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Hyperreflective foci (HF), detected in the retina of diabetic patients, suggest the presence of microglial activation and migration, while controversies still remain for the origin of HF to be precursors of hard exudates. We investigated the presence of HF and their association with dyslipidemia in serous retinal detachment (SRD)-type diabetic macular edema (DME). Forty-two eyes in 42 patients with diabetic retinopathy (DR) and 22 eyes in 22 patients with branch retinal vascular occlusion (BRVO) showing macular edema were included in this study. The medical records and OCT findings were retrospectively reviewed in patients with SRD-type DME and compared with those with BRVO. The mean number of HF, the mean choroidal thickness, and lipid profiles were analyzed and compared between groups. The mean number of HF was significantly higher in DR group compared to BRVO group. Significant correlation of HF was noted with triglycerides (r = 0.523, P = 0.002). Triglycerides were significantly associated with HF by linear regression (β = 0.012, 95% CI 0.001–0.024, P = 0.034) and remained significantly associated by multiple linear regression (β = 0.014, 95% CI 0.003–0.025, P = 0.014). HF on OCT of DME patients could be indicative of activated microglia. HF are associated with dyslipidemia, especially high triglycerides, suggesting inflammatory reaction from dyslipidemia in diabetic retina.

Diabetic macular edema (DME) is the abnormal accumulation of fluid in the subretinal or intraretinal spaces in the macula in patients with diabetic retinopathy and leads to severely impaired central vision. Technical developments in retinal imaging systems have led to many advances in the study of DME. In particular, optical coherence tomography (OCT) can provide longitudinal and microstructural analysis of the macula. A comprehensive review was provided regarding the role of inflammation using OCT-based classification of DME and current and ongoing therapeutic approaches. In this review, we first describe the pathogenesis of DME, then discuss the classification of DME based on OCT findings and the association of different types of DME with inflammation, and finally describe current and ongoing therapeutic approaches using OCT-based classification of DME. Inflammation has an important role in the pathogenesis of DME, but its role appears to differ among the DME phenotypes, as determined by OCT. It is important to determine how the different DME subtypes respond to intravitreal injections of steroids, antivascular endothelial growth factor agents, and other drugs to improve prognosis and responsiveness to treatment.

Cystoid macular edema (CME) is the abnormal collection of intraretinal fluid in the macular region, especially in the inner nuclear and outer plexiform layers. CME leads to severe visual impairment in patients with various retinal diseases, such as diabetic retinopathy, retinal vascular occlusion, choroidal neovascularization, and uveitis. Although various retinal conditions lead to CME, a shared pathogenesis of CME is involved in these diseases. Accordingly, the pathogenesis of CME based on vasogenic mechanisms is first discussed in this review, including vascular hyperpermeability, leukostasis, and inflammation. We then describe cytotoxic mechanisms based on retinal Müller cell dysfunction. This comprehensive review will provide an understanding of the pathogenesis of CME for potential therapeutic strategies.

The effect of cell cycle synchronisation on glucose metabolism in cancer cells is not known. We assessed how cell cycle synchronisation by thiazolidinediones (TZDs) can affect glucose uptake by cancer cells and investigated the anti-cancer effect of combination therapy with TZDs and 2-deoxy-glucose (2-DG) in colon cancer cells and in mouse xenograft models. Troglitazone (58.1 ± 2.0 vs 48.6 ± 1.3%, p = 0.002) or pioglitazone (82.9 ± 1.9 vs 61.6 ± 3.4%, p 3H-DG uptake (141.5% ± 12.9% of controls) and membrane GLUT1 expression levels (146.3% of controls) by 24 h; 1 mM 2-DG treatment alone decreased cell survival by 5.8% as compared with the controls.; however, combination therapy enhanced the anti-tumour effects to 34.6% or 20.3% as compared with control cells. In vivo, each combination treatment group showed significant anti-tumour effects unlike the 2-DG alone group. Cell cycle synchronisation using TZDs induced cellular glucose uptake, which significantly enhanced the therapeutic effect of 2-DG in colon cancer.

Background Protein tyrosine phosphatase receptor delta (PTPRD) is frequently inactivated in various types of cancers. Here, we explored the underlying mechanism of PTPRD-loss-induced cancer metastasis and investigated an efficient treatment option for PTPRD-inactivated gastric cancers (GCs). Methods PTPRD expression was evaluated by immunohistochemistry. Microarray analysis was used to identify differentially expressed genes in PTPRD-inactivated cancer cells. Quantitative reverse transcription (qRT-PCR), western blotting, and/or enzyme-linked immunosorbent assays were used to investigate the PTPRD-CXCL8 axis and the expression of other related genes. An in vitro tube formation assay was performed using HUVECs. The efficacy of metformin was assessed by MTS assay. Results PTPRD was frequently downregulated in GCs and the loss of PTPRD expression was associated with advanced stage, worse overall survival, and a higher risk of distant metastasis. Microarray analysis revealed a significant increase in CXCL8 expression upon loss of PTPRD. This was validated in various GC cell lines using transient and stable PTPRD knockdown. PTPRD-loss-induced angiogenesis was mediated by CXCL8, and the increase in CXCL8 expression was mediated by both ERK and STAT3 signaling. Thus, specific inhibitors targeting ERK or STAT3 abrogated the corresponding signaling nodes and inhibited PTPRD-loss-induced angiogenesis. Additionally, metformin was found to efficiently inhibit PTPRD-loss-induced angiogenesis, decrease cell viability in PTPRD-inactivated cancers, and reverse the decrease in PTPRD expression. Conclusions Thus, the PTPRD-CXCL8 axis may serve as a potential therapeutic target, particularly for the suppression of metastasis in PTPRD-inactivated GCs. Hence, we propose that the therapeutic efficacy of metformin in PTPRD-inactivated cancers should be further investigated.

Purpose Proteinuria is the second most common complication after hypertension after systemic administration of bevacizumab. Therefore we aimed to analyze the effect of intravitreal bevacizumab (IVB) injection on proteinuria in patients with diabetes. Methods Patients scheduled to receive IVB injection from May 1, 2018, to December 31, 2018, were prospectively enrolled. In total, 53 patients with diabetes (26 with nonproliferative diabetic retinopathy and 27 with proliferative diabetic retinopathy) and 37 patients without diabetes were included. Urine tests were performed within 1 month of and 7 ± 1 days after IVB injection. Urinary protein, creatinine, and albumin concentrations were quantitatively measured, and urinary protein-to-creatinine ratio and urinary albumin-to-creatinine ratio (UACR) were calculated from these data before and after IVB injection. Results The mean urinary microalbumin concentrations and urinary protein-to-creatinine ratio were significantly higher in patients with diabetes, both before and after IVB injection. There were no differences between patients with nonproliferative diabetic retinopathy and proliferative diabetic retinopathy. About 80% of patients with diabetes showed improved albuminuria or at least no harmful effect in terms of albuminuria. Patients with deteriorated baseline UACR showed more residual increase in UACR after IVB injection (P < 0.05 in all groups). Conclusions Close monitoring of renal function after IVB might be needed in patients with diabetes according to the severity of nephropathy. Translational Relevance Our results may provide information regarding the renal function of IVB-treated patients with diabetes.

Allergies are immediate hypersensitive responses to antigens and interleukin (IL)-4 is involved in the initiation and development of allergic responses. Rb₁ has been known to have a variety of biological activities including anti-inflammatory activity, but the effect of Rb₁ on allergic responses is not known yet. The present study was undertaken to examine whether Rb₁ has an inhibitory effect on allergic response in mouse model. In allergic mouse model, our results showed that topical application of Rb₁ on atopic dermatitis (AD)-like skin lesions improved skin condition and inhibited starching behaviors. In addition, Rb₁ application not only suppressed mRNA expression of IL-4 and IL-10, but also prevented the nuclear factor of activated T cells 1 transcription. Moreover, Rb₁ application suppressed IL-4’ secretion. Taken together, these results suggest that Rb₁ has a potent inhibitory effect in AD-related T cell cytokine production and may be a candidate for therapeutic agent in allergy.