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1.
Transplant Cell Ther ; 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34896653

RESUMO

Activation of antigen-presenting cells (APCs) is crucial in initiating inflammation and alloreaction during acute graft-versus-host disease (aGVHD), a common life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). IL-1 receptor-associated kinase 1 (IRAK1) regulates the activation of APCs in inflammatory settings, and inhibition of IRAK1 might decrease APC activation and aGVHD. This study was conducted to explore the impact of IRAK1 inhibition on APC activation and aGVHD in mice. We administered a selective IRAK1 inhibitor, Jh-X-119-01, to recipient mice undergoing allo-HCT or co-challenged by A20 lymphoma cells. We assessed aGVHD and the graft-versus-lymphoma (GVL) effect. T cell and APC activations were analyzed as well. Jh-X-119-01 was associated with increased survival and decreased aGVHD of recipients. Jh-X-119-01 decreased the proportions of Th1 cells and Tc1 cells in the aGVHD model and in the in vitro mixed lymphocyte reaction. The IRAK1 inhibitor reduced production of TNFα and IFNγ in macrophages of recipient mice. In in vitro cultured bone marrow dendritic cells (BMDCs), Jh-X-119-01 decreased productions of inflammatory cytokines, reduced expression levels of CD80 and CD86, and decreased protein levels of antiapoptotic Bcl2 and phosphorylated NF-κB p65. RNA-seq analysis showed that Jh-X-119-01 had an impact on several pathophysiologic processes of BMDCs, including reduction of GVHD-related genes and regulation of helper T cell differentiation. Importantly, IRAK1 inhibition did not impair cytotoxic function of T cells or the allo-HCT-related GVL effect against A20 lymphoma cells. In addition, the IRAK1 inhibitor did not retard recovery of hematopoietic cells in blood or bone marrow. Our findings show that selective IRAK1 inhibition ameliorates murine aGVHD but preserves the GVL effect. Our findings may have implications for the use of an IRAK1 inhibitor in allo-HCT.

2.
Int Immunopharmacol ; 101(Pt A): 108207, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34628269

RESUMO

OBJECTIVE: To investigate the roles and regulatory mechanisms of miR-9-5p in the development of osteoarthritis (OA). METHODS: Synovial tissues from mouse OA model and control groups were collected and miR-9-5p expression levels and macrophage markers were measured with qPCR. The function of miR-9-5p in macrophage polarization was analyzed by flow cytometry and qPCR. Various databases were employed to screen the target genes one of which was validated with dual-luciferase analysis. Following the validation, rescue research was applied, and the signaling pathways were analyzed with Western blotting. Finally, the role of miR-9-5p in the progression of OA was validated in the mouse model. RESULTS: MiR-9-5p was highly expressed in the synovial tissues of the OA model and was positively associated with M1 markers. Function analysis demonstrated that miR-9-5p could promote the progression of OA by promoting M1 polarization and inhibiting M2 polarization in vivo and in vitro. The mechanism analysis demonstrated that miR-9-5p could regulate macrophage polarization via NF-κB and AMPK signaling pathways by inhibiting SIRT1 expression. CONCLUSIONS: MiR-9-5p could promote M1 polarization and OA progression by regulating NF-κB and AMPK signaling pathways by inhibiting SIRT1 expression.

3.
J Med Genet ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544842

RESUMO

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

4.
Front Cell Dev Biol ; 9: 669285, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095137

RESUMO

Background: DCBLD2 is highly expressed in various cancers, including colorectal cancer. DCBLD2 overexpression promotes tumor occurrence, development, and metastasis. However, DCBLD2 sensitivity to chemotherapy drugs and its mechanism on tumor development are unknown. Methods: DCBLD2 expression differences in cancer and normal tissues were obtained from GEO and TCGA databases. DCBLD2 influence on prognosis was also compared, and the database analysis results were verified via the analysis of clinical samples. GDSC database was used to analyze the effect of DCBLD2 expression difference on 5-FU drug sensitivity on tumor cells. CCK-8, clone formation, scratch, Transwell invasion and migration assays were used to assess DCBLD2 effects on the proliferation, metastasis, and 5-FU drug sensitivity on HCT116 and Caco-2 colorectal cancer cells. Angiogenesis and Matrigel plug assays were used to study the effect of DCBLD2 on angiogenesis. Q-RCR and Western Blot were used to analyze DCBLD2 impact on the EMT signaling pathway, and TAP-MS assay with Co-IP verification was used to identify the downstream target proteins binding to DCBLD2. Results: Both database and clinical sample validation results showed that the expression of DCBLD2 in colorectal cancer tissues was significantly higher than that in normal tissues, leading to poor prognosis of patients. GDSC database analysis showed that DCBLD2 overexpression caused tumor cell resistance to 5-FU. The results of in vitro and in vivo experiments showed that the inhibition of DCBLD2 reduced the proliferation, migration and invasion of colorectal cancer cells, inhibited the angiogenesis of endothelial cells, and enhanced the drug sensitivity to 5-FU. The results of q-RCR and Western Blot experiments showed that the inhibition of DCBLD2 can suppress the EMT signal. The results of TAP-MS assay showed that the proteins bound to DCBLD2 were enriched to the Focal adhesion pathway. The results of Co-IP assay show that DCBLD2 can combine with ITGB1, the key factor of Focal adhesion pathway. Conclusion: DCBLD2 may affect the development of colorectal cancer by regulating cell proliferation and motility, and modulate 5-FU resistance. Down-regulation of DCBLD2 can inhibit EMT signal and angiogenesis. DCBLD2 can combine with ITGB1, the key signal factor of the Focal adhesion pathway.

5.
Int J Rheum Dis ; 24(7): 922-929, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34096679

RESUMO

BACKGROUND: Survivin have been shown to play a crucial role in rheumatoid arthritis (RA); however, the regulatory mechanism of survivin in RA has not been fully elucidated. This study aims to investigate the effect of survivin on the proliferation and apoptosis of human RA fibroblast-like synoviocyte (RA-HFLS) cells in RA and its underlying mechanism through the NOTCH pathway. METHODS: The RA synovial tissues of 65 RA patients with partial resection of synovium of knee joint by arthroscopy were collected. The expression of survivin in synovial tissue was detected by immunohistochemistry, and the correlation of survivin expression and clinical-pathological parameters of patients was analyzed. In vitro, the proliferation of HFLS and RA-HFLS were detected by MTT; the apoptosis of HFLS and RA-HFLS were detected by flow cytometry; the expression of survivin proteins, key protein factors (Notch1, Jagged1, Hes1) in the Notch pathway, and angiogenesis-related proteins (vascular endothelial growth factor receptor 1 [VEGFR1], Ang1, Ang2) were determined by western blot. RESULTS: We found that survivin was highly expressed in RA synovial tissues and RA-HFLS cells, and was positively correlated with erythrocyte sedimentation rate, cyclic citrullinated peptide, C-reactive protein, Disease Activity Score of 28 joints and other pathological indexes. Knockdown survivin induces RA-HFLS cell apoptosis, suppresses proliferation and the expression of VEGFR1, Ang1, Ang2. In addition, blocking Notch pathway using FLI-06 significantly down-regulated survivin expression. When survivin is up-regulated, it promotes RA-HFLS cell proliferation, the expression of VEGFR1, Ang1, Ang2 and suppresses apoptosis by activating the NOTCH. CONCLUSION: This study confirmed that survivin promotes RA-HFLS cell proliferation, the expression of angiogenesis-related proteins and suppresses apoptosis by activating the NOTCH pathway.

6.
Acta Pharmacol Sin ; 42(12): 1970-1980, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33589795

RESUMO

PARP inhibitors are a group of inhibitors targeting poly(ADP-ribose) polymerases (PARP1 or PARP2) involved in DNA repair and transcriptional regulation, which may induce synthetic lethality in BRCAness tumors. Systematic analyzes of genomic sequencing in prostate cancer show that ~10%-19% of patients with primary prostate cancer have inactivated DNA repair genes, with a notably higher proportion of 23%-27% in patients with metastatic castration-resistant prostate cancer (mCRPC). These characteristic genomic alterations confer possible vulnerability to PARP inhibitors in patients with mCRPC who benefit only modestly from other therapies. However, only a small proportion of patients with mCRPC shows sensitivity to PARP inhibitors, and these sensitive patients cannot be fully identified by existing response prediction biomarkers. In this review, we provide an overview of the potential response prediction biomarkers and synergistic combinations studied in the preclinical and clinical stages, which may expand the population of patients with prostate cancer who may benefit from PARP inhibitors.

7.
Medicine (Baltimore) ; 100(2): e24098, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466176

RESUMO

BACKGROUND: Radiotherapy is one of the essential components of breast cancer treatment. It destroys the remaining cells in the chest area after breast cancer surgery and is useful for reducing the necessity of mastectomies. As a single dose of radiation at the time of breast conserving surgery, intraoperative radiotherapy delivers radiotherapy directly and accurately to the tumor itself or the tumor bed whilst delivering minimal dose to the surrounding normal tissues. Hypofractionated postmastectomy radiotherapy with shorter and more convenient hypofractionated dose schedules might help to treat more patients and reduce cost. We will conduct a comprehensive systematic review and meta-analysis to compare the effectiveness of these 2 therapies in the management of early stage breast cancer. METHODS: Four English databases (PubMed, Embase, Cochrane Library, and Web of Science) and 3 Chinese databases (China National Knowledge Infrastructure, China Science and Technology Journal Database, and Chinese Biomedical Literature Database) will be searched from inception of databases to December 2020 without language limitation. Two reviewers will independently conduct selection of studies, data extraction and management, and assessment of risk of bias. Any disagreement will be resolved by the third reviewer. Review Manager 5.3 (The Cochrane Collaboration, Software Update, Oxford, UK) will be used for data synthesis. Cochrane risk of bias assessment tool will be used to assess the risk of bias. RESULTS: This study will provide a systematic synthesis of current published data to compare the effectiveness of intraoperative radiotherapy vs hypofractionated postmastectomy radiotherapy for early stage breast cancer. CONCLUSIONS: This systematic review and meta-analysis will provide clinical evidence for the effectiveness of intraoperative radiotherapy vs hypofractionated postmastectomy radiotherapy for early stage breast cancer, and inform our understanding of the value of intraoperative radiotherapy and hypofractionated postmastectomy radiotherapy for early stage breast cancer. STUDY REGISTRATION NUMBER: INPLASY2020110115.


Assuntos
Neoplasias da Mama/terapia , Cuidados Intraoperatórios/métodos , Mastectomia/métodos , Cuidados Pós-Operatórios/métodos , Radioterapia/métodos , Protocolos Antineoplásicos , Terapia Combinada , Pesquisa Comparativa da Efetividade , Fracionamento da Dose de Radiação , Feminino , Humanos , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
8.
BMJ Open ; 10(12): e042603, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277290

RESUMO

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a representative rare disease characterised by progressive, fatal motor neuron degeneration. Due to the unknown aetiology and variability of the phenotypes, there are no accurate reports concerning the epidemiology or clinical characteristics of the disease. The low prevalence, as previously reported, makes it difficult to carry out studies with large samples. The aim of this study was to explore the natural history and clinical features of ALS in mainland China through a multicentre, prospective cohort study. The findings will both offer a better understanding of ALS and also support the development of a model to study other rare diseases. METHODS AND ANALYSIS: Patients from 88 representative hospitals in different parts of mainland China will be recruited through a specially designed online data system (http://www.chalsr.net/). We aim to recruit 4752 ALS patients over a 3-year period. Baseline data will be recorded, and follow-up data will be collected every 3 months. The primary outcome is effective survival. Overall survival and indices of disease progression will be measured as the secondary outcomes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the ethics committee of Peking University Third Hospital (M2019388). Informed written consent will be obtained from each participant. Dissemination of the study protocol and data will take place primarily through a specially designed online data system (http://www.chalsr.net/). The collective results of the study will be published in peer-reviewed journals and shared in scientific presentations. TRIAL REGISTRATION NUMBER: NCT04328675.


Assuntos
Esclerose Amiotrófica Lateral , Esclerose Amiotrófica Lateral/epidemiologia , China/epidemiologia , Progressão da Doença , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Sistema de Registros
9.
BMC Public Health ; 20(1): 268, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093668

RESUMO

BACKGROUND: Many studies focused on health inequality between migrant older adults and local older adults, while few study concerned the health inequalities between urban-to-urban and rural-to-urban migrant older adults. This study aimed to compare physical health and mental health between these two groups in Hangzhou, Zhejiang Province, China, and to explore the relationship between cognitive social capital, social integration and health among migrant older adults. METHODS: A two-stage stratified sampling method was employed to recruit participants from May to August 2013 in Hangzhou. Measurement data were compared with student's t-tests and multivariate analysis of variance (MANOVA). Multiple linear regression was adopted in this study. RESULTS: A total of 1000 of participants who met the inclusion criteria were analyzed, consisting of 527 (52.7%) urban-to-urban and 473 (47.3%) rural-to-urban migrant older adults. There were no statistically significant difference in physical health and mental health between urban-to-urban and rural-to-urban groups on the whole. However, urban-to-urban migrant older adults had a higher reciprocity and social integration than did in rural-to-urban group (13.36 vs. 12.50, p < 0.01; 40.07 vs. 38.50, p < 0.01). And both of cognitive social capital and social integration were positively related to physical health (social reciprocity: t = 6.69, p < 0.01; social trust: t = 3.27, p < 0.01; social integration: t = 5.66, p < 0.01) and mental health (social reciprocity: t = 4.49, p < 0.01; social trust: t = 5.15, p < 0.01; social integration: t = 10.02, p < 0.01). Overall, the female, widowed, and the oldest among migrant older adults had a worse health. CONCLUSIONS: Social capital and social integration were played important roles in health of migrant older adults. The female rural-to-urban migrant older adults, those aged over 70 years, and older adults who were not in marriage should be especially concerned in health policy making.


Assuntos
Disparidades nos Níveis de Saúde , População Rural/estatística & dados numéricos , Migrantes/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Idoso , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Capital Social , Integração Social , Fatores Socioeconômicos
10.
Protoplasma ; 256(6): 1629-1645, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31267226

RESUMO

Carotenoids are the most important pigments determining the color of C. × morifolium; however, it is still unknown whether the changes of plastid ultrastructure affect carotenoids accumulation. In this study, we compared the change of carotenoid composition, content, and the plastid ultrastructures in the different developmental stages of capitulum among fourteen C. × morifolium cultivars from seven color groups. We found that the carotenoids and plastids detected at the early stage of capitulum development were similar in all cultivars, including violaxanthin, lutein, and ß-carotene, which were present in proplastids and immature chloroplasts. Immature chloroplasts were degraded completely, forming loosely broken plastids during the development of the capitulum in white and pink cultivars. Meanwhile, a number of lipid vesicles appeared at proplastids, which resulted in only trace amounts of carotenoid accumulation in these cultivars. For yellow, orange, red, and brown cultivars, a great number of chromoplasts were found, which contained diverse ultrastructures, such as plastoglobules, tubules, and lipid droplets; these chromoplasts were derived from proplastids or chloroplasts. Compared with the early stage of capitulum development, these cultivars accumulated large amounts of carotenoids, primarily including lutein, lutein derivatives, and their isomers. In green cultivars, proplastids and immature chloroplasts were completely transformed into mature chloroplasts. These chloroplasts mainly contained violaxanthin, lutein, ß-carotene, and two new components, (9Z)-lutein and (9'Z)-lutein, compared with carotenoid components presented in proplastids and immature chloroplasts. This research will be helpful for understanding the mechanisms of carotenoid metabolism of C. × morifolium. Furthermore, we found that two different chromoplast transformation patterns could be present in the same tissue cell, which contributed to the research on plastid differentiation and development in higher plants.


Assuntos
Carotenoides/química , Cloroplastos/química , Chrysanthemum/química , Plastídeos/química , Pigmentação
11.
BMC Cancer ; 19(1): 530, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151422

RESUMO

BACKGROUND: Histone H2AX phosphorylation at the site of Tyr-142 can participates in multiple biological progressions, which is including DNA repair. Ras pathway is closely involved in human cancers. Our study investigated the effects of Ras pathway via regulating H2AX.Y142ph. METHODS: Gastric cancer cell line SNU-16 and MKN1 cells were transfected with Ras for G12D and T35S site mutation. The phosphorylation of H2A.XY142 and ERK1/2, WSTF and MDM2 was detected by western blot. Cell viability, cell colonies and migration was analyzed by MTT assay, soft-agar colony formation assay, and Transwell assay, respectively. The expression of Ras pathway related downstream factors, EYA3 and WSTF was detected by qRT-PCR. The relationship between Ras and downstream factors were detected by ChIP. The cell cycle progression was measured by flow cytometry. RESULTS: RasG12D/T35V transection decreased the phosphorylation of H2A.XY142 and activated phosphorylation of ERK-1/2. H2A.XY142 inhibited cell viability, colonies and migration. H2A.XY142ph altered the expression of Ras downstream factors. CHIP assay revealed that RasG12D/T35V could bind to the promoters of these Ras pathway downstream factors. Silence of EYA3 increased H2A.XY142ph and inhibited cell viability, migration and percent cells in S stage. Furthermore, silence of EYA3 also changed the downstream factors expression. WSTF and H2A.XY142ph revealed the similar trend and MDM2 on the opposite. CONCLUSION: Ras/ERK signal pathway decreased H2A.XY142ph and promoted cell growth and metastasis. This Ras regulation process was down-regulated by the cascade of MDM2-WSTF-EYA3 to decrease H2A.XY142ph in SNU-16 cells.


Assuntos
Histonas/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias Gástricas/metabolismo , Fatores de Transcrição/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Transformação Celular Neoplásica , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Inativação Gênica , Humanos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Tirosina Fosfatases/genética , Proteínas Tirosina Fosfatases/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Gástricas/patologia , Fatores de Transcrição/genética
12.
Front Oncol ; 9: 508, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249811

RESUMO

Background: Despite great advances in the diagnosis and treatment of non-small cell lung cancer (NSCLC), early diagnosis remains a challenge because patients usually have advanced lung cancer at the time they are diagnosed. The limited efficacy of conventional chemotherapy is another major problem in the treatment of NSCLC. Based on a published set of sequencing data, we find that hsa_circ_0001946 is a circRNA molecule with a significantly different expression level in three cell lines (human normal lung fibroblasts cell line MRC-5, human NSCLC cell line A549, cisplatin-resistant cell line A549/DDP), NSCLC tissues and paired adjacent normal tissues. We believe that hsa_circ_0001946 may have an effect on the progression of NSCLC and its sensitivity to cisplatin. Methods: We focused on investigating the circular RNA, hsa_circ_0001946. RNA interference of hsa_circ_0001946 was carried out in A549 cell lines to determine the effect of reduced hsa_circ_0001946 expression on lung cancer progression and was analyzed by Cell Counting Kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine, clone formation, Hoechst, wound healing, and transwell assays. The nucleotide excision repair (NER) signaling pathway was identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Moreover, cellular responses to cisplatin were assessed through CCK-8 and flow cytometry assays. Western blot analysis and host-cell reactivation assay were used to determine the effect of hsa_circ_0001946 on NER signaling. Results: In this study, we found that the reduced expression of hsa_circ_0001946 promoted the viability, proliferation, migration, and invasion of NSCLC cells, as well as inhibition of cell apoptosis. Our findings suggest that hsa_circ_0001946 can affect the sensitivity of NSCLC cells to the chemotherapeutic drug cisplatin via modulation of the NER signaling pathway. Conclusions: Our study demonstrated the role of hsa_circ_0001946 in NSCLC pathogenesis, development, and chemosensitivity, and suggests that hsa_circ_0001946 may serve as a novel biomarker for the diagnosis and prediction of platinum-based chemosensitivity in patients with NSCLC.

13.
Cancer Med ; 8(9): 4159-4168, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31197975

RESUMO

Eukaryotic initiation factor 3 (EIF3) is one of the largest and most complex translation initiation factors, which consists of 13 subunits named eukaryotic translation initiation factor 3 subunit A (EIF3a) to EIF3m. EIF3a is the largest subunit of EIF3. Previous studies suggested that EIF3a is a housekeeping gene, recent results have found that EIF3a is closely related to the tumorigenesis and drug resistance. Circular RNAs (circRNAs) derived from biologically important gene can play an important role in gene regulation. However, the mechanism underlying circRNAs' biological functions is not well understood yet. In this work, we screened 31 EIF3a-derived circRNAs, in which two circEIF3as were identified to be correlated with cisplatin drug sensitivity in lung cancer. Two circEIF3as were found involved in RNA-binding proteins-mediated biological processes and may be related to translational regulation according to bioinformatics analyses. CircEIF3as, the transcriptional initiation factor EIF3a transcribed circRNAs, are associated with both drug sensitivity and translation regulation. These findings mean that they may have a functional synergy effect with EIF3a or be valuable therapeutic targets for treatment like EIF3a. This is the first study that exploits circRNAs screening from EIF3a in lung cancer, our findings provide a novel perspective on the function of EIF3a and circEIF3as in lung cancer.


Assuntos
Cisplatino/uso terapêutico , Fator de Iniciação 3 em Eucariotos/genética , Neoplasias Pulmonares/tratamento farmacológico , RNA Circular/sangue , Células A549 , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Prognóstico , Análise de Sobrevida , Resultado do Tratamento
14.
BMC Public Health ; 19(1): 311, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30876471

RESUMO

BACKGROUND: Owing to the increase in life expectancy and sickliness, caring for older adults has become a major challenge in China, where the traditional care system is disintegrating and community- and home-based care have been introduced to respond to this 'silver wave'. However, there is limited knowledge of the dilemmas associated with caring for older adults and the acceptability of community- and home-based care for this population. METHODS: Participants were recruited from Xihu District, Hangzhou, from June to July 2017. In-depth interviews were conducted using semi-structured questionnaires. Audio recording, verbatim transcription, and thematic analysis were conducted. RESULTS: A total of 64 older adults from four communities were interviewed. Half of the participants had multiple chronic diseases. The very old individuals and those with severe diseases and in poor financial conditions were observed to be struggling the most. Health status, financial capability, and personality were the main factors affecting the care process. Participants cited the following reasons for staying away from nursing homes: misunderstanding, negative environment, a sense of shame, loneliness, and financial limitations. Community- and home-based cares are popular forms of old-age care; however, some participants exhibited a lack of knowledge about such services. CONCLUSION: A multi-layered old-age care system is urgently needed for older adults in Zhejiang Province. Further, it is important that such a system integrates the care provided through community- and home-based services with that offered by nursing homes. Community- and home-based care for older adults needs to be prioritised, and the quality of care provided in nursing homes should be improved.


Assuntos
Cuidadores/psicologia , Conflito Psicológico , Idoso , Idoso de 80 Anos ou mais , Cuidadores/estatística & dados numéricos , China , Feminino , Serviços de Assistência Domiciliar , Humanos , Masculino , Pessoa de Meia-Idade , Casas de Saúde , Pesquisa Qualitativa , Inquéritos e Questionários
15.
Artigo em Inglês | MEDLINE | ID: mdl-30708979

RESUMO

Unintentional injury is the leading cause of childhood death and disability in many countries worldwide. This study aimed to quantify rates and risk factors for childhood unintentional injury in areas of rural China, where many children are left behind by migrant worker parents. We administered a questionnaire to children aged 9 to 15, in 56 schools in five counties in Zhejiang and Guizhou provinces. Of the 3791 respondents, 44% lived with both parents, 23% with one parent, and 33% with neither. Around half the children (47.9%) had suffered at least one unintentional injury in the past year, with burns (26%), animal bites (20%) and mechanical injury (18%) the most common. Left-behind children had no increased risk of unintentional injury, but children living in poorer Guizhou (p = 0.001), of divorced parents (p = 0.02), and less well-educated mothers (p = 0.02) were associated with higher risk. Virtual absence of personal level risk factors highlights the importance of addressing environmental risk to reduce childhood injury. The findings have informed a community-based intervention to reduce injury risk through raising awareness of environmental hazards, and through removal of specific hazards. Importantly, the Chinese government should ensure that known effective interventions are subject to legislation and enforcement.


Assuntos
Saúde da Criança , Saúde da População Rural , Ferimentos e Lesões/epidemiologia , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Risco , Inquéritos e Questionários
16.
BMC Geriatr ; 18(1): 174, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-30081826

RESUMO

BACKGROUND: While much literature reported the access of Chinese older migrants to health services, little was known about the differences among sub-groups of older adults, including urban-to-urban and rural-to-urban migrants, and urban and rural permanent residents. This study aimed to examine the access of these four groups to health services in Zhejiang Province, China and provide an evidence for the development of health services policies. METHODS: A cross-sectional survey was conducted in community-dwelling older adults (aged 60 years or above) in 2013. Participants were recruited by random sampling. Demographic information and access to health services for the elderly populations were obtained via interviews using a self-designed structured questionnaire. Pearson's chi-square tests and Cochran-Mantel-Haenszel (CMH) tests were performed to examine the differences in access to health services among the four groups. Binary logistic regression was conducted to explore the associations of participants' visits to doctors with their group status after controlling confounding factors. RESULTS: The two-week hospital visiting rates were significantly lower in migrants (55.56% in rural-to-urban and 62.50% in urban-to-urban) than that in urban and rural permanent residents (67.40 and 82.25%, respectively; p < 0.01). The majority of older adults who received a diagnosis indicating need for hospital treatment accepted the treatment, with no significant difference among the four groups after controlling for health service need (χ2 = 7.08, p = 0.07). On the other hand, 30.05% of the older adults did not visit a doctor when they got ailments in the past 2 weeks prior to the survey, and 16.42% (33/201) did not receive hospital treatment after receiving a diagnosis indicating need for hospital treatment. Factors including age, marital status, educational attainment, major financial source, and living with family members did not influence health services use. CONCLUSIONS: Targeted social and health policies integrating the strengths of government, society and families should be implemented to further improve health services use for different groups of older adults.


Assuntos
Acesso aos Serviços de Saúde/tendências , População Rural/tendências , Inquéritos e Questionários , Migrantes , População Urbana/tendências , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Serviços de Saúde/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória
17.
Biomed Pharmacother ; 105: 37-44, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29843043

RESUMO

OBJECTIVE: To explore the molecular mechanism of Res in regulation of pulmonary fibrosis (PF). METHODS: Rats were injected with bleomycin (BLM) to establish a PF model and treated with resveratrol (Res) and/or miR-21 agomir. After 14 days, lung tissues were collected for Hematoxylin-eosin and Masson's staining, and real-time quantitative polymerase chain reaction and Western blot were performed to detect fibrosis-related protein expression and the activation of the TGF-ß1/Smad pathway. In vitro, MRC-5 cells were pretreated with TGF-ß1, Res, and/or miR-21 agomir. After 48 h, total soluble collagen was detected with a Sircol Soluble Collagen Assay. Subsequently, a miR-21 mimic was transfected into MRC-5 cells, and a luciferase reporter assay was employed to verify whether miR-21 targeted Smad7. RESULTS: Res reversed the increased levels of miR-21 induced by BLM and alleviated serious PF symptoms, but agomiR-21 treatment effectively impaired the above manifestations. In vivo, miR-21 inhibited the decreases of TGF-ß1 and p-Smad2/3 that were induced by Res. In vitro, miR-21 significantly disrupted the positive effect of Res on TGF-ß-induced collagen deposition, as well as the levels of Fn, α-SMA, p-Smad2, and Smad7. In addition, Smad7 was found to be a direct target of miR-21-5p. TGF-ß stimulation led to an enormous increase in p-c-Jun, c-Jun, and c-Fos, which were significantly reduced by Res. Finally, miR-21 sharply reduced the increased phosphorylation levels of ERK, JNK and p38 that were induced by Res. CONCLUSION: Res inhibits BLM-induced PF by regulating miR-21 through MAPK/AP-1 pathways.


Assuntos
Antioxidantes/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , MicroRNAs/genética , Fibrose Pulmonar/tratamento farmacológico , Estilbenos/uso terapêutico , Fator de Transcrição AP-1/metabolismo , Animais , Antioxidantes/administração & dosagem , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Ratos Sprague-Dawley , Resveratrol , Estilbenos/administração & dosagem
18.
Mol Med Rep ; 17(6): 8011, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29568925

RESUMO

Following the publication of this article, we realized that the joint first author's name had been printed incorrectly in the journal: This was mispelled as "Lingqing Chen". The corrected name (Lingqiang Chen) is featured here. We regret any inconvenience this has caused, and thank the Editor for allowing us the opportunity to publish a Corrigendum. [the original article was published in the Molecular Medicine Reports 16: 3208­3216, 2017; DOI: 10.3892/mmr.2017.7028].

19.
CNS Neurosci Ther ; 24(3): 178-186, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29336114

RESUMO

AIMS: Despite therapeutic advances in glioma management including surgery, radiation, and chemotherapy, the improvement of patient outcome is far from satisfactory. Nucleolar and spindle-associated protein 1 (NUSAP1) is an important functional protein during mitosis, and its abnormal expression is implicated in progression of different types of tumors. However, the role of NUSAP1 in gliomas remains unclear. METHODS: NUSAP1 expression in gliomas with different grades was investigated based on GEO glioma datasets. Kaplan-Meier survival analysis was used to evaluate its prognostic significance. In vitro assays were also performed to evaluate effects of NUSAP1 on malignant phenotypes of glioma cells by silencing NUSAP1. RESULTS: NUSAP1 expression was correlated not only with glioma grade but also with prognosis of glioma patients. NUSAP1 depletion suppressed proliferation of U251 cells by inducing cell cycle arrest at G2/M phase and apoptosis. NUSAP1 depletion rendered U251 cells impaired migratory ability as well. CONCLUSION: NUSAP1 is a potential prognosis marker for glioma patients and therapeutic strategies targeting NUSAP1 might hold promise in improving glioma treatment.


Assuntos
Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Adulto , Apoptose/fisiologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Feminino , Glioma/genética , Glioma/mortalidade , Glioma/patologia , Humanos , Masculino , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/metabolismo
20.
Cancer Lett ; 415: 49-57, 2018 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-29196127

RESUMO

Accumulating evidence has shown that lncRNAs and circRNAs are novel regulators of gene expression. The discovery of numerous lncRNAs and circRNAs, and investigation into their structures and functions will contribute to our understanding of the pathogenesis of diseases as well as better prevention, diagnosis, and treatment of diseases. There is a close relationship between circRNAs and lncRNAs regarding their origins and functions. Recent studies have shown that non-coding linear and circular transcripts can be transcribed from the same gene and are potential super-enhancers modulating gene transcription. In this review, we summarize the categories, characteristics, biological functions and databases of both lncRNAs and circRNAs, focusing on their transcriptions derived from the same gene, which might give us a deeper understanding of and enable us to better recognize and distinguish their physiological roles.


Assuntos
Splicing de RNA , RNA Longo não Codificante/genética , RNA/genética , Transcrição Genética , Doença/genética , Expressão Gênica , Humanos , Modelos Genéticos , RNA Circular
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