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1.
Artigo em Inglês | MEDLINE | ID: mdl-34633619

RESUMO

BACKGROUND: In the context of global climate change, studies have focused on the ambient temperature and mortality of cardiovascular diseases (CVDs). However, little is known about the effect of ambient temperature on year of life lost (YLL), especially the life loss per death caused by ambient temperature. In this study, we aimed to assess the relationship between ambient temperature and life loss and estimate the impact of ambient temperature on life loss per death. METHODS: We collected daily time series of mortality and meteorological data from 70 locations in Hunan province, central China, in periods ranging from Jan. 1, 2013, to Dec. 31, 2017. Crude rates of YLL were calculated per 100,000 people per year (YLL/100,000 population) for each location. A distributed lag nonlinear model and multivariate meta-regression were used to estimate the associations between ambient temperature and YLL rates. Then, the average life loss per death attributable to ambient temperature was calculated. RESULTS: There were 711,484 CVD deaths recorded within the study period. The exposure-response curve between ambient temperature and YLL rates was inverted J or U-shaped. Relative to the minimum YLL rate temperature, the life loss risk of extreme cold temperature lasted for 10 to 12 days, whereas the risk of extreme hot temperature appeared immediately and lasted for 3 days. On average, the life loss per death attributable to non-optimum ambient temperatures was 1.89 (95% CI, 1.21-2.56) years. Life loss was mainly caused by cold temperature (1.13, 95% CI, 0.89­1.37), particularly moderate cold (1.00, 95% CI, 0.78­1.23). For demographic characteristics, the mean life loss per death was relatively higher for males (2.07, 95% CI, 1.44­2.68) and younger populations (3.72, 95% CI, 2.06­5.46) than for females (1.88, 95% CI, 1.21-2.57) and elderly people (1.69, 95% CI, 1.28-2.10), respectively. CONCLUSIONS: We found that both cold and hot temperatures significantly aggravated premature death from CVDs. Our results indicated that the whole range of effects of ambient temperature on CVDs should be given attention.

2.
ACS Appl Mater Interfaces ; 13(33): 38979-38989, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433249

RESUMO

Chronic infections caused by Pseudomonas aeruginosa pose severe threats to human health. Traditional antibiotic therapy has lost its total supremacy in this battle. Here, nanoplatforms activated by the clinical microenvironment are developed to treat P. aeruginosa infection on the basis of dynamic borate ester bonds. In this design, the nanoplatforms expose targeted groups for bacterial capture after activation by an acidic infection microenvironment, resulting in directional transport delivery of the payload to bacteria. Subsequently, the production of hyperpyrexia and reactive oxygen species enhances antibacterial efficacy without systemic toxicity. Such a formulation with a diameter less than 200 nm can eliminate biofilm up to 75%, downregulate the level of cytokines, and finally promote lung repair. Collectively, the biomimetic design with phototherapy killing capability has the potential to be an alternative strategy against chronic infections caused by P. aeruginosa.


Assuntos
Antibacterianos/química , Verde de Indocianina/química , Nanocápsulas/química , Fármacos Fotossensibilizantes/química , Polímeros/química , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/radioterapia , Células A549 , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Composição de Medicamentos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Humanos , Verde de Indocianina/farmacologia , Raios Infravermelhos , Masculino , Metacrilatos/química , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Pseudomonas aeruginosa/efeitos dos fármacos
3.
Biomacromolecules ; 22(9): 3704-3717, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34380309

RESUMO

Bacterial keratitis is a serious bacterial infection of the cornea that can cause sight loss in severe cases because of the sharp decline of efficacious antibiotics. Herein, a targeted photosensitizer based on BODIPY severing as a photobactericidal agent was developed for treating bacterial keratitis. The water solubility of the material was as high as 10 mg/mL, which was attributable to the introduction of pathogen-targeting galactose and fucose. The photosensitizer was able to preferentially bind Pseudomonas aeruginosa instead of mammalian cells and trigger the aggregation of bacteria, which ultimately facilitated effective pathogen ablation upon the generation of reactive oxygen species (ROS) via laser irradiation. Photoexcited targeted photosensitizers can promote wound healing by eradicating P. aeruginosa in rat eyes and reducing the inflammatory response, thus exhibiting the significant therapeutic effect on bacterial keratitis. We also performed molecular level mechanistic studies using the unique field-induced droplet ionization mass spectrometry methodology and confirmed that the generated ROS were mainly singlet oxygen that caused lipid peroxidation (Type II mechanism). We anticipate that the targeted photosensitizer will have great potential in the application of clinical photodynamic therapy to ocular infection.


Assuntos
Ceratite , Fotoquimioterapia , Animais , Ceratite/tratamento farmacológico , Luz , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Pseudomonas aeruginosa
4.
J Appl Toxicol ; 2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34247425

RESUMO

Despite the vast amount of research on the toxicity of copper-based nanoparticles, the toxicity of CuS nanoparticles is still largely unknown. Due to the application of CuS-based nanomaterials in biomedical engineering, it is necessary to study their potential toxicity and biological effects. In this study, we evaluated the toxicity of polymer-modified CuS nanoclusters (PATA3-C4@CuS) on embryo development through exposing zebrafish embryos to 1, 2.5, 5, 7.5, and 10 mg/L PATA3-C4@CuS at 0.75-h post-fertilization. The morphological results demonstrated that PATA3-C4@CuS at concentrations greater than 1 mg/L PATA3-C4@CuS induced abnormal phenotypes including smaller heads and eyes, pericardial edema, and epiboly retardation and it increased mortality, lowered the hatching rate, and inhibited swim bladder inflation. In situ hybridization and quantitative reverse transcription polymerase chain reaction showed that PATA3-C4@CuS could alter the expression patterns of tbxta, dlx3, and cstlb and increase the expression levels of wnt5 and wnt11, which suggested that PATA3-C4@CuS disrupts cell migration by increasing the levels of wnt5 and wnt11 during gastrulation. It was also discovered that PATA3-C4@CuS exposure caused a slow heart rate and smaller ventricles in zebrafish larvae. Immunofluorescence and behavioral analyses showed that PATA3-C4@CuS could damage the ventral projection of the primary motor neurons CaP, which was in accordance with the reduction in locomotion ability. Together, our data demonstrated that functional PATA3-C4@CuS could disrupt cell migration during gastrulation, affect cardiac development and function, and decrease locomotive activity.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34205544

RESUMO

This study aimed to evaluate the relationship between psychosocial variables (peer support, parental support, autonomous motivation, and controlled motivation), availability of physical activity resources in a neighborhood environment, and out-of-school moderate to vigorous physical activity (MVPA) among Chinese adolescents. The questionnaire of Family Life, Activity, Sun, Health, and Eating (FLASHE) Study was used to collect information on demographics, socioeconomic status, psychosocial variables, available physical activity resources in the neighborhood environment, and minutes of out-of-school MVPA. ANOVA analysis and multiple regression analysis were performed. The mean age of the 3833 adolescents included in our analysis was 14.7 years old (SD = 1.7). Peer support (b = 9.35, 95% CI: 7.55-11.15), autonomous motivation (b = 6.46, 95% CI: 4.09-8.82), parental support (b = 3.90, 95% CI: 1.75-6.07), and availability of physical activity resources in neighborhood environment (b = 3.18, 95% CI: 1.99-4.36) were significantly associated with out-of-school MVPA (p < 0.05). Controlled motivation was insignificantly related to minutes of out-of-school MVPA. Boys spent more time on out-of-school MVPA than girls (p < 0.001) and had a high level of peer support, parental support, and motivation (p < 0.05). Our findings suggest that interventions targeting the out-of-school MVPA among Chinese adolescents should focus on the psychosocial variables and neighborhood environment.


Assuntos
Exercício Físico , Características de Residência , Adolescente , China , Estudos Transversais , Feminino , Humanos , Masculino , Motivação , Instituições Acadêmicas
6.
Materials (Basel) ; 14(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34279271

RESUMO

H13 steel is often damaged by wear, erosion, and thermal fatigue. It is one of the essential methods to improve the service life of H13 steel by preparing a coating on it. Due to the advantages of high melting point, good wear, and corrosion resistance of Mo, Mo coating was fabricated on H13 steel by electro spark deposition (ESD) process in this study. The influences of the depositing parameters (deposition power, discharge frequency, and specific deposition time) on the roughness of the coating, thickness, and properties were investigated in detail. The optimized depositing parameters were obtained by comparing roughness, thickness, and crack performance of the coating. The results show that the cross-section of the coating mainly consisted of strengthening zone and transition zone. Metallurgical bonding was formed between the coating and substrate. The Mo coating mainly consisted of Fe9.7Mo0.3, Fe-Cr, FeMo, and Fe2Mo cemented carbide phases, and an amorphous phase. The Mo coating had better microhardness, wear, and corrosion resistance than substrate, which could significantly improve the service life of the H13 steel.

7.
Cell Death Dis ; 12(7): 710, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267188

RESUMO

Alcohol-related liver disease (ALD), a condition caused by alcohol overconsumption, occurs in three stages of liver injury including steatosis, hepatitis, and cirrhosis. DEP domain-containing protein 5 (DEPDC5), a component of GAP activities towards Rags 1 (GATOR1) complex, is a repressor of amino acid-sensing branch of the mammalian target of rapamycin complex 1 (mTORC1) pathway. In the current study, we found that aberrant activation of mTORC1 was likely attributed to the reduction of DEPDC5 in the livers of ethanol-fed mice or ALD patients. To further define the in vivo role of DEPDC5 in ALD development, we generated Depdc5 hepatocyte-specific knockout mouse model (Depdc5-LKO) in which mTORC1 pathway was constitutively activated through loss of the inhibitory effect of GATOR1. Hepatic Depdc5 ablation leads to mild hepatomegaly and liver injury and protects against diet-induced liver steatosis. In contrast, ethanol-fed Depdc5-LKO mice developed severe hepatic steatosis and inflammation. Pharmacological intervention with Torin 1 suppressed mTORC1 activity and remarkably ameliorated ethanol-induced hepatic steatosis and inflammation in both control and Depdc5-LKO mice. The pathological effect of sustained mTORC1 activity in ALD may be attributed to the suppression of peroxisome proliferator activated receptor α (PPARα), the master regulator of fatty acid oxidation in hepatocytes, because fenofibrate (PPARα agonist) treatment reverses ethanol-induced liver steatosis and inflammation in Depdc5-LKO mice. These findings provide novel insights into the in vivo role of hepatic DEPDC5 in the development of ALD.


Assuntos
Fígado Gorduroso Alcoólico/metabolismo , Proteínas Ativadoras de GTPase/deficiência , Fígado/metabolismo , PPAR alfa/metabolismo , Animais , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Fígado Gorduroso Alcoólico/genética , Fígado Gorduroso Alcoólico/patologia , Fígado Gorduroso Alcoólico/prevenção & controle , Feminino , Proteínas Ativadoras de GTPase/genética , Mediadores da Inflamação , Fígado/efeitos dos fármacos , Fígado/ultraestrutura , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos Knockout , Naftiridinas/farmacologia , Oxirredução , Estresse Oxidativo , PPAR alfa/genética , Transdução de Sinais
8.
ACS Appl Mater Interfaces ; 13(29): 33790-33801, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34254513

RESUMO

Hypoxia, a common characteristic of bacterial infections, is known to be closely associated with the emergence of multidrug-resistant bacteria, which hastens the need to develop advanced microbicides and antibacterial techniques. Photodynamic therapy is a promising strategy to reduce bacterial antibiotic resistance and employs photosensitizers, excitation light sources, and sufficient oxygen to generate toxic reactive oxygen species (ROS). The inherent limitation of PDT is that the generation of ROS is restricted by the hypoxic microenvironment in infection sites. Here, an oxygen self-supplying nanotherapeutic is developed to enhance antibacterial activity against multidrug-resistant bacteria on the basis of fluorinated boron dipyrromethene (BODIPY)-based glycomimetics. The nanotherapeutic not only could capture the bacteria efficiently but also was able to act as an oxygen carrier to relieve the hypoxic microenvironment of bacterial infections, thus achieving enhanced PDT efficacy. In a Pseudomonas aeruginosa infection of a rat cornea, typical administration of the nanotherapeutic decreased the infiltrate and showed a faster healing capacity in comparison with BODIPY-based glycomimetics. Self-supplying oxygen nanotherapeutics that relieve the hypoxic microenvironment and interfere with bacterial colonization have been shown to be a promising candidate for the management of drug-resistant microbial keratitis.

9.
Biomacromolecules ; 22(7): 2834-2849, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34164980

RESUMO

Antibiotics are currently first-line therapy for bacterial infections. However, the curative effect of antibiotic remedies is limited due to increasingly prevalent bacterial resistance. The strategy to reverse intrinsic acquired drug resistance presents a promising option for reinvigorating antibiotic therapy. Here, we developed a ß-lactamase-inhibiting macromolecule composed of benzoxaborole and dextran for precise transport of ß-lactam antibiotics to strains overexpressing ß-lactamase. Benzoxaborole-derived nanotherapeutics enabled specific recognition and rapid internalization, and the nanotherapeutics with a high affinity toward bacteria distinctly inhibited the catalytic activity of bacterially secreted ß-lactamase by a reversible competitive mechanism. Thus, the system entrapping cefoxitin harbored a significantly enhanced ability to kill drug-resistant Escherichia coli compared to the ability of the drug by specifically overcoming the membrane barrier and acquired resistance mechanism of ß-lactamase overproduction. The reversible competitive nanotherapeutics exhibited a robust therapeutic efficacy in rat wounds infected with drug-resistant bacteria; the efficacy was due to efficient bacterial elimination and collateral benzoxaborole-dependent amelioration of the inflammatory response. The above results offered insights into the facile design of precise macromolecular adjuvants to exclusively reverse the acquired bacterial resistance mechanism and increase the utility of antibiotic therapies against antibiotic-resistant bacterial infections.


Assuntos
Antibacterianos , Bactérias Gram-Negativas , Animais , Antibacterianos/farmacologia , Escherichia coli , Testes de Sensibilidade Microbiana , Ratos , beta-Lactamases
10.
J Phys Act Health ; : 1-6, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34186515

RESUMO

This study examined the independent associations between psychosocial factors, perceived neighborhood characteristics, and physical activity (PA) in Chinese adolescents. A cross-sectional study using a convenience sample was conducted in fall 2019 at a high school in Wuhan, China. Sociodemographic data, body weight, height, psychosocial factors, perceptions of neighborhood environment, and PA were collected using questionnaires. Hierarchical linear regression analyses were performed in 4 steps, where step 1 included demographic covariates, step 2 added psychosocial factors into the model, step 3 added perceived neighborhood environmental factors, and step 4 added interaction terms between significant psychosocial and environmental factors. A total of 4027 adolescents were included in analysis. The results of the third model indicated that friends' support (b = 4.58), friends' norms (b = 7.16), barriers to PA (b = -10.19), autonomous motivation (b = 4.75), self-efficacy (b = 8.86), the presence of shops/stores nearby (b = 5.79), and the availability of PA resources (b = 6.02) were significant predictors (P < .05) of moderate to vigorous PA. None of the interaction terms were significant in the fourth model. Our results suggest that interventions targeting the PA of Chinese adolescents should take into account the attitudes toward PA, perceived barriers to PA, controlled motivation, perceptions of neighborhood PA resource availability, and perceived neighborhood safety to maximize effectiveness.

11.
Nanotheranostics ; 5(4): 472-487, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150471

RESUMO

Purpose: The growing prevalence of multidrug-resistant (MDR) bacteria makes it clinically urgent to develop an agent able to detect and treat infections simultaneously. Silver has served as a broad-spectrum antimicrobial since ancient times but suffers from major challenges such as moderate antimicrobial activity, nonspecific toxicity, and difficulty to be visualized in situ. Here, we propose a new photoactive silver nanoagent that relies on a photosensitizer-triggered cascade reaction to liberate Ag+ on bacterial surfaces exclusively, allowing the precise killing of MDR bacteria. Additionally, the AgNP core acts as a backgroundless surface-enhanced Raman scattering (SERS) substrate for imaging the distribution of the nanoagents on bacterial surfaces and monitoring their metabolic dynamics in the infection sites. Methods: In this strategy, the photoactive antibacterial AgNP was decorated with photosensitizers (Chlorin e6, Ce6) and Raman reporter (4-Mercaptobenzonitrile, 4-MB) to provide new opportunities for clinically monitoring and fighting MDR bacterial infections. Upon 655 nm laser activation, the Ce6 molecules produce ROS efficiently, triggering the rapid release of Ag+ from the AgNP core to kill bacteria. Poly[4-O-(α-D-glucopyranosyl)-D-glucopyranose] (GP) was introduced as bacteria-specific targeting ligands. SERS spectra of the prepared GP-Ce6/MB-AgNPs were recorded after injecting for 0.5, 4, 8, 12, 24, and 48 h to track the dynamic metabolism of the nanoagents and thus guiding the antibacterial therapy. Results: This new antimicrobial strategy exerts a dramatically enhanced antibacterial activity. The in vitro antibacterial efficiencies of this non-antibiotic technique were up to 99.6% against Methicillin-resistant Staphylococcus aureus (MRSA) and 98.8% against Escherichia coli (EC), while the in vivo antibacterial efficiencies for MRSA- and Carbapenem-resistant Pseudomonas aeruginosa (CRPA)-infected mice models were 96.8% and 93.6%, respectively. Besides, backgroundless SERS signal intensity of the wound declined to the level of normal tissue until 24 h, indicating that the nanoagents had been completely metabolized from the infected area. Conclusion: Given the backgroundless monitoring ability, high antibacterial efficacy, and low toxicity, the photoactive cascading agents would hold great potential for MDR-bacterial detection and elimination in diverse clinical settings.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Nanopartículas Metálicas , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Fármacos Fotossensibilizantes , Pseudomonas aeruginosa/crescimento & desenvolvimento , Prata , Antibacterianos/química , Antibacterianos/farmacologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Prata/química , Prata/farmacologia
12.
J Mater Chem B ; 9(20): 4190-4200, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-33997882

RESUMO

Eye-drop formulations as conventional regimens to tackle ocular diseases are far from efficient due to the rapid clearance by eye tears and the blockage of the corneal epithelium barrier. Here, we describe a bioadhesive glycosylated nanoplatform with boric acid pendants as a drug carrier for noninvasive trans-corneal delivery of drugs to treat corneal neovascularization (CNV), a serious corneal disease resulting in significant vision impairment. This biocompatible nanoplatform is formulated from a synthetic amphiphilic boric acid-based copolymer self-assembling to form highly stable micelles with a high loading capacity for dexamethasone (DEX). The nanoplatform is demonstrated to be in contact with the corneal epithelium for a long period under the bioadhesive function of boric acid modules and releases the drug over 96 h in a controlled manner. Our results also suggest that the nanoplatform can be efficiently internalized by corneal epithelial cells in vitro and realize transcytosis in vivo to greatly enhance the transcorneal penetration of the loaded drugs into the pathological corneal stroma. On topical application against rat corneal alkali burn, the nanoformulation presents more robust efficacy on neovascularization suppression and inflammation elimination than free DEX with a negligible effect on normal tissues. This bioadhesive strategy which focuses on extending ocular drug retention and improving trans-corneal drug delivery not only highlights an approach for alternative noninvasive therapy of CNV but also provides a versatile paradigm for other biomedical applications by overcoming protective barriers.


Assuntos
Materiais Biocompatíveis/química , Ácidos Borônicos/química , Neovascularização da Córnea/tratamento farmacológico , Dexametasona/farmacologia , Sistemas de Liberação de Medicamentos , Animais , Materiais Biocompatíveis/síntese química , Ácidos Borônicos/síntese química , Sobrevivência Celular/efeitos dos fármacos , Córnea/efeitos dos fármacos , Dexametasona/química , Portadores de Fármacos/química , Composição de Medicamentos , Glicosilação , Humanos , Masculino , Nanopartículas/química , Ratos , Ratos Sprague-Dawley
13.
Biomacromolecules ; 22(5): 2020-2032, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33880923

RESUMO

A standardized regimen for addressing the adverse effects of bacterial keratitis on vision remains an intractable challenge due to poor epithelial penetration and a short corneal retention time. In this study, a new strategy is proposed to implement the direct transport of antibiotics to bacteria-infected corneas via topical administration of an epithelium-penetrable biodriven nanoplatform, thereby enabling the efficacious treatment of bacterial keratitis. The nanoplatforms were composed of amphiphilic glycopolymers containing boron dipyrromethene and boronic acid moieties with stable fluorescence characteristics and the ability to potentiate epithelial penetration deep into the cornea. The boronic acid-derived nanoplatforms enabled efficient cellular internalization through the high affinity of boric acid groups for the diol-containing bacterial cell wall, resulting in enhanced drug penetration and retention inside the pathogenic bacteria. The bacterial cells formed agglomerations after incorporating the nanoplatforms along with a special mechanism to release the encapsulated cargo in response to in situ bacteria. Compared with the drug alone, this smart system achieved enhanced bacterial mortality and attenuated inflammation associated with Staphylococcus aureus-induced keratitis in rats, demonstrating a paradigm for targeted ocular drug delivery and an alternative strategy for managing bacterial keratitis or other bacterial infections by heightening corneal permeability and transcorneal bioavailability.


Assuntos
Infecções Oculares Bacterianas , Ceratite , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Córnea , Epitélio , Infecções Oculares Bacterianas/tratamento farmacológico , Ceratite/tratamento farmacológico , Ratos , Infecções Estafilocócicas/tratamento farmacológico
14.
J Mater Chem B ; 9(17): 3689-3695, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33861292

RESUMO

Exogenous reactive oxygen species (ROS) generation is a promising antibacterial strategy. The short diffusion distance coupled with the transient existence of ROS restrict their precise release at inflammation sites, so it is imperative to regulate the reactive sites of ROS donors. In this work, we developed a glycomimetic-decorated fluorescent nanobiocide to mediate the release of ROS generated from CuInS/ZnS quantum dots. The introduction of glycomimetics innovatively improved the biocompatibility of the hydrophobic quantum dots, allowing pathogenic bacteria to be targeted. The functionalized CuInS/ZnS quantum dots allowed simultaneous fluorescent reporting and sterilization under 660 nm illumination. Moreover, the nanobiocide can serve as a cell-binding glue causing bacterial aggregation, disrupting bacterial adhesion to host cells and inhibiting biofilm formation. Collectively, this work indicated the far-reaching future of ROS-generating biomimetic design for multifunctional nanobiocides to combat bacterial infections.


Assuntos
Antibacterianos/química , Corantes Fluorescentes/química , Infecções/tratamento farmacológico , Pontos Quânticos/química , Células 3T3 , Adesivos/química , Animais , Antibacterianos/farmacologia , Biofilmes , Cobre/química , Eritrócitos , Humanos , Índio/química , Camundongos , Imagem Óptica , Pseudomonas aeruginosa/efeitos dos fármacos , Esterilização , Sulfetos/química , Propriedades de Superfície , Compostos de Zinco/química
15.
Artigo em Inglês | MEDLINE | ID: mdl-33916042

RESUMO

The goal of this study was to investigate the associations of midday nap duration and change in midday nap duration with hypertension in a retrospective cohort using a nationwide representative sample of middle-aged and older Chinese adults. Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) database during 2011-2015. Information on midday nap duration was collected via a self-reported questionnaire and blood pressure was objectively measured. Hazard ratios (HR) with 95% confidence interval (CI) were estimated using Cox proportional hazards regression models to quantify the associations. A sample of 5729 Chinese adults (≥45 years old) were included in the longitudinal analysis. Relative to non-nappers, participants who napping for ≥90 min/day was associated with significantly larger HR for hypertension at four-year follow-up (HR = 1.18, 95% CI = 1.01-1.40, p = 0.048). Compared with people who napped ≥90 min/day both at baseline (2011) and follow-up (2013), hypertension risk at four-year follow-up declined in individuals whose midday nap durations decreased in the 2-year study period from ≥ 90 min/day to 1-59 min/day (HR = 0.59, 95% CI = 0.36-0.97, p = 0.037) and 60-89 min/day (HR = 0.68, 95% CI = 0.47-0.99, p = 0.044). Among middle-aged and older Chinese adults, relative to non-nappers, people who had longer midday nap duration (≥90 min/day) were associated with significantly larger HR for hypertension and decreased napping duration may confer benefit for hypertension prevention.


Assuntos
Hipertensão , Sono , Adulto , Idoso , China/epidemiologia , Estudos de Coortes , Humanos , Hipertensão/epidemiologia , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Biochem Biophys Res Commun ; 544: 44-51, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33516881

RESUMO

Alcoholic liver disease (ALD) occurs as a result of chronic and excessive alcohol consumption. It encompasses a wide spectrum of chronic liver abnormalities that range from steatosis to alcoholic hepatitis, progressive fibrosis and cirrhosis. Endoplasmic reticulum (ER) stress induced by ethanol metabolism in hepatocytes has been established as an important contributor to the pathogenesis of ALD. However, whether SIRT6 exerts regulatory effects on ethanol-induced ER stress and contributes to the pathogenesis of ALD is unclear. In this study, we developed and characterized Sirt6 hepatocyte-specific knockout and transgenic mouse models that were treated with chronic-plus-binge ethanol feeding. We observed that hepatic Sirt6 deficiency led to exacerbated ethanol-induced liver injury and aggravated hepatic ER stress. Tauroursodeoxycholic acid (TUDCA) treatment remarkably attenuated ethanol-induced ER stress and ameliorated ALD pathologies caused by Sirt6 ablation. Reciprocally, SIRT6 hepatocyte-specific transgenic mice exhibited reduced ER stress and ameliorated liver injury caused by ethanol exposure. Consistently, knockdown of Sirt6 elevated the expression of ER stress related genes in primary hepatocytes treated with ethanol, whereas overexpression of SIRT6 reduced their expression, indicating SIRT6 regulates ethanol-induced hepatic ER stress in a cell autonomous manner. Collectively, our results suggest that SIRT6 is a positive regulator of ethanol-induced ER stress in the liver and protects against ALD by relieving ER stress.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas/prevenção & controle , Estresse do Retículo Endoplasmático , Etanol/toxicidade , Hepatócitos/efeitos dos fármacos , Sirtuínas/farmacologia , Animais , Células Cultivadas , Depressores do Sistema Nervoso Central/toxicidade , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Colagogos e Coleréticos/farmacologia , Modelos Animais de Doenças , Hepatócitos/metabolismo , Hepatócitos/patologia , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Ácido Tauroquenodesoxicólico/farmacologia
17.
J Mater Chem B ; 9(5): 1364-1369, 2021 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-33458729

RESUMO

Obstinate infections caused by drug-resistant bacteria severely threaten human health. And the emergence of multidrug-resistant bacteria increases the morbidity and mortality of patients, thus necessitating the development of innovative or alternative therapeutics. Here, a light-activated nanotherapeutic with broad-spectrum bacterial recognition is established as an antibiotic-free therapeutic agent against pathogens. The nanotherapeutic with external phenylboronic acid-based glycopolymers increases the stability and biocompatibility and shows the ability of bacterial recognition. Once irradiated with near-infrared light, this nanotherapeutic with high photothermal conversion efficiency disrupts the cytoplasmic membrane, thus killing bacterial cells. Importantly, it also eliminates the biofilms formed by both drug-resistant Gram-negative bacteria (Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus) effectively. Thus, this antibiotic-free nanotherapeutic with hypotoxicity offers a promising approach to fight increasingly serious antimicrobial resistance.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Bactérias Gram-Positivas/patogenicidade , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Nanotecnologia/métodos , Antibacterianos/farmacologia , Humanos
18.
Qual Life Res ; 30(1): 229-238, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32909163

RESUMO

INTRODUCTION: Weight stigma is defined as the social devaluation of people with overweight or obesity, and its negative effects on the health of adolescents from western countries are well documented, but little is known about the relationships with health behaviors and outcomes in Asian youth. The prevalence of obesity among Chinese adolescents continues to increase, potentially causing negative evaluations of youth with obesity, and potentially reduced quality of life. The health effects of these negative evaluations of Chinese youth with obesity have received little attention. PURPOSE: The purpose of this study was to examine relationships between weight stigma, stress, depression, and sleep in Chinese adolescents. METHODS: We utilized a cross-sectional study conducted in Wuhan, China. Sociodemographic, weight stigma, stress, depression, and sleep data were collected through a self-reported questionnaire. Descriptive statistics, t test, correlations, and mediation analyses were performed. A total of 1626 adolescents between 14 and 19 years of age were included in the analysis. RESULTS: The data showed that adolescents with weight stigma presented significantly higher level of stress and depression, lower global sleep quality, longer sleep latency, and shorter sleep duration than those without weight stigma (p < 0.05). Stress and depression mediated the relationship between weight stigma and global sleep quality (SE = 0.007, 95% CI = 0.053 to 0.081). CONCLUSION: These findings suggest that adolescents who experience weight stigma may have increased stress and depressive symptoms, which are associated with poorer global sleep quality and more daytime dysfunction.


Assuntos
Peso Corporal/fisiologia , Depressão/psicologia , Qualidade de Vida/psicologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Estigma Social , Estresse Psicológico/psicologia , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade/complicações , Prevalência , Inquéritos e Questionários , Adulto Jovem
19.
Biomater Sci ; 8(24): 6912-6919, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32749389

RESUMO

The Gram-negative opportunistic pathogen Pseudomonas aeruginosa is endowed with intrinsic resistance to antibiotics. It is essential to explore alternative techniques to supplement the arsenal of methods to kill drug-resistant bacteria. Herein, we established an "on-demand" nanoplatform based on acid-degradable scaffolds by conjugating glycomimetic-based galactose ligands to target a key lectin on P. aeruginosa and guanidine moieties. This nanoplatform could capture bacteria through ligand-receptor interactions and electrostatic interactions, and subsequently reactive oxygen species produced by entrapped photodynamic agent Ce6 under light irradiation eliminated drug-resistant P. aeruginosa and its biofilm. Approximately 95% of the planktonic bacteria were killed and more than 70% of the biofilm was disrupted under light irradiation. This strategy of copolymer modification could improve the biocompatibility and therapeutic efficiency levels of antibacterial therapeutics through the targeting of function. Hence, utilizing this smart nanoplatform may be of significance in developing new strategies to solve the growing problem of bacterial resistance.


Assuntos
Preparações Farmacêuticas , Fotoquimioterapia , Antibacterianos/farmacologia , Biofilmes , Pseudomonas aeruginosa
20.
Artigo em Inglês | MEDLINE | ID: mdl-32784581

RESUMO

This study examined the cross-sectional and longitudinal association of sleep timing with weight status in 14- to 19-year-old adolescents in Wuhan, China. A prospective school-based study was conducted in Wuhan, China between 28 May and 29 September 2019. Data on sociodemographic information, academic performance, diet, mental health status, physical activity, sleep characteristics, body weight, and height were collected. A linear regression model and binary logistic regression model were performed. A total of 1194 adolescents were included in the analysis. Adolescents who woke up before 05:45 had higher body mass index (BMI) Z-score (odds ratio (OR) with 95% confidence interval (CI) = 1.28 (1.05, 1.57), p = 0.02) and higher odds of overweight/obesity (odds ratio (OR) with 95% confidence interval (CI) = 1.74 (1.10, 2.76), p = 0.02) at baseline after fully adjustment for covariates, compared with those who woke up after 05:45. Longitudinal data showed a nonsignificant association between waking up time and change in BMI Z-score (p = 0.18). No association of bedtime with weight status was observed in this sample after full adjustment (p > 0.1). Earlier waking up time might contribute to overweight and obesity in adolescents; however, more data are needed to test and elucidate this relationship.


Assuntos
Peso Corporal , Ritmo Circadiano/fisiologia , Obesidade/complicações , Sono , Adolescente , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Estudos Prospectivos , Adulto Jovem
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