RESUMO
Here, we describe an approach to correct the genetic defect in fragile X syndrome (FXS) via recruitment of endogenous repair mechanisms. A leading cause of autism spectrum disorders, FXS results from epigenetic silencing of FMR1 due to a congenital trinucleotide (CGG) repeat expansion. By investigating conditions favorable to FMR1 reactivation, we find MEK and BRAF inhibitors that induce a strong repeat contraction and full FMR1 reactivation in cellular models. We trace the mechanism to DNA demethylation and site-specific R-loops, which are necessary and sufficient for repeat contraction. A positive feedback cycle comprising demethylation, de novo FMR1 transcription, and R-loop formation results in the recruitment of endogenous DNA repair mechanisms that then drive excision of the long CGG repeat. Repeat contraction is specific to FMR1 and restores the production of FMRP protein. Our study therefore identifies a potential method of treating FXS in the future.
Assuntos
Síndrome do Cromossomo X Frágil , Expansão das Repetições de Trinucleotídeos , Humanos , Estruturas R-Loop , Metilação de DNA , Síndrome do Cromossomo X Frágil/genética , Epigênese Genética , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismoRESUMO
How Polycomb repressive complex 2 (PRC2) is regulated by RNA remains an unsolved problem. Although PRC2 binds G-tracts with the potential to form RNA G-quadruplexes (rG4s), whether rG4s fold extensively in vivo and whether PRC2 binds folded or unfolded rG4 are unknown. Using the X-inactivation model in mouse embryonic stem cells, here we identify multiple folded rG4s in Xist RNA and demonstrate that PRC2 preferentially binds folded rG4s. High-affinity rG4 binding inhibits PRC2's histone methyltransferase activity, and stabilizing rG4 in vivo antagonizes H3 at lysine 27 (H3K27me3) enrichment on the inactive X chromosome. Surprisingly, mutagenizing the rG4 does not affect PRC2 recruitment but promotes its release and catalytic activation on chromatin. H3K27me3 marks are misplaced, however, and gene silencing is compromised. Xist-PRC2 complexes become entrapped in the S1 chromosome compartment, precluding the required translocation into the S2 compartment. Thus, Xist rG4 folding controls PRC2 activity, H3K27me3 enrichment, and the stepwise regulation of chromosome-wide gene silencing.
Assuntos
Quadruplex G , Histonas , Complexo Repressor Polycomb 2 , RNA Longo não Codificante , Inativação do Cromossomo X , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Camundongos , Complexo Repressor Polycomb 2/metabolismo , Complexo Repressor Polycomb 2/genética , Histonas/metabolismo , Histonas/genética , Células-Tronco Embrionárias Murinas/metabolismo , Cromatina/metabolismo , Cromatina/genética , Cromossomo X/genética , Cromossomo X/metabolismo , Inativação Gênica , Dobramento de RNA , Ligação ProteicaRESUMO
The selenium-binding protein 1 (SELENBP1) has been reported to be up-regulated in the prefrontal cortex (PFC) of schizophrenia patients in postmortem reports. However, no causative link between SELENBP1 and schizophrenia has yet been established. Here, we provide evidence linking the upregulation of SELENBP1 in the PFC of mice with the negative symptoms of schizophrenia. We verified the levels of SELENBP1 transcripts in postmortem PFC brain tissues from patients with schizophrenia and matched healthy controls. We also generated transgenic mice expressing human SELENBP1 (hSELENBP1 Tg) and examined their neuropathological features, intrinsic firing properties of PFC 2/3-layer pyramidal neurons, and frontal cortex (FC) electroencephalographic (EEG) responses to auditory stimuli. Schizophrenia-like behaviors in hSELENBP1 Tg mice and mice expressing Selenbp1 in the FC were assessed. SELENBP1 transcript levels were higher in the brains of patients with schizophrenia than in those of matched healthy controls. The hSELENBP1 Tg mice displayed negative endophenotype behaviors, including heterotopias- and ectopias-like anatomical deformities in upper-layer cortical neurons and social withdrawal, deficits in nesting, and anhedonia-like behavior. Additionally, hSELENBP1 Tg mice exhibited reduced excitabilities of PFC 2/3-layer pyramidal neurons and abnormalities in EEG biomarkers observed in schizophrenia. Furthermore, mice overexpressing Selenbp1 in FC showed deficits in sociability. These results suggest that upregulation of SELENBP1 in the PFC causes asociality, a negative symptom of schizophrenia.
Assuntos
Esquizofrenia , Humanos , Animais , Camundongos , Esquizofrenia/genética , Esquizofrenia/metabolismo , Córtex Pré-Frontal/metabolismo , Células Piramidais/metabolismo , Encéfalo/metabolismo , Camundongos Transgênicos , Proteínas de Ligação a Selênio/genética , Proteínas de Ligação a Selênio/metabolismoRESUMO
PURPOSE: To compare the effects of 2% rebamipide clear solution and 0.1% sodium hyaluronate eye drops in patients with visual display terminal (VDT)-related dry eye disease (DED). DESIGN: Prospective, randomized, double-blinded Study. METHODS: This was a prospective, double-blind, and randomized controlled study. Patients with VDT-related DED were randomly allocated to a 2% rebamipide (REB) group or a 0.1% sodium hyaluronate (HYA) group (4 times/day for 4 weeks). The ocular surface disease index (OSDI), dry eye questionnaire-5 (DEQ-5), Placido disk-tear film analyzer, fluorescein-stained tear break-up time (FBUT), ocular surface staining score, and Schirmer 1 test were examined before and after the instillation of drug. RESULTS: A total of 56 eyes of 28 patients (28 eyes of 14 patients in each group) were included. There were no significant differences in the baseline data. The OSDI, DEQ-5, FBUT, and conjunctival erosion scores improved significantly in both groups after treatment. In the REB group, corneal staining and bulbar nasal redness scores also improved significantly after treatment ( P <0.001 and 0.036, respectively), whereas no significant differences were found in these parameters in the HYA group ( P =0.326 and 0.118, respectively). The REB group showed a significantly larger decrease in the corneal staining score than the HYA group ( P =0.016). No adverse reactions were observed. CONCLUSIONS: A 2% rebamipide clear solution effectively improved the symptoms and signs in patients with VDT-related DED and was superior to 0.1% sodium hyaluronate ophthalmic solution in improving corneal epithelial damage, making it a safe and effective treatment option for VDT-related DED.
Assuntos
Alanina , Terminais de Computador , Síndromes do Olho Seco , Soluções Oftálmicas , Quinolonas , Lágrimas , Humanos , Síndromes do Olho Seco/tratamento farmacológico , Método Duplo-Cego , Estudos Prospectivos , Masculino , Feminino , Quinolonas/administração & dosagem , Quinolonas/uso terapêutico , Pessoa de Meia-Idade , Alanina/análogos & derivados , Alanina/uso terapêutico , Alanina/administração & dosagem , Adulto , Lágrimas/metabolismo , Lágrimas/fisiologia , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/análogos & derivados , Idoso , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the effects of rigid corneal lenses (RCL) in patients with keratoconus, based on eccentricity. METHODS: Eighty-four eyes from 84 patients were included in this retrospective comparative study. Based on the median value of eccentricity difference between the cornea and back surface of the RCL, the patients were divided into groups 1 (<0.08) and 2 (≥0.08). Visual acuity, refractive index, and corneal topography indices were compared before and three months after lens use. RESULTS: Visual acuity, astigmatism, refractive error, corneal curvature, and corneal thickness improved significantly in both groups. Apical power and anterior elevation improved significantly in group 1, with small differences in eccentricity, but not in group 2. Changes in apical power before and after lens use were significantly different between the two groups. CONCLUSION: The RCL was effective for the cornea of keratoconus, especially when the prescription was made with a small difference in eccentricity.
Assuntos
Lentes de Contato , Córnea , Topografia da Córnea , Ceratocone , Refração Ocular , Acuidade Visual , Humanos , Ceratocone/fisiopatologia , Ceratocone/terapia , Estudos Retrospectivos , Acuidade Visual/fisiologia , Feminino , Masculino , Adulto , Refração Ocular/fisiologia , Adulto Jovem , Córnea/patologia , Córnea/fisiopatologia , Adolescente , Astigmatismo/fisiopatologia , Astigmatismo/terapia , Pessoa de Meia-IdadeRESUMO
Mucoceles are cystic formations characterized by the presence of mucus-secreting epithelial cells, which enlarge when the excretory duct becomes obstructed. Posterior ethmoidal mucoceles are rare conditions that can lead to severe ocular complications requiring immediate intervention. The close anatomical proximity of posterior ethmoidal mucoceles to the optic nerve underscores their significance. In this case report, we present a case of rapidly progressing compressive optic neuropathy secondary to a posterior ethmoidal mucocele. A previously healthy forty-six-year-old woman presented with sudden visual loss in her left eye, preceded by left-sided headache and periorbital pain. Clinical examination and imaging studies revealed an oval-shaped mass within the posterior ethmoid cell compressing the left optic nerve. Emergency surgery was performed to alleviate optic nerve compression, which successfully relieved periocular pain. However, the patient's visual acuity and visual field defect remained unchanged postoperatively. Thinning of the ganglion cell layer in the macula region was observed during follow-up examinations. The role of corticosteroids and antibiotics in visual rehabilitation and the impact of delayed surgical decompression on visual outcome remain subjects of debate. Additional cases of mucocele-associated optic neuropathy should be published and analyzed to establish optimal treatment approaches.
Assuntos
Mucocele , Doenças do Nervo Óptico , Doenças dos Seios Paranasais , Humanos , Feminino , Pessoa de Meia-Idade , Mucocele/complicações , Mucocele/diagnóstico , Mucocele/cirurgia , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/etiologia , Doenças do Nervo Óptico/cirurgia , Nervo Óptico , Transtornos da Visão/etiologia , Dor/complicações , Doenças dos Seios Paranasais/complicações , Doenças dos Seios Paranasais/diagnóstico , Doenças dos Seios Paranasais/cirurgiaRESUMO
OBJECTIVE: The proportion of multiple births has risen rapidly worldwide. Multiple births are likely to affect birth weight, which results in low birth weight (LBW) of less than 2500 g, possibly, because multiples are more likely to be born prematurely or less than 37 weeks into pregnancy. Using data from South Korea, this study aims to estimate the contribution of the rise in multiples to the rise in LBW incidence. METHODS: Based on data from 2000 to 2017, we estimated the effect of multiples on LBW rates using linear regression analysis. Based on the regression analysis and the change in the proportion of multiples during this period, we calculated the contribution of the rise in multiples to the rise in LBW incidence using the total differential. In other words, we divided the change in LBW during the period due to the change in multiples by the total change during the period. The data are from the birth registry of the National Statistical Office, which contains information on the 8.4 million live births during the period 2000-2017. RESULTS: We found that a 1 percentage point increase in multiples increases the proportion of LBWs by 0.495 percentage points. In addition, because the changes in the proportion of multiples and LBWs from 2000 to 2017 are 2.2 and 2.4 percentage points, respectively, 1.1 percentage points or 45.8% of the increase in LBWs over the period is due to the increase in multiples. CONCLUSION: Since the Korean government introduced a measure to reduce the number of transferred embryos recently, one may expect that multiples in Korea would reduce in the near future, as it did in other countries. Subsequently, the incidence of LBW children is also likely to reduce, which is desirable in terms of the children's health outcomes.
Assuntos
Recém-Nascido de Baixo Peso , Gravidez Múltipla , Peso ao Nascer , Criança , Feminino , Humanos , Incidência , Recém-Nascido , Prole de Múltiplos Nascimentos , GravidezRESUMO
BACKGROUND: We investigate the performance of new hydrophobic diffractive multifocal intraocular lenses (IOL) with hydroxyethyl methacrylate (HEMA) and compare their optical quality, contrast sensitivity, and subjective photic phenomena. METHODS: Medical records of patients who underwent routine simple cataract surgery and insertion of an existing multifocal IOL (TFNT, TF group) or a new multifocal IOL (CNWT, CN group) were retrospectively reviewed. Clinical data was collected 2 months postoperatively and included optical quality analysis system (OQAS) indices, contrast sensitivity, and subjective degrees of photic phenomena. RESULTS: One hundred thirty-five eyes of 135 patients were included (CN group, 71; TF group, 64). There was no significant difference between the two groups in the visual acuity and defocus curve. The indices of OQAS did not show a significant difference between groups. Contrast sensitivity was significantly better in the CN group at all degrees, including the area under the log contrast sensitivity function (p = 0.01). The subjective photic phenomena survey showed better results for the CN group, with the proportion of patients reporting no photic phenomena as 9.9% and 3.1% in the CN and TF groups, respectively. The proportion of patients who reported severe photic phenomena was 11.3% in the CN group and 25.0% in the TF group. Although the follow-up period was only 2 months, glistening, surface scattering, and posterior capsule opacity were not observed in any patient. CONCLUSIONS: The new multifocal IOL with HEMA is safe, and provides stable visual acuity as well as superior contrast sensitivity and lower subjective photic phenomena, over the prior IOL.
Assuntos
Lentes Intraoculares , Lentes Intraoculares Multifocais , Facoemulsificação , Sensibilidades de Contraste , Humanos , Implante de Lente Intraocular/métodos , Metacrilatos , Estudos Prospectivos , Desenho de Prótese , Pseudofacia , Estudos RetrospectivosRESUMO
RNA-protein interactions drive key cellular pathways such as protein translation, nuclear organization and genome stability maintenance. The human telomeric protein TRF2 binds to the long noncoding RNA TERRA through independent domains, including its N-terminal B domain. We previously demonstrated that TRF2 B domain binding to TERRA supports invasion of TERRA into telomeric double stranded DNA, leading to the formation of telomeric RNA:DNA hybrids. The other telomeric protein TRF1, which also binds to TERRA, suppresses this TRF2-associated activity by preventing TERRA-B domain interactions. Herein, we show that the binding of both TRF1 and TRF2 to TERRA depends on the ability of the latter to form G-quadruplex structures. Moreover, a cluster of arginines within the B domain is largely responsible for its binding to TERRA. On the other side, a patch of glutamates within the N-terminal A domain of TRF1 mainly accounts for the inhibition of TERRA-B domain complex formation. Finally, mouse TRF2 B domain binds to TERRA, similarly to its human counterpart, while mouse TRF1 A domain lacks the inhibitory activity. Our data shed further light on the complex crosstalk between telomeric proteins and RNAs and suggest a lack of functional conservation in mouse.
Assuntos
RNA Longo não Codificante , Proteína 1 de Ligação a Repetições Teloméricas , Proteína 2 de Ligação a Repetições Teloméricas , Animais , DNA/química , Glutamatos , Humanos , Camundongos , RNA Longo não Codificante/genética , Telômero/genética , Telômero/metabolismo , Proteína 1 de Ligação a Repetições Teloméricas/química , Proteína 1 de Ligação a Repetições Teloméricas/genética , Proteína 1 de Ligação a Repetições Teloméricas/metabolismo , Proteína 2 de Ligação a Repetições Teloméricas/genéticaRESUMO
BACKGROUND: A larger optical zone for photorefractive keratectomy may improve optical quality and stability. However, there is need for limiting ablation diameter in that a larger ablation diameter requires greater ablation depth, and minimizing ablation depth may reduce adverse effects on postoperative wound healing, haze and keratoectasia. In this study, we compared the changes in clinical outcomes and the degree of regression between a 6.0 mm optical zone and 6.5 mm optical zone following PRK. METHODS: The records of 95 eyes that had undergone PRK with a 6.0 OZ (n = 40) and a 6.5 OZ (n = 55) were retrospectively reviewed. We compared data including the spherical equivalent of manifest refraction (SE of MR), simulated K (Sim K), thinnest corneal thickness, change in thinnest corneal thickness (the initial value divided by corrected diopter [ΔTCT/CD]), Q value, corneal higher order aberrations (HOAs) and spherical aberration (SA) pre-operation, at 3 and 6 months postoperative and at the last follow-up visit (Mean; 20.71 ± 10.52, 17.47 ± 6.57 months in the 6.0 and 6.5 OZ group, respectively). RESULTS: There were no significant differences in the SE of MR, Sim K and UDVA between the 6.0 OZ group and the 6.5 OZ group over 1 year of follow-up after PRK, and the 6.0 OZ group required less ΔTCT/CD than the 6.5 OZ group. The 6.5 OZ group showed better results in terms of post-operative HOAs of RMS, SA and Q value. When comparing that pattern of change in Sim K, there was no significant difference between the 6.0 OZ group and the 6.5 OZ group. CONCLUSIONS: The clinical refractive outcomes and regression after PRK using Mel 90 excimer laser with a 6.0 OZ were comparable to those with a 6.5 OZ.
Assuntos
Miopia , Ceratectomia Fotorrefrativa , Córnea/cirurgia , Humanos , Lasers de Excimer/uso terapêutico , Miopia/cirurgia , Refração Ocular , Estudos Retrospectivos , Acuidade VisualRESUMO
BACKGROUND: To report a case of lenticular infection caused by Aspergillus, which was diagnosed 13 weeks after traumatic corneal laceration. CASE PRESENTATION: A 60-year-old woman presented with traumatic corneal laceration including anterior lens capsule rupture and traumatic cataract after being hit with a chestnut in the right eye. There were multiple injuries due to tiny thorns of the chestnut, including the conjunctiva, sclera, cornea, and anterior lens capsule. But no visible foreign body was detected by slit-lamp examination. Topical corticosteroid was prescribed to resolve the conjunctival inflammation induced by the thorns of chestnut, which could have caused persistent irritation. As conjunctival injection and edema being decreased during outpatient clinical follow-up, embedded conjunctival foreign body was detected and surgically removed (1st surgery). Approximately 10 weeks after the trauma, severe inflammation of the anterior segment accompanied with hypopyon developed suddenly and at the same time embedded scleral foreign body was revealed. After removal of scleral foreign body (2nd surgery), unspecified mold species was cultured from the scleral foreign body in SDA (Sabouraud dextrose agar) plate. Suspicious corneal foreign body was removed as 3rd surgery and phacoemulsification of traumatic cataract was planned as 4th surgery. Aspergillus was finally detected from removed anterior capsule and fibrotic membrane during the operation. Fungal infection resolved successfully after administration of topical (1% voriconazole and 5% natamycin) and systemic (fluconazole) antifungal agents and phacoemulsification of traumatic cataract. CONCLUSION: Chestnut thorns can damage multiple ocular tissues simultaneously. Lens capsular rupture could result in fungal inoculation and lead to delayed lenticular fungal infection with complicated cataract formation. In cases of ocular trauma due to organic substances such as thorns and branches, the possibility of fungal infection should be considered.
Assuntos
Aspergilose/microbiologia , Lesões da Córnea/etiologia , Infecções Oculares Fúngicas/microbiologia , Ferimentos Oculares Penetrantes/etiologia , Lacerações/etiologia , Doenças do Cristalino/microbiologia , Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/terapia , Corpos Estranhos no Olho/diagnóstico , Corpos Estranhos no Olho/etiologia , Corpos Estranhos no Olho/cirurgia , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/terapia , Feminino , Humanos , Pressão Intraocular , Doenças do Cristalino/diagnóstico , Doenças do Cristalino/terapia , Implante de Lente Intraocular , Microscopia Acústica , Pessoa de Meia-Idade , Facoemulsificação , Microscopia com Lâmpada de Fenda , Acuidade VisualRESUMO
BACKGROUND: To report a case of enucleation caused by Streptococcus dysgalactiae endophthalmitis after traumatic corneal laceration. CASE PRESENTATION: A 69-year-old man with history of retinal detachment treated with vitrectomy and subsequent cataract surgery presented with traumatic corneal laceration while cutting grass. Appropriate repair of corneal laceration and intravitreal antibiotics (vancomycin, ceftazidime) injection was performed. S. dysgalactiae which was sensitive to the conventional antibiotics (Ampicillin, Ceftriaxone, Levofloxacin, etc.) detected by aqueous culture. One day following primary closure, the patient developed a complete hypopyon and vitreous membranes. Despite vigorous systemic and intravitreal antibiotics administration with vitrectomy, endophthalmitis was not controlled and patient's ocular pain was increased. The vitreous culture was also positive for S. dysgalactiae. Finally, total enucleation was performed 9 days after trauma due to fulminant endophthalmitis with severe scleritis. CONCLUSION: Progression of traumatic endophthalmitis associated with S. dysgalactiae can be fulminant. Sufficient warning to patient about enucleation and intensive care is needed in the case of this infection.
Assuntos
Lesões da Córnea/complicações , Endoftalmite/etiologia , Infecções Oculares Bacterianas/etiologia , Lacerações/complicações , Infecções Estreptocócicas/etiologia , Streptococcus/isolamento & purificação , Acuidade Visual , Doença Aguda , Idoso , Antibacterianos/uso terapêutico , Lesões da Córnea/diagnóstico , Endoftalmite/diagnóstico , Endoftalmite/terapia , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/terapia , Humanos , Lacerações/diagnóstico , Masculino , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/terapia , Ultrassonografia , VitrectomiaRESUMO
In this study, composite devices were fabricated using ferromagnetic FeSiB-based alloys (Metglas) and ferroelectric ceramics, and their magnetic field sensitivity was evaluated. Sintered 0.95Pb(Zr0.52Ti0.48)O3-0.05Pb(Mn1/3Sb2/3)O3 (PZT-PMS) ceramic exhibited a very dense microstructure with a large piezoelectric voltage coefficient (g31 = -16.8 × 10-3 VmN-1) and mechanical quality factor (Qm > 1600). Owing to these excellent electromechanical properties of the PZT-PMS, the laminate composite with a Metglas/PZT-PMS/Metglas sandwich structure exhibited large magnetoelectric voltage coefficients (αME) in both off-resonance and resonance modes. When the length-to-width aspect ratio (l/w) of the composite was controlled, αME slightly varied in the off-resonance mode, resulting in similar sensitivity values ranging from 129.9 to 146.81 VT-1. Whereas in the resonance mode, the composite with small l/w exhibited a large reduction of αME and sensitivity values. When controlling the thickness of the PZT-PMS (t), the αME of the composite showed the largest value when t was the smallest in the off-resonance mode, while αME was the largest when t is the largest in the resonance mode. The control of t slightly affected the sensitivity in the off-resonance mode, however, higher sensitivity was obtained as t increased in the resonance mode. The results demonstrate that the sensitivity, varying with the dimensional control of the composite, is related to the mechanical loss of the sensor. The composite sensor with the PZT-PMS layer exhibited excellent magnetic field sensitivity of 1.49 × 105 VT-1 with a sub-nT sensing limit, indicating its potential for application in high-performance magnetoelectric sensor devices.
RESUMO
BACKGROUND: Leukemia inhibitory factor, a novel myokine, is known to be associated with neural function, but the underlying molecular mechanism remains unclear. METHODS: HT-22 mouse hippocampal cells, primary hippocampal cells, and Drosophila Alzheimer's disease model were used to determine the effect of leukemia inhibitory factor on neurons. Immunoblot analysis and immunofluorescence method were used to analyze biological mechanism. RESULTS: Leukemia inhibitory factor increased Akt phosphorylation in a phosphoinositide-3-kinase-dependent manner in hippocampal cells. Leukemia inhibitory factor also increased the phosphorylation of the mammalian target of rapamycin and the downstream S6K. Leukemia inhibitory factor stimulated the phosphorylation of signal transducer and activator of transcription via extracellular signal-regulated kinases. Leukemia inhibitory factor increased c-fos expression through both Akt and extracellular signal-regulated kinases. Leukemia inhibitory factor blocked amyloid ß-induced neural viability suppression and inhibited amyloid ß-induced glucose uptake impairment through the block of amyloid ß-mediated insulin receptor downregulation. Leukemia inhibitory factor blocked amyloid ß-mediated induction of the autophagy marker, microtubule-associated protein 1A/1B-light chain 3. Additionally, in primary prepared hippocampal cells, leukemia inhibitory factor stimulated Akt and extracellular signal-regulated kinase, demonstrating that leukemia inhibitory factor has physiological relevance in vivo. Suppression of the autophagy marker, light chain 3II, by leukemia inhibitory factor was observed in a Drosophila model of Alzheimer's disease. CONCLUSIONS: These results demonstrate that leukemia inhibitory factor protects against amyloid ß-induced neurotoxicity via Akt/extracellular signal-regulated kinase-mediated c-fos induction, and thus suggest that leukemia inhibitory factor is a potential drug for Alzheimer's disease.
Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Autofagia/efeitos dos fármacos , Hipocampo/citologia , Fator Inibidor de Leucemia/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/toxicidade , Animais , Animais Geneticamente Modificados , Células Cultivadas , Drosophila , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 3/biossíntese , Hipocampo/metabolismo , Fator Inibidor de Leucemia/biossíntese , Masculino , Camundongos , Proteínas Associadas aos Microtúbulos/biossíntese , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-fos/biossíntese , Receptor de Insulina/biossíntese , Receptor de Insulina/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
Various commercial vaccines are used for immunization against hepatitis B. However, these immunotherapeutic vaccines require invasive administration, which can induce side effects, and require multiple shots to elicit an immune response, limiting their efficacy. Compared to traditional hepatitis B vaccines, polymer nanoparticles have more advantageous inherent properties as vaccine delivery carriers, providing increased stability of encapsulated antigen, the possibility of single-shot immunotherapy, and the capability of mucosal administration, which allows various routes of vaccination. In this review, we present up-to-date information on the potential of a biodegradable nanoparticle-based delivery system in treating hepatitis B. We also discuss the application of nanoparticles in various vaccines and highlighted strategies for eliciting an appropriate immune response.
Assuntos
Sistemas de Liberação de Medicamentos , Vacinas contra Hepatite B/administração & dosagem , Nanopartículas , Polímeros , Humanos , VacinaçãoRESUMO
The aim of this study was to determine the correlation between muscle thickness (MT) and cycling power in varsity cyclists using ultrasonography (US) and to identify any differences in MT between short- and long-distance cyclists. Twelve cyclists participated in this study. Real-time two-dimensional B-mode US was used to measure the MT in the anterior thigh, anterior lower leg, and trunk, especially in the abdominal and lumbar regions. A cycle ergometer was used to measure cycling power parameters such as maximum anaerobic power (over 5 s), mean anaerobic power (over 30 s), and aerobic power (over 3 min). This study was approved by the Ethics Committee of Korea National Sports University. There was a significant relationship between the MT and cycling power for the rectus femoris (RF) and vastus lateralis (VL) in the thigh, the rectus abdominis (RA) in the abdominal region, and the erector spinae (ES) in the lower back. The MT values of the RF, VL, and ES were strongly associated with the maximum and mean anaerobic power. There were significant differences between short- and long-distance cyclists in the MT of the RF in the thigh, the RA, the external abdominal oblique, the internal abdominal oblique, and the transverse abdominis muscle in the abdomen. We suggest that training programs attempting to improve cycling performance focus on improving the VL and ES via resistance weight or cycle training and also the core muscles for short-distance cyclists. Clin. Anat. 31:899-906, 2018. © 2018 Wiley Periodicals, Inc.
Assuntos
Músculos Abdominais/fisiologia , Ciclismo/fisiologia , Músculo Quadríceps/fisiologia , Reto do Abdome/fisiologia , Músculos Abdominais/anatomia & histologia , Músculos Abdominais/diagnóstico por imagem , Adulto , Desempenho Atlético/fisiologia , Humanos , Masculino , Tamanho do Órgão , Músculo Quadríceps/anatomia & histologia , Músculo Quadríceps/diagnóstico por imagem , Reto do Abdome/anatomia & histologia , Reto do Abdome/diagnóstico por imagem , Ultrassonografia , Adulto JovemRESUMO
BACKGROUND: Along with advances in thread lift techniques and materials, ancillary procedures such as fat grafting, liposuction, or filler injections have been performed simultaneously. Some surgeons think that these ancillary procedures might affect the aesthetic outcomes of thread lifting possibly due to inadvertent injury to threads or loosening of soft tissue via passing the cannula in the surgical plane of the thread lifts. The purpose of the current study is to determine the effect of such ancillary procedures on the outcome of thread lifts in the human and cadaveric setting. METHODS: We used human abdominal tissue after abdominoplasty and cadaveric faces. In the abdominal tissue, liposuction parallel to the parallel axis was performed in one area for 5 min. We counted 30 passes when liposuction was performed in one direction. This was repeated as we changed the direction of passages. The plane of thread lifts (dermal vs subcutaneous) and angle between liposuction and thread lifts (parallel vs perpendicular) were differentiated in this abdominal tissue study group. Then, we performed parallel or perpendicular thread lifts using a small slit incision. Using a tensiometer, the maximum holding strength was measured when pulling the thread out of the skin as much as possible. We also used faces of cadavers to prove whether the finding in human abdominal tissue is really valid with corresponding techniques. RESULTS: Our pilot study using abdominal tissue showed that liposuction after thread lifts adversely affects it regardless of the vector of thread lifts. In the cadaveric study, however, liposuction prior to thread lifting does not significantly affect the holding strength of thread lifts. CONCLUSIONS: Liposuction or fat grafting in the appropriate layer would not be a hurdle to safely performing simultaneous thread lifts if the target lift tissue is intra-SMAS or just above the SMAS layer. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Assuntos
Lipectomia , Suturas , Abdominoplastia/métodos , Cadáver , Humanos , Ritidoplastia/métodos , Fatores de Tempo , Resultado do TratamentoRESUMO
Concentrations were measured three times from 2006 to 2013 at major harbors and marine areas along the Korean coast. The Cu concentration in seawater and sediments increased, while the Zn concentration first decreased and then increased. The pattern of increase in Cu concentration with time was consistent with the increased total tonnage of ships moored at the sampling area and with the increased discharge of organic antifouling agents. To confirm the relationship between seawater and marine sediments in heavy metal pollution, all data were arrayed and compared depending on concentrations. The results revealed that the slope of Cu between seawater and marine sediment rapidly decreased, attributed to the increase in the application of copper-based antifouling agents to vessels after the ban on the use of tributyltin in 2008, rather than the contamination caused by industrial areas.
Assuntos
Cobre/análise , Monitoramento Ambiental/métodos , Sedimentos Geológicos/análise , Zinco/análise , Poluição Ambiental/análise , Metais Pesados/análise , Água do Mar/análise , Navios , Poluentes Químicos da Água/análiseRESUMO
Since the ban of tri-butyl tin, other various alternative antifouling agents have been used. In this study, the contamination levels from these antifouling agents were examined in the main harbors in Korea. The sampled harbors were classified into four types and the levels of contamination from the antifouling agents were analyzed. The highest degree of contamination was found in the big harbors, followed by the fishing harbors, harbors near agricultural areas, and military and coast guard harbors. In addition, an increase in the number of ships that entered the ports significantly influenced the contamination by the antifouling agents. Correlation analysis was conducted to characterize the alternative antifouling agents. The results revealed strong correlations between the dichlofluanid and chlorothalonil, and between the chlorothalonil and TCMTB, because unlike Irgarol 1051 and SEA-NINE 211, which are used only as antifouling agents, chlorothalonil, dichlofluanid, and TCMTB are also used in agriculture.
Assuntos
Desinfetantes/química , Fungicidas Industriais/química , Praguicidas/química , Água do Mar/química , Poluentes Químicos da Água/química , Monitoramento Ambiental/métodos , República da Coreia , NaviosRESUMO
[Purpose] This study was conducted to investigate the effects of ankle control balance training (ACBT) on postural balance and gait ability in community-dwelling older adults. [Subjects and Methods] Fifty-four subjects were randomly divided into two groups, with 27 subjects in the ACBT group and 27 subjects in the control group. Subjects in the ACBT group received ACBT for 60 minutes, twice per week for 4 weeks, and all subjects had undergone fall prevention education for 60 minutes, once per week for 4 weeks. The main outcome measures, including the Berg balance scale; the functional reach test and one leg stance test for postural balance; and the timed up-and-go test and 10-meter walking test for gait ability, were assessed at baseline and after 4 weeks of training. [Results] The postural balance and gait ability in the ACBT group improved significantly compared to those in the control group, except BBS. [Conclusion] The results of this study showed improved postural balance and gait abilities after ACBT and that ACBT is a feasible method for improving postural balance and gait ability in community-dwelling older adults.