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1.
Environ Pollut ; 260: 113961, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32006883

RESUMO

MicroRNAs (miRNAs) are a class of small, non-coding RNAs with a post-transcriptional regulatory function on gene expression and cell processes, including proliferation, apoptosis and differentiation. In recent decades, miRNAs have attracted increasing interest to explore the role of epigenetics in response to air pollution. Air pollution, which always contains kinds of particulate matters, are able to reach respiratory tract and blood circulation and then causing epigenetics changes. In addition, extensive studies have illustrated that miRNAs serve as a bridge between particulate matter exposure and health-related effects, like inflammatory cytokines, blood pressure, vascular condition and lung function. The purpose of this review is to summarize the present knowledge about the expression of miRNAs in response to particulate matter exposure. Epidemiological and experimental studies were reviewed in two parts according to the size and source of particles. In this review, we also discussed various functions of the altered miRNAs and predicted potential biological mechanism participated in particulate matter-induced health effects. More rigorous studies are worth conducting to understand contribution of particulate matter on miRNAs alteration and the etiology between environmental exposure and disease development.

2.
Environ Int ; 137: 105521, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32007688

RESUMO

The lung has been reported to be one of the target organs of polychlorinated dibenzo-dioxins and polychlorinated dibenzo-furans (PCDD/Fs) in many toxicological studies. While the associations between PCDD/Fs exposure and lung function levels have not been investigated thoroughly. This study aimed to explore these associations and the potential mediating role of oxidative stress. In this study, 201 foundry workers and 222 non-exposed general residents were recruited from central China, and their lung function parameters were measured. Air and food samples were collected to determine the PCDD/Fs levels for individual PCDD/Fs exposure estimation. Serum PCDD/Fs levels were determined in a subgroup of individuals randomly selected from the study population to reflect the body burden. It was found that each 1-unit increase in ln-transformed concentration of PCDD/Fs exposure (fg TEQ/bw/day) was associated with a 0.47 L decrease in FVC and a 0.25 L decrease in FEV1. Each 1-unit increase in ln-transformed concentration of serum PCDD/Fs (fg TEQ/g lipid) was associated with a 0.36 L decrease in FVC and a 0.24 L decrease in FEV1. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was not only positively related to PCDD/Fs exposure, but also inversely associated with FVC and FEV1 are FVC (ß = -0.15, 95% CI: -0.22 to -0.08) and FEV1 (ß = -0.07, 95% CI: -0.13 to -0.02). Mediation analysis revealed that urinary 8-OHdG mediated 12.22% of the associations of external PCDD/Fs exposure with FVC levels, 28.61% and 27.87% of the associations of serum PCDD/Fs with FVC and FEV1 levels respectively. Our findings suggested that PCDD/Fs exposure was associated with decreased lung function levels by a mechanism partly involving oxidatively generated damage to DNA.

3.
Platelets ; : 1-8, 2020 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-32009507

RESUMO

Daytime nap is associated with the risk of atherosclerotic cardiovascular disease (ASCVD). However, the contribution of platelet to the association of daytime nap with ASCVD remains unclear. We analyzed the mediation effect of abnormal platelet indices on the association between daytime nap and 10-year ASCVD risk. The participants of this study were 2445 adults aged 30 to 74 years without ASCVD from the baseline Wuhan residents (n = 3053) of the Wuhan-Zhuhai (WHZH) Cohort Study. Participants completed the questionnaire and physical examination (including blood pressure, height, weight, and blood biochemical indicators). We assessed the association of daytime nap or nocturnal sleep duration with 10-year ASCVD risk and mediation effects of platelet indices on the associations using generalized linear models (GLM). Individuals with daytime nap duration of 30 or 60 min had a 1.37- (95%CI: 1.05, 1.78) or 1.44- (95%CI: 1.17, 1.78) fold increased risk of 10-year ASCVD compared with non-nappers. As compared with non-nappers, MPV values or MPV/PLT ratio mediated 15.29% or 6.18% of the association of daytime nap duration of 30 min with 10-year ADCVD risk as well as 19.21% or 7.61% of the association of daytime nap duration of 60 min with 10-year ADCVD risk (all p < .05). Platelet might partially contribute to increased 10-year ASCVD risk in individuals with daytime nap duration of 30 or 60 min.

4.
BMC Med Res Methodol ; 20(1): 9, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937265

RESUMO

BACKGROUND: Drug safety in children is a major concern; however, there is still a lack of methods for quantitatively measuring, let alone to improving, drug safety in children under different clinical conditions. To assess pediatric drug safety under different clinical conditions, a computational method based on Electronic Medical Record (EMR) datasets was proposed. METHODS: In this study, a computational method was designed to extract the significant drug-diagnosis associations (based on a Bonferroni-adjusted hypergeometric P-value < 0.05) among drug and diagnosis co-occurrence in EMR datasets. This allows for differences between pediatric and adult drug use to be compared based on different EMR datasets. The drug-diagnosis associations were further used to generate drug clusters under specific clinical conditions using unsupervised clustering. A 5-layer quantitative pediatric drug safety level was proposed based on the drug safety statement of the pediatric labeling of each drug. Therefore, the drug safety levels under different pediatric clinical conditions were calculated. Two EMR datasets from a 1900-bed children's hospital and a 2000-bed general hospital were used to test this method. RESULTS: The comparison between the children's hospital and the general hospital showed unique features of pediatric drug use and identified the drug treatment gap between children and adults. In total, 591 drugs were used in the children's hospital; 18 drug clusters that were associated with certain clinical conditions were generated based on our method; and the quantitative drug safety levels of each drug cluster (under different clinical conditions) were calculated, analyzed, and visualized. CONCLUSION: With this method, quantitative drug safety levels under certain clinical conditions in pediatric patients can be evaluated and compared. If there are longitudinal data, improvements can also be measured. This method has the potential to be used in many population-level, health data-based drug safety studies.

5.
Cancer Med ; 9(4): 1562-1571, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31873982

RESUMO

BACKGROUND: With the rapid development of the socioeconomic status, the mortality of several cancers has been changed in China during the past 30 years. We aimed to estimate the trends of mortality and years of life lost (YLLs) of various cancers in urban and rural areas of China from 1990 to 2017. METHODS: The mortality data were collected from Chinese yearbooks and the age structure of population from the Chinese sixth population census were used as reference to calculate age-standardized mortality rates (ASMRs) and YLLs rates. Joinpoint regression analysis was implemented to calculate the annual percent change (APC) of mortality rates and YLL rates for cancers. YLLs owing to premature death were calculated as age-specific cancer deaths multiplied by the reference life expectancy at birth of 80 years for male and 82.5 years for female. RESULTS: The ASMRs of all cancers showed significant decreasing trends for urban residents from 1990 to 2017, such downward trend without significance was also observed among rural residents. Interestingly, ASMRs of lung cancer and breast cancer have raised continuously in rural areas since 1990. The age-standardized YYL rates for urban and rural residents decreased with 1.02% and 0.85% per year, respectively. YLLs in rural areas were higher than those in urban areas, whereas YLLs of urban outstripped those of rural finally with the increasing in YLLs of urban areas (216.71% for men and 207.87% for women). CONCLUSION: The ASMRs and YLL rates of all cancers have declined in urban and rural areas from 1990 to 2017. YLLs increased in urban areas and remained higher level in rural areas after 2014 year. Preventive measures should be strengthened to against cancer, especially for lung cancer.

6.
Chemosphere ; 240: 124898, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31557644

RESUMO

Urinary polycyclic aromatic hydrocarbon (PAH) metabolites, biomarkers of internal PAH exposure, are commonly used to explore the effects of PAH on human health. However, the correlation between environmental PAH exposure and the species or levels of urinary PAH metabolites remains unclear. We collected detailed information on PAH exposure sources, including cigarette smoking, cooking, traffic and diet habits via structured questionnaires, and determined 12 urinary monohydroxylated PAH metabolites (OH-PAHs) among 4092 participants from the Wuhan-Zhuhai cohort. Linear mixed models and generalized linear models were conducted to explore the associations of urinary metabolite levels with single or multiple PAH exposure sources. We also calculated the standardized regression coefficients to further compare the contributions of different sources to urinary OH-PAH levels. Our results showed that increasing levels of urinary 1-, 2-hydroxynaphthalene (1-, 2- OHNa) and 2-hydroxyfluorene (2-OHFlu) were significantly correlated with tobacco smoking (all P < 0.01). The concentrations of 1-, 2- OHNa and 9-hydroxyfluorene (9-OHFlu) were positively correlated with dietary intake (all P < 0.05). Individuals who spent a long time in traffic showed elevated levels of 9-OHFlu and 1-hydroxyphenanthrene (1-OHPh) compared with individuals who spent a short time in traffic (all P < 0.05). Self-cooking was associated only with elevated 1-hydroxypyrene (1-OHP) levels. Moreover, good kitchen ventilation resulted in significantly decreased urinary low-molecular-weight OH-PAH levels. These findings suggested that cigarette smoking, self-cooking, high dietary PAH intake and a long time spent in traffic were associated with increased levels of specific urinary PAH metabolites, and good kitchen ventilation effectively reduced the exposure to low-molecular-weight PAHs in self-cooking participants.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/urina , Hidrocarbonetos Policíclicos Aromáticos/urina , Adulto , Biomarcadores/urina , China , Estudos de Coortes , Estudos Transversais , Exposição Ambiental/estatística & dados numéricos , Feminino , Fluorenos , Humanos , Estilo de Vida , Modelos Lineares , Pulmão/metabolismo , Masculino , Naftóis , Fenantrenos
7.
J Exp Med ; 217(2)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31662347

RESUMO

Myeloid-derived suppressor cells (MDSCs) are "polarized" myeloid cells that effectively promote tumorigenesis by inhibiting antitumor immunity. How myeloid cells acquire the protumoral properties during tumorigenesis is poorly understood. We report here that the polarity protein TIPE2 (tumor necrosis factor-α-induced protein 8-like 2) mediates the functional polarization of murine and human MDSCs by specifying their pro- and antitumoral properties. Tumor cells induced the expression of TIPE2 in Gr1+CD11b+ cells through reactive oxygen species (ROS). TIPE2 in turn increased the expression of protumoral mediators such as CCAAT/enhancer-binding protein-ß while inhibiting the expression of antitumoral mediators. Consequently, tumor growth in TIPE2-deficient mice was significantly diminished, and TIPE2-deficient MDSCs markedly inhibited tumor growth upon adoptive transfer. Pharmaceutical blockade of ROS inhibited TIPE2 expression in MDSCs and reduced tumor growth in mice. These findings indicate that TIPE2 plays a key role in the functional polarization of MDSCs and represents a new therapeutic target for cancer immunotherapy.

8.
Am J Transl Res ; 11(11): 7035-7048, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814907

RESUMO

Heterogeneous nuclear ribonucleoprotein F (hnRNP-F) is crucial for gene expression and signal transduction as a tumor-promoting molecule with the ability to promote cell proliferation in various cancers. However, the role and mechanism of hnRNP-F in bladder cancer (BC) remain unclear. Therefore, we investigated the effect of hnRNP-F on the proliferation of BC cells and the potential mechanism. In this study, hnRNP-F was found to be upregulated in BC tissues and cells by western blotting. The knockdown of hnRNP-F could inhibit proliferation and delay cell cycle progression in EJ and UMUC-3 cells. Mechanistically, hnRNP-F was shown to bind to Targeting protein for Xenopus kinesin-like protein 2 (TPX2) by mass spectrometry and coimmunoprecipitation. Furthermore, Pearson correlation analysis showed that the expression of hnRNP-F was positively associated with that of TPX2 in BC tissues (P<0.001, r=0.8180). Notably, TPX2 was correspondingly markedly decreased in cells upon hnRNP-F knockdown. In addition, the decrease in TPX2 after hnRNP-F knockdown further decreased cyclin D1 protein expression and evoked p21 protein expression, eventually resulting in cell cycle arrest and proliferation inhibition in BC cells. Moreover, the overexpression of TPX2 protein was found to reverse the effect of hnRNP-F knockdown on the cell cycle and cell proliferation in BC cells. In conclusion, these findings suggest that hnRNP-F could promote cell proliferation and drive cell cycle progression by regulating TPX2 in BC, which may serve as a potential target for the treatment of BC patients.

9.
Environ Pollut ; : 113713, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31818622

RESUMO

Exposure to environmental metals has been reported to be associated with airway inflammation. Fractional exhaled nitric oxide (FeNO) is an important inflammatory biomarker of the airway. However, the associations between metal exposures and FeNO change and the underlying mechanisms remain unclear. To investigate the associations between urinary metals and FeNO, and the potential role of Club cell secretory protein (CC16), a lung epithelial biomarker, in these associations. We conducted a cross-sectional study from the Wuhan-Zhuhai cohort and measured eight urinary metals, plasma CC16 and FeNO among 3067 subjects by using inductively coupled plasma-mass spectrometry, enzyme-linked immunosorbent assay kit and Nano Coulomb Nitric Oxide Analyzer, respectively. Mixed linear models were used to quantify dose-relationships between urinary metals and FeNO, as well as urinary metals and plasma CC16. The potential role of plasma CC16 in the associations between urinary metals and FeNO was estimated using mediationanalyses. After adjusting for covariates, one percent increase in urinary vanadium, nickel or antimony was associated with a respective 6.60% (95% CI: 3.52%, 9.68%), 2.18% (0.45%, 3.91%), 4.87% (1.47%, 8.27%) increase in FeNO level. The adverse associations were much stronger among participants with low concentration of plasma CC16 than those with high CC16 level. Moreover, plasma CC16 decreased monotonically with increasing quartiles of urinary vanadium, nickel or antimony. Mediation analyses found that CC16 mediated the associations between urinary metals and FeNO by 5.64%, 39.06% and 25.18% for vanadium, nickel and antimony respectively. CC16 plays an important role in airway inflammation. General population with lower plasma CC16 concentration is more likely to suffer from airway inflammation when exposed to high levels of vanadium, nickel or antimony.

10.
J Hazard Mater ; : 121889, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31859167

RESUMO

Exposure to 1-bromopropane (1-BP) has been reported to cause glutathione depletion and increase the level of oxidative damage, which play critical roles in diabetes. However, the possible associations or mechanisms of the exposure of 1-BP with the plasma glucose level and the risk of diabetes are unclear. In this study, we explored the relationships of the urinary 1-BP metabolite N-Acetyl-S-(n-propyl)-l-cysteine (BPMA) with fasting plasma glucose (FPG) levels and the risk of diabetes, and the mediating role of oxidative damage in the above relationships in 3678 urban adults from the Wuhan-Zhuhai cohort in China. We found a significant dose-response relationship between BPMA and FPG levels with a ß of 0.09 (95 % CI: 0.04, 0.14). In addition, mediating effect of urinary BPMA on FPG levels was observed depending on elevated 8-isoprostane level, with a median proportion of 32.06 %. Furthermore, we observed a significant association between urinary BPMA and the risk of diabetes, with an adjusted odds ratio of 1.34 (1.18, 1.52) for all participants. These results indicated that urinary 1-BP metabolites were positively associated with FPG levels and the risk of diabetes among urban adults in this cross-sectional study. Lipid peroxidation partially mediated the association between urinary 1-BP metabolites and FPG levels.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31696238

RESUMO

Objectives Shift work is associated with metabolic disorders as it disturbs circadian rhythms. However, the potential association of shift work with knee osteoarthritis (KOA), a metabolic-related disease, has not been confirmed. The objective of this study was to quantify the association of shift work with the risk of KOA. Methods This retrospective cohort study comprising 13 741 retired workers from the Dongfeng Motor Corporation. KOA was defined by knee pain and clinical X-ray radiographs. Occupational history, including job description and shift work, was collected from face-to-face interviews using questionnaires. Cox proportional hazards regression models were used to estimate exposure-response relationships. Results During the 590 085 person-years of follow-up, a total of 847 cases of KOA (incidence of KOA was 143.5 per 100 000 person-years) were identified. After adjusting for potential confounders, shift work was independently associated with an elevated risk of KOA [hazard ratio (HR) 1.19, 95% confidence interval 1.03-1.36]. Compared with daytime workers, the risk of KOA increased with prolonged periods of shift work; the HR of KOA for participants with 1-9 years, 10-19 years, and ≥20 years shift work were 1.03 (95% CI 0.84-1.26), 1.19 (95% CI 0.98-1.46), and 1.42 (95% CI 1.15-1.76), respectively. The HR for KOA associated with shift work gradually decreased as the period after finishing shift work increased. Conclusion Our results indicated that shift work could be an independent risk factor for KOA.

13.
Hear Res ; 384: 107827, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31683075

RESUMO

The association between shift work and hearing loss is unclear. We aimed to evaluate this association in a Chinese population independently and in combination with occupational noise. A total of 11,196 participants of the Dongfeng-Tongji cohort study were included. Shift work was self-reported and hearing loss was defined as a pure-tone mean of 25 dB or higher at 0.5, 1, 2, and 4 kHz in any ear. The Robust Poisson method were used to assess the relationship between shift work and hearing loss, and the prevalence ratios (PRs) were calculated. Compared to individuals who reported no shift work, the PRs of bilateral hearing loss were significantly higher for a shift work duration of fewer than 10 years in women, (PR = 1.024, 95% confidence interval [CI] = 1.002-1.053), but not in men (PR = 1.016, 95% confidence interval [CI] = 0.998-1.035). The association between short duration of shift work and bilateral hearing loss was just statistically significant in women when those with occupational noise exposure were excluded (PR = 1.067, 95%CI = 1.015-1.122). When shift work and occupational noise exposure were combined, the PRs for hearing loss were highest among individuals with the longest shift work (≥10 years) and longest noise exposure (≥20 years) durations, whether for bilateral (PR = 1.114, 95%CI = 1.068-1.162) or any ear (PR = 1.065, 95%CI = 1.034-1.096). A short duration of shift work may be a risk factor for hearing loss in women and could increase the prevalence of hearing loss when combined with occupational noise.

14.
Environ Pollut ; 255(Pt 2): 113341, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31610512

RESUMO

Cadmium (Cd) is a toxic heavy metal that is widely distributed in the environment. However, the mechanisms linking Cd exposure and type 2 diabetes risks are not completely elucidated. In this study, we aim to investigate the roles of C-reactive protein (CRP) on the association between urinary Cd and type 2 diabetes risk. We determined urinary Cd and plasma CRP concentrations among 3,140 adults from Wuhan-Zhuhai cohort. Dose-response relationships between urinary Cd, plasma CRP, and type 2 diabetes were explored using multivariate logistic regression and linear mixed regression models. Mediation analysis was performed to investigate the role of plasma CRP in the associations between urinary Cd and type 2 diabetes risk. With adjustment for potential confounders, the odds ratios (ORs) of type 2 diabetes showed an upward trend when urinary Cd concentration gradually increased (P trend <0.01). Significantly positive dose-response relationships were observed between urinary Cd and plasma CRP, as well as between plasma CRP and type 2 diabetes risk. Compared to those when both Cd and CRP levels were low, the adjusted ORs (95%CI) of type 2 diabetes was the highest [2.053(1.395-3.020)] in individuals with high levels of urinary Cd and plasma CRP. Mediation analysis estimated that plasma CRP mediated 4.01% of the association between urinary Cd and type 2 diabetes risk [mediating effect: OR (95%CI) = 1.019(1.002-1.057)]. Individuals with high levels of urinary Cd and plasma CRP had a much higher risk of type 2 diabetes. Plasma CRP may serve as a mediator in the association between urinary Cd and type 2 diabetes risk, providing clues for further study on the biological pathway for type 2 diabetes related to Cd exposure.


Assuntos
Proteína C-Reativa/metabolismo , Cádmio/urina , Diabetes Mellitus Tipo 2/metabolismo , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/metabolismo , Adulto , Cádmio/toxicidade , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances
15.
Curr Opin Hematol ; 26(6): 427-433, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31577606

RESUMO

PURPOSE OF REVIEW: Although chimeric antigen receptor T (CART)-cell therapy is best recognized for its antitumor effect in relapsed/refractory B-cell hematological cancers, it is still associated with a high relapse rate. RECENT FINDINGS: We firstly analyzed internal immunological and genetic reasons of CD19+ relapse after treatment for R/R B-cell hematological cancers with CART19 cells. The reasons: murine-derived scFv may limit expansion of CART cells. Repeated antigen exposure leads to T-cell exhaustion. Activation of T cells can cause T-cell senescence and high expression of inhibitive receptors, PD-1, CTLA4, TIGIT, LAG-3, CD244, CD160, TIM3, which might be solved by some external pharmacological intervention methods [for instance, the use of FC (Fludarabine, Cyclophosphamide) lymphodepletion regimen, lenalidomide, PD-1 inhibitor, ibrutinib and humanized CD19-CART cells. Secondly, mechanism of CD19 relapse can be attributed to the preexisting of CD19 subclone, the loss or alternative RNA splicing on exon 2 of chromosome 16 on which CD19 gene is located, B-cell transcript factors - paired-box 5 (PAX5) and early B-cell factor 1 (EBF1) are down-regulated to cause lineage-switch from lymphoid to myeloid. SUMMARY: Although different preparation techniques generates various entities of CART 19 cells, these problems could be conquered by novel agents and novel CAR system. VIDEO ABSTRACT: Although Chimeric Antigen Receptor T (CART) cell therapy is best recognized for its antitumor effect in Relapsed/Refractory B-cell hematological cancers, it still shows a high relapse rate. We review mechanisms of failure of CART therapy. http://links.lww.com/COH/A18.

16.
Chin Med ; 14: 28, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31406501

RESUMO

Background: Cyclocarya paliurus (Batal.) Ijinskaja (CP) is a monotypic genus plant, also called sweet tea tree that belongs to the Juglandaceae family, which is mainly distributed in the subtropical highlands in China. Our previous work has verified that CP leaves exhibit a potent hyperglycemic effect by inhibiting pancreatic ß cell apoptosis through the regulation of MPAK and Akt signaling pathways. However, the components that contribute to this potential health benefit remain undiscovered. Method: A sensitive, reliable, and validated ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-TQ-MS/MS) method was developed to simultaneously determine the presence of six active components (neochlorogenic acid, chlorogenic acid, quercetin-3-O-glucuronide, kaempferol-3-O-rhamnoside, quercetin, and kaempferol) in rat plasma after a single oral administration (in a dosage of 10.5 g/kg) of an extract of CP leaves to rats. The separation was performed on a Waters ACQUITY BEH C18 column (50 mm × 2.1 mm, 1.7 µm). The detection was conducted by multiple reaction monitoring (MRM) in negative ionization mode. The two highest abundant MRM transitions without interference were optimized for each analyte. Acetonitrile and formic acid aqueous solution (0.1%) was used as the mobile phase at a flow rate of 0.3 ml/min. Result: The precision, accuracy, and recovery all satisfied the criteria of international guidance (Bioanalytical Method Validation Guidance for Industry, Food and Drug Administration), and the analytes were stable in plasma for all tested conditions. The main pharmacokinetic parameters were calculated by plasma concentration versus time profiles using the pharmacokinetics program. Conclusion: The pharmacokinetic parameters of each compound can facilitate future clinical studies.

17.
Oncol Rep ; 42(3): 973-990, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322243

RESUMO

MicroRNAs (miRNAs/miRs) are small non­coding RNAs that can act as oncogenes or tumor­suppressor genes in human cancer. Previous studies have revealed that abnormal expression of miRNAs is closely associated with tumor cell cycle, differentiation, growth and apoptosis. miR­543 is expressed abnormally in a wide variety of cancers and has been associated with cellular proliferation, apoptosis, and invasion; however, the effect of miR­543 remains unknown in oral squamous cell carcinoma (OSCC). In the present study, the expression level of miR­543 in OSCC cell lines and tissues was investigated by RT­qPCR. A series of experiments was then performed to elucidate the functions of miR­543 in OSCC, such as CCK­8 assay, colony formation assay, flow cytometry, cell cycle distribution assay and cell apoptosis assay and Transwell assay. miR­543 expression was significantly upregulated in tumors from patients with OSCC and in OSCC cell lines. Overexpression of miR­543 promoted the proliferation, invasion and migration of OSCC cell lines, and inhibited cell apoptosis. In addition, the present study identified cytochrome P450 family 3 subfamily A member 5 (CYP3A5) as a direct target of miR­543 using software analysis and dual­luciferase reporter assays. In conclusion, the results of the present study suggest that miR­543 acts as a tumor promoter and serves a vital role in OSCC proliferation and invasion. These results confirm that miR­543 may serve as a potential novel target for the treatment of OSCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Citocromo P-450 CYP3A/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Bucais/patologia , Adulto , Idoso , Apoptose , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Estudos de Casos e Controles , Ciclo Celular , Movimento Celular , Proliferação de Células , Citocromo P-450 CYP3A/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas
18.
Toxicol Lett ; 313: 178-187, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31284023

RESUMO

Long-term inhalation of crystalline silica particles leads to silicosis characterized by pulmonary inflammation and interstitial fibrosis. The growth arrest-specific protein 6 (Gas6) and its tyrosine receptor Mer have been implicated to involve in the regulation of inflammation, innate immunity and tissue repair. However, the role of Gas6 or Mer in silica-induced lung inflammation and fibrosis has not been investigated previously. In this study, we observed a remarkable increase of Gas6 in bronchoalveolar lavage fluid (BALF) from wild-type C57BL/6 mice after silica intratracheal administration. Then, we investigated whether genetic loss of Gas6 or Mer could attenuate silica-induced lung inflammation and fibrosis. Our results showed that Gas6-/- and Mer-/- mice exhibited reduced lung inflammation response from days 7 to 84 after silica exposure. We also uncovered an overexpression of the suppressor of cytokine signaling protein 1 in silica-treated deficient mice. Moreover, Gas6 or Mer deficiency attenuated silica-induced collagen deposition by inhibiting the expression of transforming growth factor-ß. We conclude that gene absence of Gas6 or Mer is protective against silica-induced lung inflammation and fibrosis in mice. Targeting Gas6/Mer pathway may be a potential therapeutic approach to treat pulmonary fibrosis in patients with silicosis.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Pulmão/enzimologia , Pneumonia/prevenção & controle , Fibrose Pulmonar/prevenção & controle , Silicose/prevenção & controle , c-Mer Tirosina Quinase/deficiência , Animais , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intercelular/genética , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/enzimologia , Pneumonia/genética , Pneumonia/patologia , Fibrose Pulmonar/enzimologia , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Transdução de Sinais , Silicose/enzimologia , Silicose/genética , Silicose/patologia , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Fatores de Tempo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , c-Mer Tirosina Quinase/genética
19.
Sci Total Environ ; 684: 458-465, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31154218

RESUMO

Fine particulate matter (PM2.5) exposure has been associated with lung function decline, but impact of PM2.5 constituents especially for polycyclic aromatic hydrocarbons (PAHs) on lung function is unclear among community population. We enrolled 224 Chinese participants who participated in two study periods (2014-2015 and 2017-2018) of the Wuhan-Zhuhai cohort as a panel, and quantified the associations of personal PM2.5 and sixteen PM2.5-bound PAHs with lung function levels as well as lung function change in three years by linear mixed models. Diagnostic ratios were calculated to identify potential sources of PM2.5-bound PAHs in Wuhan and Zhuhai separately. In single-constituent models, we found that each one interquartile-range increase of naphthalene, acenaphthene, fluoranthene and pyrene were associated with 26.82, 60.99, 45.25 and 23.37 mL decline in FVC respectively; while fluoranthene and pyrene were associated with 27.43 and 15.49 mL decline in FEV1 respectively. Similar results were observed in consitituent-PM2.5 joint models and single-constituent residual models. Persistently long-term high levels of three HMW-PAHs (benzo[a]anthracene, dibenzo[a,h]anthracene, and benzo[ghi]perylene) were associated with 214.65, 226.13, and 265.00 mL decline in FVC decline in three years, compared with persistently low exposure level groups. The associations were different between Wuhan and Zhuhai. The results of diagnostic ratios suggested the differences in PAH emissions between two cities. Our findings provide evidence that both short- and long-term PM2.5-bound PAH exposures might affect lung function.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Material Particulado/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Adulto , Estudos Transversais , Relação Dose-Resposta a Droga , Feminino , Humanos , Estudos Longitudinais , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória
20.
Curr Med Sci ; 39(3): 483-492, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31209822

RESUMO

The intervention of behaviors, including physical activity (PA), has become a strategy for many hospitals dealing with patients with chronic diseases. Given the limited evidence available about PA and healthcare use with chronic diseases, this study explored the association between different levels of PA and annual hospital service use and expenditure for inpatients with coronary heart disease (CHD) in China. We analyzed PA information from the first follow-up survey (2013) of the Dongfeng-Tongji cohort study of 1460 CHD inpatients. We examined factors such as PA exercise volume and years of PA and their associations with the number of inpatient visits, number of hospital days, and inpatient costs and total medical costs. We found that the number of hospital days and the number of inpatient visits were negatively associated with intensity of PA level. Similarly, total inpatient and outpatient costs declined when the PA exercise volume levels increased. Furthermore, there were also significant associations between the number of hospital days, inpatient costs or total medical costs and levels of PA years. This study provides the first empirical evidence about the effects of the intensity and years of PA on hospital service use and expenditure of CHD in China. It suggests that the patients' PA, especially the vigorous PA, should be promoted widely to the public and patients in order to relieve the financial burden of CHD.


Assuntos
Doença das Coronárias/terapia , Exercício , Gastos em Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Idoso , Serviço Hospitalar de Cardiologia , China , Estudos de Coortes , Doença das Coronárias/economia , Feminino , Pesquisas sobre Serviços de Saúde , Hospitais , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais
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