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2.
Front Pediatr ; 11: 1230366, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38250590

RESUMO

Background: Systemic lupus erythematosus is an autoimmune disease with diverse clinical manifestations. The symptoms of SLE in children are more atypical than adults. Childhood SLE complicated with Fanconi syndrome is extremely rare and even more difficult to diagnose. Case presentation: This article reports a preschool boy with SLE who presented with renal tubular acidosis, accompanied by weakness in both lower limbs, delayed growth, and malnutrition. It was later found that the patient had the complication of Fanconi syndrome with renal tubular acidosis. Ultimately, renal biopsy confirmed lupus nephritis. The patient was treated with corticosteroid combined with mycophenolate mofetil, hydroxychloroquine, and belimumab. The symptoms of the child were relieved. Conclusion: Here we report an extremely rare case of childhood SLE complicated with Fanconi syndrome. There has been no similar clinical report. It is necessary to be alert to the possibility of atypical SLE in children to avoid missed diagnosis and misdiagnosis.

3.
Front Microbiol ; 13: 993879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36238598

RESUMO

Aging is a complex multifactorial process that greatly affects animal health. Multi-omics analysis is widely applied in evolutionary biology and biomedical research. However, whether multi-omics can provide sufficient information to reveal comprehensive changes in aged non-human primates remains unclear. Here, we explored changes in host-microbe interactions with aging in Chinese rhesus macaques (Macaca mulatta lasiota, CRs) using multi-omics analysis. Results showed marked changes in the oral and gut microbiomes between young and aged CRs, including significantly reduced probiotic abundance and increased pathogenic bacterial abundance in aged CRs. Notably, the abundance of Lactobacillus, which can metabolize tryptophan to produce aryl hydrocarbon receptor (AhR) ligands, was decreased in aged CRs. Consistently, metabolomics detected a decrease in the plasma levels of AhR ligands. In addition, free fatty acid, acyl carnitine, heparin, 2-(4-hydroxyphenyl) propionic acid, and docosahexaenoic acid ethyl ester levels were increased in aged CRs, which may contribute to abnormal fatty acid metabolism and cardiovascular disease. Transcriptome analysis identified changes in the expression of genes associated with tryptophan metabolism and inflammation. In conclusion, many potential links among different omics were found, suggesting that aged CRs face multiple metabolic problems, immunological disorders, and oral and gut diseases. We determined that tryptophan metabolism is critical for the physiological health of aged CRs. Our findings demonstrate the value of multi-omics analyses in revealing host-microbe interactions in non-human primates and suggest that similar approaches could be applied in evolutionary and ecological research of other species.

4.
Anal Methods ; 13(48): 5859-5865, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34874025

RESUMO

As a kind of promising non-invasive biomarker, exosomes naturally occurring in saliva have recently attracted considerable attention in view of their potential use in the diagnosis of oral diseases. Herein, we propose a new electrochemical method for the sensitive and precise detection of salivary exosomes. A red blood cell membrane (RBCM) engineered with CD63 aptamer is the core element of the method and is used to camouflage a gold electrode, thus giving the electrode superior antifouling and targeting ability. Target exosomes presented in saliva are recognized and captured by the highly specific interaction between the exosomal CD63 and the aptamers engineered in RBCM. Then, silver nanoparticles modified with CD63 aptamers are recruited onto the electrode surface to generate significant electrochemical signals, which enables the sensitive detection of target exosomes. By using human oral squamous cell carcinoma CAL27 cell-derived exosomes as a model, the method allows target salivary exosome detection in a wide linear range from 5 × 102 to 1 × 106 particles per mL and a low detection limit of 2.07 × 102 particles per mL. Moreover, the method displays good reproducibility and is feasible for detecting target exosomes with high precision in saliva samples. Overall, the method may provide a useful tool for salivary exosome detection and may have great potential for practical use in the clinical diagnosis of oral diseases.


Assuntos
Aptâmeros de Nucleotídeos , Carcinoma de Células Escamosas , Exossomos , Nanopartículas Metálicas , Neoplasias Bucais , Aptâmeros de Nucleotídeos/metabolismo , Carcinoma de Células Escamosas/metabolismo , Membrana Celular/metabolismo , Exossomos/metabolismo , Humanos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/metabolismo , Reprodutibilidade dos Testes , Prata/metabolismo
5.
Int J Oral Sci ; 13(1): 40, 2021 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845186

RESUMO

The first branchial arch (BA1), which is derived from cranial neural crest (CNC) cells, gives rise to various orofacial tissues. Cre mice are widely used for the determination of CNC and exploration of gene functions in orofacial development. However, there is a lack of Cre mice specifically marked BA1's cells. Pax2-Cre allele was previously generated and has been widely used in the field of inner ear development. Here, by compounding Pax2-Cre and R26R-mTmG mice, we found a specific expression pattern of Pax2+ cells that marked BA1's mesenchymal cells and the BA1-derivatives. Compared to Pax2-Cre; R26R-mTmG allele, GFP+ cells were abundantly found both in BA1 and second branchial arch in Wnt1-Cre;R26R-mTmG mice. As BMP4 signaling is required for orofacial development, we over-activated Bmp4 by using Pax2-Cre; pMes-BMP4 strain. Interestingly, our results showed bilateral hyperplasia between the upper and lower teeth. We also compare the phenotypes of Wnt1-Cre; pMes-BMP4 and Pax2-Cre; pMes-BMP4 strains and found severe deformation of molar buds, palate, and maxilla-mandibular bony structures in Wnt1-Cre; pMes-BMP4 mice; however, the morphology of these orofacial organs were comparable between controls and Pax2-Cre; pMes-BMP4 mice except for bilateral hyperplastic tissues. We further explore the properties of the hyperplastic tissue and found it is not derived from Runx2+ cells but expresses Msx1, and probably caused by abnormal cell proliferation and altered expression pattern of p-Smad1/5/8. In sum, our findings suggest altering BMP4 signaling in BA1-specific cell lineage may lead to unique phenotypes in orofacial regions, further hinting that Pax2-Cre mice could be a new model for genetic manipulation of BA1-derived organogenesis in the orofacial region.


Assuntos
Região Branquial , Células-Tronco Mesenquimais , Animais , Proteína Morfogenética Óssea 4 , Camundongos , Crânio
6.
Front Cell Dev Biol ; 9: 621810, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178975

RESUMO

Distant metastasis is a major cause of treatment failure in nasopharyngeal carcinoma (NPC) patients. Cell surface proteins represent attractive targets for cancer diagnosis or therapy. However, the cell surface proteins associated with NPC metastasis are poorly understood. To identify potential therapeutic targets for NPC metastasis, we isolated cell surface proteins from two isogenic NPC cell lines, 6-10B (low metastatic) and 5-8F (highly metastatic), through cell surface biotinylation. Stable isotope labeling by amino acids in cell culture (SILAC) based proteomics was applied to comprehensively characterize the cell surface proteins related with the metastatic phenotype. We identified 294 differentially expressed cell surface proteins, including the most upregulated protein myoferlin (MYOF), two receptor tyrosine kinases(RTKs) epidermal growth factor receptor (EGFR) and ephrin type-A receptor 2 (EPHA2) and several integrin family molecules. These differentially expressed proteins are enriched in multiple biological pathways such as the FAK-PI3K-mTOR pathway, focal adhesions, and integrin-mediated cell adhesion. The knockdown of MYOF effectively suppresses the proliferation, migration and invasion of NPC cells. Immunohistochemistry analysis also showed that MYOF is associated with NPC metastasis. We experimentally confirmed, for the first time, that MYOF can interact with EGFR and EPHA2. Moreover, MYOF knockdown could influence not only EGFR activity and its downstream epithelial-mesenchymal transition (EMT), but also EPHA2 ligand-independent activity. These findings suggest that MYOF might be an attractive potential therapeutic target that has double effects of simultaneously influencing EGFR and EPHA2 signaling pathway. In conclusion, this is the first study to profile the cell surface proteins associated with NPC metastasis and provide valuable resource for future researches.

7.
Int J Oral Sci ; 13(1): 1, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33414369

RESUMO

Dental pulp can initiate its damage repair after an injury of the pulp-dentin complex by rearrangement of odontoblasts and formation of newly differentiated odontoblast-like cells. Connexin 43 (Cx43) is one of the gap junction proteins that participates in multiple tissue repair processes. However, the role of Cx43 in the repair of the dental pulp remains unclear. This study aimed to determine the function of Cx43 in the odontoblast arrangement patterns and odontoblastic differentiation. Human teeth for in vitro experiments were acquired, and a pulp injury model in Sprague-Dawley rats was used for in vivo analysis. The odontoblast arrangement pattern and the expression of Cx43 and dentin sialophosphoprotein (DSPP) were assessed. To investigate the function of Cx43 in odontoblastic differentiation, we overexpressed or inhibited Cx43. The results indicated that polarized odontoblasts were arranged along the pulp-dentin interface and had high levels of Cx43 expression in the healthy teeth; however, the odontoblast arrangement pattern was slightly changed concomitant to an increase in the Cx43 expression in the carious teeth. Regularly arranged odontoblast-like cells had high levels of the Cx43 expression during the formation of mature dentin, but the odontoblast-like cells were not regularly arranged beneath immature osteodentin in the pulp injury models. Subsequent in vitro experiments demonstrated that Cx43 is upregulated during odontoblastic differentiation of the dental pulp cells, and inhibition or overexpression of Cx43 influence the odontoblastic differentiation. Thus, Cx43 may be involved in the maintenance of odontoblast arrangement patterns, and influence the pulp repair outcomes by the regulation of odontoblastic differentiation.


Assuntos
Conexina 43 , Polpa Dentária , Animais , Diferenciação Celular , Proteínas da Matriz Extracelular , Odontoblastos , Fosfoproteínas , Ratos , Ratos Sprague-Dawley
8.
Anal Bioanal Chem ; 412(11): 2599-2606, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32055907

RESUMO

Recent studies reveal a great value of interleukin-8 (IL-8), a pro-inflammatory cytokine, as a potent biomarker for early diagnosis of oral cancer. Herein, a new electrochemical method is proposed to detect IL-8 by facilely incorporating DNA-templated quantum dots (QDs). In principle, target IL-8 is first treated with the reducing agent tris(2-carboxyethyl)phosphine (TCEP) to yield active thiols and then captured by antibody-functionalized magnetic beads (MBs). Thereafter, via the Michael addition reaction between the active thiol and maleimide group, a maleimide-modified DNA probe is linked to the surface of MBs, which can initiate a process of rolling circle amplification. In this way, long-range DNA strands are generated on the MB surface, subsequently recruiting DNA-templated CdTe/CdS QDs (DNA-QDs) to act as electrochemical reporters. By tracing the responses of DNA-QDs, the method allows IL-8 detection in a linear range from 5 to 5000 fg/mL with a detection limit of 3.36 fg/mL. The selectivity, reproducibility, and applicability in complex serum samples are also demonstrated to be favorable, indicating that the method may have a great potential in the future. More importantly, the use of TCEP treatment in the method not only provides a facile way to incorporate DNA-QDs, avoiding the complicated and time-consuming preparation process of antibody-DNA conjugates or functional nanomaterials; but also makes the method capable of being extended to detect other protein biomarkers in view of widespread presence of disulfides, which may hold a broad potential to facilitate efficient biosensing designs.


Assuntos
Ácidos Nucleicos Imobilizados/química , Interleucina-8/sangue , Neoplasias Bucais/sangue , Pontos Quânticos/química , Anticorpos Imobilizados/química , Técnicas Biossensoriais/métodos , Compostos de Cádmio/química , Técnicas Eletroquímicas/métodos , Humanos , Interleucina-8/análise , Limite de Detecção , Neoplasias Bucais/diagnóstico , Sulfetos/química , Telúrio/química
9.
Int J Oral Sci ; 12(1): 2, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31900383

RESUMO

Interleukin(IL)-1ß, a pro-inflammatory cytokine, was elevated and participates in periodontitis. Not only the link between IL-1ß and periodontitis was proved by clinical evidence, but also the increased IL-1ß triggers a series of inflammatory reactions and promotes bone resorption. Currently, IL-1ß blockage has been therapeutic strategies for autoimmune and autoinflammatory diseases such as rheumatoid arthritis, cryopyrin-associated periodic syndromes, gout and type II diabetes mellitus. It is speculated that IL-1ß be a potential therapeutic target for periodontitis. The review focuses on the production, mechanism, present treatments and future potential strategies for IL-1ß in periodontitis.


Assuntos
Inflamação/terapia , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/imunologia , Periodontite/terapia , Citocinas , Diabetes Mellitus Tipo 2 , Humanos , Inflamação/imunologia , Interleucina-1beta/efeitos dos fármacos , Periodontite/diagnóstico
10.
Oral Dis ; 26(3): 590-596, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31863612

RESUMO

OBJECTIVE: Fibroblast growth factor 8 (FGF8) signaling is essential in regulating craniofacial osteogenesis. This study aims to explore the effect of altered FGF8 signaling in maxillomandibular development during embryogenesis. MATERIALS AND METHODS: Dmp1Cre ;R26RmTmG mice were generated to trace Dmp1+ cell lineage, and Dmp1Cre ;R26RFgf8 mice were generated to explore the effects of augmented FGF8 signaling in Dmp1+ cells on osteogenesis with a focus on maxillomandibular development during embryogenesis, as assessed by whole mount skeletal staining, histology, and immunostaining. Additionally, cell proliferation rate and the expression of osteogenic genes were examined. RESULTS: Osteocytes of maxillomandibular bones were found Dmp1-positive prenatally, and Fgf8 over-expression in Dmp1+ cells led to mandibular hypoplasia. While Dmp1Cre allele functions in the osteocytes of the developing mandibular bone at as early as E13.5, and enhanced cell proliferation rate is observed in the bone forming region of the mandible in Dmp1Cre ;R26RFgf8 mice at E14.5, histological examination showed that osteogenesis was initially impacted at E15.5, along with an inhibition of osteogenic differentiation markers. CONCLUSIONS: Augmented FGF8 signaling in Dmp1+ cells lead to osteogenic deficiency in the mandibular bones, resulting in mandibular hypoplasia.


Assuntos
Desenvolvimento Embrionário , Fator 8 de Crescimento de Fibroblasto/fisiologia , Mandíbula/patologia , Osteócitos/patologia , Osteogênese , Transdução de Sinais , Animais , Embrião de Mamíferos , Proteínas da Matriz Extracelular/genética , Mandíbula/embriologia , Camundongos , Camundongos Transgênicos
11.
J Struct Biol ; 207(2): 115-122, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31153927

RESUMO

A single biomineralization of demineralized dentin is significant to restore the demineralized dentin due to dental caries or erosion. In recent years, meaningful progress has been made regarding the mechanisms involved in the biomineralization of dentin collagen. Concepts changing from the classical ion-based crystallization to non-classical particle-based crystallization, inspired a different strategy to infiltrate the demineralized dentin collagen. The remarkable discovery was the report of liquid-like amorphous calcium phosphate as nanoprecursor particles to carbonated hydroxyapatite. The non-collagenous proteins and their analogues are widely investigated, for their key role in controlling mineralization during the process of crystal nucleation and growth. The in-depth studies of the gap zone provided significant improvements in our understanding of the structure of collagen and of the intrafibrillar remineralization of collagen fibrils. The collagen is not a passive substrate as previously supposed, and the active role of guiding nanoprecursor infiltration and mediating its nucleation has been demonstrated. Furthermore, recovery of mechanical properties has been evaluated to determine the effectiveness of dentin remineralization. Finally, the problems regarding the origin formation of the calcium phosphate that is deposited in the collagen, and the exact interactions between the non-collagenous proteins, amorphous calcium phosphate and collagen are still unclear. We reviewed the importance of these findings in enriching our understanding of dentin biomineralization, while addressing certain limitations that are inherent to in vitro studies.


Assuntos
Colágeno/metabolismo , Cárie Dentária/metabolismo , Dentina/química , Erosão Dentária/metabolismo , Biomineralização , Fosfatos de Cálcio/metabolismo , Colágeno/química , Cristalização , Cárie Dentária/patologia , Dentina/metabolismo , Humanos , Fenômenos Mecânicos , Erosão Dentária/patologia
12.
J Neurooncol ; 141(1): 19-30, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30539341

RESUMO

BACKGROUND: Glioblastoma (GBM) is the most common malignant tumor originating in the brain parenchyma. The invasive and infiltrative properties of glioblastoma result in poor clinical prognosis to conventional therapies. Emerging reports on microRNAs as important regulators during the process of EMT provide new insights into treating glioblastoma through new targets. However, underlying molecular mechanism of the regulation of miR-101-3p in glioblastoma remains unclear. METHODS: Level of miR-101-3p was determined in GBM cell lines by qRT-PCR. MTT, colony formation and transwell assays were utilized to evaluate functions of overexpression of miR-101-3p/knock down of TRIM44 on proliferation, migration and invasion in GBM cells. Direct interaction between miR-101-3p and TRIM44 was validated using dual luciferase reporter system and impacts of overexpression of miR-101-3p/knock down of TRIM44 on regulation of EMT markers were assessed by Western blotting. RESULTS: MiR-101-3p was validated to be repressed expressed in glioblastoma cancer cell lines. Both overexpression of miR-101-3p and knock down of TRIM44 attenuated proliferation, migration and invasion of glioblastoma cell lines in vitro. TRIM44 was shown to promote EMT in GBM progress and reverse inhibitory function of miR-101-3p. MiR-101-3p was found to suppress the expression of TRIM44 via directly targeting its 3'UTR. CONCLUSIONS: Our findings suggested miR-101-3p regulated proliferation and migration of glioblastoma cells through attenuating TRIM44 induced EMT via direct targeting 3'UTR of TRIM44, which provided preliminary study of potential therapeutic target in future GBM treatment.


Assuntos
Neoplasias Encefálicas/metabolismo , Proteínas de Transporte/metabolismo , Proliferação de Células , Glioblastoma/metabolismo , MicroRNAs/metabolismo , Metástase Neoplásica , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas com Motivo Tripartido
13.
Connect Tissue Res ; 59(3): 255-262, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28816569

RESUMO

PURPOSE: Teeth are exposed to various forces during functional and parafunctional movements. These processes inevitably affect the dental pulp, and the mechanism of these influences has been the subject of many previous studies using different apparatuses and obtaining different results. In this study, we aimed to investigate the effects of compressive stress on the proliferation and differentiation of human dental pulp cells (hDPCs). MATERIALS AND METHODS: A four-point bending strain system was adopted to apply low-density cyclic uniaxial compressive stress (2000 microstrain, 0.5 Hz) to hDPCs for 1.5, 3, 6, 12, and 24 h. The cell cycle progression and mRNA expression of differentiation-related genes (BMP2, ALP, DMP1, DSPP, COL I) were then examined to investigate the proliferation and differentiation of hDPCs. RESULTS: The results showed that cyclic compressive stress changed the morphology of hDPCs after 12 and 24 h of mechanical loading; cell cycle progression was promoted, especially in the 24-h group (p < 0.05). The expression of BMP2 was significantly upregulated after 3 and 6 h of mechanical loading but declined in the 12- and 24-h groups, whereas the expression levels of DMP1 and DSPP were significantly upregulated in the 12- and 24-h loading groups (p < 0.05). CONCLUSIONS: Dental pulp cells were sensitive to compressive stress, especially after 12 and 24 h of applied force. Proliferation and odontogenic differentiation were significantly promoted in this in vitro model.


Assuntos
Proliferação de Células/fisiologia , Polpa Dentária/citologia , Teste de Esforço , Odontogênese/fisiologia , Adulto , Fosfatase Alcalina/metabolismo , Diferenciação Celular/fisiologia , Células Cultivadas , Células Epiteliais/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Humanos , Odontoblastos/citologia
14.
J Cancer ; 8(3): 479-489, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28261350

RESUMO

Colon cancer is one of the most common types of gastrointestinal cancers and the fourth cause of cancer death worldwide. To discover novel diagnostic biomarkers for colon cancer and investigate potential mechanisms of oncogenesis, quantitative proteomic approach using iTRAQ-tagging and 2D-LC-MS/MS was performed to characterize proteins alterations in colon cancer and non-neoplastic colonic mucosa (NNCM) using laser capture microdissection-harvested from the two types of tissues, respectively. As a result, 188 DEPs were identified, and the differential expression of two DEPs (DCN and HSPD1) was further verified by Western blotting and immunohistochemistry. KEGG pathway analysis disclosed that the DEPs were related to signaling pathways associated with cancer; furthermore, DCN and HSPD1 are in the relative central hub position among protein-protein interaction subnetwork of the DEPs. The results not only shed light on the mechanism by the DEPs contributed to colonic carcinogenesis, but also showed that DCN and HSPD1 are novel potential biomarkers for the diagnosis of colon cancer.

15.
Biosci Trends ; 11(1): 122-124, 2017 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-28250341

RESUMO

The fifth outbreak of human infection with avian influenza A (H7N9) virus has struck far and wide in China. The number of cases of infection with the avian influenza A (H7N9) suddenly increased in 2013-2014, but the number of cases reported this winter has exceeded the number reported in all previous seasons. Given this situation, the National Health and Family Planning Commission issued updated Chinese guidelines (2017 version) on diagnosis and treatment of infection with the avian influenza A (H7N9) virus on January 24, 2017. In addition, the Chinese Government closed many live poultry markets in urban and rural areas in a number of provinces and the Government has taken proactive measures to surveil, respond to, and prevent potential pandemics involving the avian influenza A (H7N9) virus.


Assuntos
Aves/virologia , Subtipo H7N9 do Vírus da Influenza A/fisiologia , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Vigilância da População , Animais , China , Geografia , Guias como Assunto , Humanos , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Prevalência , Fatores de Risco
16.
Toxicon ; 130: 11-18, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28219625

RESUMO

µ-conotoxins are a group of marine Conus peptides that inhibit sodium currents, so µ-conotoxins are valuable in sodium channel research and new analgesic drug discovery. Here, a novel µ-conotoxin TsIIIA was identified from a worm-hunting Conus tessulatus. TsIIIA was chemical synthesized according to its amino acid sequence GCCRWPCPSRCGMARCCSS and identified by mass spectrum. Patch clamp on rat dorsal root ganglion cells showed that 10 µM TsIIIA specifically inhibit TTX-resistant sodium currents but has no effect on TTX-sensitive sodium currents. TsIIIA inhibits TTX-resistant sodium currents by a dose-dependent mode with an IC50 of 2.61 µM. Further study showed 10 µM TsIIIA has no obvious effect on the current-voltage relationships, conductance-voltage relationships and voltage-dependence of steady-state inactivation of TTX-resistant sodium channels. Mice hotplate analgesic assay indicated that TsIIIA obviously increase the pain threshold at 0.5-4 h. In addition, TsIIIA has better analgesic effects than Ziconotide, indicating that TsIIIA was a valuable lead compound for development of new analgesic drug.


Assuntos
Conotoxinas/farmacologia , Bloqueadores dos Canais de Sódio/farmacologia , Animais , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Clonagem Molecular , Conotoxinas/química , Conotoxinas/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos , Dor/tratamento farmacológico , Técnicas de Patch-Clamp , Ratos , Análise de Sequência de DNA , Análise de Sequência de Proteína , Bloqueadores dos Canais de Sódio/química , Bloqueadores dos Canais de Sódio/isolamento & purificação , Tetrodotoxina/farmacologia
17.
Hum Cell ; 30(2): 98-105, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28238196

RESUMO

Focal adhesion kinase (FAK) functions as a key enzyme in the integrin-mediated adhesion-signalling pathway. Here, we aimed to investigate the effects of FAK on adhesion of human dental pulp (HDP) cells. We transfected lentiviral vectors to silence or overexpress FAK in HDP cells ex vivo. Early cell adhesion, cell survival and focal contacts (FCs)-related proteins (FAK and paxillin) were examined. By using immunofluorescence, the formation of FCs and cytoskeleton was detected, respectively. We found that both adhesion and survival of HDP cells were suppressed by FAK inhibition. However, FAK overexpression slightly inhibited cell adhesion and exhibited no change in cell survival compared with the control. A thick rim of cytoskeleton accumulated and smaller dot-shaped FCs appeared in FAK knockdown cells. Phosphorylation of paxillin (p-paxillin) was inhibited in FAK knockdown cells, verifying that the adhesion was inhibited. Less cytoskeleton and elongated FCs were observed in FAK-overexpressed cells. However, p-paxillin had no significant difference compared with the control. In conclusion, the data suggest that FAK maintains cell adhesion, survival and cytoskeleton formation, but excessive FAK has no positive effects on these aspects.


Assuntos
Adesão Celular/genética , Polpa Dentária/citologia , Proteína-Tirosina Quinases de Adesão Focal/fisiologia , Adolescente , Adulto , Adesão Celular/fisiologia , Sobrevivência Celular/genética , Células Cultivadas , Citoesqueleto/metabolismo , Polpa Dentária/metabolismo , Humanos , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Adulto Jovem
18.
Bioinformatics ; 33(8): 1187-1196, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28096083

RESUMO

Motivation: : Exploring the potential curative effects of drugs is crucial for effective drug development. Previous studies have indicated that integration of multiple types of information could be conducive to discovering novel indications of drugs. However, how to efficiently identify the mechanism behind drug-disease associations while integrating data from different sources remains a challenging problem. Results: : In this research, we present a novel method for indication prediction of both new drugs and approved drugs. This method is based on Laplacian regularized sparse subspace learning (LRSSL), which integrates drug chemical information, drug target domain information and target annotation information. Experimental results show that the proposed method outperforms several recent approaches for predicting drug-disease associations. Some drug therapeutic effects predicted by the method could be validated by database records or literatures. Moreover, with L1-norm constraint, important drug features have been extracted from multiple drug feature profiles. Case studies suggest that the extracted drug features could be beneficial to interpretation of the predicted results. Availability and Implementation: https://github.com/LiangXujun/LRSSL. Contact: proteomics@csu.edu.cn. Supplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Doença , Preparações Farmacêuticas/metabolismo , Estatística como Assunto , Colite Ulcerativa/tratamento farmacológico , Reposicionamento de Medicamentos , Humanos
19.
J Appl Oral Sci ; 24(5): 487-495, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27812619

RESUMO

OBJECTIVE:: Enterococcus faecalis is the dominant microbial species responsible for persistent apical periodontitis with ability to deeply penetrate into the dentin. Exopolysaccharides (EPS) contribute to the pathogenicity and antibiotic resistance of E. faecalis. Our aim was to investigate the antimicrobial activity of calcium hydroxide (CH), camphorated parachlorophenol (CMCP), and chlorhexidine (CHX) against E. faecalis in dentinal tubules. MATERIAL AND METHODS:: Decoronated single-canal human teeth and semicylindrical dentin blocks were incubated with E. faecalis for 3 weeks. Samples were randomly assigned to six medication groups for 1 week (n=10 per group): CH + 40% glycerin-water solution (1:1, wt/vol); CMCP; 2% CHX; CH + CMCP (1:1, wt/vol); CH + CMCP (2:3, wt/vol); and saline. Bacterial samples were collected and assayed for colony-forming units. After dentin blocks were split longitudinally, confocal laser scanning microscopy was used to assess the proportion of viable bacteria and EPS production in dentin. RESULTS:: CMCP exhibited the best antimicrobial activity, while CH was the least sensitive against E. faecalis (p<0.05). CHX showed similar antimicrobial properties to CH + CMCP (1:1, wt/vol) (p>0.05). CH combined with CMCP inhibited EPS synthesis by E. faecalis, which sensitized biofilms to antibacterial substances. Moreover, increasing concentrations of CMCP decreased EPS matrix formation, which effectively sensitized biofilms to disinfection agents. CONCLUSION:: The EPS matrix dispelled by CH paste with CMCP may be related to its bactericidal effect; the visualization and analysis of EPS formation and microbial colonization in dentin may be a useful approach to verify medicaments for antimicrobial therapy.


Assuntos
Antibacterianos/farmacologia , Hidróxido de Cálcio/farmacologia , Dentina/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Veículos Farmacêuticos/farmacologia , Polissacarídeos Bacterianos/química , Irrigantes do Canal Radicular/farmacologia , Adolescente , Adulto , Biofilmes/efeitos dos fármacos , Cânfora/farmacologia , Clorexidina/farmacologia , Clorofenóis/farmacologia , Contagem de Colônia Microbiana , Cavidade Pulpar/efeitos dos fármacos , Cavidade Pulpar/microbiologia , Dentina/microbiologia , Combinação de Medicamentos , Humanos , Viabilidade Microbiana/efeitos dos fármacos , Microscopia Confocal , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Fatores de Tempo , Adulto Jovem
20.
J. appl. oral sci ; 24(5): 487-495, Sept.-Oct. 2016. graf
Artigo em Inglês | LILACS, BBO - Odontologia | ID: lil-797977

RESUMO

ABSTRACT Objective: Enterococcus faecalis is the dominant microbial species responsible for persistent apical periodontitis with ability to deeply penetrate into the dentin. Exopolysaccharides (EPS) contribute to the pathogenicity and antibiotic resistance of E. faecalis. Our aim was to investigate the antimicrobial activity of calcium hydroxide (CH), camphorated parachlorophenol (CMCP), and chlorhexidine (CHX) against E. faecalis in dentinal tubules. Material and Methods: Decoronated single-canal human teeth and semicylindrical dentin blocks were incubated with E. faecalis for 3 weeks. Samples were randomly assigned to six medication groups for 1 week (n=10 per group): CH + 40% glycerin-water solution (1:1, wt/vol); CMCP; 2% CHX; CH + CMCP (1:1, wt/vol); CH + CMCP (2:3, wt/vol); and saline. Bacterial samples were collected and assayed for colony-forming units. After dentin blocks were split longitudinally, confocal laser scanning microscopy was used to assess the proportion of viable bacteria and EPS production in dentin. Results: CMCP exhibited the best antimicrobial activity, while CH was the least sensitive against E. faecalis (p<0.05). CHX showed similar antimicrobial properties to CH + CMCP (1:1, wt/vol) (p>0.05). CH combined with CMCP inhibited EPS synthesis by E. faecalis, which sensitized biofilms to antibacterial substances. Moreover, increasing concentrations of CMCP decreased EPS matrix formation, which effectively sensitized biofilms to disinfection agents. Conclusion: The EPS matrix dispelled by CH paste with CMCP may be related to its bactericidal effect; the visualization and analysis of EPS formation and microbial colonization in dentin may be a useful approach to verify medicaments for antimicrobial therapy.


Assuntos
Humanos , Adolescente , Adulto , Adulto Jovem , Polissacarídeos Bacterianos/química , Irrigantes do Canal Radicular/farmacologia , Veículos Farmacêuticos/farmacologia , Hidróxido de Cálcio/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Dentina/efeitos dos fármacos , Antibacterianos/farmacologia , Fatores de Tempo , Cânfora/farmacologia , Contagem de Colônia Microbiana , Clorofenóis/farmacologia , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Microscopia Confocal , Biofilmes/efeitos dos fármacos , Cavidade Pulpar/efeitos dos fármacos , Cavidade Pulpar/microbiologia , Dentina/microbiologia , Combinação de Medicamentos , Viabilidade Microbiana/efeitos dos fármacos
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