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1.
Stem Cell Res Ther ; 12(1): 474, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425902

RESUMO

Endometrial stem/progenitor cells have been proved to exist in periodically regenerated female endometrium and can be divided into three categories: endometrial epithelial stem/progenitor cells, CD140b+CD146+ or SUSD2+ endometrial mesenchymal stem cells (eMSCs), and side population cells (SPs). Endometrial stem/progenitor cells in the menstruation blood are defined as menstrual stem cells (MenSCs). Due to their abundant sources, excellent proliferation, and autotransplantation capabilities, MenSCs are ideal candidates for cell-based therapy in regenerative medicine, inflammation, and immune-related diseases. Endometrial stem/progenitor cells also participate in the occurrence and development of endometriosis by entering the pelvic cavity from retrograde menstruation and becoming overreactive under certain conditions to form new glands and stroma through clonal expansion. Additionally, the limited bone marrow mesenchymal stem cells (BMDSCs) in blood circulation can be recruited and infiltrated into the lesion sites, leading to the establishment of deep invasive endometriosis. On the other hand, cell derived from endometriosis may also enter the blood circulation to form circulating endometrial cells (CECs) with stem cell-like properties, and to migrate and implant into distant tissues. In this manuscript, by reviewing the available literature, we outlined the characteristics of endometrial stem/progenitor cells and summarized their roles in immunoregulation, regenerative medicine, and endometriosis, through which to provide some novel therapeutic strategies for reproductive and cancerous diseases.

2.
Int J Oral Sci ; 13(1): 27, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408132

RESUMO

Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.


Assuntos
Nanopartículas , Preparações Farmacêuticas , Animais , Regeneração Óssea , Indóis , Osteogênese , Polímeros , Ratos
3.
Nat Commun ; 12(1): 4230, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244494

RESUMO

Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet to be clarified. We report in this study that the secretory ECM1a isoform induces tumorigenesis through the GPR motif binding to integrin αXß2 and the activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP binding cassette subfamily G member 1 (ABCG1) transduces the ECM1a-integrin αXß2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cancer cell cisplatin resistance through up-regulation of the CD326-mediated cell stemness. On the contrary, the non-secretory ECM1b isoform binds myosin and blocks its phosphorylation, impairing cytoskeleton-mediated signaling and tumorigenesis. Moreover, ECM1a induces the expression of the heterogeneous nuclear ribonucleoprotein L like (hnRNPLL) protein to favor the alternative mRNA splicing generating ECM1a. ECM1a, αXß2, ABCG1 and hnRNPLL higher expression associates with poor survival, while ECM1b higher expression associates with good survival. These results highlight ECM1a, integrin αXß2, hnRNPLL and ABCG1 as potential targets for treating cancers associated with ECM1-activated signaling.


Assuntos
Processamento Alternativo , Carcinoma Epitelial do Ovário/genética , Proteínas da Matriz Extracelular/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ovarianas/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas da Matriz Extracelular/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/genética , Humanos , Integrina alfaXbeta2/genética , Integrina alfaXbeta2/metabolismo , Estimativa de Kaplan-Meier , Camundongos , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Ovário/patologia , Ovário/cirurgia , Fosforilação/genética , Prognóstico , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA-Seq , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
4.
J Colloid Interface Sci ; 601: 650-660, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34091312

RESUMO

Engineering a targetable nanoparticle to tumor cell is a challenge issue for clinical application. Our results demonstrated that the chemokine CXCL8 secreted by oral squamous cell carcinoma (OSCC) could act as a chemoattractant to attract dental pulp mesenchymal stem cell (DPSC), which expressed the CXCL8 binding receptor, CXCR2, to the OSCC. Therefore, to create OSCC targetable nanoparticles, we used DPSC membranes to modify nanoparticles of metal-organic framework nanoparticles (MOFs) resulting in a novel MOF@DPSCM nanoparticle. Interestingly, results from in vitro and in vivo experiments illustrated that MOF@DPSCM possessed specificity for the OSCC, and the MOF@DPSCM carried DOX (doxorubicin), MOF-DOX@DPSCM could induce CAL27 cell death in vitro and block CAL27 tumor growth in vivo. Our data suggest that this novel MOF-DOX@DPSCM nanoparticle is a potential targetable drug delivery system for the OSCC in the future clinical application.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Células-Tronco Mesenquimais , Estruturas Metalorgânicas , Neoplasias Bucais , Nanopartículas , Carcinoma de Células Escamosas/tratamento farmacológico , Linhagem Celular Tumoral , Polpa Dentária , Humanos , Neoplasias Bucais/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço
5.
Adv Healthc Mater ; 10(12): e2100196, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33987977

RESUMO

The osteogenic potential of mesenchymal stem cells (MSCs) is severely impaired under persistent inflammation of periodontitis. A highly efficient way to promote or rescue osteogenic potential of MSCs under inflammation remains an unmet goal. Herein, metformin carbon dots (MCDs) with excellent biocompatibility are prepared from metformin hydrochloride and citric acid via a hydrothermal method. The MCDs can more effectively enhance the alkaline phosphatase (ALP) activity, calcium deposition nodules formation, expression of osteogenic genes and proteins in rat bone marrow mesenchymal stem cells (rBMSCs) than metformin under both inflammatory and normal conditions. Moreover, a novel pathway of extracellular signal-regulated kinases (ERK)/AMP-activated protein kinase (AMPK) signaling is involved in the MCDs-induced osteogenesis. In periodontitis rats, MCDs can effectively regenerate the lost alveolar bone, but not the metformin. Taken together, MCDs can be the promising candidate nanomaterial for periodontitis treatment. This work may provide a new pharmacological target of ERK/AMPK pathway for treating bone loss and also give additional insights into developing nanodrugs from the numerous medications.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular , Metformina , Proteínas Quinases Ativadas por AMP , Animais , Regeneração Óssea , Carbono , Diferenciação Celular , Metformina/farmacologia , Osteogênese , Ratos
6.
J Cell Mol Med ; 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34037315

RESUMO

Oocyte ageing is a key bottleneck and intractable challenge for in vitro fertilization treatment of aged female patients. The underlying molecular mechanisms of human oocyte ageing remain to be elucidated. Hence, this study aims to investigate the key genes and relevant biological signalling pathways involved in human oocyte ageing. We isolated mRNA for single-cell RNA sequencing from MII human oocytes donated by patients undergoing intracytoplasmic sperm injection. Nine RNA-seq datasets were analyzed, which included 6 older patients(average 42.67±2.25 years) and 3 younger patients (average 25.67±2.08 years). 481 differentially expressed genes (DEGs) were identified, including 322 upregulated genes enriched in transcription, ubiquitination, epigenetic regulation, and cellular processes, and 159 downregulated genes enriched in ubiquitination, cell cycle, signalling pathway, and DNA repair. The STRING database was used to analyse protein-protein interactions, and the Cytoscape software was used to identify hub genes. From these DEGs, 17 hub genes were identified including 12 upregulated genes (UBE2C, UBC, CDC34, UBR1, KIF11, ASF1B, PRC1, ESPL1, GTSE1, EXO1, UBA1, KIF4A) and 5 downregulated genes (UBA52, UBE2V2, SKP1, CCNB1, MAD2L1). The significant key biological processes that are associated with these hub genes include ubiquitin-mediated proteolysis, ubiquitination-related pathways, oocyte meiosis, and cell cycle. Among these, UBE2C may play a crucial role in human oocyte ageing.

7.
BMC Cancer ; 21(1): 423, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33863293

RESUMO

BACKGROUND: Glia maturation factor-γ (GMFG) is reported to inhibit the actin nucleation through binding to the actin-related protein-2/3 complex (Arp2/3). Considering the main function of GMFG in actin remodeling, which is vital for immune response, angiogenesis, cell division and motility, GMFG is supposed to have important roles in tumor development, while up to now, only two studies described the role of GMFG in cancers. By investigating the clinical values of GMFG using The Cancer Genome Atlas (TCGA) data and the functional mechanisms of GMFG through analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments, this study was aimed to better understand the impact of GMFG in pan-cancers and to draw more attentions for the future research of GMFG. METHODS: RNA-seq and clinical data of cancer patients were collected from TCGA and analyzed by the Kaplan-Meier methods. GO and KEGG analyses were conducted using the online tools from the Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: Compared to the corresponding normal samples, GMFG was significantly upregulated in glioblastoma (GBM), kidney clear cell carcinoma (KIRC), lower grade glioma (LGG), acute myeloid leukemia (LAML), and pancreatic cancer (PAAD), testicular cancer (TGCT), but was downregulated in kidney chromophobe (KICH), lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) (P < 0.05 for all). High expression of GMFG predicted worse OS in GBM (HR = 1.5, P = 0.017), LGG (HR = 2.2, P < 0.001), LUSC (HR = 1.4, P = 0.022) and ocular melanomas (UVM) (HR = 7, P < 0.001), as well as worse DFS in LGG (HR = 1.8, P < 0.001) and prostate cancer (PRAD) (HR = 1.9, P = 0.004). In contrast, high expression of GMFG was associated with better OS in skin cutaneous melanoma (SKCM) (HR = 0.59, P < 0.001) and thymoma (THYM) (HR = 0.098, P = 0.031), as well as better DFS in bile duct cancer (CHOL) (HR = 0.2, P = 0.003). GMFG was mainly involved in the immune response, protein binding and cytokine-cytokine receptor interaction pathways, and was positively associated with multiple immunomodulators in most cancers. CONCLUSION: Our study preliminarily identified that GMFG may cause different survivals for different cancers through modulating tumor progression, immune response status and tissue-specific tumor microenvironment (TME).


Assuntos
Biomarcadores Tumorais , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Fator de Maturação da Glia/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Imunomodulação/genética , Estimativa de Kaplan-Meier , Estadiamento de Neoplasias , Especificidade de Órgãos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/imunologia , Prognóstico , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
8.
J Cell Physiol ; 236(6): 4580-4591, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33251612

RESUMO

Bone morphogenetic protein (BMP) signaling is well known in bone homeostasis. However, the physiological effects of BMP signaling on mandibles are largely unknown, as the mandible has distinct functions and characteristics from other bones. In this study, we investigated the roles of BMP signaling in bone homeostasis of the mandibles by deleting BMP type I receptor Acvr1 in osteoblast lineage cells with Osterix-Cre. We found mandibular bone loss in conditional knockout mice at the ages of postnatal day 21 and 42 in an age-dependent manner. The decreased bone mass was related to compromised osteoblast differentiation together with enhanced osteoclastogenesis, which was secondary to the changes in osteoblasts in vivo. In vitro study revealed that deletion of Acvr1 in the mandibular bone marrow stromal cells (BMSCs) significantly compromised osteoblast differentiation. When wild type bone marrow macrophages were cocultured with BMSCs lacking Acvr1 both directly and indirectly, both proliferation and differentiation of osteoclasts were induced as evidenced by an increase of multinucleated cells, compared with cocultured with control BMSCs. Furthermore, we demonstrated that the increased osteoclastogenesis in vitro was at least partially due to the secretion of soluble receptor activator of nuclear factor-κB ligand (sRANKL), which is probably the reason for the mandibular bone loss in vivo. Overall, our results proposed that ACVR1 played essential roles in maintaining mandibular bone homeostasis through osteoblast differentiation and osteoblast-osteoclast communication via sRANKL.

9.
PLoS One ; 15(8): e0237926, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853214

RESUMO

OBJECTIVE: At present, current didactic teaching delivery method help nursing students apply theory to clinical situations in an inefficient way. The flipped classroom (FC), a novel teaching mode emphasizing self-study and critical thinking, has generated interest in nursing education in China. However, there are a gap in the literature and no consistent outcomes of current studies which compared FC and lecture-based learning (LBL), and no systematic review has comprehensively compared theoretical scores as an affected outcome in FC versus LBL modes. METHODS: In this review, we analyze flipped-learning nursing students' scores, and aim to assess the efficacy and provide a deeper understanding of the FC in nursing education. Following the inclusion criteria, articles were obtained by searching PubMed, Embase and Chinese data, including the China National Knowledge Infrastructure, Wanfang Data, and VIP database until 3 January 2020. Data were extracted from eligible articles and quality was assessed. A meta-analysis was then performed using a random effects model with a standardized mean value (SMD) and a 95% confidence interval (CI).32 studies were included after reviewing 2,439 citations. All studies were randomized controlled trials (RCTs). The FC theoretical knowledge scores in FC were significantly positively affected compared to those of the traditional classroom (SMD = 1.33, 95% CI: 1.02-1.64; P < 0.001). In addition, 23 studies reported skill scores, indicating significant difference between the FC mode and LBL mode (SMD = 1.58, 95%CI: 1.23-1.93; P < 0.001). CONCLUSIONS: The results of this meta-analysis suggest that compared to the LBL teaching method, the FC mode dose significantly improve Chinese nursing students' theoretical scores. However, the problems of heterogeneity and publication bias in this study need to be remedied high-quality future studies.


Assuntos
Educação Médica , Aprendizagem , Estudantes de Enfermagem , China , Avaliação Educacional , Retroalimentação , Humanos , Conhecimento , Viés de Publicação , Risco
10.
Oncogenesis ; 8(10): 59, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597912

RESUMO

Chemoresistance has been the biggest obstacle in ovarian cancer treatment, and STAT3 may play an important role in chemoresistance of multiple cancers, but the underlying mechanism of STAT3 in ovarian cancer chemoresistance has long been truly illusive, particularly in association with p53 and RAS signaling. In this study, by using wild type, constitutive active, and dominant negative STAT3 constructs, wild-type p53, and RAS-mutant V12, we performed a series of in vitro and in vivo experiments by gene overexpression, drug treatment, and animal assays. We found that phosphorylation of STAT3 Y705 but not S727 promoted cancer cell EMT and metastasis through the Slug-mediated regulation of E-cadherin and Vimentin. The phosphorylation of STAT3 at Y705 also activated the MAPK and PI3K/AKT signaling to inhibit the ERS-mediated autophagy through down-regulation of pPERK, pelf2α, ATF6α, and IRE1α, which led to increased cisplatin resistance. Induction of wild type p53 in STAT3-DN-transfected cells further diminished the chemoresistance and tumor growth through the upregulation of the MAPK- and PI3K/AKT-mediated ERS and autophagy. Introduction of STAT3-DN deprived the RASV12-induced ERS, autophagy, oncogenicity, and cisplatin resistance, whereas introduction of p53 in STAT3-DN/RASV12 expressing cells induced additional tumor retardation and cisplatin sensitivity. Thus, our data provide strong evidence that the crosstalk between STAT3 and p53/RAS signaling controls ovarian cancer cell metastasis and cisplatin resistance via the Slug/MAPK/PI3K/AKT-mediated regulation of EMT and autophagy.

11.
Cell Physiol Biochem ; 50(4): 1398-1413, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30355924

RESUMO

BACKGROUND/AIMS: This study is aimed at identification of miR-195-5p/MMP14 expression in cervical cancer (CC) and their roles on cell proliferation and invasion profile of CC cells through TNF signaling pathway in CC. METHODS: Microarray analysis, gene set enrichment analysis (GSEA) and DAVID were used to analyze differentially expressed miRNAs, mRNAs and signaling pathways. MiR-195-5p and MMP14 expression levels in CC cell were determined by qRT-PCR. Western blot was employed to measure MMP14 and TNF signaling pathway-relating protein level. Luciferase reporter system was used to confirm the targeting relationship between MMP14 and miR-195-5p. Cell proliferation and invasion was respectively deeded by CCK8, transwell. In vivo experiment was carried out to study the impact of MMP14 and miR-195-5p on CC development in mice. RESULTS: The microarray analysis and the results of qRT-PCR determined that miR-195-5p was under-expressed and MMP14 was over-expressed in CC cells. GSEA and DAVID analysis showed that TNF signaling pathway was regulated by miR-195-5p/MMP14 and activated in cervical carcinoma cells. The miR-195-5p and MMP14 have a negative regulation relation. In vivo experiment found that down-regulated MMP14 and up-regulated miR-195-5p suppressed the tumor development. CONCLUSION: Our results suggest that MMP14 is a direct target of miR-195-5p, and down-regulated MMP14 and up-regulated miR-195-5p suppressed proliferation and invasion of CC cells by inhibiting TNF signaling pathway.


Assuntos
Proliferação de Células , Metaloproteinase 14 da Matriz/metabolismo , MicroRNAs/metabolismo , Transdução de Sinais , Neoplasias do Colo do Útero/patologia , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Antagomirs/uso terapêutico , Movimento Celular , Biologia Computacional , Regulação para Baixo , Feminino , Células HeLa , Humanos , Masculino , Metaloproteinase 14 da Matriz/química , Metaloproteinase 14 da Matriz/genética , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo
12.
Oncol Rep ; 38(2): 886-898, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28656201

RESUMO

The aims of the present study were to determine whether the changes in density and location of CD68-positive and CD206-positive macrophages contribute to progression of hepatocellular carcinoma (HCC) and to evaluate prognostic values of these cells in post-surgical patients. A retrospective study involving 268 HCC patients was conducted. CD68-positive and CD206-positive macrophage infiltration in HCC tissues and adjacent tissues was examined by immunohistochemistry (IHC) and the relationship between the clinicopathological features and prognosis was analyzed. Receiver operating characteristics (ROC) curve was used to calculate diagnostic accuracy. There was an increase in CD68-positive and CD206-positive macrophage infiltration in adjacent tumor tissues compared with tumor tissues. ROC curve identified their optimal diagnostic cut-off values. The survival analysis showed that increased CD68 expression in adjacent tissues conferred superior overall survival (OS) and disease-free survival (DFS), while increase of CD206 in tumor yielded inferior OS and DFS. Cox regression analysis suggested both CD68-positive macrophages in adjacent area and intratumor CD206-positive macrophages as independent prognostic biomarkers for post-surgical HCC patients. Finally, a combination of CD68/CD206 and HBV-positive further improved prognostic stratification, especially in DFS. These results provide the first evidence for region- and subset-dependent involvement of CD68 and CD206 cells in HCC progression. A combination of CD68/CD206 density and HBV-positivity improves further predictive value for post-operative recurrence of HCC. Quantification of CD68/CD206 macrophages and their distribution can be exploited for better postsurgical management of HCC patients. These findings provide a basis for developing novel treatment strategies aimed at re-educating macrophages in tumor microenvironment.


Assuntos
Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Carcinoma Hepatocelular/genética , Lectinas Tipo C/genética , Neoplasias Hepáticas/genética , Lectinas de Ligação a Manose/genética , Receptores de Superfície Celular/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Vírus da Hepatite B/patogenicidade , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Prognóstico
13.
Expert Opin Ther Targets ; 20(11): 1325-1338, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27359286

RESUMO

INTRODUCTION: MicroRNAs (miRNAs) are a set of small single-stranded noncoding RNAs with diverse biological functions. As a prototypical hypoxamir, human microRNA-210 (hsa-miR-210) is one of the most widely studied miRNAs thus far. In addition to its involvement in sophisticated regulation of numerous biological processes, miR-210 has also been shown to be associated with the development of different human diseases including various types of cancers, cardiovascular and cerebrovascular diseases, and immunological diseases. Given its multi-faceted functions, miR-210 may serve as a novel and promising theranostic target for prevention and treatment of diseases. Areas covered: This review aims to provide a comprehensive overview of miR-210, the regulation of its expression, biological functions and molecular mechanisms, with particular emphasis on its diagnostic and therapeutic potential. Expert opinion: Although the exact roles of miR-210 in various diseases have not been fully clarified, targeting miR-210 may be a promising therapeutic strategy. Further investigations are also needed to facilitate therapeutic-clinical applications of miR-210 in human diseases.


Assuntos
MicroRNAs/genética , Terapia de Alvo Molecular , Nanomedicina Teranóstica/métodos , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/terapia , Transtornos Cerebrovasculares/genética , Transtornos Cerebrovasculares/prevenção & controle , Transtornos Cerebrovasculares/terapia , Humanos , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/prevenção & controle , Doenças do Sistema Imunitário/terapia , Neoplasias/genética , Neoplasias/prevenção & controle , Neoplasias/terapia
14.
Rheumatol Int ; 35(8): 1435-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25929716

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease. Cytokine-mediated immunity plays an important role in the pathogenesis of SLE. TNF-like ligand 1A (TL1A) belongs to the TNF superfamily of cytokines and has been found to perform significantly in autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel disease. To date, no study has discussed the expression levels of TL1A in SLE. We found that plasma levels of TL1A were significantly higher in newly diagnosed SLE patients compared with controls. Correlation analysis showed that plasma levels of TL1A were positively associated with SLE disease activity index. These data indicated that TL1A may play a role in SLE and may reflect the disease activity for SLE.


Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/imunologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
15.
PLoS One ; 10(3): e0120334, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25781640

RESUMO

REV3L, the catalytic subunit of DNA Polymerase ζ (Polζ), plays a significant role in the DNA damage tolerance mechanism of translesion synthesis (TLS). The role of REV3L in chemosensitivity of cervical cancer needs exploration. In the present study, we evaluated the expression of the Polζ protein in paraffin-embedded tissues using immunohistochemistry and found that the expression of Polζ in cervical cancer tissues was higher than that in normal tissues. We then established some cervical cancer cell lines with REV3L suppression or overexpression. Depletion of REV3L suppresses cell proliferation and colony formation of cervical cancer cells through G1 arrest, and REV3L promotes cell proliferation and colony formation of cervical cancer cells by promoting G1 phase to S phase transition. The suppression of REV3L expression enhanced the sensitivity of cervical cancer cells to cisplatin, and the overexpression of REV3L conferred resistance to cisplatin as evidenced by the alteration of apoptosis rates, and significantly expression level changes of anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2), myeloid cell leukemia sequence 1 (Mcl-1) and B-cell lymphoma-extra large (Bcl-xl) and proapoptotic Bcl-2-associated x protein (Bax). Our data suggest that REV3L plays an important role in regulating cervical cancer cellular response to cisplatin, and thus targeting REV3L may be a promising way to alter chemosensitivity in cervical cancer patients.


Assuntos
Cisplatino/farmacologia , Proteínas de Ligação a DNA/biossíntese , DNA Polimerase Dirigida por DNA/biossíntese , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias do Colo do Útero/enzimologia , Proteínas de Ligação a DNA/genética , DNA Polimerase Dirigida por DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Fase G1/efeitos dos fármacos , Fase G1/genética , Células HeLa , Humanos , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fase S/efeitos dos fármacos , Fase S/genética , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
16.
Eur J Cancer ; 49(18): 3889-99, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23953057

RESUMO

Although it is reported that interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) is activated by human papillomavirus (HPV) infection in cervical cancer cells, little is known about the role of IL-6/STAT3 in tumour microenvironment during development of the disease. In this study, we found that cancer-associated fibroblasts (CAF) but not normal fibroblasts (NF) secrete high level of IL-6 with activated STAT3 and appear senescent at early passages in culture or in cervical cancer tissues infected with high-risk HPV, and that treatment of NF with recombinant IL-6 or CAF conditioned medium (CM) induces activation of STAT3 and cellular senescence. IL-6 and STAT3 are either upregulated or activated in Siha and Hela cells infected with HPV 16 or 18, but not in C33A and ME180 cells without HPV 16 or 18 infection. Overexpression of HPV early proteins 6 (E6) activates STAT3, increases IL-6 expression and tumour burden in C33A and ME180 cells, while silencing of HPV E6 by specific shRNA reduces STAT3 activation, IL-6 expression, and tumour formation in Siha and HeLa cells, so does silencing of STAT3 by specific shRNA in HeLa and C33A/E6 cells. The tumour growth of cervical cancer cells reconstituted with CAF or NF is largely affected by inhibition of fibroblast senescence with STAT3 inhibitor or with IL-6 antibody treatment. Thus, we have uncovered a mechanism that fibroblast senescence promotes cervical cancer development through high-risk HPV E6-activated IL-6/STAT3 signalling in tumour microenvironment.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Interleucina-6/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Proteínas Repressoras/metabolismo , Fator de Transcrição STAT3/metabolismo , Microambiente Tumoral , Animais , Comunicação Autócrina , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Senescência Celular , Proteínas de Ligação a DNA/genética , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibroblastos/virologia , Células HeLa , Interações Hospedeiro-Patógeno , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Papillomavirus Humano 16/fisiologia , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/metabolismo , Papillomavirus Humano 18/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Oncogênicas Virais/genética , Comunicação Parácrina , Interferência de RNA , Proteínas Repressoras/genética , Transdução de Sinais , Transplante Heterólogo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
17.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 2): o263, 2011 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-21522956

RESUMO

In the title compound, C(12)H(16)N(4) (+)·2C(7)H(4)NO(4) (-), the complete 2,2'-(p-phenyl-ene)bis-(4,5-dihydro-1H-imidazol-3-ium) (bib) dication is generated by crystallographic inversion symmetry. The bib cations reside on crystallographic inversion centers, which coincide with the centroids of the respective benzene rings. In the cation, the imidazole ring adopts an envelop conformation with the flap atom displaced by 0.082 (3) Šfrom the plane through the other ring atoms. In the crystal, the cations and anions are linked through inter-molecular N-H⋯O hydrogen bonds, forming chains running along the a axis. C-H⋯O inter-actions also occur. Weak π-π contacts between the imidazole rings of bib and between the benzene rings of NB [centroid-centroid distances = 3.501 (1) and 3.281 (2) Å, respectively] may further stabilize the structure.

18.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 1): o179, 2010 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-21522684

RESUMO

In the cation of the title compound, C(12)H(15)N(4) (+)·C(7)H(6)NO(2) (-), the benzene ring makes dihedral angles of 30.51 (9) and 25.64 (9)° with the imidazole and imidazolinium rings, respectively. In the crystal, inter-molecular N-H⋯O and N-H⋯N hydrogen-bonding inter-actions link the mol-ecules into a three-dimensional network.

19.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 5): m572-3, 2009 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-21583801

RESUMO

In the title compound, [MnCl(2)(C(11)H(13)N(5))], the Mn(II) ion is five-coordinated in a distorted square-pyramidal geometry, with three N atoms from the neutral tridentate 2,6-bis-(4,5-dihydro-1H-imidazol-2-yl)pyridine ligand and one chloride ion forming the basal plane and the other chloride ion in the apical position. Both dihydro-imidazole rings adopt envelope conformations. In the crystal structure, mol-ecules are linked into a three-dimensional network by N-H⋯Cl and C-H⋯Cl hydrogen bonds.

20.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 9): m1023-4, 2009 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-21577391

RESUMO

In the cation of the title compound, [Mn(C(11)H(13)N(5))(2)](ClO(4))(2)·CH(3)CN, the metal atom is located on a twofold rotation axis and is six-coordinated by six N atoms from two different 2,6-bis-(4,5-dihydro-1H-imidazol-2-yl)pyridine (bip) ligands in a distorted octahedral geometry. The O atoms of the perchlorate anions are disordered with occupancies in the ratio 0.593 (10):0.407 (10). In the crystal, mol-ecules are stabilized by two N-H⋯O hydrogen bonds, forming zigzag chains along the a axis, which are further inter-connected by N-H⋯O hydrogen bonds and π-π inter-actions [centroid-centroid distance = 3.50 (1) Å] into a three-dimensional network.

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