C/EBPα mediates the maturation and antitumor functions of macrophages in human hepatocellular carcinoma.

Recent studies have suggested that therapeutic upregulation of CCAAT/enhancer binding protein α (C/EBPα) prevents hepatocellular carcinoma (HCC) progression. However, the mechanisms underlying this outcome are not fully understood. In this study, we investigated the expression and functional roles of C/EBPα in human HCC, with a focus on monocytes/macrophages (Mφs). Paraffin-embedded tissues were used to visualize C/EBPα expression and analyze the prognostic value of C/EBPα+ monocytes/Mφs in HCC patients. The underlying regulatory mechanisms were examined using human monocyte-derived Mφs. The results showed that the expression of C/EBPα on monocytes/Mφs was significantly decreased in intra-tumor tissues compared to the corresponding peri-tumor tissues. C/EBPα+ monocytes/Mφs displayed well-differentiation and antitumor capacities, and the accumulation of these cells in tissue was associated with antitumor immune responses and predicted longer overall survival (OS) of HCC patients. Mechanistic studies demonstrated that C/EBPα was required for Mφ maturation and HLA-DR, CD169 and CD86 expression, which initiates antitumor cytotoxic T-cell responses; however, these effects were inhibited by monocyte autocrine IL-6- and IL-1ß-induced suppression of mTOR1 signaling. Reprogramming Mφs via the upregulation of C/EBPα may provide a novel strategy for cancer immunotherapy in patients with HCC.

Beneficial effects of protocatechuic acid on diabetic retinopathy in streptozocin-induced diabetic rats.

AIM: To determine the effects of protocatechuic acid (PCA) on streptozocin-induced diabetic retinopathy (DR) in rats. METHODS: Wistar rats were given a 50 mg/kg intraperitoneal injection of streptozocin to induce diabetes. Animals were assigned randomly one of four groups (8 rats per group): control, diabetic, diabetic plus PCA (25 mg/kg·d), and diabetic plus PCA (50 mg/kg·d). After inducing diabetes, treatments were started one week later and continued for eight weeks. After the experiment, the rats were sacrificed, and their retinas were taken for biochemical and molecular analysis. RESULTS: PCA administration diminished the blood glucose and glycated haemoglobin levels relative to the diabetic group. In diabetic rats, PCA lowered elevated levels of advanced glycosylated end products (AGEs) and receptor for AGEs (RAGE). In the retina of diabetic rats, PCA effectively decreased inflammatory cytokine, nuclear factor-κB, tumour necrosis factor-α, interleukin-1ß, and vascular endothelial growth factor, and increased antioxidant markers glutathione, superoxide dismutase, and catalase. CONCLUSION: The protective benefits of PCA against DR may be attributable to its suppression of the AGEs and RAGE and its antioxidant and anti-inflammatory properties.