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1.
Ecotoxicol Environ Saf ; 270: 115839, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38118332

RESUMO

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.


Assuntos
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 , Masculino
2.
Molecules ; 29(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38893373

RESUMO

Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeIIICl(TMPPH2)][FeIIICl4]2 (Fe-TMPP) exhibits a superior anticancer performance on a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC50) values in the range of 0.098-3.97 µM (0.066-2.68 µg mL-1), comparable to the best-reported medicines. Fe-TMPP can form stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, Fe-TMPP is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed H2O2, converting H2O2 to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.


Assuntos
Antineoplásicos , Ferroptose , Nanomedicina , Humanos , Ferroptose/efeitos dos fármacos , Linhagem Celular Tumoral , Nanomedicina/métodos , Antineoplásicos/farmacologia , Antineoplásicos/química , Nanopartículas/química , Compostos Férricos/química , Microambiente Tumoral/efeitos dos fármacos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologia
3.
Arch Biochem Biophys ; 734: 109499, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36587827

RESUMO

Parvalbumin-expressing neurons are a type of inhibitory intermediate neuron that play an important role in terminating seizures. The aim of the present study was to use lentiviral construction and packaging technology to overexpress and silence the parvalbumin gene in pheochromocytoma (PC12) cells, and to evaluate how parvalbumin influences the metabolic pathway involving glutamate and γ-aminobutyric acid (GABA). In this work, Immunofluorescence staining was used to verify the differentiation of PC12 cells into neurons after adding nerve growth factor (NGF). Western blotting and real-time quantitative polymerase chain reaction (qRT-PCR) were used to confirm lentivirus-mediated knockdown or overexpression of parvalbumin. Expression of parvalbumin, the 65-kDa GAD isoform (GAD65), and the 67-kDa GAD isoform (GAD67) in neuronal cells was examined at the mRNA and protein levels using qRT-PCR, western blotting and immunofluorescence staining, while intracellular glutamate and GABA levels were determined by high performance liquid chromatography (HPLC). We demonstrate that the expression of parvalbumin is associated with GAD65 and GAD67. Interestingly, overexpression of parvalbumin up-regulated GAD65 and GAD67, increased GABA concentration, and decreased glutamate concentration. Silencing of parvalbumin led to the opposite effects. Altogether, parvalbumin affected the expression of GAD65 and GAD67, thereby influencing the metabolic pathway involving glutamate and GABA.


Assuntos
Glutamato Descarboxilase , Ácido Glutâmico , Parvalbuminas , Animais , Ratos , Ácido gama-Aminobutírico/metabolismo , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/metabolismo , Ácido Glutâmico/metabolismo , Redes e Vias Metabólicas , Neurônios/metabolismo , Parvalbuminas/metabolismo
4.
BMC Cardiovasc Disord ; 23(1): 3, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609219

RESUMO

OBJECTIVE: The purpose of this study was to investigate the relationship between homocysteine (Hcy) levels and cardiopulmonary exercise testing (CPET) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). We also explored the relationship between Hcy levels and cardiac ultrasonography. METHODS: This study comprised 261 patients with ACS who underwent coronary angiography and PCI at Yulin First Hospital from January 2020 to June 2021. All subjects completed basic data collection, laboratory examination, CPET and cardiac ultrasonography. The CPET includes the peak oxygen uptake (peak VO2), anaerobic threshold (AT), metabolic equivalents (METs), exercise load (load), oxygen pulse (O2 pulse), end-tidal CO2 partial pressure (PETCO2), ventilatory equivalents for carbon dioxide (VE/VCO2) and Oxygen uptake efficiency (OUES). Cardiac ultrasonography was used to evaluate the left ventricular end diastolic diameter (LVEDD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT) and left ventricular ejection fraction (LVEF). A serum Hcy level ≥ 15 µmol/L was defined as hyperhomocysteinemia (HHcy). The patients were divided into the Hcy < 15 µmol/L group (n = 189) and the Hcy ≥ 15 µmol/L group (n = 72). RESULTS: The average age of the participating patients was 58.9 ± 10.1 years. The majority of participants were male (86.6%). The CPET indices of METs, load, VO2/kg, and PETCO2 were significantly decreased in the Hcy ≥ 15 µmol/L group compared with the Hcy < 15 µmol/L group. Additionally, the CPET index of the VE/VCO2 slope and the cardiac ultrasonography indices of IVST and LVPWT were significantly increased in the Hcy ≥ 15 µmol/L group compared with the Hcy < 15 µmol/L group. These differences were statistically significant (P < 0.05). Correlation analysis showed that Hcy levels were negatively correlated with METs, VO2/kg and PETCO2 and positively correlated with the VE/VCO2 slope (P < 0.05). Partial correlation analysis showed that Hcy levels were negatively correlated with METs and VO2/kg in the AT state. The correlation coefficients were - 0.172 and - 0.172, respectively (P < 0.05). Hcy levels were negatively correlated with METs, VO2/kg and PETCO2 in the peak state. The correlation coefficients were - 0.177, -0.153 and - 0.129, respectively (P < 0.05). After further adjustment for confounders, multiple linear regression analysis showed that Hcy levels were negatively correlated with METs and VO2/kg in the AT state and peak state. The standardized regression coefficients were - 0.035, -0.122, -0.048 and - 0.128, respectively (P < 0.05). Correlation analysis showed that Hcy levels were positively correlated with the IVST and LVPWT (P < 0.05), but after adjusting for confounding factors, partial correlation analysis showed that there was no correlation between them. CONCLUSION: A high Hcy level is associated with lower METs and VO2/kg and worse cardiopulmonary function in patients with ACS after PCI.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Teste de Esforço , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/terapia , Intervenção Coronária Percutânea/efeitos adversos , Volume Sistólico , Função Ventricular Esquerda , Oxigênio , Consumo de Oxigênio
5.
Ecotoxicol Environ Saf ; 263: 115371, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37643506

RESUMO

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.


Assuntos
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 , Masculino
6.
Molecules ; 28(6)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36985486

RESUMO

A class of piperazine hybridized coumarin indolylcyanoenones was exploited as new structural antibacterial frameworks to combat intractable bacterial resistance. Bioactive assessment discovered that 4-chlorobenzyl derivative 11f showed a prominent inhibition on Pseudomonas aeruginosa ATCC 27853 with a low MIC of 1 µg/mL, which was four-fold more effective than norfloxacin. Importantly, the highly active 11f with inconspicuous hemolysis towards human red blood cells displayed quite low proneness to trigger bacterial resistance. Preliminary explorations on its antibacterial behavior disclosed that 11f possessed the ability to destroy bacterial cell membrane, leading to increased permeability of inner and outer membranes, the depolarization and fracture of membrane, and the effusion of intracellular components. Furthermore, bacterial oxidative stress and metabolic turbulence aroused by 11f also accelerated bacterial apoptosis. In particular, 11f could not only effectively inset into DNA, but also bind with DNA gyrase through forming supramolecular complex, thereby affecting the biological function of DNA. The above findings of new piperazine hybridized coumarin indolylcyanoenones provided an inspired possibility for the treatment of resistant bacterial infections.


Assuntos
Antibacterianos , Infecções Bacterianas , Humanos , Piperazina/farmacologia , Testes de Sensibilidade Microbiana , Antibacterianos/química , Bactérias , DNA/farmacologia , Cumarínicos/farmacologia , Cumarínicos/química
7.
Environ Res ; 214(Pt 1): 113699, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35714687

RESUMO

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.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Síndrome Metabólica , Adulto , China , Exposição Ambiental , Humanos , Material Particulado , Temperatura
8.
Environ Res ; 214(Pt 2): 113865, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35835168

RESUMO

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.


Assuntos
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/análise
9.
Clin Exp Hypertens ; 44(5): 397-402, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35315303

RESUMO

OBJECTIVE: To investigate the effects of sacubitril/valsartan (S/V) on cardiopulmonary function and blood pressure response to exercise during hospitalization in patients with acute myocardial infarction (AMI) based on the cardiopulmonary exercise test (CPET). METHODS: A total of 265 AMI patients were treated with either perindopril or S/V within 24 hours of admission. CPET was completed for all patients before discharge. There were 182 cases in the perindopril group and 83 cases in the S/V group. RESULTS: The proportion of exercise oscillatory ventilation (EOV) was higher in the S/V group than in the perindopril group (10.8% vs 1.6%, X2 = 11.148, P = .001). The resting heart rate (HR), resting diastolic blood pressure (DBP), and warm-up DBP were lower in the S/V group than in the perindopril group (P < .05). The resting systolic blood pressure (SBP) was 9.0 mmHg lower (115.7 ± 17.5 vs 106.7 ± 15.0, P < .001), the SBP during warm-up was 9.5 mmHg lower (124.8 ± 23.7 vs 115.3 ± 22.5,P = .002), the SBP at the anaerobic threshold (AT) was 10.5 mmHg lower (135.3 ± 24.8 vs 127.1 ± 25.1,P = .021),the SBP at max watts was 11.5 mmHg lower (148.9 ± 26.4 vs 137.4 ± 26.4,P = .001), and the SBP during one-minute recovery was 12.3 mmHg lower (146.5 ± 27.1 vs 134.2 ± 24.4, P = .001)in the S/V group than in the perindopril group. The S/V group had a higher oxygen ventilation equivalent and carbon dioxide ventilation equivalent (VE/VCO2) at AT and a lower oxygen uptake-work rate relationship during max watts (P < .05). The differences in the oxygen pulse, stroke volume, peak oxygen uptake (VO2 peak), and VE/VCO2 slope were not statistically significant between the two groups. CONCLUSION: Treatment with S/V was able to reduce the exercise blood pressure in patients with AMI during hospitalization, but did not significantly improve the VO2 peak, VE/VCO2 slope, or exercise tolerance.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Aminobutiratos , Compostos de Bifenilo , Pressão Sanguínea , Teste de Esforço , Tolerância ao Exercício , Hospitalização , Humanos , Infarto do Miocárdio/tratamento farmacológico , Oxigênio , Consumo de Oxigênio , Perindopril , Valsartana/uso terapêutico
10.
Ecotoxicol Environ Saf ; 242: 113851, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35816844

RESUMO

BACKGROUND: Limited studies have examined associations between air pollutants exposure and renal function, especially in China, with the most extensive chronic kidney disease (CKD) disease burden worldwide. OBJECTIVES: This study examines associations between long-term exposure to ambient PM2.5, NO2, CO, O3, SO2 and renal function. METHODS: We included 80,225 participants aged 30-79 years from the baseline data of the China Multi-Ethnic Cohort (CMEC) study. Three-year average concentrations of PM2.5, NO2, CO, O3, and SO2 were estimated using satellite-based spatiotemporal models. Renal function is determined by the estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. After adjusting for covariates, generalized propensity scores (GPS) weighting regression was used to estimate associations between ambient air pollutants and renal function. RESULTS: An increase of 0.1 mg/m3 CO (OR [odds ratio] =1.20 95% CI [confidence interval], 1.05-1.37) was positively associated with CKD. An increase of 1 µg/m3 in SO2 (1.07, 1.00-1.14) concentration was positively associated with CKD. An increase of 10 µg/m3 in PM2.5 (1.17, 0.99-1.38), NO2 (1.12, 0.83-1.51) and O3 (1.10, 0.81-1.50) concentration was not associated with CKD. These effects are stronger in those younger than 65, smoking and with low BMI. CONCLUSIONS: In this study, we found that long-term exposure to ambient CO and SO2 were positively associated with CKD. Gaseous pollutants should also arouse the concern of relevant departments.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Insuficiência Renal Crônica , Humanos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Rim/química , Rim/fisiologia , Dióxido de Nitrogênio/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Insuficiência Renal Crônica/epidemiologia
11.
Environ Res ; 197: 111174, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33894235

RESUMO

BACKGROUND: Dyslipidemia is a crucial risk factor for cardiovascular diseases. Previous studies have suggested that air pollution is associated with blood lipids. However, little evidence exists in low- and middle-income regions. We aimed to investigate the association between air pollution and blood lipids in southwestern China. METHODS: We included 67,305 participants aged 30-79 years from the baseline data of the China Multi-Ethnic Cohort (CMEC) study. Three-year average concentrations of particles with diameters ≤1 µm (PM1), particles with diameters ≤ 2.5 µm (PM2.5), particles with diameters ≤ 10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) were estimated using satellite-based spatiotemporal models. Individual serum lipids, including cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), were measured. Linear, logistic, and quantile regression models were used to evaluate the association between ambient air pollution and blood lipids. RESULTS: All five air pollutants in our study were associated with lipid levels. Increased air pollution exposure was associated with a high risk of dyslipidemia. Each 10 µg/m3 increase in PM2.5 was associated with 0.92% (95% confidence interval (CI): 0.64%, 1.20%), 2.23% (95% CI: 1.44%, 3.02%), and 3.04% (95% CI: 2.61%, 3.47%) increases in TC, TG, and LDL-C levels, respectively, and a 2.03% (95% CI: 1.69%, 2.37%) decrease in HDL-C levels, and high risks of dyslipidemia (OR = 1.14, 95% CI: 1.10, 1.18). Stronger associations of air pollution with blood lipids were found in participants with high lipid levels than in those with low lipid levels. CONCLUSION: Long-term exposure to air pollutants was associated with blood lipid levels and the risk of dyslipidemia. People with high lipid levels were more susceptible to air pollution. Therefore, air pollution prevention and control may help reduce the incidence of dyslipidemia and the burden of CVDs.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Adulto , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Lipídeos , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/toxicidade , Material Particulado/análise , Material Particulado/toxicidade
12.
Epilepsy Behav ; 103(Pt A): 106670, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31864943

RESUMO

Evidence indicates that ferrostain-1 (Fer-1), a specific inhibitor of ferroptosis, could ameliorate cognitive dysfunction of rats with kainic acid (KA)-induced temporal lobe epilepsy (TLE) by suppressing ferroptosis processes. Recent studies suggest that P38 mitogen-activated protein kinase (MAPK) pathway could be mediated by ferroptosis processes. The activation of P38 MAPK results in cognitive impairment by suppressing the expression of synaptic plasticity-related proteins. However, it is unclear whether Fer-1 can mitigate cognitive impairment of rats with KA-induced TLE by inhibiting P38 MAPK activation. In the present study, treatment with Fer-1 blocked the activation of P38 MAPK, which resulted in an increased expression of synaptophysin (SYP) and postsynaptic density protein 95 (PSD-95) in the hippocampus of rats with KA-induced TLE, hence, ameliorating their cognitive impairment. Also, P38 MAPK activation in the hippocampus of the rats reduced the expression of both PSD-95 and SYP proteins. Treatment of the rats with SB203580, a P38 MAPK-specific inhibitor, prevented the activation of P38 MAPK, which resulted in an increase in SYP and PSD95 protein levels in the hippocampus. These results suggest that Fer-1 could mitigate the cognitive impairment by suppressing P38 MAPK activation thus restoring the expression of synaptic proteins. Ferroptosis processes might be involved in suppressing synaptic protein expression.


Assuntos
Disfunção Cognitiva/prevenção & controle , Cicloexilaminas/uso terapêutico , Epilepsia do Lobo Temporal/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Fenilenodiaminas/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Biomarcadores/metabolismo , Disfunção Cognitiva/metabolismo , Cicloexilaminas/farmacologia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/psicologia , Ferroptose/efeitos dos fármacos , Ferroptose/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Fármacos Neuroprotetores/farmacologia , Fenilenodiaminas/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
J Am Chem Soc ; 137(22): 7047-50, 2015 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-26001409

RESUMO

A novel microporous aluminoborate, denoted as PKU-3, was prepared by the boric acid flux method. The structure of PKU-3 was determined by combining the rotation electron diffraction and synchrotron powder X-ray diffraction data with well resolved ordered Cl(-) ions in the channel. Composition and crystal structure analysis showed that there are both proton and chlorine ions in the channels. Part of these protons and chlorine ions can be washed away by basic solutions to activate the open pores. The washed PKU-3 can be used as an efficient catalyst in the Strecker reaction with yields higher than 90%.

14.
ACS Chem Neurosci ; 15(10): 1951-1966, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38696478

RESUMO

Aims: the study aimed to (i) use adeno-associated virus technology to modulate parvalbumin (PV) gene expression, both through overexpression and silencing, within the hippocampus of male mice and (ii) assess the impact of PV on the metabolic pathway of glutamate and γ-aminobutyric acid (GABA). Methods: a status epilepticus (SE) mouse model was established by injecting kainic acid into the hippocampus of transgenic mice. When the seizures of mice reached SE, the mice were killed at that time point and 30 min after the onset of SE. Hippocampal tissues were extracted and the mRNA and protein levels of PV and the 65 kDa (GAD65) and 67 kDa (GAD67) isoforms of glutamate decarboxylase were assessed using real-time quantitative polymerase chain reaction and Western blot, respectively. The concentrations of glutamate and GABA were detected with high-performance liquid chromatography (HPLC), and the intracellular calcium concentration was detected using flow cytometry. Results: we demonstrate that the expression of PV is associated with GAD65 and GAD67 and that PV regulates the levels of GAD65 and GAD67. PV was correlated with calcium concentration and GAD expression. Interestingly, PV overexpression resulted in a reduction in calcium ion concentration, upregulation of GAD65 and GAD67, elevation of GABA concentration, reduction in glutamate concentration, and an extension of seizure latency. Conversely, PV silencing induced the opposite effects. Conclusion: parvalbumin may affect the expression of GAD65 and GAD67 by regulating calcium ion concentration, thereby affecting the metabolic pathways associated with glutamate and GABA. In turn, this contributes to the regulation of seizure activity.


Assuntos
Cálcio , Ácido Glutâmico , Ácido Caínico , Parvalbuminas , Estado Epiléptico , Ácido gama-Aminobutírico , Animais , Masculino , Camundongos , Cálcio/metabolismo , Modelos Animais de Doenças , Ácido gama-Aminobutírico/metabolismo , Glutamato Descarboxilase/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Camundongos Transgênicos , Parvalbuminas/metabolismo , Estado Epiléptico/metabolismo , Estado Epiléptico/induzido quimicamente
15.
Diagn Microbiol Infect Dis ; 110(1): 116392, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38875895

RESUMO

OBJECTIVE: To explore the diagnostic value of third-generation nanopore sequencing technology in patients with diabetes mellitus suspected of pulmonary tuberculosis. METHODS: Samples, including sputum and bronchoalveolar lavage fluid(BALF), were collected from patients with diabetes mellitus suspected of pulmonary tuberculosis who were admitted from October 2021 to August 2023. Nanopore sequencing, acid-fast bacilli (AFB) smear, mycobacterial solid culture, Xpert MTB/RIF, and DNA detection were performed, and their diagnostic efficacy was compared. RESULTS: Third-generation nanopore sequencing technology exhibited high accuracy in diagnosing pulmonary tuberculosis in patients with diabetes mellitus. Compared to traditional methods, nanopore sequencing showed significantly improved sensitivity (76.80 %), negative predictive value (30.40 %), coincidence (77.92 %), and diagnostic accuracy (AUC = 0.822). Combined detection with Xpert achieved the highest diagnostic performance, with increased sensitivity (81.20 %), positive predictive value (98.20 %), negative predictive value (35.00 %), coincidence (81.82 %), and AUC (0.843). Although acid-fast staining had limitations, its combination with nanopore sequencing improved screening effectiveness. CONCLUSION: Compared to established diagnostic modalities such as acid-fast staining, mycobacterial solid culture, Xpert MTB/RIF, and DNA detection, third-generation nanopore sequencing technology demonstrates a significant improvement in sensitivity for detecting suspected pulmonary tuberculosis in diabetic patients. Notably, the combined application of nanopore sequencing with Xpert testing offers a further enhancement in diagnostic accuracy.


Assuntos
Diabetes Mellitus , Mycobacterium tuberculosis , Sequenciamento por Nanoporos , Sensibilidade e Especificidade , Escarro , Tuberculose Pulmonar , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Sequenciamento por Nanoporos/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Escarro/microbiologia , Adulto , Líquido da Lavagem Broncoalveolar/microbiologia , Idoso , DNA Bacteriano/genética , Técnicas de Diagnóstico Molecular/métodos
16.
Chem Asian J ; 19(10): e202400237, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38563626

RESUMO

Herein, we report a rare example of cationic three-dimensional (3D) metal-organic framework (MOF) of [Cu5Cl3(TMPP)]Cl5 ⋅ xSol (denoted as Cu-TMPP; H2TMPP=meso-tetrakis (6-methylpyridin-3-yl) porphyrin; xSol=encapsulated solvates) supported by [Cu8Cl6]10+ cluster secondary building units (SBUs) wherein the eight faces of the Cl--based octahedron are capped by eight Cu2+. Surface-area analysis indicated that Cu-TMPP features a mesoporous structure and its solvate-like Cl- counterions can be exchanged by BF4 -, PF6 -, and NO3 -. The polyvinylpyrrolidone (PVP) coated Cu-TMPP (denoted as Cu-TMPP-PVP) demonstrated good ROS generating ability, producing ⋅OH in the absence of light (peroxidase-like activity) and 1O2 on light irradiation (650 nm; 25 mW cm-2). This work highlights the potential of Cu-TMPP as a functional carrier of anionic guests such as drugs, for the combination therapy of cancer and other diseases.

17.
Polymers (Basel) ; 15(12)2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37376393

RESUMO

The synthesis of efficient and sustainable heterogeneous Pd-based catalysts has been an active field of research due to their crucial role in carbon-carbon coupling reactions. In this study, we developed a facile and eco-friendly in situ assembly technique to produce a PdFe bimetallic hyper-crosslinked polymer (HCP@Pd/Fe) to use as a highly active and durable catalyst in the Ullmann reaction. The HCP@Pd/Fe catalyst exhibits a hierarchical pore structure, high specific surface area, and uniform distribution of active sites, which promote catalytic activity and stability. Under mild conditions, the HCP@Pd/Fe catalyst is capable of efficiently catalyzing the Ullmann reaction of aryl chlorides in aqueous media. The exceptional catalytic performance of HCP@Pd/Fe is attributed to its robust absorption capability, high dispersion, and strong interaction between Fe and Pd, as confirmed by various material characterizations and control experiments. Furthermore, the coated structure of a hyper-crosslinked polymer enables easy recycling and reuse of the catalyst for at least 10 cycles without any significant loss of activity.

18.
Postgrad Med ; 135(8): 803-808, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37864567

RESUMO

OBJECTIVE: This study aimed to analyze the correlation between the rate pressure product (RPP) and cardiopulmonary function during hospitalization in patients with acute myocardial infarction (AMI). METHODS: A total of 362 patients with AMI were selected for the study, and the median admission RPP was used as the cutoff point to divide the patients into a low-RPP group (n = 181) and a high-RPP group (n = 181). The relationship between the RPP at admission and the cardiopulmonary function during hospitalization was analyzed. RESULTS: The patients in the high-RPP group had a higher body mass index (BMI) (p = 0.014), a higher prevalence of combined hypertension and diabetes mellitus (p < 0.001), a lower incidence of smoking (p = 0.044), and a higher incidence of oscillatory ventilation (6.1% vs. 1.7%, p = 0.029). The differences in RPP at rest, during warm-up, and within 1 and 4 minutes of recovery were statistically significant between the two groups (p < 0.01 on each occasion), while the differences in anaerobic threshold (AT) and watt max (Max) were not statistically significant (p > 0.05 for both). The patients in the low-RPP group had higher oxygen uptake (VO2 [AT]: 14.9 ± 3.4 vs. 14.2 ± 3.6, p = 0.048) and (VO2peak [Max]:18.2 ± 3.8 vs. 17.3 ± 3.8, p = 0.020). The RPP at admission was negatively correlated with VO2 (AT) and VO2peak (p < 0.05) using the regression Equation VO2peak = 33.682 + (-0.012 * RPP at admission/100) + (-0.105 * Age) + (-0.350 * BMI), while there was no correlation between the RPP at admission and VO2 (AT) (p = 0.149). CONCLUSION: The RPP at admission was negatively correlated with cardiopulmonary function during hospitalization in patients with AMI. Patients with a high RPP were more likely to have a combination of obesity, hypertension, diabetes mellitus, and reduced oxygen uptake during exercise, while a high RPP at admission appeared to affect their cardiovascular response indicators during exercise.


Assuntos
Diabetes Mellitus , Hipertensão , Infarto do Miocárdio , Humanos , Infarto do Miocárdio/epidemiologia , Hospitalização , Hipertensão/epidemiologia , Diabetes Mellitus/epidemiologia , Oxigênio
19.
Eur J Med Chem ; 245(Pt 1): 114891, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36343412

RESUMO

Unique coumarin aminophosphonates as new antibacterial agents were designed and synthesized to combat severely bacterial resistance. Bioactivity assessment identified that 3-hydroxylphenyl aminophosphonate 6f with low hemolytic activity not only exhibited excellent inhibition potency against Staphylococcus aureus at low concentration (0.5 µg/mL) in vitro but also showed considerable antibacterial potency in vivo. Meanwhile, the active compound 6f was capable of eradicating the S. aureus biofilm, thus alleviating the development of S. aureus resistance. Furthermore, the drug combination of compound 6f with norfloxacin could enhance the antibacterial efficacy. Mechanistic explorations manifested that molecule 6f was able to destroy the integrity of cell membrane, which resulted in the leakage of protein and metabolism inhibition. The cellular redox homeostasis was interfered through inducing the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), leading to the reduction of glutathione (GSH) activity and lipid peroxidation. Furthermore, compound 6f could intercalate into DNA base pair to hinder normal biological function. The above results provided powerful information for the further development of coumarin aminophosphonates as antibacterial agents.


Assuntos
Aminocumarinas , Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Organofosfonatos , Antibacterianos/química , Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Aminocumarinas/química , Aminocumarinas/farmacologia , Farmacorresistência Bacteriana , Organofosfonatos/química , Organofosfonatos/farmacologia
20.
Eur J Med Chem ; 262: 115878, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37866337

RESUMO

A new type of benzopyrone-mediated quinolones (BMQs) was rationally designed and efficiently synthesized as novel potential antibacterial molecules to overcome the global increasingly serious drug resistance. Some synthesized BMQs effectively suppressed the growth of the tested strains, outperforming clinical drugs. Notably, ethylidene-derived BMQ 17a exhibited superior antibacterial potential with low MICs of 0.5-2 µg/mL to clinical drugs norfloxacin, it not only displayed rapid bactericidal performance and inhibited bacterial biofilm formation, but also showed low toxicity toward human red blood cells and normal MDA-kb2 cells. Mechanistic investigation demonstrated that BMQ 17a could effectually induce bacterial metabolic disorders and promote the enhancement of reactive oxygen species to disrupt the bacterial antioxidant defense system. It was found that the active molecule BMQ 17a could not only form supramolecular complex with lactate dehydrogenase, which disturbed the biological functions, but also effectively embed into calf thymus DNA, thus affecting the normal function of DNA and achieving cell death. This work would provide an insight into developing new molecules to reduce drug resistance and expand antibacterial spectrum.


Assuntos
Antibacterianos , Quinolonas , Humanos , Antibacterianos/farmacologia , DNA Girase/metabolismo , Testes de Sensibilidade Microbiana , Norfloxacino/farmacologia , Quinolonas/farmacologia , Quinolonas/metabolismo , Benzopiranos/metabolismo , Benzopiranos/farmacologia
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