Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are two important leading causes of acquired blindness in developed countries. As accumulation of advanced glycation end products (AGEs) in retinal pigment epithelial (RPE) cells plays an important role in both DR and AMD, and the methylglyoxal (MGO) within the AGEs exerts irreversible effects on protein structure and function, it is crucial to understand the underlying mechanism of MGO-induced RPE cell death. Using ARPE-19 as the cell model, this study revealed that MGO induces RPE cell death through a caspase-independent manner, which relying on reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) loss, intracellular calcium elevation and endoplasmic reticulum (ER) stress response. Suppression of ROS generation can reverse the MGO-induced ROS production, MMP loss, intracellular calcium increase and cell death. Moreover, store-operated calcium channel inhibitors MRS1845 and YM-58483, but not the inositol 1,4,5-trisphosphate (IP3) receptor inhibitor xestospongin C, can block MGO-induced ROS production, MMP loss and sustained intracellular calcium increase in ARPE-19 cells. Lastly, inhibition of ER stress by salubrinal and 4-PBA can reduce the MGO-induced intracellular events and cell death. Therefore, our data indicate that MGO can decrease RPE cell viability, resulting from the ER stress-dependent intracellular ROS production, MMP loss and increased intracellular calcium increase. As MGO is one of the components of drusen in AMD and is the AGEs adduct in DR, this study could provide a valuable insight into the molecular pathogenesis and therapeutic intervention of AMD and DR.

We found that HCA was significantly correlated with lower gestational age, higher CRP level of preterm infants, higher maternal WBC count, and a higher rate of prolonged PROM. Our results demonstrate a significant association between HCA with an elevated CRP level in preterm infants. These findings further confirmed the association between maternal inflammation and preterm deliveries.

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Objective The incidence of patent ductus arteriosus (PDA), a major complication of prematurity, may be reduced by restricting fluid administration. Prophylactic fresh frozen plasma (FFP) transfusion may reduce the incidence of intraventricular hemorrhage in these infants, but risks transfusion-related volume overload. We conducted a retrospective study to investigate whether FFP transfusion is a risk factor for hemodynamically significant PDA (hsPDA) in very low birth weight (BW) premature infants. Study Design From January 2009 to December 2014, 102 premature infants with gestational age (GA) less than or equal to 30 weeks were admitted to a level III neonatal intensive care unit, and 88 patients were enrolled. Patients were further divided into non-hsPDA (n = 29) and hsPDA groups (n = 59). We retrospectively reviewed demographic characteristics and various perinatal and postnatal variables. Univariate and multivariable analyses were performed to identify risk factors for hsPDA. Results Compared with non-hsPDA patients, hsPDA patients had lower mean BW and GA, a higher incidence of severe respiratory distress symptoms, perinatal infection, use of surfactant, and need for FFP transfusion. However, multivariable logistic regression analysis showed that only FFP transfusion remained an independent risk factor for hsPDA (adjusted odds ratio = 3.880, 95% confidence interval: 1.214–12.402, p = 0.022) after adjusting for confounding factors. Conclusion FFP transfusion is a significant risk factor for the subsequent development of hsPDA in our study population. FFP transfusion may complicate the fluid management of premature infants and increase the risk of hsPDA. Key Points