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1.
Nat Methods ; 21(1): 132-141, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38129618

RESUMEN

Multiphoton microscopy can resolve fluorescent structures and dynamics deep in scattering tissue and has transformed neural imaging, but applying this technique in vivo can be limited by the mechanical and optical constraints of conventional objectives. Short working distance objectives can collide with compact surgical windows or other instrumentation and preclude imaging. Here we present an ultra-long working distance (20 mm) air objective called the Cousa objective. It is optimized for performance across multiphoton imaging wavelengths, offers a more than 4 mm2 field of view with submicrometer lateral resolution and is compatible with commonly used multiphoton imaging systems. A novel mechanical design, wider than typical microscope objectives, enabled this combination of specifications. We share the full optical prescription, and report performance including in vivo two-photon and three-photon imaging in an array of species and preparations, including nonhuman primates. The Cousa objective can enable a range of experiments in neuroscience and beyond.


Asunto(s)
Colorantes , Microscopía de Fluorescencia por Excitación Multifotónica , Animales , Microscopía de Fluorescencia por Excitación Multifotónica/métodos
2.
Proc Natl Acad Sci U S A ; 119(9)2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35197290

RESUMEN

Aminoglycosides (AGs) are commonly used antibiotics that cause deafness through the irreversible loss of cochlear sensory hair cells (HCs). How AGs enter the cochlea and then target HCs remains unresolved. Here, we performed time-lapse multicellular imaging of cochlea in live adult hearing mice via a chemo-mechanical cochleostomy. The in vivo tracking revealed that systemically administered Texas Red-labeled gentamicin (GTTR) enters the cochlea via the stria vascularis and then HCs selectively. GTTR uptake into HCs was completely abolished in transmembrane channel-like protein 1 (TMC1) knockout mice, indicating mechanotransducer channel-dependent AG uptake. Blockage of megalin, the candidate AG transporter in the stria vascularis, by binding competitor cilastatin prevented GTTR accumulation in HCs. Furthermore, cilastatin treatment markedly reduced AG-induced HC degeneration and hearing loss in vivo. Together, our in vivo real-time tracking of megalin-dependent AG transport across the blood-labyrinth barrier identifies new therapeutic targets for preventing AG-induced ototoxicity.


Asunto(s)
Antibacterianos/metabolismo , Gentamicinas/metabolismo , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Animales , Antibacterianos/toxicidad , Transporte Biológico , Cilastatina/farmacología , Endolinfa/metabolismo , Gentamicinas/toxicidad , Células Ciliadas Auditivas/efectos de los fármacos , Células Ciliadas Auditivas/metabolismo , Audición/efectos de los fármacos , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad/antagonistas & inhibidores , Ratones , Estría Vascular/metabolismo
3.
Mol Cell Neurosci ; 120: 103722, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35341941

RESUMEN

Aminoglycosides are potent antibiotics that are commonly prescribed worldwide. Their use carries significant risks of ototoxicity by directly causing inner ear hair cell degeneration. Despite their ototoxic side effects, there are currently no approved antidotes. Here we review recent advances in our understanding of aminoglycoside ototoxicity, mechanisms of drug transport, and promising sites for intervention to prevent ototoxicity.


Asunto(s)
Aminoglicósidos , Ototoxicidad , Aminoglicósidos/toxicidad , Antibacterianos/efectos adversos , Humanos
4.
Nano Lett ; 22(23): 9766-9772, 2022 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-36317830

RESUMEN

Hyperfine interactions have been widely used in material science, organic chemistry, and structural biology as a sensitive probe to local chemical environments. However, traditional ensemble measurements of hyperfine interactions average over a macroscopic number of spins with different geometrical locations and nuclear isotopes. Here, we use a scanning tunneling microscope (STM) combined with electron spin resonance (ESR) to measure hyperfine spectra of hydrogenated-Ti on MgO/Ag(100) at low-symmetry binding sites and thereby determine the isotropic and anisotropic hyperfine interactions at the single-atom level. Combining vector-field ESR spectroscopy with STM-based atom manipulation, we characterize the full hyperfine tensors of 47Ti and 49Ti and identify significant spatial anisotropy of the hyperfine interactions for both isotopes. Density functional theory calculations reveal that the large hyperfine anisotropy arises from highly anisotropic distributions of the ground-state electron spin density. Our work highlights the power of ESR-STM-enabled single-atom hyperfine spectroscopy in revealing electronic ground states and atomic-scale chemical environments.


Asunto(s)
Anisotropía , Espectroscopía de Resonancia por Spin del Electrón/métodos , Sitios de Unión
5.
Int J Hosp Manag ; 102: 103163, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35017782

RESUMEN

This study investigates the effect of the COVID-19 pandemic on the hotel selection attributes and customer post-purchase behaviors. Qualitative and quantitative processes comprising an importance-performance analysis are used. This mixed-methods approach successfully (1) explores the hotel selection attributes after the COVID-19 pandemic, (2) uncovers the change of importance of these attributes before and after the outbreak of COVID-19, (3) identifies the importance and the performance level of the hotel selection attributes, and (4) explores the roles of the hotel selection attributes that form the overall image of a hotel and the subsequent intentions to revisit a hotel. This study includes a high degree of value, and this is the first empirical research that explores the guests' hotel choice behaviors before and after the pandemic, which can be helpful for the subsequent guest-behavior studies in the post-pandemic era.

6.
Proc Natl Acad Sci U S A ; 115(21): E4853-E4860, 2018 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-29735658

RESUMEN

Traumatic noise causes hearing loss by damaging sensory hair cells and their auditory synapses. There are no treatments. Here, we investigated mice exposed to a blast wave approximating a roadside bomb. In vivo cochlear imaging revealed an increase in the volume of endolymph, the fluid within scala media, termed endolymphatic hydrops. Endolymphatic hydrops, hair cell loss, and cochlear synaptopathy were initiated by trauma to the mechanosensitive hair cell stereocilia and were K+-dependent. Increasing the osmolality of the adjacent perilymph treated endolymphatic hydrops and prevented synaptopathy, but did not prevent hair cell loss. Conversely, inducing endolymphatic hydrops in control mice by lowering perilymph osmolality caused cochlear synaptopathy that was glutamate-dependent, but did not cause hair cell loss. Thus, endolymphatic hydrops is a surrogate marker for synaptic bouton swelling after hair cells release excitotoxic levels of glutamate. Because osmotic stabilization prevents neural damage, it is a potential treatment to reduce hearing loss after noise exposure.


Asunto(s)
Cóclea/fisiopatología , Enfermedades Cocleares/prevención & control , Hidropesía Endolinfática/fisiopatología , Células Ciliadas Auditivas/patología , Pérdida Auditiva Provocada por Ruido/prevención & control , Ruido/efectos adversos , Ósmosis , Animales , Umbral Auditivo , Enfermedades Cocleares/fisiopatología , Pérdida Auditiva Provocada por Ruido/fisiopatología , Ratones
7.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-34202759

RESUMEN

The use of porous three-dimensional (3D) composite scaffolds has attracted great attention in bone tissue engineering applications because they closely simulate the major features of the natural extracellular matrix (ECM) of bone. This study aimed to prepare biomimetic composite scaffolds via a simple 3D printing of gelatin/hyaluronic acid (HA)/hydroxyapatite (HAp) and subsequent biomineralization for improved bone tissue regeneration. The resulting scaffolds exhibited uniform structure and homogeneous pore distribution. In addition, the microstructures of the composite scaffolds showed an ECM-mimetic structure with a wrinkled internal surface and a porous hierarchical architecture. The results of bioactivity assays proved that the morphological characteristics and biomineralization of the composite scaffolds influenced cell proliferation and osteogenic differentiation. In particular, the biomineralized gelatin/HA/HAp composite scaffolds with double-layer staggered orthogonal (GEHA20-ZZS) and double-layer alternative structure (GEHA20-45S) showed higher bioactivity than other scaffolds. According to these results, biomineralization has a great influence on the biological activity of cells. Hence, the biomineralized composite scaffolds can be used as new bone scaffolds in bone regeneration.


Asunto(s)
Regeneración Ósea , Durapatita , Gelatina , Ácido Hialurónico , Impresión Tridimensional , Ingeniería de Tejidos , Andamios del Tejido , Biomineralización , Diferenciación Celular , Fenómenos Químicos , Durapatita/química , Módulo de Elasticidad , Gelatina/química , Análisis Espectral , Andamios del Tejido/química , Viscosidad
8.
Int J Hosp Manag ; 93: 102758, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36919173

RESUMEN

This study aims to identify how behavioral intentions are formed in the context of drone food delivery services using the moderating role before and after the outbreak of COVID-19. A conceptual model including eight hypotheses was developed and tested based on the data of two consumer samples, one collected before and the other after the outbreak of COVID-19. The data analysis results showed that perceived innovativeness positively affects attitude. In addition, the attitude, the subjective norm, and perceived behavioral control have a positive influence on behavioral intentions. Lastly, the outbreak of COVID-19 played a moderating role in the relationship between the attitude and behavioral intentions.

9.
J Hum Genet ; 65(6): 551-555, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32144408

RESUMEN

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability, especially in males. Females with FXS tend to be relatively mildly affected because of compensation by a second X chromosome with a normal FMR1 gene. In most cases, FXS is caused by an expansion of the CGG repeats (>200 triplets, full mutation, FM) in the 5'-untranslated region of the FMR1 gene. Premutation alleles (PM, 55-200 repeats), usually lack the clinical features of FXS, are highly unstable when transmitted to offspring and can give rise to FM, especially in female meiosis. We describe a 3-year-old girl with typical FXS, with only a fully expanded FMR1 allele (288 CGG repeats) due to uniparental isodisomy of X chromosome, inherited from mother carrying a premutation allele. The patient's FMR1 methylation region is completely methylated due to full mutation of CGG repeat. This unusual and rare case indicates the importance of a detailed genomic approach to explain nontraditional Mendelian inheritance pattern.


Asunto(s)
Cromosomas Humanos X/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Discapacidad Intelectual/genética , Alelos , Preescolar , Metilación de ADN/genética , Femenino , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/patología , Humanos , Discapacidad Intelectual/patología , Mutación/genética , Fenotipo , Disomía Uniparental/genética , Disomía Uniparental/patología
10.
Cell Physiol Biochem ; 50(5): 1869-1881, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30396177

RESUMEN

BACKGROUND/AIMS: The functional relevance of early growth response-1 (EGR1) on cancer invasion remains controversial. The effect of EGR1 on the expression of MMP9, which is important for HNSCC invasion, is still disputed. There is no previous data showing the effect of EGR1 on mouse double minute 2 (MDM2), an enhancer of matrix metalloproteinase 9 (MMP9) expression. Our aim is to clarify the negative correlation between EGR1 expression and head and neck squamous cell carcinoma (HNSCC) metastasis. METHODS: EGR1 mRNA and protein expressions were compared in normal and HNSCC tissues using The Cancer Genome Atlas (TCGA) dataset analysis or immunohistochemistry (IHC), respectively. In vitro cell invasion was evaluated Matrigel invasion assay. EGR1-dependent inhibition of MDM2 transcription was assessed by promoter-luciferase assay and chromatin immunoprecipitation (ChIP). RESULTS: TCGA data showed that EGR1 mRNA levels are significantly higher in normal oral tissues as compared with HNSCC tumor tissues (adjusted P = 1.64x10-16). In addition, nonmetastatic HNSCC tissues showed significantly higher EGR1 mRNA levels as compared with metastatic tissues (adjusted P = 0.023). IHC analysis showed that primary tumor tissues expressed significantly higher levels of nuclear EGR1 compared with paired metastatic lymph node tissues (P < 0.05). EGR1 overexpression downregulated MMP9 and MDM2 protein expression. Consistent with these observations, TCGA data analysis found significantly fewer metastatic patients among a subgroup of population presenting higher EGR1 expressions with lower MMP9 and/or MDM2. CONCLUSION: Our data suggests that EGR1 prevents HNSCC metastasis through downregulation of MMP9 and MDM2. EGR1 might be a potential candidate to attenuate HNSCC metastasis.


Asunto(s)
Carcinoma de Células Escamosas/patología , Regulación hacia Abajo , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Neoplasias de Cabeza y Cuello/patología , Metaloproteinasa 9 de la Matriz/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Bases de Datos Genéticas , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Neoplasias de Cabeza y Cuello/metabolismo , Humanos , Metástasis Linfática/fisiopatología , Metaloproteinasa 9 de la Matriz/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello
11.
Plant Biotechnol J ; 16(11): 1904-1917, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29604169

RESUMEN

Panax ginseng C. A. Meyer, reputed as the king of medicinal herbs, has slow growth, long generation time, low seed production and complicated genome structure that hamper its study. Here, we unveil the genomic architecture of tetraploid P. ginseng by de novo genome assembly, representing 2.98 Gbp with 59 352 annotated genes. Resequencing data indicated that diploid Panax species diverged in association with global warming in Southern Asia, and two North American species evolved via two intercontinental migrations. Two whole genome duplications (WGD) occurred in the family Araliaceae (including Panax) after divergence with the Apiaceae, the more recent one contributing to the ability of P. ginseng to overwinter, enabling it to spread broadly through the Northern Hemisphere. Functional and evolutionary analyses suggest that production of pharmacologically important dammarane-type ginsenosides originated in Panax and are produced largely in shoot tissues and transported to roots; that newly evolved P. ginseng fatty acid desaturases increase freezing tolerance; and that unprecedented retention of chlorophyll a/b binding protein genes enables efficient photosynthesis under low light. A genome-scale metabolic network provides a holistic view of Panax ginsenoside biosynthesis. This study provides valuable resources for improving medicinal values of ginseng either through genomics-assisted breeding or metabolic engineering.


Asunto(s)
Genoma de Planta/genética , Panax/genética , Adaptación Biológica/genética , Evolución Biológica , Diploidia , Genes del Cloroplasto/genética , Genes de Plantas/genética , Ginsenósidos/biosíntesis , Panax/metabolismo , Tetraploidía
12.
Bioorg Med Chem Lett ; 28(11): 2098-2102, 2018 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-29685654

RESUMEN

Syntheses of natural homoisoflavonoids, (±)-portulacanones A-C (4, 8 and 9), portulacanone D (6), isolated from Portulaca oleracea L. (POL) and their derivatives (3, 5 and 7) have been achieved for the first time along with the synthesis of known derivatives (1 and 2) and their in vitro inhibitory effect against NO production in LPS-induced RAW-264.7 macrophages was evaluated as an indicator of anti-inflammatory activity. All the compounds tested had a concentration-dependent inhibitory effect on NO production by RAW-264.7 macrophages without obvious cytotoxicity. Compounds 3 (97.2% at 10 µM; IC50 = 1.26 µM) followed by 6 (portulacanone D) (92.5% at 10 µM; IC50 = 2.09 µM), 1 (91.4% at 10 µM; IC50 = 1.75 µM) and 7 (83.0% at 10 µM; IC50 = 2.91 µM) were the most potent from the series. This finding was further correlated with the suppressed expression of iNOS induced by LPS. Our promising preliminary results may provide the basis for the assessment of compound 3 as a lead structure for a NO production-targeted anti-inflammatory drug development and also could support the usefulness of POL as a folklore medicinal plant in the treatment of inflammatory diseases.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Isoflavonas/farmacología , Macrófagos/efectos de los fármacos , Óxido Nítrico/antagonistas & inhibidores , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Isoflavonas/síntesis química , Isoflavonas/química , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Ratones , Estructura Molecular , Óxido Nítrico/biosíntesis , Células RAW 264.7 , Relación Estructura-Actividad
13.
Phytother Res ; 32(4): 698-704, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29368365

RESUMEN

Our previous study demonstrated that phlorotannin supplement had a sleep-promoting effect in rodents. In the present study, we investigated whether the phlorotannin supplement could improve sleep in subjects with self-reported sleep disturbances. In a randomized, double-blind, placebo-controlled trial, 24 subjects consumed either a placebo or phlorotannin supplement (500 mg/day) for 1 week, 30-60 min prior to bedtime. Sleep parameters were assessed at baseline and at 1 week with sleep questionnaires and polysomnography. At the end of the treatment period, the complete sets of sleep parameters from 20 subjects. Phlorotannin resulted in a significant increase in "Sleep duration" scores compared to the placebo (p = .044), although there were no significant differences on the total PSQI scores. Polysomnography revealed that wakefulness after sleep onset was significantly lower in the phlorotannin group compared to the placebo group (phlorotannin vs. placebo, -25.5 ± 30.5 vs. -1.7 ± 14.9; p = .045) as well as total wake time (phlorotannin vs. placebo, -0.9 ± 3.0 vs. -6.1 ± 6.8; p = .048). Additionally, the respiratory disturbance index during supine rapid eye movement sleep was significantly lower in the phlorotannin group (p = .035). There were no serious adverse effects in either group. Our data suggest that the phlorotannin supplement improved sleep maintenance (WHO ICTRP: KCT0001892).


Asunto(s)
Suplementos Dietéticos/efectos adversos , Polisomnografía/métodos , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Sueño/efectos de los fármacos , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Autoinforme , Encuestas y Cuestionarios , Resultado del Tratamiento
14.
J Phys Ther Sci ; 30(8): 1138-1140, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30154616

RESUMEN

[Purpose] The purpose of this study was to learn about the effects of a home-oriented program based on sensorimotor activities on executive and motor functions in children with ADHD. [Participants and Methods] In this study, a home-based sensorimotor program was conducted for two male children diagnosed with ADHD. The participants performed the program with their parents four times a week, for forty minutes each time, over a 12-week period. The participants'executive functions and gross motor skills were evaluated using the Children's Color Trails Test (CCTT) and the Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2). [Results] After participating in the home-based sensorimotor program, the participants showed improvements in both their executive and motor functions. [Conclusion] This study confirmed that a home-based sensorimotor program was effective in improving executive and motor functions in children with ADHD. This conclusion suggests the need to develop various exercise programs that can relieve the symptoms of ADHD in children and improve their abilities to adapt at home or school.

15.
J Phys Ther Sci ; 30(1): 73-76, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29410570

RESUMEN

[Purpose] This study aimed to examine the effects of a client-centered leisure activity program on satisfaction, upper limb function, self-esteem, and depression in elderly residents of a long-term care facility. [Subjects and Methods] This study included 12 elderly subjects, aged 65 or older, residing in a nursing home. The subjects were divided into an experimental and a control group. Subjects in the control group received leisure activities already provided by the facility. The experimental group participated in a client-centered leisure activity program. The subjects conducted individual activities three times per week, 30 minutes per session. The group activity was conducted three times per week for eight weeks. Each subject's performance of and satisfaction with the leisure activity programs, upper limb function, self-esteem, and depression were measured before and after the intervention. [Results] After participating in a program, significant improvements were seen in both the Canadian Occupational Performance Measure and upper limb function in the experimental group. Also after the intervention, the subjects' self-esteem significantly increased and their depression significantly decreased. [Conclusion] A client-centered leisure activity program motivates elderly people residing in a long-term care facility and induces their voluntary participation. Such customized programs are therefore effective for enhancing physical and psychological functioning in this population.

16.
J Neurosci ; 36(31): 8160-73, 2016 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-27488636

RESUMEN

UNLABELLED: The exquisite sensitivity and frequency discrimination of mammalian hearing underlie the ability to understand complex speech in noise. This requires force generation by cochlear outer hair cells (OHCs) to amplify the basilar membrane traveling wave; however, it is unclear how amplification is achieved with sharp frequency tuning. Here we investigated the origin of tuning by measuring sound-induced 2-D vibrations within the mouse organ of Corti in vivo Our goal was to determine the transfer function relating the radial shear between the structures that deflect the OHC bundle, the tectorial membrane and reticular lamina, to the transverse motion of the basilar membrane. We found that, after normalizing their responses to the vibration of the basilar membrane, the radial vibrations of the tectorial membrane and reticular lamina were tuned. The radial tuning peaked at a higher frequency than transverse basilar membrane tuning in the passive, postmortem condition. The radial tuning was similar in dead mice, indicating that this reflected passive, not active, mechanics. These findings were exaggerated in Tecta(C1509G/C1509G) mice, where the tectorial membrane is detached from OHC stereocilia, arguing that the tuning of radial vibrations within the hair cell epithelium is distinct from tectorial membrane tuning. Together, these results reveal a passive, frequency-dependent contribution to cochlear filtering that is independent of basilar membrane filtering. These data argue that passive mechanics within the organ of Corti sharpen frequency selectivity by defining which OHCs enhance the vibration of the basilar membrane, thereby tuning the gain of cochlear amplification. SIGNIFICANCE STATEMENT: Outer hair cells amplify the traveling wave within the mammalian cochlea. The resultant gain and frequency sharpening are necessary for speech discrimination, particularly in the presence of background noise. Here we measured the 2-D motion of the organ of Corti in mice and found that the structures that stimulate the outer hair cell stereocilia, the tectorial membrane and reticular lamina, were sharply tuned in the radial direction. Radial tuning was similar in dead mice and in mice lacking a tectorial membrane. This suggests that radial tuning comes from passive mechanics within the hair cell epithelium, and that these mechanics, at least in part, may tune the gain of cochlear amplification.


Asunto(s)
Estimulación Acústica/métodos , Mecanotransducción Celular/fisiología , Modelos Neurológicos , Órgano Espiral/fisiología , Percepción de la Altura Tonal/fisiología , Membrana Tectoria/fisiología , Animales , Simulación por Computador , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Presión , Resistencia al Corte/fisiología , Vibración
17.
Anticancer Drugs ; 28(6): 613-622, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28452807

RESUMEN

The effect of oxytocin (OXT) on cancer invasion is controversial. Few studies have examined the effect of early growth response-1 (EGR1) on the invasion of head and neck squamous cell carcinoma (HNSCC). Here, we evaluated how EGR1 affects HNSCC cell migration through the molecular mechanism of OXT in exerting anti-invasion activity. Matrigel invasion and wound-healing assays were used to measure the in-vitro cell migration. The molecular mechanism of OXT was assessed by knockdown or overexpression of EGR1 in HNSCC cells. Three-dimensional (3-D) spheroids formation, followed by the image analysis for quantification was performed. OXT at 500 nmol/l increased mRNA and protein expression of E-cadherin without cytotoxicity. OXT upregulated mRNA and protein expression of EGR1 in 6 h. p53, phosphatase and tensin, and p21 expression was increased in an EGR1-dependent manner with OXT treatment. In addition, OXT significantly downregulated 3-D spheroids' formation according to spheroids' number and size. Our data showed that OXT downregulated HNSCC cell migration by EGR1 upregulation. OXT inhibited spheroids' formation of HNSCC cells under 3-D culture conditions.


Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos , Proteína 1 de la Respuesta de Crecimiento Precoz/biosíntesis , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Oxitocina/farmacología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Receptores ErbB/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Humanos , Invasividad Neoplásica , Metástasis de la Neoplasia , Esferoides Celulares , Carcinoma de Células Escamosas de Cabeza y Cuello , Células Tumorales Cultivadas , Regulación hacia Arriba/efectos de los fármacos
18.
Phytother Res ; 31(9): 1449-1456, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28718964

RESUMEN

Ziyuglycoside II, a major bioactive compound of Sanguisorba officinalis L., displays anticancer potential against several human cancer cells. However, little information concerning its antiangiogenic properties and possible mechanisms is available. The aim of this study was to investigate the inhibitory effects of ziyuglycoside II on angiogenesis. Ziyuglycoside II inhibited the proliferation, migration, and tubule formation of human umbilical vein endothelial cells, as well as the number of microvessels growing from the aortic rings. The underlying antiangiogenic mechanism of ziyuglycoside II correlated with blocking vascular endothelial growth factor receptor-2 and the fibroblast growth factor receptor-1 mediated signaling pathway. Moreover, an in vivo Matrigel plug assay in mice showed a significant decrease in vascularization and hemoglobin content in the plugs from ziyuglycoside II-treated mice compared with control mice. Overall, these results suggest that ziyuglycoside II inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects. Copyright © 2017 John Wiley & Sons, Ltd.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Neovascularización Patológica/tratamiento farmacológico , Sanguisorba/química , Saponinas/farmacología , Animales , Aorta/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Técnicas In Vitro , Masculino , Ratones , Ratones Endogámicos C57BL , Ratas Sprague-Dawley , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo
19.
Int J Mol Sci ; 18(6)2017 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-28587261

RESUMEN

To protect from reactive oxygen species (ROS) damages, skin cells have evolved to have antioxidant enzymes, such as copper and zinc-dependent superoxide dismutase (SOD1), mitochondrial manganese-dependent superoxide dismutase (SOD2), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR), and suppressed the expression of matrix metalloproteinases (MMPs) through the mitogen-activated protein kinase (MAPK) signaling pathways, such as c-Jun N-terminal kinase (JNK) and p38. Bioactive compounds analyses were performed using a high-performance liquid chromatography-photodiode array detector (HPLC-PDA) system. The antioxidant activity of Ulmus macrocarpa Hance (UMH) extracts was estimated in vitro. The anti-aging activity of UMH extracts was estimated in vivo using the SKH-1 hairless mice. The UMH extracts reduced the H2O2-induced intracellular ROS production and the cell damages in human dermal fibroblasts (HDFs). Moreover, the H2O2-induced phosphorylation of JNK and p38 was detected in HDF and UMH extracts blocked the phosphorylation. These results suggest that UMH extracts can reduce the expression of MMPs and the reduced MMPs lead to the inhibition of collagen degradation. In addition, oral administration of the UMH extracts decreased the depth, thickness, and length of wrinkles on UVB exposed hairless mice. Therefore, UMH extracts play an advantage of the functional materials in antioxidant and anti-aging of skin.


Asunto(s)
Antioxidantes/farmacología , Activadores de Enzimas/farmacología , Peróxido de Hidrógeno/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Extractos Vegetales/farmacología , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Ulmus/química , Rayos Ultravioleta/efectos adversos , Animales , Catalasa/genética , Catalasa/metabolismo , Muerte Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Humanos , Masculino , Ratones , Especies Reactivas de Oxígeno/metabolismo , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Piel/efectos de la radiación , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo
20.
J Phys Ther Sci ; 29(12): 2157-2159, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29643594

RESUMEN

[Purpose] The purpose of this study is to explore the effect of a VR exercise program on falls and depression in the elderly with mild depression who reside in the local community. [Subjects and Methods] This study was performed by targeting 15 elderly subjects with mild depression who resided in the local community. The targeted subjects voluntarily selected 3 VR exercise programs (each lasting 10 minutes) among 4 activities, and a resting time of 5 minutes was given for an interval after each activity. The VR exercise program was performed for total 12 weeks (36 times), 3 times a week, 45 minutes per session. [Results] After exercise, scores of static balance test (anteroposterior), Falls Efficacy Scale, and the Activities-specific Balance Confidence Scale in the test subjects were improved and depression and internal stress scores were significantly decreased after the intervention. [Conclusion] It can be concluded that the VR exercise program exerts a positive effect not only on the physical factor but also on the mental factor of the elderly subjects with mild depression who reside in the local community. It is expected that based on the VR exercise program, diversified home programs for the elderly should be developed in the future.

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