electrophoresis was established with MMMIPs as adsorbents for simultaneous and selective extraction of four FQs in bovine milk samples. Limits of detection ranged between 12.9 and 18.8 µg L(-1), and the RSDs were between 1.8% and 8.6%. The proposed method was successfully applied to spike bovine milk samples with recoveries of 92.7%-108.6%.
Assuntos
Antibacterianos/isolamento & purificação , Resíduos de Drogas/isolamento & purificação , Eletroforese Capilar/métodos , Fluoroquinolonas/isolamento & purificação , Leite/química , Extração em Fase Sólida/métodos , Animais , Antibacterianos/análise , Bovinos , Resíduos de Drogas/análise , Fluoroquinolonas/análise , Contaminação de Alimentos/análise , Magnetismo , Impressão Molecular , Polímeros/síntese química , Polímeros/química , Extração em Fase Sólida/instrumentaçãoRESUMO
Rhabdomyosarcoma with TFCP2-related fusions (TFCP2-RMS) is a rare entity that commonly affects young adults with a predilection for skeletal involvement. We herein report a 40-year-old female patient with TFCP2-RMS who was misdiagnosed as fibrous dysplasia or low-grade central osteosarcoma of the mandible by referring institutions. Histologically, the tumor showed dominant spindle cells and focal epithelioid cells with marked immature woven bone formation. Immunophenotypically, in addition to the characteristic expression of myogenic markers, ALK, and cytokeratins, tumor cells also unusually expressed osteogenic markers, such as MDM2 and SATB2. Through fluorescence in situ hybridization, the tumor cells showed EWSR1::TFCP2 gene fusion and no MDM2 gene amplification. This is a rare case of TFCP2-RMS, which was misdiagnosed as low-grade central osteosarcoma due to its presenting immunophenotype of MDM2 and SATB2, as well as extensive osteoid matrix formation.
Assuntos
Erros de Diagnóstico , Neoplasias Mandibulares , Osteossarcoma , Rabdomiossarcoma , Fatores de Transcrição , Humanos , Feminino , Adulto , Osteossarcoma/diagnóstico , Osteossarcoma/genética , Osteossarcoma/patologia , Fatores de Transcrição/genética , Neoplasias Mandibulares/patologia , Neoplasias Mandibulares/genética , Neoplasias Mandibulares/diagnóstico , Neoplasias Mandibulares/diagnóstico por imagem , Rabdomiossarcoma/genética , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/patologia , Proteínas de Ligação a DNA/genética , Diagnóstico Diferencial , Hibridização in Situ Fluorescente , Rearranjo Gênico , Biomarcadores Tumorais/genética , Displasia Fibrosa Óssea/genética , Displasia Fibrosa Óssea/diagnóstico , Displasia Fibrosa Óssea/patologia , Tomografia Computadorizada por Raios X , Radiografia PanorâmicaRESUMO
Leukemia inhibitory factor (LIF) has been recognized as a novel inflammatory modulator in inflammation-associated diseases. This study aimed to investigate the modulation of LIF in dental pulp inflammation. Experimental pulpitis was established in wild-type (WT) and Lif-deficient (Lif-/-) mice. Histological and immunostaining analyses were conducted to assess the role of LIF in the progression of pulpitis. Mouse macrophage cell line (RAW264.7) was treated with LPS to simulate an inflammatory environment. Exogenous LIF was added to this system to examine its modulation in macrophage inflammatory response in vitro. Primary bone marrow-derived macrophages (BMDMs) from WT and Lif-/- mice were isolated and stimulated with LPS to confirm the effect of Lif deletion on macrophage inflammatory response. Supernatants from LIF and LPS-treated human dental pulp cells (hDPCs) were collected and added to macrophages. Macrophage chemotaxis was assessed using transwell assays. The results showed an increased expression of LIF and LIFR with the progression of pulpitis, and LIFR was highly expressed in macrophages. Lif deficiency alleviated experimental pulpitis with the reduction of pro-inflammatory cytokines and macrophage infiltration. Exogenous LIF promoted inflammatory response of LPS-induced macrophages through a STAT3/p65-dependent pathway. Consistently, Lif deletion inhibited macrophage inflammatory response in vitro. Supernatants of LIF-treated hDPCs enhanced macrophage migration in LPS-induced inflammatory environment. Our findings demonstrated that LIF aggravates pulpitis by promoting macrophage inflammatory response through a STAT3/p65-dependent pathway. Furthermore, LIF plays a crucial role in driving the recruitment of macrophages to inflamed pulp tissue by promoting chemokine secretion in DPCs.
Assuntos
Pulpite , Animais , Humanos , Camundongos , Polpa Dentária/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Fator Inibidor de Leucemia/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Pulpite/metabolismoRESUMO
BACKGROUND: Clear cell odontogenic carcinoma (CCOC) is an odontogenic carcinoma characterized by sheets and islands of vacuolated and clear cells. The diagnosis of atypical CCOC can pose a challenge when tumor cells deviate from their characteristic clear morphology, even with the aid of genetic profiling for CCOC identification. CASE PRESENTATION: In this manuscript, we detailed the inaugural instance of a recurrently recurring clear cell odontogenic carcinoma (CCOC) with pronounced squamous differentiation in a 64-year-old male. The primary tumor in this individual initially displayed a biphasic clear cell phenotype. However, subsequent to the third recurrence, the clear tumor cells were entirely supplanted by epidermoid cells characterized by eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli. Notable aggressive attributes such as necrosis, conspicuous cytological malignancy, perineural dissemination, and vascular invasion were noted. Additionally, the tumor progressed to manifest lung metastases. The tumor cells exhibited positive immunoreactivity for AE1/AE3, KRT19, Pan-CK, EMA, P40, P63, CK34ßE12, and P53, while they tested negative for CK35ßH11, KRT7, S-100, and neuroendocrine markers. The Ki-67 proliferation index was calculated at an average of 15%. Furthermore, FISH analysis unveiled the presence of the EWSR1::ATF1 gene fusion. CONCLUSIONS: This case illustrated a rare and aggressive case of CCOC characterized by significant squamous differentiation upon recurrence of the tumor.
Assuntos
Biomarcadores Tumorais , Tumores Odontogênicos , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Odontogênicos/patologia , Tumores Odontogênicos/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/genética , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patologia , Proteínas de Fusão Oncogênica/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Imuno-HistoquímicaRESUMO
Clear cell odontogenic carcinoma is a rare malignancy, which is vary in behavior from indolent tumor to cases with frequent recurrence and rare metastasis. In this manuscript, we report a case of clear cell odontogenic carcinoma of right lower mandible with cervical lymph node metastasis in a 50-year-old female. The tumor recurred and metastasized to vertebra and pleura after adjuvant radiation and chemotherapy, and the patient died of the disease 29 months after diagnosis. Pathologically, the tumor was composed of epithelial nests dominated by clear cells with ameloblastoma-like pattern and biphasic pattern. The tumor cells showed strong positive for AE1/AE3, KRT19, KRT5/6, P63, focal positive for KRT7, and weak positive for MUC1. Molecularly, EWSR1::ATF1 gene fusion was identified. To our knowledge, this report describes the first case of metastasis of clear cell odontogenic carcinoma involving regional lymph nodes and distant pleural and vertebral areas, demonstrating an aggressive clinical course of clear cell odontogenic carcinoma.
Assuntos
Ameloblastoma , Carcinoma , Tumores Odontogênicos , Feminino , Humanos , Pessoa de Meia-Idade , Pleura/patologia , Tumores Odontogênicos/patologia , Ameloblastoma/patologia , Coluna Vertebral/patologiaRESUMO
In recent years, the accelerated development of G-quadruplexes and hydrogels has driven the development of intelligent biomaterials. Based on the excellent biocompatibility and special biological functions of G-quadruplexes, and the hydrophilicity, high-water retention, high water content, flexibility and excellent biodegradability of hydrogels, G-quadruplex hydrogels are widely used in various fields by combining the dual advantages of G-quadruplexes and hydrogels. Here, we provide a systematic and comprehensive classification of G-quadruplex hydrogels in terms of preparation strategies and applications. This paper reveals how G-quadruplex hydrogels skillfully utilize the special biological functions of G-quadruplexes and the skeleton structure of hydrogels, and expounds its applications in the fields of biomedicine, biocatalysis, biosensing and biomaterials. In addition, we deeply analyze the challenges in preparation, applications, stability and safety of G-quadruplex hydrogels, as well as potential future development directions.
Assuntos
Materiais Biocompatíveis , Quadruplex G , Hidrogéis , Hidrogéis/química , Hidrogéis/uso terapêutico , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Humanos , Técnicas Biossensoriais , Cicatrização , Infecções/tratamento farmacológico , Neoplasias/tratamento farmacológico , AnimaisRESUMO
A simple and effective template-free synthesis method for nanosized conducting polymers with self-stability and functionality is a main challenge. Herein, a strategy is reported for the facile synthesis of poly(1,5-diaminonaphthalene) nanospherical particles by an interfacial miniemulsion oxidative polymerization of 1,5-diaminonaphthalene at mobile microinterfaces between a stirred biphase without external emulsifiers. The size of the nanospheres was carefully optimized by controlling the polymerization conditions. Formation and self-stabilization mechanisms of the nanoparticles are proposed. The constantly movable and refreshed microinterface is a key to successful synthesis of the nanospheres, for significantly suppressing secondary growth leading to agglomerated particles because vigorous stirring makes as-formed self-stabilized nanospheres instantly leave the microinterfaces. The resulting nanospheres possess several advantages: clean surface, self-stability, redispersibility, semiconductivity, electroactivity, and fluorescence emission. The fluorescence emission can be quenched by specific quenchers, thus enabling low-cost, high-performance chemosensors to be obtained for the sensitive detection of Zn(II) ions in a wide linear concentration range of more than five orders of magnitude with a superior detection limit down to 1 nM.
Assuntos
2-Naftilamina/análogos & derivados , Zinco/química , 2-Naftilamina/síntese química , 2-Naftilamina/química , Condutividade Elétrica , Estrutura Molecular , Nanopartículas/química , Tamanho da Partícula , Polimerização , Polímeros/síntese química , Polímeros/químicaRESUMO
T-cell engagers (TCEs) represent a breakthrough in hematological malignancy treatment but are vulnerable to antigen escape and lack a vaccination effect. The "immunologically cold" solid tumor presents substantial challenges due to intratumor heterogeneity and an immunosuppressive tumor microenvironment (TME). Here, a methoxy poly(ethylene glycol) (mPEG)-masked CD44×PD-L1/CD3 trispecific T-cell nanoengager loaded with the STING agonist c-di-AMP (CDA) (PmTriTNE@CDA) for the treatment of triple-negative breast cancer (TNBC) is rationally designed. PmTriTNE@CDA shows tumor-specific accumulation and is preferentially unmasked in response to a weakly acidic TME to prevent on-target off-tumor toxicity. The unmasked CD44×PD-L1/CD3 trispecific T-cell nanoengager (TriTNE) targets dual tumor-associated antigens (TAAs) to redirect CD8+ T cells for heterogeneous TNBC lysis while achieving PD-L1 blockade. PmTriTNE synergized with CDA to transform the cold tumor into a hot tumor, eradicate the large established TNBC tumor, and induce protective immune memory in a 4T1 orthotopic tumor model without causing obvious toxicity. PmTriTNE@CDA shows potent efficacy in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. This study serves as a proof-of-concept demonstration of a nanobased TCEs strategy to expand therapeutic combinations that previously could not be achieved due to systemic toxicity with the aim of overcoming TNBC heterogeneity and immunotherapy resistance.
Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Camundongos , Animais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Antígeno B7-H1/uso terapêutico , Linhagem Celular Tumoral , Imunoterapia , Modelos Animais de Doenças , Fatores Imunológicos/uso terapêutico , Vacinação , Polietilenoglicóis/uso terapêutico , Microambiente TumoralRESUMO
OBJECTIVES: To investigate caries status and its impact factors in preschool children in plateau and to provide reference for caries prevention in highlands. METHODS: Examination of caries was performed on 1 597 children aged 3-5 years old in 11 kindergartens in Changdu, Xizang, in accordance with the 4th National Oral Health Survey standards and methods. Their parents were surveyed with the questionnaire regarding oral hygiene habit and consciousness about oral health and related factors. All the data were collected and analyzed. RESULTS: The prevalence of caries among children aged 3-5 years old in Changdu was 52.85%, with dmft index of 2.44. The caries rate and dmft of children aged 3 years old were lower than those of children aged 4 and 5 years old (P<0.05). No significant difference was observed in the caries rate between males and females (P>0.05). Single-factor analysis showed that the frequency of brushing teeth more than twice a day, low frequency of eating sweets, high frequency of drinking butter tea, and regular oral examination can reduce the rate of caries (P<0.05). Multivariate logistic analysis showed that the frequency of eating sweets, drinking butter tea, and oral examination are related impact factors of caries. CONCLUSIONS: The prevalence of ca-ries in children aged 3-5 years old in Changdu increases with aging. Good oral hygiene and eating habits and regular oral examination can reduce the rate of caries.
Assuntos
Cárie Dentária , Pré-Escolar , Estudos Transversais , Índice CPO , Cárie Dentária/epidemiologia , Cárie Dentária/prevenção & controle , Suscetibilidade à Cárie Dentária , Feminino , Humanos , Masculino , Saúde Bucal , Higiene Bucal , PrevalênciaRESUMO
PURPOSE: To explore the effect of erythritol on the growth of Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans(Aa), Actinomices viscosus (Av), and to explore how Porphyromonas gingivalis affected by erythritol influence mRNA expression level of inflammatory in periodontal cells. METHODS: Pg, Aa, Av were anaerobically cultured (80%N2, 10%CO2, 10%H2) at 37â in 2, 4, 8, 16, 32, 64, 128 g/L erythritol- BHI mixture groups (experimental groups) and BHI groups (control group). The lowest erythritol concentration without turbidity or precipitation was the minimum inhibitory concentration. Pg was cultured in MIC, 1/2, 1/4, 1/8 MIC erythritol- BHI mixture groups (experimental groups) and BHI groups (control group). Each kind of bacteria in each concentration group was centrifugalled and cleaned before added into DMEM. The mixed suspension was co-cultured with the periodontal ligament cells in four generations for 24 hours, the supernatan was removed , then the total RNA in cracking cells was extracted and reversing transcription. At last, the relative expression of IL-1, IL-6, TNF-a was detected real-time fluorescent quantitative PCR. The data were analyzed with SPSS19.0 software package. RESULTS: The minimum inhibitory by concentrations of erythritol on three bacteria were as followed: Pg: 64 g/Lï¼Aa: 128 g/Lï¼Av: 128 g/L. The ability of stimulating periodontal ligament cells to produce IL-1ß, IL-6 and TNF-α was different when Pg was cultured under different concentrations of erythritol. There was no significant difference between 0 g/L of control group and 8 g/L of experimental group. As the concentration reached 16 g/L, the relative expression of IL-1ß, IL-6, TNF-α was reduced, and the higher concentration was, the less inflammatory factors was. However, the inflammatory factors in all the experimental groups were always significantly higher than that in the blank control group (P<0.05). CONCLUSIONS: Erythritol has an inhibitory effect on the growth of Pg, Aa and Av. In a certain range, higher concentration of erythritol delivers better inhibition effect. Erythritol can also reduce the periodontal pathogenicity of pathogenic bacteria in a way inhibiting the virulence of these bacteria, reducing the production of IL-1ß, IL-6, and TNF-a in periodontal cells.
Assuntos
Antibacterianos , Eritritol , Aggregatibacter actinomycetemcomitans , Interleucina-1beta , Porphyromonas gingivalis , Fator de Necrose Tumoral alfaRESUMO
Background: Platinum (II) (Pt(II))-based anticancer drugs dominate the chemotherapy field of ovarian cancer. However, the patient's quality of life has severely limited owing to dose-limiting toxicities and the advanced disease at the time of diagnosis. Multifunctional tumor-targeted nanosized ultrasound contrast agents (glutathione (GSH)-sensitive platinum (IV) (Pt(IV)) prodrug-loaded phase-transitional nanoparticles, Pt(IV) NP-cRGD) were developed for precise theranostics against ovarian cancer. Methods: Pt(IV) NP-cRGD were composed of a perfluorohexane (PFH) liquid core, a hybrid lipid-polymer shell with PLGA12k-PEG2k and DSPE-PEG1k-Pt(IV), and an active targeting ligand, the cRGD peptide (PLGA: poly(lactic-co-glycolic acid), PEG: polyethylene glycol, DSPE: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, cRGD: cyclic Arg-Gly-Asp). Pt(IV), a popular alternative to Pt(II), was covalently attached to DSPE-PEG1k to form the prodrug, which fine-tuned lipophilicity and improved cellular uptake. The potential of Pt(IV) NP-cRGD as contrast agents for ultrasound (US) imaging was assessed in vitro and in vivo. Moreover, studies on the antitumor efficiency and antitumor mechanism of Pt(IV) NP-cRGD assisted by US were carried out. Results: Pt(IV) NP-cRGD exhibited strong echogenic signals and excellent echo persistence under an US field. In addition, the GSH-sensitive and US-triggered drug delivery system maximized the therapeutic effect while reducing the toxicity of chemotherapy. The mechanistic studies confirmed that Pt(IV) NP-cRGD with US consumed GSH and enhanced reactive oxy gen species (ROS) levels, which further causes mitochondria-mediated apoptosis. Conclusion: A multifunctional nanoplatform based on phase-transitional Pt(IV) NP-cRGD with US exhibited excellent echogenic signals, brilliant therapeutic efficacy and limited side effect, suggesting precise theranostics against ovarian cancer.
Assuntos
Antineoplásicos/administração & dosagem , Terapia de Alvo Molecular/métodos , Nanocompostos/administração & dosagem , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Compostos de Platina/administração & dosagem , Ultrassonografia/métodos , Animais , Meios de Contraste/administração & dosagem , Modelos Animais de Doenças , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Feminino , Lipídeos/administração & dosagem , Camundongos Nus , Nanocompostos/química , Transplante de Neoplasias , Peptídeos Cíclicos/administração & dosagem , Polímeros/administração & dosagem , Pró-Fármacos/administração & dosagem , Nanomedicina Teranóstica/métodos , Transplante Heterólogo , Resultado do TratamentoRESUMO
OBJECTIVE: To determine cement distribution patterns on therapeutic efficacy after percutaneous vertebroplasty treatment of osteoporotic vertebral compression fractures (OVCFs) with intravertebral cleft (IVC). METHODS: Patients who were treated with percutaneous vertebroplasty for single OVCFs with IVC and met this study's inclusion criteria were retrospectively reviewed. The follow-up period was at least 2 years. Distribution patterns of cement in the IVC area were respectively specified into 2 groups: group 1: solid lump distribution pattern (n = 22); group 2: the comparatively diffused pattern (n = 90). Radiologic and clinical parameters were analyzed and compared. Then, associations of recollapse with covariates and a risk score were further analyzed and developed to predict recollapse of the augmented vertebrae. RESULTS: At the immediate postoperative period, all patients benefited from significant improvement in vertebrae height and kyphotic angle correction. However, significant recollapse was observed at the 2 years postoperative follow-up for the patients in group 1. Furthermore, we found that preoperative severe kyphotic deformity (a cutoff value of 12.5°), solid lump cement distribution pattern, and larger reduction angle (a cutoff value of 8.3°) was significantly associated with increased risk for recollapse. A risk score was developed based on the number of risk factors present in each patient and the receiver operating characteristic curve of the risk score generated an area under the curve of 0.788 (95% confidence interval 0.702-0.873, P = 0.000). CONCLUSIONS: The comparatively diffused pattern shows better long-term radiologic and clinical outcomes for the treatment for OVCFs with IVC. A risk score can be used to predict the incidence of recollapse.
Assuntos
Cimentos Ósseos/farmacocinética , Fraturas por Compressão/cirurgia , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Idoso , Feminino , Fraturas por Compressão/diagnóstico por imagem , Humanos , Cifose/diagnóstico por imagem , Cifose/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Masculino , Fraturas por Osteoporose/diagnóstico por imagem , Recidiva , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vertebroplastia/métodosRESUMO
It is interesting to note that the demineralization of natural enamel does not happen as readily as that of the synthesized hydroxyapatite (HAP), although they share a similar chemical composition. We suggest that the hierarchical structure of enamel is an important factor in the preservation of the natural material against dissolution. The anisotropic demineralization of HAP is revealed experimentally, and this phenomenon is understood by the different interfacial structures of HAP-water at the atomic level. It is found that HAP {001} facets can be more resistant against dissolution than {100} under acidic conditions. Although {100} is the largest surface of the typical HAP crystal, it is {001}, the smallest habit face, that is chosen by the living organisms to build the outer surface of enamel by an oriented assembly of the rodlike crystals. We reveal that such a biological construction can confer on enamel protections against erosion, since {001} is relatively dissolution-insensitive. Thus, the spontaneous dissolution of enamel surface can be retarded in biological milieu by such a smart construction. The current study demonstrates the importance of hierarchical structures in the functional biomaterials.
Assuntos
Esmalte Dentário/química , Durapatita/química , Ácido Clorídrico/química , Desmineralização do Dente , Adolescente , Adulto , Anisotropia , Dente Pré-Molar/química , Simulação por Computador , Cristalização , Cristalografia , Durapatita/síntese química , Humanos , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Modelos Moleculares , Prótons , Propriedades de Superfície , Água/químicaRESUMO
Small cell neuroendocrine carcinoma (SNEC) of the oral cavity is a rare and distinctive tumor with aggressive clinical behavior. Thus far, only a small number of cases have been reported and no definitive standard treatment strategy has been determined. The current study reports a case of oral SNEC arising in the lower gingiva in a 73-year-old male. Computed tomography displayed a relatively well-defined mass measuring 2.8×2×1.4 cm in size. The mass was located in the buccal side of the right mandibular posterior gingiva and exhibited no bony involvement. Histopathological examination revealed a proliferation of small cells with ovoid- to spindle-shaped nuclei, fine granular chromatin, inconspicuous nucleoli, scant cytoplasm and high mitotic activity. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3, chromogranin A, synaptophysin and neuron-specific enolase. Surgical resection and radical neck dissection were performed prior to the administration of adjuvant chemotherapy with a combination of cisplatin and etoposide. No evidence of local recurrence or metastasis was observed at 14 months post-surgery.
RESUMO
Graphene oxide (GO) immunotoxicity is not clarified well up to date. Herein we reported the effects of GOs with and without polyvinylpyrrolidone (PVP) coating on human immune cells such as dendritic cells (DCs), T lymphocytes and macrophages. Human immune cells such as dendritic cells (DCs), T lymphocytes and macrophages were isolated from health donated bloods, PVP-coating GO (PVP-GO) exhibited lower immunogenicity compared with pure GO on the aspect of inducing differentiation and maturation of dendritic cells (DCs), the levels of secreted TNF-α and IL-1ß had no obvious difference between two groups, yet the secretion of IL-6 remained in PVP-coating GO group. In addition, PVP-coating GO delayed significantly the apoptotic process of T lymphocytes, at the same time, and exhibited anti-phagocytosis ability against macrophages and markedly enhanced the physiological activity of macrophages. In conclusion, PVP-coating GO possesses good immunological biocompatibility and immunoenhancement effects in vitro, and is likely to be an available candidate of immunoadjuvant in the future.
Assuntos
Materiais Revestidos Biocompatíveis/farmacologia , Grafite/química , Grafite/toxicidade , Imunotoxinas/toxicidade , Óxidos/química , Povidona/farmacologia , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Humanos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Microscopia de Força Atômica , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Biológicos , Fenótipo , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
Tooth eruption is an orientating action which migrates teeth coronally during life, even in bone or after occlusion contact is lost. The eruption pathway is due to bone resorption near the enamel crown and bone deposition around the cementum-covered roots. Due to their proximity to bone resorption and deposition, we hypothesize that the hard tissues enamel, dentine or cementum are important during eruption. In the present study, extracted human teeth were cut into enamel samples, enamel-dentine samples or dentine-cementum samples, and implanted into bone defects in rabbit tibia. Hematoxylin and eosin, tartrate-resistant acid phosphatase activity, tetracycline tracing and scanning electron microscopy were used to investigate bone resorption and deposition 1-8 weeks after surgery. The results showed that resorption lacunae with numerous osteoclasts were observed facing enamel and significant new bone deposition occurred near the cementum surface, compared to other hard tooth surfaces. These findings indicate that the enamel crown may stimulate bone resorption and initiate the eruption pathway, and that the cementum root may stimulate bone deposition. Bone regeneration initiated by tooth hard tissues may be a potential motive force during tooth eruption.