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1.
Int J Periodontics Restorative Dent ; 40(4): e157-e162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32559040

RESUMO

Placement of short implants is a common approach to rehabilitate edentulous areas. The objective of this study was to evaluate the long-term survival of 7.0- and 8.5-mm implants placed in either a delayed or immediate loading protocol. Life table analysis revealed the implants treated with the delayed loading protocol had a 90.9% survival rate and the implants treated with the immediate loading protocol had a survival rate of 92.0%. The results of this 8-year prospective study demonstrate similar survival rates of short, cylindrical threaded implants placed by either a delayed or immediate loading protocol.


Assuntos
Implantes Dentários , Carga Imediata em Implante Dentário , Arcada Edêntula/cirurgia , Implantação Dentária Endo-Óssea , Prótese Dentária Fixada por Implante , Falha de Restauração Dentária , Prótese Parcial Fixa , Estudos Prospectivos
2.
Artigo em Inglês | MEDLINE | ID: mdl-31766175

RESUMO

Online pharmacies are an important part of the modern healthcare system. They interact with customers through well-designed web interfaces to deliver the healthcare customers need. In addition to well-designed web interfaces, online pharmacies rely on an effective supply chain system to provide medical supplies and services, and especially effective inventory management for supply systems. As green supply chain management (GSCM) becomes increasingly considered by countries, how to develop a sustainable inventory model that takes into account the revenue growth of an online pharmacy while preventing waste and reducing energy costs has become very important. In line with this trend, the study develops a sustainable inventory model that focuses on both economic aspect (profit) and environmental aspect (losses from excessive inventory) within a framework of a single period multi-product inventory model. Specifically, the sustainable inventory model applies the visual-attention-dependent demand (VADD) rate to characterize customer demand in an online trading environment, thereby seeking a profitable marketing strategy and reducing losses due to excessive inventory. Since the complexity of model optimization will drastically increase due to the inclusion of many products in the problem, a Genetic Algorithm (GA) based solution procedure is proposed to increase the feasibility of the proposed model in solving real problems. The sustainable inventory model and the solution procedure are illustrated, compared, and discussed with an online pharmacy example. Additionally, a sensitivity analysis is formulated to study the influence of model parameters on the model solution, the loss of unsold inventory that results in a waste of resources and energy, and the profit of online pharmacies.


Assuntos
Equipamentos e Provisões/economia , Equipamentos e Provisões/estatística & dados numéricos , Disponibilidade de Medicamentos Via Internet/organização & administração , Disponibilidade de Medicamentos Via Internet/estatística & dados numéricos , Humanos
3.
Quintessence Int ; 50(9): 742-753, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482155

RESUMO

OBJECTIVES: To evaluate the efficacy of diagnostic imaging for temporomandibular joint rheumatoid arthritis (TMJ RA). Inflammation of the TMJ has a high correlation (> 17%) with the late stages of RA. Clinical recognition of TMJ RA using diagnostic imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and cone beam computed tomography (CBCT), is limited to osseous and soft tissue components of the TMJ. Positron emission tomography (PET) and positron emission tomography/CT (PET/CT) are novel technologies that have shown increasing relevance in the detection and management of TMJ RA. METHOD AND MATERIALS: Following the preferred reporting items for systematic reviews and meta-analysis (PRISMA, 2009) guidelines, and using databases such as PubMed, Ovid Medline, Google Scholar, Web of Science, Scopus, and EBSCOhost, 94 publications were identified, and 27 studies were selected for this systematic review. A flowchart of the comprehensive study selection was generated. Quality assessment and data extraction were performed independently by three reviewers. RESULTS: It was noted that two-dimensional radiographs, CBCT, multidetector CT, and MRI are the most commonly used methods in TMJ RA assessment, although they are not useful for determination of active disease. MRI has excellent contrast resolution and can acquire dynamic imaging for demonstration of the functionality of the TMJ. CT and ultrasound imaging also have specific indication in imaging the TMJ. PET used in conjunction with CT is the only imaging modality that can quantify TMJ RA in active disease. CONCLUSIONS: PET/CT images provide unique quantitative information that cannot be obtained from any other imaging modalities.


Assuntos
Artrite Reumatoide , Transtornos da Articulação Temporomandibular , Tomografia Computadorizada de Feixe Cônico , Humanos , Imagem por Ressonância Magnética , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Articulação Temporomandibular
4.
Artigo em Inglês | MEDLINE | ID: mdl-31116831

RESUMO

PURPOSE: The purpose of this review was to explore the available literature and compile studies that discuss the relevance of the biofilm, onset and progression of disease, critical peri-implant pocket depth, frequency of supportive implant therapy, excess cement, and keratinized peri-implant tissues as related to peri-implant disease. MATERIALS AND METHODS: PubMed, Cochrane Oral Health Group Specialized Trial Register, and hand searches of related journals were performed in relationship to the focused question. Reports describing techniques, preclinical studies, and case reports were excluded. RESULTS: Due to the absence of controlled studies, a meta-analysis could not be performed. Summaries of relevant publications were completed for each topic area. Clinical recommendations were developed to provide guidance to the practitioner. CONCLUSION: The importance of proper diagnosis, planning, and clinical treatment cannot be overstated. Patient factors including systemic disease, periodontal status, and oral hygiene significantly impact peri-implant health. Clinician factors such as implant position, excess cement, and restorative design can contribute to development of peri-implant disease. Surveillance of implant status is essential and can be assisted by the assessment of risk factors, establishment of a proper recall program, and monitoring changes in bone and peri-implant pocket depths.


Assuntos
Cimentos Dentários/efeitos adversos , Implantes Dentários/efeitos adversos , Membrana Mucosa/patologia , Peri-Implantite/etiologia , Biofilmes , Humanos , Higiene Bucal , Peri-Implantite/prevenção & controle , Fatores de Risco
5.
Polymers (Basel) ; 11(1)2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30960168

RESUMO

A polyaniline (PANI)/tin oxide (SnO2) composite for a CO sensor was fabricated using a composite film composed of SnO2 nanoparticles and PANI deposition in the present study. Tin oxide nanoparticles were synthesized by the sol-gel method. The SnO2 nanoparticles provided a high surface area to significantly enhance the response to the change in CO concentration at low operating temperature (<75 °C). The excellent sensor response was mainly attributed to the relatively good properties of PANI in the redox reaction during sensing, which produced a great resistance difference between the air and CO gas at low operating temperature. Therefore, the combination of n-type SnO2 nanoparticles with a high surface area and a thick film of conductive PANI is an effective strategy to design a high-performance CO gas sensor.

6.
Am J Med Genet A ; 179(3): 486-493, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30653816

RESUMO

Mucopolysaccharidosis Type VII (MPS7, also called ß-glucuronidase deficiency or Sly syndrome; MIM 253220) is an extremely rare autosomal recessive lysosomal storage disease, caused by mutations in the GUSB gene. ß-glucuronidase (GUSB) is a lysosomal hydrolase involved in the stepwise degradation of glucuronic acid-containing glycosaminoglycans (GAGs). Patients affected with MPS VII are not able to completely degrade glucuronic acid-containing GAGs, including chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, and heparan sulfate. The accumulation of these GAGs in lysosomes of various tissues leads to cellular and organ dysfunctions. Characteristic features of MPS VII include short stature, macrocephaly, hirsutism, coarse facies, hearing loss, cloudy cornea, short neck, valvular cardiac defects, hepatosplenomegaly, and dysostosis multiplex. Oral manifestations in patients affected with MPS VII have never been reported. Oral manifestations observed in three patients consist of wide root canal spaces, taurodontism, hyperplastic dental follicles, malposition of unerupted permanent molars, and failure of tooth eruption with malformed roots. The unusual skeletal features of the patients include maxillary hypoplasia, hypoplastic midface, long mandibular length, mandibular prognathism, hypoplastic and aplastic mandibular condyles, absence of the dens of the second cervical vertebra, and erosion of the cortex of the lower border of mandibles. Dogs affected with MPS VII had anterior and posterior open bite, maxillary hypoplasia, premolar crowding, and mandibular prognathism. Unlike patients with MPS VII, the dogs had unremarkable mandibular condyles. This is the first report of oral manifestations in patients affected with MPS VII.


Assuntos
Doenças do Cão/diagnóstico , Anormalidades da Boca/diagnóstico , Mucopolissacaridose VII/diagnóstico , Fenótipo , Adolescente , Animais , Criança , Doenças do Cão/genética , Cães , Facies , Feminino , Glucuronidase/química , Glucuronidase/genética , Glucuronidase/metabolismo , Humanos , Lactente , Modelos Moleculares , Mucopolissacaridose VII/genética , Conformação Proteica , Radiografia , Relação Estrutura-Atividade , Tomografia Computadorizada por Raios X
7.
Cancers (Basel) ; 11(1)2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30626171

RESUMO

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Detecting and enumerating circulating tumor cells (CTCs) in patients with colorectal cancer emerged as an important prognostic tool which provides a direct estimate of metastatic potential. Improving the turnaround time and decreasing sample volume is critical for incorporating this liquid biopsy tool into routine practice. The objective of the current study was to validate the clinical feasibility of a self-assembled cell array (SACA) chip, a CTC counting platform with less than 4 h turnaround time, in patients with newly diagnosed colorectal cancers. In total, 179 patients with newly diagnosed colorectal cancers from a single institute were enrolled. Epithelial cell adhesion molecule positive (EpCAM(+)), cluster of differentiation 45 negative (CD45(-)) cells were isolated and enumerated from 2 mL of peripheral vein blood (PB) and inferior mesenteric vein blood (IMV) samples obtained during surgery. We found that the CTC count in PB but not IMV correlates with disease stages. Neoadjuvant chemotherapy did not lead to decreased CTC count in both types of blood samples. With cutoffs of four CTCs per 2 mL of blood, and serum carcinoembryonic antigen (CEA) level of 5 ng/mL, patients with non-metastatic disease were more likely to experience recurrence if they had high PB CTC count and high serum CEA concentration (odds ratio, 8.9). Our study demonstrates the feasibility of enumerating CTCs with a SACA chip in patients with colorectal cancer.

8.
J Biomed Sci ; 25(1): 60, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-30068339

RESUMO

BACKGROUND: Cancer stem cells are capable of undergoing cell division after surviving cancer therapies, leading to tumor progression and recurrence. Inhibitory agents against cancer stem cells may be therapeutically used for efficiently eradicating tumors. Therefore, the aim of this study was to identify the relevant driver genes that maintain cancer stemness in epidermal growth factor receptor (EGFR)-positive colorectal cancer (CRC) cells and to discover effective therapeutic agents against these genes. METHODS: In this study, EGFR-positive cancer stem-like cells (CSLCs) derived from HCT116 and HT29 cells were used as study models for in vitro inductions. To identify the differential genes that maintain CSLCs, RNAseq analysis was conducted followed by bioinformatics analysis. Moreover, a panel containing 172 therapeutic agents targeting the various pathways of stem cells was used to identify effective therapeutics against CSLCs. RESULTS: RNAseq analysis revealed that 654 and 840 genes were significantly upregulated and downregulated, respectively, in the HCT116 CSLCs. Among these genes, notably, platelet-derived growth factor A (PDGFA) and signal transducer and activator of transcription 3 (STAT3) were relevant according to the cancer pathway analyzed using NetworkAnalyst. Furthermore, therapeutic screening revealed that the agents targeting STAT3 and Wnt signaling pathways were efficient in reducing the cell viabilities of both HCT116 and HT29 cells. Consequently, we discovered that STAT3 inhibition using homoharringtonine and STAT3 knockdown significantly reduced the formation and survival of HT29-derived tumorspheres. We also observed that STAT3 phosphorylation was regulated by epidermal growth factor (EGF) to induce PDGFA and Wnt signaling cascades. CONCLUSIONS: We identified the potential genes involved in tumorsphere formation and survival in selective EGFR-positive CRCs. The results reveal that the EGF-STAT3 signaling pathway promotes and maintains CRC stemness. In addition, a crosstalk between STAT3 and Wnt activates the Wnt/ß-catenin signaling pathway, which is also responsible for cancer stemness. Thus, STAT3 is a putative therapeutic target for CRC treatment.


Assuntos
Neoplasias Colorretais/genética , Receptores ErbB/genética , Células-Tronco Neoplásicas/patologia , Fator de Transcrição STAT3/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Detecção Precoce de Câncer , Fator de Crescimento Epidérmico/genética , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Fosforilação , Fator de Crescimento Derivado de Plaquetas/genética , Análise de Sequência de RNA , Via de Sinalização Wnt
9.
Mol Carcinog ; 57(11): 1588-1598, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30035369

RESUMO

The epidermal growth factor (EGF) receptor (EGFR) overexpressed in many cancers, including lung and head and neck cancers, and is involved in cancer cell progression and survival. PD-L1, increases in tumor cells to evade and inhibit CD8+ T cells, is a clinical immunotherapeutic target. This study investigated the molecular mechanism of EGF on regulating PD-L1 in EGFR-positive cancers and determined potential agents to reduce PD-L1 expression. RNA sequencing (RNAseq) and bioinformatics analysis were performed to determine potential driver genes that regulate PD-L1 in tumor cells-derived tumorspheres which mimicking cancer stem cells. Then, the specific inhibitors targeting EGFR were applied to reduce the expression of PD-L1 in vitro and in vivo. We validated that EGF could induce PD-L1 expression in the selected EGFR-positive cancers. RNAseq results revealed that STAT1 increased as a driver gene in KOSC-3-derived tumorspheres; these data were analyzed using PANTHER followed by NetworkAnalyst. The blockade of EGFR by afatinib resulted in decreased STAT1 and IRF-1 levels, both are transcriptional factors of PD-L1, and disabled the IFNr-STAT1-mediated PD-L1 axis in vitro and in vivo. Moreover, STAT1 knockdown significantly reduced EGF-mediated PD-L1 expression, and ruxolitinib, a JAK1/JAK2 inhibitor, significantly inhibited STAT1 phosphorylation to reduce the IFNr-mediated PD-L1 axis. These results indicate that EGF exacerbates PD-L1 by increasing the protein levels of STAT1 to enforce the IFNr-JAK1/2-mediated signaling axis in selected EGFR-positive cancers. The inhibition of EGFR by afatinib significantly reduced PD-L1 and may be a potential strategy for enhancing immunotherapeutic efficacy.


Assuntos
Antígeno B7-H1/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica , Interferon gama/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Fator de Transcrição STAT1/genética , Afatinib/farmacologia , Animais , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores , Linhagem Celular Tumoral , Receptores ErbB/antagonistas & inibidores , Humanos , Imunofenotipagem , Masculino , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT1/metabolismo
10.
ACS Appl Mater Interfaces ; 10(25): 21160-21172, 2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29863836

RESUMO

Abnormal biochemical alteration such as unbalanced reactive oxygen species (ROS) levels has been considered as a potential disease-specific trigger to deliver therapeutics to target sites. However, in view of their minute variations in concentration, short lifetimes, and limited ranges of action, in situ generation of ROS with specific manipulations should be more effective for ROS-responsive drug delivery. Here we present a new delivery nanoplatform for photodynamic therapy (PDT) with on-demand drug release regulated by light irradiation. Rose bengal (RB) molecules, which exhibit a high yield of ROS generation, were encapsulated in a mixture of chitosan (CTS), poly(vinyl alcohol) (PVA), and branched polyethylenimine ( bPEI) with hydrophobic iron oxide nanoparticles through an oil-in-water emulsion method. The as-prepared magnetic nanoclusters (MNCs) with a tripolymer coating displayed high water dispersibility, efficient cellular uptake, and the cationic groups of CTS and bPEI were effective for RB loading through electrostatic interaction. The encapsulation efficiency of RB in MNCs could be further improved by increasing the amount of short bPEI chains. During the photodynamic process, controlled release of the host molecules (i.e., RB) or guest molecules (i.e., paclitaxel) from the bPEI-based nanoplatform was achieved simultaneously through a photooxidation action sensitized by RB. This approach promises specific payload release and highly effective PDT or PDT combined therapy in various cancer cell lines including breast (MCF-7 and multidrug resistant MCF-7 subline), SKOV-3 ovarian, and Tramp-C1 prostate. In in vivo xenograft studies, the nanoengineered light-switchable carrier also greatly augments its PDT efficacy against multidrug resistant MCF-7/MDR tumor as compared with free drugs. All the above findings suggest that the substantial effects of enhanced drug distribution for efficient cancer therapy was achieved with this smart nanocarrier capable of on demand drug release and delivery, thus exerting its therapeutic activity to a greater extent.


Assuntos
Liberação Controlada de Fármacos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Humanos , Masculino , Nanopartículas , Fotoquimioterapia , Rosa Bengala
11.
Lung Cancer ; 116: 80-89, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29413056

RESUMO

OBJECTIVES: YM155, an inhibitor of interleukin enhancer-binding factor 3 (ILF3), significantly suppresses cancer stemness property, implying that ILF3 contributes to cell survival of cancer stem cells. However, the molecular function of ILF3 inhibiting cancer stemness remains unclear. This study aimed to uncover the potential function of ILF3 involving in cell survival of epidermal growth factor receptor (EGFR)-positive lung stem-like cancer, and to investigate the potential role to improve the efficacy of anti-EGFR therapeutics. MATERIALS AND METHODS: The association of EGFR and ILF3 in expression and regulations was first investigated in this study. Lung cancer A549 cells with deprivation of ILF3 were created by the gene-knockdown method and then RNAseq was applied to identify the putative genes regulated by ILF3. Meanwhile, HCC827- and A549-derived cancer stem-like cells were used to investigate the role of ILF3 in the formation of cancer stem-like tumorspheres. RESULTS: We found that EGFR induced ILF3 expression, and YM155 reduced EGFR expression. The knockdown of ILF3 reduced not only EGFR expression in mRNA and protein levels, but also cell proliferation in vitro and in vivo, demonstrating that ILF3 may play an important role in contributing to cancer cell survival. Moreover, the knockdown and inhibition of ILF3 by shRNA and YM155, respectively, reduced the formation and survival of HCC827- and A549-derived tumorspheres through inhibiting ErbB3 (HER3) expression, and synergized the therapeutic efficacy of afatinib, a tyrosine kinase inhibitor, against EGFR-positive A549 lung cells. CONCLUSION: This study demonstrated that ILF3 plays an oncogenic like role in maintaining the EGFR-mediated cellular pathway, and can be a therapeutic target to improve the therapeutic efficacy of afatinib. Our results suggested that YM155, an ILF3 inhibitor, has the potential for utilization in cancer therapy against EGFR-positive lung cancers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Imidazóis/farmacologia , Neoplasias Pulmonares/metabolismo , Naftoquinonas/farmacologia , Células-Tronco Neoplásicas/metabolismo , Proteínas do Fator Nuclear 90/metabolismo , Células A549 , Afatinib/administração & dosagem , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Imidazóis/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Terapia de Alvo Molecular , Naftoquinonas/administração & dosagem , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Proteínas do Fator Nuclear 90/antagonistas & inibidores , Fosforilação , Inibidores de Proteínas Quinases/administração & dosagem , Distribuição Aleatória , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Front Chem ; 6: 647, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30687694

RESUMO

Dual functional drug carrier has been a modern strategy in cancer therapy because it is a platform to elicit additive and synergistic effects through combination therapy. Photo-activated external stimuli such as reactive oxygen species (ROS) also ensure adequate drug delivery in a precise temporal and spatial manner. However, current ROS-responsive drug delivery systems usually require tedious synthetic procedures. A facile one-pot approach has been reported herein, to obtain self-assembled polymeric nanocarriers (NCs) for simultaneous paclitaxel (PTX)- and Rose Bengal (RB)-loading to achieve combined chemo-photodynamic therapy and controlled drug release in responsive to a light-induced ROS stimulus. To encapsulate these hydrophobic and hydrophilic drugs, chitosan (CTS), branched polyethylenimine (bPEI) and polyvinyl alcohol (PVA) were selected and fabricated into nanoblended matrices through an oil-in-water emulsion method. The amphiphilic properties of CTS permit simultaneous entrapment of PTX and RB, while the encapsulation efficiency of RB was further improved by increasing the amount of short-chain bPEI. During the one-step assembly process, bovine serum albumin (BSA) was also added to condense the cationic tripolymer mixtures into more stable nanocarriers (BNCs). Hyaluronic acid (HA) was subsequently grafted onto the surface of BNCs through electrostatic interaction, leading to the formation of HA-BSA/CTS/PVA/bPEI-blended nanocarriers (HBNCs) to achieve an efficient prostate-cancer-cell uptake. Importantly, in response to external light irradiation, HBNCs become destabilized owing to the RB-mediated photodynamic action. It allows an on-demand dual-payload release to evoke a simultaneous photodynamic and chemo treatment for cancer cell eradication. Thus, HBNCs present a new promising approach that exhibits a specific vulnerability to RB-induced photosensitization. The consequent dual-cargo release is also expected to successfully combat cancer through a synergistic anti-tumor effect.

13.
Oncotarget ; 8(44): 76204-76213, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-29100304

RESUMO

Germline variations at JAK2, TERT, HBS1L-MYB and MECOM have been found to associate with myeloproliferative neoplasms (MPNs) in European populations. Whether these germline variations are associated with MPNs in Taiwanese population is obscure. Here we aimed to evaluate the association of five germline variations (JAK2 46/1 haplotype tagged by rs12343867, JAK2 intron 8 rs12339666, TERT rs2736100, HBS1L-MYB rs9376092 and MECOM rs2201862) and the risk of MPNs in Taiwanese population. A total of 178 MPN patients (109 essential thrombocythemia, 54 polycythemia vera and 15 primary myelofibrosis) were enrolled into this study. The information of 17033 control subjects was obtained from Taiwan Biobank database. The JAK2 46/1 haplotype, JAK2 rs12339666 and TERT rs2736100 were significantly associated with Taiwanese MPNs (P = 3.6×10-19, 1.9×10-19 and 3.1×10-6, respectively), and JAK2V617F-positive MPNs (n=121) (P = 5.6×10-21, 4.4×10-21 and 8.6×10-7, respectively). In JAK2V617F-negative cases (n=55), only the JAK2 46/1 haplotype and JAK2 rs12339666 remained statistically significant (P= 0.009 and 0.007, respectively). When stratified by disease subtypes, the JAK2 46/1 haplotype and JAK2 rs12339666 were significantly associated with all three MPN subtypes, but TERT rs2736100 was only associated with essential thrombocythemia and polycythemia vera. We did not find any association of these five SNPs with CALR mutations in our cohort. Furthermore, the risk alleles of MECOM rs2201862 and HBS1L-MYB rs9376092 were demonstrated to be negatively associated with the risk of developing polycythemia vera. In conclusion, germline variations at JAK2 (both the 46/1 haplotype and rs12339666) and TERT rs2736100 were associated with MPNs in Taiwanese population.

14.
Nanoscale ; 9(35): 13235-13244, 2017 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-28853469

RESUMO

Novel one-dimensional (1D) heterostructure arrays composed of CuO nanowire cores, intermediate In2S3 nanostructures, and ZnO nanorod sheaths (i.e. CuO/In2S3/ZnO heterostructure arrays) have been successfully synthesized by a multi-step process. First, single-crystalline CuO nanowires were directly grown on flexible Cu mesh substrates using a one-step annealing process under ambient conditions. Second, In2S3 nanostructures and ZnO nanorods were sequentially grown on the CuO nanowires by a two-step hydrothermal method at low reaction temperature. The morphology, crystal structures, and optical properties of the CuO/In2S3/ZnO heterostructure arrays were studied by scanning electron microscopy, X-ray diffraction, transmission electron microscopy, energy-dispersive spectroscopy, and photoluminescence spectroscopy. The resultant ternary CuO/In2S3/ZnO heterostructure arrays exhibit excellent photocatalytic activity in the photodegradation of rhodamine 6G (R6G) under 10 W UV light irradiation, which is much higher than that of single-component (CuO nanowire arrays) or two-component systems (CuO/In2S3 heterostructure arrays). Furthermore, the reusability test demonstrates that the CuO/In2S3/ZnO heterostructure arrays on the Cu mesh still maintain high photocatalytic activity in the degradation of three kinds of organic pollutants even after five cycles, without any significant decline. These findings provide an insight into the design and synthesis of new CuO-based composites to effectively improve their photocatalytic performance.

15.
PLoS One ; 12(8): e0182149, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28787001

RESUMO

Cancer stem cell survival is the leading factor for tumor recurrence after tumor-suppressive treatments. Therefore, specific and efficient inhibitors of cancer stemness must be discovered for reducing tumor recurrence. YM155 has been indicated to significantly reduce stemness-derived tumorsphere formation. However, the pharmaceutical mechanism of YM155 against cancer stemness is unclear. This study investigated the potential mechanism of YM155 against cancer stemness in lung cancer. Tumorspheres derived from epidermal growth factor receptor (EGFR)-mutant HCC827 and EGFR wild-type A549 cells expressing higher cancer stemness markers (CD133, Oct4, and Nanog) were used as cancer stemness models. We observed that EGFR autophosphorylation (Y1068) was higher in HCC827- and A549-derived tumorspheres than in parental cells; this autophosphorylation induced tumorsphere formation by activating G9a-mediated stemness. Notably, YM155 inhibited tumorsphere formation by blocking the autophosphorylation of EGFR and the EGFR-G9a-mediated stemness pathway. The chemical and genetic inhibition of EGFR and G9a revealed the significant role of the EGFR-G9a pathway in maintaining the cancer stemness property. In conclusion, this study not only revealed that EGFR could trigger tumorsphere formation by elevating G9a-mediated stemness but also demonstrated that YM155 could inhibit this formation by simultaneously blocking EGFR autophosphorylation and G9a activity, thus acting as a potent agent against lung cancer stemness.


Assuntos
Antineoplásicos/farmacologia , Receptores ErbB/metabolismo , Antígenos de Histocompatibilidade/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Imidazóis/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Naftoquinonas/farmacologia , Afatinib , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Receptores ErbB/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metilação/efeitos dos fármacos , Fator 3 de Transcrição de Octâmero/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Quinazolinas/farmacologia , RNA Mensageiro/metabolismo
16.
BMC Cardiovasc Disord ; 17(1): 115, 2017 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-28482853

RESUMO

BACKGROUND: Eosinophilic myocarditis encompasses a variety of etiologies and the prognosis varies. For patients with a hypersensitive response to medications, high-dose corticosteroids and discontinuation of culprit medications are the main treatments. CASE PRESENTATION: We reported a young man with biopsy-proven eosinophilic myocarditis which was possibly induced by Chinese herbal medicine. His heart failure and left ventricular hypertrophy improved soon after low-dose corticosteroid. CONCLUSION: Low-dose corticosteroid may be effective in selected patients with eosinophilic myocarditis. Early echocardiographic follow-up is mandatory for evaluation of the clinical response.


Assuntos
Corticosteroides/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Eosinofilia/tratamento farmacológico , Miocardite/tratamento farmacológico , Prednisolona/administração & dosagem , Doença Aguda , Adulto , Biópsia , Ecocardiografia , Eosinofilia/induzido quimicamente , Eosinofilia/diagnóstico , Eosinofilia/imunologia , Insuficiência Cardíaca/etiologia , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Masculino , Miocardite/induzido quimicamente , Miocardite/diagnóstico , Miocardite/imunologia , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento
17.
Oncotarget ; 8(20): 32476-32491, 2017 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-28415571

RESUMO

Essential thrombocythemia (ET) is a BCL-ABL1-negative myeloproliferative neoplasm. We have reported that increased activated B cells can facilitate platelet production mediated by cytokines regardless JAK2 mutational status in ET. Recently, calreticulin (CALR) mutations were discovered in ~30% JAK2/MPL-unmutated ET and primary myelofibrosis. Here we sought to screen for CALR mutations and to evaluate B cell immune profiles in a cohort of adult Taiwanese ET patients. B cell populations, granulocytes/monocytes membrane-bound B cell-activating factor (mBAFF) levels, B cells toll-like receptor 4 (TLR4) expression and intracellular levels of interleukin (IL)-1ß/IL-6 and the expression of CD69, CD80, and CD86 were quantified by flow cytometry. Serum BAFF concentration was measured by ELISA. 48 healthy adults were used for comparison. 19 (35.2%) of 54 ET patients harbored 8 types of CALR exon 9 mutations including 4 (7.4%) patients with concomitant JAK2V617F mutations. Compared to JAK2V617F mutation, CALR mutations correlated with younger age at diagnosis (p=0.04), higher platelet count (p=0.004), lower hemoglobin level (p=0.013) and lower leukocyte count (p=0.013). Multivariate analysis adjusted for age, sex, follow-up period and hematological parameters confirmed that increased activated B cells were universally present in JAK2-mutated, CALR-mutated and triple-negative ET patients when compared to healthy adults. JAK2- and CALR-mutated ET have significantly higher fraction of B cells with TLR4 expression when compared to triple-negative ET (p=0.019 and 0.02, respectively). CALR-mutated ET had significantly higher number of CD69-positive activated B cells when compared to triple-negative ET (p=0.035). In conclusion, increased B cell activation is present in ET patients across different mutational subgroups.


Assuntos
Linfócitos B/imunologia , Calreticulina/genética , Calreticulina/imunologia , Janus Quinase 2/genética , Janus Quinase 2/imunologia , Trombocitemia Essencial/genética , Trombocitemia Essencial/imunologia , Adulto , Idoso , Linfócitos B/patologia , Calreticulina/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Janus Quinase 2/metabolismo , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Mutação , Trombocitemia Essencial/sangue , Trombocitemia Essencial/patologia , Adulto Jovem
18.
Med Oncol ; 34(5): 83, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28389907

RESUMO

Mutations in JAK2, MPL and CALR genes have been identified in the majority of myeloproliferative neoplasm (MPN) patients, and patients negative for these three mutations are the so-called triple-negative (TN) MPN. In this study, we examined the mutational profiles of 16 triple-negative MPN patients including 7 essential thrombocythemia (ET), 1 primary myelofibrosis and 8 polycythemia vera (PV). Targeted next-generation sequencing was performed using the ACTOnco Comprehensive Cancer Panel (Ion AmpliSeq Comprehensive Cancer Panel, Life Technologies) to target all coding exons of 409 cancer-related genes. Overall, 30 nonsynonymous somatic mutations were detected in 12 (75%) patients with a range of 1-5 mutations per sample. Notably, one ET patient was found to have JAK2V617F and KITP551L mutations at very low allele frequency. One MPLP70L and 1 MPLM602T mutations were identified each in 1 ET and 1 PV, respectively. Other recurrent mutations were also identified including KMT2C, KMT2D, IRS2, SYNE1, PDE4DIP, SETD2, ATM, TNFAIP3 and CCND2. In addition, germline mutations were also found in some cancer-related genes. Copy number changes were rare in this cohort of TN MPNs. In conclusion, both somatic and germline mutations can be detected in TN MPN patients.


Assuntos
DNA de Neoplasias/genética , Mutação , Transtornos Mieloproliferativos/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Calreticulina/genética , Análise Mutacional de DNA/métodos , DNA de Neoplasias/sangue , Feminino , Mutação em Linhagem Germinativa , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/sangue , Receptores de Trombopoetina/genética , Análise de Sequência de DNA/métodos
19.
J Neurosci ; 37(16): 4391-4404, 2017 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-28330877

RESUMO

The K+ channel pore-forming subunit Kv4.3 is expressed in a subset of nonpeptidergic nociceptors within the dorsal root ganglion (DRG), and knockdown of Kv4.3 selectively induces mechanical hypersensitivity, a major symptom of neuropathic pain. K+ channel modulatory subunits KChIP1, KChIP2, and DPP10 are coexpressed in Kv4.3+ DRG neurons, but whether they participate in Kv4.3-mediated pain control is unknown. Here, we show the existence of a Kv4.3/KChIP1/KChIP2/DPP10 complex (abbreviated as the Kv4 complex) in the endoplasmic reticulum and cell surface of DRG neurons. After intrathecal injection of a gene-specific antisense oligodeoxynucleotide to knock down the expression of each component in the Kv4 complex, mechanical hypersensitivity develops in the hindlimbs of rats in parallel with a reduction in all components in the lumbar DRGs. Electrophysiological data further indicate that the excitability of nonpeptidergic nociceptors is enhanced. The expression of all Kv4 complex components in DRG neurons is downregulated following spinal nerve ligation (SNL). To rescue Kv4 complex downregulation, cDNA constructs encoding Kv4.3, KChIP1, and DPP10 were transfected into the injured DRGs (defined as DRGs with injured spinal nerves) of living SNL rats. SNL-evoked mechanical hypersensitivity was attenuated, accompanied by a partial recovery of Kv4.3, KChIP1, and DPP10 surface levels in the injured DRGs. By showing an interdependent regulation among components in the Kv4 complex, this study demonstrates that K+ channel modulatory subunits KChIP1, KChIP2, and DPP10 participate in Kv4.3-mediated mechanical pain control. Thus, these modulatory subunits could be potential drug targets for neuropathic pain.SIGNIFICANCE STATEMENT Neuropathic pain, a type of moderate to severe chronic pain resulting from nerve injury or disorder, affects 6.9%-10% of the global population. However, less than half of patients report satisfactory pain relief from current treatments. K+ channels, which act to reduce nociceptor activity, have been suggested to be novel drug targets for neuropathic pain. This study is the first to show that K+ channel modulatory subunits KChIP1, KChIP2, and DPP10 are potential drug targets for neuropathic pain because they form a channel complex with the K+ channel pore-forming subunit Kv4.3 in a subset of nociceptors to selectively inhibit mechanical hypersensitivity, a major symptom of neuropathic pain.


Assuntos
Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Proteínas Interatuantes com Canais de Kv/metabolismo , Dor Nociceptiva/metabolismo , Canais de Potássio Shal/metabolismo , Animais , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Gânglios Espinais/fisiologia , Proteínas Interatuantes com Canais de Kv/genética , Masculino , Neurônios/metabolismo , Neurônios/fisiologia , Dor Nociceptiva/fisiopatologia , Ratos , Ratos Sprague-Dawley , Canais de Potássio Shal/genética , Tato
20.
J Nucl Cardiol ; 24(4): 1282-1288, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-26979308

RESUMO

BACKGROUND: Although cardiac resynchronization therapy (CRT) has been a useful treatment of heart failure, patients with CRT are still in risk of sudden cardiac death due to ventricular arrhythmia. The aim of this study was to investigate the impact of cardiac reverse remodeling after CRT on the prevalence of ventricular tachycardia or fibrillation (VT/VF). METHODS AND RESULTS: Forty-one heart failure patients (26 men, age 66 ± 10 years), who were implanted with CRT for at least 12 months, were enrolled. All patients received myocardial perfusion imaging (MPI) under CRT pacing to evaluate left ventricle (LV) function, dyssynchrony, and scar. VT/VF episodes during the follow-up period after MPI were recorded by the CRT devices. Sixteen patients (N = 16/41, 39%) were found to have VT/VF. Multivariate Cox regression analysis and receiver operating characteristic curve analysis showed that five risk factors were significant predictors of VT/VF, including increased left ventricle ejection fraction (LVEF) by ≤7% after CRT, low LVEF after CRT (≤30%), change of intrinsic QRS duration (iQRSd) by ≤7 ms, wide iQRSd after CRT (≥121 ms), and high systolic dyssynchrony after CRT (phase standard deviation ≥45.6°). For those patients with all of the 5 risk factors, 85.7% or more developed VT/VF. CONCLUSIONS: The characteristics of cardiac reverse remodeling after CRT as assessed by MPI are associated with the prevalence of ventricular arrhythmia.


Assuntos
Terapia de Ressincronização Cardíaca , Imagem de Perfusão do Miocárdio/métodos , Miocárdio/patologia , Taquicardia Ventricular/terapia , Fibrilação Ventricular/terapia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Taquicardia Ventricular/diagnóstico por imagem , Taquicardia Ventricular/etiologia , Fibrilação Ventricular/diagnóstico por imagem , Fibrilação Ventricular/etiologia
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