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1.
J Diabetes Res ; 2020: 9705786, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32626784

RESUMO

Purpose: To evaluate the impact of restoration of foveal bulge (FB) in optical coherence tomography (OCT) images on visual acuity after resolution of diabetic macular edema with coexisting serous retinal detachment (SRD-DME). Methods: A total of 52 eyes with resolved SRD-DME and an intact ellipsoid zone at the central fovea were included. All eyes underwent best-corrected visual acuity (BCVA) examination and OCT scanning at baseline and follow-up visits (1, 3, and 6 months). The eyes were divided into two groups according to the presence of FB at 6 months. BCVA, central foveal thickness (CFT), height of SRD (SRDH), outer nuclear layer (ONL) thickness, photoreceptor inner segment (PIS), and outer segment (POS) length were compared between the two groups. Results: A FB was found in 25 of 52 (48%) eyes at 6 months. The FB (+) group had lower SRDH at baseline, and better BCVA, longer POS length at 6 months (all P < 0.05). There was no significant difference in the CFT, ONL thickness, and PIS length at 6 months between the two groups (all P > 0.05). More eyes in the FB (+) group had complete SRD resolution at 1 month (P = 0.009) and 3 months (P = 0.012). Eyes with complete SRD resolution at 1 month (P = 0.009) or 3 months (P = 0.012) were more likely to have a FB at 6 months. Conclusions: The Presence of the FB is associated with better BCVA after resolution of SRD-DME. Eyes with lower baseline SRDH or faster SRD resolution are more likely to have a FB at 6 months.

2.
BMJ Open ; 10(3): e034219, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32161158

RESUMO

OBJECTIVES: To review the pattern of primary pterygium-induced corneal astigmatism in patients with cataract in a southern Chinese population. DESIGN: Clinic-based cross-sectional retrospective study. SETTING: A secondary hospital at southern China. PARTICIPANTS: A group of 1689 eyes with primary pterygium (PT group) and the other group of 4062 eyes without pterygium (NPT group) were included. MAIN OUTCOME MEASURES: Corneal power was measured by an autokeratorefractometer. Corneal astigmatism was calculated as the difference in corneal power between the steepest and flattest meridians. Distribution of corneal astigmatism was compared between eyes with pterygium and eyes without pterygium. RESULTS: Distribution of corneal astigmatism was different between PT group (skewness=2.548, kurtosis=8.237) and NPT group (skewness=2.778, kurtosis=15.52). Mean corneal astigmatism was significantly higher in the PT group (1.62±1.49D) compared with the NPT group (1.17±0.89D, p<0.0001). The prevalence of corneal astigmatism >1D (PT 52.3%, NPT 40.9%, p<0.0001), >2D (PT 22.4%, NPT 10.6%, p<0.0001) or >3D (PT 10.5%, NPT 3.2%, p<0.0001) was significantly higher in the PT group compared with the NPT group. Eyes in the PT group had significantly higher corneal astigmatism than the NPT group in almost every age group (all p<0.05), with the exception of patients ≥90 years. Moreover, eyes in the PT group had significantly higher with-the-rule (PT 1.72±1.59D, NPT 1.19±0.88D, p<0.0001) and against-the-rule (PT 1.63±1.46D, NPT 1.18±0.88D, p<0.0001) but similar oblique astigmatism (PT 1.11±1.00D, NPT 0.99±0.89D, p=0.065) corneal astigmatism compared with the NPT group. Power vector analysis indicated that the axis of corneal astigmatism was not significantly different between the two groups (J0, PT -0.01±0.74D, NPT 0.01±0.52D, p=0.48; J45, PT -0.03±0.82D, NPT 0.00±0.52D, p=0.54). CONCLUSIONS: Pattern of corneal astigmatism in eyes with cataract and coexisting primary pterygium was different from eyes without pterygium. Pterygium is associated with higher magnitude but not different axis of corneal astigmatism.

3.
Clin Exp Optom ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32043282

RESUMO

BACKGROUND: To investigate corneal endothelial cell density in eyes with primary pterygium. METHODS: A retrospective study was conducted to compare endothelial cell density between 1,565 patients with primary pterygium and 3,448 patients without pterygium. Then a prospective study was designed to confirm the findings of the retrospective study in 95 patients with unilateral primary pterygium. RESULTS: In the retrospective study, the mean endothelial cell density in eyes with primary pterygium was significantly lower (2,454 ± 303 cells/mm2 ) than those in eyes without pterygium (2,525 ± 312 cells/mm2 , p < 0.0001). However, the difference was not as high as previously reported (71 cells/mm2 , 2.9 per cent). In the prospective study, there was no significant difference in mean endothelial cell density in eyes with unilateral primary pterygium (2,480 ± 263 cells/mm2 ) and the contralateral eyes with no pterygium (2,527 ± 277 cells/mm2 , p = 0.20). There was also no significant difference in hexagonality (p = 0.10) or co-efficient of variation of size (p = 0.15) of corneal endothelial cells between eyes with pterygium and the contralateral eyes with no pterygium. CONCLUSION: Primary pterygium may not be associated with a decrease in endothelial cell density in our study population of rural Chinese patients.

4.
Retina ; 40(2): 345-349, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31972805

RESUMO

PURPOSE: To investigate the levels of systemic heparanase, inflammatory markers, and coagulation factor activities in patients with retinal vein occlusion (RVO). METHODS: This prospective study included 18 patients with central RVO, 22 patients with branch RVO, and 40 patients with age-related cataract as the control group. Serum heparanase protein levels and activities were measured by ELISA and a heparan degrading enzyme assay kit, respectively. Serum levels of MMP-2, MMP-9, TLR-2, and TLR-4 were measured by ELISA kits. The activities of coagulation factors (V, VII, VIII, and IX) were determined with an autoanalyzer. The Mann-Whitney U test was used to compare the above parameters between patients with RVO and control subjects. The relationship between two of the above parameters was analyzed by Spearman's correlation. RESULTS: Patients with RVO had higher levels of systemic heparanase protein, heparanase activities, coagulation factors' (V, VIII, and IX) activities, MMP-2, MMP-9, TLR-2, and TLR-4 compared with the control group. Systemic heparanase levels were correlated with serum levels of MMP-2, MMP-9, TLR-2, TLR-4, and activities of coagulation factors VIII and IX. CONCLUSION: Increase of systemic heparanase in RVO is associated with activation of systemic inflammation and blood hypercoagulability.

5.
Graefes Arch Clin Exp Ophthalmol ; 257(12): 2613-2621, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31529324

RESUMO

PURPOSE: To evaluate the edema reduction after intravitreal injection of ranibizumab (IVR) in two diabetic macular edema (DME) components in the same eye using optical coherence tomography (OCT). METHODS: Totally 113 eyes with mixed OCT pattern of DME were included. All the eyes underwent best-corrected visual acuity (BCVA) examination and OCT scanning at baseline and follow-up visits (1, 3, and 6 months after 3 monthly consecutive IVR). The mixed OCT pattern of DME was classified into 2 OCT components: serous retinal detachment (SRD) component and non-SRD component. Foveal thickness of the SRD component (SRDFT) and the non-SRD component (NSRDFT) was compared between baseline and follow-up visits. Reduction and reduction ratio of the SRDFT and the NSRDFT at each follow-up were compared. When calculating the NSRDFT reduction ratio, we innovatively optimized a commonly used formula by subtracting the normal foveal thickness from the baseline NSRDFT. RESULTS: SRDFT was 265.6 ± 175.4 µm at baseline and was significantly decreased to 126.7 ± 114.4 µm at 1 month, to 110.5 ± 103.4 µm at 3 months, and to 110.4 ± 89.6 µm at 6 months (all P < 0.001). NSRDFT was 409.5 ± 173.1 µm at baseline and was significantly decreased to 274.1 ± 140.4 µm at 1 month, to 249.1 ± 95.9 µm at 3 months, and to 254.1 ± 90.4 µm at 6 months (all P < 0.001). There was no significant difference in reduction or reduction ratio between NSRDFT and SRDFT during follow-up (all P > 0.05). The correlation between BCVA and SRDFT was most significant at baseline (r = 0.366, P < 0.001) and the correlation between BCVA and NSRDFT was most significant at 6 months (r = 0.426, P < 0.001). BCVA improvement was more significantly correlated with reduction or reduction ratio of SRDFT at each follow-up timepoint (r = 0.271-0.426, all P < 0.01). CONCLUSIONS: IVR was effective in reducing both the SRD and non-SRD components of DME according to our optimized formula. The association between BCVA improvement and edema reduction was more significant in the SRD component.

6.
Theranostics ; 9(18): 5200-5213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410210

RESUMO

Producing keratinocyte cells (KCs) in large scale is difficult due to their slow proliferation, disabling their use as seed cells for skin regeneration and wound healing. Cell reprogramming is a promising inducer-based approach to KC production but only reaches very low cellular conversion. Here we reported a unique cellular conversion phenomenon, where human skin fibroblasts (FBs) were spontaneously converted into keratinocyte-like cells (KLCs) over the time without using any inducers. Methods: FBs were routinely cultured for more than 120 days in regular culture medium. Characteristics of KLCs were checked at the molecular and cellular level. Then the functionality and safety of the KLCs were verified by wound healing and tumorigenicity assay, respectively. To identify the mechanism of the cell conversion phenomenon, high-throughput RNA sequencing was also performed. Results: The global conversion started on day 90 and reached 90% on day 110. The KLCs were as functional and effective as KCs in wound healing without causing oncogenicity. The conversion was regulated via a PI3K-AKT signaling pathway mediated by a long non-coding RNA, LINC00672. Modulating the pathway could shorten the conversion time to 14 days. Conclusion: The discovered FBs-KLCs conversion in the study might open a new avenue to the scalable production of cell sources needed for regenerating skins and healing large-area wounds.

7.
Talanta ; 198: 404-411, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30876579

RESUMO

Microfluidic chips coupled with electrospray ionization (ESI) mass spectrometry (MS) is an analytical platform with high detection throughputs and low sample consumptions. However, its applications in probing real samples are limited by the absence of reliable on-chip sample pretreatments, which are indispensable due to both the low contents of analytes and the poor salt tolerance of ESI MS. Herein, we propose an automated extraction and ESI chip (AEEC), consisting of a solid phase extraction (SPE) zone, seven on-chip pneumatic micro-valves, a monolithic ESI nozzle, and other components, to implement on-chip SPE prior to on-line ESI for analytes. In the SPE zone, magnetic silica beads were immobilized by magnets, and used as the SPE sorbent. Additionally, open and closed statuses of all micro-valves were simultaneously controlled by turning off and on applied pneumatic pressures, thus regulating the direction of various flows in AEEC. Further, the SPE in AEEC, consisting of sample introduction and extraction, elution introduction, and analytes elution, was automatically implemented by regulating the direction of both sample and elution flows in AEEC. After these steps, the analytes elution was on-line introduced to the monolithic ESI nozzle, at which the ESI for analytes was achieved. After optimizations, the AEEC-MS method was used to investigate two standard chemicals and ten pesticides, achieving a limit of detection and an enrichment ratio between 0.10 and 0.75 ng µL-1 and 2.1-6.2, respectively. In addition, linear calibration curves with and without the SPE beads were compared, demonstrating the effect of the automated SPE in improving reliability and sensitivity of the AEEC method. Finally, we applied AEEC to quantify a new herbicide, quinotrione, in sorghum plant as 0.176 mg kg-1 (RSD=5.70%), presenting an improved error compared with related reports. With the AEEC method, a SPE and ESI MS investigation for analytes could be automatically implemented within 300 s, effectively reducing random error and analytical time compared with manual strategies.

8.
Retina ; 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30383717

RESUMO

PURPOSE: To investigate the levels of systemic heparanase, inflammatory markers, and coagulation factor activities in patients with retinal vein occlusion (RVO). METHODS: This prospective study included 18 patients with central RVO, 22 patients with branch RVO, and 40 patients with age-related cataract as the control group. Serum heparanase protein levels and activities were measured by ELISA and a heparan degrading enzyme assay kit, respectively. Serum levels of MMP-2, MMP-9, TLR-2, and TLR-4 were measured by ELISA kits. The activities of coagulation factors (V, VII, VIII, and IX) were determined with an autoanalyzer. The Mann-Whitney U test was used to compare the above parameters between patients with RVO and control subjects. The relationship between two of the above parameters was analyzed by Spearman's correlation. RESULTS: Patients with RVO had higher levels of systemic heparanase protein, heparanase activities, coagulation factors' (V, VIII, and IX) activities, MMP-2, MMP-9, TLR-2, and TLR-4 compared with the control group. Systemic heparanase levels were correlated with serum levels of MMP-2, MMP-9, TLR-2, TLR-4, and activities of coagulation factors VIII and IX. CONCLUSION: Increase of systemic heparanase in RVO is associated with activation of systemic inflammation and blood hypercoagulability.

9.
BMC Ophthalmol ; 17(1): 140, 2017 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-28797227

RESUMO

BACKGROUND: To evaluate the macular sensitivity changes after half-dose photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSCR). METHODS: Eighteen patients (26 eyes) with chronic CSCR were recruited in the same hospital between April 2011 and December 2012. All patients were treated with one session of half-dose PDT after complete ophthalmic examination. Macular sensitivity examination was performed at baseline and 1, 3 and 6 months post-treatment. Mean sensitivity (MS) of the central 10 degrees (10°) and 4 degrees (4°), mean deviation (MD) and pattern standard deviation (PSD) on automated static perimetry (Humphrey Field Analyzer II-750) were used for analysis. RESULTS: There was significant improvement of the 10°MS from baseline (29.76 ± 1.51 dB) to 1 month (31.74 ± 1.56 dB), 3 months (31.51 ± 1.38 dB) and 6 months (31.19 ± 1.61 dB) after treatment (P < 0.001). The 4°MS was also significantly improved with half-dose PDT from baseline (28.96 ± 1.78 dB) to 1 month (32.41 ± 1.66 dB), 3 months (32.46 ± 1.50 dB) and 6 months (31.90 ± 1.84 dB) post-treatment (P < 0.001). MD was improved from baseline (-3.39 ± 0.89 dB) to 1 month (-1.96 ± 0.29 dB), 3 months (-1.94 ± 0.29 dB) and 6 months (-2.45 ± 0.13) post-treatment (P = 0.004). PSD also improved from 1.97 ± 0.24 dB at baseline to 1.47 ± 0.27 dB, 1.34 ± 0.24 dB, and 1.53 ± 0.24 dB (P = 0.001) at 1, 3 and 6 months after treatment, respectively. CONCLUSION: Macular sensitivity in CSCR can be improved by half-dose PDT, along with improvement of visual acuity and retinal thickness. The treatment outcome at 1 month may be a predictor of the final treatment response.


Assuntos
Coriorretinopatia Serosa Central/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Adulto , Análise de Variância , Coriorretinopatia Serosa Central/fisiopatologia , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica , Verteporfina , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologia
10.
Mol Vis ; 23: 579-587, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28848320

RESUMO

PURPOSE: To observe the nuclear expression and interaction of heparanase and RNA polymerase II (RNA Pol II), an enzyme that catalyzes the transcription of DNA in eukaryotic cells) in human retinal microvascular endothelial cells (HRECs) under high glucose condition and to investigate the association of heparanase with the transcription activity of the vascular endothelial growth factor (VEGF) gene promoter. METHODS: Cultured HRECs were maintained for 3 days in media with high or normal glucose. The expressions of heparanase and RNA Pol II in each group were analyzed with immunofluorescence. Co-immunoprecipitation was applied to detect the interaction of heparanase and Pol II proteins. Cells in both groups were used for chromatin immunoprecipitation (ChIP) with anti-heparanase and anti-RNA Pol II antibodies to identify high-confidence heparanase-binding regions across the entire VEGF gene promoter. Moreover, real-time PCR was used to demonstrate the interaction between heparanase and the VEGF gene promoter region. RESULTS: The immunofluorescence studies showed that the nuclear expression of heparanase was intense in high-glucose HRECs but faint in the normal group; RNA Pol II in the nucleus was also intense in high glucose HRECs, and the distribution of heparanase was consistent with that of RNA Pol II. The co-immunoprecipitation data showed that heparanase combined with RNA Pol II in HRECs cells treated with high glucose, and the molecular size of HPA interacted with RNA Pol II was 50 kDa, while no combination of two proteins was evident in normal HRECs cells. Real-time PCR-based ChIP results showed that the high-confidence HPA-binding region was -1155 to -1018 (containing hypoxia response element) in the VEGF gene promoter, and the cells treated with high glucose showed increases in heparanase and RNA Pol II in the VEGF gene promoter region compared with the normal glucose treated cells (t = -3.244, p = 0.032; t = -6.096, p = 0.004, respectively). CONCLUSIONS: Nuclear heparanase combines directly with the VEGF gene promoter and is involved in the regulation of VEGF gene transcription in high-glucose HRECs.


Assuntos
Células Endoteliais/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Glucose/farmacologia , Glucuronidase/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Western Blotting , Proliferação de Células , Células Cultivadas , Cromatina/metabolismo , Células Endoteliais/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imunoprecipitação , RNA Polimerase II/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Vasos Retinianos/citologia , Transcrição Genética
11.
Theranostics ; 7(6): 1407-1421, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28529626

RESUMO

Understanding the interaction between cancer cells and immunocytes will inspire new cancer therapy strategies. However, how cancer-derived circulating miRNAs modulate such interaction remains unclear. Here we discovered that circulating miR-410-5p, secreted by prostate cancer cells, entered dendritic cells (DCs), with the aid of argonaute-2 protein. The cancer cell antigens stimulated the DCs to produce miR-410-3p, a highly complementary counterpart of miR-410-5p derived from pre-miR-410. The DC-internalized miR-410-5p degraded the miR-410-3p by base pairing and thus inhibited its function in suppressing tumor angiogenesis, promoting tumor growth. Furthermore, blockade of the miR-410-5p upregulated the miR-410-3p to inhibit tumor growth. Our work suggests a new miRNA-mediated role of immunocytes in cancer progression and a new strategy of cancer therapy through suppressing circulating miRNAs.


Assuntos
MicroRNA Circulante/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , MicroRNAs/metabolismo , Neovascularização Patológica/fisiopatologia , Neoplasias da Próstata/patologia , Estabilidade de RNA , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos Endogâmicos C57BL
12.
Sci Rep ; 7(1): 2329, 2017 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-28539592

RESUMO

Phagocytosis of daily shed photoreceptor outer segments is an important function of the retinal pigment epithelium (RPE) and it is essential for retinal homeostasis. RPE dysfunction, especially impairment of its phagocytic ability, plays an essential role in the pathogenesis of age-related macular degeneration (AMD). Statins, or HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, are drugs with multiple properties that have been extensively used to treat hyperlipidemia. However, their effect on RPE cells has not been fully elucidated. Here we report that high dose atorvastatin increased the phagocytic function of ARPE-19 cells, as well as rescue the cells from the phagocytic dysfunction induced by cholesterol crystals and oxidized low-density lipoproteins (ox-LDL), potentially by increasing the cellular membrane fluidity. Similar effects were observed when evaluating two other hydrophobic statins, lovastatin and simvastatin. Furthermore, atorvastatin was able to block the induction of interleukins IL-6 and IL-8 triggered by pathologic stimuli relevant to AMD, such as cholesterol crystals and ox-LDL. Our study shows that statins, a well-tolerated class of drugs with rare serious adverse effects, help preserve the phagocytic function of the RPE while also exhibiting anti-inflammatory properties. Both characteristics make statins a potential effective medication for the prevention and treatment of AMD.


Assuntos
Atorvastatina/farmacologia , Colesterol/metabolismo , Inflamação/tratamento farmacológico , Degeneração Macular/tratamento farmacológico , Linhagem Celular , Células Epiteliais , Humanos , Inflamação/metabolismo , Inflamação/patologia , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipoproteínas LDL/metabolismo , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Fagocitose/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia
13.
Immunobiology ; 222(5): 730-737, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28187901

RESUMO

The strength of immune responses induced by DNA vaccine is closely associated with the expression level of cloned antigens available to the antigen presenting cells (APCs). To acquire a larger and more persistent amount of antigen, a dual-promoter, which could double the target antigen output through its expression both in prokaryotic and eukaryotic cells, was employed in the constructed anti-caries DNA vaccine with attenuated Salmonella as mucosal delivery vector in this study. Here, both CMV and nirB promoters were included in the plasmid that harbors the genes encoding the functional epitopes of two virulence factors of S. mutans, i.e. the saliva-binding region (SBR) of PAc and the glucan-binding region (GBR) of glucosyltransferase-I (GTF-I). Delivered by attenuated Salmonella Typhimurium strain SL3261, the anti-caries vaccine was administered intragastrointestinally to BALB/c mice for evaluation of the effectiveness of this immune regime. Specific anti-SBR and anti-GBR antibodies were detected in the serum and saliva of experimental animals by week 3 after immunization. These immune responses were further enhanced after a booster vaccination at week 16. However, in mice receiving Salmonella expressing SBR and GBR under the control of nirB alone these antibody responses were significantly (P<0.01) lower. The serum IgG subclass profiles suggested a Th1/Th2-mixed but Th2 biased immune response to the cloned antigens, which was further confirmed by a significant increase in the Th1 (IFN-γ, IL-2) and Th2 (IL-4, IL-10) cytokines in splenocytes of immunized mice upon stimulation with SBR or GBR. To further determine the protective efficacy of these responses, a challenge test with S. mutans strain UA159 was performed in mice after the second immunization. Following challenge, mice immunized with Salmonella expressing SBR and GBR under the control of the CMV-nirB promoter showed a significant (P<0.01) reduction in the number of S. mutans in the dental plaque compared to the empty vector-immunized or unimmunized mice, and the reduction was also significant at weeks 3-8 (P<0.05) post-challenge when compared with those receiving Salmonella clones with nirB promoter alone. These results provide evidence for the effectiveness of a dual-promoter strategy in the anti-caries DNA vaccine when employing attenuated Salmonella as delivering vehicle for mucosal immunization.


Assuntos
Regiões Promotoras Genéticas , Infecções por Salmonella/imunologia , Vacinas contra Salmonella/genética , Vacinas contra Salmonella/imunologia , Salmonella typhimurium/imunologia , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Administração Oral , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Expressão Gênica , Ordem dos Genes , Vetores Genéticos/genética , Imunidade nas Mucosas , Imunização , Imunoglobulina A Secretora/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Camundongos , Infecções por Salmonella/prevenção & controle , Vacinas contra Salmonella/administração & dosagem , Vacinas de DNA/administração & dosagem
14.
Acta Ophthalmol ; 95(1): e62-e66, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27418016

RESUMO

PURPOSE: To investigate the serum heparanase concentration and heparanase activity of the patients with central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). METHODS: This prospective study included 23 CRVO patients, 13 BRVO patients and 28 control subjects. Serum heparanase concentration was measured by ELISA. Serum heparanase activity was determined using a heparan degrading enzyme assay kit (Mountain View, CA, USA). Multivariate logistic regression was used to adjust for the possible confounding factors when comparing the difference in serum heparanase concentration and activity between patients with RVO and control subjects. RESULTS: Patients with CRVO (3.963 ± 0.816 U/l) or BRVO (3.371 ± 1.522 U/l) had significantly higher levels of heparanase protein compared to controls (1.055 ± 0.902 U/l). This significance remained after adjusting for aforementioned confounding factors (CRVO versus control, p = 0.000, 95%CI: 2.450-4.488; BRVO versus control, p = 0.006, 95%CI: 0.776-4.050). Patients with CRVO (0.3587 ± 0.1498 U/ml) or BRVO (0.3616 ± 0.0570 U/ml) had significantly higher levels of heparanase activity compared to controls (0.1449 ± 0.0952 U/ml). The significance was maintained after adjusting for the aforementioned confounding factors (CRVO versus control, p = 0.012, 95%CI: 0.036-0.275; BRVO versus control, p = 0.000, 95%CI: 0.150-0.395). There was no significant difference in serum heparanase protein levels and activities between CRVO and BRVO groups before and after confounding factor adjustment. CONCLUSION: Our study provides the first direct clinical link between systemic heparanase protein levels and heparanase activity with RVO, suggesting a critical role for heparanase in the pathophysiology of RVO.


Assuntos
Glucuronidase/sangue , Oclusão da Veia Retiniana/enzimologia , Idoso , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
15.
J Cancer Res Clin Oncol ; 143(5): 745-757, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27686824

RESUMO

PURPOSE: Metastasis is the leading cause of death for a majority of cancer patients, and thus the need to understand the biology of metastasis becomes increasingly acute. When metastasis is initiated in tumor progression remains obscure. Better understanding of mechanisms regulating acquisition of metastatic ability in tumor cells will provide novel therapeutic targets and prevention of metastasis in clinics accompanied with the treatment of the primary tumor might be helpful in reducing metastasis-related mortality. METHODS: A literature search was performed in multiple electronic databases. Research papers from clinical reports to experimental studies on metastasis were analyzed. RESULTS: The article discusses tumor heterogeneity and genomic instability in the context of metastasis and tumor cell dissemination. And then we review biological mechanism of metastasis at an early stage in both intracellular (CSCs and CTCs) and extracellular (microenvironment) context. Finally, current development of anti-metastatic therapies is summarized. CONCLUSIONS: Metastasis could be initiated at an early point of tumor progression. Therefore, early intervention on metastasis should be applied among cancer patients in clinical settings.


Assuntos
Neoplasias/patologia , Animais , Progressão da Doença , Humanos , Metástase Neoplásica
16.
Cancer Cell Int ; 16: 12, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26900347

RESUMO

BACKGROUND: Prostate cancer (PCa) remains to be a diagnostic challenge due to its variable presentation and the lack of reliable diagnosis tool. MicroRNAs (miRNAs) regulate gene in extensive range of pathophysiologic processes. Plasma miRNAs are ideal biomarkers in heart failure, diabetes and other disease. However, using circulating miRNAs as biomarkers for the diagnosis of PCa is still unknown. METHODS: 149 PCa patients, 57 healthy controls, and 121 non-cancer patients (benign prostatic hyperplasia and other urinary diseases) were enrolled in this study. The reverse transcription of miRNA and SYBR-Green-based double standards curve miRNA quantitative polymerase chain reactions (qPCR) were used to evaluate the dysregulated miR-410-5p. Receiver operator characteristic (ROC) curve analysis was used to evaluate the diagnostic accuracy of miR-410-5p identified as the alternative biomarker. RESULTS: Circulating miRNA-410-5p (miR-410-5p) level was significantly higher in the PCa patients than in healthy controls or non-cancer patients. ROC curve analysis showed that plasma miR-410-5p was a specific diagnostic biomarker of PCa with an area under curve(AUC) of 0.8097 (95 % confidence interval, 0.7371-0.8823; P < 0.001). CONCLUSIONS: The serum miR-410-5p level is a potential biomarker for the diagnosis of PCa.

17.
PLoS One ; 11(1): e0147346, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26799405

RESUMO

PURPOSE: To investigate the cytokine concentrations in the aqueous humor of patients with refractory polypoidal choroidal vasculopathy (PCV). METHODS: Three separate groups of patients were studied-refractory PCV (Group A, 41 eyes), stable PCV (Group B, 39 eyes) and senile cataract (Group C, 44 eyes). Aqueous humor samples were collected at two time points for Groups A and B-before the first intravitreal ranibizumab injection and before the last injection. Aqueous humor samples were collected prior to phacoemulsification in Group C. The cytokine concentrations of interleukin 2, 6, and 8 (IL-2, IL-6, and IL-8), tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and vascular endothelial growth factor (VEGF) were measured by cytometric bead array and flow cytometry. RESULTS: Before the first treatment, the MCP-1, VEGF, and TNF-α levels in Group A were significantly higher than those in Group C (P < 0.05), and the MCP-1 and VEGF levels in Group A were significantly higher than those in Group B (P < 0.05). Significantly higher MCP-1 and VEGF levels were seen in Group B compared to Group C (P < 0.05). Before the final treatment, the MCP-1, VEGF, and TNF-α concentrations in Group A were significantly higher than those in Group B (P < 0.05) and Group C (P < 0.05). IL-2 levels were significantly lower in Group A compared to Group B (P < 0.05) and Group C (P < 0.05). CONCLUSION: Inflammatory cytokines such as MCP-1, VEGF, and TNF-α may be associated with the pathogenesis of both stable and refractory PCV.


Assuntos
Humor Aquoso/metabolismo , Quimiocina CCL2/metabolismo , Corioide/irrigação sanguínea , Corioidite/patologia , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Inibidores da Angiogênese/uso terapêutico , China , Corioide/imunologia , Corioide/patologia , Feminino , Humanos , Inflamação/patologia , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Ranibizumab/uso terapêutico , Epitélio Pigmentado da Retina/irrigação sanguínea , Epitélio Pigmentado da Retina/patologia , Estudos Retrospectivos
19.
Mol Med Rep ; 12(4): 5026-34, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26165373

RESUMO

The present study aimed to investigate the ability of SS31, a novel mitochondria­targeted peptide to protect against t­BHP­induced mitochondrial dysfunction and apoptosis in 661W cell lines. The 661W cells were treated with various concentrations of SS­31 and an MTT assay was used to determine cell viability. The expression of nitrotyrosine and 8­hydroxydeoxyguanosine (8­OHdG) was detected using immunofluorescent staining. Apoptosis were assessed using Hoechst staining and an annexin V/propidium iodide flow cytometer. Reactive oxygen species (ROS) were detected using MitoSOXTM with confocal microscopy. Changes in mitochondrial membrane potential were analyzed using flow cytometry. In addition, the release of cytochrome c was analyzed using confocal microscopy. The viability of the cells improved following treatment with SS31 between 100 nM and 1 µM, compared with untreated control group. Compared with the t­BHP treatment group (20.0±3.8%), the number of annexin V­positive cells decreased dose­dependently to 13.6±2.6, 9.8±0.5 and 7.4±2.0% in the SS­31 treated group at concentrations of 10 nM, 100 nM and 1 µM, respectively. Treatment with SS­31 significantly prevented the t­BHP­induced expression of nitrotyrosine and 8­OHdG, decreased the quantity of mitochondrial ROS, increased mitochondrial potential, and prevented the release of cytochrome c from mitochondria into the cytoplasm. Therefore, the SS31 mitochondria­targeted peptide protected the 661W cells from the sustained oxidative stress induced by t­BHP.


Assuntos
Antioxidantes/farmacologia , Oligopeptídeos/farmacologia , Oxidantes/antagonistas & inibidores , Espécies Reativas de Oxigênio/antagonistas & inibidores , Células Fotorreceptoras Retinianas Cones/efeitos dos fármacos , terc-Butil Hidroperóxido/antagonistas & inibidores , 8-Hidroxi-2'-Desoxiguanosina , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Oxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Células Fotorreceptoras Retinianas Cones/citologia , Células Fotorreceptoras Retinianas Cones/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo , terc-Butil Hidroperóxido/farmacologia
20.
Taiwan J Ophthalmol ; 5(1): 9-14, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-29018657

RESUMO

Since the first vitrectomy surgery was used for treatment of vitreoretinal diseases, surgical techniques and instrumentation have been rapidly improved in the past decades. However, there are complicated vitreoretinal diseases that cannot be successfully treated, even with state-of-the-art surgeries. The outcomes of some complicated cases are still poor due to different reasons and debates still remain in some areas regarding what are the best treatments. There is still a lack of full understanding on many complicated vitreoretinal diseases, such as the molecular basis of proliferative vitreoretinopathy (PVR), the role of scleral buckling (SB) in the management of rhegmatogenous retinal detachment (RRD), the optimal surgical consideration for pediatric RD, and the possibility of surgical management for various retinal degenerations and congenital retinal anomalies. This review discusses the current understandings of some complicated vitreoretinal diseases.

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