[Show abstract][Hide abstract] ABSTRACT: Purpose of this study was to validate that Subtenon (SB) Triamcinolone (TA) injection is an alternative to Intravitreal (IV) Triamcinolone (TA) injection for the treatment of diabetic macular edema (DME).
Pakistan Journal of Medical Sciences Online 07/2014; 30(4):749-54. · 0.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Studies have shown that an overproduction of mitochondrial reactive oxygen species (ROS) is an initiating cause in the pathogenesis of diabetic complications. However, uncoupling protein 2 (UCP2) can protect retinal vascular endothelial cells from damage by inhibiting the overproduction of mitochondrial ROS, although the protective mechanism involved is not completely clear. This study aimed to assess the effect and mechanism of UCP2 on the apoptosis of human umbilical vein endothelial cells (HUVECs). HUVECs were cultured in normal glucose (NG, 5.5 mmol/l) or high glucose (HG, 30 mmol/l) medium in the presence or absence of UCP2+/+ lentiviral transfection. Lentivirus-mediated UCP2 overexpression inhibited the apoptosis of HUVECs induced by HG. Treatment with HG resulted in the upregulation of caspase-3 and cytochrome c and the downregulation of Bcl-2 in vitro. Furthermore, compared with the NG group, the rate of apoptosis was significantly increased in the HG group. On day two post-infection, NG cells showed significantly greater HUVEC cell proliferation than HG cells. Notably, UCP2 overexpression inhibited these processes. Taken together, these results suggest that UCP2 promotes cell proliferation and inhibits HG-induced apoptosis in HUVECs via the Bcl-2 up‑ and downregulation of caspase-3 and cytochrome c in vitro. This may provide experimental evidence for the application of UCP2 as a new protective factor for diabetic complications, such as diabetic retinopathy.
International Journal of Molecular Medicine 02/2014; · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Although malaria remains as one of the leading infectious diseases in the world, the decline in malaria transmission in some area makes it possible to consider elimination of the disease. As countries approach elimination, malaria diagnosis needs to change from diagnosing ill patients to actively detecting infections in all carriers including asymptomatic and low-parasite load patients. However, few of the current diagnostic methods have both the throughput and the sensitivity required.Methods: We adopted a sandwich RNA hybridization assay to detect genus Plasmodium 18S rRNA directly from the whole blood of Plasmodium falciparum and Plasmodium vivax patients without RNA isolation. We tested the assay with 202 febrile patients from malaria endemic areas, using 20μl of each blood sample in 96-well plate format with a two-day ELISA-like workflow. Results were compared with diagnosis using microscopy, rapid diagnostic test (RDT) and genus specific real time PCR.Results: Our assay identified all 66 positive samples diagnosed by microscopy, including 49 poorly stored samples that underwent multiple freeze-thaw due to resource limitation. The assay uncovered three false-negative samples by microscopy and four false-negative samples by RDT, and agreed completely with real time PCR diagnosis. There was no negative sample by our assay that would show positive when tested with other methods. The detection limit of our assay for P. falciparum was 0.04 parasite/μl.Conclusions: The assay's simple workflow, high throughput and sensitivity make it suitable of active malaria screening.
Journal of clinical microbiology 10/2012; · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Necroptosis is a recently discovered programmed necrosis. Evidence demonstrated the importance of necroptosis in neuronal cell death. Necrostatin-1 is a specific inhibitor of necroptosis. In this study, we investigated the role of necrostatin-1 on photoreceptor survival and functional protection after experimental retinal detachment (RD) in rats. Necrostatin-1/inactive analogue of necrostatin-1 was introduced into the subretinal space at RD induction and 6 hours afterward, respectively. We found that necrostatin-1 attenuated retinal histopathological damage and reduced plasma membrane breakdown (a morphological hallmark of necroptosis) in outer retinal layers. Transmission electron microscopy showed that necrostatin-1 directly protected neurons by inhibiting necroptotic, not apoptotic, cell death. Treatment with necrostatin-1 inhibited the induction of receptor-interacting protein kinase phosphorylation after RD (a biomarker of necroptosis). Finally, electroretinographic recording proved that necrostatin-1 contributed to objective functional improvement after RD. These findings indicate that necrostatin-1 is a promising therapeutic agent that protects photoreceptors from necroptosis and improves functional outcome.
American Journal Of Pathology 08/2012; 181(5):1634-41. · 4.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the effects of high glucose (HG) medium on expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in cultured rat retinal Müller cells and to determine the signaling pathways mediating the effects.
Primary cultures of retinal Müller cells were prepared from Sprague-Dawley rats, and incubated in a medium containg HG (30 mmol/L) in the presence of the membrane-permeable Ca(2+) chelator BAPTA-AM (10 μmol/L) or the CaMKII inhibitor KN93 (10 μmol/L). The levels of CaMKII, p-CaMKII, CREB, p-CREB, HIF-1α, and VEGF proteins were measured with Western blotting, while HIF-1á and VEGF mRNA levels were determined using real-time RT-PCR.
The stimulation of retinal Müller cell with HG for 24 h remarkably increased the expression levels of HIF-1α and VEGF. These responses were significantly inhibited in the presence of BAPTA-AM or KN93. Both BAPTA-AM and KN93 also significantly inhibited HG-induced phosphorylation of CaMKII and CREB in the cultured retinal Müller cells. Transfection of the cultured retinal Müller cells with antisense CREB oligonucleotide (300 nmol/L) was similarly effective in blocking the HG-induced increase of HIF-1α and VEGF.
HG-induced HIF-1α and VEGF expression in cultured rat retinal Müller cells depends on intracellular free Ca(2+) and activation of CaMKII-CREB pathway. The activation of CaMKII-CREB pathway by HG may be a possible mechanism underlying the pathogenesis of diabetic retinopathy.
[Show abstract][Hide abstract] ABSTRACT: Aims: To assess the association between the NOS3 4b/a, T-786C and G894T polymorphisms and diabetic retinopathy (DR) susceptibility. Materials and Methods: Twenty-one studies covering 8,111 subjects were included. The fixed or random effect model used was based on heterogeneity. Results: A significant association of the intron 4a allele in the NOS3 4b/a polymorphism with reduced risk of DR was found in dominant (OR 0.778, 95% CI 0.654-0.926) and additive (OR 0.809, 95% CI 0.698-0.937) models. Subgroup analysis revealed that the intron 4a allele additive model (OR 0.807, 95% CI 0.697-0.935) was associated with DR risk in type 2 diabetic patients. We also found a marginally significant association of the C allele in the T-786C polymorphism with reduced risk of proliferative DR. In contrast, no statistically significant association was observed between the G894T polymorphism and DR risk, either in the overall or subgroup analyses. Conclusions: The intron 4a allele of the 4b/a polymorphism in the eNOS gene has protective effects against DR, especially in type 2 diabetic patients. The C allele of the T-786C polymorphism may be a protective factor for proliferative DR. However, the G894T polymorphism does not appear to influence the development of DR. This conclusion warrants confirmation by further studies.
[Show abstract][Hide abstract] ABSTRACT: Diabetic retinopathy (DR) is one of the most common complications of diabetes. Angiotensin-converting enzyme inhibitor is thought to play an important role in preventing and treating retinal diseases in animal models of DR. The aim of the present study was to investigate the role of angiotensin-converting enzyme inhibitor (ACEI, captopril) in the treatment of patients with non-proliferative DR.
Three hundred and seventeen type 2 diabetic patients (88.05% of participants) without or with mild to moderate non-proliferative retinopathy were randomly divided into captopril group (n = 202) and placebo group (n = 115). All subjects received 24-month follow-up. General clinical examinations, including blood pressure and glycated hemoglobin, as well as comprehensive standardized ophthalmic examinations were performed. Color fundus photography and optical coherence tomography (OCT) were used to grade diabetic retinopathy and detect macular edema respectively.
The levels of blood pressure and glycated hemoglobin in the two groups of patients remained within the normal range during the entire follow-up and no significant difference was found between the initial and last visits, suggesting that ACEI drugs play a protective role on the DR patients independent of its anti-blood pressure role. DR classification showed that 169 eyes (83.66%) remained unchanged and the DR grade of 33 eyes (16.34%) increased in captopril group, while 84 eyes (73.04%) remained unchanged and the grade of 31 eyes (26.96%) increased in placebo group (P = 0.024). Captopril treatment improved macular edema in 55.45% eyes, which was significantly higher than the 37.39% improvement in placebo group (P = 0.002). No significant difference was found in the visual acuity between the two groups (P = 0.271).
Captopril can improve or delay the development of DR and macular edema, which can be used in the early treatment of DR patients with type 2 diabetic mellitus.
Chinese medical journal 01/2012; 125(2):287-92. · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Focal organizing pneumonia is a unique form of organizing pneumonia. Little is known regarding its clinical and radiological feature, diagnosis, management, and outcome. Twenty patients with focal organizing pneumonia were investigated and compared with 40 patients with bronchogenic carcinoma. There were 38 men (63.3%) and 22 women (36.7%). The mean age was 55 ± 9.9 years. No specific feature in clinical and radiological manifestation was found to distinguish between focal organizing pneumonia and bronchogenic carcinoma. In patients with focal organizing pneumonia, wedge resection was performed in 12 cases and lobectomy in eight cases. Follow-up was complete with a median period of 26 months (range, 6 to 104 months). All patients were free from recurrence of organizing pneumonia. Clinical and radiologic findings of focal organizing pneumonia are nonspecific, and this unique form of organizing pneumonia is difficult to differentiate from lung cancer. Surgical resection allows both diagnosis and cure. However, considering the benign nature of this disease, major pulmonary resections should be avoided.
The American surgeon 01/2012; 78(1):133-7. · 0.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To test the hypothesis that a microalbuminuria (MA) threshold can help predict the risk for the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM)_ patients.
We conducted a cross-sectional study of 4739 subjects with T2DM and a prospective study of 297 subjects with T2DM in China respectively.
Clinical and laboratory data were collected and biologic risk factors associated with any DR were analysed.
In the cross-sectional study, we found that MA was an independent risk factor for DR development; further, when the patients were divided into MA deciles, odds ratio (ORs) of DR for the patients in the sixth MA decile (10.7 mg/24 h) was 1.579-fold (1.161-2.147) compared to that for patients in the first MA decile. Furthermore, the OR of DR increased with a gradual increase in MA levels. Similarly, in the prospective study, during a mean follow-up of 4.5 years, we found that 51 patients (29.0%) of the 176 subjects with high MA level (10.7-30 mg/24 h) developed DR, while 17 patients (14.1%) of the 121 subjects with lower MA (<10.7 mg/24 h) developed DR, and the relative risk ratio of the development of DR is 2.13(95% CI, 1.58-3.62, P<0.001).
These data suggest that an MA threshold can predict the risk for the development of DR in type 2 diabetes mellitus, although it is still within the traditionally established normal range.
PLoS ONE 01/2012; 7(5):e36718. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hyperglycemia-induced vascular cell apoptosis is a seminal early event in diabetic retinopathy. Prolonged hyperglycemia is known to increase intracellular cytosolic free calcium ([Ca(2+)]i) in retinal vascular endothelial cells (RECs), suggesting that [Ca(2+)]i is a critical trigger for microvascular degeneration. This study aims to elucidate Ca(2+)-dependent signaling mechanisms that mediate hyperglycemia-induced apoptosis in RECs.
A cultured macaque choroid-retinal endothelial cell line (RF/6A) was incubated in normal glucose (NG), NG plus the Ca(2+) entry blocker 2-aminoethoxydiphenyl borate (2-APB), high glucose (HG), or HG plus either 2-APB, the c-jun N-terminal kinase (JNK) inhibitor SP600125, or the calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93. Changes in [Ca(2+)]i evoked by adenosine 5'-triphosphate (ATP) were measured in fluo-3/AM-loaded RF/6A cells by confocal microscopy. The mitochondrial membrane potential (ΔΨm) and apoptosis were assessed by flow cytometry. Expression levels of CaMKII, phosphorylated CaMKII (p-CaMKII), c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), the death receptor (Fas), and cytochrome c were detected by western blotting analysis.
Prolonged exposure to HG (96 h) potentiated ATP-evoked Ca(2+) entry as well as CaMKII phosphorylation and RF/6A cell apoptosis. Enhanced apoptosis was blocked by 2-APB and KN93. Furthermore, HG increased JNK phosphorylation and Fas expression, and both responses were partially blocked by 2-APB and KN93, while the JNK inhibitor SP600125 partially reduced HG-induced Fas expression. In addition, HG depolarized the ΔΨm and triggered the release of mitochondrial cytochrome c. These early signs of mitochondria-dependent apoptosis were partially reversed by 2-APB and KN93.
HG-induced apoptosis in RF/6A cells depends on Ca(2+) entry and CaMKII activation, leading to the activation of both Fas-dependent and mitochondria-dependent apoptosis pathways. The CaMKII-JNK-Fas pathway is involved in HG-evoked apoptosis of RECs.
[Show abstract][Hide abstract] ABSTRACT: Cellular metabolic memory occurs in diabetic microvascular and macrovascular complications, but the underlying mechanisms remain unclear. Here, we investigate the role of sirtuin 1 (SIRT1) and metformin in this phenomenon. In bovine retinal capillary endothelial cells (BRECs) and retinas of diabetic rats, the inflammatory gene, nuclear factor-κB (NF-κB), and the proapoptotic gene, Bax, induced by hyperglycemia, remained elevated after returning to normoglycemia. BRECs with small interfering RNA-mediated SIRT1 knockdown had increased sensitivity to hyperglycemia stress, whereas SIRT1 overexpression or activation by metformin inhibited the increase of mitochondrial reactive oxygen species-mediated glyceraldehyde-3-phosphate dehydrogenase by poly (ADP-ribose) polymerase (PARP) activity through the upregulation of liver kinase B1/AMP-activated protein kinase (LKB1/AMPK), ultimately suppressing NF-κB and Bax expression. Furthermore, we showed that hyperglycemia led to PARP activation, which in turn may have downregulated SIRT1. Of importance, this study also demonstrated that metformin suppressed the "memory" of hyperglycemia stress in the diabetic retinas, which may be involved in the SIRT1/LKB1/AMPK pathway. Our data suggest that SIRT1 is a potential therapeutic target for the treatment of the cellular metabolic memory, and the use of metformin specifically for such therapy may be a new avenue of investigation in the diabetes field.
[Show abstract][Hide abstract] ABSTRACT: To investigate the relationship of ficolin-3 with inflammatory and angiogenic factors, namely, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF), in the vitreous of eyes with proliferative diabetic retinopathy (PDR).
Vitreous fluid and serum samples were obtained at the time of vitreoretinal surgery from 21 eyes of 21 patients with PDR and from 16 eyes of 16 nondiabetic patients with idiopathic macular hole. Ficolin-3, VEGF, and PEDF concentrations were determined by enzyme-linked immunosorbent assay.
Vitreous ficolin-3 levels were significantly higher in eyes with PDR than in eyes with idiopathic macular hole. Similarly, VEGF levels also were significantly higher in eyes with PDR than in eyes with idiopathic macular hole. In contrast, vitreous PEDF concentrations were significantly lower in eyes with PDR than in eyes with idiopathic macular hole, and the VEGF-to-PEDF ratio was higher in eyes with PDR than in eyes with idiopathic macular hole. Furthermore, a significant correlation between ficolin-3 and the VEGF-to-PEDF ratio was observed in the vitreous of eyes with PDR. In addition, serum ficolin-3 levels in eyes with PDR were higher than the levels in eyes with idiopathic macular hole, and the vitreous ficolin-3 levels also correlated with serum ficolin-3 levels.
We found that ficolin-3 levels were elevated in the vitreous fluid of patients with PDR. Our results suggest that ficolin-3 may be used as a new therapeutic target for treatment of PDR.
American Journal of Ophthalmology 08/2011; 152(6):1039-43. · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate whether rosiglitazone has a protective effect on retinal neural cells in diabetic rats, and to determine a possible anti-apoptotic mechanism.
Streptozotocin-induced diabetic rats and control animals were randomized evenly to receive rosiglitazone or not, effects were examined after 24 weeks. Retinal histology was examined and quantified using light microscopy; Apoptosis of retinal neural cells was determined by terminal dUTP nick-end labeling assay; Retinal ultrastructure was examined by transmission electron microscopy; Proteins levels of cleaved caspase-3, signal transduction and activators of transcription-3 (STAT3), phospho-STAT3 (p-STAT3), and suppressors of cytokine signaling 3 (SOCS3) in the retinal tissues were also determined by western blotting.
Compared with the control group, the thickness of the overall retina, inner plexiform layer, inner nuclear layer reduced by 13.8%, 27.4% and 4.2%, respectively (p < 0.05) in the diabetic group after 24 weeks; The number of cells in the ganglion cell layer was also decreased by 18.6% (p < 0.05). There was apoptosis of retinal neurons in the diabetic rats. Diabetes also induced mitochondrial metamorphosis in ganglion cells and evident pyknosis in the outer nuclear layer. These effects were associated with increased levels of cleaved caspase-3, p-STAT3, and decreased levels of SOCS3. After treatment of rosiglitazone, the thickness of the retina and the number of cells in the ganglion cell layer were significantly greater than those in the diabetic group (p < 0.05). Rosiglitazone also attenuated the diabetic-induced apoptosis of retinal neurons and mitochondrial metamorphosis in ganglion cells. Consistent with these effects, rosiglitazone treatment also decreased cleaved caspase-3 and p-STAT3 expression and, at the same time, increased SOCS3 expression.
Rosiglitazone attenuated diabetes-induced apoptosis in retinal neurons through activities that may involve inhibition of p-STAT3 by induction of SOCS3, which suggested that rosiglitazone might be used to prevent retinal neuronal damage in diabetes mellitus.
Current eye research 07/2011; 36(7):673-9. · 1.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Differentiation between pulmonary tuberculoma and malignancy by preoperative diagnostic imaging sometimes proves difficult. The purpose of this study is to investigate variable manifestations of pulmonary tuberculoma mimicking lung cancer on fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) image and pathologic correlation.
Twenty-five patients with a high suspicion of malignancy and histopathologically diagnosed as pulmonary tuberculoma were included. Their FDG PET/CT images, clinical data, and pathologic findings were investigated.
There were 18 men and seven women. The mean age was 52 ± 8.8 years. The maximal diameter of pulmonary tuberculoma ranged from 1.7 to 4.2 cm. CT scan revealed that abnormal signs associated with malignancy such as spicular radiation, notching, and pleural indentation also frequently manifested in tuberculoma. During early imaging, positive FDG uptake was identified in 21 patients (84%), intermediate uptake in 3 patients (12%) and negative uptake in 1 patient (4%). During delayed imaging, 16 patients (64%) showed persistent elevated FDG accumulation and 8 patients (32%) experienced a slight drop of FDG accumulation. Pathologically active tuberculoma showed significantly higher FDG radioactivity during both early and delayed imaging than inactive lesion (P < 0.05). Lymphadenopathy with positive FDG uptake was identified in nine patients (36%).
Pulmonary tuberculomas mimicking lung cancer, most of which were pathologically active lesions, commonly displayed abnormal appearances in CT scan and an increase in FDG uptake, similar to changes seen on malignancy. Coexistent lymphadenopathy made differential diagnosis even more complicated. These results suggested that positive FDG PET/CT findings should be interpreted with caution in tuberculosis-endemic regions.
Southern medical journal 06/2011; 104(6):440-5. · 0.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate the inhibitory effects of the nanoparticle-mediated delivery of plasminogen kringle 5 (K5) on choroidal neovascularization (CNV) and retinal inflammation.
CNV was induced by laser in adult rats. Nanoparticles with an expression plasmid of K5 (K5-NP) were injected into the vitreous. K5 expression was detected by immunohistochemistry. The CNV area was measured after fluorescein angiography. Retinal vascular permeability was quantified with Evans blue as a tracer. Expression of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 was measured by Western blot analysis or ELISA and real-time RT-PCR.
Intense K5 expression was detected in the retina 2 weeks after the injection of K5-NP. Areas of CNV were significantly decreased in the K5-NP treatment group compared with that in the control-NP group. The K5-NP injection also significantly reduced vascular permeability. The expression of VEGF was downregulated by K5-NP at both the protein and mRNA levels. Moreover, K5-NP also inhibited expression of TNF-α and ICAM-1. Similarly, K5-NP decreased retinal levels of total β-catenin. In cultured cells, K5-NP suppressed hypoxia-induced secretion of MCP-1 and TNF-α.
K5 has a novel anti-inflammatory activity. K5-NP mediates a sustained inhibitory effect on CNV and thus has therapeutic potential for age-related macular degeneration.
[Show abstract][Hide abstract] ABSTRACT: It has been known that facilitative glucose transporter (GLUT) is the main carrier which intervenes the glucose uptake of cell. The expression of Glut-1, Glut-3 has close relationship with the uptake of (18)Fluoro-2-deoxyglucose (FDG). The aim of this study is to discuss the relationship between expression of glucose transporter-1, 3 (Glut-1, Glut-3) and FDG uptake in NSCLC and benign pulmonary lesion.
Eighty-four NSCLC patients and twenty-four benign pulmonary lesion patients received PET/CT scan before operation. The expression of Glut-1, Glut-3 was detected by immunohistochemistry. The relationship among these factors was investigated.
The range of average SUV (SUVave) of the eighty-four patients was 3.6-13.2, and the average value was 7.8+/-3.0. The range of average SUV (SUVave) of the twenty-four patients was 1.2-9.2, and the average value was 3.2+/-1.9. In NSCLC tissues, the average immunohistochemical staining intensity of Glut-1, Glut-3 was 4.4+/-1.3 and 2.6+/-1.9, respectively. In benign pulmonary lesion, the average immunohistochemical staining intensity of Glut-1, Glut-3 was 0.9+/-0.9 and 1.2+/-1.4, respectively. Both of the Glut-1 and the Glut-3 expression levels were significantly higher in NSCLC than those in benign pulmonary lesion (P <0.01). Glut-1 expression was positively correlated to SUVave (r =0.78, P <0.01) in NSCLC patients. Glut-3 expression was positively correlated to SUVave (r =0.45, P =0.03) in benign pulmonary lesion patients.
The results show Glut-1 and Glut-3 express not only in NSCLC but also in benign pulmonary lesion. Glut-1 play an important role in FDG uptake in NSCLC. Glut-3 play an important role in FDG uptake in benign pulmonary lesion.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 08/2008; 11(4):555-8.