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PURPOSE: High myopia can lead to blindness. Genipin is a collagen cross-linking agent that may be used to treat myopia. However, the mechanism of action of genipin for the treatment of myopia is unclear. This study investigated the effect of genipin on the scleral expression of the miR-29 cluster, matrix metalloproteinase 2 (MMP2), and collagen alpha1 chain of type I (COL1A1) in a guinea pig model of myopia. METHODS: The model of myopia was established by treating guinea pigs with a - 8D lens on both eyes for 21 days, and eyes with a refractive error of - 6D or greater were included. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to examine the mRNA and protein expression, respectively. A dual-luciferase assay was used to determine the direct targeting of the miR-29 cluster on the 3'-untranslated region (UTR) of the COL1A1 gene. RESULTS: The scleral expression of miR-29a, miR-29b, and miR-29c as well as MMP2 was significantly increased, and the scleral expression of COL1A1 was significantly decreased in the myopia group. Genipin treatment reversed these effects in myopic eyes. The dual-luciferase assay showed that the luciferase activities were significantly decreased in human embryonic kidney (HEK) cells transfected with miR-29a and miR-29b, but not miR-29c, compared with those transfected with control miRNAs. CONCLUSIONS: Genipin inhibits the scleral expression of the miR-29 cluster and MMP2 and promotes COL1A1 expression in a guinea pig model of myopia. Thus, genipin may promote COL1A1 expression by reducing the expression of the miR-29 cluster.
Assuntos
Colágeno Tipo I/genética , Regulação da Expressão Gênica/fisiologia , Iridoides/farmacologia , Metaloproteinase 2 da Matriz/genética , MicroRNAs/genética , Miopia/genética , Esclera/efeitos dos fármacos , Animais , Western Blotting , Células Cultivadas , Colagogos e Coleréticos/farmacologia , Cadeia alfa 1 do Colágeno Tipo I , Modelos Animais de Doenças , Feminino , Cobaias , Células HEK293 , Humanos , Masculino , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Esclera/metabolismoRESUMO
AIM: To investigate the effects of spectral composition and light intensity on natural refractive development in guinea pigs. METHODS: A total of 124 pigmented guinea pigs (2-week-old) were randomly assigned to three groups at high (Hi; 4000 lx), medium (Me; 400 lx) and low (Lo; 50 lx) light intensities under a 12:12 light/dark cycle for 6wk. Each group was subdivided into subgroups with the following spectra: broad spectrum Solux halogen light (BS), 600 nm above-filtered continuous spectrum (600F), 530 nm above-filtered continuous spectrum (530F), and 480 nm above-filtered continuous spectrum (480F; HiBS: n=10, Hi600F: n=10, Hi530F: n=10, Hi480F: n=10, MeBS: n=10, Me600F: n=10, Me530F: n=10, Me480F: n=10, LoBS: n=11, Lo600F: n=12, Lo530F: n=10, Lo480F: n=11). Refractive error, corneal curvature radius, and axial dimensions were determined by cycloplegic retinoscopy, photokeratometry, and A-scan ultrasonography before and after 2, 4, and 6wk of treatment. Average changes from both eyes in the ocular parameters and refractive error were compared among different subgroups. RESULTS: After 6wk of exposure, high-intensity lighting enhanced hyperopic shift; medium- and low-intensity lighting enhanced myopic shift (P<0.05). Under the same spectrum, axial increase was larger in the low light intensity group than in the medium and high light intensity groups (HiBS: 0.65±0.02 mm, MeBS: 0.67±0.01 mm, LoBS: 0.82±0.02 mm; Hi600F: 0.64±0.02 mm, Me600F: 0.67±0.01 mm, Lo600F: 0.81±0.01 mm; Hi530F: 0.64±0.02 mm, Me530F: 0.67±0.01 mm, Lo530F: 0.73±0.02 mm; Hi480F: 0.64±0.01 mm, Me480F: 0.66±0.01 mm, Lo480F: 0.72±0.02 mm; P<0.05). Under 400 lx, there was a faster axial increase in the MeBS group than in the Me480F group (P<0.05). Under 50 lx, axial length changes were significantly larger in LoBS and Lo600F than in Lo530F and Lo480F (P<0.01). CONCLUSION: Under high-intensity lighting, high light intensity rather than spectrum distributions that inhibits axial increase. Under medium- and low-intensity lighting, filtering out the long wavelength inhibits axial growth in juvenile guinea pigs.
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The electronic structures, formation energy and optical properties of Cu-doped, C-doped, and (Cu, C)-codoped TiO2 were investigated by the projector augmented wave (PAW) method within GGA + U approximation. The results show that the lattice distortion of the Cu@i1&C@i2 system is the largest in all doping systems. The optical absorption edges of the C@i system and the Cu@i1&C@i2 system appear a blue-shift, which is attributed to the band gap expansion and some deep states generation. The Cu@i system exhibits a reduction in band gap and a generation of the hole state, such as it emerges the highest optical absorption in all doping systems.
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Cobre/química , Titânio/química , Eletrônica/métodos , Elétrons , Modelos Teóricos , Teoria QuânticaRESUMO
The Sb2O4:Yb3+, Tm3+ up-conversion luminescence powder with excellent physical, chemical stability and relative low phonon energy was synthesized by the high temperature solid-state reaction and its up-conversion luminescence property was investigated. Under the 980 nm excitation, infrared and blue up-conversion emissions centered at 800 and 480 nm were observed, which were assigned to the 1G4-->3H6 and 3H4-->3 He transitions of Tm2+, respectively. The influence of Yb3+ and Tm3+ concentration on the up-conversion emission property was also obtained. The up-conversion luminescence increases with increasing of Yb3+ and Tm3+ concentration. Additionally, the up-conversion luminescence mechanism was discussed based on the dependence of Tm3+ up-conversion luminescence on pump power. It is interesting that two photon excitation processes for blue and infrared emission were observed in the Sb2O04: Yb3+, Tm3+ powder under a 980 nm excitation. Based on the energy level diagram of Tma3 and Yb2+ ions, we think that two photons blue emission is contributed to the cooperation energy transfer between Tm"+ and Yb3+ ions. We believe that the Sbz04 : Yb3 , Tm2+ up-conversion luminescence powder will have potential application for new optical devices in up-conversion color displays, sensors, detection of infrared radiation, and lasers.
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The title complex, [Co2(C8H5NO4S)2(C10H8N2)3(H2O)2]·1.3H2O, was synthesized under hydro-thermal conditions. The Co(II) ion is six-coordinated in a slightly distorted octa-hedral environment resulting from two carboxyl-ate O atoms of two 2-carb-oxy-methyl-sulfanyl nicotinate (2-CMSN(2-)) anions, one water mol-ecule and three N atoms of three 4,4'-bi-pyridine ligands, with one 4,4'-bi-pyridine ligand situated on a centre of inversion. Two neighboring Co(II) ions are linked by two anions, giving a dinuclear [Co2(2-CMSN)2] subunit with a Coâ¯Co separation of 6.8600â (3)â Å. The dinuclear subunits are joined by bridging 4,4'-bi-pyridine linkers, generating a three-dimensional network structure. Disordered water mol-ecules are situated in the free space of this network. O-Hâ¯O hydrogen bonding within and between the subunits enhances the stability of the structure.
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It has been confirmed that gabapentin (GBP) induced a inhibition of the voltage-gated persistent sodium current in chronically compressed dorsal root ganglion (DRG) neurons. The persistent sodium current is found in excitable DRG neurons of painful diabetic neuropathy (PDN) rats where it is mediated by tetrodotoxin (TTX) sensitive sodium channels. Recently, many groups have used models of neurological disorder to explore the mechanism of GBP in neuropathic pain. There is no evidence, however, to explain the particular mechanism of GBP, including its analgesic actions in PDN rats. These issues were addressed in the present study. Using behavioral testing, we found that diabetes leads to mechanical allodynia and thermal hyperalgesia and these effects were reversed by a continuous GBP injection. To investigate the mechanism of GBP's reduction in neural excitability, we systematically analyzed the expression of Nav1.7 and p-ERK1/2 and tested the effect of GBP on these proteins. Diabetes significantly increased the excitability of DRG neurons and the expression of Nav1.7 and p-ERK1/2, and GBP significantly inhibited these changes. These results suggest that the inhibitory effect of GBP on the expression of Nav1.7 and p-ERK1/2 might be one of the analgesic mechanisms of action of GBP. This may partially explain the antinociceptive action of GBP in the PDN rats.
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Aminas/farmacologia , Analgésicos/farmacologia , Ácidos Cicloexanocarboxílicos/farmacologia , Neuropatias Diabéticas/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo , Ácido gama-Aminobutírico/farmacologia , Animais , Modelos Animais de Doenças , Gabapentina , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Nociceptores/efeitos dos fármacos , Nociceptores/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the effect and mechanism of Gualou Xiebai (GLXB) decoction on pulmonary fibrosis. METHOD: Pulmonary fibrosis was induced by bleomycin A5 in SD rats. Rats in treatment group were killed after being treated by GLXB by decoction daily for 28 days. The lungs of all rats were harvested for histopathological studies. The contents of platelet-derived growth factor BB (PDGF-BB) in lungs were measured and compared. RESULT: The contents of PDGF-BB in lungs have increased significantly in model group compared with normal group and treatment group (P<0.05). CONCLUSION: GLXB decoction could significantly alleviate the increased PDGF-BB expression in lungs of pulmonary fibrosis rats.