Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In this study, we investigated whether osthole ameliorates inflammatory sepsis-related ALI. Results from in vitro studies indicated that osthole treatment inhibited the LPS-induced inflammatory response in mouse peritoneal macrophages through blocking the nuclear translocation of NF-κB. Consistently, the in vivo studies indicated that osthole significantly prolonged the survival of septic mice which was accompanied by inflammation suppression. In the ALI mouse model, osthole effectively inhibited the development of lung tissue injury, leukocytic recruitment, and cytokine productions, which was associated with inhibition of NF-κB nuclear translocation. These findings provide evidence that osthole was a potent inhibitor of NF-κB and inflammatory injury and suggest that it could be a promising anti-inflammatory agent for therapy of septic shock and acute lung injury.

Diabetic retinopathy (DR) is one of the most frequently occurring microvascular complications of diabetes. Recent evidence indicates that epidermal growth factor receptors (EGFRs) are critical pathogenic players in non-neoplastic diseases, including diabetic cardiomyopathy and DR. However, the precise pathogenic mechanism of EGFR in DR has yet to be fully understood. In this study, we developed a type 1 diabetic early-stage retinopathy mouse model using injections of streptozotocin and an oxygen-induced end-stage diabetic retinopathy (OIR) model characterized by hypoxia-induced revascularization. We tested the hypothesis that the pathogenesis of DR can be reduced by the classic EGFR inhibitor, AG1478, in the mouse models. Our data indicated that treatment of AG1478 prevented retinal dysfunction, and reduced impairment of retinal structures as well as mitochondrial structures in retinal blood vessels in diabetic mice. Furthermore, AG1478 reduced neovascular tufts formation but had no effects on revascularization at the avascular sites when compared to untreated littermates in the OIR model. Our findings provide strong evidence that EGFR critically promoted retinal dysfunction, retinal structural impairment, and retinal vascular abnormalities in models of DR. We conclude that EGFR can be a potential important therapeutic target for treatment of DR.

Purpose To evaluate the efficacy, feasibility, and safety of the navigation-guided endoscopy combined with deep lateral orbitotomy for removal of small tumors at the lateral orbital apex. Design A retrospective, noncomparative case series. Methods Retrospective analysis of ten patients (10 eyes) with small tumors at the lateral orbital apex comprised navigation-guided endoscopy combined with deep lateral orbitotomy at the Eye Hospital of Wenzhou Medical University from November 2015 to November 2017. In each case, the indication of surgery was existing or imminent visual impairment due to the tumor. The removal was believed to be complete if the mass was removed intactly during the surgery. The tumor character was confirmed by pathological examination after surgery. Patients were followed up to 3 months after surgery. Best corrected visual acuity before and after surgery was compared. Results All tumors were completely removed by the navigation-guided endoscopic approach. The mean preoperative best corrected visual acuity was 6/15 (95% confidence interval (95% CI) 6/40–6/8.5), and the mean postoperative best corrected visual acuity was 6/10 (95% CI 6/15–6/7.5). 5 of 7 (71%) patients with vision loss gained visual improvement in different degrees after surgery, and the rest of the patients had preoperative best corrected visual acuity. Visual field of all patients also improved. 8 cavernous hemangiomas and 2 schwannomas were confirmed postoperatively by pathology. 4 patients accompanied with limitation of eye abduction, which recovered spontaneously in an average of 4 weeks. No other serious complications occurred. Conclusions Navigation-guided endoscopy combined with deep lateral orbitotomy seems to be a feasible, efficient, and safe approach for removing small tumors at the lateral orbital apex. This trial is registered with ChiCTR1800019244.

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Modified LDL-induced inflammation and oxidative stress are involved in the pathogenesis of diabetic retinopathy. Recent studies have also shown that modified LDL activates Toll-like receptor 4 (TLR4) to mediate retinal injury. However, the mechanism by which modified LDL activates TLR4 and the potential role of the TLR4 coreceptor myeloid differentiation protein 2 (MD2) are not known. In this study, we inhibited MD2 with the chalcone derivatives L2H17 and L6H21 and showed that MD2 blockade protected retinal Müller cells against highly oxidized glycated-LDL (HOG-LDL)-induced oxidative stress, inflammation, and apoptosis. MD2 inhibition reduced oxidative stress by suppressing NADPH oxidase-4 (NOX4). Importantly, HOG-LDL activated TLR4 and increased the interaction between NOX4 and TLR4. MD2 was required for the activation of these pathways, as inhibiting MD2 prevented the association of NOX4 with TLR4 and reduced NOX4-mediated reactive oxygen species production and TLR4-mediated inflammatory factor production. Furthermore, treatment of diabetic mice with L2H17 significantly reduced LDL extravasation in the retina and prevented retinal dysfunction and apoptosis by suppressing the TLR4/MD2 pathway. Our findings provide evidence that MD2 plays a critical role in mediating modified LDL-induced cell injury in the retina and suggest that targeting MD2 may be a potential therapeutic strategy.