Intravitreal injection of conbercept is shown to be safe and effective for the treatment of ME secondary to BRVO, based on 6-month follow-up data.

Diabetic retinopathy (DR) occurs in almost all patients with diabetes and remains as one of the major causes of vision loss worldwide. Nevertheless, the molecular mechanisms underlying the pathogenesis of DR remain elusive. The present study aimed to investigate the role and association of Notch signaling and NADPH oxidase 4 (Nox4)-mediated oxidative stress in high glucose (HG)-treated retinal cells. Human retinal endothelial cells were cultured for various durations in RPMI-1640 medium containing 30 mM glucose (HG) or 30 mM mannitol (MN) as an osmotic control; apoptotic cell death and reactive oxygen species (ROS) levels were assessed, respectively. Alterations in the expression profiles of Nox and Notch proteins were evaluated using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Knockdown of Nox4 and recombination signal-binding protein J (RBPj) was generated by transfection with specific small interfering (siRNA). Persistent activation of Notch signaling was induced via the overexpression of Notch intracellular domain (NICD). In the present study, time-dependent increases in ROS production and cell death were detected in HG-treated cells. Depletion of ROS by diphenyleneiodonium decreased HG-induced cell death, and suppressed increases in caspase 3 activity and B-cell lymphoma 2-associated X protein levels. In HG-treated cells, Nox4 expression was upregulated at the mRNA and protein levels, and inhibition of Nox4 by GKT137831 or knockdown of expression by siRNA Nox4 significantly reduced ROS levels and cell death. In the presence of HG, Notch1 expression levels were elevated, and increased NICD abundance was detected in whole cell lysates and nuclear fractions. Additionally, HG-induced cell death was decreased by treatment with γ-secretase inhibitor (GSI), but increased via the overexpression of NICD. The application of GSI or knockdown of RBPj by siRNA RBPj prevented increases in Nox4 expression within HG-treated cells. The findings of the present study demonstrated that Nox4-mediated ROS serves an important role in HG-induced retinal cell damage, in which the activation of Notch signaling may be responsible for Nox4 upregulation. Therefore, inhibition of Notch signaling or Nox4 expression may be considered as potential therapeutic targets in patients with DR.

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Oral tongue squamous cell carcinoma (OTSCC) is the most common oral malignancy with different histopathological symptoms and etiology of tumorigenesis. Migration and invasion is the most important characteristics of OTSCC, and limits tumor therapy in clinics. The epithelial‑to‑mesenchymal transition (EMT) signaling pathway is an important process in the progress of tumor cell migration and invasion. Previous studies have indicated that C‑X‑C chemokine receptor‑7 (CXCR‑7) promotes the progression and metastasis of tumor cells, presenting a potential target molecule for cancer therapy. The present study investigated the inhibitory effects of C‑X‑C chemokine‑7 (CXC‑7) on human OTSCC cells both in vitro and in vivo. The results demonstrated that the Tca8113 human OTSCC cell line expressed higher levels of CXC‑7 mRNA compared with the hNOE human normal oral epithelial cell line. MTT assays indicated that CXC‑7 suppressed Tca8113 cell growth, and the cytotoxicity of CXC‑7 was indicated as the cell survival of the negative control group was significantly decreased compared with the blank control and hNOE cells. Migration and invasion assays revealed that CXC‑7 inhibited Tca8113 cell local expansion and distant metastasis. In addition, the results demonstrated that the extracellular signal‑regulated kinase (ERK)/protein kinase B (AKT) signaling pathway was inhibited after CXC‑7 treatment in Tca8113 cells. N‑cadherin, E‑Cadherin, Snail and Slug expression levels in the ERK/AKT signaling pathway were inhibited in Tca8113 cells after treatment with CXC‑7. It was demonstrated that important extracellular matrix proteins involved in cell migration, including Slug, collagen type I and Vimentin, were significantly downregulated by CXC‑7 treatment. In conclusion, CXC‑7 inhibited growth and migration in OTSCC cells, mediated by the EMT signaling pathway. This suggests that CXC‑7 serves an inhibitory role in OTSCC migration, implicating CXCR‑7 as a promising biomarker for chemokine receptor‑based drug development.

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