Ginsenoside Rb1 attenuates diabetic retinopathy in streptozotocin-induced diabetic rats1.

PURPOSE: To investigated the effects of ginsenoside Rb1 on diabetic retinopathy in streptozotocin-induced diabetic rats. METHODS: Diabetes was induced by a single intraperitoneal injection of streptozotocin (80 mg/kg) in male Wistar rats. Ginsenoside Rb1 (20, 40 mg/kg) was injected (i.p.) once a day for 4 weeks. Then, using fundus photography, the diameter and vascular permeability of retinal vessels were investigated. Retinal histopathology was undertaken. Contents of malondialdehyde (MDA) and glutathione (GSH) in retinas were assayed. Levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione cysteine ligase catalytic subunit (GCLC), and glutathione cysteine ligase modulatory subunit (GCLM) were measured. RESULTS: Treatment with ginsenoside Rb1 attenuated the diabetes-induced increase in the diameter of retinal blood vessels. Ginsenoside Rb1 reduced extravasation of Evans Blue dye from retinal blood vessels. Ginsenoside Rb1 partially inhibited the increase in MDA content and decrease in GSH level in rat retinas. Nrf2 levels in the nuclei of retinal cells and expression of GCLC and GCLM were increased significantly in rats treated with ginsenoside Rb1. CONCLUSION: These findings suggest that ginsenoside Rb1 can attenuate diabetic retinopathy by regulating the antioxidative function in rat retinas.

Ginsenoside Rb1 attenuates diabetic retinopathy in streptozotocin-induced diabetic rats

Abstract Purpose: To investigated the effects of ginsenoside Rb1 on diabetic retinopathy in streptozotocin-induced diabetic rats. Methods: Diabetes was induced by a single intraperitoneal injection of streptozotocin (80 mg/kg) in male Wistar rats. Ginsenoside Rb1 (20, 40 mg/kg) was injected (i.p.) once a day for 4 weeks. Then, using fundus photography, the diameter and vascular permeability of retinal vessels were investigated. Retinal histopathology was undertaken. Contents of malondialdehyde (MDA) and glutathione (GSH) in retinas were assayed. Levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione cysteine ligase catalytic subunit (GCLC), and glutathione cysteine ligase modulatory subunit (GCLM) were measured. Results: Treatment with ginsenoside Rb1 attenuated the diabetes-induced increase in the diameter of retinal blood vessels. Ginsenoside Rb1 reduced extravasation of Evans Blue dye from retinal blood vessels. Ginsenoside Rb1 partially inhibited the increase in MDA content and decrease in GSH level in rat retinas. Nrf2 levels in the nuclei of retinal cells and expression of GCLC and GCLM were increased significantly in rats treated with ginsenoside Rb1. Conclusion: These findings suggest that ginsenoside Rb1 can attenuate diabetic retinopathy by regulating the antioxidative function in rat retinas.

Blood platelet and serum bilirubin in the diagnosis of central serous chorioretinopathy.

Diagnostic value of blood platelet (PLT) and serum total bilirubin (TBIL) for central serous chorioretinopathy (CSC) was investigated. A total of 537 patients with CSC and 182 people with normal physical conditions were selected from June 2012 to August 2016. The 537 patients included 294 males and 243 females with an average age of 45.5±17.8 years, and all patients were treated in the Department of Ophthalmology of Yantai Hospital of Traditional Chinese Medicine and the Department of Ophthalmology of Yantai Liuhuangding Hospital. Clinical data of the patients were retrospectively analyzed. The 182 people with normal physical conditions included 103 males and 79 females with an average age of 43.6±15.2 years, and they were set as the control group. PLT and TBIL tests at admission and after treatment were collected and compared between CSC and the control group to analyze the diagnostic values of PLT and TBIL for CSC. PLT level in the CSC group was significantly higher than that in the control group, but TBIL level in the CSC group was significantly lower than that in the control group (p<0.05). Linear correlation analysis showed that PLT was a risk factor for CSC, and TBIL was a protective factor for CSC. The sensitivity of PLT and TBIL in diagnosis of CSC was 75.2 and 72.7%, respectively, and the specificity of PLT and TBIL in diagnosis of CSC was 65.8 and 63.3%, respectively. PLT of CSC patients was significantly higher than that of the control group, and TBIL of CSC patients was significantly lower than that of the control group, but they both gradually reduced to normal levels after treatment, which can be regarded as the index for the clinical diagnosis of CSC in the future.

Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathy.

AIM: To confirm the role of angiopoietin-like protein 8 (Angptl 8) in proliferative diabetic retinopathy (PDR). METHODS: The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy (NDR) patients (idiopathic macular hole patients) were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay (ELISA). Experimental diabetes mice model was induced with streptozotocin. The expression of glycosylated hemoglobin and Angptl 8 in sera was detected. Recombinant Angptl 8 was re-infused into wild type (WT) diabetic mice and spatial frequency threshold and contrast sensitivity were measured. In vitro retinal pigment epithelium (RPE) were stimulated by recombinant Angptl 8 for 24h. MMT assay were used to detect cell proliferation. At the same time, qRT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells. RESULTS: The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients (F=99.02, P<0.0001 in sera; t=10.42, P<0.0001 in aqueous). After successfully establishing the diabetic mice model, we found that glycosylated hemoglobin and Angptl 8 expression levels were increased. Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity (P<0.01). In vitro, RPE cells stimulated by recombinant Angptl 8 could increase the relative absorbance of MMT assay (1.486±0.042 vs 1.000±0.104, P<0.05) and proliferating cell nuclear antigen (PCNA) expression (0.55±0.01 vs 0.29±0.03, P<0.05). The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1 (4.973±0.205 vs 2.720±0.197, P<0.05), cyclin F (5.690±0.219 vs 4.297±0.292, P<0.05) and E2F2 (2.297±0.102 vs 1.750±0.146, P<0.05), and reducing the expression of proliferation-inhibiting factors cdkn1 (2.370±0.074 vs 3.317±0.135, P<0.05) and cdkn2 (4.793±0.065 vs 5.387±0.149, P<0.05). CONCLUSION: The expression of Angptl 8 is increased in PDR, and the increased Angptl 8 can promote proliferation and increase proliferation-related factors.

Modified Glasgow Prognostic Score at Recurrence Predicts Poor Survival in Resected Non-Small Cell Lung Cancer (NSCLC) Patients.

BACKGROUND The purpose of this study was to investigate the impact of the modified Glasgow Prognostic Score (GPS) at the time of recurrence on post-recurrence survival (PRS) in non-small cell lung cancer (NSCLC) patients after surgical resection. MATERIAL AND METHODS The clinicopathologic characteristics and outcome data of 266 patients with recurrent NSCLC were collected and reviewed retrospectively. The prognostic impact of mGPS at recurrence in patients with recurrent NSCLC was investigated in univariate and multivariate analyses. RESULTS A total of 266 patients were analyzed. The mGPS at the time of recurrence of 0, 1, and 2 was assigned to 60.9%, 33.1%, and 6.0% of total patients, respectively. In univariate analyses, the median post-recurrence survival times for those with mGPS 0, 1, and 2 were 19, 14, and 4 months, respectively (log-rank test; P=0.005). No statistically significant difference in post-recurrence survival was observed among the patients with different mGPS before surgery (log-rank test; P=0.064). Age at surgery, histological type, C-reactive protein (CRP), albumin, and mGPS at recurrence significantly predicted PRS. After adjusting for confounding variables in the model, age (hazard ratio 1.59, P=0.003) as well as disease-free interval (DFI) (hazard ratio 1.40, P=0.023), and mGPS at recurrence (hazard ratio 1.47, P=0.002) remained independent predictors of PRS. CONCLUSIONS mGPS at the time of recurrence might be an independent adverse prognostic factor in recurrent NSCLC.

Long non-coding RNA HOTAIR regulates proliferation and invasion via activating Notch signalling pathway in retinoblastoma.

Retinoblastoma is the most frequently occurring tumour in the eyes in early childhood. Novel targets that are important for the diagnosis or treatment of retinoblastoma could be valuable in increasing the survival rate of patients affected by this disease. Long non-coding RNAs (lncRNAs) are a recently discovered type of RNAs with no proteincoding function; yet it has become increasingly clear that lncRNAs are responsible for important gene regulatory functions in various diseases. In this study, the expression of lncRNA HOTAIR was measured by qRT-PCR, and HOTAIR expression was found to be significantly upregulated in human retinoblastomas tissues as compared with that in paracancerous tissues. Knockdown of HOTAIR restricted the proliferation and invasion of the more invasive retinoblastoma Y79 cells, and led to G0/G1 arrest, possibly through inhibiting phospho-RB1, RB1 and CCNE. Furthermore, we found that the Notch signalling pathway was activated abnormally in retinoblastoma cell lines, while knockdown of HOTAIR attenuated the endogenous Notch signalling pathway in vitro and in vivo. In addition, knockdown of HOTAIR could inhibit the tumour progression in a xenograft model of retinoblastoma. In summary, our findings indicate that HOTAIR may play important roles in retinoblastoma progression via Notch pathway. HOTAIR has the potential to enhance the development of novel targeted diagnostic and therapeutic approaches for retinoblastoma.

Upregulation of lncRNA HOTAIR contributes to IL-1ß-induced MMP overexpression and chondrocytes apoptosis in temporomandibular joint osteoarthritis.

Temporomandibular joint osteoarthritis (TMJ OA) is a common and heterogeneous disease that causes painful and progressive joint degeneration, which restricts daily activities, including talking and chewing. Long noncoding RNAs (lncRNAs) are an important class of genes involved in various physiological and pathological functions, including osteoarthritis (OA).The present study aimed to identify the lncRNAs that are important in TMJ OA and their potential functions. Here, we found that HOTAIR was significantly upregulated in the synovial fluid of TMJ OA patients compared with that of normal controls. Increased HOTAIR was similarly observed in the synovial fluid of TMJ OA rabbits as compared to control rabbits. Furthermore, in interleukin-1ß (IL-1ß)-induced TMJ OA in vitro model (primary rabbit condylar chondrocytes), the expressions of matrix metalloproteinase (MMP)-1, MMP3, MMP9 and HOTAIR were all dramatically increased. Most importantly, knockdown of HOTAIR in IL-1ß-induced TMJ OA in vitro model could not only reverse the IL-1ß-stimulated expressions of MMP1, MMP3 and MMP9, but also significantly decrease the apoptosis rate induced by IL-1ß in primary rabbit condylar chondrocytes. Our data provides new insight into the mechanisms of chondrocytes destruction in TMJ OA.