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The active components of ginseng, such as ginsenosides and polysaccharides, have high therapeutic value in treating cancer, decreasing obesity, and enhancing immunity. However, simple primary ginseng treatment cannot maximize this medicinal potential. Therefore, in this study, Panax ginseng was co-fermented with multi-enzyme-coupling probiotics to obtain a fermentation broth with higher levels of ginsenosides, polysaccharides, and probiotics. When compared to other treatment methods for cyclophosphamide-induced immunosuppression in mice, the results reveal that the P. ginseng fermentation broth treated with multi-enzyme-coupling probiotics could significantly improve the immune function of immunosuppressive mice and restore intestinal flora stability. Overall, this processing method will provide a novel strategy for promoting the application of ginseng and the relief of immunosuppression.
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Ginsenosídeos , Panax , Probióticos , Camundongos , Animais , Ginsenosídeos/farmacologia , Imunidade , Polissacarídeos/farmacologiaRESUMO
During the process of aging, the retina exhibits chronic oxidative stress (OS) damage. Our preliminary experiment showed that acetaldehyde dehydrogenase 2 (ALDH2) could alleviate retinal damage caused by OS. This study aimed to explore whether ALDH2 could inhibit mice retinal cell apoptosis and enhance the function of unfolded protein response in endoplasmic reticulum (UPRER) through reducing OS in aging process. Retinal function and structure in vivo and in vitro were examined in aged ALDH2+ overexpression mice and ALDH2 agonist Alda1-treated aged mice. Levels of ALDH2, endoplasmic reticulum stress (ERS), apoptosis and inflammatory cytokines were evaluated. Higher expression of ALDH2 was observed at the outer nuclear layer (ONL) and the inner nuclear layer (INL) in aged ALDH2+ overexpression and aged Alda1-treated mice. Moreover, aged ALDH2+ overexpression mice and aged Alda1-treated mice exhibited better retinal function and structure. Increased expression of glucose-regulated protein 78 (GRP78) and ERS-related protein phosphorylated eukaryotic initiation factor 2 (peIF2α) and decreased expression of apoptosis-related protein, including C/EBP homologous protein (CHOP), caspase12 and caspase9, and retinal inflammatory cytokines were detected in the retina of aged ALDH2+ overexpression mice and aged Alda1-treated mice. The expression of ALDH2 in the retina was decreased in aging process. ALDH2 could reduce retinal oxidative stress and apoptosis, strengthen UPRER during the aging process to improve retinal function and structure.
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Envelhecimento/metabolismo , Aldeído-Desidrogenase Mitocondrial/genética , Apoptose/genética , Retículo Endoplasmático/metabolismo , Estresse Oxidativo/genética , Retina/metabolismo , Resposta a Proteínas não Dobradas/genética , Envelhecimento/patologia , Aldeído-Desidrogenase Mitocondrial/efeitos dos fármacos , Aldeído-Desidrogenase Mitocondrial/metabolismo , Animais , Apoptose/efeitos dos fármacos , Benzamidas/farmacologia , Benzodioxóis/farmacologia , Eletrorretinografia , Retículo Endoplasmático/efeitos dos fármacos , Chaperona BiP do Retículo Endoplasmático , Fundo de Olho , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Transgênicos , Estresse Oxidativo/efeitos dos fármacos , Retina/efeitos dos fármacos , Retina/patologia , Retina/fisiopatologia , Tomografia de Coerência Óptica , Fator de Necrose Tumoral alfa/metabolismo , Resposta a Proteínas não Dobradas/efeitos dos fármacosRESUMO
BACKGROUND: Oxidative stress (OS) is an essential factor in the pathogenesis of branch retinal vein occlusion (BRVO). Studies have demonstrated the role of hydrogen gas in the regulation of OS. This study was designed to evaluate the efficacy of hydrogen gas on the BRVO rat model. METHODS: Twenty-four BRVO rats were randomly divided into two groups: the hydrogen gas (H) group (42% H2, 21% O2, 37% N2) and the model (M) group (21% O2, 79% N2). Rats in the H group inhaled hydrogen gas for 8 h every day up to 30 d post-occlusion. Twelve age-matched healthy rats served as the control (C) group. Retinal function and morphology were detected at 1, 7, 14 and 30 d post-occlusion. Furthermore, the expression of vascular endothelial growth factor (VEGF-α) was detected by immunofluorescent staining. RESULTS: Full-field electroretinography (ffERG) revealed that the amplitude of the b-wave (dark-adaptation 3.0 response), the amplitude of the OPs2 wave and the light-adapted flicker response in the H group were all higher than those in the M group at 7 d post-occlusion (all p < 0.05). The reopen time of occlusive retinal vessels in the H group was 2.235 ± 1.128 d, which was shorter than that in the M group (4.234 ± 2.236 d, p < 0.05). The rats in the H group had a thinner IPL + GCL + NFL and an increased total retina compared with those in the M group at 3 d post-occlusion (p < 0.05), while the rats in the H group had a thicker INL, IPL + GCL + NFL and total retina compared with those at 7, 14 and 30 d post-occlusion (p < 0.05). Moreover, the flow velocity of ear vein blood was increased in the H group compared with that in the M group (p < 0.05). The expression of VEGF-α in the H group was dramatically decreased compared with that in the M group at 1, 7 and 14 d post-occlusion (p < 0.05), while the expression kept in similar level at 30 d post-occlusion (p > 0.05). CONCLUSIONS: Our findings demonstrate that inhalation of hydrogen gas could alleviate retinal oedema, shorten reopen time and improve retinal function, and the potential mechanism might be related to a decrease in VEGF-α expression.
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Hidrogênio/farmacologia , Retina/efeitos dos fármacos , Oclusão da Veia Retiniana/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Modelos Animais de Doenças , Eletrorretinografia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Retina/metabolismo , Retina/fisiopatologia , Oclusão da Veia Retiniana/fisiopatologiaRESUMO
BACKGROUND Molecular hydrogen (H2) has been widely reported to have benefiicial effects in diverse animal models and human disease through reduction of oxidative stress and inflammation. The aim of this study was to investigate whether hydrogen gas could ameliorate endotoxin-induced uveitis (EIU) in rats. MATERIAL AND METHODS Male Sprague-Dawley rats were divided into a normal group, a model group, a nitrogen-oxygen (N-O) group, and a hydrogen-oxygen (H-O) group. EIU was induced in rats of the latter 3 groups by injection of lipopolysaccharide (LPS). After that, rats in the N-O group inhaled a gas mixture of 67% N2 and 33% O2, while those in the H-O group inhaled a gas mixture of 67% H2 and 33% O2. All rats were graded according to the signs of uveitis after electroretinography (ERG) examination. Protein concentration in the aqueous humor (AqH) was measured. Furthermore, hematoxylin-eosin staining and immunostaining of anti-ionized calcium-binding adapter molecule 1 (Iba1) in the iris and ciliary body (ICB) were carried out. RESULTS No statistically significant differences existed in the graded score of uveitis and the b-wave peak time in the Dark-adapted 3.0 ERG among the model, N-O, and H-O groups (P>0.05), while rats of the H-O group showed a lower concentration of AqH protein than that of the model or N-O group (P<0.05). The number of the infiltrating cells in the ICB of rats from the H-O group was not significantly different from that of the model or N-O group (P>0.05), while the activation of microglia cells in the H-O group was somewhat reduced (P<0.05). CONCLUSIONS Post-treatment hydrogen gas inhalation did not ameliorate the clinical signs, or reduce the infiltrating cells of EIU. However, it inhibited the elevation of protein in the AqH and reduced the microglia activation.
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Hidrogênio/uso terapêutico , Uveíte/terapia , Animais , Humor Aquoso/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/efeitos dos fármacos , Corpo Ciliar/efeitos dos fármacos , Modelos Animais de Doenças , Endotoxinas/efeitos adversos , Hidrogênio/administração & dosagem , Hidrogênio/fisiologia , Iris/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Proteínas dos Microfilamentos/efeitos dos fármacos , Microglia/efeitos dos fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley , Uveíte/induzido quimicamenteRESUMO
The relationship between gene-specific DNA methylation in peripheral blood leukocytes and colorectal cancer (CRC) susceptibility is unclear. In this case-control study, the methylation status of a panel of 10 CRC-related genes in 428 CRC cases and 428 cancer-free controls were detected with methylation-sensitive high-resolution melting analysis. We calculated a weighted methylation risk score (MRS) that comprehensively combined the methylation status of the panel of 10 genes and found that the MRS_10 was significantly associated with CRC risk. Compared with MRS-Low group, MRS-High group and MRS-Medium group exhibited a 6.51-fold (95% CI, 3.77-11.27) and 3.85-fold (95% CI, 2.72-5.45) increased risk of CRC, respectively. Moreover, the CRC risk increased with increasing MRS_10 (Ptrend < 0.0001). Stratified analyses demonstrated that the significant association retained in both men and women, younger and older, and normal weight or underweight and overweight or obese subjects. The area under the receiver operating characteristic curves for the MRS_10 model was 69.04% (95% CI, 65.57-72.66%) and the combined EF and MRS_10 model yielded an AUC of 79.12% (95% CI, 76.22-82.15%). Together, the panel of 10 gene-specific DNA methylation in leukocytes was strongly associated with the risk of CRC and might be a useful marker of susceptibility for CRC.
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Effects of pulse electric field (PEF) on antioxidant activity of pine nut (Pinus koraiensis) peptide were discussed using H2O2-induced HepG2 cells and changes of peptide structures were measured by MIR, NMR and CD spectra. Using HPLC-MS/MS, a novel peptide was identified as QDHCH. After PEF treatment the DPPH and ABTS radical inhibition, and CAA values of QDHCH were increased to 85.13%±0.17%, 95.45%±0.12%, and 4670.10µmol of quercetin equivalents/100g. The PEF-treated QDHCH has better protective oxidative stress inhibitory of 74.22±3.70%, and the T-SOD, CAT, GSH-Px and GSH-Rx activities in cells were significantly increased by 91.92, 7.98, 18.5 and 18.79U/mg prot, while the MDA content was decreased to 8.45±0.71U/mg prot compared with H2O2 damaged group. In addition, the hydroxyl radical scavenging activity of QDHCH was increased by 10.53%; the basic structure was not changed by PEF, while the influenced secondary structures may induce the antioxidant activity improvement in HepG2 cells.
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Pinus , Antioxidantes , Células Hep G2 , Humanos , Peróxido de Hidrogênio , Nozes , Peptídeos , Espectrometria de Massas em TandemRESUMO
In the present study, two novel peptides Lys-Trp-Phe-Cys-Thr (KWFCT) and Gln-Trp-Phe-Cys-Thr (QWFCT) were purified and identified from 3 to 10kDa pine nut (Pinus koraiensis) meal protein. Their cytotoxicity and antioxidant activities in vitro were determined. Additionally, pulsed electric field technology, antioxidant activities, and circular dichroism were used together to investigate the relationship between antioxidant activities and secondary structure. The results showed that neither peptide demonstrated cytotoxicity in HepG2 cells. KWFCT had higher values for 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition (67.43%±1.33%) and ferric-reducing antioxidant power (67.86±1.03mM Fe2+/mg), and Ac-QWFCT had higher values for 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) inhibition (74.9%±1.19%) and cellular antioxidant activity (916.32µmol of QE/100g) (P<0.05). The antioxidant activities reached their highest values when parameters of PEF were 5kV/cm and 2400Hz. An increase in antioxidant activities of Ac-QWFCT was correlated with a decrease in random coil content.
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Antioxidantes/química , Eletroforese em Gel de Campo Pulsado/métodos , Nozes/química , Dicroísmo Circular , Oxirredução , Pinus/química , Estrutura Secundária de ProteínaRESUMO
Purpose. To study the effect of different electrophysiological methods to evaluate retinal function prior to cataract surgery. Methods. Cataract patients who had no significant other eye disease were chosen. VA, pattern visual evoked potential (PVEP), electroretinogram (ERG), and multifocal electroretinogram (mfERG) responses were measured from 150 cataract patients and 20 control subjects. Results. When the preoperative VA was more than 0.3 in cataract patients, the amplitude of PVEP was not significantly different between cataract and control subjects. The amplitude of central point mfERG was significantly lower in cataract patients compared with control group from HM to 0.8 of preoperative VA. The 95% confidence intervals (CIs) of the amplitudes of center point mfERG were calculated for a range of preoperative VA values. Most of the patients within 95% CI of the center point mfERG had a postoperative VA more than 0.5. Conclusions. The amplitude of central point mfERG in cataract patients was the most relevant parameter to the preoperative VA compared with PVEP and ERG. The 95% CI of the amplitude of central point mfERG for each level of VA could help to evaluate preoperative macular function which is used to predict the outcome of cataract surgery.
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The CNGA3(-/-)/Nrl(-/-) mouse is a cone-dominant model with Cnga3 channel deficiency, which partially mimics the all cone foveal structure of human achromatopsia 2 with CNGA3 mutations. Although subretinal (SR) AAV vector administration can transfect retinal cells efficiently, the injection-induced retinal detachment can cause retinal damage, particularly when SR vector bleb includes the fovea. We therefore explored whether cone function-structure could be rescued in CNGA3(-/-)/Nrl(-/-) mice by intravitreal (IVit) delivery of tyrosine to phenylalanine (Y-F) capsid mutant AAV8. We find that AAV-mediated CNGA3 expression can restore cone function and rescue structure following IVit delivery of AAV8 (Y447, 733F) vector. Rescue was assessed by restoration of the cone-mediated electroretinogram (ERG), optomotor responses, and cone opsin immunohistochemistry. Demonstration of gene therapy in a cone-dominant mouse model by IVit delivery provides a potential alternative vector delivery mode for safely transducing foveal cones in achromatopsia patients and in other human retinal diseases affecting foveal function.
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Fatores de Transcrição de Zíper de Leucina Básica/genética , Defeitos da Visão Cromática/genética , Defeitos da Visão Cromática/terapia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Proteínas do Olho/genética , Terapia Genética , Células Fotorreceptoras Retinianas Cones/fisiologia , Animais , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Defeitos da Visão Cromática/metabolismo , Defeitos da Visão Cromática/fisiopatologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Dependovirus/genética , Dependovirus/metabolismo , Modelos Animais de Doenças , Proteínas do Olho/metabolismo , Feminino , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
PURPOSE: Molecular hydrogen has been used as an antioxidant to treat many diseases in clinical and animal studies. However, the therapeutic mechanism of molecular hydrogen remains unclear. We previously reported mitigation of light-induced damage in the rat retina by intraperitoneal injection of hydrogen-rich saline (HRS). In the present study, we investigated whether Sirtuin Type 1 (Sirt1), a class III histone deacetylase, mediates the retinal protective effect of HRS in rats with light-induced retinal damage. METHODS: Rats were treated with HRS for 5 days after intense light exposure, and then ERGs were performed and retinas were collected to evaluate the effect of HRS on Sirt1 expression. The necessity of Sirt1 for the retinal protective effect of HRS was investigated using the Sirt1 activator resveratrol, the Sirt1 inhibitor EX-527, and short interfering RNAs. RESULTS: In light-damaged retinas, 5 days of HRS treatment increased Sirt1 expression, mitigated a- and b-wave amplitude reduction, and decreased the reduction of outer nuclear cell layers. The Sirt1 activator resveratrol mimicked the effect of HRS in light-damaged retinas. This result supported our hypothesis that Sirt1 mediates the protective effect of HRS. Additionally, the retinal protective effect of HRS was inhibited by both the Sirt1 inhibitor EX-527 and Sirt1 targeted short interfering RNAs. Hydrogen-rich saline also increased B-cell lymphoma 2 (Bcl-2) expression and the activity of the antioxidant enzyme superoxide dismutase (SOD). Conversely, HRS decreased Bcl2-associated X protein expression, cleaved caspase-3, and oxidant-stress product malondialdehyde (MDA) in a Sirt1-dependent manner. CONCLUSIONS: Sirt1 mediates light-induced damage mitigation by HRS through inhibition of apoptosis and oxidant-stress.
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Regulação da Expressão Gênica , Hidrogênio/farmacologia , Estresse Oxidativo , Retina/patologia , Doenças Retinianas/genética , Sirtuína 1/genética , Cloreto de Sódio/farmacologia , Animais , Apoptose , Western Blotting , Modelos Animais de Doenças , Luz/efeitos adversos , Masculino , RNA/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Retina/metabolismo , Doenças Retinianas/metabolismo , Doenças Retinianas/prevenção & controle , Sirtuína 1/biossínteseRESUMO
PURPOSE: To investigate the association between CpG island methylator phenotype (CIMP) and the overall survival of sporadic colorectal cancer (CRC) in Northeast China. METHODS: 282 sporadic CRC patients were recruited in this study. We selected MLH1, MGMT, p16, APC, MINT1, MINT31, and RUNX3 as the CIMP panel markers. The promoter methylation was assessed by methylation sensitive high resolution melting (MS-HRM). Proportional hazards-regression models were fitted with computing hazard ratios (HR) and the corresponding 95% confidence intervals (95% CI). RESULTS: 12.77% (36/282) of patients were CIMP-0, 74.1% (209/282) of patients were CIMP-L, and 13.12% (37/282) of patients were CIMP-H. The five-year survival of the 282 CRC patients was 58%. There was significant association between APC gene promoter methylation and CRC overall survival (HR = 1.61; 95% CI: 1.05-2.46; P = 0.03). CIMP-H was significantly associated with worse prognosis compared to CIMP-0 (HR = 3.06; 95% CI: 1.19-7.89; P = 0.02) and CIMP-L (HR = 1.97; 95% CI: 1.11-3.48; P = 0.02), respectively. While comparing with the combine of CIMP-L and CIMP-0 (CIMP-L/0), CIMP-H also presented a worse prognosis (HR = 2.31; 95% CI: 1.02-5.24; P = 0.04). CONCLUSION: CIMP-H may be a predictor of a poor prognosis of CRC in Northeast China patients.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ilhas de CpG/genética , Metilação de DNA/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Regiões Promotoras Genéticas , Análise de SobrevidaRESUMO
The present systematic review and meta-analysis was conducted to assess any association between breastfeeding and the risk of ovarian cancer. A systematic search of published studies was performed in PUBMED and EMBASE and by reviewing reference lists from retrieved articles through March 2013. Data extraction was conducted independently by two authors. Pooled relative risk ratios were calculated using random-effect models. Totals of 5 cohort studies and 35 case-control studies including 17,139 women with ovarian cancer showed a 30% reduced risk of ovarian cancer when comparing the women who had breastfed with those who had never breastfed (pooled RR = 0.70, 95% CI: 0.64-0.76; p = 0.00), with significant heterogeneity in the studies (p = 0.00; I2 = 76.29%). A significant decreasd in risk of epithelial ovarian cancer was also observed (pooled RR = 0.68, 95% CI: 0.61-0.76). When the participants were restricted to only parous women, there was a slightly attenuated but still significant risk reduction of ovarian cancer (pooled RR = 0.76, 95% CI: 0.69-0.83). For total breastfeeding duration, the pooled RRs in the < 6 months, 6-12 months and > 12 months of breastfeeding subgroups were 0.85 (95% CI: 0.77-0.93), 0.73 (95% CI: 0.65-0.82) and 0.64 (95%CI: 0.56-0.73), respectively. Meta-regression of total breastfeeding duration indicated an increasing linear trend of risk reduction of ovarian cancer with the increasing total breastfeeding duration (p = 0.00). Breastfeeding was inversely associated with the risk of ovarian cancer, especially long-term breastfeeding duration that demonstrated a stronger protective effect.
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Aleitamento Materno , Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Ovarianas/epidemiologia , Carcinoma Epitelial do Ovário , Estudos de Casos e Controles , China/epidemiologia , Estudos Epidemiológicos , Feminino , Humanos , Neoplasias Epiteliais e Glandulares/prevenção & controle , Neoplasias Ovarianas/prevenção & controle , Prognóstico , Fatores de RiscoRESUMO
PURPOSE: Hypermethylation of TFAP2E (AP-2E) is associated with the chemotherapy-resistant in patients with colorectal cancer (CRC), but its implications on prognosis directly remain unknown. This study was aimed to investigate the role of AP-2E methylation status and other clinicopathologic parameters as predictors of prognosis. METHODS: We detected the methylation status of AP-2E in tumor and adjacent non-tumor tissues from 311 sporadic CRC patients by methylation-sensitive high-resolution melting analysis. Log-rank tests and multivariate Cox analyses were performed to evaluate the role of AP-2E methylation status and other clinicopathologic parameters as predictors of prognosis. RESULTS: Hypermethylation of AP-2E was detected in 61 % (190/311) tumor tissues. It occurred more frequently in tumors in earlier stages (I/II; P = 0.02), lower levels of tumor invasion (T1-T3; P = 0.04), fewer lymph nodes involved (N0; P < 0.01), and higher histologic grades (G1/G2; P < 0.01). The overall 5-year survival rates in hypermethylation and hypomethylation group were 76.91 and 47.17 % (P < 0.0001), respectively. AP-2E hypermethylation was significantly associated with a favorable clinical outcome with a hazard ratio of 0.486 (95 % CI 0.342-0.692, P < 0.0001) after controlling for age, gender, tumor location, histologic type, TNM staging, and histologic grade. CONCLUSIONS: AP-2E was frequently hypermethylated in tumors from patients with CRC. Aberrant hypermethylation of AP-2E occurred more frequently in tumors with earlier stages, lower levels of tumor invasion, fewer lymph nodes involved, and higher histologic grades. AP-2E hypermethylation might be an independent predictor of survival advantage in patients with CRC.
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Neoplasias Colorretais/genética , Metilação de DNA , Fator de Transcrição AP-2/genética , Idoso , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos ProporcionaisRESUMO
AIMS: It is reported that retinal neovascularization seems to rarely co-exist with retinitis pigmentosa in patients and in some mouse models; however, it is not widely acknowledged as a universal phenomenon in all strains of all animal species. We aimed to further explore this phenomenon with an oxygen-induced retinopathy model in mice with retinal photoreceptor cell degeneration. MAIN METHODS: Oxygen-induced retinopathy of colored and albino mice with rapid retinal degeneration were compared to homologous wild-type mice. The retinas were analyzed using high-molecular-weight FITC-dextran stained flat-mount preparation, hematoxylin and eosin (H&E) stained cross-sections, an immunohistochemical test for vascular endothelial growth factor (VEGF) distribution and Western blotting for VEGF expression after exposure to hyperoxia between postnatal days 17 (P17) and 21. KEY FINDINGS: Leakage and areas of non-perfusion of the retinal blood vessels were alleviated in the retinal degeneration mice. The number of preretinal vascular endothelial cell nuclei in the retinal degeneration mice was smaller than that in the homologous wild-type mice after exposure to hyperoxia (P<0.01). The degree of oxygen-induced retinopathy was positively correlated with the VEGF expression level. However, the VEGF expression level was lower in the retinal degeneration mice. SIGNIFICANCE: Proliferative retinopathy occurred in mice with rapid retinal degeneration, but retinal photoreceptor cell degeneration could partially restrain the retinal neovascularization in this rapid retinal degeneration mouse model.
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Oxigênio/toxicidade , Células Fotorreceptoras de Vertebrados/patologia , Degeneração Retiniana/patologia , Neovascularização Retiniana/patologia , Retinose Pigmentar/patologia , Animais , Western Blotting , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Especificidade da Espécie , Coloração e Rotulagem , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
CpG island methylation in the promoter regions of the DNA mismatch repair gene mutator L homologue 1 (MLH1) and DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) genes has been shown to occur in the leukocytes of peripheral blood and colorectal tissue. However, it is unclear whether the methylation levels in the blood leukocytes and colorectal tissue are correlated. The present study analyzed and compared the levels of MGMT and MLH1 gene methylation in the leukocytes of peripheral blood and colorectal tissues obtained from patients with colorectal cancer (CRC). The methylation levels of MGMT and MLH1 were examined using methylation-sensitive high-resolution melting (MS-HRM) analysis. A total of 44 patients with CRC were selected based on the MLH1 and MGMT gene methylation levels in the leukocytes of the peripheral blood. Corresponding colorectal tumor and normal tissues were obtained from each patient and the DNA methylation levels were determined. The correlation coefficients were evaluated using Spearman's rank test. Agreement was determined by generalized κ-statistics. Spearman's rank correlation coefficients (r) for the methylation levels of the MGMT and MLH1 genes in the leukocytes of the peripheral blood and normal colorectal tissue were 0.475 and 0.362, respectively (P=0.001 and 0.016, respectively). The agreement of the MGMT and MLH1 gene methylation levels in the leukocytes of the peripheral blood and normal colorectal tissue were graded as fair and poor (κ=0.299 and 0.126, respectively). The methylation levels of MGMT and MLH1 were moderately and weakly correlated between the patient-matched leukocytes and the normal colorectal tissue, respectively. Blood-derived DNA methylation measurements may not always represent the levels of normal colorectal tissue methylation.
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Oxidative reactions are thought to be a major cause of light-induced retinal degeneration. This study was designed to investigate the effects of hydrogen-rich saline (HRS) on the prevention and treatment of light-induced retinal injury in rats. Male Sprague-Dawley rats were divided randomly into three groups: light damage, HRS prevention (5 ml/kg, 30 min before intensive light exposure), and HRS treatment (5 ml/kg per day for 5 days, after intensive light exposure), respectively. The right eye of each rat was exposed to 5000 lux constant white light-emitting diode (LED) light for 3 h, and the left eye was covered to serve as the blank control. Electroretinograms were recorded 5 days later, and the thickness of the outer nuclear layer (ONL) was measured after hematoxylin and eosin (H&E) staining. The results showed that the electroretinogram b-wave amplitudes and the mean ONL thicknesses of rats were significantly greater in the HRS prevention (P < 0.001) and treatment (P < 0.001) groups than in the light damage. These results indicated that peritoneal injection of HRS provides protection and treatment against light-induced retinal degeneration in rats.
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INTRODUCTION: Myopic eyes show structural differences from normal eyes and may respond differently to microgravity, increasing the risk for possible development of ocular hypertension and glaucoma on orbit. In this experiment we used head-down rest (HDR) at an angle of 15 degrees to produce hydrostatic changes similar to acute exposure to microgravity. METHODS: There were 65 subjects (129 eyes) who were divided into groups characterized by refraction: emmetropes (N = 46; refraction error between -0.99 D and +0.10 D), low myopes (N = 39; > or = -1.0 D to < -3.0 D), and moderate myopes (N = 44; > or = -3.0 D to < -6.0 D). Each subject was studied resting in a horizontal position and after 1, 6, 11, 16, and 21 min of HDR. Measured variables included systolic and diastolic blood pressure (SBP and DBP, respectively), intraocular pressure (IOP), and ocular perfusion pressure (OPP). RESULTS: The mean values of IOP increased significantly in all eyes during HDR, with IOP peaking at 6 min. Compared to emmetropes and low myopes, moderate myopes showed a significantly greater increase in IOP and higher peak values for IOP (18.6, 18.7, and 19.8 mmHg for emmetropes, low, and moderate myopes, respectively). Mean values of OPP in moderate myopes were significantly lower than in emmetropes and low myopes during HDR. Compared with baseline, mean SBP and DBP decreased obviously in emmetropes during HDR, while changes were minimal in the other groups. CONCLUSION: Abnormal auto-regulation of ocular blood pressure in myopes of moderate and greater severity may pose a risk factor for developing ocular hypertension and possibly glaucoma when exposed to microgravity. HDR may offer a method of screening candidates for spaceflight for this risk prior to microgravity exposure.