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1.
Front Oncol ; 14: 1389678, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38884080

RESUMO

This study employs a two-sample bidirectional Mendelian randomization (MR) approach to systematically evaluate the causal relationship between gut microbiota and oral cavity cancer (OCC). Objective: To address the challenge in establishing the causal relationship between gut microbiota and OCC, we applied a systematic MR analysis. Methods: Utilizing GWAS data from the MiBioGen consortium (18,340 individuals) and UK Biobank (n = 264,137), we selected instrumental variables and employed MR-Egger, weighted median, IVW, and weighted mode analyses. Heterogeneity and pleiotropy were assessed using Cochran's Q test and MR-Egger intercept test. Results: Our findings indicate, at the order level, Bacteroidales (OR = 0.9990, 95% CI = 0.9980-1.0000, P = 0.046), Burkholderiales (OR = 1.0009, 95% CI = 1.0001-1.0018, P = 0.033), and Victivallales (OR = 0.9979, 95% CI = 0.9962-0.9995, P = 0.037) exhibit causality on OCC in the Weighted median, IVW, and MR-Egger analyses, respectively. At the family level, Alcaligenaceae (OR = 1.0012, 95% CI = 1.0004-1.0019, P = 0.002) and Clostridiaceae1 (OR = 0.9970, 95% CI = 0.9948-0.9992, P = 0.027) show causality on OCC in IVW and MR-Egger analyses. At the genus level, Clostridiumsensustricto1 (IVW, OR = 0.9987, 95% CI = 0.9980-0.9995, P = 0.001; MR-Egger, OR = 0.9978, 95% CI = 0.9962-0.9995, P = 0.035), Desulfovibrio (IVW, OR = 1.0008, 95% CI = 1.0001-1.0015, P = 0.016), Eggerthella (IVW, OR = 0.9995, 95% CI = 0.9990-1.0000, P = 0.048), Eubacterium fissicatena group (IVW, OR = 1.0005, 95% CI = 1.0000-1.0009, P = 0.032), and Holdemanella (IVW, OR = 0.9994, 95% CI = 0.9989-0.9999, P = 0.018) are implicated in causing OCC in related analyses. Conclusion: Our study identifies Burkholderiales order, Alcaligenaceae family, Desulfovibrio genus, and Eubacterium fissicatena group as causally increasing OCC risk. In contrast, Bacteroidales order, Victivallales order, Clostridiaceae1 family, Clostridiumsensustricto1 genus, Eggerthella genus, and Holdemanella genus are causally associated with a decreased OCC risk. However, further investigations are essential to delineate an optimal gut microbiota composition and unravel the underlying mechanisms of specific bacterial taxa in OCC pathophysiology.

2.
J Hazard Mater ; 452: 131332, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37004442

RESUMO

Development of efficient absorbent materials for detection and treatment of offshore oil spillages remained a challenge. In this work, C-shaped polypropylene oil-absorbent fibers with sub-micron internal pores were prepared by combining spun-bonding technique and thermally induced phase separation (TIPS). The effect of drawing speed on the phase separation and the porous morphology of the shaped fiber non-woven fabric (NWF) was investigated. C-shaped NWF with porous morphology had large water contact angle, higher porosity, larger specific surface area, and increased oil absorption speed and capacity. An online oil spillage detection system was developed using porous C-shaped NWF and an oxygen sensing probe, showing shorter response time and higher signal-to-noise (STN) ratio. The response time for detecting the spillage of soybean oil and diluted crude oil (0.5 mL/0.8 L) in water were only 24 s and 10 s, respectively. The reliable oil detection low detection limit (RLDL) of the oxygen sensing probe was reduced 173 times (from 36.5 g/L to 0.21 g/L) when combined with C-shaped porous fiber NWF.

3.
Front Genet ; 13: 894325, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118897

RESUMO

N7-methylguanosine (m7G) modification on internal RNA positions plays a vital role in several biological processes. Recent research shows m7G modification is associated with multiple cancers. However, in hepatocellular carcinoma (HCC), its implications remain to be determined. In this place, we need to interrogate the mRNA patterns for 29 key regulators of m7G RNA modification and assess their prognostic value in HCC. Initial, the details from The Cancer Genome Atlas (TCGA) database concerning transcribed gene data and clinical information of HCC patients were inspected systematically. Second, according to the mRNA profiles of 29 m7G RNA methylation regulators, two clusters (named 1 and 2, respectively) were identified by consensus clustering. Furthermore, robust risk signature for seven m7G RNA modification regulators was constructed. Last, we used the Gene Expression Omnibus (GEO) dataset to validate the prognostic associations of the seven-gene risk signature. We figured out that 24/29 key regulators of m7G RNA modification varied remarkably in their grades of expression between the HCC and the adjacent tumor control tissues. Cluster one compared with cluster two had a substandard prognosis and was also positively correlated with T classification (T), pathological stage, and vital status (fustat) significantly. Consensus clustering results suggested the expression pattern of m7G RNA modification regulators was correlated with the malignancy of HCC strongly. In addition, cluster one was extensively enriched in metabolic-related pathways. Seven optimal genes (METTL1, WDR4, NSUN2, EIF4E, EIF4E2, NCBP1, and NCBP2) were selected to establish the risk model for HCC. Indicating by further analyses and validation, the prognostic model has fine anticipating command and this probability signature might be a self supporting presage factor for HCC. Finally, a new prognostic nomogram based on age, gender, pathological stage, histological grade, and prospects were established to forecast the prognosis of HCC patients accurately. In essence, we detected association of HCC severity and expression levels of m7G RNA modification regulators, and developed a risk score model for predicting prognosis of HCC patients' progression.

4.
Plant Cell Rep ; 41(9): 1863-1874, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35781542

RESUMO

KEY MESSAGE: Exogenous brassinolide promotes Fe absorption through mechanism I strategy, thus improving the tolerance of Malus hupehensis seedlings to Fe deficiency stress. Iron (Fe) deficiency is a common nutritional disorder that results in decreased yield and poor fruit quality in apple production. As a highly active synthetic analog of brassinosteroids, brassinolide (BL) plays numerous roles in plant responses to abiotic stresses. However, its role in Fe deficiency stress in apple plants has never been reported. Herein, we found that the exogenous application of 0.2 mg L-1 BL could significantly enhance the tolerance of apple seedlings to Fe deficiency stress and result in a low etiolation rate and a high photosynthetic rate. The functional mechanisms of this effect were also explored. We found that first, exogenous BL could improve Fe absorption through the mechanism I strategy. BL induced the activity of H+-ATPase and the expression of MhAHA family genes, resulting in rhizosphere acidification. Moreover, BL could enhance the activity of Fe chelate reductase and absorb Fe through direct binding with the E-box of the MhIRT1 or MhFRO2 promoter via the transcription factors MhBZR1 and MhBZR2. Second, exogenous BL alleviated osmotic stress by increasing the contents of osmolytes (proline, solution proteins, and solution sugar) and scavenged reactive oxygen species by improving the activities of antioxidant enzymes. Lastly, exogenous BL could cooperate with other endogenous plant hormones, such as indole-3-acetic acid, isopentenyl adenosine, and gibberellic acid 4, that respond to Fe deficiency stress indirectly. This work provided a theoretical basis for the application of exogenous BL to alleviate Fe deficiency stress in apple plants.


Assuntos
Malus , Esteroides Heterocíclicos , Brassinosteroides/metabolismo , Brassinosteroides/farmacologia , Malus/genética , Plântula , Esteroides Heterocíclicos/farmacologia , Estresse Fisiológico/genética
5.
Plant J ; 109(1): 47-63, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34695268

RESUMO

Dwarfing rootstocks and dwarf cultivars are urgently needed for modern pear cultivation. However, germplasm resources for dwarfing pear are limited, and the underlying mechanisms remain unclear. We previously showed that dwarfism in pear is controlled by the single dominant gene PcDw (Dwarf). We report here that the expression of PcAGP7-1 (ARABINOGALACTAN PROTEIN 7-1), a key candidate gene for PcDw, is significantly higher in dwarf-type pear plants because of a mutation in an E-box in the promoter. Electrophoretic mobility shift assays and transient infiltration showed that the transcription factors PcBZR1 and PcBZR2 could directly bind to the E-box of the PcAGP7-1 promoter and repress transcription. Moreover, transgenic pear lines overexpressing PcAGP7-1 exhibited obvious dwarf phenotypes, whereas RNA interference pear lines for PcAGP7-1 were taller than controls. PcAGP7-1 overexpression also enhanced cell wall thickness, affected cell morphogenesis, and reduced brassinolide (BL) content, which inhibited BR signaling via a negative feedback loop, resulting in further dwarfing. Overall, we identified a dwarfing mechanism in perennial woody plants involving the BL-BZR/BES-AGP-BL regulatory module. Our findings provide insight into the molecular mechanism of plant dwarfism and suggest strategies for the molecular breeding of dwarf pear cultivars.


Assuntos
Brassinosteroides/metabolismo , Galactanos/metabolismo , Proteínas de Plantas/metabolismo , Pyrus/genética , Esteroides Heterocíclicos/metabolismo , Mucoproteínas/genética , Mucoproteínas/metabolismo , Mutação , Fenótipo , Filogenia , Proteínas de Plantas/genética , Regiões Promotoras Genéticas/genética , Pyrus/química , Pyrus/crescimento & desenvolvimento , Pyrus/ultraestrutura , Nicotiana/química , Nicotiana/genética , Nicotiana/crescimento & desenvolvimento , Nicotiana/ultraestrutura
6.
Plant Sci ; 312: 111026, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34620431

RESUMO

Brassinosteroids (BRs) play numerous important roles in plant growth and development. Previous studies reported that BRs could promote stem growth by regulating the expression of xyloglucan endotransglucosylase/hydrolases (XTHs). However, the mechanism of XTHs involved in stem growth remains unclear. In this study, PcBRU1, which belonged to the XTH family, was upregulated by exogenous BL treatment in Pyrus communis. The expression of PcBRU1 was highest in stems and lowest in leaves. Subcellular localization analysis indicated that PcBRU1 was located in the plasma membrane. Furthermore, overexpressing PcBRU1 in tobaccos promoted the plant height and internode length. Electron microscopy and anatomical structure analysis showed that the cell wall was significantly thinner and the cells were slenderer in transgenic tobacco lines overexpressing PcBRU1 than in wild-type tobaccos. PcBRU1 promoted stem growth as it loosened the cell wall, leading to the change in cell morphology. In addition, overexpressing PcBRU1 altered the root development and leaf shape of transgenic tobaccos. Taken together, the results could provide a theoretical basis for the XTH family in regulating cell-wall elongation and stem growth.


Assuntos
Crescimento Celular , Glicosiltransferases/metabolismo , Folhas de Planta/metabolismo , Caules de Planta/metabolismo , Pyrus/crescimento & desenvolvimento , Pyrus/genética , Pyrus/metabolismo , Parede Celular/metabolismo , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo , Glicosiltransferases/genética , Fenótipo , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Caules de Planta/crescimento & desenvolvimento , Nicotiana/genética , Nicotiana/crescimento & desenvolvimento , Nicotiana/metabolismo
7.
BMC Plant Biol ; 21(1): 433, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556040

RESUMO

BACKGROUND: Resveratrol (Res), a phytoalexin, has been widely reported to participate in plant resistance to fungal infections. However, little information is available on its role in abiotic stress, especially in iron deficiency stress. Malus baccata is widely used as apple rootstock in China, but it is sensitive to iron deficiency. RESULTS: In this study, we investigated the role of exogenous Res in M. baccata seedings under iron deficiency stress. Results showed that applying 100 µM exogenous Res could alleviate iron deficiency stress. The seedlings treated with Res had a lower etiolation rate and higher chlorophyll content and photosynthetic rate compared with the apple seedlings without Res treatment. Exogenous Res increased the iron content in the roots and leaves by inducing the expression of MbAHA genes and improving the H+-ATPase activity. As a result, the rhizosphere pH decreased, iron solubility increased, the expression of MbFRO2 and MbIRT1 was induced, and the ferric-chelated reductase activity was enhanced to absorb large amounts of Fe2+ into the root cells under iron deficiency conditions. Moreover, exogenous Res application increased the contents of IAA, ABA, and GA3 and decreased the contents of DHZR and BL for responding to iron deficiency stress indirectly. In addition, Res functioned as an antioxidant that strengthened the activities of antioxidant enzymes and thus eliminated reactive oxygen species production induced by iron deficiency stress. CONCLUSION: Resveratrol improves the iron deficiency adaptation of M. baccata seedlings mainly by regulating iron absorption.


Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Transporte de Íons/efeitos dos fármacos , Deficiências de Ferro , Ferro/metabolismo , Malus/metabolismo , Doenças das Plantas/induzido quimicamente , Resveratrol/metabolismo , Estresse Fisiológico/efeitos dos fármacos , China , Produtos Agrícolas/metabolismo , Plântula/metabolismo
8.
RSC Adv ; 11(35): 21279-21290, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35478813

RESUMO

In this study, an efficient on-site marine oil spillage monitoring probe was developed by fixing oxygen consumption sensors into hydrophobic/oleophilic oil-absorbing porous materials. The impact of thickness and characters of the porous materials, the types of spilled oil, and the presence of salts and vibration in water on the parameters of the obtained signals was investigated. The probe could be used to detect the various representative types of spilled oils including lubricating oil, corn oil, soybean oil, n-hexane, petroleum ether and toluene, even in simulated sea water vibrating at different levels, having over 33 times reduced reliable low detection limit (RLDL) in detecting soybean oil in water (from 36.5 g L-1 to 1.1 g L-1). The response time and signal-to-noise ratios (SNRs) of the probe varied greatly with the dynamic absorbing speed and oxygen barrier property of the spilled oils in the porous material, respectively. The probe showing the highest SNR of 190 dB for a 50 g L-1 on-site soybean oil spillage and the fastest response time of 9 s for a 50 g L-1 on-site toluene spillage in water may potentially be used as a key component in near-shore marine oil spillage monitoring systems to provide early-stage pollution warning.

9.
Exp Ther Med ; 20(2): 1498-1504, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32765673

RESUMO

Correlation between fecal calprotectin (FC) and endoscopic activity assessed by Ulcerative Colitis Endoscopic Index of Severity (UCEIS) in acute severe colitis (ASC) patients was explored to evaluate the predictive value of FC in clinical outcomes. Seventy-one ASC patients were retrospectively evaluated. FC level within 3 days of colonoscopy was measured with ELISA. Demographic and clinical data, laboratory parameters, and medical therapy were documented, and the endoscopic severity of disease was rated by UCEIS. The end points were the rate of failed corticosteroid therapy, colectomy, and mortality. There was significant correlation between UCEIS and FC level (r=0.729, P<0.001), which was superior to CRP, ESR, and hemoglobin. FC level between endoscopic mild activity (UCEIS, 3-4) and endoscopic moderate activity (UCEIS, 5-6), and endoscopic moderate activity (UCEIS, 5-6) and endoscopic severe activity (UCEIS, 7-8) were significantly different. FC levels were associated with different outcomes (failed corticosteroid therapy or surgery); when FC >1672 µg/g, sensitivity and specificity were 80.2 and 66.7%, respectively, in prediction for colectomy using receiver operating characteristics analysis. The results indicated that FC, as a non-invasive indicator, correlates positively with the UCEIS. Baseline FC level predicts clinical outcomes in ASC patients, which make a timely treatment strategy conversion possible after accurately forecasting the likelihood of failure of intravenous steroid therapy.

10.
Int J Mol Sci ; 20(12)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216644

RESUMO

Tissue and cell damage caused by ionizing radiation is often highly genotoxic. The swift repair of DNA damage is crucial for the maintenance of genomic stability and normal cell fitness. Long noncoding RNAs (lncRNAs) have been reported to play an important role in many physiological and pathological processes in cells. However, the exact function of lncRNAs in radiation-induced DNA damage has yet to be elucidated. Therefore, this study aimed to analyze the potential role of lncRNAs in radiation-induced DNA damage. We examined the expression profiles of lncRNAs and mRNAs in 293T cells with or without 8 Gy irradiation using high-throughput RNA sequencing. We then performed comprehensive transcriptomic and bioinformatic analyses of these sequencing results. A total of 18,990 lncRNAs and 16,080 mRNAs were detected in all samples. At 24 h post irradiation, 49 lncRNAs and 323 mRNAs were differentially expressed between the irradiation group and the control group. qRT-PCR was used to verify the altered expression of six lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the predicted genes were mainly involved in the histone mRNA metabolic process and Wnt signaling pathways. This study may provide novel insights for the study of lncRNAs in radiation-induced DNA damage.


Assuntos
Regulação da Expressão Gênica/efeitos da radiação , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Radiação Ionizante , Biologia Computacional/métodos , Dano ao DNA , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Células HEK293 , Humanos , MicroRNAs/genética , Interferência de RNA , Reprodutibilidade dos Testes , Transcriptoma
11.
FASEB J ; 33(7): 8083-8093, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30939244

RESUMO

Resveratrol (RSV) has broad prospective applications as a radiation protection drug, but its mechanism of action is not yet clear. Here, we found that 5 µM RSV can effectively reduce the cell death caused by irradiation. Irradiation leads to G2/M phase arrest in the cell cycle, whereas RSV treatment increases S-phase cell cycle arrest, which is associated with sirtuin 1 (SIRT1) regulation. Meanwhile, RSV promotes DNA damage repair, mainly by accelerating the efficiency of homologous recombination repair. Under oxidative stress, tyrosyl-tRNA synthetase (TyrRS) is transported to the nucleus to protect against DNA damage. RSV can promote TyrRS acetylation, thus promoting TyrRS to enter the nucleus, where it regulates the relevant signaling proteins and reduces apoptosis and DNA damage. SIRT1 is a deacetylase, and SIRT1 knockdown or inhibition can increase TyrRS acetylation levels, further reducing radiation-induced apoptosis after RSV treatment. Our study revealed a new radiation protection mechanism for RSV, in which the acetylation of TyrRS and its translocation into the nucleus is promoted, and this mechanism may also represent a novel protective target against irradiation.-Gao, P., Li, N., Ji, K., Wang, Y., Xu, C., Liu, Y., Wang, Q., Wang, J., He, N., Sun, Z., Du, L., Liu, Q. Resveratrol targets TyrRS acetylation to protect against radiation-induced damage.


Assuntos
Apoptose , Pontos de Checagem da Fase G2 do Ciclo Celular , Lesões Experimentais por Radiação , Resveratrol/farmacologia , Transdução de Sinais , Tirosina-tRNA Ligase , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/efeitos da radiação , Dano ao DNA , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/genética , Reparo do DNA/efeitos da radiação , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos da radiação , Células HEK293 , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/genética , Pontos de Checagem da Fase M do Ciclo Celular/efeitos da radiação , Lesões Experimentais por Radiação/genética , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação , Sirtuína 1/genética , Sirtuína 1/metabolismo , Tirosina-tRNA Ligase/genética , Tirosina-tRNA Ligase/metabolismo
12.
Int J Mol Sci ; 19(12)2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30544713

RESUMO

Colorectal cancer is the most commonly reported gastrointestinal malignancy, with a recent, rapid increase of the annual incidence all over the world. Enhancing the radiosensitivity of cancer cells while preserving the health of normal cells is one of the most important tasks in clinical radiobiology. However, resistance to radiotherapy for colorectal cancer greatly decreases the therapeutic outcome. Melatonin (N-acetyl-5-methoxytryptamine), a natural secretory product that the pineal gland in the brain normally produces, has been reported to have anticancer properties. In the study, we investigated the combination of melatonin with radiotherapy as a treatment for colorectal cancer. We firstly explored the anti-tumor activity of melatonin combined with ionizing radiation (IR) against colorectal carcinoma in vitro. It was found that melatonin effectively inhibited human colorectal carcinoma cell line HCT 116 cellular proliferation, colony formation rate and cell migration counts following IR. Increasing the radiosensitivity of colorectal cancer cells by melatonin treatment was found to be associated with cell cycle arrest in the G2/M phase, downregulation of proteins involved in DNA double-strand break repair and activation of the caspase-dependent apoptotic pathway. Moreover, we also investigated the combined effect of IR and melatonin on colorectal tumor in vivo. Results from a tumor xenograft showed that melatonin plus IR treatment significantly suppressed tumor cell growth compared with melatonin or IR alone, resulting in a much higher tumor inhibition rate for the combined treatment. The data suggested that melatonin combined with IR could improve the radiosensitivity of colorectal cancer and thus enhance the therapeutic effect of the patients, implying melatonin could function as a potential sensitizer in tumor radiotherapy.


Assuntos
Neoplasias Colorretais/patologia , Raios gama , Melatonina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Carcinogênese/patologia , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dano ao DNA , Células HCT116 , Humanos , Masculino , Camundongos Nus
13.
Int J Mol Sci ; 18(8)2017 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-28758961

RESUMO

Radiation-induced intestinal injuries (RIII) commonly occur in patients who suffer from pelvic or abdominal cancer. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidant, and the radioprotective role of Nrf2 is found in bone marrow, lung, and intestine, etc. Here, we investigated the effect of Nrf2 knockout on radiation-induced intestinal injuries using Nrf2 knockout (Nrf2-/-) mice and wild-type (Nrf2+/+) C57BL/6J mice following 13 Gy abdominal irradiation (ABI). It was found that Nrf2 knockout promoted the survival of irradiated mice, protected the crypt-villus structure of the small intestine, and elevated peripheral blood lymphocyte count and thymus coefficients. The DNA damage of peripheral blood lymphocytes and the apoptosis of intestinal epithelial cells (IECs) of irradiated Nrf2-/- mice were decreased. Furthermore, compared with that of Nrf2+/+ mice, Nrf2 knockout increased the number of Lgr5⁺ intestinal stem cells (ISCs) and their daughter cells including Ki67⁺ transient amplifying cells, Villin⁺ enterocytes, and lysozyme⁺ Paneth cells. Nuclear factor-κB (NF-κB) was accumulated in the crypt base nuclei of the small intestine, and the mRNA expression of NF-κB target genes Bcl-2, uPA, and Xiap of the small intestine from irradiated Nrf2-/- mice were increased. Collectively, Nrf2 knockout has the protective effect on small intestine damage following abdominal irradiation by prompting the proliferation and differentiation of Lgr5⁺ intestinal stem cells and activation of NF-κB.


Assuntos
Diferenciação Celular , Enterócitos , Raios gama/efeitos adversos , Enteropatias , Fator 2 Relacionado a NF-E2/deficiência , Lesões Experimentais por Radiação , Células-Tronco , Animais , Diferenciação Celular/genética , Diferenciação Celular/efeitos da radiação , Enterócitos/metabolismo , Enterócitos/patologia , Enteropatias/genética , Enteropatias/metabolismo , Enteropatias/patologia , Camundongos , Camundongos Knockout , Lesões Experimentais por Radiação/genética , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Células-Tronco/metabolismo , Células-Tronco/patologia
14.
Mol Med Rep ; 15(2): 759-767, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28035407

RESUMO

The growth of biomedical research over the previous decades has been accompanied by an increase in the number, complexity and diversity of experimental animals developed as research tools, and inbred mice are some of the most widely used. However, thus far, no inbred mice have exhibited strong radioresistance for use in radiation­damage research. To develop a radioresistant mouse model, a female Japanese outbreeding strain ICR/JCL mouse was mated with a male Chinese inbred strain 615 mouse. From the F1 generation, the mouse line was maintained by brother­to­sister mating. A novel mouse strain was established over >20 continuous generations and designated the Institute of Radiation Medicine-2 (IRM-2) mouse. The biological characteristics, genetic characteristics and susceptibility to radiation of these mice were determined. The IRM­2 mice inherited traits from the parents, including strong reproductive capacity, stable physiological and biochemical indices and few differences among individuals. According to the genetic results, the IRM­2 mice exhibited homozygosity, isogenicity and consistency, in agreement with international standards for inbred strains. Radiosensitivity studies have previously suggested that the lethal dose (LD)50 values for IRM­2 mice were 7.17 Gy (male) and 7.5 Gy (female), resulting in a dose reduction factor value of 1.39 (male) and 1.37 (female). The mortality of IRM­2 mice irradiated with 8 Gy total body irradiation was 15% at day 9 and 90% at day 15 after radiation. The number of nucleated cells in bone marrow, DNA content and colony­forming unit­spleen counts in IRM­2 mice after exposure to γ­ray irradiation were markedly higher than the corresponding values for the parental strains, suggesting that the IRM­2 mice exhibit high resistance to ionizing radiation. Thus, it is suggested that this novel inbred mouse strain may be developed as an animal model of radioresistance for future use in radiation research.


Assuntos
Camundongos Endogâmicos , Tolerância a Radiação/efeitos da radiação , Radiação Ionizante , Animais , Biomarcadores/sangue , Contagem de Células Sanguíneas , Peso Corporal/efeitos da radiação , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Aberrações Cromossômicas , DNA/metabolismo , Feminino , Cariotipagem , Dose Letal Mediana , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Pigmentação da Pele/efeitos da radiação
15.
Int J Cancer ; 138(12): 2875-83, 2016 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-26860236

RESUMO

The objective of this study was to estimate solid cancer risk attributable to long-term, fractionated occupational exposure to low doses of ionizing radiation. Based on cancer incidence for the period 1950-1995 in a cohort of 27,011 Chinese medical diagnostic X-ray workers and a comparison cohort of 25,782 Chinese physicians who did not use X-ray equipment in their work, we used Poisson regression to fit excess relative risk (ERR) and excess absolute risk (EAR) dose-response models for incidence of all solid cancers combined. Radiation dose reconstruction was based on a previously published method that relied on simulating measurements for multiple X-ray machines, workplaces and working conditions, information about protective measures, including use of lead aprons, and work histories. The resulting model was used to estimate calendar year-specific badge dose calibrated as personal dose equivalent (Sv). To obtain calendar year-specific colon doses (Gy), we applied a standard organ conversion factor. A total of 1,643 cases of solid cancer were identified in 1.45 million person-years of follow-up. In both ERR and EAR models, a statistically significant radiation dose-response relationship was observed for solid cancers as a group. Averaged over both sexes, and using colon dose as the dose metric, the estimated ERR/Gy was 0.87 (95% CI: 0.48, 1.45), and the EAR was 22 per 10(4)PY-Gy (95% CI: 14, 32) at age 50. We obtained estimates of the ERR and EAR of solid cancers per unit dose that are compatible with those derived from other populations chronically exposed to low dose-rate occupational or environmental radiation.


Assuntos
Neoplasias Induzidas por Radiação/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional , Raios X/efeitos adversos , Idoso , China/epidemiologia , Feminino , Pessoal de Saúde , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Risco
16.
Exp Ther Med ; 12(6): 4035-4040, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28101182

RESUMO

Taraxasterol is an effective component of dandelion that has anti-inflammatory effects in vivo and in vitro. The present study was performed to explore whether taraxasterol exhibits a protective effect against rheumatoid arthritis through the modulation of inflammatory responses in mice. Eight-week-old CCR9-deficient mice were injected with a collagen II monoclonal antibody cocktail to create a rheumatoid arthritis model. In the experimental group, arthritic model mice were treated with 10 mg/kg taraxasterol once per day for 5 days. Treatment with taraxasterol significantly increased the pain thresholds and reduced the clinical arthritic scores of the mice in the experimental group compared with those of the model group. Furthermore, treatment with taraxasterol significantly suppressed tumor necrosis factor-α, interleukin (IL)-1ß, IL-6 and nuclear factor-κB protein expression levels compared with those in the rheumatoid arthritis model mice. Taraxasterol treatment also significantly reduced nitric oxide, prostaglandin E2 and cyclooxygenase-2 levels compared with those in the rheumatoid arthritis model group. These observations indicate that the protective effect of taraxasterol against rheumatoid arthritis is mediated via the modulation of inflammatory responses in mice.

17.
Zhongguo Fei Ai Za Zhi ; 17(2): 163-70, 2014 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-24581169

RESUMO

BACKGROUND AND OBJECTIVE: It has been proven that increase of the awareness level of lung cancer prevention and control could enhance participation of lung cancer screening of lung cancer high risk group. The aim of this study is to investigate the awareness level of lung cancer prevention and control and the effect of individual characteristics on lung cancer awareness, and to provide evidence for comprehensive lung cancer prevention in high risk areas of lung cancer. METHODS: Staffs of Tianjin Dagang Oil Field who participate low dose CT (LDCT) lung cancer screening by cluster sampling or according to voluntary principle were surveyed, data of lung cancer awareness were collected by questionnaire. RESULTS: A total of 1,633 valid questionnaires were collected. The average age of respondents was 60.08±6.58. Most participants were males (82.2%) while female only accounted for 17.8%. The proportions of awareness about lung cancer in China, risk factors, screening methods and the knowledge of health examination were 64.5%, 77.1%, 43.7%, 49.6% respectively. Result of multiple logistic regression analysis showed that education level, smoking (pack-year), age, prior tuberculosis were the influencing factors of lung cancer awareness with adjusted Ors for education and age level as of 0.567 (95%CI: 0.439-0.733) and 1.373 (95%CI: 1.084-1.739) respectively. 80.3% of the participants can accept health examination once a year, while the ability to pay the medical expenses was not high. The influencing factors of health examination willingness were gender, age, income, the knowledge of lung cancer. CONCLUSIONS: Education level and smoking affect the awareness of lung cancer prevention and control, health education for lung cancer should be conducted especially in population with low education level. Comprehensive lung cancer control in high risk areas should combined lung cancer screening, tobacco control and health education.


Assuntos
Conscientização , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/psicologia , Idoso , China , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/prevenção & controle , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Tomografia Computadorizada por Raios X
18.
Int J Mol Sci ; 15(2): 2157-71, 2014 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-24481064

RESUMO

Colon cancer is one of the most common tumors of the digestive tract. Resistance to ionizing radiation (IR) decreased therapeutic efficiency in these patients' radiotherapy. XRCC2 is the key protein of DNA homologous recombination repair, and its high expression is associated with enhanced resistance to DNA damage induced by IR. Here, we investigated the effect of XRCC2 silencing on colon tumor cells' growth and sensitivity to X-radiation in vitro and in vivo. Colon tumor cells (T84 cell line) were cultivated in vitro and tumors originated from the cell line were propagated as xenografts in nude mice. The suppression of XRCC2 expression was achieved by using vector-based short hairpin RNA (shRNA) in T84 cells. We found that the knockdown of XRCC2 expression effectively decreased T84 cellular proliferation and colony formation, and led to cell apoptosis and cell cycle arrested in G2/M phase induced by X-radiation in vitro. In addition, tumor xenograft studies suggested that XRCC2 silencing inhibited tumorigenicity after radiation treatment in vivo. Our data suggest that the suppression of XRCC2 expression rendered colon tumor cells more sensitive to radiation therapy in vitro and in vivo, implying XRCC2 as a promising therapeutic target for the treatment of radioresistant human colon cancer.


Assuntos
Neoplasias do Colo/genética , Proteínas de Ligação a DNA/genética , Técnicas de Silenciamento de Genes , RNA Interferente Pequeno/genética , Tolerância a Radiação/genética , Animais , Apoptose/genética , Apoptose/efeitos da radiação , Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/efeitos da radiação , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Expressão Gênica , Xenoenxertos , Humanos , Masculino , Camundongos , Carga Tumoral , Raios X
19.
Zhongguo Fei Ai Za Zhi ; 16(4): 184-90, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23601298

RESUMO

BACKGROUND: Smoking is a major cause of lung cancer. Studies of lung cancer among miners have shown that occupational exposure also played an important role. The aim of this study is to investigate radon, cigarette use and other risk factors of lung cancer in Yunnan tin miners and to provide a scientific basis for the prevention and control of occupational lung cancer. METHODS: A prospective cohort study was conducted among Yunnan tin miners, the associations between potential risk factors for lung cancer were analyzed by multivariate Cox regression model. Effects of age at first radon exposure and radon exposure rate on lung cancer risk were analyzed. The relationship between cumulative working level month and lung cancer was analyzed according to smoking status. The joint effect of tobacco use and cumulative radon exposure was analyzed based on additive and multiplicative models. RESULTS: Increased risk of lung cancer was associated with age at enrollment, tobacco use, prior bronchitis, and cumulative arsenic and radon exposure, while higher education level was associated with decreased lung cancer risk. An inverse effect of radon exposure rate was observed. There was no significant association between lung cancer risk and first radon exposure age. There was a significant additive interaction between tobacco use and radon exposure on lung cancer risk. CONCLUSIONS: Several risk factors may contribute to the high incidence of lung cancer in Yunnan tin miners. Further studies are warranted to evaluate joint effect of different risk factors.


Assuntos
Neoplasias Pulmonares/etiologia , Mineração , Exposição Ocupacional/efeitos adversos , Estanho/intoxicação , Idoso , Povo Asiático , China , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etnologia , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Radônio/intoxicação , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fumar/efeitos adversos
20.
Biol Trace Elem Res ; 132(1-3): 51-9, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19404590

RESUMO

The objective of the present study was to evaluate the potential effect of maternal cadmium exposure on pregnancy outcome and development in the offspring at age 4.5 years. Between November 2002 and December 2003, 109 normal pregnant women were enrolled in our cohort from Da-Ye Country, Hubei Province in Central China. The placental, whole blood, and cord blood levels of cadmium were determined by inductively coupled plasma mass spectrometer (ICP-MS). The 106 children at 4.5 years of age given birth by the aforementioned women were followed up and the following rate was 97.25%. Detailed questionnaire surveys, anthropometric measurements were performed, and IQ development was evaluated by Wechsler Preschool and Primary Scale of Intelligence Revised Edition (WPPSI-R). Multiple linear regression analysis indicated that cord blood cadmium level was significantly negatively correlated with fetus development. Low birth weight (less than 2,500 g) occurred significantly more frequently in infants with higher cord blood cadmium than in those exposed to lower levels of cord blood cadmium. Significantly negative correlation was found between cord blood cadmium exposure and WPPSI-R IQ full score after controlling for confounding variables. It was concluded that cord blood cadmium concentration was a factor that influenced fetus growth and later IQ development.


Assuntos
Cádmio/toxicidade , Resultado da Gravidez , Adulto , Peso ao Nascer/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Feminino , Sangue Fetal/metabolismo , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Adulto Jovem
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