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1.
Small ; 20(27): e2307807, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38342673

RESUMO

Sodium (Na) doping is a well-established technique employed in chalcopyrite and kesterite solar cells. While various improvements can be achieved in crystalline quality, electrical properties, or defect passivation of the absorber materials by incorporating Na, a comprehensive demonstration of the desired Na distribution in CZTSSe is still lacking. Herein, a straightforward Na doping approach by dissolving NaCl into the CZTS precursor solution is proposed. It is demonstrated that a favorable Na ion distribution should comprise a precisely controlled Na+ concentration at the front surface and an enhanced distribution within the bottom region of the absorber layer. These findings demonstrated that Na ions play several positive roles within the device, leading to an overall power conversion efficiency of 12.51%.

2.
Phytopathology ; : PHYTO09230326R, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968142

RESUMO

Early detection of rice blast disease is pivotal to ensure rice yield. We collected in situ images of rice blast and constructed a rice blast dataset based on variations in lesion shape, size, and color. Given that rice blast lesions are small and typically exhibit round, oval, and fusiform shapes, we proposed a small object detection model named GCPDFFNet (global context-based parallel differentiation feature fusion network) for rice blast recognition. The GCPDFFNet model has three global context feature extraction modules and two parallel differentiation feature fusion modules. The global context modules are employed to focus on the lesion areas; the parallel differentiation feature fusion modules are used to enhance the recognition effect of small-sized lesions. In addition, we proposed the SCYLLA normalized Wasserstein distance loss function, specifically designed to accelerate model convergence and improve the detection accuracy of rice blast disease. Comparative experiments were conducted on the rice blast dataset to evaluate the performance of the model. The proposed GCPDFFNet model outperformed the baseline network CenterNet, with a significant increase in mean average precision from 83.6 to 95.4% on the rice blast test set while maintaining a satisfactory frames per second drop from 147.9 to 122.1. Our results suggest that the GCPDFFNet model can accurately detect in situ rice blast disease while ensuring the inference speed meets the real-time requirements.

3.
Subst Use Misuse ; 59(8): 1249-1255, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38532555

RESUMO

Background: Although the prevalence of conventional tobacco product use among U.S. college students has declined, an increasing number of students use various novel tobacco products. Objectives: This study aims to examine up-to-date sex and racial/ethnic patterns of tobacco use among students at a U.S. university in 2021-2023. Methods: Data of 2,732 students at an urban university in the Southeast of the U.S. were collected in 2021-2023 as part of the National College Health Assessment of the American College Health Association. Self-reported past 3-month use of five tobacco products (cigarette, electronic vapor products, water pipe/hookah, smokeless tobacco, and cigars) was dichotomized. We conducted multinomial logistic regression analysis to examine sex (male or female) and racial/ethnic (non-Hispanic White, non-Hispanic Black, Hispanic, or non-Hispanic Other) differences in single and dual/poly (con-current use of two or more tobacco products) tobacco use compared to nonuse, adjusting for age, student status, parent education level, obese status, psychological distress level, and survey year. Results: Male students had higher odds of being dual/poly tobacco user than female students, adjusting for covariates (adjusted odds ratio [AOR] = 2.00, 95% confidence interval [CI] = 1.42, 2.82). Non-Hispanic Black students had lower odds of being single (AOR = 0.43, 95% CI = 0.26, 0.69) and dual/poly (AOR = 0.09, 95% CI = 0.02, 0.37) tobacco user compared to non-Hispanic White students, adjusting for covariates. Conclusions: Considering higher health risk of con-current use of multiple tobacco products, dual/poly tobacco use prevention strategies targeting male and non-Hispanic White students may be considered.


Assuntos
Estudantes , Uso de Tabaco , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Negro ou Afro-Americano , Etnicidade/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Grupos Raciais , Fatores Sexuais , Estudantes/estatística & dados numéricos , Estudantes/psicologia , Produtos do Tabaco/estatística & dados numéricos , Uso de Tabaco/epidemiologia , Uso de Tabaco/etnologia , Estados Unidos/epidemiologia , Universidades , Brancos
4.
Langmuir ; 39(11): 4140-4149, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36877128

RESUMO

Constructing Bi/BiOX (X = Cl, Br) heterostructures with unique electron transfer channels enables charge carriers to transfer unidirectionally at the metal/semiconductor junction and inhibits the backflow of photogenerated carriers. Herein, novel pine dendritic Bi/BiOX (X = Cl, Br) nanoassemblies with multiple electron transfer channels have been successfully synthesized with the assistance of l-cysteine (l-Cys) through a one-step solvothermal method. Such a pine dendritic Bi/BiOBr photocatalyst shows excellent activity toward the degradation of many antibiotics such as tetracycline (TC), norfloxacin, and ciprofloxacin. In particular, its photocatalytic degradation activity of TC is higher than those of reference spherical Bi/BiOBr, lamellar BiOBr, and BiOBr/Bi/BiOBr double-sided nanosheet arrays. Comprehensive characterizations demonstrate that the pine dendritic structure can construct multiple electron transfer channels from BiOBr to metallic Bi, resulting in an obviously promoted separation efficiency of photogenerated carriers. The synthesis method that uses l-Cys to control the morphology provides a guidance to prepare special metal/semiconductor photocatalysts and would be helpful to design a highly efficient photocatalytic process.


Assuntos
Antibacterianos , Bismuto , Catálise , Bismuto/química , Tetraciclina
5.
Prev Med ; 172: 107550, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37210044

RESUMO

Little is known about the association of cancer information seeking behavior with cigarette smoking and e-cigarette use. A multi-year cross-sectional analysis using a pooled data of the Health Information National Trends Survey 5, Cycles 1-4 (2017-2020) was conducted. To examine the association of cancer information seeking behavior with current cigarette smoking (currently smoke every day/some days among individuals who smoked 100+ cigarettes in lifetime) and e-cigarette use (currently use every day/some days among lifetime users) in nationally representative U.S. adults, we conducted weighted multiple logistic regression analysis, adjusting for sex, race/ethnicity, age, obese status, depressed mood, cancer diagnosis history, metropolitan status, and survey year. The regression models were stratified by education level (

Assuntos
Fumar Cigarros , Sistemas Eletrônicos de Liberação de Nicotina , Neoplasias , Vaping , Humanos , Adulto , Adolescente , Adulto Jovem , Estudos Transversais , Comportamento de Busca de Informação , Escolaridade , Neoplasias/epidemiologia
6.
J Nanobiotechnology ; 21(1): 110, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36973737

RESUMO

With increased diabetes incidence, diabetic wound healing is one of the most common diabetes complications and is characterized by easy infection, chronic inflammation, and reduced vascularization. To address these issues, biomaterials with multifunctional antibacterial, immunomodulatory, and angiogenic properties must be developed to improve overall diabetic wound healing for patients. In our study, we prepared porous poly (L-lactic acid) (PLA) nanofiber membranes using electrospinning and solvent evaporation methods. Then, sulfated chitosan (SCS) combined with polydopamine-gentamicin (PDA-GS) was stepwise modified onto porous PLA nanofiber membrane surfaces. Controlled GS release was facilitated via dopamine self-polymerization to prevent early stage infection. PDA was also applied to PLA nanofiber membranes to suppress inflammation. In vitro cell tests results showed that PLA/SCS/PDA-GS nanofiber membranes immuomodulated macrophage toward the M2 phenotype and increased endogenous vascular endothelial growth factor secretion to induce vascularization. Moreover, SCS-contained PLA nanofiber membranes also showed good potential in enhancing macrophage trans-differentiation to fibroblasts, thereby improving wound healing processes. Furthermore, our in vitro antibacterial studies against Staphylococcus aureus indicated the effective antibacterial properties of the PLA/SCS/PDA-GS nanofiber membranes. In summary, our novel porous PLA/SCS/PDA-GS nanofiber membranes possessing enhanced antibacterial, anti-inflammatory, and angiogenic properties demonstrate promising potential in diabetic wound healing processes.


Assuntos
Quitosana , Diabetes Mellitus , Nanofibras , Humanos , Porosidade , Fator A de Crescimento do Endotélio Vascular , Poliésteres/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cicatrização , Anti-Inflamatórios , Ácido Láctico
7.
Exp Eye Res ; 219: 109068, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35398207

RESUMO

In adult mammals, only minimal regeneration of the optic nerve (ON) is possible. Both the low levels of intrinsic regeneration ability of retinal ganglion cells (RGCs) and the inhibitory glial environment of ON contribute to it. To explore the influence of these two factors on the extent of axon regeneration, two ON injury models were established. A conventional optic nerve crush model (ONC) is considered a high-inhibitory environment. A long-range optic nerve injury model (LI) is considered a low-inhibitory environment. Zymosan (Zy) was used to regulate the intrinsic regeneration capability of RGCs: the injection of zymosan represented a high state; no injection represented a low state. In the low-inhibitory environment, zymosan (LI + Zy group) significantly increased both the number of regenerated axons and the number of surviving RGCs, however the Relative A/R (representing the proportion of regenerated RGCs) was similar to the LI group (no zymosan injection).Furthermore, in the highly-inhibitory environment, although zymosan (ONC + Zy group) significantly increased the number of regenerated axons and the number of surviving RGCs, the relative A/R was significantly lower than that in the low-inhibitory environment (LI or LI + Zy groups). The results suggest that the low inhibitory environment may be more important for optic nerve regeneration. Binary regression analysis also demonstrated the similar results. Also, there was a clear synergy between the two factors. These indicate that both low inhibitory environments and high regeneration capability can enhance the regeneration of ON. A low inhibitory environment is greater essential.


Assuntos
Axônios , Traumatismos do Nervo Óptico , Animais , Axônios/fisiologia , Mamíferos , Compressão Nervosa , Regeneração Nervosa/fisiologia , Nervo Óptico , Zimosan/farmacologia
8.
Psychogeriatrics ; 22(1): 84-98, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34729865

RESUMO

BACKGROUND: Mild behavioural impairment (MBI) is a neurobehavioural syndrome characterised by later life emergence of persistent neuropsychiatric symptoms. Our previous meta-analysis showed that MBI is prevalent among cognitively normal (CN), subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) subjects. This study is to calculate the pooled prevalence of MBI domains among CN, SCI, and MCI subjects. METHODS: A search of relevant literature published between 1 January 2003 and 6 August 2021 was conducted. Meta-analysis using a random effects model and meta-regression was performed. RESULTS: Ten studies conducted among 12 067 subjects (9758 CN, 1057 SCI and 1252 MCI) with retrievable MBI domains data underwent meta-analysis, revealing pooled prevalence of affective dysregulation (AFD), impulse dyscontrol (IDS), decreased motivation (DMT), social inappropriateness (SIP) and abnormal perception/thought (APT) of 32.84% (95% CI 24.44-42.5%), 26.67% (95% CI 18.24-37.23%), 12.58% (95% CI 6.93-21.75%), 6.05% (95% CI 3.44-10.42%), and 2.81% (95% CI 1.67-4.69%) respectively. AFD and APT domains demonstrated ordinal increase in pooled prevalence from CN, SCI and MCI subgroups, but meta-regression demonstrated no significant difference in MBI domains prevalence among cognitive subgroups (in contrast to the significant increase in MBI prevalence from CN to SCI to MCI). The pooled prevalence of AFD and IDS are greater than that of DMT, SIP and APT among all cognitive subgroups. Several variables were found to explain the high heterogeneity. CONCLUSIONS: AFD and IDS are the two most prevalent MBI domains and remain the same with cognitive deterioration. This finding is potentially relevant to clinical practice.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Disfunção Cognitiva/epidemiologia , Humanos , Prevalência
9.
Opt Express ; 29(10): 15747-15763, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33985270

RESUMO

A novel spatial and temporal super-resolution (SR) framework based on a recurrent neural network (RNN) is demonstrated. In this work, we learn the complex yet useful features from the temporal data by taking advantage of structural characteristics of RNN and a skip connection. The usage of supervision mechanism is not only making full use of the intermediate output of each recurrent layer to recover the final output, but also alleviating vanishing/exploding gradients during the back-propagation. The proposed scheme achieves excellent reconstruction results, improving both the spatial and temporal resolution of fluorescence images including the simulated and real tubulin datasets. Besides, robustness against various critical metrics, such as the full-width at half-maximum (FWHM) and molecular density, can also be incorporated. In the validation, the performance can be increased by more than 20% for intensity profile, and 8% for FWHM, and the running time can be saved at least 40% compared with the classic Deep-STORM method, a high-performance net which is popularly used for comparison.

10.
Psychogeriatrics ; 21(3): 396-406, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33594793

RESUMO

Alzheimer's disease (AD) is the commonest cause of dementia, characterized by the clinical presentation of progressive anterograde episodic memory impairment. However, atypical presentation of patients is increasingly recognized. These atypical AD include logopenic aphasia, behavioural variant AD, posterior cortical atrophy, and corticobasal syndrome. These atypical AD are more common in patients with young onset AD before the age of 65 years old. Since medical needs (including the behavioural and psychological symptoms of dementia) of atypical AD patients could be different from typical AD patients, it is important for clinicians to be aware of these atypical forms of AD. In addition, disease modifying treatment may be available in the future. This review aims at providing an update on various important subtypes of atypical AD including behavioural and psychological symptoms.


Assuntos
Doença de Alzheimer , Idoso , Doença de Alzheimer/diagnóstico , Atrofia , Humanos
11.
Psychogeriatrics ; 21(1): 100-111, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33260271

RESUMO

AIM: Mild behavioural impairment (MBI) is a neurobehavioural syndrome characterized by emergent neuropsychiatric symptoms in later life. There has been no systematic review or meta-analysis on the prevalence of MBI. The main aim of the study is to calculate the pooled prevalence of MBI. METHODS: A search of the literature on MBI in mild cognitive impairment (MCI), cognitively normal (CN), and subjective cognitive impairment (SCI) and CN but at risk (CN-AR) subjects published between 1 January 2003 and 28 September 2020 was conducted. Meta-analysis using a random effects model was performed to determine the pooled estimate of the prevalence of MBI. Meta-regression was performed to identify factors contributing to the variance of prevalence rate. A systematic review was also performed to study the impact of MBI in cognitive outcomes and its correlation to the pathology and genetics of Alzheimer's disease. RESULTS: Eleven studies conducted among 15 689 subjects underwent meta-analysis, revealing the pooled prevalence of MBI to be 33.5% (95% confidence interval (CI): 22.6%-46.6%). Seven studies conducted among 1358 MCI subjects underwent meta-analysis, revealing the pooled prevalence to be 45.5% (95%CI: 36.1%-55.3%). Four studies conducted among 13 153 CN subjects underwent meta-analysis, revealing the pooled prevalence to be 17.0% (95%CI: 7.2%-34.9%). Five studies conducted among 1158 SCI or CN-AR subjects underwent meta-analysis, revealing the pooled prevalence to be 35.8% (95%CI: 21.4%-53.2%). A systematic review of 13 studies showed that MBI has a significant impact on cognitive deterioration and is associated with the pathology and genetics of Alzheimer's disease. CONCLUSIONS: In MCI, CN, and SCI and CN-AR subjects, MBI is common. Our finding is potentially useful in planning future clinical trials.


Assuntos
Doença de Alzheimer , Transtornos Cognitivos , Disfunção Cognitiva , Doença de Alzheimer/epidemiologia , Disfunção Cognitiva/epidemiologia , Progressão da Doença , Humanos , Prevalência
12.
Brain Behav Immun ; 88: 844-855, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32222525

RESUMO

5-lipoxygenase (ALOX5) is an enzyme involved in arachidonic acid (AA) metabolism, a metabolic pathway in which cysteinyl leukotrienes (CysLTs) are the resultant metabolites. Both ALOX5 and CysLTs are clinically significant in a number of inflammatory diseases, such as in asthma and allergic rhinitis, and drugs antagonizing the effect of these molecules have long been successfully used to counter these diseases. Interestingly, recent advances in 'neuroinflammation' research has led to the discovery of several novel inflammatory pathways regulating many cerebral pathologies, including the ALOX5 pathway. By means of pharmacological and genetic studies, both ALOX5 and CysLTs receptors have been shown to be involved in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative/neurological diseases, such as in Parkinson's disease, multiple sclerosis, and epilepsy. In both transgenic and sporadic models of AD, it has been shown that the levels of ALOX5/CysLTs are elevated, and that genetic/pharmacological interventions of these molecules can alleviate AD-related behavioral and pathological conditions. Clinical relevance of these molecules has also been found in AD brain samples. In this review, we aim to summarize such important findings on the role of ALOX5/CysLTs in AD pathophysiology, from both the cellular and the molecular aspects, and also discuss the potential of their blockers as possible therapeutic choices to curb AD-related conditions.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Araquidonato 5-Lipoxigenase/metabolismo , Asma , Humanos , Leucotrienos/metabolismo , Metabolismo dos Lipídeos
13.
Opt Express ; 27(12): 16995-17006, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31252917

RESUMO

Pushbroom hyperspectral imaging (HSI) has been used in many areas from air to land. However, its inherent operational drawback of the bulky slit leads to a limited field of view (FOV) and high energy consumption. Accordingly, a new and versatile HSI system is proposed by employing a smart digital micromirror device (DMD) to replace the mechanical scanning component. Moreover, tunable spatial and spectral resolution is implemented through adjusting the on-chip scanning linewidth and adopting the pixel fusion method, respectively. Meanwhile, three scanning modes including rough scanning, fine scanning, and regional scanning are achieved. These multiple choices increase the system's flexibility, universality, and intelligence, which is attractive for practically different applications, especially for military and remote sensing fields in need of a large FOV, and medical and food fields in need of tunable resolution for various samples.

14.
Am J Health Promot ; : 8901171241233399, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345895

RESUMO

PURPOSE: To examine changes in obesity prevalence among US adults after the COVID-19 pandemic by level of stay-at-home order and sociodemographic characteristics. DESIGN: Quasi-experimental study using repeated cross-sectional data. SETTING: Behavioral Risk Factor Surveillance System (BRFSS). SAMPLE: Pooled data for US adults ages ≥26 years (n = 1,107,673) from BRFSS (2018-2021). MEASURES: States/territories were classified into three levels of stay-at-home order: none, advisory/only for persons at risk, or mandatory for all. Individual-level sociodemographic characteristics were self-reported. ANALYSIS: The difference-in-differences method was conducted with weighted multiple logistic regression analysis to examine obesity (body mass index ≥30 kg/m2) prevalence by stay-at-home order level and sociodemographic characteristics before/after the COVID-19 pandemic (January 2018-February 2020 vs March 2020-February 2022). RESULTS: After adjusting for a secular trend and multiple covariates, adults in states/territories with mandatory stay-at-home orders experienced a larger increase in obesity prevalence (adjusted odds ratio: 1.05; 95% confidence interval: 1.01, 1.11) than adults in states/territories with no stay-at-home order. Younger adults (vs ≥65 years) and individuals with

15.
Artigo em Inglês | MEDLINE | ID: mdl-38950182

RESUMO

OBJECTIVES: With increased lung transplantation in those aged 70 and older, limited literature addresses risk factors affecting their survival. Our study aims to identify independent factors impacting mid- and long-term mortality in this elderly population. METHODS: This study analyzed lung transplant patients over 70 from May 2005 to December 2022 using United Network for Organ Sharing data. The 3- or 5-year cohort excluded multi-organ, secondary transplantation and loss to follow-up. Univariable Cox analysis was conducted to assess recipient, donor and transplant factors. Factors with a significance level of P < 0.2 were subsequently included in a multivariable Cox model to identify correlations with 3- and 5-year mortality in patients aged over 70. RESULTS: Multivariable analysis has identified key factors affecting 3- and 5-year mortality in elderly lung transplant patients over 70. Common notable factors include recipient total bilirubin, intensive care unit status at the time of transplantation, donor diabetes, Cytomegalovirus (CMV) mismatch and single lung transplantation. Additionally, Hispanic/Latino patients and ischaemia time of the transplant significantly impact the 3-year mortality, while recipient age, diabetes, nitric oxide use before transplantation and creatinine were identified as unique independent risk factors affecting the 5-year morality. CONCLUSIONS: The study identified several independent risk factors that impact the mid- and long-term survival of lung transplantation for individuals over 70 years. These findings can contribute to the optimization of lung transplant treatment strategies and perioperative management in elderly patients, thereby enhancing the survival rate of this age group.

16.
J Ginseng Res ; 47(3): 448-457, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37252274

RESUMO

Background: Alzheimer's disease (AD) is a common form of dementia, and impaired mitophagy is a hallmark of AD. Mitophagy is mitochondrial-specific autophagy. Ginsenosides from Ginseng involve in autophagy in cancer. Ginsenoside Rg1 (Rg1 hereafter), a single compound of Ginseng, has neuroprotective effects on AD. However, few studies have reported whether Rg1 can ameliorate AD pathology by regulating mitophagy. Methods: Human SH-SY5Y cell and a 5XFAD mouse model were used to investigate the effects of Rg1. Rg1 (1µM) was added to ß-amyloid oligomer (AßO)-induced or APPswe-overexpressed cell models for 24 hours. 5XFAD mouse models were intraperitoneally injected with Rg1 (10 mg/kg/d) for 30 days. Expression levels of mitophagy-related markers were analyzed by western blot and immunofluorescent staining. Cognitive function was assessed by Morris water maze. Mitophagic events were observed using transmission electron microscopy, western blot, and immunofluorescent staining from mouse hippocampus. The activation of the PINK1/Parkin pathway was examined using an immunoprecipitation assay. Results: Rg1 could restore mitophagy and ameliorate memory deficits in the AD cellular and/or mouse model through the PINK1-Parkin pathway. Moreover, Rg1 might induce microglial phagocytosis to reduce ß-amyloid (Aß) deposits in the hippocampus of AD mice. Conclusion: Our studies demonstrate the neuroprotective mechanism of ginsenoside Rg1 in AD models. Rg1 induces PINK-Parkin mediated mitophagy and ameliorates memory deficits in 5XFAD mouse models.

17.
Chem Commun (Camb) ; 59(35): 5269-5272, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37057667

RESUMO

PbI2 films as templates are essential to the quality of perovskite (PVK) film in a two-step sequential deposition process. Herein, we demonstrate that PbI2 microcrystal powder (P-PbI2) of micrometer size is beneficial for preparing higher-quality PbI2 films in contrast to millimeter-sized PbI2 crystals (C-PbI2) under low relative humidity (RH) conditions. Surprisingly, C-PbI2 allowed the growth of denser films than P-PbI2 under heavy RH conditions. Ultimately, P-PbI2 gave PVK solar cells (PSCs) a best power conversion efficiency (PCE) of 23.30% under a low RH of 30 ± 5%, and C-PbI2 derived an impressive PCE of 21.09% when fabricated under conditions with RH = 50 ± 5%. This work provides ideas for the selection of lead iodide for the fabrication of PSCs under air conditions.

18.
CNS Neurosci Ther ; 29(7): 1848-1864, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36880288

RESUMO

INTRODUCTION AND AIMS: Alzheimer's disease (AD) is characterized by the abnormal accumulation of hyperphosphorylated tau proteins and amyloid-beta (Aß) peptides. Recent studies have shown that many microRNAs (miRNAs) are dysregulated in AD, and modulation of these miRNAs can influence the development of tau and Aß pathology. The brain-specific miRNA miR-128, encoded by MIR128-1 and MIR128-2, is important for brain development and dysregulated in AD. In this study, the role of miR-128 in tau and Aß pathology as well as the regulatory mechanism underlying its dysregulation were investigated. METHODS: The effect of miR-128 on tau phosphorylation and Aß accumulation was examined in AD cellular models through miR-128 overexpression and inhibition. The therapeutic potential of miR-128 in AD mouse model was assessed by comparing phenotypes of 5XFAD mice administered with miR-128-expressing AAVs with 5XFAD mice administered with control AAVs. Phenotypes examined included behavior, plaque load, and protein expression. The regulatory factor of miR-128 transcription was identified through luciferase reporter assay and validated by siRNA knockdown and ChIP analysis. RESULTS: Both gain-of-function and loss-of-function studies in AD cellular models reveal that miR-128 represses tau phosphorylation and Aß secretion. Subsequent investigations show that miR-128 directly inhibits the expression of tau phosphorylation kinase GSK3ß and Aß modulators APPBP2 and mTOR. Upregulation of miR-128 in the hippocampus of 5XFAD mice ameliorates learning and memory impairments, decreases plaque deposition, and enhances autophagic flux. We further demonstrated that C/EBPα transactivates MIR128-1 transcription, while both C/EBPα and miR-128 expression are inhibited by Aß. CONCLUSION: Our findings suggest that miR-128 suppresses AD pathogenesis, and could be a promising therapeutic target for AD. We also find a possible mechanism underlying the dysregulation of miR-128 in AD, in which Aß reduces miR-128 expression by inhibiting C/EBPα.


Assuntos
Doença de Alzheimer , MicroRNAs , Camundongos , Animais , Doença de Alzheimer/metabolismo , MicroRNAs/metabolismo , Fosforilação , Glicogênio Sintase Quinase 3 beta , Camundongos Transgênicos , Peptídeos beta-Amiloides/metabolismo , Proteínas tau/metabolismo , Modelos Animais de Doenças , Serina-Treonina Quinases TOR/metabolismo
19.
J Control Release ; 350: 789-802, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35961472

RESUMO

Retinopathy of prematurity (ROP) is characterized by pathological angiogenesis and associated inflammation in the retina and is the leading cause of childhood blindness. MiRNA-223 (miR-223) drives microglial polarization toward the anti-inflammatory phenotype and offers a therapeutic approach to suppress inflammation and consequently pathological neovascularization. However, miRNA-based therapy is hindered by the low stability and non-specific cell-targeting ability of delivery systems. In the present study, we developed folic acid-chitosan (FA-CS)-modified mesoporous silica nanoparticles (PMSN) loaded with miR-223 to regulate retinal microglial polarization. The FA-CS/PMSN/miR-223 nanoparticles exhibited high stability and loading efficiency, achieved targeted delivery, and successfully escaped from lysosomes. In cultured microglial cells, treatment with FA-CS/PMSN/miR-223 nanoparticles upregulated the anti-inflammatory gene YM1/2 and IL-4RA, and downregulated the proinflammatory genes iNOS, IL-1ß, and IL-6. Notably, in a mouse oxygen-induced retinopathy model of ROP, intravitreally injected FA-CS/PMSN/miR-223 nanoparticles (1 µg) decreased the retinal neovascular area by 52.6%. This protective effect was associated with the reduced and increased levels of pro-inflammatory (M1) and anti-inflammatory (M2) cytokines, respectively. Collectively, these findings demonstrate that FA-CS/PMSN/miR-223 nanoparticles provide an effective therapeutic strategy for the treatment of ROP by modulating the miR-223-mediated microglial polarization to the M2 phenotype.


Assuntos
Quitosana , MicroRNAs , Retinopatia da Prematuridade , Animais , Quitosana/uso terapêutico , Modelos Animais de Doenças , Ácido Fólico , Humanos , Imunomodulação , Recém-Nascido , Inflamação , Interleucina-6 , Camundongos , MicroRNAs/genética , MicroRNAs/uso terapêutico , Neovascularização Patológica , Oxigênio/uso terapêutico , Retinopatia da Prematuridade/tratamento farmacológico , Retinopatia da Prematuridade/patologia , Dióxido de Silício/uso terapêutico
20.
J Colloid Interface Sci ; 607(Pt 2): 1500-1515, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34583048

RESUMO

Osteoinductive, osteoconductive, and antibacterial properties of bone repair materials play important roles in regulating the successful bone regeneration. In the present work, we developed pH-sensitive gelatin methacryloyl (GelMA)-oxidized sodium alginate (OSA) hydrogels for dual-release of gentamicin sulfate (GS) and phenamil (Phe) to enhance the antibacterial activity and to promote large bone defect repair. Controlled release of GS was achieved through physical blending with GelMA-OSA solution before photo-polymeriaztion, while Phe was encapsulated into mesoporous silicate nanoparticles (MSN) within the hydrogels. In vitro antibacterial studies against Staphylococcus aureus and Escherichia coli indicated the broad-spectrum antibacterial property. Moreover, in vitro cell tests verified the synergistically enhanced osteogenic differentiation ability. Furthermore, in vivo studies revealed that the hydrogels significantly increased new bone formation in a critical-sized mouse cranial bone defect model. In summary, the novel dual-network hydrogels with both antibacterial and osteoinductive properties showed promising potential applications in bone tissue engineering.


Assuntos
Hidrogéis , Osteogênese , Animais , Antibacterianos/farmacologia , Regeneração Óssea , Gelatina/farmacologia , Hidrogéis/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Camundongos , Engenharia Tecidual
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