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1.
Opt Express ; 31(6): 10894-10904, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37157625

RESUMO

Microsphere-assisted super-resolution imaging is a promising technique that can significantly enhance the resolution of conventional optical microscopes. The focus of a classical microsphere is called photonic nanojet, which is a symmetric high-intensity electromagnetic field. Recently, patchy microspheres have been reported to have superior imaging performance than pristine microspheres, and coating microspheres with metal films leads to the formation of photonic hooks, which can enhance the imaging contrast of microspheres. Understanding the influence of metal patches on the near-field focusing of patchy particles is important for the rational design of a nanostructured microlens. In this work, we theoretically and experimentally showed that the light waves can be focused and engineered using patchy particles. When coating dielectric particles with Ag films, light beams with a hook-like structure or S-shaped structure can be generated. Simulation results show that the waveguide ability of metal films and the geometric asymmetry of patchy particles cause the formation of S-shaped light beams. Compared with classical photonic hooks, S-shaped photonic hooks have a longer effective length and a smaller beam waist at far-field region. Experiments were also carried out to demonstrate the generation of classical and S-shaped photonic hooks from patchy microspheres.

2.
Opt Lett ; 48(7): 1638-1641, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37221729

RESUMO

Transport-of-intensity diffraction tomography (TIDT) is a recently developed label-free computational microscopy technique that retrieves high-resolution three-dimensional (3D) refractive index (RI) distribution of biological specimens from 3D intensity-only measurements. However, the non-interferometric synthetic aperture in TIDT is generally achieved sequentially through the acquisition of a large number of through-focus intensity stacks captured at different illumination angles, resulting in a very cumbersome and redundant data acquisition process. To this end, we present a parallel implementation of a synthetic aperture in TIDT (PSA-TIDT) with annular illumination. We found that the matched annular illumination provides a mirror-symmetric 3D optical transfer function, indicating the analyticity in the upper half-plane of the complex phase function, which allows for recovery of the 3D RI from a single intensity stack. We experimentally validated PSA-TIDT by conducting high-resolution tomographic imaging of various unlabeled biological samples, including human breast cancer cell lines (MCF-7), human hepatocyte carcinoma cell lines (HepG2), Henrietta Lacks (HeLa) cells, and red blood cells (RBCs).

3.
J Ultrasound Med ; 42(12): 2859-2866, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37661827

RESUMO

OBJECTIVES: The aim of this study was to explore the application value of shear wave elastography in healthy adults with knee meniscus. METHODS: One hundred adult subjects who underwent health checkups at our hospital from December 2022 to February 2023 were selected as research participants. Shear wave elastography was used to evaluate the periphery of the lateral and medial meniscus in both knees. To assess the mean differences in Young's modulus values between male and female groups, a one-way analysis of variance (ANOVA) and independent samples t-test were conducted. In addition, a Pearson correlation coefficient test was used to analyze the correlation between the elastic values of the meniscus and age, height, weight, and body mass index (BMI). RESULTS: There were no significant differences in elastic values between the lateral meniscus of the left and right sides or between the medial meniscus of the left and right sides within the same gender group (P > .05). Stiffness values of the medial meniscus were higher in each gender group than those of the lateral meniscus (P < .01). Additionally, males demonstrated higher stiffness values than females (P < .01). As age increased, the Young's modulus of the meniscus increased significantly (r > .75, P < .01). CONCLUSION: Shear wave elastography can serve as an adjunctive tool to aid in the assessment of knee meniscal elasticity.


Assuntos
Técnicas de Imagem por Elasticidade , Humanos , Adulto , Masculino , Feminino , Articulação do Joelho/diagnóstico por imagem , Meniscos Tibiais/diagnóstico por imagem , Índice de Massa Corporal , Módulo de Elasticidade
4.
J Neurochem ; 161(3): 293-307, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35244207

RESUMO

The role of α1 adrenergic receptors (α1-ARs) signaling pathway in the pathogenesis of Alzheimer's disease (AD) has rarely been investigated. Clarifying the pathophysiological functions of α1-ARs in the AD brain is helpful for better understanding the pathogenesis and screening novel therapeutic targets of AD. This study included 2 arms of in vivo investigations: 1) 6-month-old female APPswe/PS1 mice were intravenously treated with AAV-PHP.eB-shRNA (α1-ARs)-GFP or AAV-PHP.eB-GFP for 3 months. 2) 3-month-old female APPswe/PS1 mice were daily treated with 0.5 mg/kg terazosin or an equal volume of saline for 6 months. SH-SY5Y cell lines bearing human amyloid precursor protein were treated with terazosin or saline for investigating possible mechanisms. α1-ARs knockdown mice exhibited improved behavioral performances in comparison with control mice. α1-ARs knockdown mice had significantly lower brain amyloid burden, as reflected by soluble Aß species, compact and total Aß plaques, than control mice. α1-ARs inhibitor terazosin substantially reduced Aß deposition, attenuated downstream pathologies including tau hyperphosphorylation, glial activation, neuronal loss, synaptic dysfunction et al., and rescued behavioral deficits in APPswe/PS1 mice. In vitro investigation demonstrated that α1-ARs inhibition down-regulated BACE1 expression, and promoted ser9 phosphorylation of GSK-3ß, thus reducing Aß production. This study indicates that inhibition of α1-ARs signaling pathway might represent a promising therapeutic strategy for AD.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Modelos Animais de Doenças , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Camundongos , Camundongos Transgênicos , Receptores Adrenérgicos/uso terapêutico , Transdução de Sinais
5.
Mol Psychiatry ; 26(10): 6074-6082, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33828237

RESUMO

Amyloid-ß (Aß) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aß produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aß clearance remain largely unknown. The kidney is thought to be responsible for Aß clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aß in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aß clearance via the kidney were assessed. We detected Aß in the kidneys and urine of both humans and animals and found that the Aß level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aß deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aß levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aß from the blood, suggesting that facilitation of Aß clearance via the kidney represents a novel potential therapeutic approach for AD.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Rim/metabolismo , Camundongos , Camundongos Transgênicos , Presenilina-1/metabolismo
6.
BMC Anesthesiol ; 21(1): 177, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34167482

RESUMO

BACKGROUND: Recent studies indicate that ultrasound can detect changes in tracheal diameter during endotracheal tube (ETT) cuff inflation. We sought to assess the accuracy of ultrasound measurement of tracheal diameter, and to determine the relationship between tracheal wall pressure (TWP), cuff inflation volume (CIV), and the degree of tracheal deformation. METHODS: Our study comprised two parts: the first included 45 porcine tracheas, the second 41 porcine tracheas. Each trachea was intubated with a cuffed ETT, which was connected to an injector and the manometer via a three-way tap. The cuff was inflated and the cuff pressure recorded before and after intubation. The tracheal diameter was measured using ultrasound. This included three separate measurements: outer transverse diameter (OTD), internal transverse diameter (ITD), and anterior tracheal wall thicknesses (ATWT). A precision electronic Vernier caliper was also used to measure tracheal diameter. We calculated TWP and the percentage change of tracheal diameter. The Bland-Altman method, linear regression, and locally weighted regression (LOESS) were used to analyze the data. RESULTS: There were strong correlation and agreement for OTD (r = 0.97, P < 0.001) and ITD (r = 0.90, P < 0.001) as measured by ultrasound and by precision electronic Vernier caliper, but a poor correlation for ATWT (r = 0.58, P < 0.001). There was a strong correlation between the percentage change of OTD (OTD%, r = 0.75, P < 0.001) and CIV, the percentage change of ITD (ITD%, r = 0.77, P < 0.001) and CIV, TWP (r = 0.75, P < 0.001) and CIV. And a strong correlation was also found between TWP and OTD% (r = 0.84, P < 0.001), TWP and ITD% (r = 0.84, P < 0.001). CONCLUSIONS: Use of ultrasound to measure OTD and ITD is accurate, but is less accurate for ATWT. There is a close correlation between OTD%, ITD%, CIV and TWP.


Assuntos
Intubação Intratraqueal/métodos , Traqueia/diagnóstico por imagem , Ultrassonografia/métodos , Animais , Desenho de Equipamento , Intubação Intratraqueal/instrumentação , Pressão , Suínos
7.
Cytokine ; 129: 155043, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32078923

RESUMO

Metabolic syndrome (MetS) has been associated with osteoarthritis (OA). Leptin, which is one of the markers of MetS, has been associated with OA pathophysiology. This study aimed to provide an update on the association between MetS and OA and on the potential role of leptin in OA. In this review, we summarized the current knowledge of the association between MetS and OA and updated the evidence on the potential role of leptin in OA. Clinical studies have investigated the epidemiologic association between MetS or its components and OA. Results suggested strong epidemiologic associations between MetS and OA, especially in the Asian population. Animal studies also indicated that metabolic dysregulation may lead to OA pathogenesis. The systemic role of MetS in OA pathophysiology is associated with obesity-related inflammation, the beneficial role of n-3 polyunsaturated fatty acids and deleterious role of cholesterol, physical inactivity, hypertension-induced subchondral ischemia, dyslipidemia-induced ectopic lipid deposition in chondrocytes, hyperglycemia-induced local effects of oxidative stress and advanced glycation end-products, low-grade systemic inflammation, and obesity-related adipokines by inducing the expression of proinflammtory factors. Leptin levels in serum/plasma and synovial fluid were associated with joint pain, radiographic progression, bone formation biomarkers, cartilage volume, knee OA incidence, and total joint arthroplasty in OA patients. Elevated leptin expression and increased effect of leptin on infrapatellar fat pad, synovium, articular cartilage, and bone were also involved in the pathogenesis of OA. Current knowledge indicates a convincing epidemiologic association between MetS and OA, especially in the Asian population. Animal studies have also shown that metabolic dysregulation may lead to OA pathogenesis. Accumulating evidence suggests that leptin may play a potential role in OA pathogenesis. Therefore, leptin and its receptor may be an emerging target for intervention in metabolic-associated OA.


Assuntos
Leptina/metabolismo , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Osteoartrite/metabolismo , Osteoartrite/patologia , Adipocinas/metabolismo , Animais , Condrócitos/metabolismo , Condrócitos/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Obesidade/metabolismo , Obesidade/patologia
8.
J Integr Neurosci ; 19(1): 39-49, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32259885

RESUMO

Depression is a common mental health disorder that can impair normal functions, cause distress, and adversely affect the quality of life. Cognitive impairment is considered one of the characteristics of major depression disorders-related dysfunction, and it has received attention in the treatment of major depressive disorders. To investigated the mechanisms underlying depression-induced cognitive disorders, we selected a rodent model of chronic unpredictable mild stress and used liquid chromatography/mass spectrometry-based metabolomics of sera. Behavioral tests, including the sucrose preference test and open field test, revealed that model rats developed depression-like symptoms in the sixth week of the chronic unpredictable mild stress period. Rats of the model group exhibited significant cognitive changes in the Morris water maze test in the tenth week of the period. Tau phosphorylation and decreased levels of postsynaptic density-95 and synaptophysin were observed in the rodent brains by the tenth week. These results suggest that rodents developed cognitive impairment in the tenth week of the period, while serum metabonomic showed that glycerophospholipid metabolism is the most relevant pathway to reveal the mechanism of depression-induced cognitive impairment. The disorders of lipid metabolism caused by the increased cholesterol efflux and reduced reuptake could be one of the mechanisms of depression-induced cognitive disorders. However, the relationship between cholesterol efflux in the brain and elevated serum cholesterol needs further research.


Assuntos
Colesterol/metabolismo , Disfunção Cognitiva/metabolismo , Depressão/metabolismo , Metabolismo dos Lipídeos , Estresse Psicológico/metabolismo , Animais , Comportamento Animal , Disfunção Cognitiva/etiologia , Depressão/etiologia , Modelos Animais de Doenças , Masculino , Ratos Wistar , Estresse Psicológico/complicações
9.
Zhongguo Zhong Yao Za Zhi ; 45(1): 196-201, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237430

RESUMO

To analyze the medication regularity of traditional Chinese medicine(TCM) prescriptions for gastropyretic excessiveness diabetes recorded in Chinese Medicine Prescriptions Dictionary. A total of 103 eligible prescriptions were input into the system platform, and the Apriori algorithm was used to analyze their medication regularity. The 103 prescriptions for gastropyretic excessiveness diabetes were selected from the system, and 29 herb medicines were found with frequency of usage more than 8. Totally 33 commonly used herbal pairs(support degree≥10), twenty-three 3-herb core combinations(support degree≥8, confidence values≥0.5), and twenty-one 4-herb core combinations(confidence values≥0.5) were discovered after the medication regularity analysis by Apriori algorithm. The herbal medicine combinations with the highest correlation degree were discovered after the association rule analysis on the 103 prescriptions(support degree≥10, confidence values≥0.5). The four properties, five tastes, channel distributions and frequency of dose of the 103 prescriptions were also obtained after the corresponding analysis. According to the analysis and summary of the above data, the combination of Trichosanthis Radix, Anemarrhenae Rhizoma, Coptidis Rhizoma and Ophiopogonis Radix could reflect the medication regularity of TCM prescriptions for gastropyretic excessiveness diabetes to a certain degree, which is of great significance in guiding value in clinic.


Assuntos
Mineração de Dados , Diabetes Mellitus/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Medicina Tradicional Chinesa
10.
Anal Bioanal Chem ; 411(8): 1509-1516, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30739196

RESUMO

Doxorubicin (DOX), an anthracycline molecule, is currently one of the most widely used anticancer drugs in clinics. Systematic treatment of patients with DOX is known to be accompanied by several unpleasant side effects due to the toxicity of the drug. Thus, monitoring of DOX concentration in serum samples has become increasingly important to avoid side effects and ensure therapeutic efficiency. In this study, we discuss the construction of a disposable electrochemical sensor for the direct monitoring of DOX in clinical blood samples. The sensor is based on coating a gold electrode in a flexible integrated electrode construct formed on polyimide sheets using photolithography, with nitrogen-doped reduced graphene oxide (N-rGO) suspended in chitosan. Under optimized conditions, a linear relationship between the oxidative peak current and the concentration of DOX in the range of 0.010-15 µM with a detection limit of 10 nM could be achieved. The sensor was adapted to monitor DOX in serum samples of patients under anticancer treatment. Graphical abstract.


Assuntos
Antibióticos Antineoplásicos/sangue , Doxorrubicina/sangue , Monitoramento de Medicamentos/métodos , Grafite/química , Nitrogênio/química , Técnicas Eletroquímicas/métodos , Eletrodos , Humanos , Limite de Detecção , Modelos Moleculares
11.
Anal Bioanal Chem ; 411(20): 5149-5157, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31250067

RESUMO

A mandatory step in any sensor fabrication is the introduction of analyte-specific recognition elements to the transducer surface. In this study, the possibility to anchor ß-cyclodextrin-modified dopamine to a reduced graphene oxide based electrochemical transducer for the sensitive and selective sensing of folic acid is demonstrated. The sensor displays good electrocatalytic activity toward the oxidation of folic acid. The strong affinity of the surface-confined ß-cyclodextrin for folic acid, together with favorable electron transfer characteristics, resulted in a sensor with a detection limit of 1 nM for folic acid and a linear response up to 10 µM. Testing of the sensor on serum samples from healthy individuals and patients diagnosed with folic acid deficiency validated the sensing capability. Graphical abstract.


Assuntos
Ciclodextrinas/química , Dopamina/química , Eletrodos , Ácido Fólico/sangue , Grafite/química , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção , Oxirredução , Espectroscopia Fotoeletrônica
12.
J Pharm Pharm Sci ; 22(1): 98-111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30786957

RESUMO

PURPOSE: Preliminary study results have shown that rats with non-alcoholic fatty liver disease (NAFLD) induced by 1% orotic acid-containing diet have decreased hepatic CYP2D activity. This study aims to evaluate the possible pharmacokinetic changes in NAFLD as a result of reduced metabolic activity of CYP2D. METHODS: The pharmacokinetics of metoprolol and its metabolites, O-desmethyl metoprolol (DMM) and α-hydroxy metoprolol (HM), was investigated in NAFLD and control rats following intravenous (1 mg/kg) and oral (2 mg/kg) administration of metoprolol. The hepatic CYP2D expression was also investigated. RESULTS: NAFLD rats had lower CYP2D expression (by 36.6%) and slower intrinsic clearance (CLint) of metoprolol and formation of HM (by 40.1% and 37.2%, respectively). There were no significant changes in the pharmacokinetics of metoprolol and its metabolites following intravenous administration. In contrast, oral administration of metoprolol resulted in significantly increased total area under plasma concentration-time curve (AUC) of metoprolol (by 127%) and decreased metabolite formation ratios (AUCDMM/AUCMetoprolol [by 42.8%], AUCHM/AUCMetoprolol [by 35.0%]) in NAFLD rats. Moreover, these changes were well correlated with severity of steatosis as quantified by hepatic triglyceride contents. CONCLUSIONS: NALFD can lead to a reduction in the hepatic CLint of a drug if it is a substrate of the CYP2D subfamily. The decreased clearance may result in elevated drug concentrations and increased exposure.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacocinética , Metoprolol/farmacocinética , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Ácido Orótico/farmacologia , Animais , Família 2 do Citocromo P450/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Ligação Proteica , Ratos Sprague-Dawley
13.
BMC Musculoskelet Disord ; 20(1): 617, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31878972

RESUMO

BACKGROUND: Despite potential for improving patient outcomes, studies using three-dimensional measurements to quantify proximal tibial sclerotic bone and its effects on prosthesis stability after total knee arthroplasty (TKA) are lacking. Therefore, this study aimed to determine: (1) the distribution range of tibial sclerotic bone in patients with severe genu varum using three-dimensional measurements, (2) the effect of the proximal tibial sclerotic bone thickness on prosthesis stability according to finite-element modelling of TKA with kinematic alignment (KA), mechanical alignment (MA), and 3° valgus alignment, and (3) the effect of short extension stem augment utilization on prosthesis stability. METHODS: The sclerotic bone in the medial tibial plateau of 116 patients with severe genu varum was measured and classified according to its position and thickness. Based on these cases, finite-element models were established to simulate 3 different tibial cut alignments with 4 different thicknesses of the sclerotic bone to measure the stress distribution of the tibia and tibial prosthesis, the relative micromotion beneath the stem, and the influence of the short extension stem on stability. RESULTS: The distribution range of proximal tibial sclerotic bone was at the anteromedial tibial plateau. The models were divided into four types according to the thickness of the sclerotic bone: 15 mm, 10 mm, 5 mm, and 0 mm. The relative micromotion under maximum stress was smallest after MA with no sclerotic bone (3241 µm) and largest after KA with 15 mm sclerotic bone (4467 µm). Relative micromotion was largest with KA and smallest with MA in sclerotic models with the same thickness. Relative micromotion increased as thickness of the sclerotic bone increased with KA and MA (R = 0.937, P = 0.03 and R = 0.756, P = 0.07, respectively). Relative micromotion decreased with short extension stem augment in the KA model when there was proximal tibial sclerotic bone. CONCLUSIONS: The influence of proximal tibial sclerotic bone on prosthesis's stability is significant, especially with KA tibial cut. Tibial component's short extension stem augment can improve stability.


Assuntos
Genu Varum/cirurgia , Prótese do Joelho , Osteoartrite do Joelho/cirurgia , Osteosclerose/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Idoso , Artroplastia do Joelho , Feminino , Análise de Elementos Finitos , Genu Varum/complicações , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteosclerose/etiologia , Falha de Prótese , Tíbia/cirurgia
14.
Biochim Biophys Acta Biomembr ; 1860(2): 624-632, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29138064

RESUMO

Antimicrobial peptides effectively kill antibiotic-resistant bacteria by forming pores in prokaryotes' biomembranes via penetration into the biomembranes' interior. Bicontinuous microemulsions, consisting of interdispersed oil and water nanodomains separated by flexible surfactant monolayers, are potentially valuable for hosting membrane-associated peptides and proteins due to their thermodynamic stability, optical transparency, low viscosity, and high interfacial area. Here, we show that bicontinuous microemulsions formed by negatively-charged surfactants are a robust biomembrane mimetic system for the antimicrobial peptide melittin. When encapsulated in bicontinuous microemulsions formed using three-phase (Winsor-III) systems, melittin's helicity increases greatly due to penetration into the surfactant monolayers, mimicking its behavior in biomembranes. But, the threshold melittin concentration required to achieve these trends is lower for the microemulsions. The extent of penetration was decreased when the interfacial fluidity of the microemulsions was increased. These results suggest the utility of bicontinuous microemulsions for isolation, purification, delivery, and host systems for antimicrobial peptides.


Assuntos
Membrana Celular/química , Emulsões/química , Meliteno/química , Tensoativos/química , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Abelhas/metabolismo , Biomimética , Membrana Celular/efeitos dos fármacos , Dicroísmo Circular , Proteínas de Insetos/química , Proteínas de Insetos/farmacologia , Meliteno/farmacologia , Difração de Nêutrons , Estrutura Secundária de Proteína , Espalhamento a Baixo Ângulo , Espectrometria de Fluorescência , Termodinâmica , Água/química
15.
Biochem Biophys Res Commun ; 502(3): 291-298, 2018 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-29772232

RESUMO

The CD133 antigen, also known as prominin-1, is a glycoprotein that specifically localizes to plasma membrane protrusions. The precise function of CD133 remains unknown, but it is expressed in various progenitor cells including those derived from the neural and hematopoietic system, as well as different tissues. In the adult mouse brain, CD133 is highly expressed in white matter. Here, we performed immunohistochemical staining and electron microscopy to demonstrate that mice lacking CD133 (CD133-/-) exhibit decreased myelin in the corpus callosum, the largest white matter tract in the brain. Hypomyelination in CD133-/- mice was associated with fewer oligodendrocyte progenitor cells and mature oligodendrocytes. Behavioral analyses revealed that significantly impaired object recognition memory and altered Y-maze performance by CD133-/- mice compared with wild-type mice, suggesting perturbed cognitive performance. These results suggest that CD133 regulates myelination and understanding the underlying molecular mechanisms may guide the development of novel therapeutic strategies for diseases characterized by myelin deficiency.


Assuntos
Antígeno AC133/deficiência , Disfunção Cognitiva/etiologia , Bainha de Mielina/metabolismo , Antígeno AC133/genética , Antígeno AC133/fisiologia , Animais , Comportamento Animal , Encéfalo/metabolismo , Encéfalo/patologia , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Bainha de Mielina/patologia , Células Precursoras de Oligodendrócitos/metabolismo , Células Precursoras de Oligodendrócitos/patologia , Oligodendroglia/metabolismo , Oligodendroglia/patologia
16.
Soft Matter ; 14(25): 5270-5276, 2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29892769

RESUMO

We demonstrate here for the first time via small-angle neutron scattering (SANS) that the middle, bicontinuous microemulsion (BµE) phase of Winsor-III systems undergoes a gradual change of structure and composition in the vertical direction, contrary to the commonly held belief of uniform structure and composition. A vertical stage was deployed to enable precise alignment of a custom-designed rectangular cell containing the WIII system with respect to the neutron beam, allowing for several different vertical positions to be analyzed. For the water/AOT/CK-2,13 (two-tailed alkyl ethoxylate containing a 1,3-dioxolane linkage)/heptane Winsor-III system, the quasi-periodic repeat distance (d) and correlation length (ξ), obtained from the Teubner-Strey model applied to the SANS data, decreased and the surface area per volume of the surfactant monolayer (via Porod analysis) increased in the downward direction, trends that reflect an increase of surfactant concentration, consistent with the ultralow interfacial tension that often occurs for the lower liquid-liquid interface of many WIII systems. The water/sodium dodecyl sulfate (SDS)/1-pentanol/dodecane system shared the same trend with regard to d as observed for AOT/CK-2,13. In contrast, for SDS/pentanol, ξ increased and the amphiphilicity factor (fa) decreased in the downward direction, trends consistent with a decrease of cosurfactant (pentanol) concentration in the downward direction. Non-uniformity in the vertical direction has implications in the transport of solutes between WIII phases during the extractive purification of proteins or the removal of heavy metals and pollutants from wastewater, or the deposition of BµEs onto hydrophilic vs. hydrophobic surfaces as thin coatings.

17.
Proc Natl Acad Sci U S A ; 112(16): 5225-30, 2015 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-25847999

RESUMO

Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-ß (Aß) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aß aggregation and attenuating Aß-induced oxidation in vitro. When given before or after the onset of Aß deposition via i.p. injection, Edaravone substantially reduces Aß deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antipirina/análogos & derivados , Transtornos Cognitivos/tratamento farmacológico , Administração Oral , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Amiloide/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Antipirina/administração & dosagem , Antipirina/química , Antipirina/farmacologia , Antipirina/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Linhagem Celular , Transtornos Cognitivos/complicações , Transtornos Cognitivos/patologia , Dendritos/efeitos dos fármacos , Dendritos/patologia , Edaravone , Humanos , Inflamação/patologia , Camundongos Transgênicos , Neurotoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Presenilina-1/metabolismo , Agregação Patológica de Proteínas/complicações , Agregação Patológica de Proteínas/tratamento farmacológico , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas tau/metabolismo
18.
Tohoku J Exp Med ; 246(1): 45-50, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30232297

RESUMO

Hearing loss is a common disease in older adults. In order to lower the prevalence of hearing loss, it is important to identify its risk factors. Although some studies have found a relationship between dental status and hearing acuity, few studies have investigated the relationship between unilateral chewing and hearing acuity. This study aimed to assess the effects of unilateral chewing on hearing acuity, with a focus on the risk of hearing loss. Eighty-one participants (aged 51-87 years) were included in the present study. Their chewing habits were determined by visual inspection. The participants were divided into two groups: the Unilateral Chewing Group (UCG; n = 43) and the Bilateral Chewing Group (BCG; n = 38). The preferred chewing side was identified for the UCG. Hearing acuity was determined using pure tone audiometry in a noise-free chamber, conducted at frequencies of 500, 1,000, 2,000, and 4,000 Hz. Hearing loss was defined as a lower hearing threshold greater than 50 dB in either ear at any frequency. Mean hearing thresholds at frequencies of 2,000 and 4,000 Hz were significantly higher, by 5.12 and 15.75 dB, respectively, for the UCG compared to the BCG (P < 0.05). The UCG had a 3.78-fold higher likelihood of suffering from hearing loss (95% confidence interval [CI]: 1.81-7.88). The results suggest that bilateral chewing could be beneficial for preventing hearing loss. This study may provide evidence to support clinical interventions aimed at reducing the risk of hearing loss in patients with unilateral chewing habits.


Assuntos
Hábitos , Perda Auditiva/etiologia , Perda Auditiva/fisiopatologia , Audição/fisiologia , Mastigação/fisiologia , Idoso , Idoso de 80 Anos ou mais , Audiometria de Tons Puros , Limiar Auditivo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
19.
Int Orthop ; 42(3): 507-511, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28761997

RESUMO

BACKGROUND: The aim was to explore the factors contributing to a high degree of satisfaction following total hip arthroplasty in patients with ankylosing spondylitis and hip joint fusion. METHODS: From January 2001 to June 2015, 43 patients with ankylosing spondylitis were treated with total hip arthroplasty. The patients were divided into two groups, including 20 patients in non-fusion groups, with 25 cases of hip non-fusion, and 23 patients in fusion groups, with 40 cases of hip fusion. Patients were followed for an average of 27 months. Harris hip scores (HHSs) and Barthel scores were recorded pre-operatively and post-operatively. The improvement rates of both groups were calculated, and the data were compared and analyzed. The Self-Administered Patient Satisfaction Scale (SAPS) was used to assess the degree of satisfaction in each group. RESULTS: The post-operative HHS and Barthel scores of two groups both significantly improved. In non-fusion groups compared with fusion groups, there were significant differences in the pre-operative HHSs, the improvement of the HHSs, the pre-operative Barthel score, the improvement of the Barthel score, and the satisfaction score. However, there were no significant differences in the post-operative HHSs and Barthel scores. CONCLUSION: Patients in the hip fusion group had higher satisfaction scores. The improvements in joint function and self-care ability after total hip arthroplasty are the decisive factors in determining patient satisfaction for patients with ankylosing spondylitis combined with hip fusion.


Assuntos
Artrodese/métodos , Artroplastia de Quadril/métodos , Articulação do Quadril/patologia , Satisfação do Paciente/estatística & dados numéricos , Espondilite Anquilosante/cirurgia , Adulto , Artroplastia de Quadril/efeitos adversos , Feminino , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Espondilite Anquilosante/complicações , Resultado do Tratamento , Adulto Jovem
20.
Yi Chuan ; 40(11): 1007-1014, 2018 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-30465533

RESUMO

REV1 is one of the major Y-family DNA polymerases. It not only functions as a scaffold protein to mediate other specialized DNA polymerases to sites of lesions, but also inserts deoxycytidine across the lesion strand during translesion DNA synthesis (TLS). Meanwhile, REV1 has been reported to be involved in homologous recombination (HR) repair. Here we further explore the roles of REV1-interacting proteins RAD51 and RAD51C in REV1-mediated DNA double-strand break (DSB) repair. We found that RAD51 but not RAD51C regulates REV1 recruitment to DSB sites via pulsed laser microirradiation. Interestingly, immunofluorescence staining exhibits that REV1 also regulates RAD51 focus formation in response to CPT treatment. These results suggest that REV1 and RAD51 might be mutually dependent on each other in the REV1-related HR pathway.


Assuntos
Quebras de DNA de Cadeia Dupla , Proteínas Nucleares/metabolismo , Nucleotidiltransferases/metabolismo , Rad51 Recombinase/metabolismo , Linhagem Celular , Reparo do DNA , Replicação do DNA , Humanos , Proteínas Nucleares/genética , Nucleotidiltransferases/genética , Ligação Proteica , Rad51 Recombinase/genética , Reparo de DNA por Recombinação
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