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Conventional fluorophores suffer from low sensitivity and selectivity in amine detection due to the inherent limitations in their "one-to-one" stoichiometric sensing mechanism. Herein, we propose a "one-to-many" chain reaction-like sensing mechanism by creating a domino chain consisting of one fluorescent molecule (e.g., PTF1) and up to 40 nonemissive polymer chains (pPFPA) comprising over thousand repeating units (PFPA). PTF1 (the domino trigger) interacts with adjacent PFPA units (the following blocks) through polar-π interactions and initiates the domino effect, creating effective through-space conjugation along pPFPA chains and generating amplified yellow fluorescent signals through charge transfer between PTF1 and pPFPA. Amine exposure causes rapid dismantling of the fluorophore-pPFPA-based domino chain and significantly reduces the amplified emissions, thus providing an ultrasensitive method for detecting amines. Relying on the above merits, we achieve a limit of detection of 177 ppq (or 1.67 × 10-12 M) for triethylamine, which is nearly 4 orders lower than that of previous methods. Additionally, the distinct reactivity of pPFPA toward different amines allows for the discrimination of primary, secondary, and tertiary amines. This study presents a "domino effect" sensing mechanism that has not yet been reported and provides a general approach for chemical detection that is beyond the reach of conventional methods.
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BACKGROUND: The combined procedure of left atrial appendage closure (LAAC) with concomitant pulmonary vein isolation (PVI) has demonstrated its efficacy and safety. However, there is still a lack of comparative investigations regarding the long-term benefits of the combined procedure when compared to LAAC alone. Our study aims to assess the long-term outcomes of combined procedure of LAAC with concomitant PVI in comparison with a propensity matched LAAC alone group. METHODS: Propensity score matching (PSM) was employed to rectify covariate imbalances, resulting in the inclusion of 153 comparable patients from the initial cohort of 333 non-valvular atrial fibrillation (AF) patients. Clinical outcomes, encompassing thrombotic events, major cardiocerebrovascular adverse events (MACCE), re-hospitalization due to cardiovascular disease (CVD), and atrial tachycardia (AT), were juxtaposed between the two groups. Bleeding events and peri-device complications, such as residual flow, device-related thrombus, and device replacement, were also compared. Additionally, a patients group underwent PVI alone was included for comparing AF recurrence rates between the PVI alone group and the combined group. RESULTS: Following PSM, 153 patients (mean age 70.3 ± 8.9, 62.7% men) were included, with 102 undergoing the combined procedure and 51 undergoing LAAC alone. No significant differences were found in baseline characteristics between the two groups. The mean follow-up time was 37.6 ± 7.9 months, and two patients were lost to follow-up in the combined procedure group. Thrombotic events were observed in 4 (7.8%) patients in the LAAC alone group and 4 (4.0%) in the combined group (Log-rank p = 0.301). The proportion of patients experiencing MACCE, re-hospitalization due to CVD, and AT between the two groups was comparable, as were bleeding events and peri-device complications. Among patients from the combined procedure group without AF recurrence, a significant difference was noted in prior-procedure left ventricular ejection fraction (LVEF) and LVEF at the 12th month after the procedure (57.2% ± 7.1% vs. 60.5% ± 6.5%, p = 0.002). CONCLUSION: The concomitant PVI and LAAC procedure did not increase procedure-related complications, nor did it confer significant benefits in preventing thrombotic events or reducing other cardiovascular events. However, the combined procedure improved heart function, suggesting potential long-term benefits.
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Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Oclusão do Apêndice Atrial Esquerdo , Veias Pulmonares/cirurgia , Pontuação de Propensão , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Hemorragia/etiologia , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND: There is growing evidence indicating a connection between fine particulate matter (PM2.5) and depressive symptoms. Metabolic risk factors are critical determinants of depressive symptoms. However, the mediating role of these factors on the association between PM2.5 and depressive symptoms remains elusive. We aimed to investigate whether and to what extent metabolic risk factors mediated the link between long-term PM2.5 exposure and depressive symptoms. METHODS: This study comprised 7794 individuals aged between 30 and 79 years who participated in two waves of the on-site surveys in the China Multi-Ethnic Cohort. Ambient PM2.5 concentrations were assessed utilizing a random forest method based on satellite data. We employed the Patient Health Questionnaire-9 to assess depressive symptoms at wave 2, and the overall as well as three sub-domain symptom scores (emotional, neurovegetative, and neurocognitive symptoms) were calculated. Three metabolic risk factors, including hypertension, diabetes, and dyslipidemia, were considered. Mediation analyses were conducted to assess the indirect effects of PM2.5 on depressive symptoms through metabolic risk factors. RESULTS: We found a positive association between chronic exposure to ambient PM2.5 and overall depressive symptoms as well as the three sub-domains. In mediation analyses, metabolic risk factors partially mediated the associations of PM2.5 on depressive symptoms. The natural indirect effects (RR, 95% CI) of PM2.5 on overall, emotional, neurovegetative, and neurocognitive symptoms mediated through metabolic risk factors were 1.004(1.001, 1.007), 1.004 (1.001, 1.008), 1.004 (1.001, 1.007), and 1.003(0.999, 1.007), respectively. Larger indirect effects were found in elderly participants (mediated proportion, 29.3%), females (13.3%), and people who did not consume alcohol (19.6%). CONCLUSIONS: Metabolic risk factors may act as mediators in the relationship between chronic PM2.5 exposure and depression. Treatment of metabolic risk factors may be an opportunity to reduce the burden of depression caused by long-term exposure to PM2.5.
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Poluentes Atmosféricos , Poluição do Ar , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China/epidemiologia , Depressão/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Material Particulado/toxicidade , Fatores de Risco , MasculinoRESUMO
BACKGROUND: Particulate matter (PM) exposure has been linked with cardiovascular disease (CVD) and metabolic syndrome (MetS), the latter characterized by concurrent multiple metabolic disorders. As a result, the mechanisms assumption from PM to CVD through MetS have emerged, thus requiring further epidemiological evidence. This cohort study aimed to assess whether MetS mediates the associations of PM with CVD risk. METHODS: This study included 14,195 participants from the Chengdu cohort of the China Multi-Ethnic Cohort (CMEC) study in 2018. The primary outcome of incident CVD diagnoses was identified using matched hospital records from the Health Information Center of Sichuan Province. Residence-specific levels of PM with aerodynamic diameters of ≤ 1 µm (PM1), ≤ 2.5 µm (PM2.5), and ≤ 10 µm (PM10) were estimated by spatiotemporal models. Causal mediation analyses were applied to evaluate the indirect effect of MetS. RESULTS: Increased exposure levels to PM were significantly associated with MetS and CVD. Mediation analyses indicated that the associations between PM exposure and CVD were mediated by MetS, with the proportion of multiple mediations being 19.3%, 12.1%, and 13.5% for PM1, PM2.5, and PM10, respectively. Further moderated mediation analyses suggested that male, overweight individuals, alcohol drinkers, and those suffering from indoor air pollution may experience more significant adverse effects from PM exposure on CVD via MetS than others. CONCLUSIONS: Our findings suggest that MetS partially mediates the association between long-term exposure to PM and CVD. These mediation effects appear to be amplified by demographic characteristics and unhealthy lifestyles.
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Poluentes Atmosféricos , Poluição do Ar , Doenças Cardiovasculares , Síndrome Metabólica , Humanos , Masculino , Material Particulado/toxicidade , Síndrome Metabólica/epidemiologia , Poluentes Atmosféricos/análise , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , China/epidemiologia , Poluição do Ar/efeitos adversos , Poluição do Ar/análiseRESUMO
INTRODUCTION: Despite early mobilization has been proposed as an effective intervention to improve prognosis of patients in intensive care unit and other clinical settings, the benefits of it in patients with atrial fibrillation undergoing catheter ablation is still unknow. METHOD: 273 geriatric patients with atrial fibrillation underwent catheter ablation in our center were included in this retrospective cohort study, with 137 in early mobilization group and 136 in routine care group. RESULT: After in-hospital observation and 90-day follow-up, we found though patients undergoing early mobilization didn't suffer more post-procedural complications, early mobilization didn't either shorten or extend the length of hospital stay. The average score of EQ-5D visual analogue scale and EHRA symptom scale were significantly improved and less unscheduled outpatient visits were recorded in early mobilization group during 90-day follow-up. CONCLUSION: Early mobilization could be a safe and favorable intervention for patients underwent catheter ablation.
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Fibrilação Atrial , Ablação por Cateter , Deambulação Precoce , Humanos , Fibrilação Atrial/cirurgia , Estudos Retrospectivos , Feminino , Masculino , Idoso , Idoso de 80 Anos ou mais , Tempo de Internação/estatística & dados numéricos , GeriatriaRESUMO
The booming demand on data security has aroused great interest for developing smart materials with temporal display feature and dynamic multicolor fluorescence. However, it remains challenging to implement both features on most responsive molecules. Herein, we construct a polymer free volume-controlled "molecular clock and emitter" via covalently embedding a multi-stimuli responsive molecular switch (i.e., spiropyran) into a polymer network (i.e., poly(pentafluorophenyl acrylate)) with programmable crosslink density and free volume. By the aminolysis of pentafluorophenyl ester with different amount of diamine crosslinkers, pPFPA-co-SP networks with controllable crosslink densities are generated, which have different confinement effects on the rate constant of SP/MC isomerization, thus leading to time-dependent photochromism. In addition, PTF1, a fluorescent probe that is sensitive to polymer rigidity, is introduced to further endow pPFPA-co-SP system with phototunable dynamic full-color emission. Therefore, relying on their synergistical responses to the rigidity of the polymer network, we have successfully developed a versatile molecular clock and emitter via an "one stone two birds" manner, which shows time-dependent data display along with dynamic multicolor fluorescence switching, providing great potential for advanced encryption and anticounterfeiting with a high security level.
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The development of electromagnetic wave absorbers operating in the sub-terahertz (sub-THz) region is necessary in 6G communications. We designed and fabricated a sub-THz metamaterial absorber based on metal microcoils embedded and periodically arranged in a dielectric substrate. The microcoil parameters were optimized by calculating the electromagnetic response of the metamaterial using finite element analysis. An actual metamaterial was then fabricated based on the optimized parameters and characterized using THz time-domain spectroscopy. Our microcoil absorber exhibits an absorptance of >80% and a high shielding performance at about 250â GHz. The resonance frequency can be precisely adjusted by modifying the microcoil array dimensions.
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BACKGROUND: Numerous studies have shown that residential greenness positively correlates with enhanced health. Metabolic dysfunction-associated fatty liver disease (MAFLD) affects about a quarter of the population while lacking specific treatments. Given that the association between green space and MAFLD is still unknown, we explored the association between residential greenness and MAFLD as well as the potential mechanisms based on the baseline survey of the China Multi-Ethnic Cohort (CMEC). METHODS: Residential greenness was expressed as normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI). MAFLD was assessed through hepatic steatosis, the presence of overweight/obesity, type 2 diabetes mellitus, and evidence of metabolic dysregulation. We used logistic regression to examine the association between NDVI/EVI and the prevalence of MAFLD. Moreover, we utilized causal mediation analyses to explore the role of physical activity and ambient particulate matters (PM1, PM2.5, and PM10) on the association between residential greenness and MAFLD. RESULTS: We included 72,368 participants from the CMEC and found that residential greenness was negatively associated with the prevalence of MAFLD. For an interquartile range (IQR) increase in NDVI500 m and EVI500 m, the odds ratio (OR) of MAFLD were 0.78 (95 %CI: 0.75, 0.81) and 0.81 (95 %CI: 0.78, 0.84), respectively. Greater association between residential greenness and MAFLD was observed among males. Air pollutants and physical activity could mediate a partial effect (8.5-22.9 %) of residential greenness on MAFLD. CONCLUSION: Higher residential greenness was associated with decreased risk of MAFLD. Moreover, the association was greater among males. The protective effects of residential greenness may be achieved by mitigating the hazardous effects of air pollutants and encouraging physical activity.
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Poluentes Atmosféricos , Poluição do Ar , Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Masculino , Humanos , Obesidade/epidemiologia , China/epidemiologia , Material Particulado/análise , Estudos Epidemiológicos , Poluição do Ar/análiseRESUMO
BACKGROUND: Exposure to particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) may increase the risk of 10-year atherosclerotic cardiovascular disease (ASCVD) risk. While PM2.5 is comprised of various components, the evidence on the correlation of its components with 10-year ASCVD risk and which component contributes most remains limited. METHODS: Data were derived from the baseline assessments of China Multi-Ethnic Cohort (CMEC). In total, 69,722 individuals aged 35-74 years were included into this study. The annual average concentration of PM2.5 and its components (black carbon, ammonium, nitrate, sulfate, organic matter, soil particles, and sea salt) were estimated by satellite remote sensing and chemical transport models. The ASCVD risk of individuals was calculated by the equations from the China-PAR Project (prediction for ASCVD risk in China). The relationship between single exposure to PM2.5 and its components and predicted 10-year ASCVD risk was assessed using the logistic regression model. The effect of joint exposure was estimated, and the most significant contributor was identified using the weighted quantile sum approach. RESULTS: Totally 69,722 participants were included, of which 95.8 % and 4.2 % had low and high 10-year ASCVD risk, respectively. Per standard deviation increases in the 3-year average concentration of PM2.5 mass (odds ratio [OR] 1.23, 95 % confidence interval [CI]: 1.12-1.35), black carbon (1.21, 1.11-1.33), ammonium (1.21, 1.10-1.32), nitrate (1.25, 1.14-1.38), organic matter (1.29, 1.18-1.42), sulfate (1.17, 1.07-1.28), and soil particles (1.15, 1.04-1.26) were related to high 10-year ASCVD risk. The overall effect (1.19, 1.11-1.28) of the PM2.5 components was positively associated with 10-year ASCVD risk, and organic matter had the most contribution to this relationship. Female participants were more significantly impacted by PM2.5, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles compared to others. CONCLUSION: Long-term exposure to PM2.5 mass, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles were positively associated with high 10-year ASCVD risk, while sea salt exhibited a protective effect. Moreover, the organic matter might take primary responsibility for the relationship between PM2.5 and 10-year ASCVD risk. Females were more susceptible to the adverse effect.
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Aterosclerose , Material Particulado , Adulto , Feminino , Humanos , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Carbono/análise , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etnologia , População do Leste Asiático , Nitratos/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Material Particulado/química , Solo , Fuligem/análise , Sulfatos/análise , MasculinoRESUMO
This article studies the impact of intervention measures with nudge characteristics on residents' waste separation behaviours under the background of new 'Beijing Municipal Regulation on Domestic Waste Management'. We analyse whether and how nudge interventions affect residents' waste separation behaviours through the Ordered Logit model and mediation analysis. Our research results show that three nudge tools, namely, the timing and fixed-point separation system, the cleaning staff guidance system and the uniform clothing and styling, can effectively promote residents from low classification levels to high classification levels. In the process of nudging interventions, factors such as residents' waste separation habit, external environmental perception and the sense of separation efficiency play a mediating role. Our study's findings suggest that effective nudge tools are helpful in cultivating residents' separation habits and hence we recommend that policy makers promote and popularise them in their attempt to improve domestic waste management behaviours.
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Fluorescent probes are attractive in diagnosis and sensing. However, most reported fluorophores can only detect one or few analytes/parameters, notably limiting their applications. Here we have designed three phenanthridine-based fluorophores (i.e., B1, F1, and T1 with 1D, 2D, and 3D molecular configuration, respectively) capable of monitoring various microenvironments. In rigidifying media, all fluorophores show bathochromic emissions but with different wavelength and intensity changes. Under compression, F1 shows a bathochromic emission of over 163â nm, which results in organic fluorophore-based full-color piezochromism. Moreover, both B1 and F1 exhibit an aggregation-caused quenching (ACQ) behavior, while T1 is an aggregation-induced emission (AIE) fluorophore. Further, F1 and T1 selectively concentrate in cell nucleus, whereas B1 mainly stains the cytoplasm in live cell imaging. This work provides a general design strategy of versatile fluorophores for microenvironmental monitoring.
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Diagnóstico por Imagem , Corantes Fluorescentes , Núcleo Celular , CitoplasmaRESUMO
CONTEXT: Recent studies in specific population subgroups (e.g., pregnant women) have suggested PM exposure increases the risk of hyperuricemia. However, no studies have examined this in the general population. Furthermore, the underlying mechanism through which PM impacts hyperuricemia risk is poorly understood. OBJECTIVE: To assess the association between long-term exposure to PM and risk of hyperuricemia and whether this association is mediated by lipid profile. METHODS: We included 5939 participants in Southwest China from the China Multi-Ethnic Cohort (baseline 2018-2019, follow-up 2020-2021). Long-term PM pollutants (PM1, PM2.5, PM10) exposure for each individual was represented by the three-year average PM levels before the baseline survey. Hyperuricemia at follow-up was defined as the serum uric acid above 7.0 mg/dL in men and 6.0 mg/dL in women. Serum lipids were measured at baseline including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). The association of PM with hyperuricemia was accessed through logistic regression. The potential mediation effects of serum lipids were evaluated through causal mediation analyses. RESULTS: A total of 837 participants were newly diagnosed with hyperuricemia. The odds ratios of hyperuricemia associated with an interquartile range (IQR) increase in PM1, PM2.5, and PM10 (IQR: 21.10, 25.78, 30.43 µg m-3) were 1.72 (95% CI: 1.23, 2.39), 2.68 (95% CI: 1.59, 4.49), and 1.81 (95% CI: 1.20, 2.72), respectively. The association between PM2.5, PM1, and PM10 on hyperuricemia was mediated by HDL-C (10%) and LDL-C (3%). CONCLUSION: Higher particulate matter exposure was associated with higher hyperuricemia incidence. The decline in HDL-C and rise in LDL-C partially mediated this association. These findings were conducive to scientific research about the underlying mechanism of PM on hyperuricemia.
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Poluentes Atmosféricos , Hiperuricemia , Poluentes Atmosféricos/análise , China/epidemiologia , LDL-Colesterol , Exposição Ambiental , Feminino , Humanos , Hiperuricemia/epidemiologia , Masculino , Material Particulado/análise , Material Particulado/toxicidade , Gravidez , Estudos Prospectivos , Ácido Úrico/análiseRESUMO
Previous studies assessing adverse health have traditionally focused on a single environmental exposure, failing to reflect the reality of various exposures present simultaneously. Air pollution, ambient temperature and greenness have been proposed as critical environmental factors associated with metabolic syndrome (MetS). However, evidence exploring their joint relationships with MetS is needed for identifying interactive factors and developing more targeted public health interventions. The baseline data was obtained from China Multi-Ethnic Cohort (CMEC). Environmental data of air pollutants (PM2.5, O3) and NDVI for greenness was calculated from satellites data. Ambient temperature data were obtained from European Center for Medium-Range Weather Forecasts (ECMWF). MetS was classified based on National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) using anthropometric measures and biomarkers. Logistic regression models were utilized to examine the combined relationship of MetS with three-year exposure to air pollutants, temperature and NDVI. Relative excess risk due to interaction (RERI) was calculated to evaluate interaction on an additive scale. We found associations between prevalent MetS and interquartile range (IQR) increases in PM2.5 (OR: 1.38; 95% confidence interval [95% CI]: 1.23, 1.55) and O3 (OR: 1.15; 95% CI: 1.09, 1.22). Additive and multiplicative interactions were observed between air pollutants and temperature exposure. Compared to low-temperature level, the relationship between PM2.5 and MetS attenuated (RERI: 0.22, 95% CI: 0.44, -0.04) at high-temperature level, while the relationship between O3 and MetS enhanced (RERI: 0.05, 95% CI: 0.02, 0.11). At low NDVI 250 m, the association between PM2.5 and MetS was stronger (RERI: 0.13, 95% CI: 0.05, 0.19) with high NDVI 250 m as the reference group. Our findings showed that ambient temperature and residential greenness could affect the relationship between air pollutants and MetS.
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Poluentes Atmosféricos , Poluição do Ar , Síndrome Metabólica , Adulto , China , Exposição Ambiental , Humanos , Material Particulado , TemperaturaRESUMO
BACKGROUND: Geographic altitude is a potent environmental factor for human microbiota and bone mineral density. However, little evidence exists in population-based studies with altitude diversity ranges across more than 3000 m. This study assessed the associations between a wide range of altitudes and bone mineral density, as well as the potential mediating role of microbiota in this relationship. METHODS: A total of 99,556 participants from the China Multi-Ethnic Cohort (CMEC) study were enrolled. The altitude of each participant was extracted from global Shuttle Radar Topography Mission (SRTM) 4 data. Bone mineral density was measured by calcaneus quantitative ultrasound index (QUI). Stool samples were collected for 16S rRNA gene sequencing (n = 1384). The metabolites of gut microbiota, seven kinds of short-chain fatty acids (SCFAs), were detected by gas chromatography-mass spectrometry (GC-MS, n = 128). After screening, 73,974 participants were selected for the "altitude-QUI" analysis and they were placed into the low-altitude (LA) and high-altitude (HA) groups. Additionally, a subgroup (n = 1384) was further selected for the "altitude-microbiota-QUI" analysis. Multivariate linear regression models and mediation analyses were conducted among participants. RESULTS: A significant negative association between high-altitude and QUI was obtained (mean difference = -0.373 standard deviation [SD], 95% confidence interval [CI]: -0.389, -0.358, n = 73,974). The same negative association was also observed in the population with microbiota data (mean difference = -0.185 SD, 95%CI: -0.360, -0.010, n = 1384), and a significant mediating effect of Catenibacteriumon on the association between altitude and QUI (proportion mediated = 25.2%, P = 0.038) was also noticed. Additionally, the acetic acid, butyric acid, and total amount of seven SCFAs of the low-altitude group were significantly higher than that of the high-altitude group (P < 0.05). CONCLUSION: High-altitude exposure may decrease bone mineral density in adults, thus increasing the risk of osteoporosis. The modulation of gut microbiota may be a potential strategy for alleviating the decrease of bone mineral density.
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Microbioma Gastrointestinal , Adulto , Humanos , Altitude , Densidade Óssea , Ácido Butírico/análise , Ácido Butírico/farmacologia , Ácidos Graxos Voláteis/análise , Fezes/química , RNA Ribossômico 16S/genéticaRESUMO
Long non-coding RNAs (lncRNAs) have been widely reported to regulate the development and chemoresistance of a variety of tumors. Temozolomide (TMZ) is a first-line chemotherapy for treatment of glioma. However, the effect and the regulatory mechanism of lncRNA MSC-AS1 (MSC-AS1) in TMZ-resistant glioma remain unrevealed. Levels of MSC-AS1, microRNA-373-3p (miR-373-3p), and cytoplasmic polyadenylation element binding protein 4 (CPEB4) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). All protein expression was detected by western blot. Cell viability and the half maximal inhibitory concentration (IC50) value of TMZ was assessed by cell counting kit-8 (CCK-8) assay. Cell cloning ability and apoptosis were examined by colony formation and flow cytometry assays, respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the correlation between miR-373-3p and MSC-AS1 or CPEB4. The xenograft models were established to determine the effect of MSC-AS1 in vivo. MSC-AS1 was up-regulated in TMZ-resistant glioma tissues and cells, and glioma patients with high MSC-AS1 expression tend to have lower overall survival rate. MSC-AS1 suppression reduced the IC50 value of TMZ and proliferation, promoted apoptosis and TMZ sensitivity, and affected PI3K/Akt pathway in TMZ-resistant glioma cells. MSC-AS1 acted as miR-373-3p sponge, and miR-373-3p directly targeted CPEB4. Silencing miR-373-3p reversed the promoting effect of MSC-AS1 or CPEB4 knockdown on TMZ sensitivity. Furthermore, MSC-AS1 knockdown inhibited TMZ-resistant glioma growth in vivo by regulating miR-373-3p/CPEB4 axis through PI3K/Akt pathway. Collectively, MSC-AS1 knockdown suppressed cell growth and the chemoresistance of glioma cells to TMZ by regulating miR-373-3p/CPEB4 axis in vitro and in vivo through activating PI3K/Akt pathway.
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Glioma/tratamento farmacológico , MicroRNAs/genética , RNA Longo não Codificante/antagonistas & inibidores , Proteínas de Ligação a RNA/metabolismo , Temozolomida/farmacologia , Animais , Antineoplásicos Alquilantes/farmacologia , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/patologia , Biologia Computacional/métodos , Bases de Dados Genéticas , Resistencia a Medicamentos Antineoplásicos , Feminino , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , MicroRNAs/agonistas , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/antagonistas & inibidores , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Interleukin (IL)-12p40, a component of IL-12 and IL-23, can be secreted as monomer and homodimer in mammals. Our previous study has proved the existence of natural three p40 isoforms and their proinflammatory properties in grass carp. In the present study, we unexpectedly found that recombinant grass carp p40a/b/c (rgcp40a, rgcp40b and rgcp40c) were able to enhance the mRNA levels of grass carp il-17a/f1 (gcil-17a/f1) in a dose- and time-dependent manner in head kidney leukocytes (HKLs). In agreement with these findings, the enzyme-linked immunosorbent assay (ELISA) showed that rgcp40a, rgcp40b and rgcp40c markedly stimulated gcIl-17a/f1 secretion from the HKLs. Together with their stimulatory effects on grass carp gcil-22 and gcil-26 expression, our data suggested their potential to mediate Th17-like response in grass carp. To support this notion, we investigated the underlying mechanisms for the regulation of rgcp40 isoforms on gcil-17a/f1 expression, and found that three rgcp40 isoforms significantly induced the activation of Erk, Jnk and Stat3 pathways in a time-dependent oscillation in the same cell model. Moreover, three rgcp40 isoforms-induced gcil-17a/f1 mRNA expression was suppressed by the inhibition on Erk, Jnk and Stat3 pathways, suggesting the signaling pathways in the p40 isoforms-mediating il-17a/f1 transcription. These studies for the first time proved the involvement of three gcp40 isoforms in mediating Th17 signature cytokine expression in fish immune cells, therefore providing new insights into the roles of p40 in teleost immunity.
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Carpas/genética , Citocinas/genética , Proteínas de Peixes/genética , Expressão Gênica/imunologia , Rim Cefálico/imunologia , Leucócitos/imunologia , Animais , Carpas/imunologia , Citocinas/imunologia , Proteínas de Peixes/imunologia , Células Th17/imunologiaRESUMO
Interleukin (IL)-2 belongs to the four-helix bundle cytokine family and plays key roles in growth, survival, activation-induced cell death and differentiation of the immune cells. In cyprinid fish, only common carp interleukin-2 (il2) has been cloned because of relatively low sequence homology between carp Il-2 and its homologs in other fish species. In the present study, the coding sequence of grass carp Il-2 (gcIl-2) was cloned and its identity was verified via bioinformatic analysis. Tissue distribution study showed that grass carp il2 (gcil2) mRNA was expressed in thymus, head kidney and gill with relatively high levels. Recombinant gcIl-2 (rgcIl-2) protein was subsequently prepared by using a prokaryotic expression system followed by a refolding method. The purified rgcIl-2 displayed an ability to stimulate the cell proliferation along with an increased mRNA expression of cd4l but not cd8a, igm or mcsfr in grass carp head kidney leukocytes (HKLs), suggesting the possible involvement of gcIl-2 in T helper (Th) cell proliferation. In the same cell model, rgcIl-2 significantly enhanced mRNA expression of some cytotoxic molecules including perforin-like protein 2, granzyme B-like and Fas ligand, indicating the modulation of cytotoxic cells by gcIl-2 in grass carp HKLs. Besides, gene expression of regulatory T (Treg) cell- and Th1/2 cell-related cytokines or transcription factors was detected in grass carp HKLs treated by rgcIl-2. Results showed that rgcIL2 treatment increased the mRNA expression of foxp3, cd25l, ifng2, il12p35, tbet, tnfa, il2, il4/13a, il4/13b and gata3l in HKLs, implying the regulatory roles of Il-2 in the expression of these immune genes and its possible involvement in differentiation of Treg and Th1/2 cells. These observations together with the related studies in other fishes suggest the existence of cytotoxic cells, Treg and Th1/2 subpopulations in fish species and the functional roles of Il-2 in these cells.
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Carpas/imunologia , Rim Cefálico/citologia , Interleucina-2/imunologia , Leucócitos/imunologia , Animais , Biologia Computacional , Citocinas/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Expressão Gênica , Rim Cefálico/imunologia , Interleucina-2/genética , RNA Mensageiro/imunologia , Transdução de SinaisRESUMO
OBJECTIVE: The 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) was revised to include molecular biomarkers as diagnostic criteria. However, conventional biopsies of gliomas were spatially and temporally limited. This study aimed to determine whether circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) could provide more comprehensive diagnostic information to gliomas. METHODS: Combined with clinical data, we analyzed gene alterations from CSF and tumor tissues of newly diagnosed patients, and detected mutations of ctDNA in recurrent patients. We simultaneously analyzed mutations of ctDNA in different glioma subtypes, and in lower-grade gliomas (LrGG) versus glioblastoma multiforme (GBM). RESULTS: CSF ctDNA mutations had high concordance rates with tumor DNA (tDNA). CSF ctDNA mutations of PTEN and TP53 were commonly detected in recurrent gliomas patients. IDH mutation was detected in most of CSF ctDNA derived from IDH-mutant diffuse astrocytomas, while CSF ctDNA mutations of RB1 and EGFR were found in IDH-wild-type GBM. IDH mutation was detected in LrGG, whereas Rb1 mutation was more commonly detected in GBM. CONCLUSIONS: CSF ctDNA detection can be an alternative method as liquid biopsy in gliomas.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/diagnóstico , DNA Tumoral Circulante/líquido cefalorraquidiano , Glioma/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/genética , Receptores ErbB/genética , Feminino , Glioma/líquido cefalorraquidiano , Glioma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/líquido cefalorraquidiano , Recidiva Local de Neoplasia/genética , PTEN Fosfo-Hidrolase/genética , Proteínas de Ligação a Retinoblastoma/genética , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
BACKGROUND: Glioma invading the corpus callosum (CC) accounts for approximately 14% of gliomas and is thought to be more aggressive. However, there is still a lack of studies on the pathogenesis and molecular features of this condition. Here, we examined the occurrence association of CC invasion with respect to patients' clinical, pathological, and genetic characteristics. METHODS: First, a cohort of 331 patients was included, with 86 cases (26%) that were diagnosed with invasion glioma. They were all analyzed for basic clinical and pathological characteristics and four routinely tested glioma molecular markers. Second, 29 pairs of patients who underwent deep sequencing of 68 glioma molecular alterations were selected from both groups for in-depth analysis. RESULTS: The results of the first part showed that there was no difference between the two groups in terms of the basic factors in univariate analysis, while in multivariate logistic analysis, WHO grade was the risk factor for CC invasion (p = 0.001). The results of the second part showed that the paired groups had different genetic expression profiles, which highlighted glioma invading the CC as a distinct biological entity. PDGFRA mutation (PDGFRAmut) was present in 9 patients with invasive gliomas (31%), but only in one case (3.4%) in the control group (OR 17.331; 95% CI 1.987-151.156). CONCLUSION: Our data revealed the clinical, pathological, and genetic characteristics of glioma invading the CC and showed that it may be associated with glioma WHO grade and PDGFRAmut, but not other factors. Thus, the risk signaling pathway may offer potential therapeutic targets for this disease.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/metabolismo , Corpo Caloso/metabolismo , Glioma/metabolismo , Adulto , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Corpo Caloso/patologia , Feminino , Glioma/genética , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Invasividade Neoplásica , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Transdução de SinaisRESUMO
Tumor necrosis factor-alpha (TNF-α) signals through two distinct cell surface receptors, TNFR1 and TNFR2 in mammals. In the present study, grass carp Tnfr2 (gcTnfr2) was isolated and characterized. Sequence alignment and phylogenetic analysis suggested that gcTnfr2 was a homolog of goldfish and zebrafish Tnfr2. Tissue distribution assay showed gctnfr2 transcripts were expressed in all examined tissues similar to gctnfr1. To functionally characterize the newly cloned molecule, gcTnfr2 was overexpressed in COS7 cell lines and it showed the ability to mediate the recombinant grass carp Tnf (rgcTnf)-α-triggered NF-κΒ activity and gcil1b promoter activity, clarifying its role in mediating Tnf-α signaling. The recombinant soluble form of gcTnfr2 (rgcsTnfr2) was prepared and it was able to interact with rgcTnf-α with higher affinity than that of rgcsTnfr1. Moreover, grass carp soluble Tnfr2 (gcsTnfr2) were detected in the culture medium of grass carp head kidney leukocytes (HKLs) and heat-inactivated A. hydrophila challenge significantly induced its production, indicating involvement of gcsTnfr2 in inflammation response. In agreement with this notion, rgcsTnfr2 effectively antagonized the effect of rgcTnf-α on il1b mRNA expression in HKLs, suggesting anti-Tnf-α property of gcsTnfr2. To strengthen the anti-inflammatory role of soluble Tnfr2, bacteria were injected intraperitoneally in grass carp followed by rgcsTnfr2. Hematoxylin-eosin (HE) staining of head kidney, spleen and intestine showed that rgcsTnfr2 could significantly improve infection-induced histopathological changes. These results functionally identified gcTnfr2 and its soluble form, particularly highlighting the role of gcsTnfr2 against Tnf-α-triggered inflammatory signaling. In this line, rgcsTnfr2 displayed anti-inflammatory potentiality during infection, thereby providing a powerful mediator of inflammation control in fish.