Search

Recent studies show a connection between glycolysis and inflammatory response in rheumatoid arthritis (RA) macrophages (MΦs) and fibroblasts (FLS). Yet, it is unclear which pathways could be targeted to rebalance RA MΦs and FLS metabolic reprogramming. To identify novel targets that could normalize RA metabolic reprogramming, TLR7-mediated immunometabolism was characterized in RA MΦs, FLS and experimental arthritis. We uncovered that GLUT1, HIF1α, cMYC, LDHA and lactate were responsible for the TLR7-potentiated metabolic rewiring in RA MΦs and FLS, which was negated by IRAK4i. While in RA FLS, HK2 was uniquely expanded by TLR7 and negated by IRAK4i. Conversely, TLR7-driven hypermetabolism, non-oxidative PPP (CARKL) and oxidative phosphorylation (PPARγ) were narrowly dysregulated in TLR7-activated RA MΦs and FLS and was reversed by IRAK4i. Consistently, IRAK4i therapy disrupted arthritis mediated by miR-Let7b/TLR7 along with impairing a broad-range of glycolytic intermediates, GLUT1, HIF1α, cMYC, HK2, PFKFB3, PKM2, PDK1 and RAPTOR. Notably, inhibition of the mutually upregulated glycolytic metabolites, HIF1α and cMYC, was capable of mitigating TLR7-induced inflammatory imprint in RA MΦs and FLS. In keeping with IRAK4i, treatment with HIF1i and cMYCi intercepted TLR7-enhanced IRF5 and IRF7 in RA MΦs, distinct from RA FLS. Interestingly, in RA MΦs and FLS, IRAK4i counteracted TLR7-induced CARKL reduction in line with HIF1i. Whereas, cMYCi in concordance with IRAK4i, overturned oxidative phosphorylation via PPARγ in TLR7-activated RA MΦs and FLS. The blockade of IRAK4 and its interconnected intermediates can rebalance the metabolic malfunction by obstructing glycolytic and inflammatory phenotypes in RA MΦs and FLS., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Cranioplasty is a common neurosurgical procedure with the goal of restoring skull integrity. Custom-made porous hydroxyapatite prostheses have long been used for cranial reconstruction in patients with traumatic brain injury. We present a large consecutive series of 2 groups of patients undergoing cranioplasty with hydroxyapatite custom bone and compare the adverse events (AEs) between the 2 groups., Methods: We examined a series of consecutive patients who underwent cranioplasty using custom-made porous hydroxyapatite implants following tumor resection and traumatic brain injury at a single center between March 2003 and May 2018. The implants were designed and produced according to the surgeon's specifications and based on the patient's computed tomography scan data obtained through a standardized protocol. AEs were recorded., Results: Information on 38 patients with tumor and 39 patients with traumatic brain injury was collected and analyzed. A significant difference in the timing of surgery was found between the 2 groups; single-stage surgery was performed in 84% of patients in the tumor versus 8% of those in the traumatic brain injury group (P < 0.0001). The rate of AEs was not significantly different between the 2 groups (P = 0.4309) and was not related to the timing of surgery., Conclusions: Custom-made hydroxyapatite cranioplasty is a solution for cranial reconstruction in patients with cranial tumors. The low incidence of AEs in a consecutive series of patients with either trauma or tumors demonstrates that these prostheses represent a safe solution independent of the characteristics of cases., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Herpes simplex virus type-1 (HSV-1) is a significant pathogen that affects vision by targeting multiple regions in the human eye including iris. Using a focused library of synthetic non-saccharide glycosaminoglycan mimetics (NSGMs), we identified sulfated pentagalloylglucoside (SPGG) as a potent inhibitor of HSV-1 entry and cell-to-cell spread in the primary cultures of human iris stromal (HIS) cells isolated from eye donors. Using in vitro β-galactosidase reporter assay and plaque reduction assay, SPGG was found to inhibit HSV-1 entry in a dosage-dependent manner (IC 50 ∼6.0 μM). Interestingly, a pronounced inhibition in HSV-1 entry and spread was observed in HIS cells, or a cell line expressing specific gD-receptor, when virions were pre-treated with mimetics suggesting a possible interaction between SPGG and the HSV-1 glycoprotein. To examine the significance of gD-SPGG interaction, HIS cells were pretreated with SPGG, which showed a significant reduction in gD binding. Taken together, our results provide strong evidence of SPGG being a novel viral entry inhibitor against ocular HSV infection., (Copyright © 2018. Published by Elsevier B.V.)

Introduction: Large cranial defects still represent a challenge in neurosurgery. Currently different biomaterials are available for cranial reconstruction including titanium, acrylic mesh and different types of calcium phosphate-based bone grafts. The goal of surgery is a perfect fit of the implant without infection and absorption, and a good aesthetic result. This paper describes a surgical method for cranioplasty, using a customised porous hydroxyapatite (HA) prosthesis., Materials and Methods: Sixty patients treated surgically with a customised porous-HA prosthesis for large cranial defects, were followed retrospectively. A two-year follow-up was carried out with periodic visits and CT scans. Safety (the incidence of adverse events and fractures of the implant) and clinical performance (biological and cosmetic results) were evaluated., Results: Fifty one patients were followed-up, no rejection occurred and only one case of infection was recorded. Five patients had minor surgery-related complications, and no spontaneous implant fractures or mobilisation were reported. Three patients exhibited implant fractures as a result of trauma and all healed spontaneously. All patients showed a satisfactory clinical outcome with good cosmetic appearance in the early postoperative period and after a long-term follow-up., Conclusions: Cranioplasty performed with a customised porous-HA prosthesis gave a positive outcome, showing it to be an appropriate technique for use in large and complex cranial reconstruction., (Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)