RESUMEN
High levels of consumption of saturated lipids have been largely associated with the increasing prevalence of metabolic diseases. In particular, saturated fatty acids such as palmitic acid (PA) have been implicated in the development of insulin resistance (IR). Scutellarin (Scu) is one of the effective traditional Chinese medicines considered beneficial for liver diseases and diabetes. In this study, we investigated the effect of Scu on IR and lipid metabolism disorders in vitro and in high fat diet (HFD)-fed mice. In vitro, we found that Scu decreased insulin-dependent lipid accumulation and the mRNA expression of CD36, Fasn, and ACC in PA-treated HepG2 cells. Additionally, Scu upregulated Akt phosphorylation and improved the insulin signalling pathway. Moreover, Scu downregulated mammalian target of rapamycin (mTOR) phosphorylation and the n-SREBP-1c protein level and also reduced lipid accumulation via the mTOR-dependent pathway, as confirmed by the molecular docking of Scu to mTOR. In HFD-fed C57BL/6 mice, Scu improved oral glucose tolerance, pyruvate tolerance and the IR index and also increased the Akt phosphorylation level. Moreover, Scu reduced hepatocyte steatosis, decreased lipid accumulation and triglyceride levels, inhibited mTOR phosphorylation, and decreased the SREBP-1c level in the liver. Taken together, these findings suggest that Scu ameliorates hepatic IR by regulating hepatocyte lipid metabolism via the mTOR-dependent pathway through SREBP-1c suppression.
Asunto(s)
Apigenina/uso terapéutico , Glucuronatos/uso terapéutico , Hepatocitos/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Simulación del Acoplamiento Molecular/métodos , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Serina-Treonina Quinasas TOR/efectos de los fármacos , Animales , Apigenina/farmacología , Técnicas de Cultivo de Célula , Glucuronatos/farmacología , Humanos , Masculino , RatonesRESUMEN
PURPOSE: To compare the orbital cerebral spinal fluid pressure (CSFP) and trans-lamina cribrosa pressure difference (TLCPD) determined noninvasively in ocular hypertensive (OH) subjects and controls. METHODS: Cross-sectional observational study. Magnetic resonance imaging was used to measure orbital subarachnoid space width (OSASW). The CSFP (mm Hg) was estimated from a published formula as 17.54 × MRI derived OSASW at 15 mm behind the globe + 0.47 × body mass index + 0.13 × mean arterial blood pressure -21.52. Estimated TLCPD was calculated as IOP- CSFP. RESULTS: The orbital subarachnoid space width was significantly wider (p = 0.01) in the OH group than in the control group at all three measurement locations. The MRI derived CSFP value in OH (14.9 ± 2.9 mm Hg) was significantly higher than in the normal group (12.0 ± 2.8 mm Hg; p < 0.01). The estimated TLCPD value in OH (9.0 ± 4.2 mm Hg) was significantly higher than in controls (3.6 ± 3.0 mm Hg; p < 0.01). CONCLUSION: The wider OSASW and higher estimated CSFP in OH subjects suggest a higher orbital CSFP. Despite a higher orbital CSFP that could be protective, the higher TLCPD in OH may play a significant role in the risk of developing glaucoma.
Asunto(s)
Presión del Líquido Cefalorraquídeo/fisiología , Presión Intraocular/fisiología , Hipertensión Ocular/fisiopatología , Adulto , Presión Sanguínea/fisiología , Estudios Transversales , Femenino , Gonioscopía , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Hipertensión Ocular/diagnóstico , Disco Óptico/diagnóstico por imagen , Disco Óptico/patología , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/patología , Órbita/diagnóstico por imagen , Órbita/patología , Espacio Subaracnoideo/diagnóstico por imagen , Tomografía de Coherencia Óptica , Tonometría Ocular , Agudeza Visual/fisiología , Pruebas del Campo VisualRESUMEN
PURPOSE: Oxidative stress-induced damage to RPE cells has been suggested to be an important factor in the pathogenesis of age-related macular degeneration. Taxifolin, a flavonol, has been shown to exhibit significant antioxidant properties. The purpose of this study was to investigate the potential protective effects of taxifolin on RPE cells cultured under oxidative stress conditions and to elucidate the underlying mechanisms. METHODS: Human RPE (ARPE-19) cells were treated with different concentrations of taxifolin and 0.4 mM of H2O2 for 24 h. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was quantitatively measured by annexin V/propidium iodide double staining, and the expression levels of poly (ADP-ribose) polymerase (PARP) were evaluated by western blotting. Reactive oxygen species (ROS) were measured using a commercially available ROS detection system. The expressions of phase II enzymes, including NAD(P)H quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase modifier (GCLM) and catalytic (GCLC) subunits, were examined using real-time PCR and western blotting. The nuclear localization of the nuclear factor (erythroid-derived 2)-like 2 (NRF2) protein was detected by western blotting. Results: Taxifolin clearly inhibited the decrease in H2O2-induced cell viability, cell apoptosis, and intracellular ROS generation. In addition, taxifolin inhibited the H2O2-induced PARP cleavage. Moreover, treatment with taxifolin activated mRNA and the protein expression of NRF2 by inducing the translocation of NRF2 to the nucleus. Consequently, the mRNA and protein levels of the phase II enzymes NQO1, HO-1, GCLM, and GCLC increased. Conclusions: Taxifolin was shown to protect RPE cells against oxidative stress-induced apoptosis. The potential mechanism appears to involve the activation of NRF2 and the phase II antioxidant enzyme system.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Quercetina/análogos & derivados , Epitelio Pigmentado de la Retina/efectos de los fármacos , Anexina A5/metabolismo , Western Blotting , Recuento de Células , Línea Celular , Supervivencia Celular , Colorantes/metabolismo , Citoprotección/efectos de los fármacos , Humanos , Peróxido de Hidrógeno/toxicidad , Factor 2 Relacionado con NF-E2/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Propidio/metabolismo , Quercetina/farmacología , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/patologíaRESUMEN
INTRODUCTION: The orbital subarachnoid space surrounding the optic nerve is continuous with the circulation system for cerebrospinal fluid (CSF) and can be visualized by using magnetic resonance imaging (MRI). We hypothesized that the orbital subarachnoid space width (OSASW) is correlated with and can serve as a surrogate for intracranial pressure (ICP). Our aim was to develop a method for a noninvasive measurement of the intracranial CSF-pressure (CSF-P) based on MRI-assisted OSASW. METHODS: The prospective observational comparative study included neurology patients who underwent lumbar CSF-P measurement and 3.0-Tesla orbital magnetic resonance imaging (MRI) for other clinical reasons. The width of the orbital subarachnoid space (OSASW) around the optic nerve was measured with MRI at 3, 9, and 15 mm behind the globe. The study population was randomly divided into a training group and a test group. After adjusting for body mass index (BMI) and mean arterial blood pressure (MABP), algorithms for the associations between CSF-P and OSASW were calculated in the training group. The algorithms were subsequently verified in the test group. Main outcome measures were the width of the orbital subarachnoid space (OSASW) and the lumbar cerebrospinal fluid pressure (CSF-P). RESULTS: Seventy-two patients were included in the study. In the training group, the algorithms for the associations between CSF-P and OSASW were as follows: (a) CSF-P = 9.31 × OSASW (at 3 mm) + 0.48 × BMI + 0.14 × MABP-19.94; (b) CSF-P = 16.95 × OSASW (at 9 mm) + 0.39 × BMI + 0.14 × MABP-20.90; and (c) CSF-P = 17.54 × OSASW (at 15 mm) + 0.47 × BMI + 0.13 × MABP-21.52. Applying these algorithms in the independent test group, the measured lumbar CSF-P (13.6 ± 5.1 mm Hg) did not differ significantly from the calculated MRI-derived CSF-P (OSASW at 3 mm: 12.7 ± 4.2 mm Hg (P = 0.07); at 9 mm: 13.4 ± 5.1 mm Hg (P = 0.35); and at 15 mm: 14.0 ± 4.9 mm Hg (P = 0.87)). Intraclass correlation coefficients (ICCs) were higher for the CSF-P assessment based on OSASW at 9 mm and at 15 mm behind the globe (all ICCs, 0.87) than for OSASW measurements at 3 mm (ICC, 0.80). CONCLUSIONS: In patients with normal, moderately decreased or elevated ICP, MRI-assisted measurement of the OSASW appears to be useful for the noninvasive quantitative estimation of ICP, if BMI and MABP as contributing parameters are taken into account. TRIAL REGISTRATION: Clinical trial registered with the Chinese Clinical Trial Registry: ChiCTR-OCC-11001271.
Asunto(s)
Presión Intracraneal/fisiología , Presión Intraocular/fisiología , Imagen por Resonancia Magnética/métodos , Espacio Subaracnoideo/fisiología , Adulto , Anciano , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Punción Espinal/efectos adversos , Espacio Subaracnoideo/patología , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the treatment outcomes of idiopathic optic neuritis with no light perception in 21 eyes. METHODS: This is a retrospective study. The hospital data of 17 patients (21 eyes) with idiopathic optic neuritis whose visual acuity were no light perception from August 2003 to April 2011 were retrospectively analyzed. These patients were treated with steroid pulse and other drugs. The clinical features, the time of appearance light perception, the best corrected visual acuity and VEP were measured. The follow-up was at least three months. RESULTS: Before the treatment, the average time of occurring no light perception were 1.0 â¼ 90.0 days, except 1 eye was 90.0 days while the other 20 eyes was (12.5 ± 10.6) days. After the treatment, vision improved in 14 eyes (66.7%) from Hand Move/30 cm to 20/20, the average time of appearance light perception was (9.9 ± 7.9) days. The best corrected vision acuity were 1 eye Hand Move, 2 eyes Finger Count, 1 eye 20/2000, 3 eyes 20/1000, 2 eyes 20/800, 1 eye 20/500, 1 eye 20/320, 1 eye 20/125, 1 eye 20/32, 1 eye 20/20. 5 eyes with no VEP wave pattern emerge P(100) after therapy, the other 2 eyes which had P(100) was flatten after therapy. The follow-up found that except 1 eye vision improve outside, the rest eye vision remained stable. CONCLUSIONS: The patients with optic neuritis who initially were no light perception should be treated promptly. The prognostic of vision can not be evaluated only by the duration time of no light perception, the appearing-time of light perception and the pattern of VEP.
Asunto(s)
Neuritis Óptica/fisiopatología , Percepción Visual , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuritis Óptica/tratamiento farmacológico , Estudios Retrospectivos , Agudeza Visual , Adulto JovenRESUMEN
PURPOSE: The purpose of this study was to investigate the role of modifier factors in the expression of Leber's hereditary optic neuropathy (LHON). METHODS: Thirty-five subjects from two Han Chinese families with maternally transmitted LHON underwent a clinical and genetic evaluation and molecular analysis of mitochondrial (mt)DNA. RESULTS: Matrilineal relatives in the two Chinese families exhibited a wide range of severity in visual impairment, from blindness to nearly normal vision. Very strikingly, all nine affected individuals of 21 matrilineal relatives (13 females/8 males) were female, which translates to 33% and 57% of penetrance for optic neuropathy in the two families. The average age at onset was 22 and 25 years. These observations were in contrast with typical features in many LHON pedigrees that have a predominance of affected males. Molecular analysis of their mtDNAs identified the homoplasmic ND4 G11778A mutation and distinct sets of variants belonging to the Asian haplogroups M1 and M10a. Of other variants, the L175F variant in CO3; the I58V variant in ND6; and the I189V, L292R, and S297A variants in CYTB were located at highly conserved residues of polypeptides. CONCLUSIONS: Only female matrilineal relatives with a wide range of penetrance, severity, and age at onset of optic neuropathy in these two Chinese pedigrees showed the involvement of X-linked or autosomal recessive modifier genes in the phenotypic manifestation of the G11778A mutation. Furthermore, mitochondrial haplogroup-specific variants, together with epigenetic and environmental factors, may contribute to the phenotypic manifestation of the primary LHON-associated G11778A mutation in these pedigrees.
Asunto(s)
Pueblo Asiatico/genética , ADN Mitocondrial/genética , Predisposición Genética a la Enfermedad , Atrofia Óptica Hereditaria de Leber/genética , Adolescente , Adulto , Edad de Inicio , Animales , China/epidemiología , Análisis Mutacional de ADN , Femenino , Genoma Mitocondrial , Humanos , Masculino , NADH Deshidrogenasa/genética , Linaje , Filogenia , Reacción en Cadena de la Polimerasa , Factores Sexuales , Adulto JovenRESUMEN
The present paper reviewes the literatures on the electromagnetic characteristic of meridians at home and abroad in the last twenty years. It generally summarize the studies on the electromagnetic characteristic of meridians from the aspects of the imaging of meridians, the electromagnetic model of meridians, and the physiological and pathological observations on the electro changes at acupoints. The results indicate that acupoints apparently have electro characteristics which are associated with the change of the health condition, time, environment, etc. By means of electromagnetic characteristic, the image of meridians can be made and the phenomena of meridians can be clarified, the essence of meridians can be explained in a certain degree. It still demands further research on this characteristic of meridians.
Asunto(s)
Puntos de Acupuntura , Fenómenos Electromagnéticos , Meridianos , Humanos , InvestigaciónRESUMEN
OBJECTIVE: To investigate the effect of Wuzi Yanzong Decoction (WYD) in treating Leber hereditary optic neuropathy (LHON). METHODS: Thirty patients of LHON up to the requirement were assigned to two groups, the treated group administered with WYD plus coenzyme Q10, and the control group with coenzyme Q10 alone, all for 3 months. Patients' visual acuity, visual field, vision evoked potential (VEP) and their Chinese medicine syndrome were observed before and after treatment. RESULTS: After treatment, all the above-mentioned indexes were improved to some extents in the treated group, but showed no evident change in the control group excepting visual acuity, comparison between groups showed the differences were significant in all items. CONCLUSION: WYD shows certain clinical therapeutic effect for treatment of LHON.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Atrofia Óptica Hereditaria de Leber/tratamiento farmacológico , Fitoterapia , Adolescente , Adulto , Potenciales Evocados Visuales , Femenino , Humanos , Masculino , Atrofia Óptica Hereditaria de Leber/genética , Ubiquinona/análogos & derivados , Ubiquinona/uso terapéutico , Agudeza Visual , Adulto JovenRESUMEN
OBJECTIVE: To analyze a pedigree of Leber's hereditary optic neuropathy, and its penetrance, anticipation, and spontaneous eyesight improvement, and its relationship with mitochondrial DNA mutation. METHODS: Eighteen members in the family were undergone routine visual check. Five cases were taken visual evoked potential and visual field examination. DNA sequencing was performed on 6 cases to check the mtDNA 11778, 3460 and 14484 loci. RESULTS: (1)The offsprings from the first wife in the first generation showed decreased acuity of the two eyes, which was optic atrophy identified by funduscopy. (2) The mtDNA had mutation at position 14484, but not at positions 11778 and 3460. CONCLUSION: The pedigree showed a typical maternal inheritance of Leber's hereditary optic neuropathy. It was caused by mtDNA 14484 mutation.